Terapie a podpůrné kroky

2,4-Dimethylphenol

• Its 2,3-, 2,5-, 2,6-dimethylphenol isomers
• Protected tracheal explants from changes after exposure to virulent M. pneumoniae strain PI 1428
• Concentration, time, and isomer dependent
• 10(-9) M or greater
• 2,4-dimethylphenol completely prevented
• Morphological (loss of ciliated cells)
• Biochemical (decreased dehydrogenase activity) changes
• 2,4-dimethylphenol
• Interfered with an early event in the infection process
• Complete protection required that it be present during the first 2 h of exposure
• pubmed.ncbi.nlm.nih.gov/6778378/

• 2,4-xylenol is a member of the class of phenols
• Phenol substituted by methyl groups at positions 2 and 4
• Disinfectant and a volatile oil component
• Aromatic fungicide
• Derives from a hydride of a m-xylene.
• Natural product found in Apis cerana včela východní

https://pubchem.ncbi.nlm.nih.gov/compound/2_4-Dimethylphenol

• Crystalline (sand-like) solid or a yellow-brown liquid
• 2,4-Dimethylphenol can affect you when inhaled and by passing through the skin.
• Contact can irritate and burn the skin and eyes.
• Inhaling 2,4-Dimethylphenol can irritate the nose, throat and lungs.
• Exposure to 2,4-Dimethylphenol can cause headache, weakness, nausea and vomiting.
• High or repeated exposure may affect the liver and kidneys.
• nj.gov/health/eoh/rtkweb/documents/fs/0764.pdf

6-thioguanin - 6-TG

Inhibition of Mpn and human HPRT with 6-TG and other purine analogs

• Of 6-TG, 6-mercaptopurine (6-MP), and two other purine analogs that did not inhibit Mpn growth on Mpn HPRT
• The 6-TG strongly inhibited Mpn HPRT with either Hx or Gua as a substrate
• Half maximal inhibitory concentration (IC50) values were 3.5 ± 0.5 µM (Hx) and 3.2 ± 0.2 µM (Gua)
• The 6-TG also inhibited human HPRT
• But with a much higher IC50 value
• The 6-MP inhibited Mpn HPRT with IC50 values of 89.7 ± 14.5 µM (Hx) and 281.9 ± 21 µM (Gua)
• Human HPRT, 6-MP had similar IC50 values to those of 6-TG.
• Theophylline and caffeine were poor inhibitors of both Mpn and human HPRT

• Both Hx and Gua are good substrates for the enzyme HPRT
• Vmax values for these substrates are in the same order of magnitude as the human enzyme
• Humans, the plasma concentrations of Hx and Gua are approximately 172 uM and 97 uM
• Close to the Km and S0.5 values of Mpn HPRT with Hx and Gua
• Mpn HPRT is capable of efficiently salvaging both Hx and Gua
• Mpn HPRT showed positive cooperativity with Gua
• At higher Gua concentration the enzyme utilizes Gua better.

• 6-TG and 6-MP are structural analogs
• Structural differences in binding of these two compounds to the respective HPRTs
• HPRT has been suggested as a target for anti-parasite drug development

Camelthorn - Alhagi maurorum

• Is a plant of the Fabaceae family
• Grows in different places around the world from North Africa to Europe and Asia
• Herbal medicine with a wide variety of applications in folklore medicine such as
• Laxative, diuretic, and expectorant properties
• Effective remedy for reducing acidity in the gastric problem
• A. maurorum is used to heal wounds
• Also as an agent for diaphoretic and antiseptic

A. maurorum essential oil

• Effective remedy for rheumatism
• Plants' secondary metabolites play a basic role in herbal medicinal uses
• Camelthorn is rich in different classes of compounds such as phenolic, alkaloids, flavonoids, fatty acids, and vitamins.
• Certainly, the existence of various compounds in the plant is the essential factor for the wide variety of pharmaceutical uses of the plant
• Project, copper NPs were formulated according to pharmacology rules by A. maurorum aqueous extract to treat the mouse model of M. pneumonia.
• doi.org/10.1080/17458080.2022.2104451

JL směs

• Astragalus arenarius - kozinec písečný
• Zmírnění astmatu
• www.ncbi.nlm.nih.gov/pmc/articles/PMC6158305/
• Borago officinalis - Brutnák lékařský
• Zmírnění astmatu
• www.ncbi.nlm.nih.gov/pmc/articles/PMC5304961/
• Echinacea purpurea - Echinacea purpurová - Třapatka
• Imperatoriea ostruthium
• Occinum basilicum -bazalka
• Antimykopl. učinky
• Peumus boldus
• Ribes nigrum - černý rybíz
• Tabebubia serratifolia
• Thymus vulgaris - tymián obecný
• Antimykopl.
• Thymus serphyllum
• Antimykopl.
• Tussilago farfara
• Uncaria tomentosa - kočičí dráp
• Verbascum densifolium

Naringenin

• The Protective Effect of Naringenin on Airway Remodeling after Mycoplasma Pneumoniae Infection by Inhibiting Autophagy-Mediated Lung Inflammation and Fibrosis
• Has a regulatory function to fibroblasts and the inflammatory response.
• Hernandez-Aquino et al. have found that NRG can prevent experimental liver fibrosis by blocking TGF-b signaling
• NRG pretreatment inhibits neuroapoptosis ameliorates cognitive impairment in rats exposed to isoflurane anesthesia
• By regulating the PI3/Akt/PTEN signaling pathway
• Suppressing NF-?B-mediated inflammation
• Inhibits stress-induced autophagy
• Protective effect on oxidative stress-induced lung damage

Qingfei Tongluo formula (QTF)

• Used for the clinical treatment of Mycoplasma pneumoniae pneumonia (MPP)
• Resulting in a significantly therapeutic effect.
• Increasing evidence has shown that naringenin (NRG), an important component of QTF,
• doi.org/10.1155/2018/8753894

Sophorolipids

• Possess antibacterial,antiviral, anti-cancer, and anti-mycoplasma activities [24–26]. In an experiment, Bluth et al. [27]induced intra-abdominal sepsis in rats and then treated them with sophorolipids; this increased thesurvival of rats and blocked the detrimental e?ect of septic shock by attenuating the production ofpro-in?ammatory cytokines and nitric oxide [27]. Sophorolipids downregulated the expression ofTLR2,PAX5,STAT3, and IL6 in U266 cell lines; thereby reducing the production of IgE
• www.researchgate.net/publication/344406883_Immunomodulatory_Role_of_Microbial_Surfactants_with_Special_Emphasis_on_Fish

Yinhuang

• Honeysuckle extract
• Baikal skullcap root extract
• Drugs for curing chronic respiratory disease infection of beasts and birds.
• Flos Lonicerae extract + Radix Scutellariae extract
• Contain Flos Lonicerae in chlorogenic acid (C16H1809)
• Every gram silver yellow soluble powder, must not be less than 1.7mg, contain Radix Scutellariae in baicalin (C21H18011), must not be less than 18.0mg.

• Take by weighing Flos Lonicerae extract 900.0g, Radix Scutellariae extract 10.0g
• Adds purified water 600ml, stirs to make it to be suspension,
• Regulates pH value to 5.0 ~ 7.0 with sodium hydroxide solution and makes its dissolving,
• Adds purified water to 1000ml,
• Packing had both got medicine

• Flos Lonicerae extract 40g, Radix Scutellariae extract 20g
• Purified water 600ml,
• Stirs to make it to be suspension,
• Regulates pH value to 5.0 ~ 7.0 with sodium hydroxide solution and makes its dissolving,
• Adds purified water to 1000ml,
• Packing had both got medicine

• Flos Lonicerae extract 16.0g, Radix Scutellariae extract 10.0g adds injection water 600ml, stirring makes it to be suspension, regulate pH value to 5.0 ~ 7.0 with sodium hydroxide solution and make its dissolving

Respirační infekce TCM 1

• Radix Bupleuri, Radix Scutellariae, Herba Houttuyniae, Herba Andrographis, Folium Isatidis, Radix Puerariae, Flos Chrysanthemi Indici, Herba Ephedrae, Semen Armeniacae Amarum, Radix Glycyrrhizae such as Yang Bin

Respirační infekce TCM 2

• Radix Isatidis, Folium Isatidis, Radix Glycyrrhizae, Venenum Bufonis, Herba Artemisiae Scopariae, Fructus Forsythiae, Herba Houttuyniae, Rhizoma Belamcandae, Herba Taraxaci, the Radix Aucklandiae, the Radix Pulsatillae, Borneolum Syntheticum etc.

Respirační infekce TCM 3

• Concha Haliotidis, Rhizoma Dioscoreae Bulbiferae, Radix Scutellariae, Radix Stephaniae Cepharanthae, Pericarpium Citri Reticulatae, Rhizoma Atractylodis, Radix Platycodonis, Fructus Gardeniae, Radix Curcumae, Radix Gentianae, Hydrargyri Oxydum Rubrum, Herba Houttuyniae, Folium Perillae, Radix Asteris, Radix Et Rhizoma Rhei, Radix Sophorae Flavescentis, Radix Glycyrrhizae

Respirační infekce TCM 4

• Bufo siccus, synthetic Calculus Bovis, Rhizoma Coptidis, Rhizoma Cyperi, Realgar, Fructus Gleditsia, Radix Platycodonis, Radix Sophorae Tonkinensis, Radix Glycyrrhizae, Alumen, Rhizoma Zingiberis etc. of Guo formed " antasthmatic powder "

Respriační infekce dobytka TCM 5

• Gypsum, honeysuckle, indigowoad root, baical skullcap root, weeping forsythia, common anemarrhena rhizome, platycodon root and liquoric root.

• patent CN102579779B

A. herba-alba

• Most effective among tested plants with MIC 3.12 mg/mL against several pathogenic Mycoplasma species (Al-Momani et al., 2007).
• prr.hec.gov.pk/jspui/bitstream/123456789/8857/1/Kamal%20Shah%20Final%20Thesis%20To%20HEC.pdf
• Dohledat zda i na m.pneumonia

A. leiocarpus

• The MIC value for acetone extract of A. leiocarpus was 0.16 mg/ml.

https://pubmed.ncbi.nlm.nih.gov/18835146/

A. occidentale leaf extract

• A. occidentale leaf extract (10,000 µg/mL) against Mycoplasma spp., using the broth microdilution method.
• Antibiotic tylosin (1,280 µg/mL) was used as a positive control
• Acetone as a negative control.
• Authors obtained a significant result for the extract as an anti-mycoplasm product (MIC = 310 ug/mL).
• www.ncbi.nlm.nih.gov/pmc/articles/PMC7303264/

Aloe vera

• Methanol extract of leaf skins and flowers of Aloe vera
• Antioxidant properties, especially the leaf skin extract
• The leaf skin extract also exhibited antimycoplasmic properties
• Phenolic Constituents, Antioxidant and Preliminary Antimycoplasmic Activities of Leaf Skin and Flowers of Aloe vera (L.) Burm. f. (syn. A. barbadensis Mill.) from the Canary Islands (Spain)
• Leaf skin extracts were characterized by the abundance of
• Catechin,
• Sinapic acid
• Quercitrin

• The most prominent phenolic compounds of the flowers
• Gentisic acid,
• Epicatechin
• Quercitrin

• Antioxidant activity
• The leaf skin extract the most active fraction

• Leaf skin extract
• Active against the microbial strains
• www.mdpi.com/1420-3049/18/5/4942
• Dohledat, zda působí i na M.pneumoniae

Anogeissus leiocarpus (Combretaceae)

• Had good antimycoplasmal activity
• 3,4,3'-tri-O-methylflavellagic acid and its glucoside identified by CitationAdigun et al. (2000)
• Could be responsible for the good antimycoplasmal activities of this plant extract
• www.tandfonline.com/doi/full/10.3109/13880200903505633

Anogeissus leiocarpus

• (3,4,3´-tri-O-methylavellagic acid and its glucoside)
• Identied by Adigun et al. (2000)
• Could be responsible for the good antimycoplas-mal activities of this plant extract.
• www.researchgate.net/publication/46157498_Antimycoplasmal_activity_of_some_plant_species_from_northern_Nigeria_compared_to_the_currently_used_therapeutic_agent#pf3

Anti-atypical pneumonia decoction

Scutellaria root

• 0.5~10 weight parts,

Gardenia

• 0.5~10 weight parts,

Honeysuckle flower

• 0.5~10 weight parts,

Weeping forsythia

• 0.5~10 weight parts,

Dried rehmannia root

• 0.5~10 weight parts,

Gypsum

• 0.5~10 weight parts,

Flos chrysanthemi indici

• 0.5~10 weight parts,

Basket fem

• 0.5~10 weight parts,

Balloonflower root

• 0.5~10 weight parts,

Mint

• 0.5~10 weight parts,

Arctium fruit

• 0.5~10 weight parts,

Liquorice

• 0.5~10 weight parts

Užívání v podobě čaje

• Those medicinal materials were decocted with water to obtain the anti

  atypical pneumonia decoction.

• The anti-atypical pneumonia decoction of the invention has satisfactory effect for preventing and treating atypical pneumonia or suspected atypical pneumonia.
• Combination of Chinese medicine and Western medicine
• Recommended oral dose is 150 g per day
• Administered as 75 g twice per day
• Suitable for 2-4 year old children
• Recommended oral dose is 300 g per day
• Administered as 150 g twice per day
• Suitable for more than 4 year old
• Symptom elimination is considered as a standard of evaluation of therapeutic effectiveness.
• After 3 doses of the anti-atypical pneumonia decoction of the invention administrated orally
• 6 patients remove heat, stop coughing and become into eupnoea
• It takes an average five days to recuperate their health completely from the day of initial administration.
• 85% of patients have significant effect
• Other patients that were not treated by the anti-atypical pneumonia decoction of the invention
• It takes an average 29 days to recuperate their health
• It takes an average 24 days less than that of patients treated by the anti-atypical pneumonia decoction of the invention.
• All the facts indicate that the anti-atypical pneumonia decoction of the invention has significant effect for preventing and treating atypical pneumonia or suspect atypical pneumonia.
• patents.google.com/patent/US20040253328

Antibiotics

• Quinolones (ciprofloxacin, sparfloxacin, levofloxacin, ofloxacin, among others) as alternative treatment
• Macrolides (azithromycin, clarithromycin, erythromycin, among others)
• M. hominis strains are usually resistant
• Ureaplasmas are moderately susceptible to macrolides
• M. hominis and Ureaplasma urealyticum are generally more resistant to tetracyclines than other species
• M. hominis strains have been observed to be resistant to quinolones

• Mycoplasmal infections
• Intravenous antibiotic therapy for only a short period of time
• P.o. daily or pulsed treatment
• Every-other-day administration, at the maximum dose recommended for a particular antibiotic
• Due to the cyclic nature of mycoplasmal proliferation
• Some organizations recommend every-other-day antibiotic regimens

• Most chronic illness patients pathogenic mycoplasma infections
• Do not respond quickly to anti-microbial therapy
• Long-term therapy must be considered
• Acute infections involving Mycoplasma species, such as atypical pneumonia
• Treated with short periods of antibiotics
• This approach is generally ineffective for chronic infections
• A major concern during long-term antibiotic - resistance
• Activation-inactivation, influx and efflux of drugs and other

Jarisch-Herxheimer Reactions

• Temporary increases in the severity of signs and symptoms
• Fevers, chills,
• Muscle aches,
• Fatigue,
• Skin rashes,
• Pain and other related to cytokine release
• Strong J-H reactions may suggest the efficacy of treatment
• Usually revert within days
• Low-dose naltrexone and Cox-2 inhibitors zmírní

When to Stop Anti-Microbial Therapy

• Limited treatments in many chronic illnesses
• Usually do not resolve the illness or the infection
• Pathogenic mycoplasmas are slow-growing, cyclic, fastidious, intracellular
• Appear to be less sensitive to antibiotics in their usual in vivo microenvironments
• O less than a majority of patients with pathogenic mycoplasmas
• Infection can be suppressed by short-term antibiotic treatments of a few weeks
• This usually does not completely resolve the infection
• Slow relapse often occurs
• Routine anti-microbial treatments may not accurately predict the time required
• Most patients this has required prolonged treatments
• Resulted in very slow recoveries
• Often requiring a year or more of treatment

• Number of factors in vivo that protect pathogenic mycoplasmas from antimicrobial therapies
• Microbial biofilms
• May protect some mycoplasmas from antibiotics “recalcitrance”
• Intracellular locations
• Microenvironments of pathogenic mycoplasmas present additional membrane barriers
• Cells naturally try to detoxify chemicals that enter intracellular compartments
• “persister tolerant” microorganisms - metabolically inactive forms
• Dormancy of some microorganisms
• Host immune responses are essential in surveying survivor mycoplasmas
• Alteration or suppression of host responses
• Antibiotic therapy alone
• Has not been successful in suppressing mycoplasmal infections in many patients

Antivirotika a nukl. analogy

• 16 drugs showed varying inhibitory effects
• 7 showed strong inhibition of Mpn growth

6-thioguanine

• MIC to cause 90% of growth inhibition 0.20 ug ml-1
• The 6-thioguanine, but not other purine analogs, strongly inhibited HPRT
• Which may in part explain the observed growth inhibition

Trifluorothymidine, gemcitabine and dipyridamole

• MIC cca 2 ug ml-1
• Gemcitabine inhibited the uptake and metabolism of all nucleobases and thymidine.

6-thioguanine and dipyridamole

• Strongly inhibited the uptake and metabolism of hypoxanthine and guanine

Trifluorothymidine and 5-fluorodeoxyuridine

• Stimulated the uptake and incorporation of radiolabeled thymidine
• This stimulation was due to induction of thymidine kinase activity
• Good substrates and inhibitors for thymidine kinase from human and Mycoplasma sources.

Apigenin

• In order to limit mycoplasma pneumoniae infection,
• apigenin activates PPARg, enhances Uhrf1 mRNA expression, increases TNF-a DNA methylation of promoter,
• Reduces TNF-a mRNA expression.
• This decreases TNF-a autocrine activity
• Inhibits the necrotic apoptosis of alveolar macrophages
• Has important implications for the treatment of mycoplasma pneumonia.
• www.mdpi.com/1467-3045/46/4/181

Aromatherapy

• Anti-mycoplasmal activita
• Phenol, camphor, boras camphor, metalhavicol, verbenol and a-terpineol
• Cure is produced by distilling pine flotation oil in a vacuum at a certain temperature.

Artemisia herba-alba and Artemisia arborescens

• In vitro
• Methanolic extracts against 32 isolates of Mycoplasma species
• Mycoplasma mycoides subsp. mycoides LC (6),
• Mycoplasma capricolum subsp. capricolum (8)
• M. putrefaciens (18)
• All isolated from either nasal swabs or milk, from sheep and goats in different regions in Jordan
• All Mycoplasma species showed susceptibility with MIC ranges from 3.125–12.5 mg/ml:
• Artemisia herba-alba
• Artemisia arborescens

Allium sativum and Punica grantum (málo)

• Limited activity against some Mycoplasma isolates

Olea europea and Citrullus colocynthis (nic)

• Showed no in vitro activity against any of the Mycoplasma species tested
• link.springer.com/article/10.1007/s11250-007-9033-1
• Dohledat, zda efekt i na M. pneumoniae

Aspergillus oryzae Fermentation Extract

• Alleviates Inflammation in Mycoplasma pneumoniae Pneumonia
• Known as koji mold,
• Production of fermented foods in East Asia.
• Can produce enzymes and metabolites with various bioactivities
• A. oryzae fermentation extract (AOFE) ethanol extract

In vitro, AOFE

• Suppressed Mp growth and invasion into A549 lung epithelial cells
• AOFE treatment also suppressed Mp-stimulated production of TNF-a, IL-6 at mRNA and protein levels in murine MH-S alveolar macrophages

Mouse model of Mp pneumonia

• Pulmonary infiltration of neutrophils was significantly reduced in mice pre-treated orally with AOFE
• AOFE administration also suppressed the production of proinflammatory cytokines and chemokines in the lungs.
• Results show that AOFE has the potential to be developed into a preventive/therapeutic agent for Mp pneumonia.
• www.mdpi.com/1420-3049/28/3/1127

• Is used for the production of various enzymes
• Amylases, proteases, and glutaminases
• Produce a variety of bioactive metabolites
• Angiotensin I-converting enzyme inhibitor peptides
• Biotin,
• Bifidobacterium-stimulating peptide
• Beta-glucan,
• citric acid,
• Deferriferrichrysin,
• 14-dehydroergosterol,
• Ergothioneine,
• Ethyl-a-D-glucoside,
• Ferulic acid,
• Glycosylceramide,
• Kojic acid,
• Oligosaccharides,
• Polyamines,
• Pyroglutamyl leucine,
• Pyranonigrin A,
• Resistant proteins

• Kojic acid and its derivatives
• Variety of biological functions
• Antimicrobial
• Antioxidant
• Anti-inflammatory
• Wound-healing
• A. oryzae fermentation products have anti-inflammatory effects
• A. oryzae fermentation extract (AOFE) may attenuate Mp-induced pneumonia
• AOFE suppressed Mp-induced inflammation in alveolar macrophage and alleviated Mp pneumonia in mice

• Neutrophils contribute to lung injury, but not Mp clearance
• AOFE administration significantly reduced the infiltration of neutrophils into the lungs

ATB při těžších formách infekce

• Citlivé
• Tetracykliny
• Erytromycin
• Semisyntetické makrolidy
• azitromycin
• ATB tuto bakterii neusmrcují, pouze zastavují její množení
• Aby byla léčba antibiotiky účinná, je nutné jejich užívání po dobu 2–3 týdnů [1]

Výčet vhodných ATB

Děti

• Erythromycin [4]
• clarithromycin [4]
• Roxithromycin [4]
• Azithromycin [4]

Dospělí

• Doxycycline [4]
• Tetracycline [4]
• Quinolones [4]

ATB X bacterial rRNA in ribosomal complexes:

• Macrolides
• Capable of reducing hyperresponsiveness
• Protecting the epithelial lining from oxidative and structural damage [5]
• Bacteriostatic
• Erythromycin and clarithromycin
• Nejč. podávané v Japonsku [5]
• Inhibit bacterial protein synthesis by binding 23S rRNA [5]
• Reduce the longevity and intensity of M. pneumoniae infections [5]
• Rezistence k terapii souvisela s nucleotide mutations in the 23S rRNA gene [5]
• Tetracycline
• None of the M. pneumoniae specimens were resistant tetracyclines
• Ketolides
• Fluoroquinolone [5]
• None of the M. pneumoniae specimens were resistant to fluoroquinolones [5]

ATB dle Medscape

• Bacteriostatic
• Tetracycline and erythromycin - very effective [6]
• Second-generation tetracyclines (doxycycline) and macrolides - drugs of choice
• Macrolide resistance in several areas of the world
• If a patient does not respond appropriately to a macrolide, a fluoroquinolone should be added [6]
• Macrolides
• Erythromycin
• Staphylococcal and streptococcal infections
• Inhibiting bacterial growth by blocking dissociation of peptidyl tRNA from ribosomes and causing RNA-dependent protein synthesis to arrest [6]
• Azithromycin (Zithromax)
• Very effective against M pneumoniae
• Most common agent used to treat M pneumoniae [6]
• Clarithromycin (Biaxin, Biaxin XL)
• Reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms
• May inhibit RNA-dependent protein synthesis by stimulating the dissociation of peptidyl tRNA from ribosomes [6]
• Tetracyclines
• Doxycycline (Vibramycin, Vibra-Tabs)
• Susceptible bacterial infections of both gram-positive and gram-negative, Mycoplasma, Chlamydophilia, and Rickettsia organisms [6]
• Inhibits bacterial protein synthesis by binding with the 30S subunit and possibly the 50S ribosomal subunit [6]
• Fluoroquinolone
• Levofloxacin (Levaquin)
• Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription [6]
• Moxifloxacin (Avelox)
• Inhibits the A subunits of DNA gyrase [6]

ATB

• Azithromycin most frequently
• For 5 days (500 mg for the first dose, followed by 250 mg daily for 4 days)
• Doxycycline or fluoroquinolones
• Should be given 7 to 14 days of treatment
• Macrolide resistance
• Continues to emerge
• Routine antibiotic prophylaxis
• Not required for the exposed contacts except for those prone to serious mycoplasmal infection
• Sickle cell disease
• Antibody deficiency
• Doxycycline or macrolides are used
• www.ncbi.nlm.nih.gov/books/NBK430780/

ATB

• Mycoplasma bacteria do not have cell walls
• Traditional antibiotics like penicillin often don’t work
• Azithromycin or doxycycline may be prescribed

• Effective antimicrobials against Mycoplasma
• Tetracyclines
• Oxytetracycline, doxycycline and chlortetracycline for the treatment of animal and human diseases
• Macrolides
• Tylosin, erythromycin, tiamulin and clindamycin
• Aminoglycosides,
• Chloramphenicol
• Fluoroquinolones
• Act on nucleic acid to inhibit the synthesis of DNA and RNA

• (Bebear et al., 1998)

• Some Mycoplasma like M. pneumoniae
• Is susceptible to streptomycin (Taylor-Robinson and Bebear, 1997).

Azadirachta indica, Calotropis procera, Artemisia herba-alba

• Mycoplasma putrefaciens from sheep of different regions of Khyber Pakhtunkhwa, Pakistan
• Antimycoplasmal activity of methanolic extract

Artemisia herba-alba

• Prominent antimycoplasmal activity
• At 30 mg by producing maximum zone of inhibition (15.4±0.52 mm)
• Against all the tested isolates
• MICs values were 0.03±0.001 mg/mL
• Only about 30 species of Artemisia are investigated
• Artemisia is dwarf shrub, commonly grow in FATA and northern regions of Pakistan, Afghanistan
• Treatment of diabetes mellitus, liver diseases, skin infections, anthelmintic, antispasmodic and in cancer
• E terpenin, camphor, davonone, herbalbin, flavonoides, acetate and borneol
• From the leaves, flowers, seed, root and stem (Baser et al., 2002; Soković et al., 2010).

Calotropis procera

• With inhibition zones of 14±0.58
• MICs values were 0.3±0.04 mg/mL

Azadirachta indica

• With inhibition zones of 11±0.7 mm
• MICs values were 3.0±0.2 mg/mL

• Methanolic extract of all the three indigenous plants exhibited strong antimycoplasmal activity against M. putrefaciens
• Might be used successfully for the treatment of mycoplasmosis
• thejaps.org.pk/docs/v-27-05/19.pdf

Azithromycin

• Has a hormone-like anti-inflammatory effect
• Sufficient evidence to confirm this effect in patients with cystic fibrosis and diffuse pan bronchiolitis.
• In the RMPP group,
• Azithromycin was intravenously dripped for 2 courses
• Followed by oral sequential treatment

IVIG treatment is also used in MP extrapulmonary complications

• Encephalopathy or encephalitis, hemolytic anemia, etc.
• Myocardial damage and liver function damage in the RMPP group were evident and the difference between the two groups was statistically significant.

Liver-protecting and heart-protecting drugs

• For symptomatic treatment.

Fiberoptic bronchoscopy

• Showed congestion and edema of the bronchial mucosa at the lesion site,
• Adherence of mucous secretions,
• Partial bronchial insufficiency, tuberous protuberances of the wall mucosa, and a narrow opening of the lumen.
• For large consolidation and atelectasis cases, fiberoptic bronchoscopy
• Can go deep into the local area,
• Wash,
• Clean mucus plugs,
• Produce secretion drainage,
• Reduce obstructions.
• In this study, 20 cases of RMPP were examined and treated by fiberoptic bronchoscopy.

• Home / Vol 9, No 5 (September 30, 2020) / An analysis of 20 clinical cases of refractory mycoplasma pneumonia in children

B cells

• Are known to be involved in pulmonary Mp clearance [16–20]. Furthermore, patients with hypogammaglobulinemia are at greater risk for Mp pulmonary disease and/or extrapulmonary manifestations [21–25]. It is likely that carriage of Mp by these patients make them susceptible to the development of symptomatic Mp infection.

https://academic.oup.com/jid/article/217/2/298/4584507

Bacilotetrins C–E

• Anti-Mycoplasma Activity
• Cyclic Lipodepsipeptides
• From the Marine-Derived Bacillus subtilis
• Marine-derived Bacillus subtilis 109GGC020
• Produce secondary metabolites, including
• Macrolactins
• Gageomacrolactins
• Linear lipopeptides
• Gageotetrins A–C
• Gageopeptides A–D
• Gageostatins A–C
• Cyclic lipopeptides
• Gageopeptins A and B
• Bacilotetrins A and B
• Antibacterial and antifungal activities
• Linear lipopeptides
• Gageopeptides A–D and gageotetrin B
• Inhibitory effects on the wheat blast fungus Magnaporthe oryzae Triticum
• Potential of these compounds for agricultural antibiotics
• www.proquest.com/openview/3aa413c980b0ba49609e7f8397fb8274/1?pq-origsite=gscholar&cbl=2032365
• Dohledat, zda to platí i vůči M. pneumonia

Baicalin

• Relieves Mycoplasma pneumoniae infection-induced lung injury
• Through regulating microRNA-221 to inhibit the TLR4/NF-kB signaling pathway

Nimba Neem (Azadirachta indica)

• www.bylinybylin.cz/vegetalis/eshop/434-1-Neem-Azadirachta-indica
• www.ajurveda-brno.cz/ucebnice-ajurvedy/herbar-bylin/zederah-indicky-nimba-neem
• www.bioobchods.sk/prirodna-lekaren/ajurvedske-bylinne-kapsule-tablety/neem-bio-kapsule-detail

UBOS (Spondias mombin)

• rostlinyzperu.cz/sk/ubos/

Achiote (Bixa orellana)

• rostlinyzperu.cz/sk/achiote/

DRAČÍ KREV tinktura - Sangre de Drago (Croton Lechleri)

• rostlinyzperu.cz/sk/sangre-de-drago/
• www.bylinybylin.cz/vegetalis/eshop/60-1-Zdravotni-potize/184-2-Bakterie/5/2755-DRACI-KREV-tinktura-Sangre-de-Drago-50-ml

Vilcacora (Uncaria tomentosa)

• rostlinyzperu.cz/sk/vilcacora/

Juan de Alonso (Xantium spinosum)

• rostlinyzperu.cz/sk/juan-de-alonso/

Kozinec Blanitý (Astragalus membranaceus)

• www.bylinybylin.cz/vegetalis/eshop/60-1-Zdravotni-potize/184-2-Bakterie/5/3446-Astragalus-koren-mlety-Kozinec-Blanity-100g

Horká tekvička (Momordica charantiau)

• www.biomajak.sk/p/1519/karela-horka-tekvicka

Šalvia

Skorocel

Byliny na Mycoplasma hominis

• Nevíme, zda budou efektivní i u mycoplasma pneumoniae

• 30 clinical strains of M. hominis were isolated and identified from the clinical specimen
• Findings laid a foundation in treating M. hominis infection with Chinese herbs
• Susceptibilities of M. hominis to 19 herbs were determined by serial dilution methods in vitro

M. hominis was susceptible to:

Radix Isatidis

Radix Angelicae Dahuricae

Cortex Phellodendri

Radix et Rhizoma Rhei

Fructus Kochiae

Herba Houttuyniae

• www.worldscientific.com/doi/abs/10.1142/S0192415X05002862

Calotropis procera

• Antimicrobial action of the extract of C. procera could be attributed to 3-O-acetyl-calotropin
• Powerful bacteriolytic agent
• Present in the latex (Mueen-Ahmed et al., 2005)
• C. procera efect may be explained by the presence of
• Alkaloids,
• Tannins,
• Favonoids in the acetone extract of C. procera.
• Compounds in these classes show antibacterial activities (Silva et al., 1996; Cowan, 1999).
• Extract of Calotropis procera
• Was less cytotoxic
• Had good MIC
• Better MMC activities than the conventional antimycoplasmal drug tylosin
• Isolating the active compounds from C. procera and determining in vivo toxicicty and efficacy appear to be the logical next steps
• www.researchgate.net/publication/46157498_Antimycoplasmal_activity_of_some_plant_species_from_northern_Nigeria_compared_to_the_currently_used_therapeutic_agent#pf3

• Commonly known as “milk weed”
• Family Asclepiadaceae
• 280 genera and 2000 species
• Tropic and sub-tropic areas of Pakistan
• Ethanolic, methanolic and chloroform extracts good antibacterial properties
• Triterpinoids, alkaloids, resins, calotropin, anthocyanins and proteolytic enzymes in latex,
• flavonoids, tannins, saponins, mudarin, sterol and cardiac glycosides
• Terpenes, multiflorenol and cyclisadol (Nenaah, 2013)

Calotropis procera (Aiton) R.Br (Asclepiadaceae) extract

• Had the best antimycoplasmal effect
• MIC of 80 ug/mL
• Minimum mycoplasmacidal concentration (MMC) of 160 ug/mL
• Contained saponins, tannins, cardiac glycosides, alkaloids, and flavonoids
• Calotropis procera is a promising plant for an alternative antimycoplasmal agent
• Crude acetone extract had a higher mycoplasmacidal activity than the conventional drug tylosin in Nigeria.
• pubmed.ncbi.nlm.nih.gov/20819025/

Vernonia amygdalina Delile (Compositae) extract

• Was the most cytotoxic with median lethal concentration (LC(50)) of approximately 17 ug/mL
• pubmed.ncbi.nlm.nih.gov/20819025/

Anacardium occidentale L. (Anacardiaceae)

• Cytotoxic with an LC(50) of approximately 1919 ug/mL.
• pubmed.ncbi.nlm.nih.gov/20819025/

Calotropis procera

• Had good antimycoplasmal activity
• Had the best activities
• MIC of 80 ug/mL
• C. procera possessed the best MMC value of 160 ug/mL
• Better than drug tylosin with an MMC value of 320 ug/mL
• Could be attributed to 3-O-acetyl-calotropin
• Powerful bacteriolytic agent
• Present in the latex (CitationMueen-Ahmed et al., 2005)
• Presence of alkaloids, tannins, and flavonoids in the acetone extract of C. procera
• Show antibacterial activities (CitationSilva et al., 1996; CitationCowan, 1999).
• Extract of Calotropis procera had a better antimycoplasmal activity of 80 ug/mL and was less cytotoxic (LC50 = 0.204 mg/mL).
• www.tandfonline.com/doi/full/10.3109/13880200903505633

Cineol - eucalyptol

• Natural organic compound
• Found in essential oils of various plants
• Extensively studied for its pharmacological properties
• Anti-inflammatory, analgesic, and antimicrobial effects
• Potential benefits of cineol in poultry production

Antimicrobial properties

• Potent antimicrobial properties against a range of bacteria, fungi, and viruses
• Mycoplasma gallisepticum in chicken
• Salmonella enteritidis, Escherichia coli, and other pathogenic bacteria in vitro

Anti-inflammatory effects

• Cineol can help reduce inflammation in the respiratory tract of poultry birds
• Improve their overall health and reduce the risk of respiratory infections
• Reduced the production of pro-inflammatory cytokines in the lungs of chickens infected with avian influenza virus.
• Newcastle Disease (ND) and Infectious Bronchitis (IB)
• Viral diseases that can affect poultry birds
• Can help to improve the respiratory function of poultry birds
• Boosting the immune system

Improvement of feed efficiency

• Improving the digestion and absorption
• Feed intake and weight gain, resulting in improved feed conversion ratios with dose of 100-500 ml / per MT of feed.
• Cineol oil has a cooling effect on the body when applied topically or when birds inhale its vapors.
• www.vprintinfotech.com/effects-of-cineol-on-poultry-birds/

• Jedna měkká enterosolventní tobolka
• Cineolum 200 mg.
• Střední nasycené triacylglyceroly,
• Nekrystalizující sorbitol 70%, Želatina, Glycerol 85%, Ethylcelulosa, Roztok amoniaku 28%, Kyselina oleová, Natrium-alginát, Kyselina stearová, Kandelilový vosk.
• Registrovaný léčivý přípravek, výrobce M.C.M. Klosterfrau
• Dospělí a dospívající (od 12 let) užívají 3x denně 1 tobolku.
• Soledum 200 mg se polykají celé (bez kousání) a zapíjejí se větším množstvím nepříliš horké tekutiny (nejlépe sklenicí (200 ml) pitné vody), asi půl hodiny před pravidelným jídlem. Jestliže máte citlivý žaludek, doporučuje se užívat Soledum 100 mg během pravidelného jídla.

• Mp cineol je doplněk stravy
• Extrakt z rostlinných drog z Blahovičníku (Eucalyptus globulus)
• Děti ve věku 3-10 let 1 kapsli 3x denně.
• Děti nad 10 let a dospělí 2 kapsle 3x denně.
• Mp cineol snad obsahuje 100mg v 1 cps

• 1,8-cineol-treamtent
• Leads to significantly decreased levels of MUC gene expression after their LPS-dependent stimulation

Cinnamon bark oil, carvacrol and eugenol

• All showed valuable antimicrobial activity against in vitro Mycoplasma hominis
• Oil from the bark of Cinnamomum zeylanicum
• (MBC90 = 500 µg/mL) the most effective
• Carvacrol
• (MBC90 = 600 µg/mL)
• Eugenol
• (MBC90 = 1000 µg/mL) also possessed strong antimycoplasmal activity.
• Results indicate that cinnamon bark oil, carvacrol and eugenol
• Have strong antimycoplasmal activity
• Potential for use as antimicrobial agents in the treatment of mycoplasmal infections

• biomed.papers.upol.cz/artkey/bio-201402-0008_In_vitro_antimicrobial_activities_of_cinnamon_bark_oil_anethole_carvacrol_eugenol_and_guaiazulene_against_My.php Radek Slehaa,b, Petra Mosioa, Marketa Vydrzalovaa, Alexandra Jantovskaa, Vanda Bostikovab, Jaroslava Mazurovaa, Department of Biology and Biochemistry, Faculty of Chemical Technology, University of Pardubice, Pardubice, Czech Republic, Faculty of Military Health Sciences, University of Defence, Hradec Kralove

Citrus bergamia essential oil and its major components

• In vitro antimycoplasmal activity
• Limonene, linalyl acetate and linalool
• Forty-two strains of Mycoplasma hominis (including PG21), 2 strain of Mycoplasma fermentans (Pg18 and K7), 1 strain of Mycoplasma pneumoniae (strain m129)
• C. bergamia essential oil
• Inhibited mycoplasmas at concentrations from 0.5 to 1% (MIC value as % v/v).
• M. hominis showed MIC(50)
• 0.5% and MIC(90) values of 1%;
• M. pneumoniae
• MIC value of 0.5%
• M. fermentans strains
• MIC values of 1%.
• M. pneumoniae and M. hominis
• Same susceptibility to linalyl acetate
• MIC values of 0.015% (corresponding to MIC(50) and MIC(90) for M. hominis)
• M. fermentans strains
• Less susceptible with MIC values of 0.12%.
• Linalool
• Showed higher activity against M. pneumoniae and M. fermentans (MIC values of 0.015 and 0.06%, respectively)
• But was less active against M. hominis (MIC(50) and MIC(90) values of both 1%);
• Limonene
• Was active against M. pneumoniae (MIC value of 0.03%)
• But was less active against M. fermentans (MIC values of 1%) and M. hominis (both MIC(50) and MIC(90) values of ?4%).
• The results indicated that C. bergamia essential oil and its major components
• Had shown an interesting in vitro antimycoplasmal activity.

• Pio Maria Furneri 1, Luigi Mondello, Giuseppina Mandalari, Donatella Paolino, Paola Dugo, Adriana Garozzo, Giuseppe Bisignano, PMID: 22465092 DOI: 10.1016/j.ejmech.2012.03.005

Combretum molle (Combretaceae)

• Had good antimycoplasmal activity
• www.tandfonline.com/doi/full/10.3109/13880200903505633

Curcumin

• Anti-mycoplasma activity of Curcuma longa extracts and your isolated compound, the curcumin
• Curcuma longa (saffron)
• Rhizomes of C. longa were submitted to different processes of conservation
• Followed by maceration to obtain ethanolic and acetonic extracts
• Decoction to obtain aqueous extracts
• Extracts were analyzed to quantify curcumin
• Anti-mycoplasma activity of the extracts and curcumin were evaluated
• The best activity was observed in the ethanolic and acetonic extracts
• Had the higher curcumin content
• Rhizomes of C. longa were collected in Blumenau (SC, Brazil)

Konzervace

• Rhizomes (50 g) were submitted to different thermal processes to evaluate the best method of conservation of the main constituent of the plant, curcumin
• Three ethanolic extracts were prepared
• Process 1:
• Rhizomes were frozen at -18°C for six months
• Extracted with 96% ethanol (EFH)
• Process 2:
• Rhizomes were stored away from light for six months
• Extracted with 96% ethanol (ESL)
• Process 3:
• Rhizomes in natura extracted after collection with 96% ethanol (EIH)

Extrakce

• Extractive solvent for the curcuminoid compounds using samples (50 g)
• Oven-dried rhizomes at 60°C were extracted with 3 different solvents:
• 96% ethanol (EID),
• Acetone (KID)
• water (AID)
• Extraction procedure:
• To obtain ethanolic (EtOH 96%) and acetonic extracts
• Rhizomes were crushed in a turbolizer
• Macerated with shaking for 4 hours
• Filtration
• Concentrated on a rotary evaporator under reduced pressure to constant weight
• To obtain the aqueous extract
• Rhizomes were crushed,
• Macerated and extracted by decoction at 90°C for 10 minutes
• Mimicking the popular use in the form of tea.
• After filtration, the extracts were frozen at -18°C for 24 hours
• Lyophilized for 72 hours to constant weight

• www.researchgate.net/publication/326194317_Anti-mycoplasma_activity_of_Curcuma_longa_extracts_and_your_isolated_compound_the_curcumin

• 111 Revista Fitos. Rio de Janeiro. 2018; 12(2): 112-118 | e-ISSN: 2446-4775 | www.revistafitos.far.fiocruz.br

Daptomycin

• Lipopeptide antibiotic
• Rapidly bactericidal against Gram-positive bacteria
• Directly targets the cell membrane
• May rapidly kill mycoplasma organisms
• Gram-negative bacteria are intrinsically resistant to daptomycin
• Because they reportedly do not contain the target of daptomycin
• Porins in Gram-negative bacteria do not allow large molecules, including those of daptomycin, to pass through the outer membrane

Erythromycin thiocyanate

• 04/24/2013 CN103054891A Compound erythromycin thiocyanate composition for controlling poultry bacterial and mycoplasma infection and preparation method thereof

Eugenia brevistyla, Eugenia handroana, Eugenia catharinae and Eugenia stigmatosa

• 8 extracts and 18 fractions were screened
• Plants were rich in terpenes and phenolic compounds
• E. handroana (FAEF-EH) and E. brevistyla (FAEF-EB)
• Highest activity against Staphylococcus aureus
• (MIC) of 15.62 ug/ml

• FAEF-EH also presented the best activity with MIC of 62.5 µg/ml against Mycoplasma pneumonia M129.
• academicjournals.org/journal/JMPR/article-abstract/144530266319

Fluoroquinolones and ketolides

• Only ATB having mycoplasmicidal qualities
• www.researchgate.net/publication/226918048_Antimycoplasmal_Agents

Flurithromycin

• 14-membered macrolide drug,
• Similar to thatof erythromycin
• Against 41 strains of Mycoplasma spp. and 100 strains of Ureaplasma urealyticum
• All 28 strains of Mycoplasma hominis were uniformly resistant to both macrolides
• With MICs > 256mg/L,
• U. urealyticum
• Showed intermediate resistance with MIC50, s of 0.5 and 1 mg/Lfor erythromycin and flurithromycin,
• Ten strains of Mycoplasma pneumonia
• Were susceptible to ≤ 0.03 mg/L of both macrolides
• academic.oup.com/jac/article-abstract/35/1/161/851481

Fucoxanthin

• A Marine Carotenoid,
• Suppresses Mycoplasma pneumoniae-Triggered Inflammatory Cytokine Production
• Promotes Bacterial Clearance in a Murine Model
• Natural product of carotenoids,
• Widely recognized as a potential drug source obtained from marine algae
• Antioxidant, anti-inflammatory, and antimicrobial
• Attenuates LPS-induced acute lung injury
• Ameliorates the inflammatory responses
• Fx treatment significantly inhibited the production of proinflammatory cytokines IL-6, TNF-a, and IL-1b in peritoneal macrophages of mice after MP infection
• This may be the first study to report the protective role of Fx against M. pneumoniae infection, providing a potential therapeutic reagent for MP.
• www.hindawi.com/journals/ecam/2022/6238162/

• Fucoxanthin
• A Marine Carotenoid, Suppresses Mycoplasma pneumoniae-Triggered Inflammatory Cytokine Production
• And Promotes Bacterial Clearance in a Murine Model

Mice

• Concentrations of proinflammatory cytokines, including IL-6, TNF-a and IL-1b
• Significantly decreased by Fx treatment in the BAL samples of infected mice

In vitro study

• Fx treatment markedly suppressed the production cytokines in mouse peritoneal macrophages after M. pneumoniae infection

Fuyan Pill

• www.einpresswire.com/article/354942503/chlamydia-mycoplasma-or-ureaplasma-can-be-cured-by-purely-herbal-medicine-fuyan-pill-instead-of-disturbing-antibiotics
• Složení:
• patents.google.com/patent/CN101574459A/en

Radix bupleuri,

Tuckahoe,

Radix scutellariae,

Gardenia,

Atractylis ovata,

Yam,

Rhizoma atractylodis,

Angelica,

Peach kernel,

Safflower

Liquorice.

• Vyhodil som z toho "talcum", je to pomocná látka, ktorá v EÚ môže obsahovať chryzotil, teda karcinogénny biely azbest.

Geraniol

• Antitumor Activity of Monoterpenes from Essential Oils
• Geraniol relieves mycoplasma pneumonia infection-induced lung injury in mice
• Through the regulation of ERK/JNK and NF-ÎşB signaling pathways
• Antibacterial and Anti-Biofilm Activities of Essential Oil Compounds
• Against New Delhi Metallo-b-Lactamase-1-Producing Uropathogenic Klebsiella pneumoniae Strains
• Geraniol enhances inhibitory inputs to the paraventricular thalamic nucleus and induces sedation in mice
• Dose-dependent alteration of neurobehavioral activities by geraniol a component of essential oil: A study in rats
• cannakeys.com/geraniol-terpene-research/

• Geraniol treatment effectively reduced lung weight, NO level, and MPO activity in the pneumonia mice.
• The total cells and M. pneumoniae DNA load
• Were also decreased by the geraniol.
• The SOD activity and GSH level
• Were improved
• MDA was decreased by the geraniol treatment
• The IL-1, IL-6, IL-8, TNF-a, and TGF status
• Were appreciably depleted by the geraniol in the pneumonia mice
• Geraniol also suppressed the ERK1/2 and NF-kB expressions in the lung tissues.
• Histological findings also suggest the therapeutic roles of geraniol against pneumonia in mice.
• doi.org/10.1002/jbt.22984

Inhibice glycerophosphodiester phosphodiesterase enzyme

• protein database code1YDY
• Involved in glycerolipid metabolism
• Very crucial for the survival of the particular microbe
• journaljpri.com/index.php/JPRI/article/view/1345/2696

Green tea and black tea

• Has been used, and its microbicidal activity
• Demonstrated against M. pneumonia at a concentration of 0.2% (Chosa et al 1992)

A mini-review on antimycoplasma antibiotics; Oveas Rafiq Parraya*; Izhar Ul Haqa; Amatul Muheea; Muzaffar Shaheena; Mohammad Iqbal Yatooa; Sher-e-Kashmir University of Agricultural Sciences and Technology–Kashmir, Shalimar, Jammu and Kashmir 190 025, India.

Artemisia herba- alba + Artemisia arborescens

• Against mycoplasma infections
• In-vitro susceptibility of mycoplasma isolates to these plants (AlMomani et al 2007)

A mini-review on antimycoplasma antibiotics; Oveas Rafiq Parraya*; Izhar Ul Haqa; Amatul Muheea; Muzaffar Shaheena; Mohammad Iqbal Yatooa; Sher-e-Kashmir University of Agricultural Sciences and Technology–Kashmir, Shalimar, Jammu and Kashmir 190 025, India.

Elderberry

• Has shown activity against mycoplasma
• Inhibits the growth of Mycoplasma mycoides subspp. capri (Arjoon et al 2012)

A mini-review on antimycoplasma antibiotics; Oveas Rafiq Parraya*; Izhar Ul Haqa; Amatul Muheea; Muzaffar Shaheena; Mohammad Iqbal Yatooa; Sher-e-Kashmir University of Agricultural Sciences and Technology–Kashmir, Shalimar, Jammu and Kashmir 190 025, India.

Oregano leaves

• Has shown activity against mycoplasma
• Inhibits the growth of Mycoplasma mycoides subspp. capri (Arjoon et al 2012)

A mini-review on antimycoplasma antibiotics; Oveas Rafiq Parraya*; Izhar Ul Haqa; Amatul Muheea; Muzaffar Shaheena; Mohammad Iqbal Yatooa; Sher-e-Kashmir University of Agricultural Sciences and Technology–Kashmir, Shalimar, Jammu and Kashmir 190 025, India.

Goldenseal root extract

• Has shown activity against mycoplasma
• Inhibits the growth of Mycoplasma mycoides subspp. capri (Arjoon et al 2012)

A mini-review on antimycoplasma antibiotics; Oveas Rafiq Parraya*; Izhar Ul Haqa; Amatul Muheea; Muzaffar Shaheena; Mohammad Iqbal Yatooa; Sher-e-Kashmir University of Agricultural Sciences and Technology–Kashmir, Shalimar, Jammu and Kashmir 190 025, India.

Photoactivated porphyrins

Hematoporphyrin

• Potent cytotoxic activity against mycoplasma
• Its peroxidative and oxidative reactions independent of light

Hemin

• Exerts its cytotoxic effect on microbial cells (Malik et al 1990)

A mini-review on antimycoplasma antibiotics; Oveas Rafiq Parraya*; Izhar Ul Haqa; Amatul Muheea; Muzaffar Shaheena; Mohammad Iqbal Yatooa; Sher-e-Kashmir University of Agricultural Sciences and Technology–Kashmir, Shalimar, Jammu and Kashmir 190 025, India.

Guiera senegalensis (Combretaceae),

• Had good antimycoplasmal activity
• MIC values of 160 ug/mL
• www.tandfonline.com/doi/full/10.3109/13880200903505633

Herbal medicine compound preparation capable of treating children recurrent respiratory tract infection

• Invention relates to a herbal medicine compound preparation

Astragalus root

• 1 to 20 % of

Ledebouriella root

• 1 to 15 % of

Black plum

• 1 to 15 % of

Malaytea scurfpea

• 1 to 15 % of

Baikal skullcap root

• 1 to 20 % of

Bighead atractylodes rhizome

• 1 to 15 % of

Chinese thorowax

• 1 to 15 % of

• Adding 4 to 12 folds of water into the ingredients according to the mixture ratio
• Decocting the ingredients,
• Filtering out medicinal juice;
• Then adding 4 to 12 folds of the water again,
• Decocting the ingredients,
• Filtering out medicinal juice;
• Putting the decoction liquor together, standing, leaching medicinal liquor,
• Concentrating the medicinal liquor
• Cooling down the medicinal liquor naturally;
• Adding alcohol, carrying out precipitation while agitating, leaching a supernatant,
• Concentrating the supernatant into thick extractum to be prepared into various formulations
• Preparation is applied to the treatment of the children recurrent respiratory tract infection
• Has high curative effect,
• no toxic and side effects,
• Low price
• The preparation method is simple and environmental friendly.
• The preparation is a prepared Chinese medicinal formulation completely meeting Chinese pharmacopoeia.
• patents.google.com/patent/CN101543543B/en

Hydroxytyrosol

In vitro antimycoplasmal activity on Twenty strains of Mycoplasma hominis, three strains of Mycoplasma fermentans, and one strain of Mycoplasma pneumoniae

• For M. pneumoniae,
• MICs 0.5 microg/ml
• M. hominis,
• MICs 0.03 microg/ml (for 90% of the strains tested)
• M. fermentans
• MICs 0.25 microg/ml
• Olive oil belong to three different classes:
• Simple phenols (hy-droxytyrosol and tyrosol),
• Secoiridoids (oleuropein, the agly-cone of ligstroside, and their respective decarboxylated dialde-hyde derivatives),
• Lignans [1-acetoxypinoresinol andpinoresinol]
• Oleuropein
• The bitter molecule presentin large amounts in olives
• Hydroxytyrosol
• Which derives from oleuropein by acidic or enzymatic hydrolysis and is responsible for the high stability of olive oil

Dipartimento di ScienzeMicrobiologiche e Scienze Ginecologiche, Universita` di Catania, ViaAndrone 81, 95124 Catania, Italy. Phone: 39 095316038. Fax: 39095312798. E-mail: furneri@unict.it

• Since oleuropein has also been shown to inhibit mycoplasmas
• Olive polyphenols (including hydroxytyrosol)
• Generally claimed to be free of toxicity against mammalian cells
• Hydroxytyrosol might be considered as a promising antimicrobial agent for treating human infections
• www.fabriceleu.com/wp-content/uploads/2018/05/HYDROXYTYROSOL_mycoplasma.pdf

Slabý roztok hypemanganu

• Sedací koupel v teplém světle růžovém - fialovém roztoku na 10-20 minut
• Desinfikuje - max. účinek hlavně v začátku infekce než ta vleze hlouběji do močových cest

Interleukin-12 (IL-12) inhibice

• M. pneumoniae pneumonia in IL-12 (p35) knockout (KO) mice

8-week-old wild-type BALB/c mice and 8-week-old IL-12 (p35) KO BALB/c mice

• Inoculated once intranasally with 107 CFU of M. pneumoniae.
• Mice were evaluated at days 2, 4, and 7 after inoculation
• IL-12 (p35) KO mice infected with M.pneumoniae were found to have significantly lower BAL M. pneumoniae concentrations
• Lack of IL-12 in experimental M. pneumoniae pneumonia was associated
• With less severe pulmonary disease
• More rapid microbiologic and histologic resolution
• europepmc.org/backend/ptpmcrender.fcgi?accid=PMC1828434&blobtype=pdf

Supplements to rebuild and support the immune system

The INACTINE PEN110 technology

• Is a pathogen reduction process that is in Phase 3 clinical studies.
• The present study investigated the ability of this process to eradicate mycoplasmas in human blood.
• No viable microorganisms were detected in PEN110-treated units after 24 hours of incubation.
• Sham controls showed no changes to mycoplasma titers during the incubation.
• In 4°C controls, minor decrease of mycoplasma titers was observed during the storage.
• doi.org/10.1111/j.1537-2995.2004.00647.x

Inactivation of the mycoplasmas

0.5% Triton X-100

0.5% sodium deoxycholate

Cetyltrimethylammonium bromide

• At concentrations of ?0.08% was also able to rapidly inactivate (in less than 30 min) all mycoplasmas tested

Beta-propiolactone

• 0.1% for 1 to 24 h
• Had a marked mycoplasmacidal effect

Formaldehyde.

• 0.0125 to 0.025% - nedostatečná koncentrace
• Increasing the concentration of formaldehyde to 0.1 to 0.2% improved the mycoplasmacidal effect

Diet and Integrative Treatments of Mycoplasmal Infections

• Only marginally effective in achieving stable patient recoveries
• Patients have been inappropriately diagnosed with psychological problems due to their partial or incomplete recoveries
• Persistence of psychiatric symptoms
• Should not be considered the basis of an inability to recover using conventional anti-microbial treatments
• Addition of proper diet and integrative medical management along with conventional anti-microbial treatments
• Should be considered, instead of assuming that patients have psychological reasons for not recovering

Avoidance of high-sugar, yeast-containing and processed foods

• Is essential
• Decreasing or eliminating simple or refined sugars, alcohol, acid-forming, high-yeast- and trans-fat-containing foods
• Increasing intake of cruciferous vegetables, fish, soluble fiber foods and whole grains
• Are useful for maintaining healthy digestive and immune systems

Doplnit spotř. živiny mykoplasmou (?)

• Part of any mycoplasma treatment programs
• To je s otázkou, kdy, aby to zase neposílilo víc infekci než člověka
• Lépe až po úspěšném zahájení antibiotické terapie a utlumení metabolismu mykoplasmat
• Vitamin B complex, vitamins A, C and E, coenzyme Q-10 (CoQ10) L-carnitine, Alpha-lipoic acid, and glycerolphospholipids
• Zinc, magnesium chromium and selenium
• Beta-carotene, bioflavoids, and amino acids, such as L-cyseine, L-tyrosine and L-glutamine
• Fatigue RevivaTM

Mitochondrial support

• L-carnitine, ALA, CoQ10, membrane glycerolphospholipids
• ALA

Přerůstání plísní a kvasinek po ATB

• Redukce curků
• Anti-fungal foods and supplements can be useful
• Grapefruit extract,
• Olive leaf extract,
• Garlic extract,
• berberine,
• Oregano oil
• Curcumine
• Antimykotika v nouzi při obtížích
• Nystatin and diflucan
• Probiotika, prebitoika
• “Mediterranean” diets

Modifying Mycoplasma Microenvironments

pH

• Extracellularly
• Antacids
• Diet that is not acidic (???)
• Intracellular
• vitamin C
• Lemon-lime water
• Lemon-olive oil drink
• Fruits and vegetables that raise intracellular pH to more alkaline states (???)

Biofilm-disruption and inhibition

• Useful during anti-microbial treatments
• Nattokinase,
• Lumbrokinase,
• Serrapeptase
• monolaurin or glycerol monolaurate from lauric acid found in coconut and other oils
• Stevia, extracted from the leaves of Stevia rebaudiana plant
• Also been shown to be a natural biofilm disrupter
• Extracts of pomegranate,
• Maple syrup,
• Cinnamon
• Peppermint
• To inhibit biofilms

Reduction of inflammation

• curcumin,
• Broccoli seed extracts,
• Cordyceps,
• Chinese skullcap,
• Isatis
• Houttuynia extracts
• Smilix,
• Redroot,
• Boneset
• Stephania root,
• Andrographis,
• Polygonum (a form of resveratrol)
• Baicalein
• Wagonin,
• Acacia catechu

Anitoxidanty

• Beta-cryptoxanthin
• In fruits and vegetables
• Hydrogenized water
• Reduces oxidative stress and cytotoxic oxygen radicals

Podpora imunity

• To vidím jako velmi důležité
• Mykoplazma uniknou imunitní reakci, antibiotika samy o sobě mohou imunitu potlačovat a protizánětlivé léky a doplňky taky
• Kromě toho makrolidy a tetracykliny mykoplasmu nezabíjí, jen dočasně uspí
• Definitivní vyléčení totálně stojí na akci našeho imunitního systému
• Pokud nás mykoplasma dostala a zlomila až tak, že antibiotika byla nutná, byla imunita slabá a je potřeba ji podpořit

Dlouhodobé netoxické byliny a doplňky k další inhibici mykoplazmat

• Ne vždy je možné užívat ATB dlouhodobě - dostupnost, NÚ, rizika aj.

Cardamom Derived Phytochemicals

• Against Mycoplasma pneumonia Causing Bronchitis
• Cardamom extract is a traditional medicine that is used to treat Bronchitis
• “High positive values of -CDOCKER energy and -CDOCKER interaction energy” suggested that
• Acetic acid
• Can effectively deactivate glycerophosphodiester phospho diesterase enzyme
• Thereby interrupting the life cycle of the organism
• journaljpri.com/index.php/JPRI/article/view/1345

• Cardamom belongs to family Zingiberaceae.
• Cardamom contains phytochemicals
• “4-terpineol, acetic acid,
• Cinnamaldehyde,
• Eucalyptol,
• 3,7-dimethyl,
• Santolina alcohol” etc.
• These phytochemicals might act against bronchitis.
• journaljpri.com/index.php/JPRI/article/view/1345/2696

Klarytromycinem přelečene astma

• Among asthmatics, a subgroup of patients with MP infections
• Showed improved lung function when treated with 6 weeks of Clarithromycin
• Macrolides have anti-inflammatory effects that may play a significant independent role toward improving lung function

Kortikoidy

• Some high-dose steroid therapies have shown to reverse neurological effects in children with complicated infections [5]

Lipopeptide in B. mojavensis

• Has antiviral, antitumoral, antifungal, and antimycoplasmatic properties. Based on the research of Hmidet et al. (2017),

Magainin 2 - derived new molecules

• Rationally designed antimicrobial peptides on Mycoplasma pneumoniae
• Antimicrobial
• Haemolytic effects of a natural AMP, magainin 2 (Mag2)
• Isolated from the skin of Xenopus laevis (the African clawed frog)
• Four types of synthesised Mag2 derivatives
• Three types of rationally designed AMPs on gram-positive and gram-negative bacteria
• Effect of AMPs on Mycoplasma pneumoniae four strains
• 17base-Ac6c, 17base-Hybrid, and Block, had anti-M. pneumoniae (anti-Mp) effect at 8–30 uM
• NK2A, did not have any such effect
• Membrane disruption activities of AMPs were measured by propidium iodide (PI) uptake assays
• Suggested the direct interaction of AMPs to the cell membrane
• NK2A strong interaction to cell membrane, indicating unknown anti-Mp determinant factors related to the peptide sequences
• Sequence of AMPs were important for killing of M. pneumoniae
• journals.plos.org/plosone/article?id=10.1371/journal.pone.0261893

• Magainin 2
• Antimicrobial peptide (AMP)
• Isolated from the skin of the African clawed frog Xenopus laevis.
• Antibiotic activity against numerous gram-negative and gram-positive bacteria.
• Active against protozoa.
• Cytotoxicity effects by preferential interactions with anionic phospholipids abundant in bacterial membranes
• Bactericidal effects
• Morphological changes in Escherichia coli regarding early apoptosis
• Expression of a bacterial protein with affinity for the caspase substrate
• Effects the expression of RecA as a caspase-like protein
• Kill bacteria by permeabilizing the cell membranes
• Without exhibiting significant toxicity against mammalian cells
• 10 ug /mL magainin 2 to Paramecium caudatum, a protozoan, in pond water
• Osmotic swelling of the cell and a subsequent cell burst,
• Permeabilizes bacterial and mammalian membranes in significantly different ways.
• Forms pores with a diameter of about 2.8 nm (less than 6.6 nm) in B. megaterium,
• Translocates into the cytosol.
• Significantly perturbes the membrane of CHO-K1 cells,
• Permitting the entry of a large molecule (larger than 23 nm) into the cytosol,
• Accompanied by membrane budding and lipid flip-flop,
• Mainly accumulating in mitochondria and nuclei
• www.medchemexpress.com/Magainin_2.html

Lauric acid

• High lauric acid oils
• Preferably 20% lauric acid as acylated fatty acids in the triglyceride
• More preferably at least about 40%
• Most preferably at least about 50%
• Such natural oils include, but are not limited to
• Coconut oil,
• Rapeseed oil,
• Palm kernel oil, murumuru tallow, and tucum oil.
• Canola oil, rapeseed oil or soybean oil, derived from plants that have been genetically modified to have a high lauric acid content
• May be employed
• Laurical® from Calgene Inc., Davis, California
• High lauric acid oils
• Ingested by an animal, the digestive enzymes release lauric acid and monolaurin
• Lauric acid and monolaurin are then either absorbed through the intestinal wall into the blood stream
• Can exert an anti-microbial effect systemically within the animal or within the digestive tract.
• High lauric acid oil
• Part of the feed or as a feed supplement
• Lauric acid will preferably comprise about 0.5% - 10% of the animal feed
• 2% to about 7%
• Most preferably about 3% - 5% of the feed
• High lauric acid oils which contain approximately 50% lauric acid as acylated fatty acids
• Such as coconut oil or palm kernel oil
• Feed will typically comprise about 1% - 20% high lauric acid oil
• More preferably about 6% - 10%
• High lauric acid oil
• To the feed of poultry
• Promote the health of the chickens
• Prevent bacterial contamination of poultry products
• Including contamination by Salmonella typhimurium

Melittin

• včelího jedu protein

Gramicidin D

Peptidy inhibující M. pulmonis

• Gramicidin D (0.0015 µM)
• Globomycin (0.8 µM)
• Melittin and gramicidin S (3.12 µM)
• Alamethicin (6.25 µM)
• Iturin A
• Surfactin (25 µM)
• Dermaseptin B5, polymyxin B, and polymyxin E (>100 µM)

• Lack of susceptibility to polymyxin B
• Shared by other mycoplasmas, including Mycoplasma gallisepticum and Mycoplasma genitalium

https://journals.asm.org/doi/full/10.1128/aac.49.10.4154-4165.2005

Mentofin

• Application on the clearance of Mycoplasma gallisepticum (MG) from naturally infected layer chickens’ trachea
• Mentofin, a natural product
• 10% eucalyptus oil,
• 10% menthol,
• 33% liquid builders,
• 47% saponins
• Safely used in broiler and layer chicken production
• www.cabidigitallibrary.org/doi/pdf/10.5555/20153016336

• Preventing respiratory problems,
• Increasing performance and strengthening the immune system

• MG-infected bird numbers had significantly and continuously decreased in the Mentofin group,
• Recommend the use of rPCR in MG detection in the flocks
• Mentofin clearly had an effect on MG clearance from the tracheal epithelium
• www.cabidigitallibrary.org/doi/pdf/10.5555/20153016336

• Mentofin at 0.5% concentration
• Inactivated the lentogenic strain of ND virus within 15 minutes at interaction temperature of 37 deg
• At 0.01%
• Inactivated Proteus vulgarus in nutrient broth
• 0.0001% concentration
• Inactivated the same bacteria in urease broth
• www.researchgate.net/publication/289292744_Antimicrobial_activity_of_mentofin_and_its_effect_on_antibody_response_of_broilers_to_Newcastle_disease_virus_vaccine

Micacocidin

• Derivatives with activity against Mycoplasma pneumoniae
• Promising natural product for the treatment of Mycoplasma pneumoniae infections
• Fatty acid-AMP ligase (FAAL) activates the starter unit hexanoic acid as acyl-adenylate
• Forwards it to an iteratively acting polyketide synthase
• Biochemical analysis of the FAAL revealed an extended substrate tolerance
• Modification of a micacocidin residue that is barely accessible via semisynthesis
• Total of six new analogues were generated
• By precursor-directed biosynthesis in this study and profiled against M. pneumoniae

https://pubmed.ncbi.nlm.nih.gov/24202877/

• Metal-containing novel heterocyclic antibiotics
• Micacocidin A (1), B (2), and C (3)
• Isolated from the culture filtrate of Pseudomonas sp. No. 57-250
• Micacocidin A
• Octahedral Zn2+ complex
• Micacocidin B (Cu2+ complex)
• C (Fe3+ complex)

https://pubmed.ncbi.nlm.nih.gov/9589069/

Micacocidin

• Type I Polyketide Synthase Initiates the Biosynthesis of the Antimycoplasma Agent Micacocidin
• Micacocidin is a thiazoline-containing natural product
• From the bacterium Ralstonia solanacearum
• Shows significant activity against Mycoplasma pneumoniae
• Pentylphenol moiety
• Distinguishes micacocidin from the structurally related siderophore yersiniabactin
• Contributes to the potent antimycoplasma effects
• Biosynthesis of the pentylphenol moiety
• Final conversion into 6-pentylsalicylic acid
• Depends on a ketoreductase domain within the iPKS
• Demonstrated by heterologous expression in E. coli
• New antibiotic
• Strong inhibitory effects in the nanomolar range against several Mycoplasma species
• Including M. pneumoniae (Kobayashi et al., 1998)
• In vivo efficacy after oral administration in chicken that had been infected with M. gallisepticum
• Thiazoline-containing natural product micacocidin
• Structurally closely related to the siderophore yersiniabactin (Drechsel et al., 1995)
• Might also be involved in iron acquisition of the producing bacterium Ralstonia solanacearum (Kreutzer et al., 2011).
• Antimycoplasma activity of micacocidin is not linked to its metal-chelating properties
• Iron(III)-loaded complex exhibits the same level of activity as the free ligand (Kobayashi et al., 2000)
• Blockage of the metal coordination sites by chemical modification
• Does not affect the growth-inhibitory effects against Mycoplasma species (Ino et al., 2001).

• Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes
• Account for the assembly of micacocidin (Kreutzer et al., 2011)
• Highly reminiscent of the yersiniabactin assembly line (Gehring et al., 1998b; Miller et al., 2002)
• Some minor deviations were found to be sufficient to translate into chemical diversity

• Both yersiniabactin and micacocidin
• phenolic moiety in their structures
• Corresponding residue is further decorated with a pentyl side chain in miacocidin
• The phenolic moiety in yersiniabactin derives from salicylic acid
• Incorporated by the stand-alone AMP-dependent ligase YbtE (Gehring et al., 1998a)
• Micacocidin pathway
• Adenylation domain MicC-A1 represents the enzymatic counterpart of YbtE (Stachelhaus et al., 1999; May et al., 2002)
• Feeding study in R. solanacearum with [1-13C]hexanoic acid
• Led to an increased incorporation of label at C-3 of micacocidin
• www.sciencedirect.com/science/article/pii/S107455211300166X

Moxifloxacin

• Mycoplasma genitalium
• Sexually transmissible non-gonococcal urethritis (NGU)
• Cervicitis,
• Rectal infections in men who have sex with men
• In men with symptomatic urethritis varies from 15% to 25%
• Increasing rates of treatment failures with azithromycin
• Widespread use of azithromycin 1 g single-dose treatment for NGU
• Is thought to trigger the selection of 23S rRNA gene mutations
• Causing macrolide resistance
• Extended azithromycin 1.5 g regimen (500 mg on day 1, followed by 250 mg on days 2–5)
• Was more effective than a single dose in one study
• In case of treatment failure after a single dose azithromycin
• An extended 5-day treatment is not effective
• Moxifloxacin
• 100% effective after azithromycin treatment failure
• Few reports of moxifloxacin treatment failure have been published
• Clinical trials have shown a low clinical cure rate using tetracyclines
• Without treatment, it is not known how long M. genitalium infection persists.
• www.medicaljournals.se/acta/content/html/10.2340/00015555-2055

Morusin

• Cortex Mori (CM), the root bark of Morus alba L.,
• Is a commonly used drug in Chinese medicine
• Compounds isolated from CM including
• Polyhydroxylated alkaloids,
• flavonoids,
• Stilbenoids
• Morusin is one of the major active substances isolated from CM
• Anti-tumor, anti-inflammation, and anti-fungal activities
• Morusin
• Reported to induce apoptosis
• Inhibit NF-?B signaling in human cervical, liver, and colorectal carcinoma cells
• May exhibit efficacy on MPP via inhibiting NF-?B signaling
• Alleviates mycoplasma pneumonia
• Via the inhibition of Wnt/beta-catenin and NF-kB signaling

Cunrong Chen,1,* Jingjing Wang,1,* Jianfei Chen,2,* Lili Zhou,1 Hui Wang,1 Junnian Chen,1 Zhihui Xu,1 Shuaijun Zhu,1 Wei Liu,1 Ranjie Yu,1 Junli Lu,1 Haoteng Luo,1 Min Chen,2 and Weiwen Chen3

• Morusin traditionally used for the treatment of Mycoplasma pneumoniae pneumonia (MPP)

Mycoplasma pneumonia model in BALB/c mouse

• Morusin was isolated from the chloroform extract of M. alba root bark
• Mice were given nasal drops containing 100 ul M.
• Morusin (20 mg/kg), and morusin (50 mg/kg)
• Gavage once at 10 am each day for 7 consecutive days
• DNA amount of M. pneumoniae decreased by
• 24.6 ± 3.14% in low morusin (20 mg/kg)
• 47.6 ± 6.78% in high morusin (50 mg/kg) groups
• Morusin treatment led to decreased levels of pro-inflammatory cytokines
• (IL)-6, IL-1beta, tnf a
• Increased anti-inflammatory IL-10 in mice lung tissue
• Morusin treatment inhibited the activation of Wnt/beta-catenin and NF-?B pathways in mice lung tissue
• Morusin relieves mycoplasma pneumonia
• Via the inhibition of the activation of Wnt/beta-catenin and NF-?B pathways
• Is a potential natural agent for the treatment of mycoplasma pneumonia.
• Treatment with azithromycin and morusin significantly alleviated inflammatory response in M. pneumoniae-infected mice.
• www.ncbi.nlm.nih.gov/pmc/articles/PMC6616039/

Mycoplasma-eliminating lab agents

• Myco-1 & 2
• Tiamulin and minocycline
• Myco-3
• Ciprofloxacin
• Myco-4
• Including any type of mycoplasma, acholeplasma, spiroplasma and entomoplasma
• Very low cytotoxicity
• Low resistance risk due to an initial biophysical mode of action

• PanReac AppliChem

• nl.vwr.com/cms/mycoplasma_detection_and_elimination

Airway Epithelial NF-kB Activation

• Promotes Mycoplasma pneumoniae Clearance in Mice
• We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1) serves as a novel host defense protein
• Is up-regulated upon Mp infection
• Through NF-?B activation in cultured human and mouse primary airway epithelial cells
• In vivo airway epithelial NF-?B activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

• Published: December 28, 2012 https://doi.org/10.1371/journal.pone.0052969

• Aktivace NF-kB může být při příliš silném zánětu příliš destruktivní, ale v začátku nemoci a nebo na konci k dokončení clearance to bude asi nezbytné

Natto

• Zdroj bacillus subtilis

Natto

• "Léčí i astma bronchiale"
• Obsahuje bacillus subtilis
• Narozdíl od probiotk s bacillus subtillis za 1500 kč a více, stojí natto jen 27-35 kč a je zaručeně živé. Jen bude trochu výzva to do sebe pravidelně soukat.

Neem

• LEAF EXTRACTS OF AZADIRACHTA INDICA (NEEM) AGAINST MYCOPLASMA PUTREFACIENS
• www.researchgate.net/publication/337334172_ANTIBACTERIAL_ACTIVITY_OF_LEAF_EXTRACTS_OF_AZADIRACHTA_INDICA_NEEM_AGAINST_MYCOPLASMA_PUTREFACIENS
• Dohledat, zda i vůči M.pneumoniae

Occimum gratissimum (Lamiaceae)

• Had good antimycoplasmal activity
• MIC values of 160 ug/mL
• www.tandfonline.com/doi/full/10.3109/13880200903505633

Ofloxacin

• Ofloxacin (DL-8280; (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- pipera-zinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid)
• Showed a broader spectrum and a greater potency of antimycoplasmal activity
• Than did pipemidic acid, norfloxacin, tetracyclines, and lincomycin,
• But was inferior to erythromycin
• Mycoplasmacidal potency against clinical isolates of Mycoplasma pneumoniae
• Was also greater than that of other quinolones and tetracyclines.
• journals.asm.org/doi/10.1128/aac.23.3.509

O. europea

• Ethanol extract of O. europea

Oleuropein

• Strong antimicrobial activity against both Gram-negative and Gram-positive bacteria,
• As well as Mycoplasma species
• phenolic structures similar to those of oleuropein
• Seem to have antibacterial activities through damaging the bacterial membrane and/or disrupting cell peptidoglycans
• brieflands.com/articles/jjm-56370

• The activity of oleuropein, a phenolic glycoside contained in olive oil
• Oleuropein inhibited mycoplasmas at concentrations from 20 to 320 mg/l:
• M. pneumoniae
• MICs 160 mg/l
• M. pirum,
• MICs 320 mg/l
• M. hominis
• MICs 20 mg/l
• M. fermentans
• MICs 20 mg/l
• www.researchgate.net/publication/11075217_In_vitro_antimycoplasmal_activity_of_oleuropein

Olive leaf extract, Neem, and uva ursi

Pinocembrin

• Pinocembrin—An Isolated Flavonoid from
• Honey and Propolis
• Anti-allergic potential in in vitro
• Pinocembrin Relieves Mycoplasma pneumoniae Infection
• Induced Pneumonia in Mice Through the Inhibition of Oxidative Stress and Inflammatory Response
• In rhizomes of fingerroot (Boesenbergia pandurata)
• Antimicrobial, antioxidant, and anti-inflammatory
• cdnsciencepub.com/doi/abs/10.1139/apnm-2015-0108

Pinocembrin chalcone (2',4',6'-Trihydroxychalcone)

• Is an antibacterial compound from Helichrysum Trilineatum.
• Pinocembrin chalcone can prevent gastric ulcers in rats.
• www.medchemexpress.com/pinocembrin-chalcone.html

Plaquenil (hydroxychloroquine)

• Anti-malarial drug
• Used to alkalize intracellular compartments
• Improve antimicrobial entry and cytotoxic effects

Semisynthetic derivatives of pleuromutilin

• Such as tiamulin, valnemulin, and retapamulin
• Used as drugs to treat mycoplasma infections and bacterial pathogens that affect livestock

Na horečku

• Aspirin
• Not to children ! [3]
• Nonsteroidal anti-inflammatory drugs
• Ibuprofen
• Naproxen
• Acetaminophen [3]

Antitusika

• Mohou zhoršit odkašlávání sputa [3]

Dostatek tekutin

Odpočinek

Kyslík

• Dušnost při hospitalizaci

Mírnění symptomů

• Prednisolone [4]
• Methylprednisone [4]

Imunopodpora

• I.v. IgG [4]

Primin

• Antimycoplasmal metabolite from Eugenia hiemalis
• Eugenia hiemalis extracts in CH2Cl2 and methanol was performed
• Mycoplasma capricolum subsp. capricolum, M. genitalium and M. pneumoniae FH [3], and MLA broth for M. hominis
• Dichloromethanic extracts of leaves (DEL) and flower buds (DEF)
• Were the most active
• Extracts of stems (DES and MES)
• Were less active

Benzoquinone primin

• Active compound that was present in both extracts
• MIC ranged from 2.60 - 6.94 ug/mL
• www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0035-1565570

Propolis

Brazilian and Venezuelan propolis

• From stingless bees, Melipona quadrifasciata, Melipona compresssipes, Tetragonisca angustula, and Nannotrigona sp.
• High antibacterial activity (Dos Santos et al., 2017b)
• Hydroalcoholic extract of propolis from Melipona quadrifasciata
• High antibacterial activity against S. aureus and P. aeruginosa
• Significant antimollicute s activity against Mycoplasma pneumoniae (Hochhein et al., 2020, Dos Santos et al., 2017b)

Geopropolis from Heterotrigona itama

• Antibacterial activity against Gram-positive
• Bacillus subtilis and Staphylococcus aureus
• Gram-negative bacteria
• Escherichia coli and Pseudomonas aeruginosa (Abdullah et al., 2019)

Geopropolis from Melipona mondury

• Bacteriostatic and bactericidal activity against
• Pseudomonas aeruginosa,
• Staphylococcus aureus,
• Methicillin resistant Staphylococcus aureus (Dos Santos et al., 2017c).

Geopropolis from Melipona quadrifasciata quadrifasciata

• Effective against S. aureus and methicillin-resistant S. aureus (Torres et al., 2018)

Propolis from stingless bees Tetragonisca fiebrigi

• Antimicrobial activity against gram-positive and gram-negative bacteria and fungi (Campos et al., 2015).

• Propolis acted more efficaciously against Gram-positive than Gram-negative bacteria

• Gram-positive bacteria
• Cell wall, with predominant share of peptidoglycan
• Allows hydrophobic molecules to penetrate the cells
• Act on wall as well as cell membrane and within the cytoplasm

• Gram-negative bacteria
• The cell wall of is more complex
• Less peptidoglycan
• With outer membrane composed of double layer of phospholipids
• Linked with inner membrane by lipopolysaccharides (Ristivojević et al., 2016)
• Can produce a wide range of hydrolytic enzymes
• Gram-negative may be more resistant to active constituents of propolis (Ristivojević et al., 2016)

• Antiviral activity of propolis
• Can be attributed to the cell lysis
• Disruption of the cytoplasmic membrane of virus
• Leakage of cellular components and eventually cell death (Górniak et al., 2019, Tagousop et al., 2018, Coelho et al., 2015, 2018).

• Propolis has different antibacterial mechanisms
• Inhibition of cell division,
• Collapsing microbial cytoplasm cell membranes
• Inhibition of bacterial motility,
• Different bacterial enzymes activity (Okińczyca et al., 2020)
• Bacteriolysis
• protein synthesis inhibition (AlAni et al., 2018, Aboody and Mickymaray, 2020, Górniak et al., 2019, Tagousop et al., 2018)

• Some studies demonstrated antifungical activity of propolis against Candida genus
• This propolis sample did not exhibited antifungical activity this fungus.
• www.biorxiv.org/content/10.1101/2021.07.01.450350v3.full

Landova ústní voda ke kloktání

Propolis

• Poor solubility
• Low oral bioavailability

Propolisina®

• Developed to overcome these limitations

Retrospective, open-label, controlled study of Streptococcus pyogenes-negative children

• With a diagnosis of acute otitis media or pharyngitis
• Propolis supplement for 72 hours
• Lessens the severity of AOM and viral pharyngitis
• Reduces the use of antipyretics and anti-inflammatory drugs
• Decreases the rate of evolution to tracheitis, bronchitis, and rhinosinusitis
• Propolis could be used as a safe add-on therapy in case of AOM and/or viral pharyngitis.

Anti-Inflammatory Treatments

• Children with severe M. pneumoniae infections
• Corticosteroid treatment was temporally associated with clinical and radiographic improvements
• Was considered important in reducing patient morbidity

Tetracyclines and macrolides

• Immunomodulatory effects in patients
• May have some advantage by reducing the inflammation associated with pathogenic mycoplasma infections.

Pseudomonic acids

• The antimycoplasmal activities
• Pseudomonic acids isolated from Pseudomonas fluorescens NCIB 10586
• Enhanced antimycoplasmal activity is reported for a number of monic acid A esters
• And the most potent derivative, m-nitrobenzyl monate A,
• Is a 100-fold more active against Mycoplasma hyopneumoniae than pseudomonic acid A.
• pubmed.ncbi.nlm.nih.gov/3133344/

Psidium guajava

• Extract at different concentration
• Able to inhibit the growth of S. aureus, Pasteruella multocida and Mycoplasma gallisepticum
• scholar.cu.edu.eg/sites/default/files/sher/files/antimicrobial_effect_of_different_herbal_plant_extracts_against_different_9.pdf
• Dohledat, zda i m.pneumonia

Pyridone-carboxylic acid or its salt

• As an active component
• Pyridonecarboxylic acid of formula (R is H, halogen or 1-5 alkyl) or its salt
• Antimycoplasmatic agent having low toxicity,
• Exhibiting antimycoplasmatic action to human and animal
• Effective in preventing or eliminating the mycoplasma infection of cultured animal or vegetable cell

Qingfei Tongluo formular (QT)

• Homemade agent for the MPP treatment
• Developed by pediatrics of Shanghai Longhua hospital
• Has better clinical curative effect

Cortex mori from Morus alba L. (9 g),

Cortex lycii Lycium chinense Mill. (9 g)

Peach kernel from Prunus persica L. (9 g)

Aidicha from Ardisia japonica (Thumb.)

Blume (9 g),

Lumbricus from Pheretimaas pergilum (E Perrier) (9 g),

Almond from Amygdalus communis Vas (9 g),

Perillaseed from Perilla frutescens L. Britt. (9 g)

Semen lepidii from Heleocharis dulcis (Burm. f.) Trin. (9 g)

Liquorice from Glycyrrhiza uralensis Fisch (3 g)

The aqueous extract of mixed 9 Chinese medicinal materials

• Kukoamine A (1),
• Bergenin (2),
• Mulberroside A (3),
• Isorhamnetin-3-O-b-D-glucoside (4),
• Amygdalin (5),
• Liquiritin (6),
• Kaempferol-7-O-b-D-glucopyranoside (7),
• Rosmarinic acid (8),
• Licoricesaponin G2 (9),
• Glycyrrhizinic acid (10)

Previous studies

• Clinical cure rate was 94.67% by QT combining with azithromycin treatment

BALB/c mouse model of MP infection

• AZM and QT effectively reduced the pulmonary interstitial inflammation.
• QT played better role in inflammation reduction than AZM
• Combination of QT and AZM provided the best.

https://www.longdom.org/open-access/qingfei-tongluo-formula-attenuated-pulmonary-inflammation-and-embolism-in-mycoplasma-pneumonia-mice-98158.html

The most refractory cases

• Plasma exchange + immunosuppressive drugs
• IVIG + plasma exchange remains a good option

Sigma Aldrich lab

Fungin™ - Antifungal Reagent

Primocin®

InvivoGen

• Contamination of cell culture is a major concern for research laboratories as well as biotechnological industries.
• Working with contaminated cells can lead to disastrous results, unreliable experiments, lost time, and wasted resources.
• Mycoplasma, bacteria, or fungi, can be avoided and eliminated using the right antibiotic formulation.
• Prevention reagents
• Elimination reagents

Prevention of cell culture contamination

Normocin:

• Complete protection against mycoplasma, bacteria, and fungi;
• Designed for routine addition to cultured cell lines

Primocin®:

• Complete protection against mycoplasma, bacteria, and fungi;
• Routine addition to primary cells

Fungin™:

• Antimycotic solution for protection against different forms of fungi (yeasts, hyphae, and molds);
• Designed for routine addition to cell cultures.
• At high concentrations for contamination removal (see section below).

Plasmocin® prophylactic:

• Protection against broad-spectrum mycoplasma and related wall-less bacteria;
• Designed for routine addition to cultured cell lines and primary cells
• www.invivogen.com/cell-culture-contamination?gclid=CjwKCAjw26KxBhBDEiwAu6KXt5Udh4wE8qu6MwjgEJdW2tQrbww4Q6Lg-RawFEjxBXh9EnesHSbmyRoCPR0QAvD_BwE

Elimination

Normocure™:

• Multidrug-resistant bacteria removal agent

Fungin™:

• Antimycotic solution for removal of different forms of fungi (yeasts, hyphae, and molds). Note: Fungin™ can be used at low concentrations to prevent contamination (see section above).

Plasmocure®:

• A second-line anti-mycoplasma reagent, recommended for the elimination of mycoplasma that appear to be resistant to Plasmocin®.

Solanum aculeastrum

• CH2Cl2/MeOH extracts from the berries of S. aculeastrum yielded
• New b-sitosterol derivative
• Six known ones including
• Lupeol
• Undecyl alcohol = moderate antimyc.act.
• Lauryl alcohol
• Myristic acid
• Nervonic acid
• Glycosidic steroid alalkaloid;
• (25R)-3β-{O-α-L-rhamnopyranosyl-(1→2)-O-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranosyloxy-22α-N-spirosol-5-ene (7) from the MeOH extracts = moderate antimyc.act.

Piliostigma thonningii

• Extracts interesting antimycoplasmal activities

--A new furandiglycoside,

• (2,5-D-diglucopyranosyloxy-furan) from theCH2Cl2/MeOH extract of stem bark of P. thonningii
• www.readcube.com/articles/10.3389/fphar.2017.00920

Surface protein 170-kDa P1 and the 30-kDa P30 protein - inhibice

• Function as adhesins

Surfactins and iturins

• Cyclic lipoheptapeptides of Bacillales.
• Heptapeptide compounds
• Surfactins and iturins produced by numerous B. subtilis and B. amyloliquefaciens strains
• Antimicrobial, antiviral and antimycoplasmatic
• Medical and biotechnological applications
• www.bashanfoundation.org/contributions/Borriss-R/7.%202018.-Borris-CBC.pdf

Bacillus subtilis (B. subtilis)

• Probiotic ("good" bacteria) found naturally in the human gut
• In fermented foods
• Nato
• Sometimes added to fermented foods like yogurt and also found in dietary supplements.
• People use B. subtilis for diarrhea from antibiotics. It is also used for athletic performance, eczema, constipation, indigestion, gas, irritable bowel syndrome (IBS), and many other conditions

• Gram-positive, aerobic bacterium
• Rod-shaped and catalase-positive.
• In soil and the gastrointestinal tract of ruminants and humans.
• The best studied Gram-positive bacterium
• Study of bacterial chromosome replication and cell differentiation.
• As hay bacillus, grass bacillus or Bacillus globigii.
• Often used as a probiotic preparation in the treatment or prevention of intestinal disorders
• Produce antibiotics, as a fungicide
• Part of the same family as Bacillus anthracis (anthrax).
• When stressed, B. subtilis transforms itself into a spore
• Tolerate extreme environmental conditions.
• Holds the record for surviving in space for the longest duration, 6 years on a NASA satellite.
• B. subtilis is generally considered non-pathogenic
• Implicated in food poisoning caused by poor quality bakery products
• Rapid onset and with acute vomiting, commonly follow by diarrhoea.
• Spores can survive the heat applied during cooking.
• Used in the Quality Control of media for Microbiological Quality testing.
• Compliance with Ph Eur 9.0 2.6.12, USP 40 <61> & JP XVII 4.05
• Common source of environmental contamination in the laboratory
• Ubiquitous nature of the microorganism in the environment.
• Safer substitute for other pathogenic varieties of Bacillus
• To determine the likely effects on Bacillus species and/or spore-forming microorganisms in general.
• Optimum growth temperature in the range of 30-39°C.
• Certain strains of subtilis can be used in biological indicators
• Effectiveness of low temperature steam sterilisation processes
• Confirm the information on the manufacturer’s certificate (ISO 11138).

https://wickhammicro.co.uk/knowledge-and-education/bacillus-subtilis

TCM směs na prevenci a terapii mykoplasmy penumonia u prasat

• Parts by weight of each raw medicinal material are:

• Rhizoma Polygonati Odorati 33 weight portion?
• Rhizoma Polygonati Odorati: another name Rhizoma Polygonati Odorati, beautiful ginseng, tail ginseng, bell are as dish, little shaft of a writing brush dish, Herba Hedyotis cantonensis root, Kao Shanzhu.This product is the dry rhizome of liliaceous plant Rhizoma Polygonati Odorati.Autumn excavates, and removes fibrous root, cleans, and shines to softness, repeatedly rub, dry in the sun to without hard-core, dry;

• Folium Mori 25 weight portion?
• Folium Mori: this product is the dried leaves of moraceae plants Mulberry.Gather after first frost, remove impurity, dry.

• Herba nepenthis 14 weight portion
• Herba nepenthis: another name zhuzailong, monkey cage, the monkey field of razor clam, danshuitong, gongzaiping.The herb of Nepenthaceae nepenthes plant Herba nepenthis.

• Radix Asparagi 38 weight portion
• Radix Asparagi: another name is big when door root, Radix Asparagi.Tuber for liliaceous plant Radix Asparagi.Autumn, winter excavate, but better with the person's of adopting quality in winter.Digging out afterwash earth, remove fibrous root, separate by size, entering to boil in boiling water or steam when easily peeling off to crust is degree.Pulling out in immersion clear water, remove crust while hot, clean, low baking temperature is dried after drying or smoking with sulfur again.

• Pericarpium Metaplexis 9 weight portion?
• Another name sky is by shell, trailing plants pod.Shell for trailing plants section plant trailing plants.Gather autumn mature fruit, strip shell and dry.

• Fructus Trichosanthis 18 weight portion
• Another name fruit is naked, king Bodhisattva, building, ground, pool smelting huge, damp, Wang Bai, sky melon, melon certain herbaceous plants with big flowers, pool aunt, Fructus Cucumidis sativi, sky dumpling made of glutinous rice flour, Fructus Kaki melon, wild Fructus Momordicae charantiae, shut out melon, big tripe melon, medicine melon, duck dung melon.Fruit for cucurbitaceous plant Fructus Trichosanthis.The Frost's Descent, peel surface began with white lead and for, time faint yellow, gathering to fruit maturation in the Beginning of Winter.Even fruit stem is cut, and fruit stem is knitted bunchiness, first piles up 2~3 days within doors, then is hung on shady and cool ventilation place and dries (about 2 months);Then cut off fruit stem, wrap up one by one with soft paper, to keep color and luster.Prevent from wounding and break, otherwise easy to be infested mouldy.

• Folium Eriobotryae 33 weight portion
• Folium Eriobotryae: another name Lu's Fructus Citri tangerinae.This product is the dried leaves of rosaceous plant Folium Eriobotryae.The whole year all can gather, shine to seven, most probably dry time, be bundled into wisp, then dry

• Flos Paulowniae 8 weight portion
• Steep the flower of ketone for goatweed Paulownia or hair.Bitter in the mouth;

• Rhizoma Marantae arundinaceae 28 weight portion
• Another name knot powder, BULBUS LILII.Marantaceae Rhizoma Marantae arundinaceae, is used as medicine with tuber.

• Semen Ginkgo 4 weight portion
• Another name Semen Ginkgo core.This product is the dry mature seed of Ginkgoaceae plant Ginkgo biloba (maidenhair tree, Gong Sunshu).Gather during seed maturity in autumn, remove meat episperm, clean, after slightly steaming or slightly boil, dry.

• Semen Lepidii (Semen Descurainiae) 39 weight portion
• Dry mature seed of crucifer Lepidium sativum L. or descurainia sophia (l.) webb ex prantl.The former practises title " lepidii,semen ", and the latter practises title " Semen Descurainiae ".Tap plant during fruit maturation in summer, dry, rub seed, remove impurity.

• The Radix Stemonae 7 weight portion
• Another name Radix Stemonae, Herba delphinii grandiflori, noisy louse medicine, medicine louse medicine.This product is the dried root of Stemonaceae plant Radix Stemonae, Radix stemonae japonicae or radix stemonae tuberosae.Spring, season in autumn two excavate, and remove fibrous root, clean, and put and slightly scald in boiling water or steam to without the white heart, taking out, dry.

• Fructus Perillae 33 weight portion
• Another name Fructus Perillae, FRUCTUS PERILLAE.This product is the dry mature fruit of labiate Folium Perillae.Gather during fruit maturation in autumn, remove impurity, dry.

• Radix Asteris 24 weight portion
• Another name Radix Asteris, short braid, clamping plate dish, donkey ear dish, soft Radix Asteris.This product is the dry root and rhizome of feverfew Radix Asteris.Spring, season in autumn two excavate, and remove the rhizome (practise and claim " parent root ") and silt that there are joint, weave into pigtail and dry, or directly dry.

• Cortex Mori 11 weight portion
• Another name Radix Mori skin.This product is the dry root bark of moraceae plants Mulberry.Fall last years of a century in autumn and excavate root before the secondary spring germinates, scrape off yellowish-brown rough bark, longitudinally cut open, strip root bark, dry.

• Herba Arthraxonis Hispidi 13 weight portion
• Another name Dendrocalamopsis oldhami(Munro)Keng f., horse Auricled Hedyotis Herb, horse ear grass, Central Asia Herba Arthraxonis Hispidi.Grass family Herba Arthraxonis Hispidi, with root, all herbal medicine.Hardship, flat.

• Herba Chlamydoboeae Sinensis 19 weight portion
• Call hick-skinned, stone food, China by calyx lettuce tongue.Gesneriaceae is by calyx lettuce carex width calyx lettuce tongue, with all herbal medicine.

• Abies nephrolepis 13 weight portion
• Another name black bear Chinese cabbage.Rhizome for aroid abies nephrolepis.

• Radix Glycyrrhizae 22 weight portion
• This product is the dry root of glycyrrhizic legume, Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L..Spring, season in autumn two excavate, and remove fibrous root, dry.

• Herba pronephrii triphylli 14 weight portion
• Call three marks, Tectaria subtriphlla (Hook. Et Arn.).Herb for Thelypteridaceae plant three plumage crescent Herba pteridii latiusculi.

• Radix Isatidis 32 weight portion
• Another name great Lan root, Radix Clerodenri Cyrtophylli.This product is the dry root of cruciferae isatis.Autumn excavates, and removes silt, dries

• Radix Sophorae Viciifoliae 15 weight portion
• Another name spends thorn, bitter tattooing in vain.Root for leguminous plant Radix Sophorae Viciifoliae.Summer gathers

• Fructus Forsythiae 26 weight portion
• Another name Fructus Forsythiae, Hemerocallis citrina Baroni bar, yellow chain barriness, Huang Qidan, green grass or young crops stick up, fall to sticking up.This product is the dry fruit of Oleaceae plants Fructus Forsythiae.

• Pericarpium Citri Reticulatae 30 weight portion
• Another name Pericarpium Citri tangerinae.This product is the dry mature skin of rutaceae orange and variety thereof.Medical material is divided into " Pericarpium Citri Reticulatae " and " Pericarpium citri reticuatae chachiensis ".Harvesting ripe fruit, strips peel, dries or cold drying

• Cor Cervi grass 8 weight portions
• Another name Balanophora dioica R Br ex Royle, see root life, slope basis, Herba seu Fructus Luzulae Multiflorae, bloom in Lu, ten thousand star bacterium, rattan woods, Adeps Sus domestica medicine, Hao Zhihua, soil, red bacterium, milk bacterium.Herb for the thick fringe Balaenoptera borealis Lesson of Balanophoraceae plant

• Lentinus Edodes 12 weight portion
• Another name Lentinus Edodes, conjunction gill fungus, platform gill fungus, platform bacterium, the frightened gill fungus of thunder, Dai Sha, stone gill fungus, vertebra gill fungus, fragrant letter, Flammulina velutipes, Flos Chrysanthemi mushroom, fragrant stricture of vagina.Sporophore for Bai Mo section fungus Lentinus Edodes

• Fructus Rosae Davuricae 8 weight portion
• Another name Fructus Rosae.Fruit for rosaceous plant Rosa bella.Fruit is taken when by maturation, dries at once, removes calyx, or fresh fruit is cut in half after dry, removes pit, then row is dry.

CN105770650A China

RND injekce formula

Artemisia annua,

Gardenia jasminoides

Lonicera japonica

• Inhibit bacterial and viral replication
• Effective in treating respiratory diseases
• Pneumonia and acute upper respiratory tract infection
• Significantly alleviate elderly patients with acute lung injuries,
• Improve the results
• RDN + cefoperazone sodium and sulbactam sodium
• Effective and safe in COPD and pulmonary infection
• RDN + azithromycin
• For the treatment of mycoplasma pneumonia and asthma in children.
• 84 pediatric patients with mycoplasma pneumoniae and asthma 2017- 2018
• e-century.us/files/ijcem/12/12/ijcem0101256.pdf

TCM smes na Mycoplasma pneumonia

• By weight,
• 9 parts of rhus chinensis mill,
• Fructus rhois chinensis , slave's salt of betraing, salt Fructus Armeniacae Mume, wood Radix Aconiti Lateralis Preparata, Fructus rhois chinensis Fructus Schisandrae Chinensis, false, oil salt fruit, ursolic acid Fructus Persicae, red-leaf peach, red salt fruit, salt tart fruit, hydrochloric acid are white?
• Fruit of Anacardiaceae plant Fructus rhois chinensis?Gather and store: be real when October gathers maturely, using fresh herb or dry?

• 15 parts of involute spikemoss herb,
• Herba Selaginellae Involventis [another name] Radix Stephaniae Sinicae (Radix Stephaniae Dielsianae), Herba Selaginellae Involventis, gold almond, Shi Yangcao, Rana nigromaculata pawl, flower lung gold, Poria Herba pteridii latiusculi, fly upward Herba pteridii latiusculi, bark rot Serpentis, fan Herba Selaginellae, stone Herba Selaginellae, Herba Stenolomatis Chusani, cypress in thousand, peafowl hair, Herba Selaginellae Moellendorfii, red Herba Pteridis Multifidae, chicken glue splits, phoenix tail, not Dendrobium denneanum Kerr., wall limit cypress, cake flowers and plants, flower eyebrow glue, Cacumen Platycladi (Cacumen Biotae) grass, spire Rhizoma Seu Herba Pteridis Dactylinae, ground Cacumen Platycladi, Dens Tigris bone, tiger hair grass, Herba Saniculae lamelligerae, pine and cypress grass, little Bai, Herba pteridis vittatae, mountain Cupressus funebris, the Yellow River mother-in-law grass, wall cypress, red Herba pteridii latiusculi son grass, dry Herba pteridii latiusculi base, gold shoulder pole, Herba monochasmatis, Membrana Follicularis ovi, volume muscle grass?
• Spikemoss plant Herba Selaginellae Involventis?Gather and store: the whole year all can gather, drying or using fresh herb?

• 12 parts of lonicera caerulea,
• Black bear food, Canis familiaris L. milk?[source] medical material Ji Yuan: locate the fruit of plant Lonicera caerulea for Radix Ophiopogonis?Gather and store: gathering after 8-9 month fruit maturation, dry?

• 10 parts of thunbergia fragrans,
• Thunbergia fragrans Roxb. [another name] ferrum passes through rattan, crow mouth?[source] medical material Ji Yuan: for the stem and leaf of acanthaceous plant Thunbergia fragrans Roxb.?Gather and store: the whole year all can gather, using fresh herb or dry?

• 9 parts of pyrolusite,
• Apios fortunei Maxim, dry son, baldhead, iron ore?[source] medical material Ji Yuan: for the Ore of oxide-based mineral pyrolusite?Gather and store: adopt after, pick clean assorted stone

• 6 parts of adenophora remotiflora,
• Sweet Radix Platycodonis, soil Radix Platycodonis, RADIX ADENOPHORAE, Mei Can, come into leaves Radix Adenophorae (Radix Glehniae)?[source] medical material Ji Yuan: for the root of Campanulaceae shepherd's purse, slender lobule shepherd's purse?Gather and store: spring excavates, removing stem and leaf, cleaning, dry

• 18 parts of parish's ironweed
• Disperse greatly [another name] Semen Sojae Preparatum leaf, Caulis et folium clerodendri bungei Radix Polygalae?[source] medical material Ji Yuan: for the root of Burma, feverfew Yunnan Herba Vernonia esculenta?Gather and store: the whole year all can excavate, using fresh herb, or clean section is dried

• 1.5 parts of benzoin.
• The clumsy shellfish Luo Xiang of Benzoinum [another name]?[source] medical material Ji Yuan: for the resin of Styracaceae plant Benzoinum and Styrax tonkinensis?Gather and store: the stalwartness growing more than 10 years becomes tree in age, cutting swollen in summer, season in autumn two?

• 1: Fructus rhois chinensis 9 grams, Herba Selaginellae Involventis 15 grams, Lonicera caerulea 12 grams, Thunbergia fragrans Roxb. 10 grams, pyrolusitum 9 grams, shepherd's purse 6 grams, disperse 18 grams, Benzoinum 1.5 grams greatly;Add 8 times amount water, decoct 1.5 hours, filter;Filtering residue adds 6 times amount water, decocts 1 hour, filters;Merging filtrate, is concentrated into 120 grams, must meet the decoct of one day consumption of adult normal?

For treating mycoplasma pneumonia?Oral, every bu Morning Afternoon Evening is taken for three times?

• 2: Fructus rhois chinensis 9 grams, Herba Selaginellae Involventis 15 grams, Lonicera caerulea 12 grams, Thunbergia fragrans Roxb. 10 grams, pyrolusitum 9 grams, shepherd's purse 6 grams, disperse 18 grams, Benzoinum 1.5 grams greatly;Add 10 times amount water, decoct 2 hours, filter;Filtering residue adds 8 times amount water, decocts 1.5 hours, filters;Merging filtrate, concentration, dry, packaging, the powder of one day consumption of adult normal must be met?

For treating mycoplasma pneumonia?Oral, every bu Morning Afternoon Evening is taken for three times?

• 3: Fructus rhois chinensis 9 grams, Herba Selaginellae Involventis 15 grams, Lonicera caerulea 12 grams, Thunbergia fragrans Roxb. 10 grams, pyrolusitum 9 grams, shepherd's purse 6 grams, disperse 18 grams, Benzoinum 1.5 grams greatly;Add 6 times amount water, decoct 3 times, decoct 1 hour every time, merge decoction liquor, concentration, dry, load capsule shells, the capsule of one day consumption of adult normal must be met?

Patent CN105687287A, China Google patents

TCM na M. pneumonia

• Herba Lobeliae Sessilifoliae 3 ~ 5 parts, 3 parts,
• Herba Caryopteridis Terniflorae 10 ~ 20 parts, 12 parts
• Fructus Aurantii 15 ~ 35 parts, 16 parts
• Fructus Arctii 12 ~ 22 parts, 22 parts
• Radix Platycodonis 11 ~ 31 parts, 30 parts
• Radix et Rhizoma Thalictri 15 ~ 45 parts, 42 parts
• Herba Houttuyniae 14 ~ 34 parts, 33 parts, 15 parts,??
• Radix Glycyrrhizae 10 ~ 20 parts,, 34 parts ??
• Herba Ardisiae Japonicae 12 ~ 36 parts; 34, 15 parts ??
• Rhizoma Zingiberis Recens 10 ~ 20 parts,
• Fructus Elaeagni 12 ~ 38 parts, 35 parts
• Magnetitum 10 ~ 20 parts, 14 parts
• Herba Boschniakiae Rossicae 11 ~ 32 parts, 30 parts
• Succus Bambusae 10 ~ 30 parts, 20 parts
• Semen Plantaginis 15 ~ 35 parts, 35 parts
• Semen Sinapis Albae 10 ~ 20 parts, 12 parts
• Halberd Ye Wawei 12 ~ 32 parts, 28 parts
• Fructus Perillae 10 ~ 20 parts, 15 parts
• Lignum Aquilariae Resinatum 14 ~ 28 parts, 20 parts
• Cortex Mori 15 ~ 35 parts, 35 parts
• Fructus Rubi 10 ~ 22 parts, 16 parts
• Fructus chebulae immaturus 15 ~ 30 parts, 20 parts
• Semen Lepidii (Semen Descurainiae) 10 ~ 40 parts, 30 parts
• Fructus Alpiniae Oxyphyllae 10 ~ 20 parts, 13 parts
• Herba Thlaspis 10 ~ 35 parts, 32 parts
• Radix Crepidis Ligneae 10 ~ 22 parts 22 parts
• Dominoes Herba pteridii latiusculi 10 ~ 30 parts.26 parts.

• Pericarpium Metaplexis 13 ~ 26 parts,
• Herba Kalimeridis 11 ~ 21 parts,
• The Radix Stemonae 3 ~ 4 parts, 14 ~ 28 parts, ??
• Polished rod fine jade and Concretio Silicea Bambusae 10 ~ 40 parts.

Granulát

• Get Herba Lobeliae Sessilifoliae 30g, Herba Caryopteridis Terniflorae 120g, Fructus Aurantii 160g, Fructus Arctii 220g, Radix Platycodonis 300g, Radix et Rhizoma Thalictri 420g, Herba Houttuyniae 330g, Radix Glycyrrhizae 150g, Herba Ardisiae Japonicae 340g, Rhizoma Zingiberis Recens 150g, Fructus Elaeagni 350g, Magnetitum 140g, Herba Boschniakiae Rossicae 300g, Succus Bambusae 200g, Semen Plantaginis 350g, Semen Sinapis Albae 120g, halberd Ye Wawei 280g, Fructus Perillae 150g, Lignum Aquilariae Resinatum 200g, Cortex Mori 350g, Fructus Rubi 160g, Fructus chebulae immaturus 200g, Semen Lepidii (Semen Descurainiae) 300g, Fructus Alpiniae Oxyphyllae 130g, Herba Thlaspis 320g, Radix Crepidis Ligneae 220g and dominoes Herba pteridii latiusculi 260g,

• Granules in Treating group (děti v klinické studii s M. pn.): use the embodiment of the present invention 1 to prepare granule, every day 3 times, once a bag, every bag of 6g every 7 days is 1 course for the treatment of;

Kapsle

• Herba Lobeliae Sessilifoliae 40g, Herba Caryopteridis Terniflorae 160g, Fructus Aurantii 320g, Fructus Arctii 220g, Radix Platycodonis 140g, Radix et Rhizoma Thalictri 420g, Herba Houttuyniae 330g, Radix Glycyrrhizae 150g, Herba Ardisiae Japonicae 280g, Rhizoma Zingiberis Recens 170g, Fructus Elaeagni 350g, Magnetitum 130g, Herba Boschniakiae Rossicae 240g, Succus Bambusae 180g, Semen Plantaginis 260g, Semen Sinapis Albae 150g, halberd Ye Wawei 300g, Fructus Perillae 140g, Lignum Aquilariae Resinatum 230g, Cortex Mori 320g, Fructus Rubi 200g, Fructus chebulae immaturus 300g, Semen Lepidii (Semen Descurainiae) 400g, Fructus Alpiniae Oxyphyllae 160g, Herba Thlaspis 330g, Radix Crepidis Ligneae 170g and dominoes Herba pteridii latiusculi 270g,

Capsule treatment group (děti v klinické studii s M. pn.): take the embodiment of the present invention 2 prepare capsule, every day 3 times, one time 1, within every 7 days, be a course for the treatment of;

Tableta

• Herba Lobeliae Sessilifoliae 40g, Herba Caryopteridis Terniflorae 160g, Fructus Aurantii 320g, Fructus Arctii 220g, Radix Platycodonis 140g, Radix et Rhizoma Thalictri 420g, Herba Houttuyniae 330g, Radix Glycyrrhizae 150g, Herba Ardisiae Japonicae 280g, Rhizoma Zingiberis Recens 170g, Fructus Elaeagni 350g, Magnetitum 130g, Herba Boschniakiae Rossicae 240g, Succus Bambusae 180g, Semen Plantaginis 260g, Semen Sinapis Albae 150g, halberd Ye Wawei 300g, Fructus Perillae 140g, Lignum Aquilariae Resinatum 230g, Cortex Mori 320g, Fructus Rubi 200g, Fructus chebulae immaturus 300g, Semen Lepidii (Semen Descurainiae) 400g, Fructus Alpiniae Oxyphyllae 160g, Herba Thlaspis 330g, Radix Crepidis Ligneae 170g, dominoes Herba pteridii latiusculi 270g, Pericarpium Metaplexis 160g, Herba Kalimeridis 130g, Radix Stemonae 30g, polished rod fine jade 250g and Concretio Silicea Bambusae 360g,

• Tablet in treatment group (děti v klinické studii s M. pn.): use the embodiment of the present invention 3 prepare tablet, every day 3 times, one time 1, within every 7 days, be a course for the treatment of.

Treating the Chinese materia medica syrup of mycoplasma pneumonia in children

• Weight proportion At:
• 6 13 parts of Fen , Common St.Paulswort Herb of nepal fleshspike herb,
• 6 parts of negundo chastetree fruit,
• 10 parts of German tamarisk,
• 10 parts of hispid arthraxon,
• 10 parts of russianolive flower,
• 15 parts of farges fir cone,
• 10 parts of Hypericum przewalskii Maxim,
• 8 parts of grass of spoon leaf,
• 5 parts of twoleaf platanthera rhizome,
• 15 parts of british inula root,
• 20 parts of Radix Angelicae Pubescentis,
• 10 parts of oxtongue,
• water wax gourd 6 Part,
• 15 parts of foxtail millet seed,
• 7 parts of lance asiabell root,
• 12 parts, 0.5 part of xylitol of deer grass.

• Above-mentioned Chinese medicine material is mixed in proportion,
• Pulverize,
• Add 8-10 Times water decocts 1-2h,
• Filtering takes filtrate that corrigent xylitol is added,
• Continues to boil 20-30min,
• Obtains Chinese materia medica syrup.

Tea tree oil

• Essential oil of Melaleuca alternifolia [i.e. tea tree oil (TTO)]
• Long history of use as a topical antiseptic in Australia since the 1920s.
• Antimicrobial activity against
• Gram-positive and Gram-negative bacteria
• Aerobic and anaerobic,
• Yeasts and fungi
• Fluconazole-resistant Candida strains
• Exposure of Escherichia coli, Staphylococcus aureus and Candida albicans to minimum inhibitory and minimum bactericidal/fungicidal concentrations of TTO
• Inhibits respiration
• Increases the permeability of bacterial cytoplasmic and yeast plasma membranes
• Antimicrobial activity of TTO
• Terpinen-4-ol.1
• Relatively non-toxic when applied topically
• Cases of allergic contact dermatitis have been reported
• In vitro susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis and Mycoplasma fermentans to TTO.
• Oil appeared to be characterized by
• High proportion of terpinen-4-ol (36.71%)
• G-terpinene (22.20%),
• Moderate levels of 1,8-cineole (2.49%)
• P-cymene (2.52%),
• A-terpinene (10.10%)
• Terpinolene (3.53%)
• Stock solutions of TTO were prepared in fetal calf serum (Biokrom by Bio-Spa, Milan, Italy).

• MIC was defined as
• The lowest concentration of the essential oil that inhibited a colour change in the broth
• Colour of the control tube changed
• PH of the medium decreased from 7.5 to 7.0 (M. pneumoniae and M. fermentans)
• Increased from 6.0 to 6.5 (M. hominis)
• Required incubation times were
• 24–48 h for M. hominis and M. fermentans
• 3–5 days for M. pneumoniae

• TTO inhibited mycoplasmas at concentrations from 0.01% to 0.12% (v/v)
• M. pneumoniae showed MIC values of 0.01% (v/v).
• M. fermentans, showed MIC90 values of 0.06% (v/v).
• M. hominis was the least susceptible with MIC90 values of 0.12% (v/v).
• academic.oup.com/jac/article/58/3/706/746513

• The most common morphological shape of M. pneumoniae

is the typical �pear shape’ with a tip structure at one end of thecell. There are specific protein filaments inside the tip structure which form the cytoskeleton [25]. When M. pneumoniaewas treated with 0.006% TTO in ethanol (1%) for 12 h, thecells lost their typical �pear-shaped’ appearance and becamerounded. The rounded shape resembles mutants which havelost their virulence as a result of this morphological changeand the loss of their attachment site. TTO seems to affect theintracellular cytoskeletal structure in a way that M. pneumoniae cells become rounded and lose their virulen

Temafloxacin, ofloxacin, and ciprofloxacin

• 50 strains of Mycoplasma pneumoniae were tested for susceptibility
• Possessed the most mycoplasmacidal activity against these organisms
• The MBC for 50% of the strains (MBC50)-to-MIC50 ratio for each of these drugs was 4.
• The MBC50-to-MIC50 ratios for the tetracyclines and macrolides
• Were markedly higher, within a range of 32 to 2,000.
• Temafloxacin and ofloxacin
• Might be promising antimicrobial agents for the treatment of mycoplasmal infection
• journals.asm.org/doi/10.1128/aac.36.6.1322

Terminalia mollis (Combretaceae)

• Had good antimycoplasmal activity
• www.tandfonline.com/doi/full/10.3109/13880200903505633

Terpenické látky

• Rozmarýn
• Bazalka
• Coriandr

Tetracyclines

• Bacteriostatic
• First choice for
• Mycoplasmal urogenital infections like nongonococcal urethritis
• Pelvic inflammatory disease
• Respiratory tract infections due to M. pneumoniae in adults
• Cannot be used in children and during pregnancy
• Publications reported the efficient use doxycycline in central nervous system (CNS) infections in neonates
• www.researchgate.net/publication/226918048_Antimycoplasmal_Agents

Macrolides

• Treatment of choice for mycoplasma infections in children
• Penetrate poorly across the blood-brain barrier and into the cerebrospinal fluid (CSF)
• Bind to the 50S subunit of the ribosome
• Block the growth of the nascent peptide chain
• Probably causing premature dissociation of the peptidyl-tRNA from the ribosome
• Macrolides and other MLS drugs
• Central loop in domain V of 23S rRNA,
• Associated with the peptidyl transferase activity

Erythromycin and its derivative ketolides

• JeštÄ› na hairpin 35 in domain II of the 23S rRNA
• Erythromycin is the first-choice drug for
• Ureaplasmal infections of the respiratory tract in neonates
• www.researchgate.net/publication/226918048_Antimycoplasmal_Agents

Fluoroquinolones

• Broad-spectrum antibiotics
• Intracellular targets of fluoroquinolones in bacteria
• Type II topoisomerases,
• DNA gyrase
• Topoisomerase IV
• Essential for bacterial DNA replication
• Gyrase is composed of two A and two B subunits
• Encoded by the gyrA and gyrB genes
• Tetrameric enzyme catalyzes ATP-dependent negative supercoiling of DNA
• Topoisomerase IV
• A C2E2 tetramer encoded by the parC and parE genes
• Essential for chromosome partitioning
• ParC is homologous to GyrA
• ParE is homologous to GyrB

Nalidixic acid

• The original non-fluorinated molecule of the quinolone class
• inactive against gram-positive bacteria and mycoplasmas

Norfloxacin, pefloxacin, ofloxacin, and ciprofloxacin

Sparfloxacin, levofloxacin, grepafloxacin, trovafloxacin, gatifloxacin, moxifloxacin, gemifloxacin, and BMS-284756

• Newer fluoroquinolones
• Grepafloxacin or trovafloxacin
• Never been commercialized or were withdrawn
• Gemifloxacin and BMS-284756
• Still under development
• Show an enhanced activity against all the human mycoplasmas compared to the older ones
• Cidal activity against these microorganisms
• Should not be given to children
• Possible juvenile cartilage damage
• Increasing occurrence of bacterial resistance to fluoroquinolones including mycoplasmas
• Limit their use in clinical settings
• www.researchgate.net/publication/226918048_Antimycoplasmal_Agents

Chloramphenicol

• Inhibiting protein synthesis.
• Binding to the 50S subunit of the ribosome
• Inhibition of the peptidyltransferase step
• Mycoplasmas show a susceptibility level similar to that of gram-positive bacteria like Staphylococcus aureus
• Potential toxicity
• Not used for treatment of mycoplasmal diseases
• Exceptions are ureaplasmal or mycoplasmal infections of CNS in neonates
• www.researchgate.net/publication/226918048_Antimycoplasmal_Agents

Aminoglycosides

• Broad-spectrum antimicrobials
• Bactericidal
• Target the bacterial ribosome
• Bind on different sites in the 16S rRNA of the 30S subunit
• To some ribosomal proteins,
• Decreasing the fidelity of translation
• Not used for the treatment of human mycoplasmal infections
• Employed to eliminate mycoplasma contamination from cell cultures
• Moderately to highly effective in elimination of mycoplasmas
• Only at concentrations cytotoxic for the eukaryotic cells
• Alternative treatment could be
• Fluoroquinolones
• Combining macrolides and tetracyclines
• www.researchgate.net/publication/226918048_Antimycoplasmal_Agents

Triclosan

• In-vitro Antimycoplasmal Activity of Triclosan in Combination with Fluoroquinolones against Five mycoplasma Species
• Triclosan has demonstrated antiplaque, antigingivitis, antibacterial, and anti-inflammatory (12-14) properties
• no reports of triclosan-resistant microbes in the wild

Pulmonary activation of vitamin D3

• Preventive effect against interstitial pneumonia
• Calcitriol [1,25(OH)2D3] - effect of activated vitamin D against interstitial pneumonia
• Cholecalciferol (vitamin D3)
• Has a longer half-life than calcitriol
• Few investigations of its effect on interstitial pneumonia

Human pulmonary fibroblast cell lines (HPFCs) and a mouse model of bleomycin-induced pulmonary fibrosis

• Vitamin D3 suppressed bleomycin-induced expression of inflammatory cytokines and fibrosis markers by the HPFCs
• In mice, symptoms of bleomycin-induced pulmonary fibrosis were improved
• Expression of fibrosis markers/fibrosis inducers was decreased by a high vitamin D3 diet.
• Vitamin D3 is activated locally in lung tissues,
• Suggesting that high dietary intake of vitamin D3 may have a preventive effect against interstitial pneumonia.

https://www.jstage.jst.go.jp/article/jcbn/65/3/65_19-48/_article/-char/ja/

Vitamin E + Vitamin A

• Tvedten et al., 1973

Sprague-Dawley rats

• 6 wk, 180 mg/kg diet + 6,000 IU vitamin A
• Increased rats resistance to infection Mycoplasma pulmonis