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Nature Reviews. Microbiology Jul 2023Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever... (Review)
Review
Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. Fluctuating global GAS epidemiology is characterized by the emergence of new GAS clones, often associated with the acquisition of new virulence or antimicrobial determinants that are better adapted to the infection niche or averting host immunity. The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. The World Health Organization (WHO) has developed a GAS research and technology road map and has outlined preferred vaccine characteristics, stimulating renewed interest in the development of safe and effective GAS vaccines.
Topics: Humans; Anti-Bacterial Agents; Macrolides; Drug Resistance, Bacterial; Streptococcal Infections; Streptococcus pyogenes; Penicillins
PubMed: 36894668
DOI: 10.1038/s41579-023-00865-7 -
Emerging Infectious Diseases Jul 2020A high prevalence rate of macrolide-resistant Mycoplasma pneumoniae (MRMP) has been reported in Asia. We performed a systematic review and meta-analysis to investigate... (Meta-Analysis)
Meta-Analysis
A high prevalence rate of macrolide-resistant Mycoplasma pneumoniae (MRMP) has been reported in Asia. We performed a systematic review and meta-analysis to investigate the effect of macrolide resistance on the manifestations and clinical judgment during M. pneumoniae infections. We found no difference in clinical severity between MRMP and macrolide-sensitive Mycoplasma pneumoniae (MSMP) infections. However, in the pooled data, patients infected with MRMP had a longer febrile period (1.71 days), length of hospital stay (1.61 day), antibiotic drug courses (2.93 days), and defervescence time after macrolide treatment (2.04 days) compared with patients infected with MSMP. The risk of fever lasting for >48 hours after macrolide treatment was also significantly increased (OR 21.24), and an increased proportion of patients was changed to second-line treatment (OR 4.42). Our findings indicate diagnostic and therapeutic challenges after the emergence of MRMP. More precise diagnostic tools and clearly defined treatment should be appraised in the future.
Topics: Anti-Bacterial Agents; Asia; Child; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Macrolides; Mycoplasma pneumoniae; Pneumonia, Mycoplasma
PubMed: 32568052
DOI: 10.3201/eid2607.200017 -
Pulmonary Pharmacology & Therapeutics Dec 2021Macrolide antibiotics are well known for their antibacterial properties, but extensive research in the context of inflammatory lung disease has revealed that they also... (Review)
Review
Macrolide antibiotics are well known for their antibacterial properties, but extensive research in the context of inflammatory lung disease has revealed that they also have powerful immunomodulatory properties. It has been demonstrated that these drugs are therapeutically beneficial in various lung diseases, with evidence they significantly reduce exacerbations in patients with COPD, asthma, bronchiectasis and cystic fibrosis. The efficacy demonstrated in patients infected with macrolide tolerant organisms such as Pseudomonas aeruginosa supports the concept that their efficacy is at least partly related to immunomodulatory rather than antibacterial effects. Inconsistent data and an incomplete understanding of their mechanisms of action hampers the use of macrolide antibiotics as immunomodulatory therapies. Macrolides recently demonstrated no clinically relevant immunomodulatory effects in the context of COVID-19 infection. This review provides an overview of macrolide antibiotics and discusses their immunomodulatory effects and mechanisms of action in the context of inflammatory lung disease.
Topics: Anti-Bacterial Agents; COVID-19; Cystic Fibrosis; Humans; Immunomodulation; Macrolides; SARS-CoV-2
PubMed: 34740749
DOI: 10.1016/j.pupt.2021.102095 -
Journal of the European Academy of... May 2022Mycoplasma genitalium infection contributes to 10-35% of non-chlamydial non-gonococcal urethritis in men. In women, M. genitalium is associated with cervicitis and...
UNLABELLED
Mycoplasma genitalium infection contributes to 10-35% of non-chlamydial non-gonococcal urethritis in men. In women, M. genitalium is associated with cervicitis and pelvic inflammatory disease (PID) in 10-25%. Transmission of M. genitalium occurs through direct mucosal contact.
CLINICAL FEATURES AND DIAGNOSTIC TESTS
Asymptomatic infections are frequent. In men, urethritis, dysuria and discharge predominate. In women, symptoms include vaginal discharge, dysuria or symptoms of PID - abdominal pain and dyspareunia. Symptoms are the main indication for diagnostic testing. Diagnosis is achievable only through nucleic acid amplification testing and must include investigation for macrolide resistance mutations.
THERAPY
Therapy for M .genitalium is indicated if M. genitalium is detected. Doxycycline has a cure rate of 30-40%, but resistance is not increasing. Azithromycin has a cure rate of 85-95% in macrolide-susceptible infections. An extended course of azithromycin appears to have a higher cure rate, and pre-treatment with doxycycline may decrease organism load and the risk of macrolide resistance selection. Moxifloxacin can be used as second-line therapy but resistance is increasing.
RECOMMENDED TREATMENT
Uncomplicated M. genitalium infection without macrolide resistance mutations or resistance testing: Azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral). Second-line treatment and treatment for uncomplicated macrolide-resistant M. genitalium infection: Moxifloxacin 400 mg od for 7 days (oral). Third-line treatment for persistent M. genitalium infection after azithromycin and moxifloxacin: Doxycycline or minocycline 100 mg bid for 14 days (oral) may cure 40-70%. Pristinamycin 1 g qid for 10 days (oral) has a cure rate of around 75%. Complicated M. genitalium infection (PID, epididymitis): Moxifloxacin 400 mg od for 14 days. MAIN CHANGES FROM THE 2016 EUROPEAN M.
GENITALIUM GUIDELINE
Due to increasing antimicrobial resistance and warnings against moxifloxacin use, indications for testing and treatment have been narrowed to primarily involve symptomatic patients. The importance of macrolide resistance-guided therapy is emphasised.
Topics: Anti-Bacterial Agents; Azithromycin; Doxycycline; Drug Resistance, Bacterial; Dysuria; Female; Humans; Macrolides; Male; Moxifloxacin; Mycoplasma Infections; Mycoplasma genitalium; Urethritis
PubMed: 35182080
DOI: 10.1111/jdv.17972 -
JAMA Network Open Jul 2022The proportion of macrolide-resistant Mycoplasma pneumoniae (MRMP) infections has changed, and it differs according to geographical region. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The proportion of macrolide-resistant Mycoplasma pneumoniae (MRMP) infections has changed, and it differs according to geographical region.
OBJECTIVE
To analyze the global patterns, including the temporal trends, regional variations, and variant types, in the proportion of MRMP infections in this systematic review and meta-anaysis.
DATA SOURCES
PubMed, Cochrane Library, and Embase databases were searched for observational studies from inception to September 10, 2021.
STUDY SELECTION
Observational studies reporting the proportion of MRMP infections were screened independently by 2 authors. The presence of MRMP infection was defined as any case of M pneumoniae infection positive for any variants associated with macrolide resistance identified using respiratory samples.
DATA EXTRACTION AND SYNTHESIS
Data were extracted independently and in duplicate by 2 reviewers. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was used. Random-effects meta-analyses were used to estimate the proportion of MRMP infections.
MAIN OUTCOMES AND MEASURES
The global patterns in the proportion of MRMP infections were estimated, and the temporal trends and variant types of MRMP infection with regional differences were investigated.
RESULTS
This study included 153 studies from 150 articles (27 408 samples in 26 countries) in the meta-analysis. The global patterns in the proportion of MRMP infections showed an increasing trend with regional differences. The proportion of MRMP infections was highest in the Western Pacific regions (53.4%; 95% CI, 47.4%-60.3%), followed by the South East Asian region (9.8%; 95% CI, 0.8%-100%), the region of the Americas (8.4%; 95% CI, 6.1%-11.6%), and the European region (5.1%; 95% CI, 3.3%-8.0%). The most commonly identified variant of MRMP infection was A2063G (96.8%; 95% CI, 95.8%-97.7%), followed by A2064G (4.8%; 95% CI, 3.5%-6.7%). The proportion of MRMP infections was the highest in studies including only children (37.0%; 95% CI, 29.8%-46.1%), followed by those including only adults (15.9%; 95% CI, 6.4%-39.7%) and those including both children and adults (16.7%; 95% CI, 10.1%-27.6%).
CONCLUSIONS AND RELEVANCE
This study provides global trends in the proportion of MRMP infections and suggests that strategies to prevent the spread of MRMP infection and to treat MRMP infections are needed to decrease disease burden.
Topics: Adult; Anti-Bacterial Agents; Child; Drug Resistance, Bacterial; Humans; Macrolides; Microbial Sensitivity Tests; Pneumonia, Mycoplasma; United States
PubMed: 35816304
DOI: 10.1001/jamanetworkopen.2022.20949 -
Infectious Disease Clinics of North... Jun 2023Mycoplasma genitalium is a frequent cause of urogenital syndromes in men and women and is associated with adverse sequelae in women. M genitalium also infects the... (Review)
Review
Mycoplasma genitalium is a frequent cause of urogenital syndromes in men and women and is associated with adverse sequelae in women. M genitalium also infects the rectum, and may cause proctitis, but rarely infects the pharynx. Diagnosis requires nucleic acid amplification testing. Antibiotic resistance is widespread: more than half of infections are resistant to macrolides and fluoroquinolone resistance is increasing. Resistance-guided therapy is recommended for symptomatic patients, involving initial treatment with doxycycline to reduce organism load followed by azithromycin for macrolide-sensitive infections or moxifloxacin for macrolide-resistant infections. Neither screening nor tests of cure are recommended in asymptomatic persons.
Topics: Male; Humans; Female; Mycoplasma genitalium; Mycoplasma Infections; Drug Resistance, Bacterial; Anti-Bacterial Agents; Macrolides
PubMed: 37105645
DOI: 10.1016/j.idc.2023.02.009 -
BMC Infectious Diseases Sep 2021Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia in school-age children. Macrolides are considered a first-line treatment for M.... (Meta-Analysis)
Meta-Analysis
Efficacy of tetracyclines and fluoroquinolones for the treatment of macrolide-refractory Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis.
BACKGROUND
Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia in school-age children. Macrolides are considered a first-line treatment for M. pneumoniae infection in children, but macrolide-refractory M. pneumoniae (MRMP) strains have become more common. In this study, we assessed the efficacy of tetracyclines and fluoroquinolones in MRMP treatment in children through a systematic review and meta-analysis.
METHODS
Two reviewers individually searched 10 electronic databases (Medline/Pubmed, Embase, the Cochrane Library, and core Korean, Chinese, and Japanese journals) for papers published from January 1, 1990 to March 8, 2018. The following data for each treatment group were extracted from the selected studies: intervention (tetracyclines and fluoroquinolones/comparator), patient characteristics (age and sex), and outcomes (fever duration, hospital stay length, treatment success rate, and defervescence rates 24, 48, and 72 h after starting treatment).
RESULTS
Eight studies involving 537 participants were included. Fever duration and hospital stay length were shorter in the tetracycline group than in the macrolide group (weighted mean difference [WMD] = - 1.45, 95% confidence interval [CI]: - 2.55 to - 0.36, P = 0.009; and WMD = - 3.33, 95% CI: - 4.32 to - 2.35, P < 0.00001, respectively). The therapeutic efficacy was significantly higher in the tetracycline group than in the macrolide group (odds ratio [OR]: 8.80, 95% CI: 3.12-24.82). With regard to defervescence rate, patients in the tetracycline group showed significant improvement compared to those in the macrolide group (defervescence rate after 24 h, OR: 5.34, 95% CI: 1.81-15.75; after 48 h, OR 18.37, 95% CI: 8.87-38.03; and after 72 h, OR: 40.77, 95% CI: 6.15-270.12). There were no differences in fever improvement within 24 h in patients in the fluoroquinolone group compared to those in the macrolide group (OR: 1.11, 95% CI: 0.25-5.00), although the defervescence rate was higher after 48 h in the fluoroquinolone group (OR: 2.78, 95% CI: 1.41-5.51).
CONCLUSION
Tetracyclines may shorten fever duration and hospital stay length in patients with MRMP infection. Fluoroquinolones may achieve defervescence within 48 h in patients with MRMP infection. However, these results should be carefully interpreted as only a small number of studies were included, and they were heterogeneous.
Topics: Anti-Bacterial Agents; Child; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Macrolides; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Tetracyclines
PubMed: 34563128
DOI: 10.1186/s12879-021-06508-7 -
Frontiers in Cellular and Infection... 2023is an important pathogen causing upper and lower respiratory tract infections in children and other age groups. Macrolides are the recommended treatments of choice for...
is an important pathogen causing upper and lower respiratory tract infections in children and other age groups. Macrolides are the recommended treatments of choice for infections. However, macrolide resistance in is increasing worldwide, which complicates the treatment strategies. The mechanisms of macrolide resistance have been extensively studied focusing on the mutations in and ribosomal proteins. Since the secondary treatment choice for pediatric patients is very limited, we decided to look for potential new treatment strategies in macrolide drugs and investigate possible new mechanisms of resistance. We performed an selection of mutants resistant to five macrolides (erythromycin, roxithromycin, azithromycin, josamycin, and midecamycin) by inducing the parent strain M129 with increasing concentrations of the drugs. The evolving cultures in every passage were tested for their antimicrobial susceptibilities to eight drugs and mutations known to be associated with macrolide resistance by PCR and sequencing. The final selected mutants were also analyzed by whole-genome sequencing. Results showed that roxithromycin is the drug that most easily induces resistance (at 0.25 mg/L, with two passages, 23 days), while with midecamycin it is most difficult (at 5.12 mg/L, with seven passages, 87 days). Point mutations C2617A/T, A2063G, or A2064C in domain V of were detected in mutants resistant to the 14- and 15-membered macrolides, while A2067G/C was selected for the 16-membered macrolides. Single amino acid changes (G72R, G72V) in ribosomal protein L4 emerged during the induction by midecamycin. Genome sequencing identified sequence variations in , , , , and in one of the () genes in the mutants. Mutants induced by the 14- or 15-membered macrolides were resistant to all macrolides, while those induced by the 16-membered macrolides (midecamycin and josamycin) remained susceptible to the 14- and 15-membered macrolides. In summary, these data demonstrated that midecamycin is less potent in inducing resistance than other macrolides, and the induced resistance is restrained to the 16-membered macrolides, suggesting a potential benefit of using midecamycin as a first treatment choice if the strain is susceptible.
Topics: Humans; Child; Anti-Bacterial Agents; Mycoplasma pneumoniae; Macrolides; Roxithromycin; Josamycin; RNA, Ribosomal, 23S; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Pneumonia, Mycoplasma
PubMed: 37284499
DOI: 10.3389/fcimb.2023.1186017 -
International Journal of Antimicrobial... Sep 2023Guidelines recommend respiratory fluoroquinolone monotherapy or β-lactam plus macrolide combination therapy as first-line options for hospitalized adults with... (Meta-Analysis)
Meta-Analysis Review
Respiratory fluoroquinolone monotherapy vs. β-lactam plus macrolide combination therapy for hospitalized adults with community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials.
INTRODUCTION
Guidelines recommend respiratory fluoroquinolone monotherapy or β-lactam plus macrolide combination therapy as first-line options for hospitalized adults with mild-to-moderate community-acquired pneumonia (CAP). Efficacy of these regimens has not been adequately evaluated.
METHODS
A systematic review of randomized controlled trials (RCTs) comparing respiratory fluoroquinolone monotherapy and β-lactam plus macrolide combination therapy in hospitalised adults with CAP was performed. A meta-analysis was performed using a random effects model. The primary outcome was clinical cure rate. Quality of evidence (QoE) was evaluated using GRADE methodology.
RESULTS
A total of 4140 participants in 18 RCTs were included. Levofloxacin (11 trials) or moxifloxacin (6 trials) were the predominant respiratory fluoroquinolones evaluated, and the β-lactam plus macrolide group used ceftriaxone plus a macrolide (10 trials), cefuroxime plus azithromycin (5 trials), and amoxicillin/clavulanate plus a macrolide (2 trials). Patients receiving respiratory fluoroquinolone monotherapy had a significantly higher clinical cure rate (86.5% vs. 81.5%; odds ratio [OR] 1.47; 95% confidence interval [95% CI: 1.17-1.83]; P = 0.0008; I = 0%; 17 RCTs; moderate QoE) and microbiological eradication rate (86.0% vs. 81.0%; OR 1.51 [95% CI: 1.00-2.26]; P = 0.05; I = 0%; 15 RCTs; moderate QoE) than patients receiving β-lactam plus macrolide combination therapy. All-cause mortality (7.2% vs. 7.7%; OR 0.88 [95% CI: 0.67-1.17]; I = 0%; low QoE) and adverse events (24.8% vs. 28.1%; OR 0.87 [95% CI: 0.69-1.09]; I = 0%; low QoE] were similar in the two groups.
CONCLUSION
Respiratory fluoroquinolone monotherapy demonstrated an advantage in clinical cure and microbiological eradication; however, it did not impact mortality.
Topics: Adult; Humans; beta-Lactams; Fluoroquinolones; Macrolides; Pneumonia, Bacterial; Drug Therapy, Combination; Randomized Controlled Trials as Topic; Anti-Bacterial Agents; Community-Acquired Infections
PubMed: 37385561
DOI: 10.1016/j.ijantimicag.2023.106905 -
Respiratory Investigation Mar 2024The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine the efficacy and safety of macrolide therapy for adult asthma.
METHODS
We searched randomized controlled trials from MEDLINE via the PubMed, CENTRAL, and Ichushi Web databases. The primary outcome was asthma exacerbation. The secondary outcomes were serious adverse events (including mortality), asthma-related quality of life (symptom scales, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire), rescue medication (puffs/day), respiratory function (morning peak expiratory flow, evening peak flow, and forced expiratory volume in 1 s), bronchial hyperresponsiveness, and minimum oral corticosteroid dose. Of the 805 studies, we selected seven studies for the meta-analysis, which was conducted using a random-effects model.
SYSTEMATIC REVIEW REGISTRATION
University Hospital Medical Information Network Clinical Trials Registry (UMIN000050824).
RESULTS
No significant difference between macrolide and placebo for asthma exacerbations was observed (risk ratio 0.71, 95 % confidence interval [CI] 0.46-1.09; p = 0.12). Macrolide therapy for adult asthma showed a significant improvement in rescue medication with short-acting beta-agonists (mean difference -0.41, 95 % CI -0.78 to -0.04; p = 0.03). Macrolide therapy did not show more serious adverse events (odd ratio 0.61, 95 % CI 0.34-1.10; p = 0.10) than those with placebo. The other secondary outcomes were not significantly different between the macrolide and placebo groups.
CONCLUSIONS
Macrolide therapy for adult asthma may be more effective than placebo and could be a treatment option.
Topics: Adult; Humans; Macrolides; Quality of Life; Disease Progression; Asthma; Anti-Bacterial Agents; Adrenal Cortex Hormones
PubMed: 38211545
DOI: 10.1016/j.resinv.2023.12.015