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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 -
Veterinary Research Nov 2022Streptococcus suis is a zoonotic agent that causes sepsis and meningitis in pigs and humans. S. suis infections are responsible for large economic losses in pig... (Review)
Review
Streptococcus suis is a zoonotic agent that causes sepsis and meningitis in pigs and humans. S. suis infections are responsible for large economic losses in pig production. The lack of effective vaccines to prevent the disease has promoted the extensive use of antibiotics worldwide. This has been followed by the emergence of resistance against different classes of antibiotics. The rates of resistance to tetracyclines, lincosamides, and macrolides are extremely high, and resistance has spread worldwide. The genetic origin of S. suis resistance is multiple and includes the production of target-modifying and antibiotic-inactivating enzymes and mutations in antibiotic targets. S. suis genomes contain traits of horizontal gene transfer. Many mobile genetic elements carry a variety of genes that confer resistance to antibiotics as well as genes for autonomous DNA transfer and, thus, S. suis can rapidly acquire multiresistance. In addition, S. suis forms microcolonies on host tissues, which are associations of microorganisms that generate tolerance to antibiotics through a variety of mechanisms and favor the exchange of genetic material. Thus, alternatives to currently used antibiotics are highly demanded. A deep understanding of the mechanisms by which S. suis becomes resistant or tolerant to antibiotics may help to develop novel molecules or combinations of antimicrobials to fight these infections. Meanwhile, phage therapy and vaccination are promising alternative strategies, which could alleviate disease pressure and, thereby, antibiotic use.
Topics: Humans; Swine; Animals; Streptococcus suis; Streptococcal Infections; Anti-Bacterial Agents; Macrolides; Swine Diseases
PubMed: 36371221
DOI: 10.1186/s13567-022-01111-3 -
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 -
Current Opinion in Infectious Diseases Apr 2022Community-acquired pneumonia (CAP) is known as a major worldwide health concern considering it has been shown to account for 78% of infection-related deaths in the USA.... (Review)
Review
PURPOSE OF REVIEW
Community-acquired pneumonia (CAP) is known as a major worldwide health concern considering it has been shown to account for 78% of infection-related deaths in the USA. It is a common cause for hospitalization with a continued incidence rise in the elderly, high mortality rate and long-term sequelae in critically ill patients. Severe CAP (sCAP) is an accepted terminology used to describe ICU admitted patients with CAP. The aim of this review is to further report on the major advances in treatment for patients with sCAP including new antibiotic treatments despite macrolide resistance as seen in the ICU, and multifaceted antibiotic stewardship interventions that may lead to the reduction broad-spectrum antibiotic use in CAP.
RECENT FINDINGS
We aim to examine the most recent findings in order to determine appropriate empirical antibiotic choices, timing regimens and evidence for clinical effectiveness. This will be addressed by focusing on the use combination therapies, the usefulness of severity scores and the difficulty to treat multidrug-resistant pathogens, including gram negatives such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Relevant reports referenced within included randomized controlled trials, meta-analyses, observational studies, systematic reviews and international guidelines where applicable.
SUMMARY
New antibiotics have been recently launched with direct agent-specific properties that have been shown to avoid the overuse of previous broad-spectrum antibiotics when treating patients sCAP. Although narrow-spectrum antibiotics are now recommended and imperative in improving a patients' prognosis, there are also some considerations when prescribing antibiotics that are beyond the spectrum. There is a need to implement effective policies of de-escalation to avoid antibiotic resistance and the risk for developing subsequent infections by combining informed clinical judgement and the application of biomarkers. Reaching clinical stability and avoidance of treatment failure are the most important pillars in treatment success.
Topics: Aged; Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Macrolides; Methicillin-Resistant Staphylococcus aureus; Pneumonia
PubMed: 35190510
DOI: 10.1097/QCO.0000000000000819 -
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 -
Nature Nov 2021Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease. Despite this...
Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species. Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for β-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal and human gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacteria, Anaerobic; Bacteroides; Clostridioides difficile; Dicumarol; Erythromycin; Feces; Female; Gastrointestinal Microbiome; Germ-Free Life; Humans; Macrolides; Male; Mice; Microbiota; Symbiosis; Tetracyclines
PubMed: 34646011
DOI: 10.1038/s41586-021-03986-2 -
Indian Journal of Medical Microbiology 2023Mycoplasmas are the smallest prokaryotic microorganisms found in nature. Mycoplasma pneumoniae (M. pneumoniae) is the most commonly studied among human mycoplasmas. (Review)
Review
BACKGROUND
Mycoplasmas are the smallest prokaryotic microorganisms found in nature. Mycoplasma pneumoniae (M. pneumoniae) is the most commonly studied among human mycoplasmas.
OBJECTIVES
In this review, we briefly focus on the recent developments that have enhanced our understanding of M. pneumoniae, one of the smallest pathogenic bacteria of great clinical importance in children.
CONTENT
M. pneumoniae infections may involve either upper or lower respiratory tract or both of them. Extrapulmonary manifestations have been reported in almost every organ, including the skin and the hematologic, cardiovascular, musculoskeletal, and nervous system due to direct local effects, after dissemination of bacteria or indirect effects. The correct identification of M. pneumoniae infections is vital for prescription of the appropriate therapy.There are scarce specific findings of clinical laboratory results for the diagnosis of M. pneumoniae infection. Detection of M. pneumoniae infections can be achieved using culture, serology, or molecular-based methods. Culture is time-consuming, laborious, and expensive. The major types of serological tests for M. pneumoniae include the microtiter plate enzyme immunoassay (EIA), the membrane EIA, indirect immunofluorescence, and particle agglutination. Nucleic acid amplification tests (NAATs) include traditional PCR, nested PCR, real-time quantitative PCR, nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP) technology, and RNA simultaneous amplification and testing (SAT). Macrolides have been the drug of choice for treating M. pneumoniae infection in past years. Clinically significant acquired macrolide-resistant M. pneumoniae (MRMP)has emerged worldwide which may be associated with more extrapulmonary complications, and severe clinical and radiological features. Since molecular-based assays can detect M. pnueumoniae in clinical specimens, there is a need for real point of care testing for fast detection of M. pneumoniae or its DNA and mutations in macrolide resistance gene. It is necessary to develop safe vaccines that provide protective immunity against M.pneumoniae infection.
Topics: Child; Humans; Mycoplasma pneumoniae; Anti-Bacterial Agents; Pneumonia, Mycoplasma; Clinical Relevance; Macrolides; Drug Resistance, Bacterial; Real-Time Polymerase Chain Reaction
PubMed: 37741157
DOI: 10.1016/j.ijmmb.2023.100480