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Nature Reviews. Microbiology Apr 2019Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most successful modern pathogens. The same organism that lives as a commensal and is transmitted in both... (Review)
Review
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most successful modern pathogens. The same organism that lives as a commensal and is transmitted in both health-care and community settings is also a leading cause of bacteraemia, endocarditis, skin and soft tissue infections, bone and joint infections and hospital-acquired infections. Genetically diverse, the epidemiology of MRSA is primarily characterized by the serial emergence of epidemic strains. Although its incidence has recently declined in some regions, MRSA still poses a formidable clinical threat, with persistently high morbidity and mortality. Successful treatment remains challenging and requires the evaluation of both novel antimicrobials and adjunctive aspects of care, such as infectious disease consultation, echocardiography and source control. In this Review, we provide an overview of basic and clinical MRSA research and summarize the expansive body of literature on the epidemiology, transmission, genetic diversity, evolution, surveillance and treatment of MRSA.
Topics: Anti-Bacterial Agents; Bacteremia; Clinical Trials as Topic; Community-Acquired Infections; Cross Infection; Evolution, Molecular; Genetic Variation; Humans; Incidence; Methicillin; Methicillin-Resistant Staphylococcus aureus; Soft Tissue Infections; Staphylococcal Infections
PubMed: 30737488
DOI: 10.1038/s41579-018-0147-4 -
Clinical Infectious Diseases : An... Sep 2020Cefazolin and ertapenem combination therapy was used successfully to salvage 11 cases (6 endocarditis) of persistent methicillin-susceptible Staphylococcus aureus (MSSA)...
Cefazolin and ertapenem combination therapy was used successfully to salvage 11 cases (6 endocarditis) of persistent methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including immediate clearance (≤24 hours) in 8 cases. While in vitro synergy was modest, cefazolin plus ertapenem exhibited synergistic action in a rat model of MSSA endocarditis. The combination of cefazolin and ertapenem provides potent in vivo activity against MSSA beyond what is predicted in vitro and warrants further clinical study in the treatment of refractory MSSA bacteremia and endocarditis.
Topics: Animals; Anti-Bacterial Agents; Bacteremia; Cefazolin; Ertapenem; Methicillin; Rats; Salvage Therapy; Staphylococcal Infections; Staphylococcus aureus
PubMed: 31773134
DOI: 10.1093/cid/ciz995 -
JPMA. the Journal of the Pakistan... Mar 2022Staphylococcus aureus is a common gram-positive human pathogen involved in both community-acquired and nosocomial infections ranging from localised superficial lesions... (Review)
Review
Staphylococcus aureus is a common gram-positive human pathogen involved in both community-acquired and nosocomial infections ranging from localised superficial lesions to food poisoning and fatal systemic infections owing to its impressive array of virulence factors responsible for attaching, colonising, invading, and avoiding host immune system. The discovery of antibiotics effectively checked the once deadly infections. However, resistance started soon after their discovery and the first methicillin-resistant strain of staphylococcus aureus was reported in the early 1960s. The most important attribute of methicillin-resistant staphylococcus aureus is its acquisition of mecA gene coding for penicillin-binding protein-2a that blocks inhibitory action on peptidoglycan cross-linking. Methicillin-resistant staphylococcus aureus presents a serious global healthcare concern being responsible for prolonged hospital stays and increased mortality. The precise information of virulence factors and resistant traits of methicillin-resistant staphylococcus aureus and their interplay in a community is key to minimize the intermixing of resistant and susceptible pathogens in the community.
Topics: Humans; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Staphylococcus aureus; Virulence
PubMed: 35320234
DOI: 10.47391/JPMA.0504 -
Toxins Jan 2021The global impact of methicillin-resistant (MRSA) clonal lineages on human and animal health continues, even considering the decreasing MRSA rates in some parts of the...
The global impact of methicillin-resistant (MRSA) clonal lineages on human and animal health continues, even considering the decreasing MRSA rates in some parts of the world [...].
Topics: Animals; Anti-Bacterial Agents; Bacterial Toxins; Drug Resistance, Multiple, Bacterial; Exotoxins; Host-Pathogen Interactions; Humans; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Staphylococcaceae; Staphylococcal Infections
PubMed: 33466773
DOI: 10.3390/toxins13010061 -
Nature Medicine Oct 2023Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .
Topics: Adult; Humans; Anti-Bacterial Agents; Bacteremia; Cloxacillin; Fosfomycin; Methicillin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Drug Therapy, Combination
PubMed: 37783969
DOI: 10.1038/s41591-023-02569-0 -
Medicine in Drug Discovery Mar 2021This review covers some of the recent progress in the field of peptide antibiotics with a focus on compounds with novel or established mode of action and with... (Review)
Review
This review covers some of the recent progress in the field of peptide antibiotics with a focus on compounds with novel or established mode of action and with demonstrated efficacy in animal infection models. Novel drug discovery approaches, linear and macrocyclic peptide antibiotics, lipopeptides like the polymyxins as well as peptides addressing targets located in the plasma membrane or in the outer membrane of bacterial cells are discussed.
PubMed: 33398258
DOI: 10.1016/j.medidd.2020.100078 -
The Journal of Antimicrobial... Nov 2022Anti-staphylococcal penicillins (ASPs) are among the most commonly prescribed antibiotics in children and are associated with a risk of drug-induced liver injury (DILI).... (Review)
Review
INTRODUCTION
Anti-staphylococcal penicillins (ASPs) are among the most commonly prescribed antibiotics in children and are associated with a risk of drug-induced liver injury (DILI). Despite the frequent use of ASPs in children, there is no consensus on whether liver function tests (LFTs) should be routinely monitored during treatment.
OBJECTIVES
To review the literature on the frequency of ASP-related DILI in children to determine the incidence, risk factors and outcomes of hepatotoxicity.
METHODS
PubMed, MEDLINE and Embase were searched in January 2022 for original studies of children who received cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin or oxacillin that included ≥10 children aged up to 18 years, and presented data on the incidence of DILI in children exposed to ASPs.
RESULTS
Overall, two studies of oral flucloxacillin, two of intravenous (IV) methicillin, three of IV nafcillin and four of IV oxacillin were included. The mean onset of DILI ranged between 7.0 and 19.0 days following commencement of antibiotic treatment and all episodes resolved between 14.2 and 16.0 days after drug discontinuation, with no specific treatment required. This review found that the incidence of DILI in children was 1 in 50 000 for oral flucloxacillin and ranged from 1 in 3 to 13 for IV oxacillin, methicillin and nafcillin.
CONCLUSIONS
This review found that routine LFT monitoring is not required in children receiving low dose oral flucloxacillin in a primary care setting, although pharmacovigilance is critical. For IV preparations, the existing data support routine LFT monitoring in those receiving treatment for at least 7 days.
Topics: Child; Humans; Nafcillin; Methicillin; Penicillins; Floxacillin; Oxacillin; Cloxacillin; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury
PubMed: 36203386
DOI: 10.1093/jac/dkac325 -
PloS One 2022Staphylococcus aureus is the primary cause of bacteremia, and methicillin-resistant S. aureus bacteremia is associated with a high mortality rate. Methicillin-resistant...
Staphylococcus aureus is the primary cause of bacteremia, and methicillin-resistant S. aureus bacteremia is associated with a high mortality rate. Methicillin-resistant S. aureus clones are widespread worldwide, and molecular epidemiological studies are important. Therefore, this study aimed to determine the characteristics of patients who died due to methicillin-resistant S. aureus bacteremia and microbiological characteristics of methicillin-resistant S. aureus strains in a tertiary teaching hospital. This single-center, retrospective study included patients with methicillin-resistant S. aureus isolated from blood bacterial culture performed at Kyoto Prefectural University of Medicine Hospital, from October 2016 to May 2019. The data analyzed included patient background, clinical strain characteristics, and molecular epidemiology. Of 41 patients with methicillin-resistant S. aureus bacteremia (median age, 60 [28-70] years; 24 (59%) were men), and 7 (17%) died due to methicillin-resistant S. aureus bacteremia. The median age of those who died in the methicillin-resistant S. aureus bacteremia group was predominantly higher than that of those in the alive group (p = 0.03). The most common cause of methicillin-resistant S. aureus bacteremia was endovascular devices, which occurred in 20 (49%), 18 (53%), and 2 (29%) patients in the total, alive, and died groups, respectively. Bacteriological characteristics showed that type IV Staphylococcal Cassette Chromosome mec genotype was most frequently detected in the total (n = 34 [83%]), alive (n = 29 [85%]), and died (n = 5 [71%]) groups. In the molecular cluster analysis, CC8, ST8, staphylococcal Cassette Chromosome mec type IV, and community-acquired-methicillin-resistant S. aureus formed the largest groups. The diversity of methicillin-resistant S. aureus clones is evident, and it is possible that clones with new virulence factors may still emerge. In the future, it will be crucial to monitor the epidemiological trends of methicillin-resistant S. aureus to respond quickly to changes in pathogenic and clonal factors, to clarify the gene expression network by identifying old and new virulence factors.
Topics: Anti-Bacterial Agents; Bacteremia; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Molecular Epidemiology; Retrospective Studies; Staphylococcal Infections; Tertiary Care Centers; Virulence Factors
PubMed: 35802589
DOI: 10.1371/journal.pone.0271115 -
Microbiology Spectrum Jun 2022Staphylococcus aureus is one of the most common pathogens associated with infection in wounds. The current standard of care uses a combination of disinfection and...
Staphylococcus aureus is one of the most common pathogens associated with infection in wounds. The current standard of care uses a combination of disinfection and drainage followed by conventional antibiotics such as methicillin. Methicillin and vancomycin resistance has rendered these treatments ineffective, often causing the reemergence of infection. This study examines the use of antimicrobial peptoids (sequence-specific poly--substituted glycines) designed to mimic naturally occurring cationic, amphipathic host defense peptides, as an alternative to conventional antibiotics. These peptoids also show efficient and fast (<30 min) killing of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) at low micromolar concentrations without having apparent cytotoxic side effects . Additionally, these novel peptoids show excellent efficacy against biofilm formation and detachment for both MSSA and MRSA. In comparison, conventional antibiotics were unable to detach or prevent formation of biofilms. One cationic 12mer, Peptoid 1, shows great promise, as it could prevent formation of and detach biofilms at concentrations as low as 1.6 μM. The use of a bioluminescent S. aureus murine incision wound model demonstrated clearance of infection in peptoid-treated mice within 8 days, conveying another advantage these peptoids have over conventional antibiotics. These results provide clear evidence of the potential for antimicrobial peptoids for the treatment of S. aureus wound infections. Staphylococcus aureus resistance is a consistent problem with a large impact on the health care system. Infections with resistant S. aureus can cause serious adverse effects and can result in death. These antimicrobial peptoids show efficient killing of bacteria both as a biofilm and as free bacteria, often doing so in less than 30 min. As such, these antimicrobials have the potential to alleviate the burden that Staphylococcus infections have on the health care system and cause better outcomes for infected patients.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Cationic Peptides; Biofilms; Methicillin; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Peptoids; Staphylococcal Infections; Staphylococcus aureus; Cathelicidins
PubMed: 35467395
DOI: 10.1128/spectrum.00534-22