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Antimicrobial Agents and Chemotherapy Dec 2023is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and...
is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and small-colony-variants. The inoculum effect (IE) is characterized by reduced β-lactam susceptibility when assessed at high inoculum. The IE associates with worse outcomes in bacteremia and other high-density infections, and may therefore be relevant to CF. The prevalence of IE amongst a CF cohort (age ≥18 years), followed from 2013 to 2016, was investigated. Yearly methicillin-sensitive (MSSA) isolates were screened at standard (5 × 10 CFU/mL) and high (5 × 10 CFU/mL) inoculum against narrow-spectrum anti-Staphylococcal β-lactams and those with anti-pseudomonal activity common to CF. A ≥ 4-fold increase in minimum inhibitory concentration between standard and high inoculum defined IE. Isolates underwent sequencing and genotyping and were compared against published genomes. Fifty-six percent (99/177) of individuals had MSSA infection. MSSA was observed at ≥10 CFU/mL in 44.8% of entry sputum samples. The prevalence of the IE was 25.0%-cefazolin; 13.5%-cloxacillin; 0%-meropenem; 1.0%-cefepime; 5.2%-ceftazidime; and 34.4%-piperacillin-tazobactam amongst baseline MSSA isolates assessed. A associated with cefazolin IE ( = 0.0011), whereas C associated with piperacillin-tazobactam IE ( < 0.0001). Baseline demographics did not reveal specific risk factors for IE-associated infections, nor were long-term outcomes different. Herein, we observed the IE in CF-derived MSSA disproportionally for cefazolin and piperacillin-tazobactam and this phenotype strongly associated with underlying genotype. The confirmation of CF being a high density infection, and the identification of high prevalence of MSSA with IE in CF supports the need for prospective pulmonary exacerbation treatment studies to understand the impact of this phenotype.
Topics: Adult; Humans; Adolescent; Methicillin; Cefazolin; Staphylococcus aureus; Anti-Bacterial Agents; Prospective Studies; Cystic Fibrosis; Staphylococcal Infections; Monobactams; Piperacillin, Tazobactam Drug Combination; Ceftazidime; beta Lactam Antibiotics; Microbial Sensitivity Tests
PubMed: 37966229
DOI: 10.1128/aac.00136-23 -
Biochemical Society Transactions Jun 2024Mupirocin is a broad-spectrum antibiotic that acts predominantly against Gram-positive bacteria. It is produced by Pseudomonas fluorescens NCIMB 10586 and has been... (Review)
Review
Mupirocin is a broad-spectrum antibiotic that acts predominantly against Gram-positive bacteria. It is produced by Pseudomonas fluorescens NCIMB 10586 and has been clinically used to treat primary and secondary skin infections and to eradicate nasal colonisation of methicillin-resistant Staphylococcus aureus strains. Mupirocin inhibits protein synthesis by blocking the active site of isoleucyl-tRNA synthetase (IleRS), which prevents the enzyme from binding isoleucine and ATP for Ile-tRNAIle synthesis. Two types of IleRS are found in bacteria - while IleRS1 is susceptible to mupirocin inhibition, IleRS2 provides resistance to cells. These two types belong to distinct evolutionary clades which likely emerged from an early gene duplication in bacteria. Resistance in IleRS2 is based on the loss of interactions that govern mupirocin binding to IleRS1, such as hydrogen bonding to the carboxylate moiety of mupirocin. IleRS2 enzymes with Ki in the millimolar range have recently been discovered. These hyper-resistant IleRS2 variants surprisingly have a non-canonical version of the catalytic motif, which serves as a signature motif of class I aminoacyl-tRNA synthetases to which IleRS belongs. The non-canonical motif, in which the 1st and 3rd positions are swapped, is key for hyper-resistance and can be accommodated without abolishing enzyme activity in IleRS2 but not in IleRS1. Clinical use of mupirocin led to the emergence of resistance in S. aureus. Low-level resistance arises by mutations of the housekeeping IleRS1, while high-level resistance develops by the acquisition of the resistant IleRS2 on a plasmid. There is no evidence that hyper-resistant variants have been found in clinical isolates.
Topics: Mupirocin; Isoleucine-tRNA Ligase; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus
PubMed: 38884776
DOI: 10.1042/BST20230581 -
Journal of Nanobiotechnology Jul 2023The rapid and accurate identification of methicillin-resistant Staphylococcus aureus at an early antibiotic therapy stage would be benefit to disease diagnosis and...
The rapid and accurate identification of methicillin-resistant Staphylococcus aureus at an early antibiotic therapy stage would be benefit to disease diagnosis and antibiotic selection. Herein, we integrated cross-priming amplification (CPA) and CRISPR/Cas 12a (designated as CPA-Cas 12a) systems to establish a sensitive and efficient lateral flow assay to detect methicillin-resistant Staphylococcus aureus. This assay relies on the CPA isothermal nucleic acid amplification strategy which can amplify the DNA extracted from Staphylococcus aureus and accompanying the indiscriminately trans-cleavage process of Cas 12a/CrRNA duplex after recognizing specific sequence. Taking the advantage of reporter and high turnover Cas 12a activity, a dramatic change in response was achieved to produce a significant increase in the analytical sensitivity. The signal conversion and output were realized using a lateral flow strip to achieve field-deployable detection. Furthermore, this bioassay was accommodated with a microfluidic device to realize automatically portable detection. This proposed assay completed within 30 min with the detection limit of 5 CFU mL, was verified by testing bacterial suspension and 202 clinical samples. Given the high sensitivity, specificity and efficiency, this colorimetric readout assay through strip could be further promoted to the clinical diagnosis, clinical medication of multidrug-resistant bacteria.
Topics: Methicillin-Resistant Staphylococcus aureus; CRISPR-Cas Systems; Cross-Priming; Staphylococcus aureus; Anti-Bacterial Agents; Biological Assay
PubMed: 37481551
DOI: 10.1186/s12951-023-02002-1 -
Infection and Drug Resistance 2023Antimicrobial resistance (AMR) represents a major threat to global health. Infection caused by Methicillin-resistant (MRSA) is one of the well-recognized global public... (Review)
Review
Antimicrobial resistance (AMR) represents a major threat to global health. Infection caused by Methicillin-resistant (MRSA) is one of the well-recognized global public health problem globally. In some regions, as many as 90% of infections are reported to be MRSA, which cannot be treated with standard antibiotics. WHO reports indicated that MRSA is circulating in every province worldwide, significantly increasing the risk of death by 64% compared to drug-sensitive forms of the infection which is attributed to its antibiotic resistance. The emergence and spread of antibiotic-resistant MRSA strains have contributed to its increased prevalence in both healthcare and community settings. The resistance of to methicillin is due to expression of penicillin-binding protein 2a (PBP2a), which renders it impervious to the action of β-lactam antibiotics including methicillin. The other is through the production of beta-lactamases. Although the treatment options for MRSA are limited, there are promising alternatives to antibiotics to combat the infections. Innovative therapeutic strategies with wide range of activity and modes of action are yet to be explored. The review highlights the global challenges posed by MRSA, elucidates the mechanisms underlying its resistance development, and explores mitigation strategies. Furthermore, it focuses on alternative therapies such as bacteriophages, immunotherapy, nanobiotics, and antimicrobial peptides, emphasizing their synergistic effects and efficacy against MRSA. By examining these alternative approaches, this review provides insights into the potential strategies for tackling MRSA infections and combatting the escalating threat of AMR. Ultimately, a multifaceted approach encompassing both conventional and novel interventions is imperative to mitigate the impact of MRSA and ensure a sustainable future for global healthcare.
PubMed: 38111667
DOI: 10.2147/IDR.S428103 -
BMC Health Services Research Jul 2023Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of...
BACKGROUND AND OBJECTIVE
Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceed the national average drug resistance level, and vancomycin and linezolid are the primary antibacterial drugs used for these resistant bacteria according to the results of etiological examinations. However, a comprehensive evaluation of their costs and benefits in late-onset neonatal sepsis in a neonatal intensive care unit (NICU) has not been conducted. This study aimed to compare the cost and effectiveness of vancomycin and linezolid in treating neonatal sepsis in the NICU.
METHODS
A cost-effectiveness analysis of real-world data was carried out by retrospective study in our hospital, and the cost and effectiveness of vancomycin and linezolid were compared by establishing a decision tree model. The drug doses in the model were 0.6 g for linezolid and 0.5 g for vancomycin. The cost break down included cost of medical ward, NICU stay, intravenous infusion of vancomycin or linezolid, all monitoring tests, culture tests and drugs. The unit costs were sourced from hospital information systems. The effectiveness rates were obtained by cumulative probability analysis. One-way sensitivity analysis was used to analyze uncertain influencing factors.
RESULTS
The effectiveness rates of vancomycin and linezolid in treating neonatal sepsis in the NICU were 89.74% and 90.14%, respectively, with no significant difference. The average cost in the vancomycin group was ¥12261.43, and the average cost in the linezolid group was ¥17227.96. The incremental cost effectiveness was ¥12416.33 cost per additional neonate with treatment success in the linezolid group compared to vancomycin group at discharge. Factors that had the greatest influence on the sensitivity of the incremental cost-effectiveness ratio were the price of linezolid and the effectiveness rates.
CONCLUSIONS
The cost for treatment success of one neonate in linezolid group was ¥5449.17 more than that in vancomycin group, indicating that vancomycin was more cost-effective. Therefore, these results can provide a reference for a cost effectiveness treatment scheme for neonatal sepsis in the NICU.
Topics: Vancomycin; Linezolid; Anti-Bacterial Agents; Neonatal Sepsis; Cost-Effectiveness Analysis; Humans; Methicillin-Resistant Staphylococcus aureus; Male; Female; Infant; Coagulase; Retrospective Studies; Drug Costs; Treatment Outcome; China
PubMed: 37468855
DOI: 10.1186/s12913-023-09628-9 -
Microorganisms Aug 2023The objective of this study was to evaluate the microbiological quality and safety of 37 fresh quail meats. Mesophiles, spp., , and staphylococci counts were 5.25 ±...
The objective of this study was to evaluate the microbiological quality and safety of 37 fresh quail meats. Mesophiles, spp., , and staphylococci counts were 5.25 ± 1.14, 3.92 ± 1.17, 3.09 ± 1.02, and 2.80 ± 0.64 log CFU/g, respectively. was detected in seven samples (18.92%). was detected in one sample (2.70%). was not detected in any sample. The dominant bacteria were spp. (30.46%), (19.87%), lactic acid bacteria (14.57%), and (11.92%). and enterococci were isolated to a lesser extent, 7.28% and 1.99%, respectively. The dominant found were (42.53%). ESBL-producing was detected in one sample (2.70%), showing resistance to 16 antibiotics. Sixteen different spp. and three spp. were identified, the most common being (19.86%) and (17.02%). and were also found in one and four samples, respectively. Methicillin-resistant and were found in 13.51% and 10.81% of quail samples, respectively. These bacteria showed an average of 6.20 and 18.50 resistances per strain, respectively. The high resistance observed in ESBL-producing and methicillin-resistant is of special concern. Measures should be adopted to reduce the contamination of quail meat.
PubMed: 37764057
DOI: 10.3390/microorganisms11092213 -
Cell Host & Microbe Jul 2023New classes of antibiotics are desperately needed in our fight against antibiotic-resistant bacterial infections. Jia et al. publish a new "multi-armed" antibiotic...
New classes of antibiotics are desperately needed in our fight against antibiotic-resistant bacterial infections. Jia et al. publish a new "multi-armed" antibiotic scaffold that effectively treats methicillin-resistant Staphylococcus aureus infections in mice. These compounds are structurally unlike pre-clinical or approved antibiotics, and they may hit an "irresistible" target.
Topics: Animals; Mice; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Staphylococcal Infections; Microbial Sensitivity Tests
PubMed: 37442092
DOI: 10.1016/j.chom.2023.06.011 -
The Journal of Antimicrobial... Aug 2023Methicillin-resistant Staphylococcus pseudintermedius (MRSP) lineages harbouring staphylococcal cassette chromosome (SCC) mec types IV, V and ΨSCCmec57395 usually...
BACKGROUND
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) lineages harbouring staphylococcal cassette chromosome (SCC) mec types IV, V and ΨSCCmec57395 usually display low oxacillin MICs (0.5-2 mg/L).
OBJECTIVES
To evaluate how oxacillin MICs correlate with PBP mutations and susceptibility to β-lactams approved for veterinary use.
METHODS
Associations between MICs and PBP mutations were investigated by broth microdilution, time-kill and genome sequence analyses in 117 canine MRSP strains harbouring these SCCmec types. Clinical outcome was retrospectively evaluated in 11 MRSP-infected dogs treated with β-lactams.
RESULTS
Low-level MRSP was defined by an oxacillin MIC <4 mg/L. Regardless of strain genotype, all low-level MRSP isolates (n = 89) were cefalexin susceptible, whereas no strains were amoxicillin/clavulanate susceptible according to clinical breakpoints. Exposure to 2× MIC of cefalexin resulted in complete killing within 8 h. High (≥4 mg/L) oxacillin MICs were associated with substitutions in native PBP2, PBP3, PBP4 and acquired PBP2a, one of which (V390M in PBP3) was statistically significant by multivariable modelling. Eight of 11 dogs responded to systemic therapy with first-generation cephalosporins (n = 4) or amoxicillin/clavulanate (n = 4) alone or with concurrent topical treatment, including 6 of 7 dogs infected with low-level MRSP.
CONCLUSIONS
Oxacillin MIC variability in MRSP is influenced by mutations in multiple PBPs and correlates with cefalexin susceptibility. The expert rule recommending that strains with oxacillin MIC ≥0.5 mg/L are reported as resistant to all β-lactams should be reassessed based on these results, which are highly clinically relevant in light of the shortage of effective antimicrobials for systemic treatment of MRSP infections in veterinary medicine.
Topics: Dogs; Animals; Methicillin-Resistant Staphylococcus aureus; Cephalexin; Methicillin Resistance; Retrospective Studies; Dog Diseases; Staphylococcal Infections; Oxacillin; Amoxicillin-Potassium Clavulanate Combination; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37294541
DOI: 10.1093/jac/dkad182 -
Cureus Oct 2023Methicillin-resistant (MRSA) is a common hospital-acquired pathogen and can cause a wide spectrum of infections. In recent years, MRSA has emerged as a significant... (Review)
Review
Methicillin-resistant (MRSA) is a common hospital-acquired pathogen and can cause a wide spectrum of infections. In recent years, MRSA has emerged as a significant public health concern, particularly in hospitals. Intensive care units (ICUs) and burn units are high-risk areas for hospital-acquired MRSA infections, which can lead to increased morbidity, mortality, and healthcare costs. MRSA exhibits resistance to multiple antibiotics and can cause serious infections, including but not limited to pneumonia, endocarditis, and cutaneous infections, particularly in patients with burn injuries. The prevention and effective management of MRSA infections in both burn patients and those in ICUs is crucial, with strategies like isolation, regular disinfection, and prophylactic intranasal mupirocin. Early diagnosis of MRSA infection and isolation of patients is vital to prevent the spread of MRSA. Implementation of prevention strategies faces many challenges, such as cost, and the most successful infection management practices are still debated. This review has highlighted the substantial concern of MRSA colonization in intensive care and burn units. MRSA poses a significant risk to vulnerable patients, influenced by factors such as compromised immunity and invasive procedures. The prevalence of MRSA colonization varies, influenced by regional factors and infection control practices. Combating MRSA requires a multifaceted approach, including stringent infection control measures and education for healthcare workers and patients. As we move forward, continued research and cooperation are essential to reduce the burden of MRSA in these critical care settings.
PubMed: 38021721
DOI: 10.7759/cureus.47139 -
Microbiology Spectrum Aug 2023Methicillin-resistant Staphylococcus aureus (MRSA) is a clinical threat with high morbidity and mortality. Here, we describe a new simple, rapid identification method...
Methicillin-resistant Staphylococcus aureus (MRSA) is a clinical threat with high morbidity and mortality. Here, we describe a new simple, rapid identification method for MRSA using oxacillin sodium salt, a cell wall synthesis inhibitor, combined with Gram staining and machine vision (MV) analysis. Gram staining classifies bacteria as positive (purple) or negative (pink) according to the cell wall structure and chemical composition. In the presence of oxacillin, the integrity of the cell wall for methicillin-susceptible S. aureus (MSSA) was destroyed immediately and appeared Gram negative. In contrast, MRSA was relatively stable and appeared Gram positive. This color change can be detected by MV. The feasibility of this method was demonstrated in 150 images of the staining results for 50 clinical S. aureus strains. Based on effective feature extraction and machine learning, the accuracies of the linear linear discriminant analysis (LDA) model and nonlinear artificial neural network (ANN) model for MRSA identification were 96.7% and 97.3%, respectively. Combined with MV analysis, this simple strategy improved the detection efficiency and significantly shortened the time needed to detect antibiotic resistance. The whole process can be completed within 1 h. Unlike the traditional antibiotic susceptibility test, overnight incubation is avoided. This new strategy could be used for other bacteria and represents a new rapid method for detection of clinical antibiotic resistance. Oxacillin sodium salt destroys the integrity of the cell wall of MSSA immediately, appearing Gram negative, whereas MRSA is relatively stable and still appears Gram positive. This color change can be detected by microscopic examination and MV analysis. This new strategy has significantly reduced the time to detect resistance. The results show that using oxacillin sodium salt combined with Gram staining and MV analysis is a new, simple and rapid method for identification of MRSA.
Topics: Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcus aureus; Microbial Sensitivity Tests; Oxacillin; Methicillin; Staining and Labeling; Anti-Bacterial Agents; Staphylococcal Infections
PubMed: 37395643
DOI: 10.1128/spectrum.05282-22