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Staphylococcus aureus or methicillin-resistant Staphylococcus aureus (MRSA) is an important issue associated with significant morbidity and mortality and well known as a predominant pathogen causing bloodstream infection (BSIs) globally. To estimate the antibiotic resistance and molecular characteristics of S. aureus causing BSIs in Shanghai, 120  S. aureus isolates (20 isolates each year) from the patients with S. aureus BSIs from 2013 to 2018 were randomly selected and enrolled in this study. Fifty-three (44.2%) MRSA isolates were determined, and no isolate was found resistant to vancomycin, daptomycin, synercid, linezolid and ceftaroline. The toxin genes tst , sec , seg and sei were found more frequently among MRSA isolates compared with MSSA isolates (all P  < 0.0001). Twenty-nine sequence types (STs) were identified, and ST5 (23.3%) was the most common ST, followed by ST398 (11.7%) and ST764 (10.0%). SCC mec II (73.6%) was the most frequent SCC mec type among MRSA isolates. The dominant clonal complexes (CCs) were CC5 (ST5, ST764, ST965 and ST3066; 36.7%) and the livestock-associated clone CC398 (ST398, 11.7%). MRSA-CC5 was the predominant CC among MRSA isolates (37/53, 69.8%), and CC5-II MRSA was found in 34 isolates accounting for 91.9% (34/37) among CC5 MRSA isolates. In addition, all 29 tst -positive MRSA isolates were CC5-MRSA as well. Our study provided the properties and genotypes of S. aureus causing BSIs at Ruijin Hospital in Shanghai from 2013 to 2018, and might suggest of value clues for the further study insights into pathogenic mechanisms intrinsically referring to the development of human-adapted S. aureus clones and their diffusions.

Methicillin-Resistant Staphylococcus aureus (MRSA) is a significant threat to human health. Additionally, biofilm forming bacteria becomes more tolerant to antibiotics and act as bacterial reservoir leading to chronic infection. In this study, we characterised the antibiotic susceptibility, biofilm production and sequence types (ST) of 74 randomly selected clinical isolates of S. aureus causing ocular infections. Antibiotic susceptibility revealed 74% of the isolates as resistant against one or two antibiotics, followed by 16% multidrug-resistant isolates (MDR), and 10% sensitive. The isolates were characterized as MRSA (n = 15), Methicillin-sensitive S. aureus (MSSA, n = 48) and oxacillin susceptible mecA positive S. aureus (OS-MRSA, n = 11) based on oxacillin susceptibility, mecA gene PCR and PBP2a agglutination test. All OS-MRSA would have been misclassified as MSSA on the basis of susceptibility test. Therefore, both phenotypic and genotypic tests should be included to prevent strain misrepresentation. In addition, in-depth studies for understanding the emerging OS-MRSA phenotype is required. The role of fem XAB gene family has been earlier reported in OS-MRSA phenotype. Sequence analysis of the fem XAB genes revealed mutations in fem  × (K3R, H11N, N18H and I51V) and fem B (L410F) genes. The fem XAB genes were also found down-regulated in OS-MRSA isolates in comparison to MRSA. In OS-MRSA isolates, biofilm formation is regulated by fibronectin binding proteins A & B. Molecular typing of the isolates revealed genetic diversity. All the isolates produced biofilm, however, MRSA isolates with strong biofilm phenotype represent a worrisome situation and may even result in treatment failure.

Background Foot infections are a major cause of morbidity in people with diabetes and the most common cause of diabetes-related hospitalization and lower extremity amputation. Staphylococcus aureus is by far the most frequent species isolated from these infections. In particular, methicillin-resistant S. aureus (MRSA) has emerged as a major clinical and epidemiological problem in hospitals. MRSA strains have the ability to be resistant to most β-lactam antibiotics, but also to a wide range of other antimicrobials, making infections difficult to manage and very costly to treat. To date, there are two fifth-generation cephalosporins generally efficacious against MRSA, ceftaroline and ceftobripole, sharing a similar spectrum. Biofilm formation is one of the most important virulence traits of S. aureus. Biofilm growth plays an important role during infection by providing defence against several antagonistic mechanisms. In this study, we analysed the antimicrobial susceptibility patterns of biofilm-producing S. aureus strains isolated from diabetic foot infections. The antibiotic minimum inhibitory concentration (MIC) was determined for ten antimicrobial compounds, along with the minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC), followed by PCR identification of genetic determinants of biofilm production and antimicrobial resistance. Results Results demonstrate that very high concentrations of the most used antibiotics in treating diabetic foot infections (DFI) are required to inhibit S. aureus biofilms in vitro, which may explain why monotherapy with these agents frequently fails to eradicate biofilm infections. In fact, biofilms were resistant to antibiotics at concentrations 10–1000 times greater than the ones required to kill free-living or planktonic cells. The only antibiotics able to inhibit biofilm eradication on 50 % of isolates were ceftaroline and gentamicin. Conclusions The results suggest that the antibiotic susceptibility patterns cannot be applied to biofilm established infections. Selection of antimicrobial therapy is a critical step in DFI and should aim at overcoming biofilm disease in order to optimize the outcomes of this complex pathology.

Background Staphylococcus aureus clinical isolates with vancomycin MICs of 2 µg/ml have been associated with vancomycin therapeutic failure and the heterogenous vancomycin-intermediate S. aureus (hVISA) phenotype. While carriage of van genes has usually been associated with higher level of MIC and frank vancomycin resistance, the unrecognized risk of hetero-resistance is frequently underestimated. Methods used for assessing vancomycin susceptibility have also shown different concordance and variable performance and accessibility in routine clinical diagnostics posing a challenge to inform treatment selection in hospital settings. Methods A total of 195 clinical samples were obtained among which 100 S. aureus isolates were identified. Ninety-six MRSA isolates have been identified using cefoxitin disc and mec A gene detection. The van A and van B genes have been screened for in the studied isolates using conventional PCR amplification. Examination of reduced vancomycin susceptibility has been performed using vancomycin screen agar, Broth Micro Dilution method (BMD), and VITEK2. Blood isolates were screened for hVISA using PAP-AUC method. Results Vancomycin screening agar applied to 96 MRSA isolates revealed 16 isolates with reduced vancomycin susceptibility. Further MIC testing revealed that 7 isolates were VISA and only 1 isolate was identified as VRSA using both BMD MIC method and VITEK2. Among 24 tested blood isolates, 4 isolates (16.7%) revealed the hVISA phenotype as identified using PAP-AUC method. Using PCR, van A gene was identified in 5 S. aureus isolates (5%). Three of them were VSSA while the other two isolates were VISA. Conclusion In this study, we report the very low prevalence of VRSA among the tested S. aureus clinical isolates (1%) and the existence of hVISA phenotype among studied S. aureus blood isolates at the rate of 16.7% in our setting. Fifty percent (8/16) of isolates that demonstrated reduced vancomycin susceptibility using vancomycin agar screen tested susceptible using both broth dilution method and VITEK2. These finding together with the concerning silent carriage of van A gene among VSSA and VISA (5%) may underly hidden and uninvestigated factors contributing to vancomycin treatment failure that warrant cautious vancomycin prescription.

Objective This research study was undertaken to investigate antimicrobial resistance patterns and the prevalence of hospital-acquired infections (HAIs). The study focuses on common microorganisms responsible for HAIs and explores emerging challenges posed by antimicrobial drug-resistant isolates. Methods A comprehensive analysis of 123 patients with HAIs, hospitalized in surgical department and intensive care unit (ICU) at Imam Khomeini Hospital, Ilam, Iran, was conducted over a six-month period. Pathogenic bacterial isolates, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA), were isolated and subjected to antibiotic susceptibility testing. Results The study findings revealed a significant prevalence of multidrug-resistant (MDR) isolates, of which 73.3% were MRSA. Notably, 6.7% of S. aureus isolates exhibited resistance to vancomycin, indicating the emergence of VRSA. Respiratory infections were identified as the most prevalent HAI, constituting 34.67% of cases, often arising from extended ICU stays and invasive surgical procedures. Furthermore, patients aged 60 and above, particularly those associated with MDR, exhibited higher vulnerability to HAI. Conclusions This research sheds light on the intricate interplay between drug resistance and HAI, highlighting the imperative role of rational antibiotic use and infection control in addressing this critical healthcare challenge.

Background Staphylococcus aureus and beta-hemolytic streptococci (BHS) diseases disproportionately affect populations in middle/low-income countries. To assess if this disparity is reflected in colonization by these organisms, we compared their colonization frequency among children from different socioeconomic status (SES) communities in a city with high income inequality. Methods Between May–August 2014, we collected nasal and throat swabs to investigate S. aureus and BHS colonization among children who attended private and public pediatric clinics. Patients were classified as high SES, middle/low SES, and slum residents. We investigated the antimicrobial resistance profile, the SCC mec types and the presence of PVL genes among methicillin-resistant S. aureus (MRSA). We also examined the antimicrobial resistance profile and serogroups of BHS. Results Of 598 children, 221 (37%) were colonized with S. aureus , of which 49 (22%) were MRSA. MRSA colonization was higher in middle/low SES ( n  = 18; 14%) compared with high SES ( n  = 17; 6%) and slum ( n  = 14; 8%) residents ( p  = 0.01). All MRSA strains were susceptible to clindamycin, nitrofurantoin, and rifampin. The highest non-susceptibility frequency (42.9%) was observed to erythromycin. SCC mec type V was only found in isolates from high SES children; types I and II were found only in middle/low SES children. Ten (20%) MRSA isolates carried PVL genes. Twenty-four (4%) children were BHS carriers. All BHS ( n  = 8) found in high SES children and six (67%) isolates from slum patients belonged to group A. All group B streptococci were from middle/low SES children, corresponding to five (71%) of the seven BHS isolated in this group. BHS isolates were susceptible to all drugs tested. Conclusions Children from different SES communities had distinct bacterial colonization profiles, including MRSA carriage. Public health officials/researchers should consider SES when assessing disease transmission and control measures.

ABSTRACT Invasive Staphylococcus aureus infections are a leading cause of morbidity and mortality in both hospital and community settings, especially with the widespread emergence of virulent and multi-drug resistant methicillin-resistant S. aureus strains. There is an urgent and unmet clinical need for non-antibiotic immune-based approaches to treat these infections as the increasing antibiotic resistance is creating a serious threat to public health. However, all vaccination attempts aimed at preventing S. aureus invasive infections have failed in human trials, especially all vaccines aimed at generating high titers of opsonic antibodies against S. aureus surface antigens to facilitate antibody-mediated bacterial clearance. In this review, we summarize the data from humans regarding the immune responses that protect against invasive S. aureus infections as well as host genetic factors and bacterial evasion mechanisms, which are important to consider for the future development of effective and successful vaccines and immunotherapies against invasive S. aureus infections in humans. The evidence presented form the basis for a hypothesis that staphylococcal toxins (including superantigens and pore-forming toxins) are important virulence factors, and targeting the neutralization of these toxins are more likely to provide a therapeutic benefit in contrast to prior vaccine attempts to generate antibodies to facilitate opsonophagocytosis. This review summarizes the data from humans regarding the immune responses that protect against invasive Staphylococcus aureus infections as well as host genetic factors and bacterial evasion mechanisms, which form the basis for a hypothesis that future vaccines and immune-based therapies that target the neutralization of staphylococcal toxins superantigens and pore-forming toxins are more likely to provide a therapeutic benefit.

SCC mec is a large mobile genetic element that includes the mecA gene and confers resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA). There is evidence that SCC mec disseminates among staphylococci, but the transfer mechanisms are unclear. Here, we show that two-component systems mediate the upregulation of natural competence genes in S. aureus under biofilm growth conditions, and this enhances the efficiency of natural transformation. We observe SCC mec transfer via natural transformation from MRSA, and from methicillin-resistant coagulase-negative staphylococci, to methicillin-sensitive S. aureus . The process requires the SCC mec recombinase genes ccrAB , and the stability of the transferred SCC mec varies depending on SCC mec types and recipients. Our results suggest that natural transformation plays a role in the transfer of SCC mec and possibly other mobile genetic elements in S. aureus biofilms. SCC mec is a large mobile genetic element that confers resistance to β-lactam antibiotics in methicillin-resistant Staphylococcus aureus . Here, the authors show that biofilm growth conditions enhance the efficiency of natural transformation in S. aureus and allow the transfer of SCC mec to methicillin-sensitive strains.

Staphylococcus aureus is an important human and livestock pathogen that is well-protected against environmental insults by a thick cell wall. Accordingly, the wall is a major target of present-day antimicrobial therapy. Unfortunately, S. aureus has mastered the art of antimicrobial resistance, as underscored by the global spread of methicillin-resistant S. aureus (MRSA). The major cell wall component is peptidoglycan. Importantly, the peptidoglycan network is not only vital for cell wall function, but it also represents a bacterial Achilles’ heel. In particular, this network is continuously opened by no less than 18 different peptidoglycan hydrolases (PGHs) encoded by the S. aureus core genome, which facilitate bacterial growth and division. This focuses attention on the specific functions executed by these enzymes, their subcellular localization, their control at the transcriptional and post-transcriptional levels, their contributions to staphylococcal virulence and their overall importance in bacterial homeostasis. As highlighted in the present review, our understanding of the different aspects of PGH function in S. aureus has been substantially increased over recent years. This is important because it opens up new possibilities to exploit PGHs as innovative targets for next-generation antimicrobials, passive or active immunization strategies, or even to engineer them into effective antimicrobial agents.

Vancomycin is a glycopeptide antibiotic used for the treatment of Gram-positive bacterial infections. Traditionally, it has been used as a drug of last resort; however, clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) strains with decreased susceptibility to vancomycin (vancomycin intermediate-resistant S. aureus [VISA]) and more recently with high-level vancomycin resistance (vancomycin-resistant S. aureus [VRSA]) have been described in the clinical literature. The rare VRSA strains carry transposon Tn1546, acquired from vancomycin-resistant Enterococcus faecalis, which is known to alter cell wall structure and metabolism, but the resistance mechanisms in VISA isolates are less well defined. Herein, we review selected mechanistic aspects of resistance in VISA and summarize biochemical studies on cell wall synthesis in a VRSA strain. Finally, we recapitulate a model that integrates common mechanistic features of VRSA and VISA strains and is consistent with the mode of action of vancomycin.