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Background: Post-surgical invasive Staphylococcus aureus infections among spinal fusion patients are serious complications that can worsen clinical outcomes and increase healthcare utilization. Ris...

Introduction. In 2012, the Canary Islands Health Service implemented a new surveillance system for nosocomial infections caused by multi-resistant microorganisms and Clostridioides difficile. This system will make it possible to know the incidence rates of these pathogens, periodically contrast them to monitor their trend and compare them with those of other national and European health institutions. Patients and method. Observational, prospective study of the density of incidence of multi-resistant pathogens and Clostridioides difficile in the healthcare centers of the Canary Islands Health Service from 2012 to 2019. Results. The incidence density of methicillin-resistant Staphylococcus aureus infections for 2012 was 1.96 cases per 10,000 stays and decreased to 0.80 in 2019, reaching the lowest figure in the surveillance period. Infections due to carbapenemase-producing Enterobacterales (CPE) showed an upward trend, 0.47 (2014) and 2.35 (2019). The slight upward trend in imipenem-resistant Acinetobacter baumannii infections in observed bacteraemias 0.17 (2012) and 0.09 (2019) has been corrected. No cases of infection with vancomycin-resistant enterococci were observed. With regard to C. difficile, an upward trend that began in 2012 has consolidated, producing an increase of 216% in the number of cases detected at the end of the study period. Conclusion. The most relevant problem detected today is the CPE. The data analyzed in this period showed an evident change in the trend of the multi-resistant pathogens studied. This fact must be confirmed in the future.

Staphylococcus aureus infections are known to cause leukocytoclastic vasculitis (LCV). Herein, we describe a case of an 18-month-old with LCV caused by enterotoxin-producing methicillin-sensitive Staphylococcus aureus (MSSA) emanating from an unrecognized pharyngeal abscess. It is critical to consider the possibility of extracutaneous sources of MSSA infection when investigating an infant with vasculitis. Prompt diagnosis and appropriate treatment are vital in preventing potentially life-threatening complications.

The enormous spread of Staphylococcus aureus infections through biofilms is a major concern in hospital-acquired infections. Biofilm formation by S. aureus on any surface is facilitated by adjusting its redox status. This organism is a facultative anaerobe shift more towards reductive conditions by enhancing nitrogen metabolism where glutamine synthesis plays a key role. Glutamine is synthesized by glutamine synthetase (GS) encoded by the glnA gene. The gene was amplified by PCR from the chromosomal DNA of S. aureus, sequenced (HQ329146.1), and cloned. The pure recombinant GS exhibited Km of 11.06 ± 0.05 mmol·L−1 for glutamate and 2.4 ± 0.03 mmol·L−1 for ATP. The glnA gene sequence showed a high degree of variability with its human counterpart, while it was highly conserved in bacteria. Structural analysis revealed that the GS structure of S. aureus showed close homology with other Gram-positive bacteria and exhibited a high degree of variation with Escherichia coli GS. In the present study, we observed the increased presence of GS activity in multidrug-resistant strains of S. aureus with elevated biofilm units, grown in brain heart infusion broth; among them methicillin-resistant strains S. aureus LMV 3, 4, and 5 showed higher biofilm units. All these results explain the important role of glutamine biosynthesis with elevated biofilm units in the pathogenesis of S. aureus.

To evaluate the impact of active surveillance cultures (ASC) for Staphylococcus aureus (SA) and decolonization on the rate of infection in neonates in a neonatal intensive care unit (NICU). Using a quasi-experimental design with control groups, rates of SA infections before and after implementing weekly ASC and topical mupirocin decolonization in a level IV NICU were compared. Comparators were the rates of gram negative bloodstream infections (BSI) and of SA BSI at an affiliated NICU where the intervention was not implemented. There was a 77% (p

The American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists have recently published revised guidelines for the therapeutic monitoring of vancomycin. Previous iterations of the guideline largely focused on targeting vancomycin trough concentrations (VTCs) in the range of 15 to 20 mg/L for therapeutic efficacy. The revised guidelines shift the focus of therapeutic monitoring directly to AUC/MIC-based therapeutic monitoring for children, with a suggestion of a goal AUC/MIC 400 to 800. The primary hesitation in applying these recommendations to children stems from the absence of pediatric clinical data demonstrating correlations with clinical outcomes and either VTC or AUC and no benefit in other secondary outcomes (e.g., recurrence, duration of bacteremia). One can glean indirectly from this that such aggressive dosing and monitoring strategies are unnecessary to achieve therapeutic success in the majority of children with serious methicillin-resistant Staphylococcus aureus infections. Providers should carefully weigh the potential unknown benefits of targeting vancomycin AUC 400 to 800 mg*hr/L in children with the known risks of acute kidney injury associated with increasing the dose of vancomycin as well as the substantial time, effort, and costs of this process.

Background Although Staphylococcus aureus is a leading cause of postsurgical infections, national estimates of these infections after elective surgeries based on microbiology data are limited. This study assessed cumulative 180-day postsurgical S. aureus incidence in real-world hospital settings. Methods A retrospective study of adults (≥18 years) undergoing inpatient or hospital-based outpatient elective surgeries from 1/7/2010–30/6/2015 at hospitals (N = 181) reporting microbiology results in the Premier Healthcare Database (PHD). 86 surgical categories were identified from the National Healthcare Safety Network procedures. We classified positive S. aureus cultures using a hierarchy (bloodstream [BSI], surgical site [SSI], and all other types [urinary tract, respiratory, other/unknown site]) and calculated incidence (number of infections divided by the number of elective surgery discharges). We estimated national infection case volumes by multiplying incidence by national inpatient elective surgical discharge estimates using the entire PHD and weights based on hospital characteristics. Results Following 884 803 inpatient elective surgical discharges, 180-day S. aureus infection incidence was 1.35% (0.30% BSI, 0.74% SSI no BSI, 0.32% all other types only). Among 1 116 994 hospital-based outpatient elective surgical discharges, 180-day S. aureus incidence was 1.19% (0.25% BSI, 0.75% SSI no BSI, 0.19% all other types only). Methicillin resistance was observed in ~45% of the S. aureus infections. We estimated 55 764 S. aureus postsurgical infections occurred annually in the US following 4.2 million elective inpatient surgical discharges. Conclusions The high burden of S. aureus infections after both inpatient and outpatient elective surgeries highlights the continued need for surveillance and novel infection prevention efforts.

Staphylococcus aureus is a major cause of severe invasive infections. The increasing incidence of infections caused by antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA), calls for exploration of new approaches to treat these infections. Mupirocin is an antibiotic with a unique mode of action that is active against MRSA, but its clinical use is restricted to topical administration because of its limited plasma stability and rapid degradation to inactive metabolites. Mupirocin was identified by a machine learning approach to be suitable for nano-liposome encapsulation. The computational predictions were verified experimentally and PEGylated nano-liposomal formulation of mupirocin (Nano-mupirocin) was developed. The aim of this study was to investigate the efficacy of this formulation when administered parenterally for the treatment of S. aureus invasive infections. Nano-mupirocin exhibited prolonged half-life of active antibiotic and displayed superior antimicrobial activity against S. aureus than free mupirocin in the presence of plasma. Parenteral application of Nano-mupirocin in a murine model of S. aureus bloodstream infection resulted in improved antibiotic distribution to infected organs and in a superior therapeutic efficacy than the free drug. Parenterally administered Nano-mupirocin was also more active against MRSA than free mupirocin in a neutropenic murine lung infection model. In addition, Nano-mupirocin was very efficiently taken up by S. aureus-infected macrophages via phagocytosis leading to enhanced delivery of mupirocin in the intracellular niche and to a more efficient elimination of intracellular staphylococci. The outcome of this study highlights the potential of Nano-mupirocin for the treatment of invasive MRSA infections and support the further clinical development of this effective therapeutic approach.

GUIDELINE TITLE: Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists RELEASE DATE: Online: March 19, 2020 PRIOR VERSION: 2009 DEVELOPERS: American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) FUNDING SOURCE: ASHP, IDSA, PIDS, SIDP TARGET POPULATION: Adults, children, and neonates treated for documented or presumed methicillin-resistant Staphylococcus aureus infection

Background:Staphylococcus aureus has long been an important cause of healthcare-associated infections (HAIs) and remains the second most common HAI pathogen in the United States. Often resistant to several antibiotics, S. aureus infections are difficult to treat and can leave patients at risk for serious complications such as pneumonia and sepsis. HAI pathogens and their antimicrobial susceptibility testing (AST) results have been reported to NHSN since its inception in 2005. Previous NHSN surveillance reports have presented national annual benchmarks for antimicrobial resistance phenotypes, such as methicillin-resistant S. aureus (MRSA). Whether there have been any significant changes over time in the prevalence of methicillin resistance among S. aureus infections reported to NHSN has not been previously assessed. Methods:S. aureus AST data from central-line–associated bloodstream infections, catheter-associated urinary tract infections, and inpatient surgical site infections reported from acute-care hospitals between 2009 and 2018 were analyzed. S. aureus was defined as MRSA if it was reported as resistant to oxacillin, cefoxitin, or methicillin. A national percentage resistant (%R) was calculated for each year as the number of resistant pathogens divided by the number of pathogens tested for susceptibility multiplied by 100. A generalized linear mixed model with logistic function was created to evaluate annual changes in the percentage resistant. Several patient-level and hospital-level characteristics were assessed as potential covariates. To account for differential baseline %R values between individual hospitals, specification of random intercept and slope were used during model creation. Differences in the trend of %R between HAI types were assessed using interaction terms. Data were analyzed using SAS v 9.3 software, and P < .05 was considered significant. Results: Overall, 3,317 hospitals reported at least 1 S. aureus pathogen tested for susceptibility between 2009 and 2018. The national unadjusted %R decreased from 49.2% (2009) to 41.2% (2018), with similar decreases seen in each HAI type (Table 1). After adjusting for significant covariates, a statistically significant annual 3% decrease in the prevalence of resistance was observed (Fig. 1). Significant differences between HAI types did not exist. Conclusions: The percentage of healthcare-associated S. aureus resistant to oxacillin, cefoxitin, or methicillin has declined consistently over the past 10 years. Continued efforts in infection prevention and antimicrobial stewardship are vital to sustaining this decline.Funding: NoneDisclosures: None

Background: Epidemiological studies have utilized administrative discharge diagnosis codes to identify methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA) infections and trends, despite debate regarding the accuracy of utilizing codes for this purpose. We assessed the sensitivity and positive predictive value (PPV) of MRSA- and MSSA-specific diagnosis codes, trends, characteristics, and outcomes of S. aureus hospitalizations by method of identification. Methods: Clinical micro biology results and discharge data from geographically diverse US hospitals participating in the Premier Healthcare Database from 2012–2017 were used to identify monthly rates of MRSA and MSSA. Positive MRSA or MSSA clinical cultures and/or a MRSA- or MSSA-specific International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9/10 CM) diagnosis codes from adult inpatients (aged ≥18 years) were included as S. aureus hospitalizations. Septicemia was defined as a positive blood culture or a MRSA or MSSA septicemia code. Sensitivity and PPV for codes were calculated for hospitalizations where admission status was not listed as transfer; true infection was considered a positive clinical culture. Negative binominal regression models measured trends in rates of MRSA and MSSA per 1,000 hospital discharges. Results: We identified 168,634 MRSA and 148,776 MSSA hospitalizations in 256 hospitals; 17% of MRSA and 21% of MSSA were septicemia. Less than half of all S. aureus hospitalizations (49% MRSA, 46% MSSA) and S. aureus septicemia hospitalizations (37% MRSA, 38% MSSA) had both a positive culture and diagnosis code (Fig. 1). Sensitivity of MRSA codes in identifying positive cultures was 61% overall and 56% for septicemia, PPV was 62% overall and 53% for septicemia. MSSA codes had a sensitivity of 49% in identifying MSSA cultures and 52% for MSSA septicemia; PPV was 69% overall and 62% for septicemia. Despite low sensitivity, MRSA trends are similar for cultures and codes, and MSSA trends are divergent (Fig. 2). For hospitalizations with septicemia, mortality was highest among those with a blood culture only (31.3%) compared to hospitalizations with both a septicemia code and blood culture (16.6%), and septicemia code only (14.7%). Conclusions: ICD diagnosis code sensitivity and PPV for identifying infections were consistently poor in recent years. Less than half of hospitalizations have concordant microbiology laboratory results and diagnosis codes. Rates and trend estimates for MSSA differ by method of identification. Using diagnosis codes to identify S. aureus infections may not be appropriate for descriptive epidemiology or assessing trends due to significant misclassification.Funding: NoneDisclosures: Scott Fridkin reports that his spouse receives consulting fees from the vaccine industry.

Background:Evidence suggests the standard vancomycin trough goal of 15 to 20 mg/L for serious Staphylococcus aureus infections is associated with acute kidney injury, whereas appropriate monitoring of 24-hour area under the curve (AUC) may decrease nephrotoxicity. As a result, institutions have transitioned to AUC monitoring, the predictive pharmacokinetic/pharmacodynamic parameter of vancomycin to improve safety outcomes. However, this method may require increased pharmacist time and effort. Pharmacist perception of the practice change is largely unknown and warrants investigation.Methods:An electronic survey was disseminated via e-mail to pharmacists 5 months post-AUC implementation. Items of interest were focused on pharmacist perception, including quantity of patients monitored using AUC, justification of the practice change, differences in efficacy and safety, and changes in monitoring time requirements.Results:The pharmacist survey was distributed to 196 pharmacists and 84 responded (43% response rate). Eighty-one pharmacists had monitored patients using AUC methods. Sixty-nine percent of these respondents perceived the change to result in increased or slightly increased patient safety, 27% described no difference, and 4% stated safety was decreased or slightly decreased. Forty-two percent perceived the transition to result in increased or slightly increased efficacy, while 48% noted no difference and 10% responded that efficacy was decreased or slightly decreased. Pharmacists stated the creation of an institutional calculator decreased the time required to calculate AUC.Conclusion:After the change to AUC monitoring, pharmacists perceived improvements in safety outcomes while efficacy was at least similar if not increased.

[Image: see text] β-Lactams are used routinely to treat Staphylococcus aureus infections. However, the emergence of methicillin-resistant S. aureus (MRSA) renders them clinically precarious. We describe a class of cinnamonitrile adjuvants that restore the activity of oxacillin (a penicillin member of the β-lactams) against MRSA. The lead adjuvants were tested against six important strains of MRSA, one vancomycin-intermediate S. aureus (VISA) strain, and one linezolid-resistant S. aureus strain. Five compounds out of 84 total compounds showed broad potentiation. At 8 μM (E)-3-(5-(3,4-dichlorobenzyl)-2-(trifluoromethoxy)phenyl)-2-(methylsulfonyl)acrylonitrile (26) potentiated oxacillin with a >4000-fold reduction of its MIC (from 256 to 0.06 mg·L(–1)). This class of adjuvants holds promise for reversal of the resistance phenotype of MRSA.

Panton-Valentine leukocidin (PVL) is a virulent cytotoxin and an indicator of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection. In this study, we evaluated the prevalence and clinical and molecular characteristics of PVL-positive invasive S. aureus (ISA) infections in Korea.A collection of 1,962 nonduplicate clinical isolates were screened for multilocus sequence typing, staphylococcal cassette chromosome mec (SCCmec), accessory gene regulator typing, major toxins, and antimicrobial susceptibility. Twenty-eight (1.4%) PVL-positive S. aureus samples were found; of them 19 (67.9%) were MRSA (8 CA and 11 healthcare-associated infections). Seventeen patients (60.7%) were men (median age: 63 years; range: 13-93 years) and 12 patients (42.9%) had no underlying comorbidities. The most common infections were skin and skin structure infection (SSSI) and pneumonia. The 30-day mortality rate was 37.0%. The most common PVL-positive MRSA clones were ST8-SCCmec IVa and ST30-SCCmec IVc along with their single-locus variants. Antimicrobial susceptibility and toxin-gene profile differed according to the clone.ISA infections caused by PVL-positive strains are rare in Korea, with the two most common infections being SSSI and pneumonia. Our findings indicated that several PVL-positive MRSA clones, predominantly ST8-SCCmecIVa and ST30-SCCmecIVc, were circulating and causing sporadic cases of ISA infections in the community and hospital settings.

Objective To determine and quantitatively measure the protective and/or therapeutic effect of Lactobacillus plantarum (LP) application on a burn wound before and after the onset of meticillin-resistant Staphylococcus aureus (MRSA) infection. Method Third-degree scald burns affecting 10% of body surface area were formed on the back of five groups of rats. Group 1 was designated as the control group. In Group 2, LP was applied immediately after the burn and then MRSA inoculated. In Group 3, MRSA was applied immediately after the burn and then LP inoculated. Groups 4 and 5 were designated as controls of LP and MRSA. On the fifth and tenth days, bacterial loads and compositions were assessed by tissue biopsies. Results Each group contained seven rats (n=35). In Group 2, MRSA colony counts were found to be significantly lower compared with the other groups (p0.05). Conclusion LP was shown to have a protective role in non-infected, burn wounds when applied before MRSA infection but a therapeutic effect of LP was not demonstrated. LP is thought to have a promising role in the prevention and treatment of burn wound infections.

Objectives Trimethoprim/sulfamethoxazole (SXT) is used to treat Staphylococcus aureus infections. However, the effect of treatment with SXT is sometimes not sufficient and there are patients whose treatment has to be prolonged. There are few reports of isolated strains of SXT-resistant S. aureus, but it is possible that some resistant strains cannot be detected by current testing methods We have therefore developed a tool to identify these resistant strains. Methods The mutant selection window (MSW) of SXT for 40 clinical isolates of S. aureus, including 20 methicillin-resistant S. aureus (MRSA), was determined. The optimum concentration of SXT and thymidine in agar for detecting SXT-resistant small colony variants (SCVs) of S. aureus was investigated. Results The MSW50 and MSW90 of SXT, presented as a multiple of the minimum inhibitory concentration (MIC), were 16× MIC and >256× MIC, respectively. SCVs were detected within the MSW in 32 (80%) of the 40 clinical isolates studied. To maintain the morphology of SCVs, the most suitable concentrations of SXT and thymidine for screening were 4 mg/L and 0.01 μg/mL, respectively. All 32 SCVs were resistant to SXT (MIC >32 mg/L). The sensitivity and specificity of this screening method was 100% and 88.9%, respectively. Conclusions SXT-resistant SCVs are not usually detected by routine laboratory tests performed in hospitals. However, the screening test described here can easily distinguish SXT-resistant SCVs among S. aureus isolated from specimens. This newly developed screening test could become an important tool to prevent inappropriate use of SXT.

Introduction: Staphylococcus aureus is a Gram-positive coconut that causes various life-threatening infections and, in turn, represents a major producer of healthcare-associated infections. This pathogen is highly resistant to antibiotics, which has made it difficult to eradicate in recent decades. Photodynamic therapy is a promising approach to address the notable shortage of antibiotic options against multidrug-resistant Staphylococcus aureus. This therapy combines the use of a photosensitizing agent, light, and oxygen to eradicate pathogenic microorganisms. The purpose of this study is to provide relevant bibliographic information about the application of photodynamic therapy as an alternative antimicrobial therapy for Staphylococcus aureus infections. Methods: This review was achieved through a bibliographic search in various databases and the analysis of relevant publications on the subject. Results: A large body of evidence demonstrates the efficacy of photodynamic therapy in eliminating biofilm- or biofilm-producing strains of Staphylococcus aureus, as well as antibiotic-resistant strains. Conclusion: We conclude that photodynamic therapy against Staphylococcus aureus is a recommended antibacterial therapy that may complement antibiotic treatment.

Background: Staphylococcus aureus (S. aureus) is the most common pathogen that causes osteomyelitis (OM). However, OM's pathogenesis, which is not clear, involves many factors such as environment, genetics and immunity dysregulation. This study aims to explore the key genes involved in the pathogenesis and development of OM following S. aureus infection. Methods: After obtaining the datasets of GSE6269 and GSE16129, we performed weighted gene co-expression network analysis (WGCNA) to find clusters modules of highly correlated genes and recursive feature elimination (RFE) method to narrow the range of feature genes. For determining the effect of feature genes, we constructed a random forest (RF) model with feature genes and validated the predictive validity of the RF model using independent data from GSE11908. The protein-protein interaction (PPI) network identifies essential proteins that contributed to OM development. Results: There were 12,401 genes from 77 samples that 48 S. aureus patients developed to OM and 29 of those without OM. We divided 31 significant gene modules into different modules, and the brown module significantly related to OM. Biological Functions of the brown module mainly enriched in the inflammatory response, metabolic, cancer, viral pathways, protein binding and RNA binding. After screening, 19 genes, including CYP2E1, BBS10, ARPC5L, GAPVD1, PURA, RBMS1, BTN2A2, EXOSC8, METTL8, FYCO1, KHK, PRPF38B, CD72, C2CD5, ABHD6, CD200, FAM53C, HCP5 and ELP1, were defined as feature genes for constructing RF model. After validating the external data, the average area under the curve was 85%, and the accuracy of the RF model was 85.7%. The protein function of modules enriched in the RNA exosome complex's catalytic component and regulation of actin polymerization. Conclusions: This study aimed to identify related genes involved in the occurrence and development of OM. We constructed the RF model with 19 genes, which effectively classify the patients with OM or non-OM. Despite its limitations, the study certainly adds to our understanding of OM's pathogenesis, and therefore, has significant implications for potential therapeutic targets and the predicted value of OM.

We demonstrate an automated, cost-effective system that delivers early antimicrobial-susceptibility-testing results, minimizing incubation time and eliminating human errors, while remaining compatible with standard clinical workflow. A neural network processes the time-lapse intensity information from a fiber-optic array to detect growth in each well of a 96-wellplate. Our blind testing on clinical Staphylococcus aureus infections reveals that 95.03% of all the wells containing growth were correctly identified, with an average incubation time of 5.72-h. This deep learning-based optical system met the FDA-defined essential and categorical agreement criteria for all 14 antibiotics tested, after an average of

Antibiotic treatment failure of Staphylococcus aureus infections is very common. In addition to genetically encoded mechanisms of antibiotic resistance, numerous additional factors limit the efficacy of antibiotics in vivo. Identifying and removing the barriers to antibiotic efficacy are of major importance, as even if new antibiotics become available, they will likely face the same barriers to efficacy as their predecessors. One major obstacle to antibiotic efficacy is the proficiency of S. aureus to enter a physiological state that is incompatible with antibiotic killing. Multiple pathways leading to antibiotic tolerance and the formation of tolerant subpopulations called persister cells have been described for S. aureus. Additionally, S. aureus is a versatile pathogen that can infect numerous tissues and invade a variety of cell types, of which some are poorly penetrable to antibiotics. It is therefore unlikely that there will be a single solution to the problem of recalcitrant S. aureus infection. Instead, specific approaches may be required for targeting tolerant cells within different niches, be it through direct targeting of persister cells, sensitization of persisters to conventional antibiotics, improved penetration of antibiotics to particular niches, or any combination thereof. Here, we examine two well-described reservoirs of antibiotic-tolerant S. aureus, the biofilm and the macrophage, the barriers these environments present to antibiotic efficacy, and potential solutions to the problem.

BACKGROUND: Staphylococcal aureus is both a human commensal and a frequent cause of clinically important infections. It is a colonizer of the skin and mucosa, being present in the anterior nostrils of up to 30-50% of the healthy human population. There are certain conditions that predispose to a greater risk of developing an invasion with the subsequent infection by this microorganism. One of these well-known conditions is to undergo an orthopaedic surgery. Although there are many studies about the clear benefit of pre-surgical Staphylococcal aureus decolonization in patients undergoing elective orthopaedic surgery in the reduction of surgical site infection related to this microorganism, there are few studies focused on the application of a decolonization protocol in non-elective surgeries, with the subsequent shorter pre-surgical treatment regimen. OBJECTIVE: to demonstrate that the detection of a Staphylococcus aureus’ carrier state in patients undergoing non-elective surgery with their consequent decolonization, significantly reduces the risk of a surgical site infection due to this microorganism compared to those patients who only receive the standard pre-surgical antiseptic treatment. DESIGN: the study will be a multicentre, longitudinal, prospective, double-blind, randomized and controlled clinical trial. It will be carried out in 6 hospitals of Girona’s province. Hospital Santa Caterina will be the coordinator centre. INTERVENTION AND METHODS: the subjects of the study will be those patients who must be operated (in a non-elective trauma and orthopaedic surgery) due to a third proximal femoral fracture, and with the condition of being Staphylococcus aureus’ nasal carriers. They will be randomly divided into two groups: group A (n = 125), patients will be treated with the standard pre-surgical antiseptic therapy plus concomitant Staphylococcal aureus’ decolonization treatment (topical intranasal mupirocin with topical chlorhexidine shower); in group B (n = 125), patients will receive the same standard antiseptic scheme plus concomitant placebo treatment. Recruitment of patients will last 12 months, with subsequent follow up of each patient for 12 months

Staphylococcus aureus infections are associated with increased morbidity, mortality, hospital stay, and health care costs. S aureus colonization has been shown to increase risk for invasive and noninvasive infections. Decolonization of S aureus has been evaluated in multiple patient settings as a possible strategy to decrease the risk of S aureus transmission and infection. In this article, we review the recent literature on S aureus decolonization in surgical patients, patients with recurrent skin and soft tissue infections, critically ill patients, hospitalized non-critically ill patients, dialysis patients, and nursing home residents to inform clinical practice.

New virulence factors, such as the Panton-Valentine leukocidin (PVL), are appearing during Staphylococcus aureus infections occurring in the pediatric population. Such factors increase the aggressiveness and risk of dissemination of the bacteria, causing infections to be life-threatening. An early diagnosis is thus especially important. We present a case of osteomyelitis, venous thrombosis, and septic emboli occurring in a pediatric patient that should trigger suspicion of a PVL-positive strain. A multidisciplinary approach is necessary to enable rapid diagnosis and early treatment, which is essential for successful management of these infections. Management is based on broad-spectrum antibiotics, in combination with aggressive surgical treatment and antithrombotic therapy. In patients infected with S. aureus whose condition worsens quickly, PVL gene sequencing should be considered.

In this counterpoint we critically appraise the evidence supporting therapeutic drug monitoring based on the vancomycin 24-hour area under the concentration-time curve (AUC24) for serious methicillin-resistant Staphylococcus aureus infections. We reveal methodologically weaknesses and inconsistencies in the data and suggest that, in the absence of clear and convincing evidence of benefit compared with modestly reducing trough targets, alternative strategies are more likely to result in superior safety and efficacy. These include focusing on fundamental antibiotic stewardship to limit vancomycin exposure overall, achieving earlier and more complete source control, and establishing alternative therapeutic options to vancomycin. Implementation of AUC24-based therapeutic drug monitoring will take resources away from these more promising, alternative solutions.

Background Staphylococcus aureus (S. aureus) remains a serious cause of infections in the U.S. and worldwide. Non antibiotic resistant Staphylococcus aureus (methicillin susceptible or MSSA) is the cause of half of all health care–associated staphylococcal infections, and methicillin resistant Staphylococcus aureus (MRSA) still is the leading cause of community onset skin and soft tissue infections in the U.S. This is the first study to spatially look at trends of both community onset MRSA and MSSA infections over nine years and determine ‘best’ to ‘worst’ infection trends over a nine year period (2002-2010),which spanned when community onset MRSA infections were occurring in epidemic proportions across the U.S. MethodsRetrospective study from 2002-2010, using electronic health records of children living in the southeastern U.S. (Atlanta, Georgia) with S. aureus infections and relevant U.S. census data (at the census tract level). The Proc Traj for SAS was applied to generate community onset MRSA and MSSA trajectory infection groups (low, high, very high, or deviant trends), and then, mapping of these trajectory groups using census tract boundaries.ResultsFrom community onset MRSA infection trend patterns (low, high, very high), only 0.8% of the census tracts showed a dramatic increase from 2002-2007 and then a gradual decline from 2008 to 2010. From community onset MSSA infection trend patterns (low and high), 85.7% of ‘high infection’ group persisted throughout the nine year period, compared to 14.3% of ‘low infection’ group over this same period. Low community onset MRSA and MSSA trend patterns were seen throughout the 20 counties of Atlanta, Georgia’s metropolitan statistical area, but more often seen in those counties less densley populated. Census tracts reflecting Atlanta’s ‘innercity’ had the highest proportion of the worst infection trend pattern (community onset MRSA-Very High-CO-MSSA-High or community onset MRSA-High-CO-MSSA-High). The deviant trend of community onset MRSA Very High- CO-MSSA Low infection were in census tracts east of downtown Atlanta. Conclusions ‘Trends’ of S. aureus infection patterns, stratified by antibiotic resistance, over geographic areas and time identify communities with higher risks for community onset MRSA infection compared to community onset MSSA infection.

To analyze host and pathogen factors related to disease severity of community-acquired bone and joint infections in children, a cohort of pediatric patients was prospectively recruited from 13 centers in 7 European countries. A total of 85 children were included, 11 (13%) had a severe infection. Panton-Valentine leukocidin-positive isolates were 17%, and 6% of the isolates were methicillin-resistant Staphylococcus aureus. Multivariate analysis identified Panton-Valentine leukocidin presence (adjusted odds ratio, 12.6; P = 0.01) as the only factor independently associated with severe outcome, regardless of methicillin resistance.

We presented a case of subtherapeutic linezolid concentration in a patient with bullous pemphigoid characterized by large area skin anabrosis complicated by methicillin-resistant Staphylococcus aureus infections.

Staphylococcus aureus small colony variants (SCVs) are frequently associated with chronic infection, yet they lack expression of many virulence determinants associated with the pathogenicity of wild-type strains. We found that both wild-type S. aureus and a ΔhemB SCV prototype potently activate glycolysis in host cells. Glycolysis and the generation of mitochondrial reactive oxygen species were sufficient to induce necroptosis, a caspase-independent mechanism of host cell death that failed to eradicate S. aureus and instead promoted ΔhemB SCV pathogenicity. To support ongoing glycolytic activity, the ΔhemB SCV induced over a 100-fold increase in the expression of fumC, which encodes an enzyme that catalyses the degradatin of fumarate, an inhibitor of glycolysis. Consistent with fumC-dependent depletion of local fumarate, the ΔhemB SCV failed to elicit trained immunity and protection from a secondary infectious challenge in the skin. The reliance of the S. aureus SCV population on glycolysis accounts for much of its role in the pathogenesis of S. aureus skin infection.

Vancomycin is frequently used to treat methicillin-resistant Staphylococcus aureus infections in pediatric patients. Vancomycin exposure may lead to an increase in frequency of nephrotoxicity. Our aim was to conduct a systematic review to describe predictors of nephrotoxicity associated with vancomycin, including documented trough concentrations ≥15 mg/L. We also aimed to use a meta-analysis to assess the impact of a vancomycin trough ≥15 mg/L on nephrotoxicity.A literature search was performed using PubMed, Cochrane Library, Embase and Web of Sciences database. We included randomized clinical trials and observational studies evaluating the relationship between vancomycin troughs and nephrotoxicity in pediatric-age patients. Studies not measuring troughs or defining a different cut-off point than 15 mg/L were excluded. Data on age, exclusion criteria, nephrotoxicity definition, risk factors for nephrotoxicity and vancomycin trough levels were extracted from selected papers.Ten studies were identified for meta-analysis. All subjects had comparatively normal baseline serum creatinine values. Common risk factors identified included elevated (≥15 mg/L) trough levels, renal impairment, hypovolemia and concurrent use of nephrotoxic medications. Troughs ≥15 mg/L increased nephrotoxicity by 2.7-fold (odds ratio (OR), 2.71; 95% confidence interval: 1.82-4.05; I(2) = 40%; Q = 0.09). These odds were further increased among patients in the pediatric intensive care unit (OR, 3.61; 95% confidence interval: 1.21-10.74; I(2) = 45%; Q = 0.18).Though the rate of vancomycin-induced nephrotoxicity is increased in pediatric patients with higher vancomycin troughs, other factors such as intensive care unit admission, hypovolemia and concurrent nephrotoxic drug use appear to contribute to the development of nephrotoxicity.

Human and camel lactoferrin, were labeled with technetium-99m using a simple technique that yielded a labelling efficiency of 98% and stable complexes over time. The camel Lactoferrin was purified. The proteins were investigated for targeting infections in experimental animals. The biodistribution of those labeled proteins in mice infected with Staphylococcus aureus at the femoral muscle was investigated and test ratios of 3.43 and 3.71 were obtained after 60 min for the camel and the human Lactoferrin, respectively. These values were compared to each other and to those reported in the literature, leading us to conclude that the radiotracers are efficient.

Antimicrobial peptides (AMPs) are small molecules produced by virtually all living organisms as a part of the innate immune system. They present a broad spectrum antimicrobial activity against a myriad of microorganisms, but also anti-inflammatory, immunomodulatory and antitumor effects, among others. Therefore, it was our objective to compile and analyze the current information about natural and synthetic AMPs, regarding their general mechanisms of action, potentials, and limitations for clinical use, especially for the treatment of Staphylococcus aureus infections. Furthermore, we intended to briefly discuss new routes of administration and the emergence of bacterial resistance to AMPs. To do so, two databases, PubMed and Scopus, and the keywords “Staphylococcus aureus”, “antimicrobial peptide” and “novel antibiotics” were used, and the articles were filtered by the English language for the period between 2011 and 2016. We found that AMPs possess different properties, with characteristic antimicrobial activities and secondary effects. Moreover, we also pointed some modifications that could be used to design new AMPs and different routes of administration that could be used to improve AMP capacity or to adapt it to a specific purpose, such as preventing biofilm formation in catheters or treating a specific disease. On the other hand, they also present limitations that include: development of bacterial resistance, cytotoxicity, and reduced stability, sometimes lower efficacy when compared to the actual treatment, high costs of production and also some inconsistent results between articles, which we believe that may be related to differences in methods and/or strains of S. aureus investigated.

We investigated surgical site infections (SSIs) following hip and knee arthroplasties to evaluate predictors of SSI. We found a significant increase in deep Staphylococcus aureus (SA) SSIs despite the decreasing overall SSI rate. The risk of deep SA-SSI differed between genders and among age groups and was affected by timing of surgery.

Background Staphylococcus aureus is a Gram-positive spherical bacterium that commonly causes various infections which can range from superficial to life-threatening. Hospital strains of S. aureus are often resistant to antibiotics, which has made their treatment difficult in recent decades. Other therapeutic alternatives have been postulated to overcome the drawbacks of antibiotic multi-resistance. Of these, photodynamic therapy (PDT) is a promising approach to address the notable shortage of new active antibiotics against multidrug-resistant S. aureus. PDT combines the use of a photosensitizer agent, light, and oxygen to eradicate pathogenic microorganisms. Through a systematic analysis of published results, this work aims to verify the usefulness of applying PDT in treating multidrug-resistant S.aureus infections. Methods This review was based on a bibliographic search in various databases and the analysis of relevant publications. Results There is currently a large body of evidence demonstrating the efficacy of photodynamic therapy in eliminating S.aureus strains. Both biofilm-producing strains, as well as multidrug-resistant strains. Conclusion We conclude that there is sufficient scientific evidence that PDT is a useful adjunct to traditional antibiotic therapy for treating S. aureus infections. Clinical application through appropriate trials should be introduced to further define optimal treatment protocols, safety and efficay.

Invasive infections caused by antibiotic-resistant Staphylococcus aureus have posed a great threat to human health. To tackle this problem, a cationic liposomal Curcumin (C-LS/Cur) was developed and its effect against antibiotic-resistant S. aureus was investigated in this study. As expected, C-LS/Cur exhibited greater bactericidal capacity compared with its counterparts, probably because the negatively charged S. aureus favors electrostatic interactions rather than intercalation with cationic liposomal vesicles at the beginning of endocytic process, thereby effectively delivering Cur to its targets. We confirmed this hypothesis by monitoring zeta potential variation, collecting visual evidences through CLSM, FCM and TEM, and determining binding kinetics by BLI. Moreover, an excellent therapeutic efficacy of C-LS/Cur against invasive murine infection was also observed, which was due to the enhanced accumulation and retention in the targets. Therefore, cationic liposomes have great potential for the clinical application in the treatment of invasive antibiotic-resistant S. aureus infections.

This study assessed Staphylococcus aureus infection risk in patients with type 2 diabetes mellitus (T2DM) undergoing an orthopedic knee, hip, or spine surgery.All patients with a diagnosis of T2DM in the period from 2010 to 2012 were identified from a German claims database. First inpatient knee, hip, or spine surgery was used as index date. Cumulative incidence of S. aureus infections was calculated for several time intervals. Risk factors were identified based on a multi-variable Cox regression analysis. A case control analysis was conducted to assess mortality, healthcare resource utilization, and healthcare costs of S. aureus.In total, 9,401 patients with T2DM underwent a knee, hip, or spine surgery. Mean age was 72.58 years, 63.32% were female, and 1.08% experienced an S. aureus infection in the 365-day follow-up period. The difference in all-cause direct treatment costs per patient-year between infected and non-infected patients was 24,437.50$. Mortality rates were 25.52% (S. aureus group) versus 5.22% (non-S. aureus group), based on a 365-day follow-up.Staphylococcus aureus is associated with a substantial healthcare burden and high mortality. Effective infection control measures should be considered to reduce post-surgical S. aureus infection risk in patients with T2DM.

Staphylococcus aureus persistently colonizes the nasopharynx of about one-third of the human population, a key risk factor for community- and hospital-acquired invasive infections. Current strategies for S. aureus decolonization include topical and systemic administration of antibiotics, which is associated with selection for antibiotic resistance and posttreatment recolonization. Using a mouse model for S. aureus colonization, we show here that systemic administration of a recombinant monoclonal antibody neutralizing staphylococcal protein A (SpA) can stimulate antibacterial immunoglobulin G and immunoglobulin A responses and promote S. aureus decolonization. These results suggest that antibody neutralizing SpA, a B-cell superantigen, may also be useful for S. aureus decolonization in humans.

Multi-drug resistant Staphylococcus aureus infections have created a critical need for the development of new classes of antibacterials. Discovery of new naturally derived antibacterial agents with new mechanism of action remains a high priority globally. Several of the available antibacterial agents like β-lactams, polyketides, phenylpropanoids, aminoglycosides, macrolides, glycopeptides, streptogramins and lipopeptides are natural products or their semisynthetic variations. In the current scenario of alarming rise in antibacterial resistance, revisiting natural products with modern chemistry and biology tools has fascinated many medicinal chemists for discovery and development of natural products or derived semisynthetic derivatives as effective antibacterial agents. This review underlines the structures and anti-MRSA activity of various natural product derivatives covering recent reports, in vivo activities and brief Structure Activity Relationships (SARs).

Objective:To estimate the additional health and economic burden of antimicrobial-resistant (AMR) infections in Australian hospitals.Methods:A simulation model based on existing evidence was developed to assess the additional mortality and costs of healthcare-associated AMR Escherichia coli (E. coli), Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, and Staphylococcus aureus infections.Setting:Australian public hospitals.Findings:Australian hospitals spent an additional AUD$5.8 million (95% uncertainty interval [UI], $2.2–$11.2 million) per year treating ceftriaxone-resistant E.coli bloodstream infections (BSI), and an estimated AUD$5.5 million per year (95% UI, $339,633–$22.7 million) treating MRSA patients. There are no reliable estimates of excess morbidity and mortality from AMR infections in sites other than the blood and in particular for highly prevalent AMR E. coli causing urinary tract infections (UTIs).Conclusion:The limited evidence-base of the health impact of resistant infection in UTIs limits economic studies estimating the overall burden of AMR. Such data are increasingly important and are urgently needed to support local clinical practice as well as national and global efforts to curb the spread of AMR.

Background Community- associated methicillin resistant Staphylococcus aureus (CA-MRSA) cause serious infections and rates continue to rise worldwide. Use of geocoded electronic health record (EHR) data to prevent spread of disease is limited in health service research. We demonstrate how geocoded EHR and spatial analyses can be used to identify risks for CA-MRSA in children, which are tied to place-based determinants and would not be uncovered using traditional EHR data analyses. Methods An epidemiology study was conducted on children from January 1, 2002 through December 31, 2010 who were treated for Staphylococcus aureus infections. A generalized estimated equations (GEE) model was developed and crude and adjusted odds ratios were based on S. aureus risks. We measured the risk of S. aureus as standardized incidence ratios (SIR) calculated within aggregated US 2010 Census tracts called spatially adaptive filters, and then created maps that differentiate the geographic patterns of antibiotic resistant and non-resistant forms of S. aureus. Results CA-MRSA rates increased at higher rates compared to non-resistant forms, p = 0.01. Children with no or public health insurance had higher odds of CA-MRSA infection. Black children were almost 1.5 times as likely as white children to have CA-MRSA infections (aOR 95% CI 1.44,1.75, p

Antibiotic-resistant bacteria can cause intractable infections in humans and animals, with damaging effects to health care and economics. Phage therapy is considered a possible alternative to chemotherapy for treating infections, but still requires laborious in vivo experiments before its introduction into society and its further development. Recently, silkworm larvae have been recognized as highly convenient and useful model animals, and an alternative to higher animals. We describe the procedure for experimental phage therapy to treat Staphylococcus aureus infections in silkworm larvae.

During 2005–2014, community-associated methicillin-resistant Staphylococcus aureus infections increased in Shanghai, China. Most infections were caused by sequence type 59 S. aureus that lacked Panton-Valentine leukocidin. This finding challenges the notion that Panton-Valentine leukocidin is necessary for epidemiologic success of community-associated methicillin-resistant S. aureus.

DSTA4637A, a novel THIOMAB™ antibody antibiotic conjugate (TAC) against Staphylococcus aureus (S. aureus), is currently being investigated as a potential therapy against S. aureus infections. Structurally, TAC is composed of an anti-S. aureus antibody linked to a potent antibiotic, dmDNA31. The goal of the current study was to characterize the pharmacokinetics (PK) of TAC in mice, assess the effect of S. aureus infection on its PK, and evaluate its pharmacodynamics (PD) by measuring the bacterial load in various organs at different timepoints following TAC treatment. Plasma concentrations of 3 analytes, total antibody (TAb), antibody-conjugated dmDNA31 (ac-dmDNA31), and unconjugated dmDNA31, were measured in these studies. In non-infected mice (target antigen absent), following intravenous (IV) administration of a single dose of TAC, systemic concentration-time profiles of both TAb and ac-dmDNA31 were bi-exponential and characterized by a short distribution phase and a long elimination phase as expected for a monoclonal antibody-based therapeutic. Systemic exposures of both TAb and ac-dmDNA31 were dose proportional over the dose range tested (5 to 50 mg/kg). In a mouse model of systemic S. aureus infection (target antigen present), a single IV dose of TAC demonstrated PK behavior similar to that in the non-infected mice, and substantially reduced bacterial load in the heart, kidney, and bones on 7 and 14 d post dosing. These findings have increased our understanding of the PK and PK/PD of this novel molecule, and have shown that at efficacious dose levels the presence of S. aureus infection had minimal effect on TAC PK.

Catheter-associated thrombosis (CAT) in patients with infected long-term central venous catheter (LTCVC) has been poorly studied.We prospectively included patients with infected LTCVC and collected clinical data. Doppler ultrasound was systematically performed to screen for CAT. Outcome (death or infection relapse) was evaluated 12 weeks after infection diagnosis.90 patients were included and CAT was diagnosed in 27 (30%). Local signs suggesting infection were more frequent in patients with CAT than without (11/27 versus 8/63, p = 0.03). Outcome was similar in patients with and without CAT. However, median duration of antimicrobials was longer (18 versus 14 days, p = 0.02), catheter removal tended to be more frequent (24/27 versus 46/63, p = 0.08), and anticoagulant therapy more often prescribed (17/27 versus 6/63, p 0.01) in patients with CAT than without. Patients with occlusive thrombosis were more likely to have Staphylococcus aureus infections (4/7 versus 1/17, p = 0.02) and prolonged positivity of blood-cultures (3/7 versus 1/15, p = 0.02), than patients with non-occlusive thrombosis.CAT is associated with local signs suggesting infection. A more aggressive treatment in CAT cases allowed a similar outcome at 12 weeks between patients with and without CAT. Occlusive thrombosis represented a subgroup of patients at risk of delayed clearance of bacteremia.

The growing incidence of serious infections mediated by methicillin-resistant Staphylococcus aureus (MRSA) strains poses a significant risk to public health. This risk is exacerbated by a prolonged void in the discovery and development of truly novel antibiotics and the absence of a vaccine. These gaps have created renewed interest in the use of biologics in the prevention and treatment of serious staphylococcal infections. In this review, we focus on efforts towards the discovery and development of antibody-based biologic agents and their potential as clinical agents in the management of serious S. aureus infections. Recent promising data for monoclonal antibodies (mAbs) targeting anthrax and Ebola highlight the potential of antibody-based biologics as therapeutic agents for serious infections.