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BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are becoming increasingly prevalent. There is geographic variation in their reported prevalence across the United States; however, studies reporting on CA-MRSA prevalence also demonstrate great variability in their case-finding methodology. We conducted a study to see how three different methods to ascertain CA-MRSA prevalence would lead to different estimates.METHODS: Different methods were used to identify cases of CA-MRSA colonization and/or infection in New York City. Method 1: retrospective review of clinical and surveillance cultures identified through a hospital computer database. Method 2: prospective collection of surveillance cultures in the same hospital's emergency department. Method 3: prospective collection of surveillance cultures in a community setting.RESULTS: Differing values for CA-MRSA prevalence resulted depending on the method and denominator used. All nares cultures as the denominator led to prevalence estimates of 0.3%-0.6%; all S. aureus as the denominator led to rates of 1.2%-5%; all MRSA as the denominator led to estimates of 5.5%-50%.CONCLUSIONS: A comparison of three methods revealed that variability in case-finding methodologies can lead to different prevalence estimates. Key factors to consider when comparing CA-MRSA rates include the definition of CA-MRSA, choice of denominator, and method and setting of sample collection. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus skin and soft tissue infections (SA-SSTIs) are common in healthcare and community settings, and recurrences occur at variable frequency, even after successful initial treatment. Knowing the exact burden and timing of recurrent disease is critical to planning and evaluating interventions to prevent recurrent SSTIs., Methods: In this retrospective study, SSTI cases in patients aged ≥18 years at 3 US medical centers (Columbia, Chicago, Vanderbilt) between 2006 and 2016 were analyzed according to a biennial cohort design. Index SSTIs (with or without key comorbidities), either microbiologically confirmed to be SA-SSTI or not microbiologically tested (NMT-SSTI), were recorded within 1 calendar year and followed up for 12 months for recurrent infections. The number of index cases, proportion of index cases with ≥1 recurrence(s), time to first recurrence, and number of recurrences were collected for both SA-SSTI and NMT-SSTI events., Results: In the most recent cohorts, 4755 SSTI cases were reported at Columbia, 2873 at Chicago, and 6433 at Vanderbilt. Of these, 452, 153, and 354 cases were confirmed to be due to S. aureus. Most cases were reported in patients without key comorbidities. Across centers, 16.4%-19.0% (SA-SSTI) and 11.0%-19.2% (NMT-SSTI) of index cases had ≥1 recurrence(s). In patients without key comorbidities, more than 60% of index SSTIs with recurrences had only 1 recurrence, half of which occurred in the first 3 months following primary infection., Conclusions: SA-SSTI recurrences are common among healthy adults and occur in at least 1 in 6 individuals during the 1 year following the primary event., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Understanding the changing epidemiology of Staphylococcus aureus bacteremia, as well as the variables associated with poor outcomes, can yield insight into potential interventions., Methods: This study was a retrospective, observational cohort study of adult patients at an academic medical center in New York City who had S. aureus bloodstream infections between 1 January 2007 and 31 December 2015. Participants were divided into 3 periods: group 1 (2007-2009), group 2 (2010-2012), and group 3 (2013-2015) for trend analysis. All clinical strains were genotyped (spa.). The main outcome was 30-day all-cause mortality., Results: There were 1264 episodes of methicillin-susceptible S. aureus (MSSA) and 875 episodes of methicillin-resistant S. aureus (MRSA) bacteremia, with a rising proportion due to MSSA (55% group 1; 59% group 2; 63% group 3; P = .03.) There were no significant changes in average age, gender, Charlson score, and distribution of strain genotypes. Mortality in MRSA infection was unchanged (25% group 1; 25% group 2; 26% group 3), while mortality in MSSA infection significantly declined (18% group 1; 18% group 2; 13% group 3). The average time to antistaphylococcal therapy (AST) in MSSA infection declined during the study (3.7 days group 1; 3.5 group 2; 2.2 group 3). In multivariate analysis, AST within 7 days of initial positive MSSA culture was associated with survival., Conclusions: Mortality in MSSA bloodstream infection is declining, associated with a decrease in time to targeted therapy. These results emphasize the potential for rapid diagnostics and early optimization of treatment to impact outcomes in MSSA bacteremia., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Antibiotic resistance in bacterial pathogens threatens the future of modern medicine. One such resistant pathogen is methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to nearly all β-lactam antibiotics, limiting treatment options. Here, we show that a significant proportion of MRSA isolates from different lineages, including the epidemic USA300 lineage, are susceptible to penicillins when used in combination with β-lactamase inhibitors such as clavulanic acid. Susceptibility is mediated by a combination of two different mutations in the mecA promoter region that lowers mecA-encoded penicillin-binding protein 2a (PBP2a) expression, and in the majority of isolates by either one of two substitutions in PBP2a (E246G or M122I) that increase the affinity of PBP2a for penicillin in the presence of clavulanic acid. Treatment of S. aureus infections in wax moth and mouse models shows that penicillin/β-lactamase inhibitor susceptibility can be exploited as an effective therapeutic choice for 'susceptible' MRSA infection. Finally, we show that isolates with the PBP2a E246G substitution have a growth advantage in the presence of penicillin but the absence of clavulanic acid, which suggests that penicillin/β-lactamase susceptibility is an example of collateral sensitivity (resistance to one antibiotic increases sensitivity to another). Our findings suggest that widely available and currently disregarded antibiotics could be effective in a significant proportion of MRSA infections.

Objective: Postoperative surgical site infections (SSIs) in neurosurgical patients carry a significant risk of increased morbidity and mortality. With SSIs accounting for approximately 20% of nosocomial infections and costing approximately $1.6 billion USD annually, there is a need for additional prophylaxis to improve current standards of care. Topical vancomycin is increasingly utilized in instrumented spinal and cardiothoracic procedures, where it has been shown to reduce the risk of SSIs. A randomized controlled trial assessing its efficacy in the general neurosurgical population is currently underway. Here, the authors report their initial impressions of topical vancomycin safety among patients enrolled during the 1st year of the trial., Methods: This prospective, multicenter, patient-blinded, randomized controlled trial will enroll 2632 patients over 5 years. Here, the authors report the incidence of adverse events, the degree of systemic vancomycin absorption in treated patients, and pattern changes of antibiotic-resistant profiles of Staphylococcus aureus flora among patients enrolled during the 1st year., Results: The topical vancomycin treatment group comprised 257 patients (514 total enrolled patients), of whom 2 exhibited weakly positive serum levels of vancomycin (> 3.0 mg/dl). S. aureus was detected preoperatively in the anterior nares of 35 (18.1%) patients and the skin near the surgical site of 9 (4.7%). Colonization in the nares remained for many patients (71.4%) through postoperative day 30. The authors found a significant association between preoperative S. aureus colonization and postoperative colonization. Seven methicillin-resistant isolates were detected among 6 different patients. Two isolates were detected preoperatively, and 5 were de novo postoperative colonization. No adverse responses to treatment have been reported to date., Conclusions: The authors' data indicate that the use of topical vancomycin is safe with no significant adverse effects and minimal systemic absorption, and no development of vancomycin-resistant microorganisms.Clinical trial registration no.: NCT02284126 (clinicaltrials.gov).

House mice ( Mus musculus ) thrive in large urban centers worldwide. Nonetheless, little is known about the role that they may play in contributing to environmental contamination with potentially pathogenic bacteria. Here, we describe the fecal microbiome of house mice with emphasis on detection of pathogenic bacteria and antimicrobial resistance genes by molecular methods. Four hundred sixteen mice were collected from predominantly residential buildings in seven sites across New York City over a period of 13 months. 16S rRNA sequencing identified Bacteroidetes as dominant and revealed high levels of Proteobacteria A targeted PCR screen of 11 bacteria, as indicated by 16S rRNA analyses, found that mice are carriers of several gastrointestinal disease-causing agents, including Shigella , Salmonella , Clostridium difficile , and diarrheagenic Escherichia coli Furthermore, genes mediating antimicrobial resistance to fluoroquinolones ( qnrB ) and β-lactam drugs ( bla SHV and bla ACT/MIR ) were widely distributed. Culture and molecular strain typing of C. difficile revealed that mice harbor ribotypes associated with human disease, and screening of kidney samples demonstrated genetic evidence of pathogenic Leptospira species. In concert, these findings support the need for further research into the role of house mice as potential reservoirs for human pathogens and antimicrobial resistance in the built environment. IMPORTANCE Mice are commensal pests often found in close proximity to humans, especially in urban centers. We surveyed mice from seven sites across New York City and found multiple pathogenic bacteria associated with febrile and gastrointestinal disease as well as an array of antimicrobial resistance genes., (Copyright © 2018 Williams et al.)

Surgical-site infections (SSIs) account for 20% of all healthcare-associated infections, are the most common nosocomial infection among surgical patients, and are a focus of quality improvement initiatives. Despite implementation of many quality care measures (e.g. prophylactic antibiotics), SSIs remain a significant cause of morbidity, mortality, and economic burden, particularly in the field of neurosurgery. Topical vancomycin is increasingly utilized in instrumented spinal and cardiothoracic procedures, where it has been shown to reduce the risk of SSIs. However, a randomized controlled trial assessing its efficacy in the general neurosurgical population has yet to be done. The principle aim of "Topical Vancomycin for Neurosurgery Wound Prophylaxis" (NCT02284126) is to determine whether prophylactic, topical vancomycin reduces the risk of SSIs in the adult neurosurgical population. This prospective, multicenter, patient-blinded, randomized controlled trial will enroll patients to receive the standard of care plus topical vancomycin, or the standard of care alone. The primary endpoint of this study is a SSI by postoperative day (POD) 30. Patients must be over 18years of age. Patients are excluded for renal insufficiency, vancomycin allergy, and some ineligible procedures. Univariate analysis and logistic regression will determine the effect of topical vancomycin on SSIs at 30days. A randomized controlled trial is needed to determine the efficacy of this treatment. Results of this trial are expected to directly influence the standard of care and prevention of SSIs in neurosurgical patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Skin and soft tissue infections (SSTIs) are a common problem in jails in the United States. This study aimed to identify factors associated with purulent SSTIs in the New York City jail system., Methods: We conducted a case-control study of purulent SSTIs at the New York City jail. Cases were matched to controls by visit date to the jail's urgent care clinic. Bivariate and multivariable analyses were conducted using conditional logistic regression., Results: From April 2011 to April 2015, 1010 cases of SSTIs were identified and matched to 1010 controls. In multivariable analyses, report upon entry to jail of current injection drug use (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.77-4.31), current snorting of drugs (OR, 1.50; 95% CI, 1.12-2.00), current heroin use (OR, 1.53; 95% CI, 1.08-2.17), current cocaine use (OR, 1.76; 95% CI, 1.18-2.65), and antibiotic use within the previous 6 months (OR, 4.05; 95% CI, 2.98-5.49) were significantly associated with SSTI diagnosis., Conclusions: Skin and soft tissue infections were strongly associated with a history of drug use at jail entry. Targeting intravenous drug use may be a preventive strategy for SSTIs in this population. Strategies such as harm reduction programs may be investigated., (© The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Prisons/jails are thought to amplify the transmission of Staphylococcus aureus (SA) particularly methicillin-resistant SA infection and colonisation. Two independently pooled cross-sectional samples of detainees being admitted or discharged from two New York State maximum-security prisons were used to explore this concept. Private interviews of participants were conducted, during which the anterior nares and oropharynx were sampled and assessed for SA colonisation. Log-binomial regression and correspondence analysis (CA) were used to evaluate the prevalence of colonisation at entry as compared with discharge. Approximately 51% of admitted (N = 404) and 41% of discharged (N = 439) female detainees were colonised with SA. Among males, 59% of those admitted (N = 427) and 49% of those discharged (N = 393) were colonised. Females had a statistically significant higher prevalence (1·26: P = 0·003) whereas males showed no significant difference (1·06; P = 0·003) in SA prevalence between entry and discharge. CA demonstrated that some strains, such as spa types t571 and t002, might have an affinity for certain mucosal sites. Contrary to our hypothesis, the prison setting did not amplify SA transmission, and CA proved to be a useful tool in describing the population structure of strains according to time and/or mucosal site.

Methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSIs) often lead to severe complications despite the availability of effective antibiotics. It remains unclear whether elevated vancomycin MICs are associated with worse outcomes. We conducted a 2-year retrospective cohort study ( n = 252) of patients with MSSA BSIs at a tertiary care hospital. We defined reduced vancomycin susceptibility (RVS) as a Microscan MIC of 2 mg/liter. All strains were genotyped ( spa ) and assessed for agr functionality. Multivariable logistic regression models were used to examine the impact of RVS phenotype and strain genotype on 30-day all-cause mortality and complicated bacteremia (metastatic spread, endovascular infection, or duration ≥3 days). One-third of patients (84/252) were infected with RVS isolates. RVS Infections were more frequently associated with metastatic or embolic sites of infection (36% versus 17%, P < 0.001), and endovascular infection (26% versus 12%, P = 0.004). These infections occurred more often in patients with fewer underlying comorbidities (Charlson comorbidity index of ≥3 [73% versus 88%, P = 0.002]). Genotyping identified 127 spa -types and 14 Spa-clonal complexes (Spa-CCs). Spa-CC002 and Spa-CC008 were more likely to exhibit the RVS phenotype versus other Spa-CCs (OR = 2.2, P < 0.01). The RVS phenotype was not significantly associated with 30-day mortality; however, it was associated with complicated bacteremia (adjusted odds ratio of 2.35 [range, 1.26 to 4.37]; P = 0.007) in adjusted analyses. The association of RVS strains with complicated infection and fewer underlying comorbidities suggests the phenotype as a potential marker of strain virulence in MSSA BSIs. The RVS phenotype itself was not a significant predictor of mortality in this patient cohort. Further studies are necessary to explore this host-pathogen relationship., (Copyright © 2017 American Society for Microbiology.)

Background: Staphylococcus epidermidis, a major component of skin flora, is an opportunist, often causing prosthetic device infections. A family of structurally related proteins mediates staphylococcal attachment to host tissues, contributing to the success of S. epidermidis as a pathogen. We examined the ability of the surface protein SdrF to adhere to keratin, a major molecule expressed on the skin surface., Methods: A heterologous Lactococcus lactis expression system was used to express SdrF and its ligand-binding domains. Adherence to keratin types 1 and 10, human foreskin keratinocytes, and nasal epithelial cells was examined., Results: SdrF bound human keratins 1 and 10 and adhered to keratinocytes and epithelial cells. Binding involved both the A and B domains. Anti-SdrF antibodies reduced adherence of S. epidermidis to keratin and keratinocytes. RNA interference reduced keratin synthesis in keratinocytes and, as a result, SdrF adherence. Direct force measurements using atomic force microscopy showed that SdrF mediates bacterial adhesion to keratin 10 through strong and weak bonds involving the A and B regions; strong adhesion was primarily mediated by the A region., Conclusions: These studies demonstrate that SdrF mediates adherence to human keratin and suggest that SdrF may facilitate S. epidermidis colonization of the skin., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Lactobacillus rhamnosus is commonly found in gastrointestinal flora and used in probiotics but is a rare human pathogen. We report a case of L. rhamnosus endocarditis following upper endoscopy in a frequent consumer of yogurt containing the organism, who required aortic and mitral valve replacement for cure.

We have previously shown that 207-nm ultraviolet (UV) light has similar antimicrobial properties as typical germicidal UV light (254 nm), but without inducing mammalian skin damage. The biophysical rationale is based on the limited penetration distance of 207-nm light in biological samples (e.g. stratum corneum) compared with that of 254-nm light. Here we extended our previous studies to 222-nm light and tested the hypothesis that there exists a narrow wavelength window in the far-UVC region, from around 200-222 nm, which is significantly harmful to bacteria, but without damaging cells in tissues. We used a krypton-chlorine (Kr-Cl) excimer lamp that produces 222-nm UV light with a bandpass filter to remove the lower- and higher-wavelength components. Relative to respective controls, we measured: 1. in vitro killing of methicillin-resistant Staphylococcus aureus (MRSA) as a function of UV fluence; 2. yields of the main UV-associated premutagenic DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts) in a 3D human skin tissue model in vitro; 3. eight cellular and molecular skin damage endpoints in exposed hairless mice in vivo. Comparisons were made with results from a conventional 254-nm UV germicidal lamp used as positive control. We found that 222-nm light kills MRSA efficiently but, unlike conventional germicidal UV lamps (254 nm), it produces almost no premutagenic UV-associated DNA lesions in a 3D human skin model and it is not cytotoxic to exposed mammalian skin. As predicted by biophysical considerations and in agreement with our previous findings, far-UVC light in the range of 200-222 nm kills bacteria efficiently regardless of their drug-resistant proficiency, but without the skin damaging effects associated with conventional germicidal UV exposure.

Antimicrobial resistance in gram-positive bacteria remains a challenge in infectious diseases. The mission of the Gram-Positive Committee of the Antibacterial Resistance Leadership Group (ARLG) is to advance knowledge in the prevention, management, and treatment of these challenging infections to improve patient outcomes. Our committee has prioritized projects involving methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) due to the scope of the medical threat posed by these pathogens. Approved ARLG projects involving gram-positive pathogens include (1) a pharmacokinetics/pharmacodynamics study to evaluate the impact of vancomycin dosing on patient outcome in MRSA bloodstream infection (BSI); (2) defining, testing, and validating innovative assessments of patient outcomes for clinical trials of MRSA-BSI; (3) testing new strategies for "step-down" antibiotic therapy for MRSA-BSI; (4) management of staphylococcal BSIs in neonatal intensive care units; and (5) defining the impact of VRE bacteremia and daptomycin susceptibility on patient outcomes. This article outlines accomplishments, priorities, and challenges for research of infections caused by gram-positive organisms., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Methicillin-susceptible Staphylococcus aureus (MSSA) accounts for the majority of S. aureus infections globally, and yet surprisingly little is known about its clonal evolution. We applied comparative whole-genome sequencing (WGS) analyses to epidemiologically and geographically diverse ST398-MSSA, a pandemic lineage affecting both humans and livestock. Bayesian phylogenetic analysis predicted divergence of human-associated ST398-MSSA ~40 years ago. Isolates from Midwestern pigs and veterinarians differed substantially from those in New York City (NYC). Pig ST398 strains contained a large region of recombination representing imports from multiple sequence types (STs). Phylogeographic analyses supported the spread of ST398-MSSA along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. Applying pairwise single-nucleotide polymorphism (SNP) distances as a measure of genetic relatedness between isolates, we observed that ST398 not only clustered in households but also frequently extended across local social networks. Isolates collected from environmental surfaces reflected the full diversity of colonizing individuals, highlighting their potentially critical role as reservoirs for transmission and diversification. Strikingly, we observed high within-host SNP variability compared to our previous studies on the dominant methicillin-resistant Staphylococcus aureus (MRSA) clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300-MRSA and ST398-MSSA. Taken together, our study reveals local and international routes of transmission for a major MSSA clone, indicating key impacts of recombination and mutation on genetic diversification and highlighting important ecological differences from epidemic USA300. Our study demonstrates extensive local and international routes of transmission for a major MSSA clone despite the lack of substantial antibiotic resistance., Importance: Unlike methicillin-resistant Staphylococcus aureus (MRSA), surprisingly little is known about the clonal evolution of methicillin-susceptible S. aureus (MSSA), although these strains account for the majority of S. aureus infections. To better understand how MSSA spreads and becomes established in communities, we applied comparative bacterial whole-genome sequencing to pandemic ST398-MSSA, a clone of clinical importance affecting humans and livestock in different geographic regions. Phylogeographic analyses identified that ST398-MSSA spread along local cultural and migratory links between parts of the Caribbean, North America, and France, respectively. We observed high within-host SNP variability compared to our previous studies on the dominant MRSA clone USA300. Our data indicate that the dynamics of colonization, persistence, and transmission differ substantially between USA300 MRSA and ST398 MSSA., (Copyright © 2017 Uhlemann et al.)

Background: People living with human immunodeficiency virus (PLWH) have been disproportionally affected by methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection, in particular by clones USA300 and USA500. However, the contribution of epidemiological, bacterial, and immunological risk factors to the excess of S aureus in PLWH remain incompletely understood., Methods: In this cross-sectional study, we determined the prevalence and molecular epidemiology of S aureus colonization in 93 PLWH attending an urban human immunodeficiency virus (HIV) clinic. Participants completed a structured interview assessing demographic information and risk factors for MRSA. Swabs were obtained from the nose, throat, and groin and cultured for S aureus and Staphylococcus epidermidis ., Results: Most participants had well controlled HIV infection (89, 96% CD4 >200). Thirty-six (39%) individuals were colonized with S aureus at 1 or more body sites, including 6 (6%) with MRSA. Regular gym use was a risk factor for S aureus but not MRSA carriage. In contrast, S epidermidis was present in almost all individuals (n = 84, 90%), predominantly in the nares (n = 66, 71%). Using generalized estimating equation models, we observed that the odds of S aureus colonization were significantly and drastically reduced when S epidermidis was detected ( P = .0001). After controlling for site, gender, and age, we identified that the odds of S aureus colonization were 80% less if S epidermidis was present (adjusted odds ratio, 0.20; 95% confidence interval, .09-.45; P < .0001)., Conclusions: Taken together, we observed a lower prevalence of S aureus and MRSA colonization than has been previously reported in PLWH. In this cohort, colonization with S epidermidis was protective against S aureus colonization., (© The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Objective: To evaluate the association between HIV and Staphylococcus aureus colonization after confounding by incarceration is removed., Method: A cross sectional stratified study of all HIV infected and a random sample of HIV-uninfected inmates from two maximum-security prisons in New York State. Structured interviews were conducted. Anterior nares and oropharyngeal samples were cultured and S. aureus isolates were characterized. Log-binomial regression was used to assess the association between HIV and S. aureus colonization of the anterior nares and/or oropharynx and exclusive oropharynx colonization. Differences in S. aureus strain diversity between HIV-infected and uninfected individuals were assessed using Simpson's Index of Diversity., Results: Among 117 HIV infected and 351 HIV uninfected individuals assessed, 47% were colonized with S. aureus and 6% were colonized with methicillin resistant S. aureus. The prevalence of S. aureus colonization did not differ by HIV status (PR = 0.99, 95% CI = 0.76-1.24). HIV infected inmates were less likely to be exclusively colonized in the oropharynx (PR = 0.55, 95% CI = 0.30-0.99). Spa types t571 and t064 were both more prevalent among HIV infected individuals, however, strain diversity was similar in HIV infected and uninfected inmates., Conclusions: HIV infection was not associated with S. aureus colonization in these maximum-security prison populations, but was associated with decreased likelihood of oropharyngeal colonization. Factors that influence colonization site require further evaluation., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

OBJECT Preoperative corticosteroids and chemotherapy are frequently prescribed for patients undergoing cranial neurosurgery but may pose a risk of postoperative infection. Postoperative surgical-site infections (SSIs) have significant morbidity and mortality, dramatically increase the length and cost of hospitalization, and are a major cause of 30-day readmission. In patients undergoing cranial neurosurgery, there is a lack of data on the role of patient-specific risk factors in the development of SSIs. The authors of this study sought to determine whether chemotherapy and prolonged steroid use before surgery increase the risk of an SSI at postoperative Day 30. METHODS Using the national prospectively collected American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database for 2006-2012, the authors calculated the rates of superficial, deep-incisional, and organ-space SSIs at postoperative Day 30 for neurosurgery patients who had undergone chemotherapy or had significant steroid use within 30 days before undergoing cranial surgery. Trauma patients, patients younger than 18 years, and patients with a preoperative infection were excluded. Univariate analysis was performed for 25 variables considered risk factors for superficial and organ-space SSIs. To identify independent predictors of SSIs, the authors then conducted a multivariate analysis in which they controlled for duration of operation, wound class, white blood cell count, and other potential confounders that were significant on the univariate analysis. RESULTS A total of 8215 patients who had undergone cranial surgery were identified. There were 158 SSIs at 30 days (frequency 1.92%), of which 52 were superficial, 27 were deep-incisional, and 79 were organ-space infections. Preoperative chemotherapy was an independent predictor of organ-space SSIs in the multivariate model (OR 5.20, 95% CI 2.33-11.62, p < 0.0001), as was corticosteroid use (OR 1.86, 95% CI 1.03-3.37, p = 0.04), but neither was a predictor of superficial or deep-incisional SSIs. Other independent predictors of organ-space SSIs were longer duration of operation (OR 1.16), wound class of ≥ 2 (clean-contaminated and further contaminated) (OR 3.17), and morbid obesity (body mass index ≥ 40 kg/m(2)) (OR 3.05). Among superficial SSIs, wound class of 3 (contaminated) (OR 6.89), operative duration (OR 1.13), and infratentorial surgical approach (OR 2.20) were predictors. CONCLUSIONS Preoperative chemotherapy and corticosteroid use are independent predictors of organ-space SSIs, even when data are controlled for leukopenia. This indicates that the disease process in organ-space SSIs may differ from that in superficial SSIs. In effect, this study provides one of the largest analyses of risk factors for SSIs after cranial surgery. The results suggest that, in certain circumstances, modulation of preoperative chemotherapy or steroid regimens may reduce the risk of organ-space SSIs and should be considered in the preoperative care of this population. Future studies are needed to determine optimal timing and dosing of these medications.

Importance: The role of environmental contamination in recurrent Staphylococcus aureus infections within households and its potential effect on intervention strategies has been debated recently., Objective: To assess whether household environmental contamination increases the risk for recurrent infection among individuals with a community-associated methicillin-resistant S aureus (MRSA) infection., Design, Setting, and Participants: This cohort study was conducted from November 1, 2011, to June 30, 2014, in the Columbia University Medical Center catchment area. All patients within 72 hours of presentation with skin or soft-tissue infections and blood, urine, or sputum cultures positive for MRSA were identified. Two hundred sixty-two patients met study inclusion criteria; 83 of these (31.7%) agreed to participate (index patients) with 214 household members. Participants were followed up for 6 months, and 62 of the 83 households (74.7%) completed follow-up. Participants and researchers were blinded to exposure status throughout the study. Follow-up was completed on June 30, 2014, and data were assessed from July 1, 2014, to February 19, 2016., Exposure: Concordant environmental contamination, defined as having an isolate with the identical staphylococcal protein A and staphylococcal chromosomal cassette mec type or antibiogram type as the index patient's clinical isolate, present on 1 or more environmental surfaces at the time of a home visit to the index patient after infection., Main Outcomes and Measures: Index recurrent infection, defined as any self-reported infection among the index patients during follow-up., Results: One patient did not complete any follow-up. Of the remaining 82 index patients, 53 (64.6%) were female and 59 (72.0%) were Hispanic. The mean age was 30 (SD, 20; range, 1-79) years. Forty-nine of 61 MRSA infections where the clinical isolate could be obtained (80.3%) were due to the epidemic strain USA300. Among the 82 households in which a patient had an index MRSA infection, the clinical isolate was present in the environment in 20 (24.4%) and not found in 62 (75.6%). Thirty-five patients (42.7%) reported a recurrent infection during follow-up, of whom 15 (42.9%) required hospitalization. Thirteen recurrent infections were from the 20 households (65.0%) with and 22 were from the 62 households (35.5%) without environmental contamination (P = .04). Environmental contamination increased the rate of index recurrent infection (incident rate ratio, 2.05; 95% CI, 1.03-4.10; P = .04)., Conclusions and Relevance: Household environmental contamination was associated with an increased rate of recurrent infection. Environmental decontamination should be considered as a strategy to prevent future MRSA infections, particularly among households where an infection has occurred.

Coagulase negative staphylococci (CoNS) are important opportunistic pathogens. Staphylococcus epidermidis, a coagulase negative staphylococcus, is the third leading cause of nosocomial infections in the US. Surface proteins like Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) are major virulence factors of pathogenic gram positive bacteria. Here, we identified a new chimeric protein in S. epidermidis, that we call SesJ. SesJ represents a prototype of a new subfamily of MSCRAMMs. Structural predictions show that SesJ has structural features characteristic of a MSCRAMM along with a N-terminal repeat region and an aspartic acid containing C-terminal repeat region, features that have not been previously observed in staphylococcal MSCRAMMs but have been found in other surface proteins from gram positive bacteria. We identified and analyzed structural homologs of SesJ in three other CoNS. These homologs of SesJ have an identical structural organization but varying sequence identities within the domains. Using flow cytometry, we also show that SesJ is expressed constitutively on the surface of a representative S. epidermidis strain, from early exponential to stationary growth phase. Thus, SesJ is positioned to interact with protein targets in the environment and plays a role in S. epidermidis virulence.

Few studies have focused on the risks of peripheral intravenous catheters (PIVs) as sources for Staphylococcus aureus bacteremia (SAB), a life-threatening complication. We identified 34 PIV-related infections (7.6%) in a cohort of 445 patients with SAB. Peripheral intravenous catheter-related SAB was associated with significantly longer bacteremia duration and thrombophlebitis at old PIV sites rather than current PIVs.

Obesity increases a person's susceptibility to a variety of infections, including Staphylococcus aureus infections, which is an important cause of morbidity in correctional settings. Using a cross-sectional design, we assessed the association between obesity and S. aureus colonization, a risk factor for subsequent infection, in New York State maximum-security prisons (2011-2013). Anterior nares and oropharyngeal cultures were collected. Structured interviews and medical records were used to collect demographic, behavioral, and medical data. Body mass index (BMI; weight (kg)/height (m(2))) was categorized as 18.5-24.9, 25-29.9, 30-34.9, or ≥35. The association between BMI and S. aureus colonization was assessed using log-binomial regression. Thirty-eight percent of 638 female inmates and 26% of 794 male inmates had a BMI of 30 or higher. More than 40% of inmates were colonized. Female inmates with a BMI of 25-29.9 (prevalence ratio (PR) = 1.37, 95% confidence interval (CI): 1.06, 1.76), 30-34.9 (PR = 1.52, 95% CI: 1.17, 1.98), or ≥35 (PR = 1.49, 95% CI: 1.13, 1.96) had a higher likelihood of colonization than did those with a BMI of 18.5-24.9 after we controlled for age, educational level, smoking status, diabetes status, and presence of human immunodeficiency virus. Colonization was higher among male inmates with a BMI of 30-34.9 (PR = 1.27, 95% CI: 1.01, 1.61). Our findings demonstrate an association between BMI and S. aureus colonization among female prisoners. Potential contributory biologic and behavioral factors should be explored., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bacterial virulence is a multifaceted trait where the interactions between pathogen and host factors affect the severity and outcome of the infection. Toxin secretion is central to the biology of many bacterial pathogens and is widely accepted as playing a crucial role in disease pathology. To understand the relationship between toxicity and bacterial virulence in greater depth, we studied two sequenced collections of the major human pathogen Staphylococcus aureus and found an unexpected inverse correlation between bacterial toxicity and disease severity. By applying a functional genomics approach, we identified several novel toxicity-affecting loci responsible for the wide range in toxic phenotypes observed within these collections. To understand the apparent higher propensity of low toxicity isolates to cause bacteraemia, we performed several functional assays, and our findings suggest that within-host fitness differences between high- and low-toxicity isolates in human serum is a contributing factor. As invasive infections, such as bacteraemia, limit the opportunities for onward transmission, highly toxic strains could gain an additional between-host fitness advantage, potentially contributing to the maintenance of toxicity at the population level. Our results clearly demonstrate how evolutionary trade-offs between toxicity, relative fitness, and transmissibility are critical for understanding the multifaceted nature of bacterial virulence.

Background: Large outbreaks of Staphylococcus aureus (SA) infections have occurred in correctional facilities across the country. We aimed to define the epidemiological and microbiological determinants of SA infection in prisons to facilitate development of prevention strategies for this underserved population., Methods: We conducted a case-control study of SA infection at 2 New York State maximum security prisons. SA-infected inmates were matched with 3 uninfected controls. Subjects had cultures taken from sites of infection and colonization (nose and throat) and were interviewed via structured questionnaire. SA isolates were characterized by spa typing. Bivariate and multivariable analyses were conducted using conditional logistic regression., Results: Between March 2011 and January 2013, 82 cases were enrolled and matched with 246 controls. On bivariate analysis, the use of oral and topical antibiotics over the preceding 6 months was strongly associated with clinical infection (OR, 2.52; P < .001 and 4.38, P < .001, respectively). Inmates with clinical infection had 3.16 times the odds of being diabetic compared with inmates who did not have clinical infection (P < .001). Concurrent nasal and/or oropharyngeal colonization was also associated with an increased odds of infection (OR, 1.46; P = .002). Among colonized inmates, cases were significantly more likely to carry the SA clone spa t008 (usually representing the epidemic strain USA300) compared to controls (OR, 2.52; P = .01)., Conclusions: Several inmate characteristics were strongly associated with SA infection in the prison setting. Although many of these factors were likely present prior to incarceration, they may help medical staff identify prisoners for targeted prevention strategies., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Staphylococcus aureus, both methicillin susceptible and resistant, are now major community-based pathogens worldwide. The basis for this is multifactorial and includes the emergence of epidemic clones with enhanced virulence, antibiotic resistance, colonization potential, or transmissibility. Household reservoirs of these unique strains are crucial to their success as community-based pathogens. Staphylococci become resident in households, either as colonizers or environmental contaminants, increasing the risk for recurrent infections. Interactions of household members with others in different households or at community sites, including schools and daycare facilities, have a critical role in the ability of these strains to become endemic. Colonization density at these sites appears to have an important role in facilitating transmission. The integration of research tools, including whole-genome sequencing (WGS), mathematical modeling, and social network analysis, has provided additional insight into the transmission dynamics of these strains. Thus far, interventions designed to reduce recurrent infections among household members have had limited success, likely due to the multiplicity of potential sources for recolonization. The development of better strategies to reduce the number of household-based infections will depend on greater insight into the different factors that contribute to the success of these uniquely successful epidemic clones of S. aureus., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Staphylococcus epidermidis is the leading etiologic agent of device-related infections. S. epidermidis is able to bind, by means of the adhesins of its cell wall, the host matrix proteins filming the artificial surfaces. Thence, bacteria cling to biomaterials and infection develops. The effect of temperature on integrity, structure, and biological activity of the collagen-binding adhesin (SdrF) of S. epidermidis has been here investigated. By cloning in E. coli XL1-Blue, a recombinant of the SdrF binding domain B (rSdrFB), carrying an N-terminal polyhistidine, was obtained. Purification was by HiTrap(TM) Chelating HP columns. Assessment of purity, molecular weight, and integrity was by SDS-PAGE. The rSdrFB-collagen binding was investigated by ELISA. A full three-dimensional reconstruction of rSdrFB was achieved by small-angle X-ray scattering (SAXS). At 25 °C, rSdrFB bound to type I collagen in a dose-dependent, saturable manner, with a Kd of 2.48 × 10(-7) M. When temperature increased from 25 to 37 °C, a strong conformational change occurred, together with the abolition of the rSdrFB-collagen binding. The rSdrFB integrity was not affected by temperature variation. SdrFB-collagen binding is switched on/off depending on the temperature. Implications with the infection pathogenesis are enlightened.

This study estimated the prevalence of chronic medical conditions and risk predictors of 759 newly admitted inmates in two New York State maximum-security prisons. The most prevalent conditions were respiratory (34.1%), cardiovascular (17.4%), and sexually transmitted diseases (STD; 16.1%); least prevalent were HIV (3.6%), cancer (1.7%), and kidney disease (1.7%). Results of the multivariable logistic regression showed that females had higher risk for all conditions except cardiovascular and liver disease; individuals aged 40 years and older had significantly higher risk for all conditions except asthma and STD; non-Hispanic Black inmates had higher risk for respiratory disease and STD; cigarette smoking was associated with asthma; and obesity was significantly associated with diabetes, asthma, and cardiovascular conditions. These findings highlight the heavy burden of chronic illnesses among newly admitted inmates and the need to address adequate screening, prevention, and treatment services., (© The Author(s) 2015.)

Diverse strain types of methicillin-resistant Staphylococcus aureus (MRSA) cause infections in community settings worldwide. To examine heterogeneity of spread within households and to identify common risk factors for household transmission across settings, primary data from studies conducted in New York (USA), Breda (The Netherlands), and Melbourne (Australia) were pooled. Following MRSA infection of the index patient, household members completed questionnaires and provided nasal swabs. Swabs positive for S. aureus were genotyped by spa sequencing. Poisson regression with robust error variance was used to estimate prevalence odds ratios for transmission of the clinical isolate to non-index household members. Great diversity of strain types existed across studies. Despite differences between studies, the index patient being colonized with the clinical isolate at the home visit (P < 0·01) and the percent of household members aged <18 years (P < 0·01) were independently associated with transmission. Targeted decolonization strategies could be used across geographical settings to limit household MRSA transmission.

Inmates of Rikers Island jail potentially introduce Staphylococcus aureus into New York State prisons upon transfer. In this study, methicillin-resistant Staphylococcus aureus isolates (n = 452), collected from infected inmates (2009 to 2013), were characterized. spa type t008 was the predominant clone identified, accounting for 82.3% of the isolates, with no evidence of mupirocin or chlorhexidine resistance., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

During the last 2 decades, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have dramatically increased the global burden of S. aureus infections. The pandemic sequence type (ST)8/pulsed-field gel type USA300 is the dominant CA-MRSA clone in the United States, but its evolutionary history and basis for biological success are incompletely understood. Here, we use whole-genome sequencing of 387 ST8 isolates drawn from an epidemiological network of CA-MRSA infections and colonizations in northern Manhattan to explore short-term evolution and transmission patterns. Phylogenetic analysis predicted that USA300 diverged from a most common recent ancestor around 1993. We found evidence for multiple introductions of USA300 and reconstructed the phylogeographic spread of isolates across neighborhoods. Using pair-wise single-nucleotide polymorphism distances as a measure of genetic relatedness between isolates, we observed that most USA300 isolates had become endemic in households, indicating their critical role as reservoirs for transmission and diversification. Using the maximum single-nucleotide polymorphism variability of isolates from within households as a threshold, we identified several possible transmission networks beyond households. Our study also revealed the evolution of a fluoroquinolone-resistant subpopulation in the mid-1990s and its subsequent expansion at a time of high-frequency outpatient antibiotic use. This high-resolution phylogenetic analysis of ST8 has documented the genomic changes associated with USA300 evolution and how some of its recent evolution has been shaped by antibiotic use. By integrating whole-genome sequencing with detailed epidemiological analyses, our study provides an important framework for delineating the full diversity and spread of USA300 and other emerging pathogens in large urban community populations.

Background: Self- administered questionnaires or interviews and medical records are often used as sources of research data; thus it is essential to evaluate their concordance and reliability. The aim of this paper was to assess the concordance between medical and behavioral data obtained from medical records and interview questionnaires in two correctional facilities., Methods: Medical record and interview data were compared for 679 inmates from one male and one female maximum security prison between April 2010 and February 2013. Gender non-stratified and gender-stratified analyses were conducted in SPSS to calculate the prevalence and kappa coefficient scores (κ) for medical (e.g., HIV, diabetes, hypertension) and behavioral (e.g., smoking, drug use, tattoos) conditions. Sensitivity/specificity between medical records and interview were calculated in the gender non-stratified data., Results: In the gender non-stratified analysis, κ score for HIV, hepatitis C, diabetes, asthma, and history of tattoos had strong or good concordance (0.66-0.89). Hypertension, renal/kidney disease, cigarette smoking, antibiotic use in the last 6 months, and cocaine use ever were moderately correlated (0.49-0.57). Both history of any illicit drug use ever (0.36) and marijuana use ever (0.23) had poor concordance. Females had higher κ scores and prevalence rates than males overall. Medical conditions were reported more frequently in medical records and behavioral conditions had higher prevalence in interviews. Sensitivity for medical conditions in the combined facility data ranged from 50.0% to 86.0% and 48.2% to 85.3% for behavioral conditions whereas specificity ranged from 95.9% to 99.5% for medical conditions and 75.9% to 92.8% for behavioral conditions., Conclusion: Levels of agreement between medical records and self-reports varied by type of factor. Medical conditions were more frequently reported by chart review and behavioral factors more frequently by self-report. Data source used may need to be chosen carefully depending upon the type of information sought.

To assess the prevalence and risk factors for colonization with Staphylococcus aureus in inmates entering two maximum-security prisons in New York State, USA, inmates (N=830) were interviewed and anterior nares and oropharyngeal samples collected. Isolates were characterized using spa typing. Overall, 50·5% of women and 58·3% of men were colonized with S. aureus and 10·6% of women and 5·9% of men were colonized with MRSA at either or both body sites. Of MSSA isolates, the major subtypes were spa type 008 and 002. Overall, risk factors for S. aureus colonization varied by gender and were only found in women and included younger age, fair/poor self-reported general health, and longer length of prior incarceration. Prevalence of MRSA colonization was 8·2%, nearly 10 times greater than in the general population. Control of epidemic S. aureus in prisons should consider the constant introduction of strains by new inmates.

Staphylococcus aureus is a prominent cause of human infections globally. The high prevalence of infections is compounded by antibiotic resistance--a significant problem for treatment. Methicillin-resistant S. aureus (MRSA) is endemic in hospitals and healthcare facilities worldwide, and is an increasingly common cause of community-associated bacterial infections in industrialized countries. Although much focus is placed on the role of S. aureus as a human pathogen, it is in fact a human commensal organism that has had a relatively long coexistence with the human host. Many S. aureus infections can be explained by host susceptibility or other predisposing risk factors. On the other hand, the emergence/re-emergence of successful S. aureus clones (referred to as epidemic waves) suggests a rapid bacterial adaption and evolution, which includes the emergence of antibiotic resistance and increased virulence and/or transmissibility. It is within this context that we review our understanding of selected S. aureus epidemic waves, and highlight the use of genome sequencing as a means to better understand the evolution of each lineage., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: 0.5% to 10% of clean surgeries result in surgical-site infections, and attempts to reduce this rate have had limited success. Germicidal UV lamps, with a broad wavelength spectrum from 200 to 400 nm are an effective bactericidal option against drug-resistant and drug-sensitive bacteria, but represent a health hazard to patient and staff. By contrast, because of its limited penetration, ~200 nm far-UVC light is predicted to be effective in killing bacteria, but without the human health hazards to skin and eyes associated with conventional germicidal UV exposure., Aims: The aim of this work was to test the biophysically-based hypothesis that ~200 nm UV light is significantly cytotoxic to bacteria, but minimally cytotoxic or mutagenic to human cells either isolated or within tissues., Methods: A Kr-Br excimer lamp was used, which produces 207-nm UV light, with a filter to remove higher-wavelength components. Comparisons were made with results from a conventional broad spectrum 254-nm UV germicidal lamp. First, cell inactivation vs. UV fluence data were generated for methicillin-resistant S. aureus (MRSA) bacteria and also for normal human fibroblasts. Second, yields of the main UV-associated pre-mutagenic DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts) were measured, for both UV radiations incident on 3-D human skin tissue., Results: We found that 207-nm UV light kills MRSA efficiently but, unlike conventional germicidal UV lamps, produces little cell killing in human cells. In a 3-D human skin model, 207-nm UV light produced almost no pre-mutagenic UV-associated DNA lesions, in contrast to significant yields induced by a conventional germicidal UV lamp., Conclusions: As predicted based on biophysical considerations, 207-nm light kills bacteria efficiently but does not appear to be significantly cytotoxic or mutagenic to human cells. Used appropriately, 207-nm light may have the potential for safely and inexpensively reducing surgical-site infection rates, including those of drug-resistant origin.

The methicillin-susceptible Staphylococcus aureus (MSSA) clone sequence type (ST) 398 has increasingly been identified as a pathogen in diverse geographic settings, yet its epidemiology remains incompletely understood. In this case-control study of MSSA infections, we identified ST398 MSSA as both a major community- and hospital-associated MSSA pathogen in the Dominican neighborhood of northern Manhattan.

Sequence type 398 (ST398) Staphylococcus aureus, frequently carried by livestock, has caused severe human infections and often carries transmissible antibiotic resistance genes. Among methicillin-susceptible S. aureus isolates colonizing Dallas County Jail detainees, 13.2% were ST398, spa type t571, and were genetically similar to human colonization isolates from New York, Chicago, and the Dominican Republic.

While much is known about the geographic distribution of different clonal types of methicillin-resistant Staphylococcus aureus (MRSA), few studies have assessed the molecular epidemiology of methicillin-susceptible S. aureus (MSSA), despite its continued clinical importance. In each U.S. Census region, reference laboratories collected successive MSSA isolates from patients with invasive or superficial staphylococcal infections for use in the Tigecycline Evaluation and Surveillance Trial. All isolates from the periods of 2004 to 2005 and 2009 to 2010 underwent antimicrobial susceptibility testing and characterization of their staphylococcal protein A (spa) type. Of the 708 isolates analyzed, 274 spa types were identified and divided into 15 genetic clusters. The most common clones were spa t002 (n = 63, 8.9%) and t008 (n = 56, 7.9%). While the distribution of the predominant spa types did not differ by U.S. Census region or time period, spa t008 was nearly twice as common in community skin and soft tissue infections than in nosocomial bloodstream infections (11.1% versus 5.6%, respectively; P = 0.008). Despite such differences, both community and nosocomial settings had diverse staphylococcal clonal types representing all major spa clusters. In contrast to those of MRSA, MSSA infectious isolates show wide genetic diversity without clear geographical or temporal clustering. Notably, the prevalent MSSA strains (spa t002 and spa t008) are analogous to the predominant MRSA clones, further demonstrating the importance of both lineages.

Background: Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections., Methods and Results: One hundred fifty patients scheduled for VAD implantation were enrolled (2006-2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073-0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001)., Conclusions: This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.

Fiberoptic bronchoscopy is a valuable diagnostic tool in solid-organ and hematopoietic stem cell transplant recipients presenting with a range of pulmonary complications. This article provides a comprehensive overview of the utility and potential adverse effects of diagnostic bronchoscopy for transplant recipients. Recommendations are offered on the selection of patients, the timing of bronchoscopy, and the samples to be obtained across the spectrum of suspected pulmonary complications of transplantation. Based on review of the literature, the authors recommend early diagnostic bronchoscopy over empiric treatment in transplant recipients with evidence of certain acute, subacute, or chronic pulmonary processes. This approach may be most critical when an underlying infectious etiology is suspected. In the absence of prompt diagnostic information on which to base effective treatment, the risks associated with empiric antimicrobial therapy, including medication side effects and the development of antibiotic resistance, compound the potential harm of delaying targeted management.

Staphylococcus aureus clonal complex 398 (CC398) isolates colonize livestock and can spread to human contacts. Genetic analysis of isolates epidemiologically associated with human-to-human, but not livestock, transmission in multiple countries and continents identified a common clade that was negative for tet(M) and positive for bacteriophage 3. Another group of human-to-human-transmitted isolates belonged to the common livestock-associated clade but had acquired a unique 7 bacteriophage.