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Background: Novel treatments are needed for Staphylococcus aureus bacteremia, particularly for methicillin-resistant S. aureus (MRSA). Exebacase is a first-in-class antistaphylococcal lysin that is rapidly bactericidal and synergizes with antibiotics., Methods: In Direct Lysis of Staph Aureus Resistant Pathogen Trial of Exebacase (DISRUPT), a superiority-design phase 3 study, patients with S. aureus bacteremia/endocarditis were randomly assigned to receive a single dose of intravenous exebacase or placebo in addition to standard-of-care antibiotics. The primary efficacy outcome was clinical response at day 14 in the MRSA population., Results: A total of 259 patients were randomized before the study was stopped for futility based on the recommendation of the unblinded Data Safety Monitoring Board. Clinical response rates at day 14 in the MRSA population (n = 97) were 50.0% (exebacase + antibiotics; 32/64) versus 60.6% (antibiotics alone; 20/33) (P = .392). Overall, rates of adverse events were similar across groups. No adverse events of hypersensitivity related to exebacase were reported., Conclusions: Exebacase + antibiotics failed to improve clinical response at day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics-alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis. Clinical Trials Registration.NCT04160468., Competing Interests: Potential conflicts of interest. V. G. F. reports grants to his institution and personal consulting fees from ContraFect. Grants/research support: MedImmune, Cerexa/Forest/Actavis/Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Cubist/Merck, Medical Biosurfaces, Locus, Affinergy, ContraFect, Karius, Genentech, Regeneron, Basilea. Paid Consultant: Pfizer, Novartis, Galderma, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Cubist, Basilea, Affinergy, Janssen, xBiotech, ContraFect, Regeneron, Basilea, Destiny. Membership: Merck Co-Chair V710 Vaccine. Educational fees: Green Cross, Cubist, Cerexa, Durata, Theravance; Debiopharm. Royalties: UpToDate. Patent pending: sepsis diagnostics. ArcBio and Valanbio stock. A. F. D. reports personal consulting fees from ContraFect, Achaogen, IterumTx, Paratek, Nabriva, Wockhardt, UTILITY, Zavante, Tetraphase, Theravance, and Cempra. Membership: Scynexis. Stock options from Utility. J. L. D. reports personal consulting fees and membership for ContraFect. J. E. A. is an employee of ContraFect and has a PCT Application with publication no. W0/2022/261360 and reports grants from the Cystic Fibrosis Foundation (CONTRAFECT20XO-SC; CONTRAFECT21WO-SC). R. S. is an employee of ContraFect and has US Patent No. 9,889,181 issued and US Patent No. 9,499,594 issued, stock options and support for meetings and/or travel from ContraFect. R. P. is an employee of ContraFect. C. C. was an employee of ContraFect and reports stock options from ContraFect. L. J. P. reports grants from ContraFect. G. J. M. reports grants from ContraFect; grants and personal consulting fees from Nabriva. Consulting fees and stock options for Light AT, payment for lectures from Hippo Education. M. E. R. reports grants from ContraFect and Magnolia; personal consulting fees from Citius, Teleflex, Armata, and 3M. Payment for lectures from ACP- Dynamed, Membership: Armata Pharmaceuticals. A. M. L. reports grants/research support from ContraFect, Cidara, Veru, Shionogi, and Novartis. J. L. K. reports grants from ContraFect, bioMeriuex, Entasis, Food and Drug Administration, Merck, Pfizer, Shionogi, and Venatorx; consulting/advisory board/speaker fees from Abbvie, GSK, and Shionogi. R. A. W. reports personal consulting fees from ContraFect, Pulmonx, Roche, Merck, AbbVie, Kamada, Galderma, AstraZeneca, Savara, Bristol-Myers, Boehringer-Ingelheim, and Chiesi; grants from Shinogi, Sanofi-Aventis, AstraZeneca, Verona, and Chiesi, Pfizer, Moderna. Membership: ContraFect. K. S. K. reports personal consulting fees from ContraFect, Merck, Spero, Abbvie, Allecra, Carb-X, Shionogi, VenatoRX, MicuRx, Glaxo SmithKline, Entasis; DSMB for Entasis. Membership: Venato-Rx, Meiji, ContraFect M. J. Z. reports personal consulting fees from ContraFect; grants from Pfizer, Merck, Medimmune, and Genetech. W. G. N. reports personal consulting fees from ContraFect and Istari Oncology, stock options from ContraFect Corporation Inc. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Vancomycin remains the mainstay treatment for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) despite increased treatment failures. Daptomycin has been shown to improve clinical outcomes in patients with BSIs caused by MRSA isolates with vancomycin MICs of >1 mg/liter, but these studies relied on automated testing systems. We evaluated the outcomes of BSIs caused by MRSA isolates for which vancomycin MICs were determined by standard broth microdilution (BMD). A retrospective, matched cohort of patients with MRSA BSIs treated with vancomycin or daptomycin from January 2010 to March 2015 was completed. Patients were matched using propensity-adjusted logistic regression, which included age, Pitt bacteremia score, primary BSI source, and hospital of care. The primary endpoint was clinical failure, which was a composite endpoint of the following metrics: 30-day mortality, bacteremia with a duration of ≥7 days, or a change in anti-MRSA therapy due to persistent or worsening signs or symptoms. Secondary endpoints included MRSA-attributable mortality and the number of days of MRSA bacteremia. Independent predictors of failure were determined through conditional backwards-stepwise logistic regression with vancomycin BMD MIC forced into the model. A total of 262 patients were matched. Clinical failure was significantly higher in the vancomycin cohort than in the daptomycin cohort (45.0% versus 29.0%; P = 0.007). All-cause 30-day mortality was significantly higher in the vancomycin cohort (15.3% versus 6.1%; P = 0.024). These outcomes remained significant when stratified by vancomycin BMD MIC. There was no significant difference in the length of MRSA bacteremia. Variables independently associated with treatment failure included vancomycin therapy (adjusted odds ratio [aOR] = 2.16, 95% confidence interval [CI] = 1.24 to 3.76), intensive care unit admission (aOR = 2.46, 95% CI = 1.34 to 4.54), and infective endocarditis as the primary source (aOR = 2.33, 95% CI = 1.16 to 4.68). Treatment of MRSA BSIs with daptomycin was associated with reduced clinical failure and 30-day mortality; these findings were independent of vancomycin BMD MIC., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: Contact precautions (CPs) are recommended to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission in institutions. Rising doubts about CP effectiveness and recognition of unintended consequences for patients have raised questions about the benefit. The objective of this study was to evaluate the effectiveness and adverse outcomes associated with CPs for prevention of MRSA transmission., Methods: We searched PubMed, Embase, and the Cochrane Library for articles related to effectiveness and adverse outcomes of CPs in patients with MRSA. Criteria for inclusion included the following: articles conducted in the United States, articles performed in an acute care setting, articles that were not a case series or review, and those with standardized collection of data or inclusion of case and control groups. Results were summarized and examined for potential limitations. Recommendations were based on our findings., Results: CPs reduced MRSA transmission in epidemic settings and in instances with high compliance, but a decrease in infection rates was not shown. Unintended consequences of CPs include decreased health care provider (HCP) time spent with patients, low HCP compliance, decreased perceptions of comfort from patients, and greater likelihood of patient complaints and negative psychologic implications., Conclusion: In endemic settings, there are few data to support routine use of CPs to control the spread of MRSA. Education should be performed in hospitals to improve patients' perception of care and understanding of CPs when implemented and HCPs' adherence to good hand hygiene and standard precautions practices., (Published by Elsevier Inc.)

We assessed for vancomycin-resistant Staphylococcus aureus (VRSA) precursor organisms in southeastern Michigan, an area known to have VRSA. The prevalence was 2.5% (pSK41-positive methicillin-resistant S. aureus, 2009-2011) and 1.5% (Inc18-positive vancomycin-resistant Enterococcus, 2006-2013); Inc18 prevalence significantly decreased after 2009 (3.7% to 0.82%). Risk factors for pSK41 included intravenous vancomycin exposure.

Background: Of the 13 US vancomycin-resistant Staphylococcus aureus (VRSA) cases, 8 were identified in southeastern Michigan, primarily in patients with chronic lower-extremity wounds. VRSA infections develop when the vanA gene from vancomycin-resistant enterococcus (VRE) transfers to S. aureus. Inc18-like plasmids in VRE and pSK41-like plasmids in S. aureus appear to be important precursors to this transfer., Objective: Identify the prevalence of VRSA precursor organisms., Design: Prospective cohort with embedded case-control study., Participants: Southeastern Michigan adults with chronic lower-extremity wounds., Methods: Adults presenting to 3 southeastern Michigan medical centers during the period February 15 through March 4, 2011, with chronic lower-extremity wounds had wound, nares, and perirectal swab specimens cultured for S. aureus and VRE, which were tested for pSK41-like and Inc18-like plasmids by polymerase chain reaction. We interviewed participants and reviewed clinical records. Risk factors for pSK41-positive S. aureus were assessed among all study participants (cohort analysis) and among only S. aureus-colonized participants (case-control analysis)., Results: Of 179 participants with wound cultures, 26% were colonized with methicillin-susceptible S. aureus, 27% were colonized with methicillin-resistant S. aureus, and 4% were colonized with VRE, although only 17% consented to perirectal culture. Six participants (3%) had pSK41-positive S. aureus, and none had Inc18-positive VRE. Having chronic wounds for over 2 years was associated with pSK41-positive S. aureus colonization in both analyses., Conclusions: Colonization with VRSA precursor organisms was rare. Having long-standing chronic wounds was a risk factor for pSK41-positive S. aureus colonization. Additional investigation into the prevalence of VRSA precursors among a larger cohort of patients is warranted.

Background: Recent reports have described decreased effectiveness with vancomycin treatment for methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) when the vancomycin minimum inhibitory concentration (MIC) is >1 µg/mL., Methods: This matched, retrospective cohort study compared the clinical effectiveness of daptomycin with that of vancomycin for the treatment of MRSAB with vancomycin MICs >1 µg/mL. The primary outcome was clinical failure, defined as a composite of 30-day mortality or bacteremia persisting for ≥7 days., Results: One hundred seventy patients were matched 1:1 with respect to the antimicrobial administered. In the daptomycin group, all patients received <72 hours of vancomycin (median, 1.7 days [interquartile range, 1.1-2.3 days]) prior to switching to daptomycin. The rate of clinical failure at 30 days was significantly lower in the daptomycin arm compared to the vancomycin arm (20.0% vs 48.2%; P < 0.001). Both 30-day mortality and persistent bacteremia were significantly lower in the daptomycin group compared to the vancomycin group (3.5% vs 12.9% [P = .047] and 18.8% vs 42.4% [P = .001], respectively). Logistic regression confirmed the association between vancomycin treatment and increased risk of clinical failure (adjusted odds ratio, 4.5; 95% confidence interval, 2.1-9.8)., Conclusions: This is the first matched study comparing early daptomycin versus vancomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL. Treatment with daptomycin resulted in significantly improved outcomes, including decreased 30-day mortality and persistent bacteremia. These results support the practice of switching early from vancomycin to daptomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL.

In the majority of cases of vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant Enterococcus faecalis (VR E. faecalis) served as the vanA donor to S. aureus. Previous studies that evaluated the risk factors for co-colonization with VRE and MRSA did not differentiate between VR E. faecalis and VR E. faecium. This study aimed to identify variables associated with VR E. faecalis and MRSA co-colonization. A retrospective case-control study from January 2008 to December 2009 was conducted at the Detroit Medical Center. Data were extracted from charts and pharmacy records. Unique patients co-colonized with VR E. faecalis and MRSA (defined as isolation of MRSA within 7 days of VR E. faecalis isolation) were compared with patients with VR E. faecalis who were not co-colonized with MRSA. A total of 546 patients with VR E. faecalis isolation were identified. 85 (15.6 %) VR E. faecalis patients were co-colonized with MRSA and 461 (84.4 %) VR E. faecalis patients were not co-colonized with MRSA. The mean age of the study cohort was 65.9 ± 16.4 years, 424 (77.7 %) were African-American, and 270 (49.5 %) were residing in long-term care institutions. Independent predictors of co-colonization of VR E. faecalis and MRSA were male gender, impaired consciousness, ICU stay prior to VR E. faecalis isolation, indwelling devices, and isolation of VR E. faecalis from wounds. MRSA was frequently isolated from the same culture specimen as VR E. faecalis (n = 39, 45.9 %), most commonly from wounds. This large study of patients with VR E. faecalis identified the severity of illness, indwelling devices, and chronic wounds as independent predictors of co-colonization with VR E. faecalis and MRSA.

Objective: We evaluated the clinical and molecular epidemiology of bloodstream infections (BSIs) due to methicillin-resistant Staphylococcus aureus (MRSA) in older versus younger patients treated with vancomycin, determining the independent effect of increased age on outcomes., Design: Observational retrospective cohort study., Setting: Detroit Medical Center, level I trauma center., Patients: Adult older (65 years and older) and younger (younger than 65 years) patients with documented BSIs due to MRSA treated with vancomycin (2005-2010)., Methods: Collected demographics, comorbidities, microbiology, treatment, outcomes. Multivariable model used to generate propensity score for each patient on the basis of the probability of being 65 years of age or older., Results: Three hundred twenty patients were eligible (69 patients 65 years and older; 251 patients younger than 65 years). Catheter-related infections and endocarditis were the most common sites of infection for older (20.3%) and younger (19.1%) adults, respectively. Median first total 24-hour vancomycin dose (1,000 vs 2,000 mg; [Formula: see text]) and initial trough (13.1 vs 15.0 mg/L; [Formula: see text]) was significantly lower in older versus younger patients. Vancomycin treatment failure rates were similar among older and younger patients (49.3% vs 53.4%; [Formula: see text]). In multivariable analysis of outcomes, after controlling for predictors of older age, there was no difference in clinical outcomes between older and younger adults., Conclusions: After accounting for confounders associated with increased age, failure rate of patients with BSIs due to MRSA treated with vancomycin was similar between older and younger patients. Older adults were less likely to have optimal vancomycin dosing and initial trough levels than younger patients. Efforts should be made to optimize dosing of medications such as vancomycin in older adults.

Study Objective: To evaluate a clinical pathway using daptomycin in patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibiting vancomycin minimum inhibitory concentrations (MICs) greater than 1 mg/L., Design: Two-phase quasi-experimental study., Setting: Level I trauma center in Detroit, Michigan., Patients: The study population consisted of a total of 170 patients with MRSA bacteremia susceptible to vancomycin: 70 patients who had initial blood MRSA isolates exhibiting a vancomycin MIC > 1 mg/L and were treated with vancomycin were included in phase I (retrospective baseline period [2005-2007]) and 100 patients who were switched to daptomycin after initial vancomycin therapy according to the institutional MRSA bacteremia treatment pathway were included in phase II (the period after implementation of the treatment pathway [2008-2010])., Intervention: The MRSA bacteremia treatment pathway was as follows: vancomycin therapy was initiated, optimizing target trough concentrations to 15-20 mg/L; for isolates demonstrating vancomycin MICs greater than 1 mg/L, therapy was switched to daptomycin, initiated at dosages of 6 mg/kg/day or higher., Measurements and Main Results: Infection characteristics, patient outcomes, and costs were evaluated. Patient characteristics were similar between the phase I and phase II groups. Phase II patients were more likely to achieve clinical success than were phase I patients (75.0% vs 41.4%, p<0.001). Phase II patients demonstrated a shorter total hospital length of stay and shorter durations of inpatient therapy, fever, and bacteremia. Treatment during phase I was independently associated with failure. Nine patients during phase I experienced nephrotoxicity, and two patients during phase II experienced increases in creatine kinase level. Costs were similar between phases I and II ($18,385 vs $19,755, p>0.05), although the hospital readmission rate was higher in phase I (33% vs 21%, p=0.08)., Conclusion: Among the patients with bacteremia who had MRSA isolates that exhibited elevated vancomycin MICs, the switch to daptomycin improved clinical success without increasing treatment cost., (© 2013 Pharmacotherapy Publications, Inc.)

Background: Guidelines recommend that agents other than vancomycin be considered for some types of infection due to methicillin-resistant Staphylococcus aureus (MRSA) when the minimum inhibitory concentration (MIC) to vancomycin is 2 μg/mL or more. Alternative therapeutic options include daptomycin and linezolid, 2 relatively new and expensive drugs, and trimethoprim/sulfamethoxazole (TMP/SMX), an old and inexpensive agent., Objective: To compare the clinical efficacy and potential cost savings associated with use of TMP/SMX compared to linezolid and daptomycin., Methods: A retrospective study was conducted at Detroit Medical Center. For calendar year 2009, unique adults (age >18 years) with infections due to MRSA with an MIC to vancomycin of 2 μg/mL were included if they received 2 or more doses of TMP/SMX and/or daptomycin and/or linezolid. Data were abstracted from patient charts and pharmacy records., Results: There were 328 patients included in the study cohort: 143 received TMP/SMX alone, 89 received daptomycin alone, 75 received linezolid alone, and 21 patients received a combination of 2 or more of these agents. In univariate analysis, patients who received TMP/SMX alone had significantly better outcomes, including in-hospital (p = 0.003) and 90-day mortality (p < 0.001) compared to patients treated with daptomycin or linezolid. Patients receiving TMP/SMX were also younger (p < 0.001), had fewer comorbid conditions (p < 0.001), had less severe acute severity of illness (p < 0.001), and received appropriate therapy more rapidly (p = 0.001). In multivariate models the association between TMP/SMX treatment and mortality was no longer significant. Antimicrobial cost savings associated with using TMP/SMX averaged $2067.40 per patient., Conclusions: TMP/SMX monotherapy compared favorably to linezolid and daptomycin in terms of treatment efficacy and mortality. Use of TMP/SMX instead of linezolid or daptomycin could potentially significantly reduce antibiotic costs. TMP/SMX should be considered for the treatment of MRSA infection with MIC of 2 μg/mL to vancomycin.

Objective: To determine the epidemiological characteristics of postoperative invasive Staphylococcus aureus infection following 4 types of major surgical procedures.design. Retrospective cohort study., Setting: Eleven hospitals (9 community hospitals and 2 tertiary care hospitals) in North Carolina and Virginia., Patients: Adults undergoing orthopedic, neurosurgical, cardiothoracic, and plastic surgical procedures., Methods: We used previously validated, prospectively collected surgical surveillance data for surgical site infection and microbiological data for bloodstream infection. The study period was 2003 through 2006. We defined invasive S. aureus infection as either nonsuperficial incisional surgical site infection or bloodstream infection. Nonparametric bootstrapping was used to generate 95% confidence intervals (CIs). P values were generated using the Pearson chi2 test, Student t test, or Wilcoxon rank-sum test, as appropriate., Results: In total, 81,267 patients underwent 96,455 procedures during the study period. The overall incidence of invasive S. aureus infection was 0.47 infections per 100 procedures (95% CI, 0.43-0.52); 227 (51%) of 446 infections were due to methicillin-resistant S.aureus. Invasive S. aureus infection was more common after cardiothoracic procedures (incidence, 0.79 infections per 100 procedures [95%CI, 0.62-0.97]) than after orthopedic procedures (0.37 infections per 100 procedures [95% CI, 0.32-0.42]), neurosurgical procedures (0.62 infections per 100 procedures [95% CI, 0.53-0.72]), or plastic surgical procedures (0.32 infections per 100 procedures [95% CI, 0.17-0.47]) (P < .001). Similarly, S. aureus bloodstream infection was most common after cardiothoracic procedures (incidence, 0.57 infections per 100 procedures [95% CI, 0.43-0.72]; P < .001, compared with other procedure types), comprising almost three-quarters of the invasive S. aureus infections after these procedures. The highest rate of surgical site infection was observed after neurosurgical procedures (incidence, 0.50 infections per 100 procedures [95% CI, 0.42-0.59]; P < .001, compared with other procedure types), comprising 80% of invasive S.aureus infections after these procedures., Conclusion: The frequency and type of postoperative invasive S. aureus infection varied significantly across procedure types. The highest risk procedures, such as cardiothoracic procedures, should be targeted for ongoing preventative interventions.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with increased mortality. Delay in appropriate antimicrobial therapy (DAAT) is an important risk factor for death, although confounding between carriage of MRSA and DAAT has not been resolved. We studied the association of risk factors with mortality and searched for specific populations vulnerable to DAAT. We conducted a case-control study comparing patients with MRSA bacteraemia who died during hospitalization (cases) with patients with MRSA bacteraemia who survived (controls) in three medical centres in two states. Patients were identified using computerized hospital databases for the years 2001-2005. Medical records were retrieved and various epidemiological data extracted. Bivariate and multivariate logistic regression analyses were performed. Overall, 388 patients with MRSA bacteraemia were included, 164 cases and 224 controls. According to bivariate analyses, cases were significantly more likely than controls to (i) be older (>65 years), (ii) have transferred from an institution, (iii) have stayed in an ICU, (iv) have had more invasive devices, (v) have a poorer prognosis on admission, (vi) have higher disease severity at the time of bacteraemia, and (vii) have a DAAT of > or = 2 days. Upon multivariate analysis, among patients >65 years, DAAT was significantly associated with increased mortality (p 0.04). Furthermore, patients >65 years with severe sepsis were much more likely to experience DAAT (p 0.02). In elderly patients with MRSA bacteraemia, DAAT is associated with increased mortality. Moreover, advanced age is a predictor for DAAT. These significant epidemiological associations mandate early coverage of MRSA in septic elderly patients.

Background: Hand hygiene noncompliance is a major cause of nosocomial infection. Nosocomial infection cost data exist, but the effect of hand hygiene noncompliance is unknown., Objective: To estimate methicillin-resistant Staphylococcus aureus (MRSA)-related cost of an incident of hand hygiene noncompliance by a healthcare worker during patient care., Design: Two models were created to simulate sequential patient contacts by a hand hygiene-noncompliant healthcare worker. Model 1 involved encounters with patients of unknown MRSA status. Model 2 involved an encounter with an MRSA-colonized patient followed by an encounter with a patient of unknown MRSA status. The probability of new MRSA infection for the second patient was calculated using published data. A simulation of 1 million noncompliant events was performed. Total costs of resulting infections were aggregated and amortized over all events., Setting: Duke University Medical Center, a 750-bed tertiary medical center in Durham, North Carolina., Results: Model 1 was associated with 42 MRSA infections (infection rate, 0.0042%). Mean infection cost was $47,092 (95% confidence interval [CI], $26,040-$68,146); mean cost per noncompliant event was $1.98 (95% CI, $0.91-$3.04). Model 2 was associated with 980 MRSA infections (0.098%). Mean infection cost was $53,598 (95% CI, $50,098-$57,097); mean cost per noncompliant event was $52.53 (95% CI, $47.73-$57.32). A 200-bed hospital incurs $1,779,283 in annual MRSA infection-related expenses attributable to hand hygiene noncompliance. A 1.0% increase in hand hygiene compliance resulted in annual savings of $39,650 to a 200-bed hospital., Conclusions: Hand hygiene noncompliance is associated with significant attributable hospital costs. Minimal improvements in compliance lead to substantial savings.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has become a common surgical site infection (SSI) pathogen, particularly in older adults. Risk factors for MRSA SSI in elderly patients have not been described., Methods: A nested case-control study was conducted. Patients were enrolled from seven study hospitals (one medical center and six community hospitals) between January 1, 1998, and April 1, 2003. Risk factors for MRSA SSI were identified by comparing cases with two reference groups: uninfected surgical patients and patients with SSI due to methicillin-susceptible S. aureus (MSSA). Two separate multivariate models were created using logistic regression and then compared and contrasted., Results: Eighty-six patients with MRSA and 64 with MSSA SSI were identified. One hundred sixty-seven uninfected surgical patients were selected. In multivariate analysis using uninfected surgical patients as controls, requiring assistance in three or more activities of daily living (ADLs) was an independent risk factor for MRSA SSI (odds ratio (OR)=2.73, 95% confidence interval (CI)=1.16-6.46). Using patients with MSSA SSIs as a reference group, requiring assistance in three or more ADLs was also a significant predictor for MRSA SSI (OR=3.78, 95% CI=1.43-9.98) in multivariate analysis. Other independent predictors included Charlson score, wound class, and surgical duration. Lack of independence in ADLs was an independent risk factor for MRSA SSI in elderly patients in both models., Conclusion: Poor functional status (requiring assistance in >or=3 ADLs) was specifically associated with MRSA SSI. Functional status is an objective, readily available variable that can be used to stratify patients at risk for MRSA SSI.

Background: The clinical and financial outcomes of SSIs directly attributable to MRSA and methicillin-resistance are largely uncharacterized. Previously published data have provided conflicting conclusions., Methodology: We conducted a multi-center matched outcomes study of 659 surgical patients. Patients with SSI due to MRSA were compared with two groups: matched uninfected control patients and patients with SSI due to MSSA. Four outcomes were analyzed for the 90-day period following diagnosis of the SSI: mortality, readmission, duration of hospitalization, and hospital charges. Attributable outcomes were determined by logistic and linear regression., Principal Findings: In total, 150 patients with SSI due to MRSA were compared to 231 uninfected controls and 128 patients with SSI due to MSSA. SSI due to MRSA was independently predictive of readmission within 90 days (OR = 35.0, 95% CI 17.3-70.7), death within 90 days (OR = 7.27, 95% CI 2.83-18.7), and led to 23 days (95% CI 19.7-26.3) of additional hospitalization and $61,681 (95% 23,352-100,011) of additional charges compared with uninfected controls. Methicillin-resistance was not independently associated with increased mortality (OR = 1.72, 95% CI 0.70-4.20) nor likelihood of readmission (OR = 0.43, 95% CI 0.21-0.89) but was associated with 5.5 days (95% CI 1.97-9.11) of additional hospitalization and $24,113 (95% 4,521-43,704) of additional charges., Conclusions/significance: The attributable impact of S. aureus and methicillin-resistance on outcomes of surgical patients is substantial. Preventing a single case of SSI due to MRSA can save hospitals as much as $60,000.

Background: Despite the high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection in the hospital, the proportion of patients with MRSA bacteremia who receive appropriate empirical therapy remains suboptimal., Objective: To investigate the proportion of patients with MRSA bloodstream infection (BSI) who received appropriate empirical antibiotic therapy and to identify risk factors associated with receipt of appropriate empirical therapy., Methods: We studied a cohort of patients from 10 hospitals. The primary outcome was the proportion of patients who received appropriate empirical antibiotic therapy for MRSA BSI. Appropriate therapy was defined as receipt of daptomycin, linezolid, quinupristin-dalfopristin, or vancomycin within 1 calendar day after the first blood culture result positive for S. aureus (ie, before antimicrobial susceptibilities were known). Multivariable logistic regression was used to determine variables associated with receipt of appropriate empirical therapy., Results: The study included 562 patients with MRSA BSI. The mean (+/-standard deviation) age of the patients was 64 +/- 16 years, and 288 (51.2%) were male. Only 291 (51.8%) patients received appropriate empirical therapy. Patients were more likely to receive appropriate therapy if they required hemodialysis (odds ratio [OR], 1.36 [95% confidence interval {CI}, 1.00-1.85]), had undergone knee or hip arthroplasty (OR, 3.04 [95% CI, 1.21-7.6]), had a central venous catheter at admission (OR, 1.72 [95% CI, 1.01-2.93]), or had a McCabe score of 1 at admission (OR, 1.83 [95% CI, 1.16-2.83]). Bowel incontinence (OR, 0.41 [95% CI, 0.19-0.92]) and BSIs categorized as primary (OR, 0.41 [95% CI, 0.27-0.63]) were associated with a decreased likelihood of receiving appropriate empirical therapy., Conclusions: Only half of patients with MRSA BSI received appropriate empirical therapy. Factors associated with receiving appropriate empirical antibiotics included the presence of a central venous catheter at admission and a history of joint arthroplasty. Surprisingly, prior MRSA infection was not predictive of receipt of appropriate antimicrobial therapy.

Objective: Staphylococcus aureus infections after cardiac surgery result in significant morbidity and mortality. Identifying patients at elevated risk for these infections preoperatively could facilitate efforts to reduce infection rates. The objectives of this study were to estimate the incidence of postoperative S. aureus infections in cardiac surgery patients, to identify preoperative risk factors for these infections, and to establish a patient risk profile by means of data available to clinicians prior to surgery., Design: Cohort study., Setting: Eight medical centers that participate in the Society of Thoracic Surgeons National Cardiac Database., Patients: Patients who were undergoing elective cardiac surgery during the period January 1, 2000 through December 31, 2004., Methods: Clinical and microbiological data from 16,386 patients were combined. Multivariable stepwise logistic regression analysis was performed to predict S. aureus infection, which was defined by culture results., Results: Of the 16,386 patients, 205 (1.3%) developed S. aureus bloodstream or chest wound infection within 90 days after surgery. On multivariable analysis, bootstrap-validated preoperative risk factors for S. aureus bloodstream or chest wound infection included a body mass index greater than 40 (adjusted odds ratio [aOR], 1.9 [95% confidence interval {CI}, 1.1-3.2]), chronic renal failure (aOR, 1.8 [95% CI, 1.1-2.9]), and chronic lung disease (aOR, 1.4 [95% CI, 1.0-2.0]). Only 8 patients had all 3 risk factors., Conclusions: Although preoperative risk factors can be easily identified, the majority of patients who developed S. aureus infections after cardiac surgery did not have any risk factors. Preventive measures should not be restricted to a select group of cardiac surgery patients and should rather address the entire patient population.

Staphylococcus aureus is the leading cause of surgical site infections (SSI) in the United States. In particular, SSI caused by methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a devastating complication, leading to increased mortality rates, increased length of hospitalization, and increased costs. Proven strategies for prevention of SSI caused by S aureus include addressing modifiable risk factors and correct choice and timing of antimicrobial prophylaxis. Other strategies, including decolonization and the use of vancomycin, remain controversial.

Objective: To identify risk factors for surgical site infection (SSI) due to methicillin-resistant Staphylococcus aureus (MRSA)., Design: Prospective case-control study., Setting: One tertiary and 6 community-based institutions in the southeastern United States., Methods: We compared patients with SSI due to MRSA with 2 control groups: matched uninfected surgical patients and patients with SSI due to methicillin-susceptible S. aureus (MSSA). Multivariable logistic regression was used to determine variables independently associated with SSI due to MRSA, compared with each control group., Results: During the 5-year study period, 150 case patients with SSI due to MRSA were identified and compared with 231 matched uninfected control patients and 128 control patients with SSI due to MSSA. Two variables were independently associated with SSI due to MRSA in both multivariable regression models: need for assistance with 3 or more activities of daily living (odds ratio [OR] compared with uninfected patients, 3.97 [95% confidence interval {CI}, 2.18-7.25]; OR compared with patients with SSI due to MSSA, 3.88 [95% CI, 1.91-7.87]) and prolonged duration of surgery (OR compared with uninfected patients, 1.98 [95% CI, 1.11-3.55]; OR compared with patients with SSI due to MSSA, 2.33 [95% CI, 1.17-4.62]). Lack of independence (ie, poor functional status) remained associated with an increased risk of SSI due to MRSA after stratifying by age., Conclusions: Poor functional status was highly associated with SSI due to MRSA in adult surgical patients, regardless of age. A patient's level of independence can be easily determined, and this information can be used preoperatively to target preventive interventions.

Introduction: Data regarding the epidemiology, treatment, and outcomes of methicillin-resistant Staphylococcus aureus (MRSA) infections in rural and community hospitals are limited., Methods: This cohort study was conducted at 1 tertiary care hospital and 8 community hospitals in the southeastern United States. Patients with a surgical site infection (SSI) and/or bacteremia due to MRSA were prospectively identified at each study hospital during the period 1994-2003., Results: A total of 129 patients with SSI and 564 patients with bacteremia due to MRSA were identified. Only 57 patients with SSI (44.2%) received antibiotics active against MRSA on the initial date of diagnosis; only 95 (73.6%) received an agent active against MRSA by day 7 after diagnosis of SSI due to MRSA. Ninety-five patients with SSI due to MRSA (73.6%) were readmitted to the hospital within 90 days after their original surgery. The 1-year mortality rate among patients with SSI due to MRSA was 22%. Inadequate therapy was also commonly given to patients with bacteremia: only 216 (38.3%) received antibiotics active against MRSA on the initial day of infection, and only 383 (67.9%) received an agent active against MRSA by day 7 after diagnosis. Approximately one-third of patients with bloodstream infection died during their initial hospitalization. Patients hospitalized in community hospitals were less likely to receive effective antimicrobial therapy on both the day of infection and within 7 days after infection, compared with patients in the tertiary care hospital., Conclusion: Inadequate therapy is commonly administered after diagnosis of SSI and bacteremia due to MRSA in patients in community hospitals.

We evaluated costs and outcomes of patients with S. aureus bacteremia and orthopedic device infections (ODI). Patients with ODI had higher relapse of S. aureus infection, compared to bacteremic patients without ODI. Costs and outcomes were similar among ODI patients undergoing device removal and those treated with debridement and retention.

Objective: To characterize the epidemiology of severe (ie, nonsuperficial) surgical site infection (SSI) in community hospitals., Methods: SSI data were collected prospectively at 26 community hospitals in the southeastern United States. Two analyses were performed: (1) a study of the overall prevalence rates of SSI and the prevalence rates of SSI due to specific pathogens in 2005 at all participating hospitals and (2) a prospective study of consecutive surgical procedures at 9 of the 26 community hospitals from 2000 through 2005., Results: In 2005, a total of 1,010 SSIs occurred after 89,302 procedures (prevalence rate, 1.13 infections per 100 procedures). Methicillin-resistant S. aureus (MRSA) was the pathogen most commonly recovered (from 175 SSIs). Trend data from 2000 through 2005 demonstrated that the prevalence rate of MRSA SSI almost doubled during this period, increasing from 0.12 infections per 100 procedures (95% confidence interval [CI], 0.12-0.13) to 0.23 infections per 100 procedures (95% CI, 0.22-0.24) (P<.0001). In adjusted analysis, MRSA SSI was significantly more prevalent at the end of the study period than at the beginning (prevalence rate ratio, 1.48 [95% CI, 1.36-1.61]; P<.0001)., Conclusions: MRSA was the pathogen that most commonly caused SSI in our network of community hospitals during 2005. The prevalence of MRSA SSI has increased significantly over the past 6 years.

Background: After surveillance surveys documented the absence of methicillin-resistant Staphylococcus aureus (MRSA) in our intensive care nursery, an outbreak of MRSA infection occurred there during a 7-month period in 2005., Methods: Control measures included reinforcement of hand hygiene and contact precautions procedures. Active surveillance cultures were obtained on all neonates, including interinstitutional transfers. A cohort unit was dedicated exclusively for neonates with MRSA. Pulsed-field gel electrophoresis was performed on isolates to determine relatedness. We surveyed transferring hospitals to evaluate MRSA activity and surveillance practices in their nurseries., Results: Twenty-five neonates were colonized with MRSA; 9 of these had clinical infections. Isolates from 18 of 21 neonates from this outbreak and 4 neonates from a previous cluster were identical, including 1 isolate obtained upon transfer from another institution. Admission and discharge logs from a 9-month period showed that 127 of 460 admissions (27.6%) were admitted from 34 hospitals, and 247 of 460 (53.7%) were discharged to 32 hospitals. Among 30 transferring hospitals responding to our survey, MRSA activity occurred in 2 of 28 (7%) level 1 nurseries, 4 of 11 (36%) level 2 nurseries and 6 of 10 (60%) level 3 nurseries. Nine of the 30 hospitals (30%) performed some active surveillance., Conclusions: Interinstitutional transfer can play a role in the initiation and propagation of MRSA outbreaks in neonatal nurseries. The burden of MRSA in area nurseries and the rate of transfers affect the potential for interhospital spread of MRSA and may justify changes in policy regarding surveillance for MRSA and communication between hospitals.

Background: Decreasing the duration of antimicrobial therapy is an attractive strategy for delaying the emergence of antimicrobial resistance. Limited data regarding optimal treatment durations for most clinical infections hinder the adoption of this approach and impair optimal physician-patient communication under the shared decision-making model. We aimed to identify acceptable failure rates among infectious disease consultants (IDCs) for treatment of central venous catheter-associated bacteremia., Methods: A case scenario involving a representative patient who developed central venous catheter-associated bacteremia caused by coagulase-negative staphylococci and who received standard-of-care therapy was distributed to all nonpediatric IDC members of the Infectious Diseases Society of America's Emerging Infections Network in August 2003. Each member was suggested 1 of 10 treatment failure rates and asked whether he or she would accept or reject the given value. Logistic regression was used to evaluate the relationship between specific failure rates offered to respondents and their willingness to accept them using a methodology derived from contingent valuation., Results: Among the 374 respondents (response rate, 54%), the median acceptable failure rate was 6.8%. Thus, one-half of the IDCs would have found a failure rate of 6.8% to be acceptable. Seventy-five percent of IDCs would have found a failure rate of 1.6% to be acceptable, and 25% of IDCs would have found a failure rate as high as 11.9% to be acceptable., Conclusions: The quantified acceptable failure rates, when used to interpret clinical trial or cohort study results, will help select optimal antimicrobial therapy durations for this specific condition. These findings are a critical step in the development of effective shared decision-making models.

Purpose: Although Staphylococcus aureus is a leading cause of nosocomial infection, little is known about the impact of S. aureus bacteremia on patients with prosthetic devices. This investigation sought to define the clinical outcome, health care resource use, and infection-associated costs of S. aureus bacteremia in patients with prostheses., Subjects and Methods: All hospitalized patients with a prosthetic device and S. aureus bacteremia during the 96-month study period were identified prospectively. Clinical data were collected at the time of hospitalization. Data regarding infection-related resource utilization and infection-related costs within 12 weeks of the initial bacteremia were also recorded., Results: 298 patients with > or =1 prosthesis and S. aureus bacteremia were identified (cardiovascular device--122 patients, orthopedic device--73 patients, long-term catheter--71 patients, and other devices-32 patients). Overall, 58% of patients underwent surgery as a consequence of the infection. Infection-related complications occurred in 41% and the overall 12-week mortality was 27%. The mean infection-related cost was 67439 dollars for patients with hospital-acquired S. aureus bacteremia and 37868 dollars for community-acquired S. aureus bacteremia (cost difference 29571 dollars; 95% confidence interval, 14370 dollars-49826 dollars). Rates of device infection, complications, 12-week mortality, and mean cost varied by prosthesis type., Conclusion: S. aureus bacteremia in patients with prosthetic devices is associated with frequent complications, substantial cost, and significant health care resource utilization.

Objective: To examine the clinical outcomes and costs associated with Staphylococcus aureus bacteremia among hemodialysis-dependent patients., Design: Prospectively identified cohort study., Setting: A tertiary-care university medical center in North Carolina., Patients: Two hundred ten hemodialysis-dependent adults with end-stage renal disease hospitalized with S. aureus bacteremia., Results: The majority of the patients (117; 55.7%) underwent dialysis via tunneled catheters, and 29.5% (62) underwent dialysis via synthetic arteriovenous fistulas. Vascular access was the suspected source of bacteremia in 185 patients (88.1%). Complications occurred in 31.0% (65), and the overall 12-week mortality rate was 19.0% (40). The mean cost of treating S. aureus bacteremia, including readmissions and outpatient costs, was $24,034 per episode. The mean initial hospitalization cost was significantly greater for patients with complicated versus uncomplicated S. aureus bacteremia ($32,462 vs $17,011; P = .002)., Conclusion: Interventions to decrease the rate of S. aureus bacteremia are needed in this high-risk, hemodialysis-dependent population.

Objective: To evaluate the impact of methicillin resistance in Staphylococcus aureus on mortality, length of hospitalization, and hospital charges., Design: A cohort study of patients admitted to the hospital between July 1, 1997, and June 1, 2000, who had clinically significant S. aureus bloodstream infections., Setting: A 630-bed, urban, tertiary-care teaching hospital in Boston, Massachusetts., Patients: Three hundred forty-eight patients with S. aureus bacteremia were studied; 96 patients had methicillin-resistant S. aureus (MRSA). Patients with methicillin-susceptible S. aureus (MSSA) and MRSA were similar regarding gender, percentage of nosocomial acquisition, length of hospitalization, ICU admission, and surgery before S. aureus bacteremia. They differed regarding age, comorbidities, and illness severity score., Results: Similar numbers of MRSA and MSSA patients died (22.9% vs 19.8%; P = .53). Both the median length of hospitalization after S. aureus bacteremia for patients who survived and the median hospital charges after S. aureus bacteremia were significantly increased in MRSA patients (7 vs 9 days, P = .045; 19,212 dollars vs 26,424 dollars, P = .008). After multivariable analysis, compared with MSSA bacteremia, MRSA bacteremia remained associated with increased length of hospitalization (1.29 fold; P = .016) and hospital charges (1.36 fold; P = .017). MRSA bacteremia had a median attributable length of stay of 2 days and a median attributable hospital charge of 6916 dollars., Conclusion: Methicillin resistance in S. aureus bacteremia is associated with significant increases in length of hospitalization and hospital charges.

Objective: Comorbid conditions have complicated previous analyses of the consequences of methicillin resistance for costs and outcomes of Staphylococcus aureus bacteremia. We compared costs and outcomes of methicillin resistance in patients with S. aureus bacteremia and a single chronic condition., Design, Setting, and Patients: We conducted a prospective cohort study of hemodialysis-dependent patients with end-stage renal disease and S. aureus bacteremia hospitalized between July 1996 and August 2001. We used propensity scores to reduce bias when comparing patients with methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus bacteremia. Outcome measures were resource use, direct medical costs, and clinical outcomes at 12 weeks after initial hospitalization., Results: Fifty-four patients (37.8%) had MRSA and 89 patients (62.2%) had MSSA. Compared with patients with MSSA bacteremia, patients with MRSA bacteremia were more likely to have acquired the infection while hospitalized for another condition (27.8% vs 12.4%; P = .02). To attribute all inpatient costs to S. aureus bacteremia, we limited the analysis to 105 patients admitted for suspected S. aureus bacteremia from a community setting. Adjusted costs were higher for MRSA bacteremia for the initial hospitalization (21,251 dollars vs 13,978 dollars; P = .012) and after 12 weeks (25,518 dollars vs 17,354 dollars; P = .015). At 12 weeks, patients with MRSA bacteremia were more likely to die (adjusted odds ratio, 5.4; 95% confidence interval, 1.5 to 18.7) than were patients with MSSA bacteremia., Conclusions: Community-dwelling, hemodialysis-dependent patients hospitalized with MRSA bacteremia face a higher mortality risk, longer hospital stays, and higher inpatient costs than do patients with MSSA bacteremia.

Two types of cohort studies examining patients infected with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) were contrasted, using different reference groups. Cases were compared to uninfected patients and patients infected with the corresponding, susceptible organism. VRE and MRSA were associated with adverse outcomes. The effect was greater when uninfected control patients were used.

Risk factors for developing postoperative mediastinitis (POM) due to methicillin-resistant Staphylococcus aureus (MRSA) were analyzed in a case-case control study of patients who underwent median sternotomy during the period from 1994 through 2000. Three patient groups were studied. The first consisted of 64 patients with POM due to MRSA; the second consisted of 79 patients with POM due to methicillin-susceptible S. aureus (MSSA); and the third consisted of 80 uninfected control patients. In multivariable analysis, patients who were diabetic (adjusted OR, 2.86; 95% CI, 1.22-6.70), female (OR, 2.70; 95% CI, 1.25-5.88), and >70 years old (OR, 3.43; 95% CI, 1.53-7.71) were more likely to develop POM due to MRSA. In contrast, the only independent risk factor associated with POM due to MSSA was obesity (OR, 2.49; 95% CI, 1.25-4.96). Antimicrobial prophylaxis consisted primarily of cephalosporin antibiotics (administered to 97% of the patients). Changes in perioperative antimicrobial prophylaxis, in addition to other interventions, should be considered for prevention of POM due to MRSA in targeted, high-risk populations.

Objectives: To examine the impact of surgical-site infection (SSI) due to Staphylococcus aureus on mortality, duration of hospitalization, and hospital charges among elderly surgical patients and the impact of older age on these outcomes by comparing older and younger patients with S. aureus SSI., Design: A nested cohort study., Setting: A 750-bed, tertiary-care hospital and a 350-bed community hospital., Patients: Ninety-six elderly patients (70 years and older) with S. aureus SSI were compared with 2 reference groups: 59 uninfected elderly patients and 131 younger patients with S. aureus SSI., Results: Compared with uninfected elderly patients, elderly patients with S. aureus SSI were at risk for increased mortality (odds ratio [OR], 5.4; 95% confidence interval [CI95], 1.5-20.1), postoperative hospital-days (2.5-fold increase; CI95, 2.0-3.1), and hospital charges (2.0-fold increase; CI95, 1.7-2.4; dollar 41,117 mean attributable charges per SSI). Compared with younger patients with S. aureus SSI, elderly patients had increased mortality (adjusted OR, 2.9; CI95, 1.1-7.6), hospital-days (9 vs 13 days; P = .001), and median hospital charges (dollar 45,767 vs dollar 85,648; P < .001)., Conclusions: Among elderly surgical patients, S. aureus SSI was independently associated with increased mortality, hospital-days, and cost. In addition, being at least 70 years old was a predictor of death in patients with S. aureus SSI.

Data for 479 patients were analyzed to assess the impact of methicillin resistance on the outcomes of patients with Staphylococcus aureus surgical site infections (SSIs). Patients infected with methicillin-resistant S. aureus (MRSA) had a greater 90-day mortality rate than did patients infected with methicillin-susceptible S. aureus (MSSA; adjusted odds ratio, 3.4; 95% confidence interval, 1.5-7.2). Patients infected with MRSA had a greater duration of hospitalization after infection (median additional days, 5; P<.001), although this was not significant on multivariate analysis (P=.11). Median hospital charges were 29,455 dollars for control subjects, 52,791 dollars for patients with MSSA SSI, and 92,363 dollars for patients with MRSA SSI (P<.001 for all group comparisons). Patients with MRSA SSI had a 1.19-fold increase in hospital charges (P=.03) and had mean attributable excess charges of 13,901 dollars per SSI compared with patients who had MSSA SSIs. Methicillin resistance is independently associated with increased mortality and hospital charges among patients with S. aureus SSI.