Marin L. Schweizer

Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia

BackgroundThe high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, vancomycin has been associated with poor outcomes such as nephrotoxicity, persistent bacteremia and treatment failure. The objective of this study was to compare the effectiveness of vancomycin versus the beta-lactam antibiotics nafcillin and cefazolin among patients with MSSA bacteremia. The outcome of interest for this study was 30-day in-hospital mortality.MethodsThis retrospective cohort study included all adult in-patients admitted to a tertiary-care facility between January 1, 2003 and June 30, 2007 who had a positive blood culture for MSSA and received nafcillin, cefazolin or vancomycin. Cox proportional hazard models were used to assess independent mortality hazards comparing nafcillin or cefazolin versus vancomycin. Similar methods were used to estimate the survival benefits of switching from vancomycin to nafcillin or cefazolin versus leaving patients on vancomycin. Each model included statistical adjustment using propensity scores which contained variables associated with an increased propensity to receive vancomycin.Results267 patients were included; 14% (38/267) received nafcillin or cefazolin, 51% (135/267) received both vancomycin and either nafcillin or cefazolin, and 35% (94/267) received vancomycin. Thirty (11%) died within 30 days. Those receiving nafcillin or cefazolin had 79% lower mortality hazards compared with those who received vancomycin alone (adjusted hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.09, 0.47). Among the 122 patients who initially received vancomycin empirically, those who were switched to nafcillin or cefazolin (66/122) had 69% lower mortality hazards (adjusted HR: 0.31; 95% CI: 0.10, 0.95) compared to those who remained on vancomycin.ConclusionsReceipt of nafcillin or cefazolin was protective against mortality compared to vancomycin even when therapy was altered after culture results identified MSSA. Convenience of vancomycin dosing may not outweigh the potential benefits of nafcillin or cefazolin in the treatment of MSSA bacteremia.

Effect of antibiotic stewardship programmes on Clostridium difficile incidence: a systematic review and meta-analysis

OBJECTIVES Despite vigorous infection control measures, Clostridium difficile continues to cause significant disease burden. Antibiotic stewardship programmes (ASPs) may prevent C. difficile infections by limiting exposure to certain antibiotics. Our objective was to perform a meta-analysis of published studies to assess the effect of ASPs on the risk of C. difficile infection in hospitalized adult patients. METHODS Searches of PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and two Cochrane databases were conducted to find all published studies on interventions related to antibiotic stewardship and C. difficile. Two investigators independently assessed study eligibility and extracted data. Risk of bias was assessed using the Downs and Black tool. Risk ratios were pooled using random effects models. Heterogeneity was evaluated using the I(2) statistic. RESULTS The final search yielded 891 articles; 78 full articles were reviewed and 16 articles were identified for inclusion. Included articles used quasi-experimental (interrupted time series or before-after) or observational (case-control) study designs. When the results of all studies were pooled in a random effects model, a significant protective effect (pooled risk ratio 0.48; 95% CI: 0.38, 0.62) was observed between ASPs and C. difficile incidence. When stratified by intervention type, a significant effect was found for restrictive ASPs (complete removal of drug or prior approval requirement). Furthermore, ASPs were particularly effective in geriatric settings. CONCLUSIONS Restrictive ASPs can be used to reduce the risk of C. difficile infection.

Association of a Bundled Intervention With Surgical Site Infections Among Patients Undergoing Cardiac, Hip, or Knee Surgery

IMPORTANCE Previous studies suggested that a bundled intervention was associated with lower rates of Staphylococcus aureus surgical site infections (SSIs) among patients having cardiac or orthopedic operations. OBJECTIVE To evaluate whether the implementation of an evidence-based bundle is associated with a lower risk of S. aureus SSIs in patients undergoing cardiac operations or hip or knee arthroplasties. DESIGN, SETTING, AND PARTICIPANTS Twenty hospitals in 9 US states participated in this pragmatic study; rates of SSIs were collected for a median of 39 months (range, 39-43) during the preintervention period (March 1, 2009, to intervention) and a median of 21 months (range, 14-22) during the intervention period (from intervention start through March 31, 2014). INTERVENTIONS Patients whose preoperative nares screens were positive for methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) were asked to apply mupirocin intranasally twice daily for up to 5 days and to bathe daily with chlorhexidine-gluconate (CHG) for up to 5 days before their operations. MRSA carriers received vancomycin and cefazolin or cefuroxime for perioperative prophylaxis; all others received cefazolin or cefuroxime. Patients who were MRSA-negative and MSSA-negative bathed with CHG the night before and morning of their operations. Patients were treated as MRSA-positive if screening results were unknown. MAIN OUTCOMES AND MEASURES The primary outcome was complex (deep incisional or organ space) S. aureus SSIs. Monthly SSI counts were analyzed using Poisson regression analysis. RESULTS After a 3-month phase-in period, bundle adherence was 83% (39% full adherence; 44% partial adherence). Overall, 101 complex S. aureus SSIs occurred after 28,218 operations during the preintervention period and 29 occurred after 14,316 operations during the intervention period (mean rate per 10,000 operations, 36 for preintervention period vs 21 for intervention period, difference, -15 [95% CI, -35 to -2]; rate ratio [RR], 0.58 [95% CI, 0.37 to 0.92]). The rates of complex S. aureus SSIs decreased for hip or knee arthroplasties (difference per 10,000 operations, -17 [95% CI, -39 to 0]; RR, 0.48 [95% CI, 0.29 to 0.80]) and for cardiac operations (difference per 10,000 operations, -6 [95% CI, -48 to 8]; RR, 0.86 [95% CI, 0.47 to 1.57]). CONCLUSIONS AND RELEVANCE In this multicenter study, a bundle comprising S. aureus screening, decolonization, and targeted prophylaxis was associated with a modest, statistically significant decrease in complex S. aureus SSIs.

Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: systematic review and meta-analysis

Objective To evaluate studies assessing the effectiveness of a bundle of nasal decolonization and glycopeptide prophylaxis for preventing surgical site infections caused by Gram positive bacteria among patients undergoing cardiac operations or total joint replacement procedures. Design Systematic review and meta-analysis. Data sources PubMed (1995 to 2011), the Cochrane database of systematic reviews, CINAHL, Embase, and clinicaltrials.gov were searched to identify relevant studies. Pertinent journals and conference abstracts were hand searched. Study authors were contacted if more data were needed. Eligibility criteria Randomized controlled trials, quasi-experimental studies, and cohort studies that assessed nasal decolonization or glycopeptide prophylaxis, or both, for preventing Gram positive surgical site infections compared with standard care. Participants Patients undergoing cardiac operations or total joint replacement procedures. Data extraction and study appraisal Two authors independently extracted data from each paper and a random effects model was used to obtain summary estimates. Risk of bias was assessed using the Downs and Black or the Cochrane scales. Heterogeneity was assessed using the Cochran Q and I2 statistics. Results 39 studies were included. Pooled effects of 17 studies showed that nasal decolonization had a significantly protective effect against surgical site infections associated with Staphylococcus aureus (pooled relative risk 0.39, 95% confidence interval 0.31 to 0.50) when all patients underwent decolonization (0.40, 0.29 to 0.55) and when only S aureus carriers underwent decolonization (0.36, 0.22 to 0.57). Pooled effects of 15 prophylaxis studies showed that glycopeptide prophylaxis was significantly protective against surgical site infections related to methicillin (meticillin) resistant S aureus (MRSA) compared with prophylaxis using β lactam antibiotics (0.40, 0.20 to 0.80), and a non-significant risk factor for methicillin susceptible S aureus infections (1.47, 0.91 to 2.38). Seven studies assessed a bundle including decolonization and glycopeptide prophylaxis for only patients colonized with MRSA and found a significantly protective effect against surgical site infections with Gram positive bacteria (0.41, 0.30 to 0.56). Conclusions Surgical programs that implement a bundled intervention including both nasal decolonization and glycopeptide prophylaxis for MRSA carriers may decrease rates of surgical site infections caused by S aureus or other Gram positive bacteria.

The role of imaging in the management of progressive glioblastoma: A systematic review and evidence-based clinical practice guideline

QuestionWhich imaging techniques most accurately differentiate true tumor progression from pseudo-progression or treatment related changes in patients with previously diagnosed glioblastoma?Target populationThese recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process.RecommendationsLevel IIMagnetic resonance imaging with and without gadolinium enhancement is recommended as the imaging surveillance method to detect the progression of previously diagnosed glioblastoma.Level IIMagnetic resonance spectroscopy is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma.Level IIIThe routine use of positron emission tomography to identify progression of glioblastoma is not recommended.Level IIISingle-photon emission computed tomography imaging is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma.

Increased Mortality with Accessory Gene Regulator (agr) Dysfunction in Staphylococcus aureus among Bacteremic Patients

ABSTRACT Accessory gene regulator (agr) dysfunction in Staphylococcus aureus has been associated with a longer duration of bacteremia. We aimed to assess the independent association between agr dysfunction in S. aureus bacteremia and 30-day in-hospital mortality. This retrospective cohort study included all adult inpatients with S. aureus bacteremia admitted between 1 January 2003 and 30 June 2007. Severity of illness prior to culture collection was measured using the modified acute physiology score (APS). agr dysfunction in S. aureus was identified semiquantitatively by using a δ-hemolysin production assay. Cox proportional hazard models were used to measure the association between agr dysfunction and 30-day in-hospital mortality, statistically adjusting for patient and pathogen characteristics. Among 814 patient admissions complicated by S. aureus bacteremia, 181 (22%) patients were infected with S. aureus isolates with agr dysfunction. Overall, 18% of patients with agr dysfunction in S. aureus died, compared to 12% of those with functional agr in S. aureus (P = 0.03). There was a trend toward higher mortality among patients with S. aureus with agr dysfunction (adjusted hazard ratio [HR], 1.34; 95% confidence interval [CI], 0.87 to 2.06). Among patients with the highest APS (scores of >28), agr dysfunction in S. aureus was significantly associated with mortality (adjusted HR, 1.82; 95% CI, 1.03 to 3.21). This is the first study to demonstrate an independent association between agr dysfunction and mortality among severely ill patients. The δ-hemolysin assay examining agr function may be a simple and inexpensive approach to predicting patient outcomes and potentially optimizing antibiotic therapy.

Effectiveness of local vancomycin powder to decrease surgical site infections: a meta-analysis

BACKGROUND CONTEXT Some surgeons use systemic vancomycin to prevent surgical site infections (SSIs), but patients who do not carry methicillin-resistant Staphylococcus aureus have an increased risk of SSIs when given vancomycin alone for intravenous prophylaxis. Applying vancomycin powder to the wound before closure could increase the local tissue vancomycin level without significant systemic levels. However, the effectiveness of local vancomycin powder application for preventing SSIs has not been established. PURPOSE Our objective was to systematically review and evaluate studies on the effectiveness of local vancomycin powder for decreasing SSIs. STUDY DESIGN Meta-analysis. SAMPLE We included observational studies, quasi-experimental studies, and randomized controlled trials of patients undergoing surgical procedures that involved vancomycin powder application to surgical wounds, reported SSI rates, and had a comparison group that did not use local vancomycin powder. OUTCOME MEASURES The primary outcome was postoperative SSIs. The secondary outcomes included deep incisional SSIs and S. aureus SSIs. METHODS We performed systematic literature searches in PubMed, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials via Wiley, Scopus (including EMBASE abstracts), Web of Science, ClinicalTrials.gov, BMC Proceedings, ProQuest Dissertation, and Thesis in Health and Medicine, and conference abstracts from IDWeek, the Interscience Conference on Antimicrobial Agents and Chemotherapy, the Society for Healthcare Epidemiology of America, and the American Academy of Orthopedic Surgeons annual meetings, and also the Scoliosis Research Society Annual Meeting and Course. We ran the searches from inception on May 9, 2013 with no limits on date or language. After reviewing 373 titles or abstracts and 22 articles in detail, we included 10 independent studies and used a random-effects model when pooling risk estimates to assess the effectiveness of local vancomycin powder application for preventing SSIs, the outcome of interest. We used the I²-index, Q-statistic, and corresponding p value to assess the heterogeneity of the risk estimates, and funnel plots to assess publication bias. RESULTS We included seven quasi-experimental studies, two cohort studies, and one randomized controlled trial, encompassing 5,888 surgical patients. The pooled effects showed that applying local vancomycin powder was significantly protective against SSIs (pooled odds ratio [pOR] 0.19; 95% confidence interval [CI] 0.09-0.38), deep incisional SSIs (pOR 0.23; 95% CI 0.09-0.57), and SSIs caused by S. aureus (pOR 0.22; 95% CI 0.08-0.58). However, significant heterogeneity was present for studies evaluating all SSIs or deep incisional SSIs. When we pooled the risk estimates from the eight studies that assessed patients undergoing spinal operations, vancomycin powder remained significantly protective against SSIs (pOR 0.16; 95% CI 0.09-0.30), deep incisional SSIs (pOR 0.18; 95% CI 0.09-0.36), and SSIs caused by S. aureus (pOR 0.11; 95% CI 0.03-0.36). The pooled ORs from studies of spinal operations were lower than those for all studies and the estimates from spinal operation studies were homogeneous. However, there was evidence of publication bias. CONCLUSIONS Local administration of vancomycin powder appears to protect against SSIs, deep incisional SSIs, and S. aureus SSIs after spinal operations. Large, high-quality studies should be performed to evaluate this intervention before it is used routinely.

Seasonal and Temperature-Associated Increases in Gram-Negative Bacterial Bloodstream Infections among Hospitalized Patients

Background Knowledge of seasonal trends in hospital-associated infection incidence may improve surveillance and help guide the design and evaluation of infection prevention interventions. We estimated seasonal variation in the frequencies of inpatient bloodstream infections (BSIs) caused by common bacterial pathogens and examined associations of monthly BSI frequencies with ambient outdoor temperature, precipitation, and humidity levels. Methods A database containing blood cultures from 132 U.S. hospitals collected between January 1999 and September 2006 was assembled. The database included monthly counts of inpatient blood cultures positive for several clinically important Gram-negative bacteria (Acinetobacter spp, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and Gram-positive bacteria (Enterococcus spp and Staphylococcus aureus). Monthly mean temperature, total precipitation, and mean relative humidity in the postal ZIP codes of participating hospitals were obtained from national meteorological databases. Results A total of 211,697 inpatient BSIs were reported during 9,423 hospital-months. Adjusting for long-term trends, BSIs caused by each Gram-negative organism examined were more frequent in summer months compared with winter months, with increases ranging from 12.2% for E. coli (95% CI 9.2–15.4) to 51.8% for Acinetobacter (95% CI 41.1–63.2). Summer season was associated with 8.7% fewer Enterococcus BSIs (95% CI 11.0–5.8) and no significant change in S. aureus BSI frequency relative to winter. Independent of season, monthly humidity, monthly precipitation, and long-term trends, each 5.6°C (10°F) rise in mean monthly temperature corresponded to increases in Gram-negative bacterial BSI frequencies ranging between 3.5% for E. coli (95% CI 2.1–4.9) to 10.8% for Acinetobacter (95% CI 6.9–14.7). The same rise in mean monthly temperature corresponded to an increase of 2.2% in S. aureus BSI frequency (95% CI 1.3–3.2) but no significant change in Enterococcus BSI frequency. Conclusions Summer season and higher mean monthly outdoor temperature are associated with substantially increased frequency of BSIs, particularly among clinically important Gram-negative bacteria.

Accuracy of Administrative Code Data for the Surveillance of Healthcare-Associated Infections: A Systematic Review and Meta-Analysis

Administrative code data (ACD), such as International Classifications of Diseases, Ninth Revision, Clinical Modification codes, are widely used in surveillance and public reporting programs that seek to identify healthcare-associated infections (HAIs); however, little is known about their accuracy. This systematic review summarizes evidence for the accuracy of ACD for the detection of selected HAIs, including catheter-associated urinary tract infection, Clostridium difficile infection (CDI), central line-associated bloodstream infection, ventilator-associated pneumonia/events, postprocedure pneumonia, methicillin-resistant Staphylococcus aureus, and surgical site infections (SSIs). We conducted meta-analysis for SSIs and CDIs, where acceptable numbers of primary studies were available. For these 2 conditions, ACD have moderate sensitivity and high specificity, but evidence for detection of other HAIs is limited. With current low prevalence of HAIs, the positive predictive value of ACD algorithms would be low. ACD may be inaccurate for detection of many HAIs and should be used cautiously for surveillance and reporting purposes.

Strategies to Prevent Healthcare-Associated Infections through Hand Hygiene

Previously published guidelines provide comprehensive recommendations for hand hygiene in healthcare facilities. The intent of this document is to highlight practical recommendations in a concise format, update recommendations with the most current scientific evidence, and elucidate topics that warrant clarification or more robust research. Additionally, this document is designed to assist healthcare facilities in implementing hand hygiene adherence improvement programs, including efforts to optimize hand hygiene product use, monitor and report back hand hygiene adherence data, and promote behavior change. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA) and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise. The list of endorsing and supporting organizations is presented in the introduction to the 2014 updates.