Self-controlled assessment of thromboembolic event (TEE) risk following intravenous immune globulin (IGIV) in the U.S. (2006-2012).

Since 2013, the U.S. Food and Drug administration (FDA) has required that intravenous immune globulin (IGIV) products carry a boxed warning concerning the risk of thromboembolic events (TEEs). This study assessed the incidence of TEEs attributable to IGIV in a large population-based cohort. A self-controlled risk interval design was used to quantify the transient increase in TEE risk during the risk interval (days 0-2 and 0-13 following IGIV for arterial and venous TEEs, respectively) relative to a later control interval (days 14-27 following IGIV). Potential IGIV-exposed TEE cases from 2006 to 2012 were identified from the FDA-sponsored Sentinel Distributed Database and confirmed through medical record review. Inpatient IGIV exposures were not included in the venous TEE analysis due to concerns about time-varying confounding. 19,069 new users of IGIV who received 93,555 treatment episodes were included. Charts were retrieved for 62% and 70% of potential venous and arterial cases, respectively. There was a transient increase in the risk of arterial TEEs during days 0-2 following IGIV treatment (RR = 4.69; 95% CI 1.87, 11.90; absolute increase in risk = 8.86 events per 10,000 patients, 95% CI 3.25, 14.6), but no significant increase in venous TEE risk during days 0-13 following outpatient IGIV treatments (RR = 1.07, 95% CI 0.34, 3.48). Our results suggest there is a small increase in the absolute risk of arterial TEEs following IGIV. However, lower-than-expected chart retrieval rates and the possibility of time-varying confounding mean that our results should be interpreted cautiously. Continued pharmacovigilance efforts are warranted.

Hand Hygiene Compliance at Critical Points of Care.

BACKGROUND: Most articles on hand hygiene report either overall compliance or compliance with specific hand hygiene moments. These moments vary in the level of risk to patients if healthcare workers (HCWs) are noncompliant. We assessed how task type affected HCWs' hand hygiene compliance. METHODS: We linked consecutive tasks individual HCWs performed during the Strategies to Reduce Transmission of Antimicrobial Resistant Bacteria in Intensive Care Units (STAR*ICU) study into care sequences and identified task pairs-2 consecutive tasks and the intervening hand hygiene opportunity. We defined tasks as critical and/or contaminating. We determined the odds of critical and contaminating tasks occurring, and the odds of hand hygiene compliance using logistic regression for transition with a random effect adjusting for isolation precautions, glove use, HCW type, and compliance at prior opportunities. RESULTS: Healthcare workers were less likely to do hand hygiene before critical tasks than before other tasks (adjusted odds ratio [aOR], 0.97 [95% confidence interval {CI}, .95-.98]) and more likely to do hand hygiene after contaminating tasks than after other tasks (aOR, 1.12 [95% CI, 1.10-1.13]). Nurses were more likely to perform both critical and contaminating tasks, but nurses' hand hygiene compliance was better than physicians' (aOR, 0.94 [95% CI, .91-.97]) and other HCWs' compliance (aOR, 0.87 [95% CI, .87-.94]). CONCLUSIONS: Healthcare workers were more likely to do hand hygiene after contaminating tasks than before critical tasks, suggesting that habits and a feeling of disgust may influence hand hygiene compliance. This information could be incorporated into interventions to improve hand hygiene practices, particularly before critical tasks and after contaminating tasks.

Expanding an Economic Evaluation of the Veterans Affairs (VA) Methicillin-resistant Staphylococcus aureus (MRSA) Prevention Initiative to Include Prevention of Infections From Other Pathogens.

BACKGROUND: In October 2007, Veterans Affairs (VA) launched a nationwide effort to reduce methicillin-resistant Staphylococcus aureus (MRSA) transmission called the National MRSA Prevention Initiative. Although the initiative focused on MRSA, recent evidence suggests that it also led to a significant decrease in hospital-onset (HO) gram-negative rod (GNR) bacteremia, vancomycin-resistant Enterococci (VRE), and Clostridioides difficile infections. The objective of this analysis was to evaluate the cost-effectiveness and the budget impact of the initiative taking into account MRSA, GNR, VRE, and C. difficile infections. METHODS: We developed an economic model using published data on the rate of MRSA hospital-acquired infections (HAIs) and HO-GNR bacteremia in the VA from October 2007 to September 2015, estimates of the attributable cost and mortality of these infections, and the costs associated with the intervention obtained through a microcosting approach. We explored several different assumptions for the rate of infections that would have occurred if the initiative had not been implemented. Effectiveness was measured in life-years (LYs) gained. RESULTS: We found that during fiscal years 2008-2015, the initiative resulted in an estimated 4761-9236 fewer MRSA HAIs, 1447-2159 fewer HO-GNR bacteremia, 3083-3602 fewer C. difficile infections, and 2075-5393 fewer VRE infections. The initiative itself was estimated to cost $561 million over this 8-year period, whereas the cost savings from prevented MRSA HAIs ranged from $165 to $315 million and from prevented HO-GNR bacteremia, CRE and C. difficile infections ranged from $174 to $200 million. The incremental cost-effectiveness of the initiative ranged from $12 146 to $38 673/LY when just including MRSA HAIs and from $1354 to $4369/LY when including the additional pathogens. The overall impact on the VA's budget ranged from $67 to$195 million. CONCLUSIONS: An MRSA surveillance and prevention strategy in VA may have prevented a substantial number of infections from MRSA and other organisms. The net increase in cost from implementing this strategy was quite small when considering infections from all types of organisms. Including spillover effects of organism-specific prevention efforts onto other organisms can provide a more comprehensive evaluation of the costs and benefits of these interventions.

Comparative Effectiveness of Switching to Daptomycin Versus Remaining on Vancomycin Among Patients With Methicillin-resistant Staphylococcus aureus (MRSA) Bloodstream Infections.

BACKGROUND: Patients with methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA BSI) usually receive initial treatment with vancomycin but may be switched to daptomycin for definitive therapy, especially if treatment failure is suspected. Our objective was to evaluate the effectiveness of switching from vancomycin to daptomycin compared with remaining on vancomycin among patients with MRSA BSI. METHODS: Patients admitted to 124 Veterans Affairs Hospitals who experienced MRSA BSI and were treated with vancomycin during 2007-2014 were included. The association between switching to daptomycin and 30-day mortality was assessed using Cox regression models. Separate models were created for switching to daptomycin any time during the first hospitalization and for switching within 3 days of receiving vancomycin. RESULTS: In total, 7411 patients received vancomycin for MRSA BSI. Also, 606 (8.2%) patients switched from vancomycin to daptomycin during the first hospitalization, and 108 (1.5%) switched from vancomycin to daptomycin within 3 days of starting vancomycin. In the multivariable analysis, switching to daptomycin within 3 days was significantly associated with lower 30-day mortality (hazards ratio [HR] = 0.48; 95% confidence interval [CI]: .25, .92). However, switching to daptomycin at any time during the first hospitalization was not significantly associated with 30-day mortality (HR: 0.87; 95% CI: .69, 1.09). CONCLUSIONS: Switching to daptomycin within 3 days of initial receipt of vancomycin is associated with lower 30-day mortality among patients with MRSA BSI. This benefit was not seen when the switch occurred later. Future studies should prospectively assess the benefit of early switching from vancomycin to other anti-MRSA antibiotics.

Perceived Benefits and Challenges of Ebola Preparation Among Hospitals in Developed Countries: A Systematic Literature Review.

The 2014-2016 Ebola epidemic in West Africa provided an opportunity to improve our response to highly infectious diseases. We performed a systematic literature review in PubMed, Cochrane Library, CINAHL, EMBASE, and Web of Science of research articles that evaluated benefits and challenges of hospital Ebola preparation in developed countries. We excluded studies performed in non-developed countries, and those limited to primary care settings, the public health sector, and pediatric populations. Thirty-five articles were included. Preparedness activities were beneficial for identifying gaps in hospital readiness. Training improved health-care workers' (HCW) infection control practices and personal protective equipment (PPE) use. The biggest challenge was related to PPE, followed by problems with hospital infrastructure and resources. HCWs feared managing Ebola patients, affecting their willingness to care for them. Standardizing protocols, PPE types, and frequency of training and providing financial support will improve future preparedness. It is unclear whether preparations resulted in sustained improvements. Prospero Registration. CRD42018090988.

Novel methodology to measure pre-procedure antimicrobial prophylaxis: integrating text searches with structured data from the Veterans Health Administration's electronic medical record.

BACKGROUND: Antimicrobial prophylaxis is an evidence-proven strategy for reducing procedure-related infections; however, measuring this key quality metric typically requires manual review, due to the way antimicrobial prophylaxis is documented in the electronic medical record (EMR). Our objective was to electronically measure compliance with antimicrobial prophylaxis using both structured and unstructured data from the Veterans Health Administration (VA) EMR. We developed this methodology for cardiac device implantation procedures. METHODS: With clinician input and review of clinical guidelines, we developed a list of antimicrobial names recommended for the prevention of cardiac device infection. We trained the algorithm using existing fiscal year (FY) 2008-15 data from the VA Clinical Assessment Reporting and Tracking-Electrophysiology (CART-EP), which contains manually determined information about antimicrobial prophylaxis. We merged CART-EP data with EMR data and programmed statistical software to flag an antimicrobial orders or drug fills from structured data fields in the EMR and hits on text string searches of antimicrobial names documented in clinician's notes. We iteratively tested combinations of these data elements to optimize an algorithm to accurately classify antimicrobial use. The final algorithm was validated in a national cohort of VA cardiac device procedures from FY2016-2017. Discordant cases underwent expert manual review to identify reasons for algorithm misclassification. RESULTS: The CART-EP dataset included 2102 procedures at 38 VA facilities with manually identified antimicrobial prophylaxis in 2056 cases (97.8%). The final algorithm combining structured EMR fields and text note search results correctly classified 2048 of the CART-EP cases (97.4%). In the validation sample, the algorithm measured compliance with antimicrobial prophylaxis in 16,606 of 18,903 cardiac device procedures (87.8%). Misclassification was due to EMR documentation issues, such as antimicrobial prophylaxis documented only in hand-written clinician notes in a format that cannot be electronically searched. CONCLUSIONS: We developed a methodology with high accuracy to measure guideline concordant use of antimicrobial prophylaxis before cardiac device procedures using data fields present in modern EMRs. This method can replace manual review in quality measurement in the VA and other healthcare systems with EMRs; further, this method could be adapted to measure compliance in other procedural areas where antimicrobial prophylaxis is recommended.

Infectious complications of laparoscopic and robotic hysterectomy: a systematic literature review and meta-analysis.

OBJECTIVE: We performed a systematic review of the literature and meta-analysis of the infectious complications of hysterectomy, comparing robotic-assisted hysterectomy to conventional laparoscopic-assisted hysterectomy. METHODS: We searched PubMed, CINAHL, CDSR, and EMBASE through July 2018 for studies evaluating robotic-assisted hysterectomy, laparoscopic-assisted hysterectomy, and infectious complications. We employed random-effect models to obtain pooled OR estimates. Heterogeneity was evaluated with I2 estimation and the Cochran Q statistic. Pooled ORs were calculated separately based on the reason for hysterectomy (eg, benign uterine diseases, endometrial cancer, and cervical cancer). RESULTS: Fifty studies were included in the final review for the meta-analysis with 176 016 patients undergoing hysterectomy. There was no statistically significant difference in the number of infectious complication events between robotic-assisted hysterectomy and laparoscopic-assisted hysterectomy (pooled OR 0.97; 95 % CI 0.74 to 1.28). When we performed a stratified analysis, similar results were found with no statistically significant difference in infectious complications comparing robotic-assisted hysterectomy to laparoscopic-assisted hysterectomy among patients with benign uterine disease (pooled OR 1.10; 95 % CI 0.70 to 1.73), endometrial cancer (pooled OR 0.97; 95 % CI 0.55 to 1.73), or cervical cancer (pooled OR 1.09; 95 % CI 0.60 to 1.97). CONCLUSION: In our meta-analysis the rate of infectious complications associated with robotic-assisted hysterectomy was no different than that associated with conventional laparoscopic-assisted hysterectomy.

Attributable Cost and Length of Stay Associated with Nosocomial Gram-Negative Bacterial Cultures.

Few studies have estimated the excess inpatient costs due to nosocomial cultures of Gram-negative bacteria (GNB), and those that do are often subject to time-dependent bias. Our objective was to generate estimates of the attributable costs of the underlying infections associated with nosocomial cultures by using a unique inpatient cost data set from the U.S. Department of Veterans Affairs that allowed us to reduce time-dependent bias. Our study included data from inpatient admissions between 1 October 2007 and 30 November 2010. Nosocomial GNB-positive cultures were defined as clinical cultures positive for Acinetobacter, Pseudomonas, or Enterobacteriaceae between 48 h after admission and discharge. Positive cultures were further classified by site and level of resistance. We conducted analyses using both a conventional approach and an approach aimed at reducing the impact of time-dependent bias. In both instances, we used multivariable generalized linear models to compare the inpatient costs and length of stay for patients with and without a nosocomial GNB culture. Of the 404,652 patients included in the conventional analysis, 12,356 had a nosocomial GNB-positive culture. The excess costs of nosocomial GNB-positive cultures were significant, regardless of specific pathogen, site, or resistance level. Estimates generated using the conventional analysis approach were 32.0% to 131.2% greater than those generated using the approach to reduce time-dependent bias. These results are important because they underscore the large financial burden attributable to these infections and provide a baseline that can be used to assess the impact of improvements in infection control.

Association Between Hospital and Surgeon Volume and Rectal Cancer Surgery Outcomes in Patients With Rectal Cancer Treated Since 2000: Systematic Literature Review and Meta-analysis.

BACKGROUND: Previous reviews and meta-analyses, which predominantly focused on patients treated before 2000, have reported conflicting evidence about the association between hospital/surgeon volume and rectal cancer outcomes. Given advances in rectal cancer resection, such as total mesorectal excision, it is essential to determine whether volume plays a role in rectal cancer outcomes among patients treated since 2000. OBJECTIVE: The purpose of this study was to determine whether there is an association between hospital/surgeon volume and rectal cancer surgery outcomes among patients treated since 2000. DATA SOURCES: We searched PubMed and EMBASE for articles published between January 2000 and December 29, 2017. STUDY SELECTION: Articles that analyzed the association between hospital/surgeon volume and rectal cancer outcomes were selected. INTERVENTION: Rectal cancer resection was the study intervention. MAIN OUTCOME MEASURES: The outcome measures of this study were surgical morbidity, postoperative mortality, surgical margin positivity, permanent colostomy rates, recurrence, and overall survival. RESULTS: Although 2845 articles were retrieved and assessed by the search strategy, 21 met the inclusion and exclusion criteria. There was a significant protective association between higher hospital volume and surgical morbidity (OR = 0.80 (95% CI, 0.70-0.93); I = 35%), permanent colostomy (OR = 0.51 (95% CI, 0.29-0.92); I = 34%), and postoperative mortality (OR = 0.62 (95% CI, 0.43-0.88); I = 34%), and overall survival (OR = 0.99 (95% CI, 0.98-1.00); I = 3%). Stratified analysis showed that the magnitude of association between hospital volume and rectal cancer surgery outcomes was stronger in the United States compared with other countries. Surgeon volume was not significantly associated with overall survival. The articles included in this analysis were high quality according to the Newcastle-Ottawa scale. Funnel plots suggested that the potential for publication bias was low. LIMITATIONS: Some articles included rectosigmoid cancers. CONCLUSIONS: Among patients diagnosed since 2000, higher hospital volume has had a significant protective effect on rectal cancer surgery outcomes.

Chart validation of inpatient ICD-9-CM administrative diagnosis codes for acute myocardial infarction (AMI) among intravenous immune globulin (IGIV) users in the Sentinel Distributed Database.

BACKGROUND: The Sentinel Distributed Database (SDD) is a large database of patient-level administrative health care records, primarily derived from insurance claims and electronic health records, and is sponsored by the US Food and Drug Administration for medical product safety evaluations. Acute myocardial infarction (AMI) is a common study endpoint for drug safety studies that rely on health records from the SDD and other administrative databases. PURPOSE: In this chart validation study, we report on the positive predictive value (PPV) of inpatient International Classification of Diseases, Ninth Revision, Clinical Modification AMI administrative diagnosis codes (410.x1 and 410.x0) in the SDD. METHODS: As part of an assessment of thromboembolic adverse event risk following treatment with intravenous immune globulin, charts were obtained for 103 potential post-intravenous immune globulin AMI cases. Charts were abstracted by trained nurses and physician-adjudicated based on prespecified diagnostic criteria. RESULTS: Acute myocardial infarction status could be determined for 89 potential cases. The PPVs for the inpatient AMI diagnoses recorded in the SDD were 75% overall (95% CI, 65-84%), 93% (95% CI, 78-99%) for principal-position diagnoses, 88% (95% CI, 72-97%) for secondary diagnoses, and 38% (95% CI, 20-59%) for position-unspecified diagnoses (eg, diagnoses originating from separate physician claims associated with an inpatient stay). Of the confirmed AMI cases, demand ischemia was the suspected etiology more often for those coded in secondary or unspecified positions (72% and 40%, respectively) than for principal-position AMI diagnoses (21%). CONCLUSIONS: The PPVs for principal and secondary AMI diagnoses were high and similar to estimates from prior chart validation studies. Position-unspecified diagnosis codes were less likely to represent true AMI cases.

A systematic review and meta-analysis of the association between vitamin A intake, serum vitamin A, and risk of liver cancer.

BACKGROUND: Previous evidence supports that vitamin A decreases the risk of several types of cancer. However, the association between vitamin A and liver cancer is inconclusive. AIM: This systematic review and meta-analysis summarizes the existing literature, discussing the association between vitamin A intake, serum vitamin A, and liver cancer in adult populations. METHODS: A systematic literature review was performed by searching the EMBASE, PubMed, Scopus and International Pharmaceutical Abstract databases using terms related to vitamin A (e.g. retinol, α-carotene, ß-carotene, and ß-cryptoxanthin) and hepatic cancer without applying any time restriction. A meta-analysis was performed using random effect models. RESULTS: The meta-analysis of five studies showed no association between serum retinol and liver cancer (pooled risk ratio = 1.90 (0.40-9.02); n = 5 studies, I2 = 92%). In addition, the systematic review of studies from 1955 to July 2017 found studies that indicated no association between the intake and serum level of α-carotene ( n = 2) and ß-cryptoxanthin ( n = 1) and the risk of liver cancer. Further, the associations between retinol intake ( n = 3), ß-carotene intake ( n = 3), or serum ß-carotene ( n = 3) and liver cancer were inconclusive. CONCLUSIONS: Current information on the association between vitamin A intake and liver cancer or serum vitamin A and liver cancer are limited. Most studies demonstrated no association between dietary vitamin A and the risk of liver cancer. However, the finding was based on a small number of studies with potential publication bias. Therefore, large observational studies should be conducted to confirm these associations.

Decolonization in Prevention of Health Care-Associated Infections.

Colonization with health care-associated pathogens such as Staphylococcus aureus, enterococci, Gram-negative organisms, and Clostridium difficile is associated with increased risk of infection. Decolonization is an evidence-based intervention that can be used to prevent health care-associated infections (HAIs). This review evaluates agents used for nasal topical decolonization, topical (e.g., skin) decolonization, oral decolonization, and selective digestive or oropharyngeal decontamination. Although the majority of studies performed to date have focused on S. aureus decolonization, there is increasing interest in how to apply decolonization strategies to reduce infections due to Gram-negative organisms, especially those that are multidrug resistant. Nasal topical decolonization agents reviewed include mupirocin, bacitracin, retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, photodynamic therapy, omiganan pentahydrochloride, and lysostaphin. Mupirocin is still the gold standard agent for S. aureus nasal decolonization, but there is concern about mupirocin resistance, and alternative agents are needed. Of the other nasal decolonization agents, large clinical trials are still needed to evaluate the effectiveness of retapamulin, povidone-iodine, alcohol-based nasal antiseptic, tea tree oil, omiganan pentahydrochloride, and lysostaphin. Given inferior outcomes and increased risk of allergic dermatitis, the use of bacitracin-containing compounds cannot be recommended as a decolonization strategy. Topical decolonization agents reviewed included chlorhexidine gluconate (CHG), hexachlorophane, povidone-iodine, triclosan, and sodium hypochlorite. Of these, CHG is the skin decolonization agent that has the strongest evidence base, and sodium hypochlorite can also be recommended. CHG is associated with prevention of infections due to Gram-positive and Gram-negative organisms as well as Candida. Conversely, triclosan use is discouraged, and topical decolonization with hexachlorophane and povidone-iodine cannot be recommended at this time. There is also evidence to support use of selective digestive decontamination and selective oropharyngeal decontamination, but additional studies are needed to assess resistance to these agents, especially selection for resistance among Gram-negative organisms. The strongest evidence for decolonization is for use among surgical patients as a strategy to prevent surgical site infections.

Comparative Effectiveness of Cefazolin Versus Nafcillin or Oxacillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study.

Background: To treat patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections, ß-lactams are recommended for definitive therapy; however, the comparative effectiveness of individual ß-lactams is unknown. This study compared definitive therapy with cefazolin vs nafcillin or oxacillin among patients with MSSA infections complicated by bacteremia. Methods: This retrospective study included patients admitted to 119 Veterans Affairs hospitals from 2003 to 2010. Patients were included if they had a blood culture positive for MSSA and received definitive therapy with cefazolin, nafcillin, or oxacillin. Cox proportional hazards regression and ordinal logistic regression were used to identify associations between antibiotic therapy and mortality or recurrence. A recurrent infection was defined as a MSSA blood culture between 45 and 365 days after the first MSSA blood culture. Results: Of 3167 patients, 1163 (37%) patients received definitive therapy with cefazolin. Patients who received cefazolin had a 37% reduction in 30-day mortality (hazard ratio [HR], 0.63; 95% confidence interval [CI], .51-.78) and a 23% reduction in 90-day mortality (HR, 0.77; 95% CI, .66-.90) compared with patients receiving nafcillin or oxacillin, after controlling for other factors. The odds of recurrence (odds ratio, 1.13; 95% CI, .94-1.36) were similar among patients who received cefazolin compared with patients who received nafcillin or oxacillin, after controlling for other factors. Conclusions: In this large, multicenter study, patients who received cefazolin had a lower risk of mortality and similar odds of recurrent infections compared with nafcillin or oxacillin for MSSA infections complicated by bacteremia. Physicians might consider definitive therapy with cefazolin for these infections.

Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study.

BACKGROUND: The optimal regimen for perioperative antimicrobial prophylaxis is controversial. Use of combination prophylaxis with a beta-lactam plus vancomycin is increasing; however, the relative risks and benefits associated with this strategy are unknown. Thus, we sought to compare postoperative outcomes following administration of 2 antimicrobials versus a single agent for the prevention of surgical site infections (SSIs). Potential harms associated with combination regimens, including acute kidney injury (AKI) and Clostridium difficile infection (CDI), were also considered. METHODS AND FINDINGS: Using a multicenter, national Veterans Affairs (VA) cohort, all patients who underwent cardiac, orthopedic joint replacement, vascular, colorectal, and hysterectomy procedures during the period from 1 October 2008 to 30 September 2013 and who received planned manual review of perioperative antimicrobial prophylaxis regimen and manual review for the 30-day incidence of SSI were included. Using a propensity-adjusted log-binomial regression model stratified by type of surgical procedure, the association between receipt of 2 antimicrobials (vancomycin plus a beta-lactam) versus either single agent alone (vancomycin or a beta-lactam) and SSI was evaluated. Measures of association were adjusted for age, diabetes, smoking, American Society of Anesthesiologists score, preoperative methicillin-resistant Staphylococcus aureus (MRSA) status, and receipt of mupirocin. The 7-day incidence of postoperative AKI and 90-day incidence of CDI were also measured. In all, 70,101 procedures (52,504 beta-lactam only, 5,089 vancomycin only, and 12,508 combination) with 2,466 (3.5%) SSIs from 109 medical centers were included. Among cardiac surgery patients, combination prophylaxis was associated with a lower incidence of SSI (66/6,953, 0.95%) than single-agent prophylaxis (190/12,834, 1.48%; crude risk ratio [RR] 0.64, 95% CI 0.49, 0.85; adjusted RR 0.61, 95% CI 0.46, 0.83). After adjusting for SSI risk, no association between receipt of combination prophylaxis and SSI was found for the other types of surgeries evaluated, including orthopedic joint replacement procedures. In MRSA-colonized patients undergoing cardiac surgery, SSI occurred in 8/346 (2.3%) patients who received combination prophylaxis versus 4/100 (4.0%) patients who received vancomycin alone (crude RR 0.58, 95% CI 0.18, 1.88). Among MRSA-negative and -unknown cardiac surgery patients, SSIs occurred in 58/6,607 (0.9%) patients receiving combination prophylaxis versus 146/10,215 (1.4%) patients who received a beta-lactam alone (crude RR 0.61, 95% CI 0.45, 0.83). Based on these associations, the number needed to treat to prevent 1 SSI in MRSA-colonized patients is estimated to be 53, compared to 176 in non-MRSA patients. CDI incidence was similar in both exposure groups. Across all types of surgical procedures, risk of AKI was increased in the combination antimicrobial prophylaxis group (2,971/12,508 [23.8%] receiving combination versus 1,058/5,089 [20.8%] receiving vancomycin alone versus 7,314/52,504 [13.9%] receiving beta-lactam alone). We found a significant association between absolute risk of AKI and receipt of combination regimens across all types of procedures. If the observed association is causal, the number needed to harm for severe AKI following cardiac surgery would be 167. The major limitation of our investigation is that it is an observational study in a predominantly male population, which may limit generalizability and lead to unmeasured confounding. CONCLUSIONS: There are benefits but also unintended consequences of antimicrobial and infection prevention strategies aimed at "getting to zero" healthcare-associated infections. In our study, combination prophylaxis was associated with both benefits (reduction in SSIs following cardiac surgical procedures) and harms (increase in postoperative AKI). In cardiac surgery patients, the difference in risk-benefit profile by MRSA status suggests that MRSA-screening-directed prophylaxis may optimize benefits while minimizing harms in this selected population. More information about long-term outcomes and patient and societal preferences regarding risk of SSI versus risk of AKI is needed to improve clinical decision-making.

Association between polypharmacy and death: A systematic review and meta-analysis.

OBJECTIVE: Polypharmacy has been linked to a myriad of adverse consequences, and escalating rates of polypharmacy present an emerging concern, particularly among older adults. This systematic review and meta-analysis summarizes the existing literature concerning the association between polypharmacy and mortality. DATA SOURCES: A systematic literature review was done by searching the EMBASE, PubMed, Scopus, and International Pharmaceutical Abstract databases to identify studies assessing the association between polypharmacy and death published until June 2016. STUDY SELECTION: Studies that investigated the association between polypharmacy and mortality were eligible for this systematic review and meta-analysis. DATA EXTRACTION: Data were extracted by the first and second authors independently using a data extraction form. Disagreement was resolved by consensus. A meta-analysis was performed using random effect models. Heterogeneity was assessed using the I2 statistic. RESULTS: Forty-seven studies were included in this meta-analysis. The underlying populations were heterogeneous (I2= 91.5%). When defined as a discrete variable, pooled risk estimates demonstrated a significant association between polypharmacy and death (pooled-adjusted odds ratio [aOR] 1.08 [95% CI 1.04-1.12]). When defined categorically, a dose-response relationship was observed across escalating thresholds for defining polypharmacy. Categorical thresholds for polypharmacy using values of 1-4 medications, 5 medications, and 6-9 medications were significantly associated with death (P <0.05; aOR 1.24 [1.10-1.39], aOR 1.31 [1.17, 1.47], and aOR 1.59 [1.36-1.87], respectively). Excessive polypharmacy (ie, the use of 10 or more medications) was also associated with death (aOR 1.96 [1.42-2.71]). CONCLUSIONS: Pooled risk estimates from this meta-analysis reveal that polypharmacy is associated with increased mortality risk, using both discrete and categorical definitions. The causality of this relationship remains unclear, but it emphasizes the need for approaches to health care delivery that achieve an optimal balance of risk and benefit in medication prescribing.

Clinical Effectiveness of Mupirocin for Preventing Staphylococcus aureus Infections in Nonsurgical Settings: A Meta-analysis.

A systematic literature review and meta-analysis was performed to identify effectiveness of mupirocin decolonization in prevention of Staphylococcus aureus infections, among nonsurgical settings. Of the 15 662 unique studies identified up to August 2015, 13 randomized controlled trials, 22 quasi-experimental studies, and 1 retrospective cohort study met the inclusion criteria. Studies were excluded if mupirocin was not used for decolonization, there was no control group, or the study was conducted in an outbreak setting. The crude risk ratios were pooled (cpRR) using a random-effects model. We observed substantial heterogeneity among included studies (I(2) = 80%). Mupirocin was observed to reduce the risk for S. aureus infections by 59% (cpRR, 0.41; 95% confidence interval [CI], .36-.48) and 40% (cpRR, 0.60; 95% CI, .46-.79) in both dialysis and nondialysis settings, respectively. Mupirocin decolonization was protective against S. aureus infections among both dialysis and adult intensive care patients. Future studies are needed in other settings such as long-term care and pediatrics.

Increased Mortality Rates Associated with Staphylococcus aureus and Influenza Co-infection, Maryland and Iowa, USA(1).

We retrospectively analyzed data for 195 respiratory infection patients who had positive Staphyloccocus aureus cultures and who were hospitalized in 2 hospitals in Iowa and Maryland, USA, during 2003-2009. Odds for death for patients who also had influenza-positive test results were >4 times higher than for those who had negative influenza test results.

Comparative effectiveness of beta-lactams versus vancomycin for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections among 122 hospitals.

BACKGROUND: Previous studies indicate that vancomycin is inferior to beta-lactams for treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections. However, it is unclear if this association is true for empiric and definitive therapy. Here, we compared beta-lactams with vancomycin for empiric and definitive therapy of MSSA bloodstream infections among patients admitted to 122 hospitals. METHODS: This retrospective cohort study included all patients admitted to Veterans Affairs hospitals from 2003 to 2010 who had positive blood cultures for MSSA. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Empiric therapy was defined as starting treatment 2 days before and up to 4 days after the first MSSA blood culture was collected. Definitive therapy was defined as starting treatment between 4 and 14 days after the first positive blood culture was collected. RESULTS: Patients who received empiric therapy with a beta-lactam had similar mortality compared with those who received vancomycin (HR, 1.03; 95% CI, .89-1.20) after adjusting for other factors. However, patients who received definitive therapy with a beta-lactam had 35% lower mortality compared with patients who received vancomycin (HR, 0.65; 95% CI, .52-.80) after controlling for other factors. The hazard of mortality decreased further for patients who received cefazolin or antistaphylococcal penicillins compared with vancomycin (HR, 0.57; 95% CI, .46-.71). CONCLUSIONS: For patients with MSSA bloodstream infections, beta-lactams are superior to vancomycin for definitive therapy but not for empiric treatment. Patients should receive beta-lactams for definitive therapy, specifically antistaphylococcal penicillins or cefazolin.

The Incidence of and Risk Factors for 30-Day Surgical Site Infections Following Primary and Revision Total Joint Arthroplasty.

The authors assessed the incidence of and risk factors associated with 30-day surgical site infections (SSIs) following primary (p) and revision (r) THA and TKA. In total, 23,128 primary and 2170 revision TJAs were identified between 2005 and 2010 in the ACS NSQIP database. The 30-day SSI rates, overall and deep, were 1.1 and 0.1% for pTKA, 1.18 and 0.4% for pTHA, 1.68 and 0.7% for rTKA, and 2.9 and 1.7% for rTHA. After primary TJA, independent risk factors were BMI>40, hypertension, prolonged operative time, electrolyte disturbance and previous infection, and after revision TJA, dyspnea and bleeding disorder were risk factors. This study should help provide benchmark data for SSI following TJA.