Aisling R. Caffrey

The Effect of Molecular Rapid Diagnostic Testing on Clinical Outcomes in Bloodstream Infections: A Systematic Review and Meta-analysis.

Background. Previous reports on molecular rapid diagnostic testing (mRDT) do not consistently demonstrate improved clinical outcomes in bloodstream infections (BSIs). This meta-analysis seeks to evaluate the impact of mRDT in improving clinical outcomes in BSIs. Methods. We searched PubMed, CINAHL, Web of Science, and EMBASE through May 2016 for BSI studies comparing clinical outcomes between mRDT and conventional microbiology methods. Results. Thirty-one studies were included with 5920 patients. The mortality risk was significantly lower with mRDT than with conventional microbiology methods (odds ratio [OR], 0.66; 95% confidence interval [CI], .54–.80), yielding a number needed to treat of 20. The mortality risk was slightly lower with mRDT in studies with antimicrobial stewardship programs (ASPs) (OR, 0.64; 95% CI, .51–.79), and non-ASP studies failed to demonstrate a significant decrease in mortality risk (0.72; .46–1.12). Significant decreases in mortality risk were observed with both gram-positive (OR, 0.73; 95% CI, .55–.97) and gram-negative organisms (0.51; .33–.78) but not yeast (0.90; .49–1.67). Time to effective therapy decreased by a weighted mean difference of −5.03 hours (95% CI, −8.60 to −1.45 hours), and length of stay decreased by −2.48 days (−3.90 to −1.06 days). Conclusions. For BSIs, mRDT was associated with significant decreases in mortality risk in the presence of a ASP, but not in its absence. mRDT also decreased the time to effective therapy and the length of stay. mRDT should be considered as part of the standard of care in patients with BSIs.

Risk factors associated with mupirocin resistance in meticillin-resistant Staphylococcus aureus☆

Implementation of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation programmes has been increasing and the emergence of mupirocin resistance has been reported. However, the patient-level risk factors associated with mupirocin resistance are not clear. In this study, independent predictors of mupirocin resistance in MRSA among Providence Veterans Affairs Medical Center patients with MRSA-positive culture dates between 1 July 2004 and 30 June 2008 were identified using a frequency-matched case-control study. Forty cases (mupirocin-resistant) were matched on culture date quarter and year to 270 controls (mupirocin-susceptible). The adjusted conditional logistic regression model identified three significant independent predictors associated with mupirocin resistance in MRSA: (1) exposure to mupirocin in the year prior to the culture date [odds ratio (OR): 9.84; 95% confidence interval (CI): 2.93-33.09]; (2) Pseudomonas aeruginosa infection in the year before the culture-related admission (4.85; 1.20-19.61); and (3) cefepime use in the year prior to culture (2.80; 1.03-7.58). In sensitivity analyses, previous mupirocin exposure was associated with low-level [minimum inhibitory concentration (MIC) 8-128mg/L; 23 cases, 202 controls; OR: 6.32; 95% CI: 1.58-25.33] and high-level (MIC ≥256mg/L; 17 cases, 151 controls; OR: 11.18; 95% CI: 1.89-66.30) mupirocin resistance. To our knowledge, this is the first case-control study to reveal a strong association between previous mupirocin exposure and subsequent mupirocin resistance in MRSA, with demonstrated robustness in low- and high-level mupirocin resistance. Mupirocin susceptibility monitoring is critical for facilities instituting decolonisation with mupirocin as increased use may reduce effectiveness through resistance.

Risk of hepatotoxicity associated with fluoroquinolones: A national case–control safety study

PURPOSE Results of a pharmacoepidemiologic evaluation of fluoroquinolone-associated hepatotoxicity using national hospital admissions data on Veterans Affairs (VA) patients are reported. METHODS In a retrospective case-control study, all adults with a primary diagnosis of hepatotoxicity on admission to a VA facility during a 6.5-year period (January 2002-June 2008) were identified. After the exclusion of patients whose records indicated known causes of hepatotoxicity or a history of liver disease, a subgroup of 7,862 patients with exposure to fluoroquinolone antibiotics in the six months prior to hospital admission were matched with nonexposed controls (n = 45,512). Conditional logistic regression was used to assess the overall and drug-specific risks of hepatotoxicity in the case group, controlling for comorbidities, concomitant use of known hepatotoxic medications, and other variables. RESULTS After adjusting for confounders, logistic regression analysis indicated a significantly higher overall risk of hepatotoxicity development among fluoroquinolone users relative to controls (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.38). Drug-specific risk analyses focused on three fluoroquinolone agents (ciprofloxacin, levofloxacin, and moxifloxacin) indicated a significant association between ciprofloxacin use and an increased risk of hepatotoxicity (OR, 1.29; 95% CI, 1.05-1.58); when considered as independent variables, levofloxacin use and moxifloxacin use were not significantly associated with hepatotoxicity risk. CONCLUSION The findings of a national VA safety study suggested an increased hepatotoxicity risk asssociated with fluoroquinolone exposure in the study population.

Low Adherence to Outpatient Preoperative Methicillin-Resistant Staphylococcus aureus Decolonization Therapy

care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007;122(2):160-166. 8. Harbarth S, Sax H, Gastmeier P. The preventable proportion of nosocomial infections: an overview of published reports. / Hosp Infect 2003;54(4):258-266. 9. Scott RD. The direct medical costs of healthcare-associated infections in US hospitals and the benefits of prevention, http:// www.cdc.gov/ncidod/dhqp/pdf/Scott_CostPaper.pdf. Accessed June 2, 2011. 10. Graves N, Harbarth S, Beyersmann J, Barnett A, Halton K, Cooper B. Estimating the cost of health care-associated infections: mind your ps and qs. Clin Infect Dis 2010;50(7): 1017-1021.

Comparative effectiveness of linezolid and vancomycin among a national cohort of patients infected with methicillin-resistant Staphylococcus aureus.

ABSTRACT While newer antibiotics play a key role in treating methicillin-resistant Staphylococcus aureus (MRSA) infections, knowledge of their real-world clinical impact is limited. We sought to quantify the effectiveness of linezolid compared to that of vancomycin among MRSA-infected patients. This national retrospective cohort study included adult patients admitted to all Veterans Affairs hospitals between January 2002 and June 2008, infected with MRSA, and treated with either linezolid (oral or intravenous [i.v.]) or vancomycin (i.v.). Patients were followed from their treatment initiation date until the event of interest, discharge, death, or December 2008. Utilizing propensity score methods, we estimated the treatment effects of linezolid primarily on time to discharge and secondarily on time to all-cause in-hospital mortality, therapy discontinuation, and all-cause 90-day readmission with Cox proportional-hazard models. We identified 20,107 patients treated with linezolid (3.2%) or vancomycin (96.8%). Baseline covariates were well balanced by treatment group within propensity score quintiles and between propensity score matched patients (626 pairs). The discharge rate was significantly higher among patients treated with linezolid, representing a decreased length of stay, in both the propensity score adjusted (hazard ratio [HR], 1.38; 95% confidence interval [95% CI], 1.27 to 1.50) and matched (HR, 1.70; 95% CI, 1.44 to 2.00) analyses. A significantly decreased rate of therapy discontinuation, indicating longer therapy duration, was observed in the linezolid group (adjusted HR, 0.64; 95% CI, 0.54 to 0.75; matched HR, 0.49; 95% CI, 0.36 to 0.65). In this clinical population of MRSA-infected patients, linezolid therapy was as effective as vancomycin therapy with respect to in-hospital survival and readmission.

Antimicrobial Stewardship in Long-Term Care Facilities: A Call to Action.

Antimicrobial resistance is a global public health crisis and a national security threat to the United States, as stated in an executive order signed by the president in September 2014. This crisis is a result of indiscriminant antimicrobial use, which promotes selection for resistant organisms, increases the risk of adverse drug events, and renders patients vulnerable to drug-resistant infections. Antimicrobial stewardship is a key measure to combat antimicrobial resistance and specifically seeks to do this by improving antimicrobial use. Antimicrobial stewardship compliments infection control practices and it is important to note that these 2 disciplines are distinct and cannot be discussed interchangeably. Antimicrobial stewardship promotes the appropriate diagnosis, drug, dose, and duration of treatment. The appropriate diagnosis falls into the hands of the prescriber and clinical staff. Optimal antimicrobial drug selection, dosing strategy, and duration of treatment, however, often require expertise in antimicrobial therapy, such as an infectious disease-trained physician or pharmacist. Therefore, successful antimicrobial stewardship programs must be comprehensive and interdisciplinary. Most antimicrobial stewardship programs focus on hospitals; yet, in long-term care, up to 75% of antimicrobial use is inappropriate or unnecessary. Thus, one of the most pressing areas in need for antimicrobial stewardship is in long-term care facilities. Unfortunately, there is little evidence that describes effective antimicrobial stewardship interventions in this setting. This review discusses the need for and barriers to antimicrobial stewardship in long-term care facilities. Additionally, this review describes prior interventions that have been implemented and tested to improve antimicrobial use in long-term care facilities.

Comparative Effectiveness of Linezolid and Vancomycin Among a National Veterans Affairs Cohort with Methicillin‐Resistant Staphylococcus aureus Pneumonia

As variability in vancomycin dosing, susceptibility, and tolerability has driven the need to compare newer agents with vancomycin in real‐world clinical settings, we sought to quantify the effectiveness of linezolid compared with vancomycin on clinical outcomes for the treatment of methicillin‐resistant Staphylococcus aureus (MRSA) pneumonia.

Impact of a Prospective Audit and Feedback Antimicrobial Stewardship Program at a Veterans Affairs Medical Center: A Six-Point Assessment.

Background Prospective audit and feedback is a core antimicrobial stewardship program (ASP) strategy; however its impact is difficult to measure. Methods Our quasi-experimental study measured the effect of an ASP on clinical outcomes, antimicrobial use, resistance, costs, patient safety (adverse drug events [ADE] and Clostridium difficile infection [CDI]), and process metrics pre- (9/10–10/11) and post-ASP (9/12–10/13) using propensity adjusted and matched Cox proportional-hazards regression models and interrupted time series (ITS) methods. Results Among our 2,696 patients, median length of stay was 1 day shorter post-ASP (5, interquartile range [IQR] 3–8 vs. 4, IQR 2–7 days, p<0.001). Mortality was similar in both periods. Mean broad-spectrum (-11.3%), fluoroquinolone (-27.0%), and anti-pseudomonal (-15.6%) use decreased significantly (p<0.05). ITS analyses demonstrated a significant increase in monthly carbapenem use post-ASP (trend: +1.5 days of therapy/1,000 patient days [1000PD] per month; 95% CI 0.1–3.0). Total antimicrobial costs decreased 14%. Resistance rates did not change in the one-year post-ASP period. Mean CDI rates/10,000PD were low pre- and post-ASP (14.2 ± 10.4 vs. 13.8 ± 10.0, p = 0.94). Fewer patients experienced ADEs post-ASP (6.0% vs. 4.4%, p = 0.06). Conclusions Prospective audit and feedback has the potential to improve antimicrobial use and outcomes, and contain bacterial resistance. Our program demonstrated a trend towards decreased length of stay, broad-spectrum antimicrobial use, antimicrobial costs, and adverse events.

Vancomycin Dosing Considerations in a Real-World Cohort of Obese and Extremely Obese Patients

To compare the effects of empiric vancomycin dosing regimens on attainment of optimal target trough concentrations in obese (body mass index [BMI] 30–40 kg/m2) and extremely obese (BMI ≥ 40 kg/m2) patients.

Vancomycin Plus Piperacillin-Tazobactam and Acute Kidney Injury in Adults: A Systematic Review and Meta-Analysis

Objectives: The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy. Data Sources: Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched. Study Selection: Articles not in English, pediatric studies, and case reports were excluded. Data Extraction: Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3. Data Synthesis: Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, –1.30; 95% CI, –3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57–4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83–3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97–3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48–20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83–2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86–2.11). Conclusions: The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed.