Improvement of gram-negative susceptibility to fluoroquinolones after implementation of a pre-authorization policy for fluoroquinolone use: A decade-long experience.

OBJECTIVE: Due to concerns over increasing fluoroquinolone (FQ) resistance among gram-negative organisms, our stewardship program implemented a preauthorization use policy. The goal of this study was to assess the relationship between hospital FQ use and antibiotic resistance. DESIGN: Retrospective cohort. SETTING: Large academic medical center. METHODS: We performed a retrospective analysis of FQ susceptibility of hospital isolates for 5 common gram-negative bacteria: Acinetobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Primary endpoint was the change of FQ susceptibility. A Poisson regression model was used to calculate the rate of change between the preintervention period (1998-2005) and the postimplementation period (2006-2016). RESULTS: Large rates of decline of FQ susceptibility began in 1998, particularly among P. aeruginosa, Acinetobacter spp., and E. cloacae. Our FQ restriction policy improved FQ use from 173 days of therapy (DOT) per 1,000 patient days to <60 DOT per 1,000 patient days. Fluoroquinolone susceptibility increased for Acinetobacter spp. (rate ratio [RR], 1.038; 95% confidence interval [CI], 1.005-1.072), E. cloacae (RR, 1.028; 95% CI, 1.013-1.044), and P. aeruginosa (RR, 1.013; 95% CI, 1.006-1.020). No significant change in susceptibility was detected for K. pneumoniae (RR, 1.002; 95% CI, 0.996-1.008), and the susceptibility for E. coli continued to decline, although the decline was not as steep (RR, 0.981; 95% CI, 0.975-0.987). CONCLUSIONS: A stewardship-driven FQ restriction program stopped overall declining FQ susceptibility rates for all species except E. coli. For 3 species (ie, Acinetobacter spp, E. cloacae, and P. aeruginosa), susceptibility rates improved after implementation, and this improvement has been sustained over a 10-year period.

Practical methods for effective vancomycin-resistant enterococci (VRE) surveillance: experience in a liver transplant surgical intensive care unit.

OBJECTIVE: We evaluated the utility of vancomycin-resistant Enterococcus (VRE) surveillance by varying 2 parameters: admission versus weekly surveillance and perirectal swabbing versus stool sampling. DESIGN: Prospective, patient-level surveillance program of incident VRE colonization. SETTING: Liver transplant surgical intensive care unit (SICU) of a tertiary-care referral medical center with a high prevalence of VRE.PatientsAll patients admitted to the SICU from June to August 2015. METHODS: We conducted a point-prevalence estimate followed by admission and weekly surveillance by perirectal swabbing and/or stool sampling. Incident colonization was defined as a negative screen followed by positive surveillance. VRE was detected by culture on Remel Spectra VRE chromogenic agar. Microbiologically-confirmed VRE bloodstream infections (BSIs) were tracked for 2 months. Statistical analyses were calculated using the McNemar test, the Fisher exact test, the t test, and the χ2 test. RESULTS: In total, 91 patients underwent VRE surveillance testing. The point prevalence of VRE colonization was 60.9%; VRE prevalence on admission was 30.1%. Weekly surveillance identified an additional 7 of 28 patients (25.0%) with incident colonization. VRE BSIs were more common in VRE-colonized patients than in noncolonized patients (8 of 43 vs 2 of 48; P=.028). In a direct comparison, perirectal swabs were more sensitive than stool samples in detecting VRE (64 of 67 vs 56 of 67; P=.023). Compliance with perirectal swabbing was 89% (201 of 226) compared to 56% (127 of 226) for stool collection (P≤0.001). CONCLUSIONS: We recommend weekly VRE surveillance over admission-only screening in high-burden units such as liver transplant SICUs. Perirectal swabs had greater collection compliance and sensitivity than stool samples, making them the preferred methodology. Further work may have implications for antimicrobial stewardship and infection control.

Evaluation of baseline corrected QT interval and azithromycin prescriptions in an academic medical center.

BACKGROUND: Azithromycin is used in the inpatient setting for a variety of conditions. In 2013, the US Food and Drug Administration released a warning regarding risk for corrected QT (QTc) prolongation and subsequent arrhythmias. Knowledge of inpatient prescribing patterns of QTc prolonging medications with respect to patient risk factors for adverse cardiovascular events can help recognize safe use in light of these new warnings. OBJECTIVE: To assess inpatient prescribing patterns, risk factors for QTc prolongation, and relationship between drug-drug interactions and cardiac monitoring in patients receiving azithromycin. DESIGN: Retrospective cohort study. PARTICIPANTS: One hundred inpatients ≥ 19 years of age were randomly selected from 1610 patient encounters between October 2012 and April 2013 who were administered at least 1 dose of azithromycin. MEASUREMENTS: Length of stay, reason for use, therapy duration, and concomitant medications were recorded. Telemetry charges and baseline electrocardiogram (ECG) prior to administration were assessed. RESULTS: Seventy-nine percent of azithromycin use was empiric. Sixty-five percent of patients received a baseline ECG prior to prescribing azithromycin, of which 60% had borderline or abnormal QTc prolongation. Seventy-six percent of patients were prescribed 2 or more QTc prolonging medications, of which there were more abnormal ECGs at baseline (P = 0.03) despite having telemetry ordered less than half of the time. CONCLUSIONS: In a cohort of hospitalized patients, azithromycin was prescribed despite risk factors for QTc prolongation and administration of interacting medications. Selection of azithromycin by providers appears to be independent from these risk factors, and education and vigilance to drug-drug interactions may be useful in limiting cardiac events with prescribing azithromycin.

Initial management of candidemia at an academic medical center: evaluation of the IDSA guidelines.

Treatment of candidemia is more complicated because of the changing epidemiology of Candida and introduction of newer antifungal agents. Utilization and benefit of practice guidelines and infectious disease consultation for the management of candidemia has not been previously described in the routine clinical setting. We prospectively studied the impact of the Infectious Disease Society of America (IDSA) guidelines for the management of candidemia and infectious disease consultation on clinical outcomes in 119 patients with candidemia at a tertiary care hospital. Medical records were reviewed to capture data concerning use of antifungal agents, management of central venous catheters, and infectious disease consultation. Initial antifungal therapy was consistent with the IDSA guidelines in 76% of patients. Variation from the guidelines was independently associated with higher mortality (24% versus 57%, P = 0.003). Infectious disease consultation was independently associated with lower mortality (18% versus 39%, P < 0.01). Use of the IDSA guidelines and infectious disease consultation service was found to improve patient outcomes in patients with candidemia at our institution. Further studies should be performed to validate newer guidelines in a clinical setting at other institutions.

Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: A randomized controlled trial.

BACKGROUND: Pleiotropic effects of statins decrease intrahepatic resistance and portal hypertension. AIM: We evaluated the effects of simvastatin on hepatic venous pressure gradient (HVPG) and azygos vein blood flow in cirrhotic patients. METHODS: A 3-month prospective, randomized, triple-blind trial with simvastatin (40 mg/day) vs. placebo was conducted in patients with cirrhotic portal hypertension. HVPG and azygos blood flow, measured by colour Doppler endoscopic ultrasound, were assessed before and after treatment. The primary endpoint was a decrease in the HVPG of at least 20% from baseline or to ≤12 mmHg after the treatment. RESULTS: 34 patients were prospectively enrolled, and 24 completed the protocol. In the simvastatin group 6/11 patients (55%) presented a clinically relevant decrease in the HVPG; no decrease was observed in the placebo group (p=0.036). Patients with medium/large oesophageal varices and previous variceal bleeding had a higher response rate to simvastatin. HVPG and azygos blood flow values were not correlated. No significant adverse events occurred. CONCLUSION: Simvastatin lowers portal pressure and may even improve liver function. The haemodynamic effect appears to be more evident in patients with severe portal hypertension.

Association between vancomycin-resistant Enterococci bacteremia and ceftriaxone usage.

OBJECTIVE: Vancomycin-resistant enterococci (VRE) have become a public health concern with implications for patient mortality and costs. Hospital antibiotic usage may impact VRE incidence, but the relationship is poorly understood. Animal investigations suggest that ceftriaxone may be associated with VRE proliferation. We measured antimicrobial usage and VRE bloodstream infection (VRE-BSI) incidence to test our hypothesis that increased ceftriaxone usage would be associated with a higher incidence of VRE-BSI. DESIGN: Retrospective cohort study. SETTING: University of Alabama at Birmingham Medical Center, a 900-bed urban tertiary care hospital. PARTICIPANTS: All patients admitted during the study period contributed data. METHODS: We conducted a retrospective analysis of antimicrobial usage and VRE-BSI from 2005 to 2008 (43 months). Antimicrobial usage was quantified as days of therapy (DOTs) per 1,000 patient-days. VRE-BSI incidence was calculated as cases per 1,000 patient-days. Negative binomial regression with adjustment for correlation between consecutive observations was used to measure the association between antimicrobial usage and VRE-BSI incidence at the hospital- and care-unit levels. RESULTS: VRE-BSI incidence increased from 0.06 to 0.17 infections per 1,000 patient-days. Hospital VRE-BSI incidence was associated with prior-month ceftriaxone DOTs (incidence rate ratio, 1.38 per 10 DOTs; P = .005). After controlling for ceftriaxone, prior-month cephalosporin usage (class) was not predictive of VRE-BSI (P = .70). Similarly, prior-month usage of piperacillin-tazobactam, ceftazidime, cefepime, cefazolin, or vancomycin was not predictive of VRE-BSI when considered individually (P≥ .4 for all comparisons). The final model suggests that type of intensive care unit was related to VRE-BSI incidence. CONCLUSIONS: Ceftriaxone usage in the prior month, but not cephalosporin (class) or vancomycin usage, was related to VRE-BSI incidence. These findings suggest that an antimicrobial stewardship program that limits ceftriaxone may reduce nosocomial VRE-BSI incidence.