Faculty Bibliography

STUDY OBJECTIVE: Despite recent reports of relatively high rates (16-37%) of acute kidney injury (AKI) in patients receiving the combination of intravenous piperacillin-tazobactam (PTZ) and vancomycin, data are limited evaluating the impact of PTZ infusion strategy on the occurrence of nephrotoxicity. The objective of this study was to compare the rates of nephrotoxicity in patients receiving vancomycin in combination with PTZ administered as an extended infusion (EI) versus a standard infusion (SI). DESIGN: Single-center, retrospective, matched-cohort study. SETTING: Large academic tertiary care hospital. PATIENTS: Two hundred eighty adults with a creatinine clearance (CrCl) of 40 ml/minute or higher who received at least 96 hours of vancomycin plus PTZ EI (140 patients) or vancomycin plus PTZ SI (140 patients) between January 1, 2009, and December 31, 2011, and between January 1, 2013, and December 31, 2014 (year 2012 was skipped due the closure of inpatient units following Superstorm Sandy); 48 patients in each group were admitted to the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The median age of all patients was 67 (interquartile range [IQR] 54-77) years, and CrCl was 75 (IQR 55-107) ml/minute. Nephrotoxicity was assessed by the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) criteria. Rates of AKI, according to these criteria, were similar between groups: 17.9% versus 17.1% (p=1) and 32.9% versus 29.3% (p=0.596) for the PTZ EI and PTZ SI groups, respectively. When controlling for residual differences between groups in a conditional logistic regression analysis, no association was observed between receipt of PTZ EI and RIFLE-defined AKI (odds ratio 0.522, 95% confidence interval 0.043-6.295, p=0.609). Time to onset of nephrotoxicity was 4 (IQR 3-6) days, with no significant difference noted between groups (p=0.887). CONCLUSION: Our findings suggest a similar rate of nephrotoxicity between patients who received vancomycin in combination with PTZ EI versus PTZ SI. These results need to be further validated in a prospective randomized controlled study.

PURPOSE: The integration of pharmacy residents into an antimicrobial stewardship program (ASP) is described, and data on the residents' ASP interventions and outcomes are reported. SUMMARY: ASP coverage of nighttime, holiday, and weekend shifts is often provided by infectious diseases (ID) medical fellows and staff pharmacists, potentially leading to inconsistent stewardship practices. As part of an initiative by a large urban hospital to provide around-the-clock, comprehensive ASP services 7 days a week, postgraduate year 2 (PGY2) pharmacy residents in ID or critical care were assigned to provide ASP coverage on weekends. Over a 12-month period, residents providing ASP weekend coverage documented a total of 1,443 interventions, of which 1,000 (69%) were pursuant to 72-hour prospective audit and feedback review and 443 (31%) occurred during ASP phone coverage. A comparison of overall antimicrobial utilization (mean +/- S.D. days of therapy [DOT] per 1,000 patient-days [PD]) before and after implementation of resident ASP coverage on weekends showed a decrease in aggregate antimicrobial use from 799.3 +/- 46.8 to 740.7 +/- 17.3 DOT/1,000 PD (a difference of 58.6 DOT/1,000 PD, p = 0.08), with a corresponding decline in the incidence of hospital-onset Clostridium difficile infection (from 1.18 cases to 0.9 case per 1,000 PD). CONCLUSION: By expanding the hospital's ASP services by assigning PGY2 pharmacy residents to weekend coverage, the institution was able to provide high-level clinical care 7 days per week, which benefited both patients and PGY2 pharmacy residents while meeting national ASP regulatory requirements.

BACKGROUND: Cefepime and meropenem are used frequently in hospitalized patients for broad-spectrum empiric coverage, however, practitioners are often reluctant to prescribe these antibiotics for patients with a self-reported nonsevere, nontype I allergic reaction to penicillin. METHODS: Retrospective review of electronic medical records of adults with a self-reported allergy to penicillin who received at least 1 dose of cefepime, ceftriaxone, cefoxitin, cephalexin, or meropenem to assess incidence and type of allergic reactions. RESULTS: Of 175 patients included, 10 (6%) patients experienced an allergic reaction. The incidence for individual study drugs were cefepime 6% (6 of 96), meropenem 5% (3 of 56), cefoxitin 8% (1 of 13), ceftriaxone 0% (0 of 69), and cephalexin 0% (0 of 8). The majority of patients experienced a rash with or without pruritus and fever. Patients with a concomitant "sulfa" allergy (odds ratio [OR] 5.4, 95% confidence interval [CI] 1.4-21, P = .02) or >/=3 other drug allergies (OR 6.4, 95% CI 1.3-32, P = .025) were more likely to have an allergic reaction. CONCLUSIONS: In one of the largest retrospective reviews of hospitalized patients who received full dose therapy with cefepime, ceftriaxone, and meropenem, the incidence of allergic reactions was low and reactions were mild. Cefepime, ceftriaxone, and meropenem can be considered for use in patients with a self-reported nontype I penicillin allergy.

Background. Mortality due to severe LD remains high with 20-25% of patients requiring mechanical ventilation. TG, a minocycline derivative, is active against L. pneumophila in animal and cell models, achieves high concentrations intracellularly and demonstrated minimal in vitro synergy with levofloxacin (LVX). Clinical data on TG for LD are limited to two case reports in immunocompromised hosts. We describe our experience with TG as salvage therapy in severely ill patients with LD. Methods. Patient demographics, clinical data and treatment details were collected retrospectively. Clinical failure was defined based on vital signs (temperature >=37.2degreeC, heart rate >=100 beats/min, respiratory rate >=24 breath/min, systolic <=100 mm Hg, oxygen saturation on room air <90%) and/or physician-documented deterioration in clinical parameters or death. Results. At our University Medical Center 12 patients with severe LD (positive Legionella urinary antigen n = 8, elevated L. pneumophilia antibody n = 4) received TG salvage therapy after failure of initial treatment with azithromycin (AZ) n = 6 or LVX and AZ n = 6 between January 2008 and February 2016. Median age of these patients was 81 (37-90) years. More than half had >=2 comorbidities, with cardiovascular and pulmonary being more common. Two patients were immunocompromised due to active chemotherapy. PSI score on admission was 130 (97-223); at the time of switch to TG, SOFA score was 6 (1-9) with respiratory worsening present in 11/12 patients after median of 4 (2-8) days of initial therapy. Seventy percent of patients required intensive care unit stay for 12 (1-18) days, 42% (5/12) had septic shock and were intubated for 10 (1-22) days. These patients received salvage therapy with TG 100 mg x 1 dose, followed by 50 mg IV q12h in addition to LVX n = 5, AZ n = 3, LVX and AZ n = 3, or as monotherapy n = 1 for median of 8 (4-17) days. After TG salvage therapy, clinical improvement was seen in 67% (8/12). Two patients died and 2 were made comfort care. No patients experienced adverse events attributable to TG salvage therapy. Total duration of therapy was 18 (9-24) days. Conclusion. This small cohort of patients provides evidence that TG can be considered for salvage therapy in patients failing macrolide or fluoroquinolone therapy

Polymyxin B is increasingly used as a treatment of last resort for multidrug-resistant Gram-negative infections. Despite being available as a mixture of several structurally related analogues, the properties are commonly reported as an aggregate of the individual components. We compared the pharmacokinetics of individual polymyxin B components in an animal model and in humans. There were no considerable differences observed in the pharmacokinetics among major components of polymyxin B. Combining different components for pharmacokinetic analysis appeared reasonable.

We describe a case of Bacteroides fragilis bacteremia associated with paraspinal and psoas abscesses in the United States. Resistance to b-lactam/b-lactamase inhibitors, carbapenems, and metronidazole was encountered despite having a recent travel history to India as the only possible risk factor for multidrug resistance. Microbiological cure was achieved with linezolid, moxifloxacin, and cefoxitin.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection that can lead to significant morbidity and mortality in immunocompromised pediatric hematology/oncology patients. Trimethoprim/sulfamethoxazole is the gold standard for prophylaxis. Intravenous (IV) pentamidine is the preferred second-line agent for PCP prophylaxis at our institution and is used first-line under certain circumstances. The purpose of this study is to evaluate the effectiveness and safety of IV pentamidine for PCP prophylaxis in pediatric hematology/oncology patients. MATERIALS AND METHODS: A retrospective analysis of pediatric hematology/oncology patients (N=121) who received >/=1 dose of IV pentamidine between January 2009 and July 2014 was conducted. Electronic health records were reviewed to determine baseline characteristics, rate of breakthrough PCP infection, characteristics of IV pentamidine use, and adverse events. The follow-up period was 6 months after the last reported IV pentamidine dose or the last recorded clinic visit/hospital admission. RESULTS: No patients developed PCP during the entirety of their IV pentamidine course or during the follow-up period. Nineteen patients (16%) experienced adverse events and 5 of the 19 patients required discontinuation of IV pentamidine. CONCLUSIONS: IV pentamidine is a safe, tolerable, and effective agent for PCP prophylaxis in pediatric hematology/oncology patients and may be considered a reasonable therapeutic alternative when trimethoprim/sulfamethoxazole cannot be used for PCP prophylaxis.