Jennifer Sekeres

Treatment and Outcomes in Carbapenem-resistant Klebsiella pneumoniae Bloodstream Infections

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is an emerging multidrug-resistant nosocomial pathogen. This is a retrospective chart review describing the outcomes and treatment of 60 cases of CR-Kp bloodstream infections. All CR-Kp isolated from blood cultures were identified retrospectively from the microbiology laboratory from January 2007 to May 2009. Clinical information was collected from the electronic medical record. Patients with 14-day hospital mortality were compared to those who survived 14 days. The all-cause in-hospital and 14-day mortality for all 60 CR-Kp bloodstream infections were 58.3% and 41.7%, respectively. In this collection, 98% of tested isolates were susceptible in vitro to tigecycline compared to 86% to colistimethate, 45% to amikacin, and 22% to gentamicin. Nine patients died before cultures were finalized and received no therapy active against CR-Kp. In the remaining 51 patients, those who survived to day 14 (n = 35) were compared to nonsurvivors at day 14 (n=16). These patients were characterized by both chronic disease and acute illness. The 90-day readmission rate for hospital survivors was 72%. Time to active therapy was not significantly different between survivors and nonsurvivors, and hospital mortality was also similar regardless of therapy chosen. Pitt bacteremia score was the only significant factor associated with mortality in Cox regression analysis. In summary, CR-Kp bloodstream infections occur in patients who are chronically and acutely ill. They are associated with high 14-day mortality and poor outcomes regardless of tigecycline or other treatment regimens selected.

Experience with fosfomycin for treatment of urinary tract infections due to multidrug-resistant organisms

ABSTRACT Fosfomycin has shown promising in vitro activity against multidrug-resistant (MDR) urinary pathogens; however, clinical data are lacking. We conducted a retrospective chart review to describe the microbiological and clinical outcomes of urinary tract infections (UTIs) with MDR pathogens treated with fosfomycin tromethamine. Charts for 41 hospitalized patients with a urine culture for an MDR pathogen who received fosfomycin tromethamine from 2006 to 2010 were reviewed. Forty-one patients had 44 urinary pathogens, including 13 carbapenem-resistant Klebsiella pneumoniae (CR-Kp), 8 Pseudomonas aeruginosa, and 7 vancomycin-resistant Enterococcus faecium (VRE) isolates, 7 extended-spectrum beta-lactamase (ESBL) producers, and 9 others. In vitro fosfomycin susceptibility was 86% (median MIC, 16 μg/ml; range, 0.25 to 1,024 μg/ml). Patients received an average of 2.9 fosfomycin doses per treatment course. The overall microbiological cure was 59%; failure was due to either relapse (24%) or reinfection UTI (17%). Microbiological cure rates by pathogen were 46% for CR-Kp, 38% for P. aeruginosa, 71% for VRE, 57% for ESBL producers, and 100% for others. Microbiological cure (n = 24) was compared to microbiological failure (n = 17). There were significantly more solid organ transplant recipients in the microbiological failure group (59% versus 21%; P = 0.02). None of the patients in the microbiological cure group had a ureteral stent, compared to 24% of patients within the microbiological failure group (P = 0.02). Fosfomycin demonstrated in vitro activity against UTIs due to MDR pathogens. For CR-KP, there was a divergence between in vitro susceptibility (92%) and microbiological cure (46%). Multiple confounding factors may have contributed to microbiological failures, and further data regarding the use of fosfomycin for UTIs due to MDR pathogens are needed.

Reducing Time to Antibiotic Administration for Febrile Neutropenia in the Emergency Department

PURPOSE Febrile neutropenia (FN) is an oncologic emergency, and prolonged time to antibiotic administration (TTA) is associated with increased hospital length of stay (LOS) and worse outcomes. We hypothesized that a febrile neutropenia pathway (FNP) quality initiative project would reduce TTA delays for febrile patients with cancer presenting to the emergency department (ED). METHODS This prospective study compared ED FNP patients (> 18 years old), between June 2012 and June 2013 with both historical and direct admissions (DA) cohorts at a multispecialty academic center. Interventions included providing patients with FN-Alert cards, standardizing the definition of FN and recognizing it as a distinct chief complaint, revising ED triage level for FN, creating electronic FN order sets, administering empiric antibiotics before neutrophil count result, and relocating FN antibiotics to the ED. The primary outcome was TTA, with a target goal of 90 minutes after ED presentation. RESULTS In total, 276 FN episodes in 223 FNP patients occurred over the 12-month study period and were compared with 107 episodes in 87 patients and 114 episodes in 101 patients in the historical and DA cohorts, respectively. Use of the FNP reduced TTA from 235 and 169 minutes in historical and DA cohorts, respectively, to 81 minutes, and from 96 to 68 minutes when the order set was not used versus used in the FNP group (P < .001 for all comparisons). Decrease in hospital LOS was not statistically significant. CONCLUSION The ED FNP is a significant quality initiative with sustainable interventions, and was able to demonstrate value by decreasing TTA compared to both historical and DA controls in cancer patients presenting to the ED.

Antimicrobial stewardship program to reduce antiretroviral medication errors in hospitalized patients with human immunodeficiency virus infection.

OBJECTIVE Evaluate antimicrobial stewardship interventions targeted to reduce highly active antiretroviral therapy (HAART)- or opportunistic infection (OI)-related medication errors and increase error resolution. DESIGN Retrospective before-after study. SETTING Academic medical center. PATIENTS Inpatients who were prescribed antiretroviral therapy before the intervention (January 1, 2011, to October 31, 2011) and after the intervention (July 1, 2012, to December 31, 2012). Patients treated with lamivudine or tenofovir monotherapy for hepatitis B were excluded. METHODS Antimicrobial stewardship interventions included education, modification of electronic medication records, collaboration with the infectious diseases (ID) department, and prospective audit and review of HAART and OI regimens by an ID clinical pharmacist. RESULTS Data for 162 admissions from the preintervention period and 110 admissions from the postintervention period were included. The number of admissions with a medication error was significantly reduced after the intervention (81 [50%] of 162 admissions vs 37 (34%) of 110 admissions; P < .00)1. A total of 124 errors occurred in the preintervention group (mean no. of errors, 1.5 per admission), and 43 errors occurred in the postintervention group (mean no. of errors, 1.2 per admission). The most common error types were major drug interactions and dosing in the preintervention group and renal adjustment and OI-related errors in the postintervention group. A significantly higher error resolution rate was observed in the postintervention group (36% vs 74%; P < .001). After adjustment for potential confounders with logistic regression, admission in the postintervention group was independently associated with fewer medication errors (odds ratio, 0.4 [95% confidence interval, 0.24-0.77]; P = .005). Overall, presence of an ID consultant demonstrated a higher error resolution rate (32% without a consultation vs 68% with a consultation; P = .002). CONCLUSIONS Multifaceted, multidisciplinary stewardship efforts reduced the rate and increased the overall resolution of HAART-related medication errors.

Implementation of a pharmacy-driven program to improve nasal mupirocin use

Staphylococcus aureus is a leading cause of serious hospital-acquired infections and is associated with significant morbidity and mortality. Colonization with S. aureus within the anterior nares is a risk factor for invasive disease.[1][1] Previous work at our institution revealed that active

Evaluation of Antimicrobial Stewardship–Related Alerts Using a Clinical Decision Support System:

Background: Information technology, including clinical decision support systems (CDSS), have an increasingly important and growing role in identifying opportunities for antimicrobial stewardship–related interventions. Objective: The aim of this study was to describe and compare types and outcomes of CDSS-built antimicrobial stewardship alerts. Methods: Fifteen alerts were evaluated in the initial antimicrobial stewardship program (ASP) review. Preimplementation, alerts were reviewed retrospectively. Postimplementation, alerts were reviewed in real-time. Data collection included total number of actionable alerts, recommendation acceptance rates, and time spent on each alert. Time to de-escalation to narrower spectrum agents was collected. Results: In total, 749 alerts were evaluated. Overall, 306 (41%) alerts were actionable (173 preimplementation, 133 postimplementation). Rates of actionable alerts were similar for custom-built and prebuilt alert types (39% [53 of 135] vs 41% [253 of 614], P = .68]. In the postimplementation group, an intervention was attempted in 97% of actionable alerts and 70% of interventions were accepted. The median time spent per alert was 7 minutes (interquartile range [IQR], 5-13 minutes; 15 [12-17] minutes for actionable alerts vs 6 [5-7] minutes for nonactionable alerts, P < .001). In cases where the antimicrobial was eventually de-escalated, the median time to de-escalation was 28.8 hours (95% confidence interval [CI], 10.0-69.1 hours) preimplementation vs 4.7 hours (95% CI, 2.4-22.1 hours) postimplementation, P < .001. Conclusions: CDSS have played an important role in ASPs to help identify opportunities to optimize antimicrobial use through prebuilt and custom-built alerts. As ASP roles continue to expand, focusing time on customizing institution specific alerts will be of vital importance to help redistribute time needed to manage other ASP tasks and opportunities.

Evaluation of a Clinical Decision Support System for Antimicrobial De-escalation at a Large Academic Medical Center

components of antimicrobial stewardship programs (ASPs). TheraDocTM, a CDSS, has both pre-built as well as customizable stewardship alerts. Prior studies have demonstrated clinical benefit but also a low rate of actionable alerts (24-36%). A pilot study was undertaken to assess the time and value of the CDSS, both pre-built and custom built alerts, for ASP interventions with a focus on de-escalation. Methods: 15 different types of alerts (1 pre-built and 14 custom) were chosen for the initial ASP review. Pre-intervention, alerts were generated retrospectively from March 1-31, 2014. Post intervention, alerts were reviewed for ASP intervention by a pharmacist in real-time from May 19June 20, 2014. Data collection included the total actionable (an intervention was or could have been attempted), acceptance of recommendation, and time spent for each type of alert. For de-escalation alerts, time to de-escalation to a more narrow spectrum agent was collected. Results: 749 alerts were evaluated (373 pre) and (376 post). The primary service was medical (52% vs. 57%) and there was an infectious diseases consult in 48% and 47% of alerts in pre vs. post groups, respectively. Overall, 306 (41%) alerts were actionable (173 pre and 133 post). Custom built alerts were more actionable (53/95, 56%) vs. pre-built alerts (253/614, 41%), p<0.01. The most common alert types were drug-bug mismatch, custom de-escalation, and drug-interaction alerts. In the post group, an intervention was attempted in 97% of actionable alerts and 70% (91/131) of interventions were accepted. The average time spent per alert was 7 minutes, with actionable alerts taking average 15 min and non-actionable 6 min, p<0.01. For de-escalation alerts, time to de-escalation was 28.8 hours in pre vs. 4.7 hours in the post group, p<0.01. Conclusions: ASP programs evaluating CDSS should consider customizing alerts to improve rate of actionable alerts and minimize time spent on non-actionable alerts. Overall, the use of CDSS as part of an ASP helped identify targets for de-escalation and decreased broad spectrum antimicrobial usage. Abstract Methods Results