Ryan P. Mynatt

Automated Alerts Coupled with Antimicrobial Stewardship Intervention Lead to Decreases in Length of Stay in Patients with Gram-Negative Bacteremia

OBJECTIVE To assess the impact of active alerting of positive blood culture data coupled with stewardship intervention on time to appropriate therapy, length of stay, and mortality in patients with gram-negative bacteremia. DESIGN Quasi-experimental retrospective cohort study in patients with gram-negative bacteremia at the Detroit Medical Center from 2009 to 2011. SETTING Three hospitals (1 community, 2 academic) with active antimicrobial stewardship programs within the Detroit Medical Center. PATIENTS All patients with monomicrobial gram-negative bacteremia during the study period. INTERVENTION Active alerting of positive blood culture data coupled with stewardship intervention (2010-2011) compared with patients who received no formalized stewardship intervention (2009). RESULTS Active alerting and intervention led to a decreased time to appropriate therapy (8 [interquartile range (IQR), 2-24] vs 14 [IQR, 2-35] hours; P = .014) in patients with gram-negative bacteremia. After controlling for differences between groups, being in the intervention arm was associated with an independent reduction in length of stay (odds ratio [OR], 0.73 [95% confidence interval (CI), 0.62-0.86]), correlating to a median attributable decrease in length of stay of 2.2 days. Additionally, multivariate modeling of patients who were not on appropriate antimicrobial therapy at the time of initial culture positivity showed that patients in the intervention group had a significant reduction in both length of stay (OR, 0.76 [95% CI, 0.66-0.86]) and infection-related mortality (OR, 0.24 [95% CI, 0.08-0.76]). CONCLUSIONS Active alerting coupled with stewardship intervention in patients with gram-negative bacteremia positively impacted time to appropriate therapy, length of stay, and mortality and should be a target of antimicrobial stewardship programs.

Risk of Acute Kidney Injury in Patients on Concomitant Vancomycin and Piperacillin/tazobactam Compared to those on Vancomycin and Cefepime

Background. Recent evidence suggests that among patients receiving vancomycin, receipt of concomitant piperacillin–tazobactam increases the risk of nephrotoxicity. Well-controlled, adequately powered studies comparing rates of acute kidney injury (AKI) among patients receiving vancomycin + piperacillin–tazobactam (VPT) compared to similar patients receiving vancomycin + cefepime (VC) are lacking. In this study we compared the incidence of AKI among patients receiving combination therapy with VPT to a matched group receiving VC. Methods. A retrospective, matched, cohort study was performed. Patients were eligible if they received combination therapy for ≥48 hours. Patients were excluded if their baseline serum creatinine was >1.2mg/dL or they were receiving renal replacement therapy. Patients receiving VC were matched to patients receiving VPT based on severity of illness, intensive care unit status, duration of combination therapy, vancomycin dose, and number of concomitant nephrotoxins. The primary outcome was the incidence of AKI. Multivariate modeling was performed using Cox proportional hazards. Results. A total of 558 patients were included. AKI rates were significantly higher in the VPT group than the VC group (81/279 [29%] vs 31/279 [11%]). In multivariate analysis, therapy with VPT was an independent predictor for AKI (hazard ratio = 4.27; 95% confidence interval, 2.73–6.68). Among patients who developed AKI, the median onset was more rapid in the VPT group compared to the VC group (3 vs 5 days P =< .0001). Conclusion. The VPT combination was associated with both an increased AKI risk and a more rapid onset of AKI compared to the VC combination.

Epidemiology of Acute Kidney Injury among Patients Receiving Concomitant Vancomycin and Piperacillin-Tazobactam: Opportunities for Antimicrobial Stewardship

ABSTRACT Despite their common use as an empirical combination therapy for the better part of a decade, there has been a recent association between combination therapy with vancomycin and piperacillin-tazobactam and high rates of acute kidney injury (AKI). The reasons for this increased association are unclear, and this analysis was designed to investigate the association. Retrospective cohort and case-control studies were performed. The primary objective was to assess if there is an association between extended-infusion piperacillin-tazobactam in combination with vancomycin and development of AKI. The secondary objectives were to identify risk factors for AKI in patients on the combination, regardless of infusion strategy, and to evaluate the impact of AKI on clinical outcomes. AKI occurred in 105/320 (33%) patients from the cohort receiving combination therapy with vancomycin and piperacillin-tazobactam, with similar rates seen in those receiving intermittent (53/160 [33.1%]) and extended infusions (52/160 [32.5%]) of piperacillin-tazobactam. Independent risk factors for AKI in the cohort included having a documented Gram-positive infection, the presence of sepsis, receipt of a vancomycin loading dose (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.05 to 4.71), and receipt of any concomitant nephrotoxin (OR, 2.44; 95% CI, 1.41 to 4.22). For at-risk patients remaining on combination therapy, the highest rates of AKI occurred on days 4 (10.7%) and 5 (19.3%). The incidence of AKI in patients on combination therapy with vancomycin and piperacillin-tazobactam is high, occurring in 33% of patients. Receipt of piperacillin-tazobactam as an extended infusion did not increase this risk. Modifiable risk factors for AKI include receipt of a vancomycin loading dose, concomitant nephrotoxins, and longer durations of therapy.

Carbapenem-Resistance in Gram-Negative Bacilli and Intravenous Minocycline: An Antimicrobial Stewardship Approach at the Detroit Medical Center

In the era of carbapenem-resistance in Acinobacter baumannii and Enterobacteriaceae, there are limited treatment options for these pathogens. It is essential that clinicians fully assess all available therapeutic alternatives for these multidrug-resistant organisms. We herein describe the approach of the antimicrobial stewardship team at the Detroit Medical Center (DMC) for the evaluation and use of intravenous (IV) minocycline for the treatment of these resistant organisms, given potential advantages of IV minocycline over tigecycline and doxycycline. In vitro analyses at the DMC demonstrated good activity against A. baumannii (78% susceptibility), including 74% of carbapenem-resistant strains, but limited activity against our carbapenem-resistant K.pneumoniae (12% susceptibility.) Based in part on these results, IV minocycline was added to the formulary, primarily for the treatment of carbapenem-resistant A. baumannii. Early experience has been positive: 6/9 (67%) of patients who received IV minocycline had infections due to these organisms cured, including 6/7 (86%) who received doses of 200 mg twice daily.

Moving antimicrobial stewardship from restriction to facilitation.

A comprehensive antimicrobial stewardship program can effectively improve the use of antimicrobial agents in a hospital. These programs are often able to document reductions in resistance rates and antimicrobial costs.[1][1] Infectious disease physicians and pharmacists are considered core personnel

Nephrotoxicity Comparison of Two Commercially Available Generic Vancomycin Products

ABSTRACT To date, no comparative clinical studies have investigated the effects of different vancomycin products on nephrotoxicity. The objective of this single-center, retrospective, matched-cohort study was to investigate the impact of two different vancomycin products on the development of nephrotoxicity. The study population included adults receiving a single vancomycin product, from either Pfizer or Hospira, for their entire course of therapy. Patients were matched based on underlying nephrotoxicity risk factors. Secondary outcomes included the need for renal replacement therapy, length of hospital stay, and in-hospital mortality. One-hundred forty-six matched pairs (n = 292) were included, and they had no significant differences in demographics, comorbid conditions, severity of illness, or vancomycin-associated nephrotoxicity risk factors. The frequency of nephrotoxicity was 8.9% in the Pfizer group and 11.0% in the Hospira group as defined by the 2009 consensus vancomycin guidelines (P = 0.56), 17.1% in the Pfizer group and 13.0% in the Hospira group as defined by the Acute Kidney Injury Network (AKIN) (P = 0.33), and 10.3% in the Pfizer group and 11.6% in the Hospira group as defined by RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria (P = 0.71). There were no differences between groups in regard to nephrotoxicity by any definition or in secondary outcomes. In multivariate analysis of overall nephrotoxicity risk factors, the type of vancomycin product was not independently associated with increased odds of developing nephrotoxicity according to the RIFLE criteria. Based on our results, there are no discernible differences between Pfizer and Hospira vancomycin products in the frequency of nephrotoxicity. Confirmation of these results with other types of vancomycin and different patient populations is warranted.

Implementation and outcomes of a pharmacy residency mentorship program.

PURPOSE The implementation and outcomes of a pharmacy residency mentorship program are described. SUMMARY The mentorship program at the Detroit Medical Center was formally implemented during the residency orientation period in 2013. Residents had up to two months after the start of the residency to choose a mentor, which we believed was an adequate amount of time to meet all members of the department of pharmacy. One year after implementation of the mentorship program, an anonymous survey was administered to all 16 residents to gather feedback about the mentorship program. Eleven (70%) of the 16 residents completed the survey. A majority agreed that having a mentor was a beneficial aspect of their residency training, often citing their mentor as integral in their career planning and helpful in balancing their personal and professional lives. Further, 91% (n = 10) of the respondents indicated that they planned on remaining in contact with their mentor after their residency. Nearly half of the residents met multiple times per month or weekly. All respondents stated that their mentor was available and accessible when needed. The year after program implementation, all residents were either offered a position for employment or matched to a residency before the completion of the residency. Although the mentors were not assessed with an anonymous survey, there continues to be overwhelming support for the continuation and improvement of the program as part of residency training. CONCLUSION Implementation of a mentorship program during residency training was viewed as beneficial for personal and professional development by many of the residents.

The State of Antimicrobial Stewardship in Michigan: Results of a Statewide Survey on Antimicrobial Stewardship Efforts in Acute Care Hospitals.

Clinical Pharmacy Specialist, Infectious Diseases, St. Joseph Mercy Health System, Ann Arbor, Michigan; Chief Operations Officer, Michigan Pharmacists Association, Lansing Michigan; Pharmacy Specialist, Antimicrobial Stewardship, Henry Ford Hospital, Detroit, Michigan; Clinical Pharmacist Specialist, Infectious Diseases, Detroit Receiving Hospital, Detroit Medical Center, Detroit, Michigan; ¶Clinical Pharmacy Specialist in Infectious Diseases, Department of Pharmacy and Infectious Diseases, Munson Medical Center, Traverse City, Michigan; Antimicrobial Stewardship Pharmacist, The University of Toledo, Main and Health Science Campuses, Toledo, Ohio; Infectious Diseases Pharmacist, Baptist Health Louisville Pharmacy Department, Louisville, Kentucky; Clinical Pharmacist, Infectious Diseases, Sinai-Grace Hospital, Detroit Medical Center, Detroit, Michigan; Clinical Assistant Professor of Medicine, Wayne State University School of Medicine, Detroit, Michigan. Corresponding author: Curtis Collins, PharmD, MS, BCPS (AQ-ID), FASHP, Clinical Pharmacy Specialist, Infectious Diseases, St. Joseph Mercy Health System, 5301 East Huron River Drive, Ann Arbor, MI 48106; phone: 734-712-6023; e-mail: cdc008@yahoo.com To the Editor: Infections due to drug-resistant organisms are associated with considerable morbidity and mortality.1 While resistant gram-positive infections, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE), remain a significant threat, the rise of resistant gramnegative infections due to P. aeruginosa, A. baumannii, and carbapenem-resistant enterobacteriaceae (CRE) have led to scenarios where clinicians are forced into treatment with highly toxic, often older, and pharmacologically suboptimal treatment regimens with drugs such as polymyxins or tigecycline.2 Despite the Infectious Diseases Society of America’s (IDSA) 10x20 initiative that promotes the development of 10 novel antimicrobials by 2020, the antimicrobial pipeline remains relatively dry, with only a few agents currently in phase III trials and none of these with a novel mechanism of action.3 These data highlight the need for antimicrobial stewardship efforts aimed at promoting the optimal use of current agents in an effort to limit further development of drug resistance. In addition, antimicrobial use, both appropriate and inappropriate, is the number one driver of Clostridium difficile infection (CDI), which has been shown to be a significant complication of hospitalization, leading to increased length of stay, hospital costs, morbidities, and ultimately mortality.4 In 2007, the IDSA developed and published guidelines and recommendations for antimicrobial stewardship within institutions.5 In this document, the authors recommended 2 core methods for stewardship: prospective audit and feedback (which involves daily monitoring of target antimicrobials and direct feedback with the prescribing team) and formulary restriction and preauthorization (requiring approval, usually by infectious diseases [ID], or predetermined criteria to be met, prior to dispensing an antimicrobial).5 They also recommended additional supplemental methods including education, guidelines and pathway development, intravenous to oral switching, de-escalation, and dose optimization to complement the 2 core methods. The authors suggested that the core stewardship team should consist of an ID physician and an ID-trained pharmacist, with support and collaboration of a clinical microbiologist, information technology, and hospital administration.5 Although these recommendations are commendable, the applicability to a large majority of institutions remains questionable and poorly described.

Making the change to area under the curve–based vancomycin dosing

Vancomycin, a glycopeptide antimicrobial, is commonly employed for empirical and definitive treatment of infections due to resistant gram-positive pathogens, notably methicillin-resistant Staphylococcus aureus (MRSA). Given wide interpatient and intrapatient pharmacokinetic variability coupled with

944Outbreak of Colistin-Resistant Acinetobacter baumannii in Intensive Care Units in Detroit, Michigan

Background: A. baumannii is commonly recognized as an emerging multi-drug resistant (MDR) organism frequently impervious to majority of the commonly prescribed antibiotics. Colistin is one of the few therapeutic agents which possess activity against this pathogen, and its use has dramatically increased. As a result, colistin resistance is increasingly reported among A. baumannii and presents a unique challenge. Methods: A cluster of colistin-resistant A. baumannii cases at Detroit Receiving Hospital were identified from May 1st, 2013 to October 31st, 2013. Colistin resistance was defined as an MIC of >2 μg/ml (E-test). Epidemiologic data for these cases were collected and isolates assayed for clonality with Diversilab rep-PCR and multi-locus sequence typing (ST). Results: 11 cases were identified. The mean age of the patients was 48.8 years (range 17-76) and 10 (91%) resided in one of two intensive care units. All patients were treated with broad spectrum antimicrobials (but not colistin) prior to isolation of the colistin-resistant isolate. 9 (82%) patients were mechanically ventilated and the pathogen was detected from sputum specimen in 8 (73%) of patients. Other features frequently identified in these cases were the use of glucometer (73%) and tube feeds (82%). Colistin MIC ranged from 3-32. Environmental surveillance cultures were performed, but only one specimen was positive for the same organism. Genotyping was performed on 5 patient isolates which revealed 95% similarity between strains (Figure 1) and all isolates were ST281. In order to contain the outbreak, optimal infection prevention practices were reinforced, active surveillance screening of high risk patients implemented, with presumptive contact isolation. Conclusion: To our knowledge this is the first reported outbreak of colistin-resistant A. baumannii in United States. The hands of healthcare workers and environmental reservoirs are hypothesized to be the source of the outbreak. We observed a wide range of colistin MICs among outbreak strains, possibly due to 1) the emergence of heteroresistance or 2) differences in the population structure. A case-control study will help to further help delineate the cause of the outbreak. OXA23