Infection Control & Hospital Epidemiology (2018), 39, 1262–1265 doi:10.1017/ice.2018.181
Concise Communication
The epidemiological impact and significance of carbapenem resistance in Pseudomonas aeruginosa bloodstream infections: a matched case–case-control analysis
Tzach Aviv MD1, Tsillia Lazarovitch PhD2, David Katz MD, MPH3, Ronit Zaidenstein MD4, Mor Dadon BS4,
Chen Daniel BS4, Ruthy Tal-Jasper MD1, Keith S. Kaye MD, MPH5 and Dror Marchaim MD1,4 1Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel, 2Clinical Microbiology Laboratory, Assaf Harofeh Medical Center, Zerifin, Israel, 3Department of Internal Medicine, Shaare Zedek Medical Center, Jerusalem, Israel, 4Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, Israel, and 5Department of Medicine, University of Michigan, Ann Arbor, Michigan, United States
Abstract
Acase–case-control investigation (N = 255 patients) explored the epidemiology of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Recent exposure to carbapenems and a rapidly fatal condition should prompt practitioners to shorten delays in initiating appropriate therapy, which can adversely impact CRPA outcomes, as opposed to the isolated impact of the carbapenem resistance determinant.
(Received 13 March 2018; accepted 29 June 2018; electronically published August 14, 2018)
Carbapenems are effective and safe; they are the mainstay of therapy for serious Pseudomonas aeruginosa infections.1–3 However, there is a significant association between carbapenem nonsusceptibility and adverse clinical outcomes.4 Carbapenem- resistant P. aeruginosa (CRPA) is a major epidemiological threat, specifically in countries where the new antipseudomonal β-lactam agents (eg, ceftolozane-tazobactam and ceftazidime-avibactam) are not yet available. Currently, prevention efforts frequently target CRPA strains.
Contact isolation precautions are utilized for CRPA carriers, and screening programs are frequently aimed at CRPA strains.2 How- ever, the mechanisms of resistance of P. aeruginosa to carbapenems are frequently mediated through chromosomal genes.2 Therefore, it might be appropriate to target the prevention of transmission of all P. aeruginosa strains. In addition, the studies that have reported on the association between CRPA and poor outcomes have major limitations: (1) many were not conducted using the matched case– case-control study design,4 (2) many did not strictly adhere to infection definitions that differentiate infection from asymptomatic carriage,3 and (3) many have not controlled for delay in initiation of appropriate antimicrobial therapy (DAAT).4 All of these factors might have led to the overestimation of the independent associa- tion between resistance to carbapenems and poor clinical out- comes. For CRPA prevention programs to be effective, it is important to differentiate DAAT from the isolated impact of the resistance determinant to appropriately allocate prevention resources. Moreover, exploring the independent predictors of
Author for correspondence: Dror Marchaim, MD, Unit of Infectious Diseases, Assaf Harofeh Medical Center, Zerifin, 70300, Israel. E-mail:
drormarchaim@gmail.com
Cite this article: Aviv T, et al. (2018) The epidemiological impact and significance of carbapenem resistance in Pseudomonas aeruginosa bloodstream infections: a matched case–case-control analysis. Infection Control & Hospital Epidemiology 2018, 39, 1262–1265. doi: 10.1017/ice.2018.181
© 2018 by The Society for Healthcare Epidemiology of America. All rights reserved.
CRPA using an appropriate design can help guide stewardship interventions aimed at reducing DAAT and improving outcomes.
Methods
A retrospective matched case–case-control analysis was con- ducted among adults (>18 years old) at the Assaf Harofeh Medical Center, Israel, from 2007 to 2012. The institutional ethics committee approved the study. Resistant cases were defined as patients with bloodstream infections (BSIs) due to P. aeruginosa that were not susceptible to either meropenem or imipenem (MIC ≥ 4 µg/dL for both).5 Susceptible cases were defined as patients with P. aeruginosa BSIs that were susceptible to both meropenem and imipenem. The uninfected control group consisted of patients without P. aeruginosa infection or BSI. Patients were included in the analysis only once. A susceptible case and an uninfected control were matched to a resistant case (1:1:1 ratio) according to time at risk,6 hospital unit, and calendar year. Eli- gible susceptible cases and uninfected controls were randomly selected (Excel software, Microsoft, Redmond WA). Data were collected from available records. Posthospitalization
deaths were captured from a national registry. The primary outcome
was14-daymortality.Assuminga21% mortalityrateamongcases and 10% among controls,3 we calculated that a population of 225 patients would be needed to provide adequate power (β = 0.8) to detect significant differences between cases and controls. Logistic and Cox regressions were used to capture predictors and outcomes of CRPA infections. All models were assessed for collinearity and were controlled for confounding. A matched analysis was performed comparing resistant cases and uninfected controls. We forced 2 variables into each outcome model: carbapenem resistance and DAAT (as a continuous variable and DAAT > 48 hours, whichever statistical association was stronger). All tests were 2-tailed.
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