International Journal of Antimicrobial Agents 34 (2009) 246–251 Contents lists available at ScienceDirect International Journal of Antimicrobial Agents journal homepage: http://www.elsevier.com/locate/ijantimicag Carbapenems and subsequent multiresistant bloodstream infection: does treatment duration matter? Annabelle D. Donaldson a,b , Lubna Razak b , Li Jia Liang c , Dale A. Fisher a,b , Paul A. Tambyah a,b,∗ a Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore b Department of Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore c Department of Statistics, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore article info Article history: Received 29 December 2008 Accepted 6 April 2009 Keywords: Antimicrobial resistance Intensive care Nosocomial infection Carbapenem abstract It has been proposed that initial empirical broad-spectrum antibiotic therapy will result in better clinical outcomes and that shorter courses will reduce the ‘collateral damage’ of promoting antibiotic resistance. There are few data from Intensive Care Units (ICUs) that support this latter conclusion. A prospec- tive observational study was undertaken at the National University Hospital, Singapore, to examine the relationship between duration of carbapenem therapy and subsequent nosocomial multidrug-resistant (MDR) bloodstream infection (BSI). Over a 2-year period, 415 ICU patients receiving empirical carbapenem therapy were prospectively followed. MDR BSI occurred on 35 occasions in 31 patients, comprising 21 carbapenem-resistant Acinetobacter baumannii, 3 carbapenem-resistant Pseudomonas aeruginosa and 11 meticillin-resistant Staphylococcus aureus (MRSA). There was no difference in the duration of carbapen- ems for those who developed MDR BSI compared with those who did not [median duration 8 days (range 3–23 days) vs. 9 days (range 3–59 days); P = 0.78]. On multivariate analysis using the Cox proportional haz- ard model the hazard ratio was 0.935 (P = 0.070). In this cohort of critically ill patients, a shorter duration of carbapenem therapy was not shown to protect against subsequent development of MDR BSI. Strategies that depend primarily on reducing broad-spectrum antibiotic duration may be inadequate in preventing the emergence of MDR organisms. © 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. 1. Introduction Multiresistant organisms are a significant cause of morbid- ity and mortality at the National University Hospital (NUH) of Singapore. In 2005, 62 (76%) of 82 Acinetobacter baumannii bloodstream infections (BSIs) were carbapenem resistant. There were also 49 Pseudomonas aeruginosa BSIs in the hospital, with 36% and 32% being resistant to imipenem and meropenem, respectively. In the Intensive Care Unit (ICU) population, the inci- dence of meticillin-resistant Staphylococcus aureus (MRSA) BSI was 2.66/1000 patient-days. Reports of increased mortality in critically ill patients given inadequate initial antibiotics [1–5] have led to a strategy of ‘de- escalation’. This approach recommends initial broad-spectrum antimicrobial therapy in critically ill patients followed by narrowing the spectrum in accordance with microbiology results and clinical response [6,7]. The aim is to reduce mortality as well as to minimise ∗ Corresponding author at: Department of Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. Tel.: +65 6779 5555; fax: +65 6779 4112. E-mail address: mdcpat@nus.edu.sg (P.A. Tambyah). the risk of antimicrobial resistance that may emerge with con- tinued broad-spectrum antibiotics [6,7]. However, there is limited evidence supporting the fundamental assumption that a reduction in the risk of subsequent infection by resistant pathogens occurs with shorter duration of broad-spectrum antibiotic therapy. A prospective observational study in an ICU was undertaken to examine the relationship between duration of carbapenem therapy and subsequent nosocomial multidrug-resistant (MDR) BSIs. Only MDR BSIs, rather than other infections or colonisation with MDR organisms, were used because of the indisputable impli- cations for the patient as well as the difficulty in distinguishing colonisation from infection in an intensive care setting for other infections. Empirical carbapenems are advocated at NUH because of high rates of extended-spectrum -lactamases in ICU patients [8]. 2. Materials and methods A prospective observational cohort study was undertaken among critically ill patients at the 900-bed NUH of Singapore. All adult patients (>15 years) admitted to one of the ICUs or High Dependency Units (HDUs) with a significant exposure to car- bapenems between 1 July 2003 and 30 June 2005 were enrolled. 0924-8579/$ – see front matter © 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2009.04.007