Impact of Multidrug-resistant Pseudomonas aeruginosa Infection on Patient Outcomes

Elizabeth B Hirsch; Vincent H Tam

Disclosures

Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(4):441-451. 

In This Article

Abstract and Introduction

Abstract

Rates of antibiotic resistance in Pseudomonas aeruginosa are increasing worldwide. The multidrug-resistant (MDR) phenotype in P. aeruginosa could be mediated by several mechanisms including multidrug efflux systems, enzyme production, outer membrane protein (porin) loss and target mutations. Currently, no international consensus on the definition of multidrug resistance exists, making direct comparison of the literature difficult. Inappropriate empirical therapy has been associated with increased mortality in P. aeruginosa infections; delays in starting appropriate therapy may contribute to increased length of hospital stay and persistence of infection. In addition, worse clinical outcomes may be associated with MDR infections owing to limited effective antimicrobial options. This article aims to summarize the contemporary literature on patient outcomes following infections caused by drug-resistant P. aeruginosa. The impact of antimicrobial therapy on patient outcomes, mortality and morbidity; and the economic impact of MDR P. aeruginosa infections will be examined.

Introduction

Pseudomonas aeruginosa is an important pathogen frequently implicated in healthcare-associated infections (HAIs), particularly in critically ill or immunocompromised patients.[1,2] It is a versatile pathogen with the ability to cause diverse infection types. Data from the National Nosocomial Infections Surveillance system from 1986–2003 reported P. aeruginosa as the second most common cause of pneumonia (18.1%), the third most common cause of urinary tract infection (16.3%) and the eighth most frequently isolated pathogen from the bloodstream (3.4%).[3] While the overall proportion of infections caused by P. aeruginosa has remained stable during 1986–2003, the proportion of resistant isolates had alarming increases in 2003 compared with 1998 through 2002.[4] Rates of resistance to imipenem, quinolones and third-generation cephalosporins increased by 15, 9 and 20%, respectively. Similarly, a national surveillance study of intensive care unit (ICU) patients from 1993 to 2002, reported a significant increase in multidrug-resistant (MDR; defined as resistance to at least three of four agents: imipenem, ceftazidime, ciprofloxacin and tobramycin) P. aeruginosa isolates.[5]

The true prevalence of MDR P. aeruginosa is not well established, presumably for several reasons: first, there is considerable disagreement within the medical community as to the definition of multidrug resistance. Multidrug resistance is a heterogeneous phenotype, which could result from different (a combination of) resistance mechanism(s). A review of studies reporting on MDR and 'pan-drug resistant' P. aeruginosa infections revealed considerably different definitions used in the literature, ranging from resistance to a single antibiotic agent/class to resistance to all tested antibiotics.[6] In the majority of the published studies, multidrug resistance was defined as resistance to at least three drugs from a variety of antibiotic classes, mainly aminoglycosides, antipseudomonal penicillins, cephalosporins, carbapenems and fluoroquinolones. Although there have been attempts to establish a precise definition for multidrug resistance, there is currently no international consensus. Second, there is no international surveillance system specifically designed to track MDR organisms. The SENTRY antimicrobial surveillance program is designed to track antimicrobial resistance trends nationally and internationally. However, annual variations in geographic regions and participating centers limit the ability to track the true prevalence of MDR P. aeruginosa.[7] Data from our own institution revealed the prevalence rate of multidrug resistance (defined as resistance to all agents in at least three out of four classes: fluoroquinolones, aminoglycosides, carbapenems, antipseudomonal penicillins/cephalosporins) in P. aeruginosa bloodstream isolates to be approximately 10–17% from 2005 to 2007.[8] Furthermore, diverse resistance mechanisms were found in these MDR isolates.

Broad spectrum antimicrobial resistance in MDR isolates significantly limits effective therapeutic options. Commonly, the agents of last resort for MDR organisms include the aminoglycosides and polymyxins. Recent articles have highlighted that these agents may or may not be as effective as first-line agents, but may also be associated with more significant adverse effects (i.e., nephrotoxicity, ototoxicity and neurotoxicity).[9–15] This contributes (at least partially) to our difficulty in assessing whether MDR pathogens are truly associated with worse clinical outcomes (Figure 1). Available clinical data suggest that MDR P. aeruginosa infections may be associated with poorer outcomes; however, these investigations are often confounded by varied definitions of multidrug resistance and publication bias.

Figure 1.

Factors challenging and supporting the argument that multidrug-resistant pathogens are associated with worse clinical outcomes.

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