Redefining Success for VAP: 360-Degree Approach

Abstract

BACKGROUND: Ventilator-associated pneumonia (VAP) in hospital intensive care units (ICUs) is associated with high morbidity and mortality. Effective treatment of VAP can be challenging due to a high prevalence of Pseudomonas aeruginosa and multidrug-resistant (MDR) pathogens as causative organisms. OBJECTIVE: To present the etiology of VAP in the United States (including national resistance trends of common nosocomial pathogens) and review dosing strategies aimed to optimize pharmacokinetic-pharmacodynamic parameters of antimicrobial agents. SUMMARY: The majority of nosocomial pneumonia cases are caused by gram-negative pathogens, most commonly P. aeruginosa, Enterobacter spp., A. baumannii, and K. pneumoniae. S. aureus is the most common gram-positive pathogen, with 55% of VAP isolates exhibiting methicillin resistance. Combination therapy is recommended when MDR pathogens and P. aeruginosa are suspected, although short-course therapy and deescalation should be considered when appropriate to reduce the risk of resistance. Optimized dosing strategies are important in increasing the probability of achieving successful outcomes. For example, when administering intravenous β-lactam therapy, prolonged infusion can be effective in increasing the T > MIC. CONCLUSION: Clinicians need to be familiar with local antibiograms as well as regional resistance trends in order to choose appropriate therapy for VAP. Optimized dosing strategies can be effective in increasing the probability of attaining pharmacokinetic-pharmacodynamic targets predictive of successful clinical outcomes. J Manag Care Pharm. 2009;15(5)(Suppl):S5-S9 Copyright © 2009, Academy of Managed Care Pharmacy. All rights reserved. DAVID S. BURGESS, PharmD, FCCP, is Clinical Professor of Pharmacy and Medicine, University of Texas at Austin, Austin, Texas, and the University of Texas Health Science Center at San Antonio, San Antonio, Texas. CORRESPONDENCE: David S. Burgess, PharmD, FCCP, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MSC 6220, San Antonio, TX 78229-3900. Tel.: 210.567.8329; Fax: 210.567.8328; E-mail: burgessd@uthscsa.edu Author Introduction Ventilator-associated pneumonia (VAP) is among the most common nosocomial infections originating in the intensive care unit (ICU), affecting 9% to 27% of all intubated patients.1,2 The attributable mortality can be as high as 33% to 50%.1,2 The risk of VAP is correlated to the length of stay (LOS) in the hospital or ICU as well as to the duration of mechanical ventilation.2 Pseudomonas aeruginosa and multidrug-resistant (MDR) organisms account for over 20% of VAP infections, with higher rates observed in those with prolonged hospitalization.3 Infection by these problematic pathogens is associated with increased mortality, duration of mechanical ventilation, and hospital LOS.3 Therefore, when managing patients at high risk for VAP, it is important to recognize the local epidemiology and resistance trends in order to select the most appropriate initial antimicrobial therapy. Etiology of Hospital-Acquired Pneumonia Surveillance data from the National Healthcare Safety Network (NHSN, formerly the National Nosocomial Infections Surveillance System) have shown that gram-negative pathogens are the predominant cause of nosocomial pneumonia, accounting for approximately 70% of infections.4 Among the infections caused by gram-negative pathogens, P. aeruginosa is the leading cause (accounting for approximately 20%) followed by Enterobacter spp., Klebsiella pneumoniae, and Acinetobacter baumannii.4 The proportion of infections due to Acinetobacter has nearly doubled over the past 2 decades (from 4% in 1986 to 7% in 2003). However, there has been a gradual trend of increasing infections due to grampositive pathogens, mainly Staphylococcus aureus. The etiology of VAP can vary based on (a) local epidemiological trends as well as (b) the timing of onset of infection. According to the 2006–2007 NHSN data, the most common pathogen associated with VAP is S. aureus (24.4%) followed by P. aeruginosa (16.3%), Enterobacter spp. (8.4%), A. baumannii (8.4%), and K. pneumoniae (7.5%) (Table 1).5 The time of onset is also an important predictor of causative pathogens. Early-onset VAP, defined as VAP occurring within the first 5 days of hospitalization, is caused by enteric gram-negative bacteria (including Escherichia coli, K. pneumoniae, and Enterobacter spp.), Haemophilus influenzae, Streptococcus pneumoniae, and methicillin-susceptible S. aureus (MSSA).2,6 Late-onset VAP, defined as VAP occurring after 5 days of hospitalization, is more likely to be caused by MDR pathogens,2,6 including those associated with early-onset VAP as well as P. aeruginosa and A. baumannii. The variety and complexity of pathogens associated with VAP make choosing an appropriate initial therapy challenging. Appropriate Antimicrobial Therapy for VAP The American Thoracic Society (ATS) and the Infectious Diseases