Potentially multidrug-resistant non-fermentative Gram-negative pathogens causing nosocomial pneumonia

Abstract

Owing to its high morbidity and mortality, nosocomial pneumonia represents a particularly serious illness and one of the most frequent complications in ventilated patients admitted to the Intensive Care Unit. Gram-negative microorganisms, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, are the most relevant pathogens responsible for particularly difficult-to-treat nosocomial pneumonia. The intrinsic resistance of these bacteria to many antimicrobial agents and, in addition, the variety of their increasingly recognised acquired resistance mechanisms make their management in the hospital setting problematic. Antimicrobials that retain the best activity against P. aeruginosa include carbapenems, piperacillin, cefepime, ceftazidime, ciprofloxacin and certain aminoglycosides, whilst carbapenems and sulphamethoxazole/trimethoprim remain the most active agents against A. baumannii and S. maltophilia, respectively. However, the growing emergence among these microorganisms of multidrug-resistant (MDR) isolates and the severity of associated infections call for potential alternative drugs. Sulbactam alone or in combination with ampicillin may represent an acceptable option for MDR A. baumannii as well as colistin, which also covers MDR P. aeruginosa. Newer fluoroquinolones and some tetracyclines may be alternative drugs both for MDR S. maltophilia and A. baumannii. However, large-scale controlled clinical trials are needed to confirm these promising therapeutic options.

Introduction

Nosocomial pneumonia, defined as pneumonia occurring ≥48 h after hospital admission and excluding any infection that is incubating at the time of admission, remains the major cause of morbidity and mortality especially in Intensive Care Units (ICUs) [1]. Crude mortality rates range from 20% to 70% depending on the population and clinical setting studied [2], [3], [4]. Nosocomial pneumonia may occur both in mechanically-ventilated and in non-ventilated patients, but ventilator-associated pneumonia (VAP) represents the most important subset [5]. In accordance with the American Thoracic Society guidelines, early onset and late onset pneumonia usually occur within the first 5 days or more than 5 days after hospital admission, respectively, and depict two subgroups with well established differences in epidemiology, risk factors and prognosis [1]. The starting point for defining the concept of early onset VAP is, however, controversial; hospital admission time or intubation time are all possible crucial factors, although from the treatment and prognosis perspective the factor ‘previous days of hospitalisation’ appears more important than ‘previous days of ventilation’ [6], [7]. Subject to much controversy is also the cut-off time differentiating early and late onset VAP [8], [9].

The aetiology of nosocomial pneumonia varies from institution to institution and by the kind of patients admitted; however, the spectrum of potential pathogens can be defined by the assessment of various factors, including the severity of the pneumonia itself (mild to moderate or severe nosocomial pneumonia), the presence of specific risk factors, prior antimicrobial regimen, length of hospitalisation and the time point of occurrence of pneumonia [1], [5], [8]. Community-acquired pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, methicillin-susceptible Staphylococcus aureus and non-highly resistant enteric Gram-negative bacilli are generally the principal organisms of early onset pneumonia; conversely, classical nosocomial pathogens such as methicillin-resistant S. aureus, Pseudomonas aeruginosa, Acinetobacter spp. and, less frequently, Stenotrophomonas maltophilia are traditionally associated with late onset pneumonia [1], [10]. The intrinsic resistance of these microorganisms to multiple classes of antimicrobials and their ability to acquire adaptive resistance during therapy make the management of pneumonia due to these pathogens particularly problematic. Appropriate and timely antimicrobial treatment is crucial to improve outcome and to reduce the patient mortality rate [11]. Guidelines for initial antibiotic treatment of patients with nosocomial pneumonia can help physicians in therapeutic decision-making [1], [5], [11]. However, guidelines need to be constantly updated on new available antimicrobials as well as on local patterns of antimicrobial resistance, since a continuous shift towards more resistant bacteria has been reported for several decades, becoming even more alarming in pathogens responsible for nosocomial infections [12], [13], [14]. The aim of this article is to analyse some aspects of potentially multidrug-resistant (MDR) microorganisms such as P. aeruginosa, Acinetobacter baumannii and S. maltophilia, focusing on their mechanisms of antimicrobial resistance and on opportunities for optimal treatment of nosocomial pneumonia due to such difficult pathogens.