Acinetobacter Infection in the Intensive Care Unit

The rising incidence of Acinetobacter infection in the intensive care unit (ICU) causes a great concern to all clinicians and intensivists worldwide due to their extraordinary ability to develop resistance to multiple classes of antibiotics. Acinetobacter can infect virtually any body site, particularly the lower respiratory tract, the bloodstream, and the urinary tract. Infection is mainly related to the inappropriate or previous use of antibiotics and the increasing use of invasive devices in the ICU. Although carbapenem is currently considered the drug of choice for these pathogens, the occurrence of carbapenem-resistant strains has led to fewer treatment options. Due to limited therapeutic options, prevention and infection control measures are essential. (J Infect Dis Antimicrob Agents 2005;22:77-92.) 77 INTRODUCTION Until 1970, Acinetobacter spp. were considered rare causes of nosocomial infections in the intensive care unit (ICU). In recent years, however, the incidence of Acinetobacter infections has reached a point of concern and poses a threat to hospitalized populations around the world. 8 Outbreaks have been increasingly reported regularly. Moreover, most of those outbreaks were caused by multidrug-resistant (MDR) strains of this organism. The initial concern about MDR-Acinetobacter strains began in 1991 when the first hospital-wide outbreak occurred in New York. Now MDR-Acinetobacter strains are observed worldwide. In Thailand, MDR-Acinetobacter infections have been described repeatedly. This phenomenon is due to their extraordinary ability to develop multiple resistance mechanisms against major antibiotic classes used in the ICU including cephalosporins, aminoglycosides, carbapenems, and quinolones. In addition, their ubiquitous nature in the ICU environment and inadequate infection-control 78 J INFECT DIS ANTIMICROB AGENTS May-Aug. 2005 practice have continuously raised the incidence of Acinetobacter infections over the past two decades. Despite the global alarm caused by Acinetobacter, relatively few studies on this issue have been published. The understanding and recognition of Acinetobacter infections in the ICU is critically needed. This article reviews the current aspects of microbiology, epidemiology, clinical characteristics, treatment, and prevention of Acinetobacter infections in the ICU. MICROBIOLOGY Acinetobacter is a gram-negative coccobacillus that has emerged as an important nosocomial pathogen. It is non-motile, encapsulated, and non-fermentative. It belongs to the family Neisseriaceae. Frequently, it can be misidentified as Neisseria or Moraxella species on gram staining, although the negative oxidase reaction is useful in distinguishing Acinetobacter from other gram-negative organisms in the same family. Furthermore, it is indole negative and catalase positive. Acinetobacter is ubiquitous in the outside environment and has been isolated from hospital personnel, and hospital equipments. It is strictly aerobic, and does not require unusual nutrients to survive in the environment. Acinetobacter is easily grown on routine laboratory media (e.g. Tryptic soy agar), however, the specialized culture media are also available. Colonies are 1-2 mm in diameter, dome-shaped, non-pigmented, with smooth or pitted surfaces (Figure 1). Nowadays, there are more than 20 species of Acinetobacter reported. However, the most common one known to cause major nosocomial infections in the ICU is Acinetobacter baumannii, formerly known as Acinetobacter calcoaceticus var. anitratus. This species makes up to 80 percent of total Acinetobacter clinical isolates and has been reported worldwide. 15,21-22 Acinetobacter can be grown from several human sources, including skin, pharynx, sputum, urine, vaginal secretions, and stool. Acinetobacter spp. have, therefore, been implicated in a wide spectrum of infections, including pneumonia, meningitis, bacteremia, soft tissue infections, surgical site infections, peritonitis, endocarditis, catheter-related infections, and urinary tract infections. These infections mostly occur in critically-ill patients. One of the most striking features of Acinetobacter spp. is their extraordinary ability to develop multiple resistance mechanisms against several major antibiotic classes. The precise mechanisms that explain how multiple-drug resistance occurs are not fully known. However, recent studies have shown that MDR Acinetobacter can produce a great diversity of chromosomal and plasmid-mediated enzymes. Acinetobacter spp. can produce aminoglycosidemodifying enzymes to neutralize aminoglycosides and thus become resistant to this class of antimicrobial agents. β-lactamases are another type of modifying enzymes that give them potential to become resistant to penicillins, cephalosporins, and carbapenems. 29 More interestingly, they can also diminish uptake of antibiotics into their cells by either changes in the outer membrane porins to decrease permeability to the agents or by creating active antimicrobial efflux systems. Furthermore, Acinetobacter can alter the target protein to prevent the antibiotics from reaching their target, and thus becomes resistant. Examples of target modification include mutational changes of topoisomerase IV gene contributing to quinolone-resistance, and altered penicillin-binding proteins causing penicillin resistance. EPIDEMIOLOGY Two decades ago, Acinetobacter infections were rare. According to the data from the United States National Nosocomial Infection Surveillance (NNIS) System, nosocomial infections caused by Acinetobacter spp. were ranked in the tenth position in 1988. Since then, the incidence of Acinetobacter infections Vol. 22 No. 2 Acinetobacter infection in the Intensive Care Unit:Rungruanghiranya S, et al. Figure 1. Acinetobacter calcoaceticus-baumannii complex isolated from clinical specimens. (A) blood cultures from a patient with chronic lymphocytic leukemia grew Acinetobacter calcoaceticus-baumannii as dome-shaped, non-pigmented, smooth-surfaced colonies on blood agar. (B) a highpower view of gram stain showing encapsulated, gram-negative coccobacilli, consistent with Acinetobacter spp. (Courtesy of Salinee Phansuwan, B.Sc. (MT), Division of Laboratory Medicine, Praram 9 Hospital, Bangkok, Thailand) 1A