Infections with bacteria of the genus Acinetobacter have become a significant problem worldwide. Acinetobacter baumannii is particularly formidable because of its propensity to acquire antibiotic resistance determinants. Outbreaks of infection caused by strains of A. baumannii resistant to multiple antibiotic classes, including carbapenems, are a serious concern in many specialized hospital units, including intensive care units (ICUs). The foremost implication of infection with carbapenem-resistant A. baumannii is the need to use “last-line” antibiotics such as colistin, polymyxin B, or tigecycline; these options have the potential to render these bacteria resistant to all available antibiotics.
Acinetobacter species are oxidase-negative, nonmotile, nonfermenting, short gram-negative bacilli that grow well at 37° C in aerobic conditions on a range of laboratory media (e.g., blood agar). Some species may not grow on MacConkey agar. Differentiation of Acinetobacter species is difficult with the means typically available to most clinical microbiology laboratories, including commercial semiautomated identification systems. DNA-DNA hybridization is a method used for speciation in reference laboratories. Identification of the most clinically relevant species, A. baumannii, by detection of the blaOXA-51-like carbapenemase gene intrinsic to this species has been described.
Widely distributed in nature, Acinetobacter species can be found in water, in soil, and on vegetables. Acinetobacter is a component of the human skin flora and is sometimes identified as a contaminant in blood samples collected for culture. Fecal carriage can be detected in both healthy and hospitalized individuals. Despite the ubiquity of some Acinetobacter species, the natural habitat of A. baumannii remains to be fully defined.
A. baumannii infections have been diagnosed in patients on all inhabited continents. The vast majority of infections occur in hospitalized patients and other patients with significant health care contact. Outbreaks of carbapenem-resistant A. baumannii are particularly problematic. A significant issue is the introduction of carbapenem-resistant A. baumannii into hospitals as a result of medical transfers, especially from hospitals where the organism is highly endemic.
In 1991 and 1992, outbreaks of carbapenem-resistant A. baumannii infection occurred in a hospital in New York City. Subsequently, numerous other hospitals in the United States and South America have had outbreaks of carbapenem-resistant A. baumannii. The incidence of infections with A. baumannii among military personnel from the United States and Canada has increased since 2002; 102 patients had bloodstream infections at facilities treating U.S. military personnel injured in Iraq or Afghanistan from January 1, 2002, through August 31, 2004. An epidemiologic investigation revealed that A. baumannii could be grown from environmental sites in field hospitals and that the environmental strains were closely related genotypically to clinical isolates. A. baumannii strains from injured military personnel from the United States and the United Kingdom were also genotypically related; this finding provided further evidence that A. baumannii was being acquired in field hospitals.
A. baumannii infections have posed a substantial clinical challenge in many parts of Europe since the early 1980s. Three clones (European clones I, II, and III) have been the predominant causes of A. baumannii infection in hospitals in Europe. Carbapenem resistance in A. baumannii is a significant issue in many European countries, most notably the United Kingdom, Greece, Italy, Spain, and Turkey.
Asia, Australia, the Middle East, and Africa
Although surveillance data are sparse from many countries in these regions, problems with carbapenem-resistant A. baumannii abound. Community-acquired infections are well described in northern Australia and some parts of Asia. These infections may be more likely in men >45 years of age who have histories of cigarette smoking, alcoholism, diabetes mellitus, or chronic obstructive airway disease. Community-acquired strains are more susceptible to antimicrobial agents than are hospital-acquired strains.
A. baumannii colonizes patients exposed to heavily contaminated hospital environments or to the hands of health care workers in these locations. Colonization of the upper airways in mechanically ventilated patients may lead to nosocomial pneumonia. Colonization of the skin may lead to central line–associated bloodstream infection, catheter-associated urinary tract infection (UTI), wound infection, or postneurosurgical meningitis. Throat carriage and microaspiration may be involved in the pathogenesis of community-acquired pneumonia due to A. baumannii.
Much less is known about the virulence mechanisms of and host responses to A. baumannii than about these aspects of other pathogenic gram-negative bacteria. Because of the emergence of multidrug-resistant strains, including those resistant to all available antibiotics, the impetus to study A. baumannii pathogenesis has grown. Novel targets for antibacterial drug development are desperately required, and drugs that have antivirulence mechanisms may provide new therapeutic options. Specific virulence mechanisms in A. baumannii include iron acquisition and transport systems; outer-membrane protein A (OmpA), which mediates mammalian cell adhesion, invasion, and cytotoxicity through mitochondrial damage and initiation of caspase-dependent apoptosis; lipopolysaccharide (LPS); and the ability to form biofilm on abiotic and biotic surfaces. Biofilm formation on abiotic surfaces is dependent on a pilus assembly system, which in turn is controlled by a traditional two-component regulatory system mediated by bfmR. Also important in biofilm formation are biofilm-associated protein; OmpA; the quorum-sensing gene abaI, which controls the secretion of 3-hydroxy-C12-homoserine lactone; and the pga locus, which is essential for the production of the polysaccharide poly-β-1,6-N-acetylglucosamine.
New model systems for the study of A. baumannii infection, including both nonmammalian (invertebrate) and mammalian models, have been described. Furthermore, the use of A. baumannii transposon-generated mutant libraries to screen for mutants with attenuated growth in human biological fluids (serum and ascites fluid) has allowed the identification of new virulence mechanisms. These include phospholipase D; capsule production mediated by ptk and epsA; penicillin-binding protein 7/8 encoded by the pbpG gene; and a glycosyltransferase important for LPS biosynthesis ...