TREATMENT Acinetobacter Infection (Table 59-1)
Treatment is hampered by the remarkable ability of A. baumannii to upregulate or acquire antibiotic resistance determinants. The most prominent example is that of β-lactamases, including those capable of inactivating carbapenems, cephalosporins, and penicillins. These enzymes, which include the OXA-type β-lactamases (e.g., OXA-23), the metallo-β-lactamases (e.g., NDM), and rarely KPC-type carbapenemases, are typically resistant to currently available β-lactamase inhibitors such as clavulanate or tazobactam. Plasmids that harbor genes encoding these β-lactamases may also harbor genes encoding resistance to aminoglycosides and sulfur antibiotics. The end result is that carbapenem-resistant A. baumannii may become truly multidrug resistant.
Selection of empirical antibiotic therapy when A. baumannii is suspected is challenging and must rely on a knowledge of local epidemiology. Receipt of prompt, effective antibiotic therapy is the goal. Given the diversity of resistance mechanisms in A. baumannii, definitive therapy should be based on the results of antimicrobial susceptibility testing. Carbapenems (imipenem, meropenem, and doripenem but not ertapenem) have long been thought of as the agents of choice for serious A. baumannii infections. However, the clinical utility of carbapenems is now widely jeopardized by the production of carbapenemases, as described above. Sulbactam may be an alternative to carbapenems. Unlike other β-lactamase inhibitors (e.g., clavulanic acid and tazobactam), sulbactam has intrinsic activity against Acinetobacter; this activity is mediated by the drug’s binding to penicillin-binding protein 2 rather than by its ability to inhibit β-lactamases. Sulbactam is commercially available in a combined formulation with either ampicillin or cefoperazone and may also be available as a single agent in some countries. Despite the absence of randomized clinical trials, sulbactam seems to be equivalent to carbapenems in clinical effectiveness against susceptible strains.
Therapy for carbapenem-resistant A. baumannii is particularly problematic. The only currently available choices are polymyxins (colistin and polymyxin B) and tigecycline. Neither option is perfect. Polymyxins may be nephrotoxic and neurotoxic. Definition of the optimal dose and schedule for administration of polymyxins to patients in vulnerable groups (e.g., those requiring renal replacement therapy) remains challenging, and emergence of resistance in association with monotherapy is a concern. Conventional doses of tigecycline may not result in serum concentrations adequate to treat bloodstream infections. Resistance of A. baumannii to tigecycline may develop during treatment with this drug.
As a consequence of these issues with the polymyxins and tigecycline, combination therapy is now favored for carbapenem-resistant Acinetobacter. However, in a randomized controlled trial, 30-day mortality was not reduced by the addition of rifampin to colistin. Nevertheless, a significant increase in microbiologic eradication was observed in the colistin plus rifampin arm over that attained with colistin alone. Combinations of polymyxins with a carbapenem look more promising and are being evaluated in prospective clinical trials. Fosfomycin has poor activity against Acinetobacter and should not be relied upon for treatment. Clearly, new treatment options are needed for serious Acinetobacter infections.