Acinetobacter baumannii: An Emerging Multidrug-resistant Threat

Thomas D Gootz; Andrea Marra

Disclosures

Expert Rev Anti Infect Ther. 2008;6(3):309-325. 

In This Article

Therapeutic Approaches for MDR

Few new antibiotics have become available to treat MDR acinetobacters. An excellent review includes a summary table of doses and clinical results information regarding many of the older antimicrobials that have been used to treat serious infections with A. baumannii.[141]in vitro, the carbapenems remain the most active of the broad-spectrum antimicrobials against this group. Doripenem is a new carbapenem that is administered three-times daily by standard infusion; however, it is not clear whether this agent has any significant potency advantage over other agents in this class. A new filing has occurred for hospital-acquired pneumonia, with doripenem administered as a prolonged infusion. It will be interesting to see if this mode of administration improves efficacy against MDR strains. Combinations of imipenem and amikacin have been tested, both clinically and in experimental models of infection, in an attempt to identify dosing regimens that could optimize efficacy.[142] Other combinations have been evaluated clinically, including cefepime plus amikacin, as well as polymyxin B with a carbapenem, aminoglycoside, fluoroquinolone or another ß-lactam.[143]In vitro synergy against acinetobacters has been observed with polymyxins and imipenem, rifampin or azithromycin.[144] The new agent tigecycline appeared to be a promising antibiotic for A. baumannii; however, its relatively low blood levels achieved at the doses administered, coupled with the potential for rapid development of efflux-mediated resistance as described in the review, has limited initial enthusiasm regarding this drug.[145]

Older agents have also been tested clinically against MDR A. baumannii infections, including colistin[146] and sulbactam.[147,148] Efficacy of colistin for MDR strains varies widely.[146] Mutation to colistin resistance during therapy observed with other species,[149] as well as in vitro colistin- or polymyxin-dependence, has been documented.[150] Interestingly, sulbactam has surprising affinities for some PBPs of A. baumannii (primarily PBP2), resulting in growth inhibition and, in some cases, a bactericidal effect, producing MICs in the range of 1-4 µg/ml.[8,151] Sulbactam, which is difficult to obtain as a single agent, has been tested in several clinical trials against MDR A. baumannii with reasonable results; yet, the potency of this agent probably limits its use in treating infections with this organism.

Cationic detergents, such as polymyxin B, are finding renewed roles in the chemotherapy of MDR A. baumannii infections as a result of the failure of many other agents. More recent clinical studies with polymyxin B suggest that careful monitoring of dose administration can lead to a reduced observation of neurotoxicity; however, the incidence of nephrotoxicity can be up to 36%.[152]

Clearly, there is an absence of new antibiotics for use with MDR acinetobacters. Supportive methods to address this problem include aggressive methods of infection control in the hospital in order to limit colonization of patients,[153] including strict contact isolation procedures, as well as using methods such as quantitative culture techniques to help distinguish patient colonization from infection in clinical cases of ventilator-associated pneumonia.[154] Clearly, increased diligence needs to be paid to the incorporation of modern surveillance techniques, including PCR probing of acinetobacters, in order to identify specific antibiotic-resistance genes that can transfer multidrug resistance in the hospital setting.

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