Resistance in nonfermenting gram-negative bacteria: Multidrug resistance to the maximum

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Nonfermenting gram-negative bacteria pose a particular difficulty for the healthcare community because they represent the problem of multidrug resistance to the maximum. Important members of the group in the United States include Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia. These organisms are niche pathogens that primarily cause opportunistic healthcare-associated infections in patients who are critically ill or immunocompromised. Multidrug resistance is common and increasing among gram-negative nonfermenters, and a number of strains have now been identified that exhibit resistance to essentially all commonly used antibiotics, including antipseudomonal penicillins and cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, trimethoprim-sulfamethoxazole, and carbapenems. Polymyxins are the remaining antibiotic drug class with fairly consistent activity against multidrug-resistant strains of P aeruginosa, Acinetobacter spp, and S maltophilia. However, most multidrug-resistant B cepacia are not susceptible to polymyxins, and systemic polymyxins carry the risk of nephrotoxicity for all patients treated with these agents, the elderly in particular. A variety of resistance mechanisms have been identified in P aeruginosa and other gram-negative nonfermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target-site alterations. Multiple resistance genes frequently coexist in the same organism. Multidrug resistance in gram-negative nonfermenters makes treatment of infections caused by these pathogens both difficult and expensive. Improved methods for susceptibility testing are needed when dealing with these organisms, including emerging strains expressing metallo-β-lactamases. Improved antibiotic stewardship and infection-control measures will be needed to prevent or slow the emergence and spread of multidrug-resistant, nonfermenting gram-negative bacilli in the healthcare setting.

Section snippets

Resistance prevalence in nonfermenting gram-negative bacteria

As mentioned above, members of the nonfermenting gram-negative bacteria often use several different mechanisms of resistance, including the production of enzymes, alterations in target sites, production of efflux pumps, and loss of outer membrane proteins or porins. Thus, multidrug resistance is common among these organisms, often severely limiting the therapeutic options available to treat infections caused by them. Nonsusceptibility of gram-negative nonfermenters is typically due to both

Challenges posed by gram-negative nonfermenters

The high proportion of nonfermenting gram-negative bacteria exhibiting multidrug resistance in the United States, and the increasing number among these that possess resistance to virtually all commonly used agents, pose a number of challenges in managing patients with infections caused by these pathogens. The resistance patterns of these bacteria not only negatively impact health and economic outcomes, but also create difficulties for diagnostic testing and controlling the further emergence and

Summary

Gram-negative nonfermenting bacilli are common healthcare-associated pathogens that have multiple resistance mechanisms. In fact, some of these strains are resistant to all or almost all of our currently available drugs. Multidrug resistance makes treatment of these organisms difficult and expensive, and methods for susceptibility testing need to be improved in this area. In the past, new antimicrobials were developed and served as a defense against newly resistant organisms. For a variety of

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