This discussion will center upon the problem of antibiotic resistance (multidrug resistance, MDR) in A. baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Here we will summarize the rapidly expanding knowledge of resistance determinants in these problematic Gram negative pathogens and review available treatment options.
MDR A. baumannii are among the most resistant pathogens encounter the hospital environment. Resistance to beta-lactams is mediated by beta-lactamases (AmpC -type), efflux pumps, alterations in penicillin binding proteins, and changes in outer membrane proteins. Of these mechanisms, the primary concern is the presence of carbapenemases (OXA, MBL). Resistance to aminoglycosides is usually mediated by specific aminoglycoside modifying enzymes, efflux pumps, or by specific ribosomal methylases. Quinolone resistance arises by mutations in the gyrase enzymes or by efflux pumps. Taken together, the melding of these genes on to a specific resistance island poses unique challenges. In the case of Pseudomonas, the number of efflux pumps vastly contributes to the overall resistance phenotype. In addition, loss of permeability and biofilm formation contributes significantly to resistance. In Klebsiellae, the emergence of carbapenemases (KPC)and plasmid mediated quinolone resistance significantly adds to the MDR phenoytpe.
Novel agents such as doripenem and tigecycline are offered as alternatives to current antibiotics, but these are limited. The clinician now resorts to the use of colistin, rifampin and azithromycin as novel therapies. Novel combinations may offer hope in seriously ill patients . The future of effective therapy against MDR pathogens remains elusive.