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JOURNAL ARTICLE
REVIEW
Impact of changing pathogens and antimicrobial susceptibility patterns in the treatment of serious infections in hospitalized patients.
American Journal of Medicine 1996 June 25
The selection of drug-resistant pathogens in hospitalized patients with serious infections such as pneumonia, urinary tract infections (UTI), skin and skin-structure infections, and primary or secondary bacteremia has generally been ascribed to the widespread use of antimicrobial agents. Issues of concern regarding gram-negative bacilli include the expression of extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumonias and constitutive resistance in some Enterobacteriaceae caused by Bush group 1 beta-lactamases. Current concerns with gram-positive pathogens are increasing multidrug resistance in methicillin-resistant Staphylococcus aureus, enterococci, and coagulase-negative staphylococci, and increasing incidence of penicillin-resistant Streptococcus pneumoniae. Contemporary treatment strategies for pneumonia in hospitalized patients mandate early empiric therapy for the most likely gram-positive and gram-negative pathogens. Newer beta-lactams, such as fourth-generation cephalosporins, may be useful in the treatment of pneumonia, including those cases associated with bacteremia. Combination beta-lactam/beta-lactamase inhibitor drugs, an aminoglycoside co-drug, or a carbapenem may also be indicated. The initial treatment of UTI in the hospital setting also may be empirically treated with the newer cephalosporins, combination broad-spectrum penicillins plus an aminoglycoside, a quinolone, or a carbapenem. Current problems in treating UTI include the emergence of extended spectrum beta-lactamase-producing Escherichia coli, the tendency of fluoroquinolones both to select for resistant strains of major UTI pathogens and to induce cross-resistance among different drug classes, and beta-lactam and vancomycin resistance of enterococci and coagulase-negative staphylococci. Treatment of skin and skin-structure infections is complicated by the coexistence of gram-positive and gram-negative infections, which may be drug resistant. Both fourth-generation beta-lactams and carbapenems may have in vitro activity against these pathogens; however, where these drugs--with their increased spectra and lower affinity for beta-lactamases and less susceptibility to beta-lactamase hydrolysis--fit into the therapeutic armamentarium remains to be determined. Initial clinical studies appear to be promising, nonetheless. The ability of both nosocomial and community-acquired pathogens to develop resistance to powerful broad-spectrum agents presents a great challenge for prescribing patterns and in the development of new drugs to be relatively resistant to inactivation.
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