Impact of changing pathogens and antimicrobial susceptibility patterns in the treatment of serious infections in hospitalized patients.
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.
Jones
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RN
Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects / Q000472:pathogenicity*; D001424:Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000382:microbiology*; D003428:Cross Infection / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000382:microbiology*; D004352:Drug Resistance, Microbial; D006801:Humans; D015995:Prevalence; D014481:United States / Q000453:epidemiology
D000900:Anti-Bacterial Agents