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 β-lactamase-producing Escherichia coli and Klebsiella pneumoniae and constitutive resistance in some Enterobacteriaceae caused by Bush group 1 β-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 β-lactams, such as fourth-generation cephalosporins, may be useful in the treatment of pneumonia, including those cases associated with bacteremia. Combination β-lactam/β-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 β-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 β-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 β-lactams and carbapenems may have in vitro activity against these pathogens; however, where these drugs—with their increased spectra and lower affinity for β-lactamases and less susceptibility to β-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.