title: Impact of antibiotic resistance on the treatment of sepsis.
abstract: Antibiotics are essential to the treatment of bacterial sepsis as they reduce the bacterial burden. The impact of bacterial resistance has recently been studied and found to be important in a range of conditions. Resistance to antibiotics can be defined genotypically, phenotypically and clinically through pharmacokinetic/pharmacodynamic studies and their correlations with clinical outcomes. Although the kinetics of antibiotics has been shown to be favourably altered in sepsis, a range of studies in sepsis has revealed that for most pathogens resistance contributes to significant increases in mortality. This has been clearly demonstrated in bacteraemia, including community- and hospital-acquired infection, and with bacteraemia caused by vancomycin-resistant enterococci, methicillin-resistant staphylococci and extended-spectrum producing Gram-negative bacteria. Significant mortality increases have also been seen with ventilator-associated pneumonia and serious infections requiring admission to intensive care. Gentotypic and phenotypic resistance in coagulase-negative staphylococci causing bacteraemia, and in invasive pneumococcal disease has not shown differences in mortality. In the latter case, dosage regimens have to date been adequate to overcome laboratory-defined resistance. Early indications are that de-escalating therapy from broad-spectrum initial coverage after results of cultures and susceptibility tests become available does not jeopardize outcomes, and further prospective studies are warranted. There is now convincing evidence that broad-spectrum initial therapy to cover the likely pathogens and their resistances pending culture results is mandatory in sepsis to minimize adverse outcomes.
authors: Women's and Children's Hospital, North Adelaide, South Australia, Australia. turnidgej@wch.sa.gov.au
authors: John
authors: J
authors: Turnidge
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D004351:Drug Resistance; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents