Abstract
The treatment of patients with serious Gram-negative infections must be both prompt and correct. Numerous studies have demonstrated that mortality risk is significantly increased when the initial antibiotic regimen does not adequately cover the infecting pathogen. Furthermore, changing to an appropriate regimen once culture results are available does not reduce this risk. Therefore, one must empirically treat serious infections with a regimen that covers likely pathogens. Selecting such a regimen is complicated by the increasing prevalence of resistance to commonly used antibiotics. Moreover, multidrug-resistant pathogens, once limited to hospital-acquired infections, are increasingly being detected in community-acquired infections, especially those involving the urinary and gastrointestinal tracts or in immunocompromised patients. Consequently, the initial antibiotic regimen must have a broad spectrum of activity that includes potential resistant pathogens, as indicated by the local antibiogram. Many multidrug-resistant pathogens remain susceptible to carbapenems despite increasing worldwide antibiotic resistance. This article reviews the role played by carbapenems in the initial treatment of serious Gram-negative infections and the potential effect of emerging resistance on this role.
Highlights
Appropriate antibiotic therapy for any given circumstance requires consideration of three factors: the pathogen, the timing, and the patient, including the site of infection
Multicenter evaluation [2], 19% of Klebsiella pneumoniae bacteremias were caused by organisms that produced extended-spectrum β-lactamase (ESBL)
In one evaluation [11], 73% of patients with ventilatorassociated pneumonia (VAP) received an initial empiric antibiotic regimen that was inappropriate for their infection based on subsequent culture results. This inappropriate antibiotic selection was a significant and independent risk factor for in-hospital mortality. In another evaluation of patients with VAP [5], inappropriate initial antibiotic therapy was associated with a 2.4-fold increase in mortality risk (95% confidence interval 1.5-fold to 5.0-fold)
Summary
Appropriate antibiotic therapy for any given circumstance requires consideration of three factors: the pathogen, the timing, and the patient, including the site of infection. In another evaluation of patients with VAP [5], inappropriate initial antibiotic therapy was associated with a 2.4-fold increase in mortality risk (95% confidence interval 1.5-fold to 5.0-fold). Shown is the mortality risk associated with adequate versus inadequate initial antibiotic therapy in patients with ICU-acquired pneumonia [3] or VAP [4,5,6].
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