Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
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Increasing drug resistance rates among gram-negative pathogens that frequently cause ventilator-associated pneumonia have resulted in increased hospital mortality, longer hospital stays, and higher inpatient health care costs. There is an urgent need for effective therapies that lessen the clinical and economic consequences of this nosocomial infection. ⋯ In addition, the duration of intensive care unit stay tended to be shorter for patients who received doripenem. The reduced medical resource use achieved with use of doripenem for treatment of ventilator-associated pneumonia may provide not only clinical benefits to patients but also economic benefits to hospitals and health care systems.
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Carbapenems remain a mainstay for the empirical treatment of serious nosocomial infection. Although the tolerance and safety profile of the carbapenems as a class is favorable, the primary safety concern is the potential for treatment-emergent seizures. ⋯ Safety data were available from 1817 patients who received doripenem and 1325 patients who received 1 of 4 active comparator drugs as part of this development program. Overall, intravenous doripenem was found to be safe and well tolerated, demonstrating a safety profile comparable to that of comparator agents and a limited propensity to induce seizures, including when administered via 1-h or 4-h infusion. j.
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Data suggest that higher doses of vancomycin can increase the risk of nephrotoxicity. No study has been undertaken to determine the pharmacodynamic index (ie, the area under the curve [AUC] or the trough value) that best describes the relationship between vancomycin exposure and onset of nephrotoxicity. ⋯ The results indicate that a vancomycin exposure-toxicity response relationship exists. The vancomycin trough value is the pharmacodynamic index that best describes this association.
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We assessed the kinetics of the humoral immune response to pertussis antigens following vaccination of health care personnel with adult tetanus-diphtheria-acellular pertussis vaccine (Tdap). By 2 weeks after vaccination, 88%-94% of subjects demonstrated a booster response. This brisk response of adults to Tdap supports a role for vaccination in pertussis outbreak control.
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Gram-negative bacterial pathogens are a common cause of infection, and the prevalence and rates of resistance among these pathogens to existing antimicrobial agents are increasing. beta-Lactamase-mediated resistance is of particular concern. High-level resistance attributable to beta-lactamase expression alone or in combination with other mechanisms is becoming increasingly prevalent among Enterobacteriaceae and gram-negative nonfermenting organisms. ⋯ Its activity against Pseudomonas aeruginosa exceeds that of other carbapenems, and it has equivalent activity against Acinetobacter species and most Enterobacteriaceae. Thus, doripenem may be valuable alone or in combination with other agents in the treatment of serious gram-negative infections.