Marin H. Kollef

Prolonged Infusion Antibiotics for Suspected Gram-Negative Infections in the ICU: A Before-After Study

BACKGROUND: β-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results. OBJECTIVE: To determine whether prolonged infusion of β-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection. METHODS: We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011). RESULTS: A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329). CONCLUSIONS: Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Appropriate antibiotic therapy for ventilator-associated pneumonia and sepsis: a necessity, not an issue for debate.

3 (p<0.001), age over 64 years (p<0.01), time to onset of pneumonia longer than 3 days (p<0.01), mottling (p<0.05), and hypotension (p<0.05). Among the 322 microbiologically confirmed cases of POP only those with ASA grade greater than 3, time to onset of pneumonia longer than 3 days, and hypotension remained independently associated with mortality. Based on these data the authors conclude that the importance of initial appropriate antibiotic therapy for POP is a matter of debate. However, it is important to recognize that this investigation may have missed a statistically significant relationship between the appropriateness of initial antibiotic therapy and mortality for this patient population. The conclusions of this study are also contrary to those of several other investigations associating the appropriateness of antimicrobial therapy for patients with severe infections and clinical outcome. Dupont et al. examined a population of surgical patients. It is possible that the influence of appropriate antibiotic therapy is more important in nonsurgical patients or medical patients. Timely evaluation of pulmonary infiltrates and the administra

Critical Care Infectious Diseases Textbook

The selection of antimicrobial agents in the hospital setting is still a largely manual task and, therefore, fraught with the potential for error. This includes the choice of agents, dosage regimens, and monitoring for response and toxicity. The authors describe current and future strategies to use information technology to improve the process of antimicrobial selection, avoid dosing errors and contraindicated drug

The Resuscitation Package in Sepsis

Sepsis and its attendant complications are commonly encountered in the intensive care unit. Early recognition of sepsis is critical because it allows for rapid deployment of a multifaceted resuscitation package. The cornerstones of sepsis management are antibiotic therapy, source control, and hemodynamic resuscitation. In select patients, ancillary therapies are indicated, such as activated protein C, corticosteroids, and glycemic control. Given the complexity of sepsis management, optimal care can be delivered as a bundle—a protocol encompassing the above interventions. The evidence behind the various components of sepsis management are reviewed here.

High levels of C-reactive protein and positive troponin T test results predicted 14-day mortality in unstable angina or non-Q-wave MI

Source Citation Morrow DA, Rifai N, Antman EM,et al. C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11...