Daryl D. DePestel

Evaluation of Hospital Room Assignment and Acquisition of Clostridium difficile Infection

BACKGROUND AND OBJECTIVE Clostridium difficile spores persist in hospital environments for an extended period. We evaluated whether admission to a room previously occupied by a patient with C. difficile infection (CDI) increased the risk of acquiring CDI. DESIGN Retrospective cohort study. SETTING Medical intensive care unit (ICU) at a tertiary care hospital. METHODS Patients admitted from January 1, 2005, through June 30, 2006, were evaluated for a diagnosis of CDI 48 hours after ICU admission and within 30 days after ICU discharge. Medical, ICU, and pharmacy records were reviewed for other CDI risk factors. Admitted patients who did develop CDI were compared with admitted patients who did not. RESULTS Among 1,844 patients admitted to the ICU, 134 CDI cases were identified. After exclusions, 1,770 admitted patients remained for analysis. Of the patients who acquired CDI after admission to the ICU, 4.6% had a prior occupant without CDI, whereas 11.0% had a prior occupant with CDI (P = .002). The effect of room on CDI acquisition remained a significant risk factor (P = .008) when Kaplan-Meier curves were used. The prior occupants CDI status remained significant (p = .01; hazard ratio, 2.35) when controlling for the current patients age, Acute Physiology and Chronic Health Evaluation III score, exposure to proton pump inhibitors, and antibiotic use. CONCLUSIONS A prior room occupant with CDI is a significant risk factor for CDI acquisition, independent of established CDI risk factors. These findings have implications for room placement and hospital design.

Incidence of Carbapenem-Associated Allergic-Type Reactions among Patients with versus Patients without a Reported Penicillin Allergy

This retrospective analysis sought to determine the comparative incidence of cross-reactivity associated with carbapenem antibiotic treatment among patients with versus those without penicillin allergy. We sought to determine whether the incidence of cross-reactivity is different between imipenem-cilastatin and meropenem. A total of 211 patients were treated with a carbapenem antibiotic. Included were 100 patients with and 111 patients without a documented or reported penicillin allergy. Within each group, subgroups of penicillin-allergic and penicillin-nonallergic patients were balanced equally between imipenem-cilastatin and meropenem. The incidence of patients with a reported or documented penicillin allergy experiencing an allergic-type reaction to a carbapenem was 11%, which is 5.2 times greater than the risk in patients who were reportedly not allergic to penicillin (P=.024). No difference in the occurrence of allergic-type reactions was observed between the 2 carbapenems.

Daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis.

Objective:To investigate daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis to develop dosing recommendations. Design:Prospective, open-label pharmacokinetic study. Setting:Intensive care units located within a teaching medical center. Patients:Eight adults with known/suspected Gram-positive infections receiving continuous venovenous hemodialysis and daptomycin. Interventions:Daptomycin at 8 mg/kg intravenously over 30 mins. Serial blood and effluent samples were collected over the next 48 hrs. Daptomycin protein binding was determined by equilibrium dialysis. Daptomycin continuous venovenous hemodialysis transmembrane clearance was determined by dividing daptomycin effluent by serum concentrations and multiplying by mean effluent production rate for each subject. Equations describing a two-compartment, open-pharmacokinetic model were fitted to each subjects daptomycin concentration-time data and pharmacokinetic parameters were determined by standard methods. Serum concentration-time profiles were simulated for two daptomycin regimens (8 mg/kg every 48 hrs and 4 mg/kg every 24 hrs). Measurements and Main results:A total of 7.7 ± 0.6 mg/kg (mean ± sd) of daptomycin was administered, resulting in an observed peak concentration of 81.2 ± 19.0 &mgr;g/mL. Daptomycin steady-state volume of distribution (0.23 ± 0.14 L/kg) and free fraction (17.5% ± 5.0%) were increased in critically ill subjects receiving continuous venovenous hemodialysis compared with previous values reported in healthy volunteers. Daptomycin transmembrane clearance (6.3 ± 2.9 mL/min) accounted for more than half of total clearance (11.3 ± 4.7 mL/min). Simulations demonstrated 8 mg/kg daptomycin every 48 hrs would result in higher peak (88.8 ± 20.0 &mgr;g/mL vs. 53.0 ± 12.3 &mgr;g/mL) and lower trough concentrations (7.2 ± 5.2 &mgr;g/mL vs. 12.3 ± 5.1 &mgr;g/mL) than 4 mg/kg every 24 hrs. Conclusions:Daptomycin at 8 mg/kg every 48 hrs in critically ill patients receiving continuous venovenous hemodialysis resulted in good drug exposure, achieved high peak concentrations to maximize daptomycins concentration-dependent activity, and resulted in trough concentration that would minimize the risk of myopathy. ClinicalTrials.gov Identifier:NCT00663403.

Impact of mecA Gene Testing and Intervention by Infectious Disease Clinical Pharmacists on Time to Optimal Antimicrobial Therapy for Staphylococcus aureus Bacteremia at a University Hospital

ABSTRACT In patients with Staphylococcus aureus bacteremia, intervention by infectious disease clinical pharmacists on the basis of the results of tests for mecA resulted in a 25.4-h reduction in the time to optimal antimicrobial therapy, from 64.7 ± 36.8 to 39.3 ± 15.5 h (P = 0.002), which may result in decreased mortality.

Managing antimicrobial resistance in intensive care units.

The challenges in managing patients with infection in the intensive care unit are increased in an era where there are dwindling antimicrobial choices for multidrug-resistant pathogens. Clinicians in the intensive care unit must balance between choosing appropriate antimicrobial treatment for patients with suspected infection and utilizing antimicrobials in a judicious fashion. Improving antimicrobial utilization is a critical component to reducing antimicrobial resistance. Although providing effective antimicrobial therapy and improving antimicrobial utilization may seem to be competing goals, there are effective strategies to accomplish both. Antimicrobial stewardship programs provide an organized way to implement these strategies and can enhance the intensive care unit physicians success in improving patient outcomes and combating antimicrobial resistance in the intensive care unit.

Dalbavancin: A New Option for the Treatment of Gram-Positive Infections

Objective: To review the pharmacology, microbiology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of dalbavancin, a new semisynthetic lipoglycopeptide. Data Sources: A MEDLINE search, restricted to the English language, was conducted from 1966 through January 2006. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society of Microbiology, and the Infectious Diseases Society of America from 2000 to 2005 and information available from the manufacturers Web site. Study Selection and Data Extraction: In vitro and preclinical studies, as well as Phase I, II, and III clinical trials, were evaluated to summarize the microbiology, pharmacology, clinical efficacy, and safety of dalbavancin. All published trials and abstracts citing dalbavancin were selected. Data Synthesis: Dalbavancin, a novel lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has in vitro activity against a variety of gram-positive organisms, but no activity against gram-negative or vancomycin-resistant enterococci that possess VanA gene. Due to its prolonged half-life (6–10 days), dalbavancin can be administered intravenously once weekly. In Phase II and III clinical trials, dalbavancin was effective and well tolerated for the treatment of skin and soft-tissue infections, catheter-related bloodstream infections, and skin and skin-structure infections. To date, adverse events are mild and limited; the most common include pyrexia, headache, nausea, oral candidiasis, diarrhea, and constipation. Conclusions: Dalbavancin appears to be a promising antimicrobial agent for the treatment of gram-positive infections. A new drug application was filed with the Food and Drug Administration (FDA) in December 2004. The FDA issued an approvable letter in 2005 for dalbavancin. If approved, dalbavancin is expected to be launched in the first quarter of 2006.

The effect of an antimicrobial restriction program on Pseudomonas aeruginosa resistance to β-lactams in a large teaching hospital

Study Objectives. To compare the use of β‐lactams and subsequent Pseudomonas aeruginosa sensitivity patterns before and after implementation of a clinical pharmacist‐facilitated antimicrobial restriction program in August 1997.

Pharmacoeconomic Analysis of Liposomal Amphotericin B versus Voriconazole for Empirical Treatment of Febrile Neutropenia

AbstractBackground: Liposomal amphotericin B (LAmB) has demonstrated similar efficacy to conventional amphotericin B for antifungal treatment in patients with febrile neutropenia; however, it is not without toxicities and is associated with a high acquisition cost. Despite this high cost, LAmB has been shown to have a pharmacoeconomic advantage over less expensive agents. Voriconazole is a potential alternative for empirical antifungal treatment of febrile neutropenia. The objective of this study was to assess the economic outcomes of voriconazole versus LAmB in patients with fever and neutropenia. Methods: A decision analytical model was developed from a hospital perspective based on a 2-year (2002–2003) review of outcomes and prescribing practices in febrile neutropenic patients at a tertiary care medical centre. Literature reports and expert opinion were used to further populate the model. Sensitivity analyses and Monte Carlo simulation enhanced the robustness of the model through variation of all probabilities and costs that populated the model. Results: Sixty-three cases were evaluated in the retrospective review. Thirty-two were initially given voriconazole and 31 were given LAmB. Patient demographic data were similar in each group. In the base case, patients initially given voriconazole displayed a 27% reduction in overall treatment cost over patients initially given LAmB (

Concurrent administration of sirolimus and voriconazole: a pilot study assessing safety and approaches to appropriate management.

US14 950 vs

Ertapenem clearance during modeled continuous renal replacement therapy

US20 591). Sensitivity analysis determined that the cost advantage in the voriconazole arm was maintained over a wide range of costs and probabilities. Variance in the cost of nephrotoxicity and medication cost did not significantly alter results. Monte Carlo simulation determined the voriconazole arm to be the optimal path in 65% of cases. Conclusion: The decision model indicated that use of voriconazole as the preferred antifungal agent in adult haematology patients with febrile neutropenia should result in lower overall treatment costs relative to LAmB.