Peggy S. McKinnon

Clinical Outcomes for Patients with Bacteremia Caused by Vancomycin-Resistant Enterococcus in a Level 1 Trauma Center

To assess the degree of morbidity and mortality attributable to vancomycin resistance in enterococcal bacteremia (EB), a matched case-control study was conducted. Patients with bacteremia due to vancomycin-resistant enterococcus (VRE) were matched to control patients with bacteremia due to vancomycin-susceptible enterococcus. During 1996--2000, 65 patients with cases of clinically significant VRE bacteremia were identified, and 53 of these patients were successfully matched. In this group of patients, VRE bacteremia was found to be an independent predictor of crude mortality (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.2--13.3) and the infection-related mortality rate (OR, 5.2; 95% CI, 1.4--20.0). It was also an independent predictor of the rate of clinical failure at day 7 after the onset of EB (OR, 4.6; 95% CI, 1.2--17.3) and overall clinical failure (OR, 4.3; 95% CI, 1.3--14.5) and was associated with a longer mean length of hospitalization after the onset of EB, compared with that for control patients (22.7plus minus1.88 vs. 15.9 +/- 1.7, P=.006). These observations indicate that vancomycin resistance in EB independently affects outcomes.

Pharmacokinetics and Pharmacodynamics of Cefepime in Patients with Various Degrees of Renal Function

ABSTRACT This study evaluated the pharmacokinetics of cefepime in 36 patients with different levels of renal function. Pharmacokinetic and pharmacodynamic parameters were calculated using samples obtained at steady state. Patients with creatinine clearance (CLCR) of >100 ml/min had more rapid clearance (CL) and a lower minimum concentration in serum (Cmin). Cmin in this group was found to be 3.3 ± 3.6 mg/liter (mean and standard deviation), compared to 19.5 ± 21.5 mg/liter in patients with a CLCR of between 60 and 100 ml/min (P = 0.025) and 14.0 ± 11.5 mg/liter in patients with a CLCR of <60 ml/min (P = 0.009). Patient data were also analyzed by the nonparametric expectation maximization method and Bayesian forecasting. The median volume of distribution in the central compartment was 27.08 liters. CL and CLCR were highly correlated (P = 0.00033) according to the equation CL= 0.324 liters/h + (0.0551 × CLCR). The median rate constants from the central compartment to the peripheral compartment and from the peripheral compartment to the central compartment were 12.58 and 41.09 h−1, respectively. The time-concentration profiles for 1,000 patients (CLCRs, 120, 60, and 30 ml/min) each receiving various dosing regimens were simulated by using Monte Carlo simulations. Standard dosing resulted in a Cmin that was greater than or equal to the MIC in more than 80% of the simulated profiles with MICs ≤2 mg/liter. Current dosing recommendations may be suboptimal for monotherapy of infections due to less susceptible pathogens (e.g., those for which MICs are ≥4 mg/liter), particularly when CLCR exceeds 120 ml/min.

Prediction model to identify patients with Staphylococcus aureus bacteremia at risk for methicillin resistance.

OBJECTIVES To identify institution-specific risk factors for MRSA bacteremia and develop an objective mechanism to estimate the probability of methicillin resistance in a given patient with Staphylococcus aureus bacteremia (SAB). DESIGN A cohort study was performed to identify institution-specific risk factors for MRSA. Logistic regression was used to model the likelihood of MRSA. A stepwise approach was employed to derive a parsimonious model. The MRSA prediction tool was developed from the final model. SETTING A 279-bed, level 1 trauma center. PATIENTS Between January 1, 1999, and June 30, 2001, 494 patients with clinically significant episodes of SAB were identified. RESULTS The MRSA rate was 45.5%. Of 18 characteristics included in the logistic regression, the only independent features for MRSA were prior antibiotic exposure (OR, 9.2; CI95, 4.8 to 17.9), hospital onset (OR, 3.0; CI95, 1.9 to 4.9), history of hospitalization (OR, 2.5; CI95, 1.5 to 3.8), and presence of decubitus ulcers (OR, 2.5; CI95, 1.2 to 4.9). The prediction tool was derived from the final model, which was shown to accurately reflect the actual MRSA distribution in the cohort. CONCLUSION Through multivariate modeling techniques, we were able to identify the most important determinants of MRSA at our institution and develop a tool to predict the probability of methicillin resistance in a patient with SAB. This knowledge can be used to guide empiric antibiotic selection. In the era of antibiotic resistance, such tools are essential to prevent indiscriminate antibiotic use and preserve the longevity of current antimicrobials.

Epidemiology, Resistance, and Outcomes of Acinetobacter baumannii Bacteremia Treated with Imipenem‐Cilastatin or Ampicillin‐Sulbactam

Study Objective. To evaluate epidemiology, resistance, and treatment outcomes of Acinetobacter baumannii bacteremia treated with imipenemcilastatin or ampicillin‐sulbactam for 72 hours or longer.

Pharmacoeconomic Considerations Associated with the Use of Intravenous-to-Oral Moxifloxacin for Community-Acquired Pneumonia

BACKGROUND Intravenous-to-oral (iv/po) conversion is one cost-effective approach to the management of community-acquired pneumonia (CAP). METHODS Consecutive patients with CAP were enrolled during 3 study periods (January-March of 2001, 2002, and 2004) with different pharmacy intervention (PI) strategies: iv beta -lactam plus a macrolide (no PI), iv beta-lactam plus a macrolide with iv/po PI (PI switch), and iv moxifloxacin with pharmacist-initiated automatic po moxifloxacin conversion (PI sequential). Costs and outcomes were compared among groups. RESULTS Two hundred fifty-one patients were enrolled. The average Fine score was 75, and the mean age of patients was 51 years. In the PI groups, the duration of treatment with iv antibiotics was decreased. Clinical success on day 3 of therapy was improved in the PI sequential group but was similar in all 3 groups on day 7 of therapy and at the end of therapy. The length of stay in the hospital was similar for patients in all 3 groups (mean, 4.39 days). Antibiotic costs were significantly reduced, by

Direct medical costs associated with using vancomycin in methicillin-resistant Staphylococcus aureus infections: an economic model.

110/patient, in the PI sequential group. CONCLUSIONS Conversion from iv to po therapy was accomplished more quickly when converting to the same agent with pharmacist-initiated automatic iv/po conversion, thus reducing the associated cost without compromising efficacy.

Bioavailability of gatifloxacin by gastric tube administration with and without concomitant enteral feeding in critically ill patients

SUMMARY Objectives: To quantify the direct medical costs associated with using vancomycin, as inpatient treatment, in methicillin-resistant Staphylococcus aureus infections, in four clinical indications: complicated skin and soft tissue infections (SSTI), bacteremia, infective endocarditis (IE), and hospital-acquired pneumonia (HAP). Research design and methods: A decision-analytic model was constructed to evaluate the cost of administering intravenous vancomycin. Cost inputs included hospitalization, drug procurement, materials, preparation and administration, renal function and drug monitoring, treating adverse events, and treatment failure. Probabilities and lengths of stay and treatment were obtained from the literature, an antimicrobial therapy database and clinical expert opinion. Univariate and multivariate sensitivity analyses were conducted to confirm the robustness of the baseline scenario. Main outcome measures: The cost of using vancomycin in the four indications, including and excluding hospital cost. Results: Whereas the drug acquisition price of vancomycin 1 g is

An evaluation of the cost effectiveness of drotrecogin alfa (activated) relative to the number of organ system failures

9.01 per dose, when all costs associated with using vancomycin were included, the cost per dose rose to

Once-Daily Aminoglycoside in the Treatment of Enterococcus faecalis Endocarditis: Case Report and Review

29–

Clinical and economic impact of methicillin resistance in patients with Staphylococcus aureus bacteremia

43 per patient. Total costs per patient receiving multiple doses in a single course of treatment, excluding hospital room costs, were for SSTI, bacteremia, IE, and HAP,