Archive for December 21, 2009

Identification of Optimal Renal Dosage Adjustments for Traditional and Extended-Infusion Piperacillin-Tazobactam Dosing Regimens in Hospitalized Patients

Antimicrobial Agents and Chemotherapy  1 Jan 2010  V.54  N.1  p.460-465

N. Patel,1 M. H. Scheetz,2,3 G. L. Drusano,4 and T. P. Lodise1,4*

Albany College of Pharmacy and Health Sciences, Albany, New York,1 Midwestern College of Pharmacy, Department of Pharmacy Practice, Downers Grove, Illinois,2 Northwestern Memorial Hospital, Department of Pharmacy, Chicago, Illinois,3 Ordway Research Institute, Albany, New York4

This study examined the effect of various levels of renal impairment on the probability of achieving free drug concentrations that exceed the MIC for 50% of the dosing interval (50% fT > MIC) for traditional and extended-infusion piperacillin-tazobactam (TZP) dosing strategies. It also identified optimal renal dosage adjustments for traditional and extended-infusion dosing schemes that yielded probability of target attainment (PTA) and exposure profiles that were isometric to those of the parent regimens. Data from 105 patients were analyzed using the population pharmacokinetic modeling program BigNPAG. To assess the effect of creatinine clearance (CLCR) on overall clearance, TZP clearance was made proportional to the estimated CLCR. A Monte Carlo simulation (9,999 subjects) was performed for the traditional dosing scheme (4.5 g infused during 30 min every 6 h) and the extended-infusion TZP dosing scheme (3.375 g infused during 4 h every 8 h). The fraction of simulated subjects who achieved 50% fT > MIC was calculated for the range of piperacillin MICs from 0.25 to 32 mg/liter and stratified by CLCR. The traditional TZP regimen displayed the greatest variability in PTA across MIC values, especially for MIC values exceeding 4 mg/liter, when stratified by CLCR. In contrast, the PTA for the extended-infusion TZP regimen exceeded 80% for MIC values of 8 mg/liter across all CLCR strata. All regimens were associated with suboptimal PTA for MIC values of 32 mg/liter irrespective of the CLCR. The CLCR adjustments for traditional and extended-infusion TZP dosing regimens should be considered at a CLCR of 20 ml/min.


December 21, 2009 at 12:23 am Leave a comment

Sustained Reductions in Invasive Pneumococcal Disease in the Era of Conjugate Vaccine

The Journal of Infectious Diseases  1 January 2010  V.201  N.1  p.32-41

Tamara Pilishvili,1 Catherine Lexau,8 Monica M. Farley,3,4 James Hadler,5 Lee H. Harrison,6 Nancy M. Bennett,7 Arthur Reingold,9 Ann Thomas,10 William Schaffner,11 Allen S. Craig,12 Philip J. Smith,2

Bernard W. Beall,1 Cynthia G. Whitney,1 and Matthew R. Moore,1 for the Active Bacterial Core Surveillance/Emerging Infections Program Networka

1Division of Bacterial Diseases and 2Immunization Services Division, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, 3Emory University School of Medicine, and the 4Veterans Affairs Medical Center, Atlanta, Georgia; 5Connecticut Department of Public Health, Hartford; 6Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 7University of Rochester School of Medicine and Dentistry, Rochester, New York; 8Minnesota Department of Health, Minneapolis; 9School of Public Health, University of California, Berkeley; 10Oregon Department of Human Service, Public Health Division, Portland; 11Vanderbilt University School of Medicine and 12Tennessee Department of Health, Nashville

Background. Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children.

Methods. Laboratory-confirmed IPD cases were identified during 1998–2007 by 8 active population‐based surveillance sites. We compared overall, age group–specific, syndrome-specific, and serotype group–specific IPD incidence in 2007 with that in 1998–1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations.

Results. Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively ( for all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively ( for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups ( ), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006–2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old.

Conclusions. Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.


December 21, 2009 at 12:22 am Leave a comment


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