Gail S. Itokazu

Antimicrobial Dosing in Obese Patients

Although the dose of some drugs is commonly adjusted for weight, weight-related dosage adjustments are rarely made for most antimicrobials. We reviewed the English-language literature on antimicrobial pharmacokinetics and dosing in obesity. Although there are many potential pharmacokinetic consequences of obesity, the actual effect on the pharmacokinetics and clinical efficacy of most antimicrobials is unknown. Since approximately 30% of adipose is water, an empirical approach is use of the Devine formula to calculate ideal body weight (IBW), to which is added a dosing weight correction factor (DWCF) of 0.3 times the difference between actual body weight (ABW) and IBW (IBW + 0.3 x [ABW-IBW]) to arrive at a weight on which to base dosage of hydrophilic antibiotics. No studies confirm this approach for beta-lactam drugs. Clinical studies suggest a DWCF of approximately 0.40 for aminoglycosides and 0.45 for quinolones. Final dosage adjustments for antimicrobials with a narrow toxic-therapeutic window should be based on serum concentrations.

Antibiotic Combinations with Redundant Antimicrobial Spectra: Clinical Epidemiology and Pilot Intervention of Computer-Assisted Surveillance

Redundant antibiotic combinations are a potentially remediable source of antibiotic overuse. At a public teaching hospital, we determined the incidence, cost, and indications for such combinations and measured the effects of a pharmacist-based intervention. Of 1189 inpatients receiving >or=2 antibiotics, computer-assisted screening identified 192 patients (16.1%) receiving potentially redundant combinations. Chart reviews showed that 137 episodes (71%) were inappropriate. Physician overprescribing errors were found in 77 episodes (56%); most involved redundant coverage for gram-positive or anaerobic organisms. In 76 episodes (55%), lapses in the medication ordering and distribution system led to the persistence in the pharmacy records of regimens no longer active according to the patient charts. The incidence of redundant antibiotic combinations was significantly higher in the intensive care unit and surgery services, compared with medical services. Interventions to discontinue redundant agents were successful in 134 (98%) of the 137 episodes. Potential drug cost savings and reduction in redundant antibiotic combination days were 10,800 dollars and 584 days, respectively; pharmacist time for patient review and intervention cost 2880 dollars. Use of redundant antibiotic combinations was common, and a pharmacist-based intervention was feasible, with a potential annualized cost savings of 48,000 dollars.

Multi-hospital analysis of antimicrobial usage and resistance trends

We report a pilot study comparing antimicrobial usage and antimicrobial resistance trends for prominent nosocomial pathogens between 1994-1996. A convenience sample of ten hospitals participated in this retrospective review. We found a large variation in antimicrobial use and resistance trends and that many hospitals did not have data readily available to evaluate drug usage and resistance rates. A significant strong positive correlation was observed between the usage of ceftazidime and the prevalence of ceftazidime resistant Pseudomonas aeruginosa (r = 0.8, p = 0.005) and of ceftazidime resistant Enterobacter species (r = 0.8, p = 0.02). The presence of antibiotic control policies correlated with lower rates of some resistant strains and less antibiotic use. Our findings can be a useful starting point for hospitals that want to systematically measure antimicrobial use and resistance. Hospital laboratories, pharmacies, and infection control departments must work together to develop databases that will facilitate such measurements.

Implementation of an extended-infusion piperacillin–tazobactam program at an urban teaching hospital

PURPOSE The development and implementation of an extended-infusion piperacillin-tazobactam program at an urban teaching hospital are described. SUMMARY A multidisciplinary team was formed to address the feasibility of converting from the standard 30-minute infusion to an extended infusion of piperacillin- tazobactam. Before hospitalwide implementation, feasibility studies were performed in a subset of patients to identify potential barriers to program implementation. On the day of hospitalwide conversion, the orderables for piperacillin-tazobactam were reprogrammed in the computerized prescriber-order-entry system to allow separate options for the 30-minute infusion (for pediatric patients) and the extended-infusion regimen. After selecting the orderable for the extended-infusion regimen, an electronic message appeared to remind prescribers of the rationale for this change and recommended indications for piperacillin-tazobactam. Program success was prospectively evaluated on 11 weekdays after hospitalwide conversion for all 96 adult inpatients receiving piperacillin-tazobactam. Of the 194 piperacillin-tazobactam doses observed, 90% were appropriate, with compliance increasing to 100% by the end of the observation period. There was near-complete cessation of the every-6-hour dosage interval and a marked increase in the every-8-hour and every-12-hour dosage intervals. The number of piperacillin-tazobactam doses per 1000 patient-days significantly decreased during the postimplementation period. During the postimplementation period, pharmacy expenditures related to piperacillin-tazobactam decreased by 18% and the total number of grams of piperacillin-tazobactam purchased decreased by 24%. CONCLUSION A hospitalwide program for the administration of extended-infusion piperacillin-tazobactam was safely and successfully implemented using a multi-disciplinary approach in an urban teaching hospital.

Antimicrobial consumption data from pharmacy and nursing records: How good are they?

OBJECTIVE To determine whether randomly selected intravenous (IV) antimicrobial doses dispensed from an inpatient pharmacy were administered. DESIGN This was a prospective, cross-sectional study in which dose administration was confirmed by direct observation and by assessment of the medication administration record (MAR). A retrospective analysis of the return rate of unused IV antimicrobial doses was performed subsequently. SETTING Medical and surgical intensive care units (ICUs) and non-ICUs of a 550-bed urban public teaching hospital. PARTICIPANTS Hospitalized patients with an order in the pharmacy database for an IV antimicrobial during 9 non-consecutive weekdays in June 1999. RESULTS Of 397 doses, 221 (55.7%) assessed by bedside observation and 238 (59.9%) assessed by MAR review were classified as administered; 139 doses (35.0%) were dispensed but changes in the drug order or the patients status prevented their administration. In the subsequent assessment, of 745 IV antimicrobial doses dispensed during 24 hours, 322 (43.2%) were returned to the pharmacy unused; 423 (56.8%) of the doses-consistent with our prior observations-were presumably administered. CONCLUSIONS Because computerized pharmacy data may overestimate actual antimicrobial consumption, such data should be validated when used in studies of hospital antimicrobial use. Dispense-return analysis offers a simple validation method.

Ampicillin-sulbactam and ticarcillin-clavulanic acid: a comparison of their in vitro activity and review of their clinical efficacy.

Sulbactam (SB) and clavulanic acid (CA) are irreversible inhibitors of the β‐lactamases in the Richmond and Sykes classes II—VI. When combined with ampicillin and ticarcillin, SB and CA, respectively, extend the spectrum of activity of these penicillins to include some β‐lactamase‐producing aerobes (Enterobacteriaceae, Hemophilus influenzae, staphylococci) and anaerobes (Bacteroides fragilis group) which would otherwise be resistant. Neither effectively inhibits the class I β‐lactamases frequently produced by Pseudomonas aeruginosa, Enierobacter, and Serratia, in part explaining the resistance observed with these organisms. Clinically, both agents were as effective as the comparative therapies in all but two of the trials reviewed. Given the current data, the decision to add these agents to the formulary should be based on hospital resistance patterns and on the cost of these antimicrobials in comparison to conventional therapies.

The Comparative in vitro Activity of Clinafloxacin and Other Antimicrobials against Vancomycin-Susceptible and Vancomycin-Resistant Enterococci

The susceptibilities of 50 unique vancomycin-susceptible (n = 15) and vancomycin-resistant (n = 35) enterococci to 6 antimicrobials were compared. Teicoplanin was consistently the most active agent for all strains. Ampicillin and imipenem were active primarily for vancomycin-sensitive Enterococcus faecalis. Clinafloxacin and ciprofloxacin showed poorer activity compared to prior studies, suggesting that the emergence of quinolone resistance is now occurring in enterococci.

Selective Decontamination of the Digestive Tract as an Infection-Control Measure in Intensive Care Unit Patients

Infection is responsible for a large percentage of morbidity and mortality in intensive care unit (ICU) patients. Conventional infection‐control measures are directed at decreasing infection by exogenous sources and have had variable success in significantly reducing nosocomial infection rates. Selective gastrointestinal decontamination with topical nonabsorbable antibiotics attempts to reduce infection by eliminating intestinal mucosal colonization by pathogenic microorganisms. These antibiotics are selectively bactericidal against gram‐negative organisms and yeasts, thereby leaving the normal flora (mainly anaerobes) unharmed. In the majority of clinical trials, selective decontamination effectively reduced colonization and infection among ICU patients, with the most significant reductions observed in gram‐negative respiratory infections. Resistance to the antimicrobials was not documented in the majority of trials; however, follow‐up periods were minimal and may not have been adequate to detect selection of resistant strains. Reductions in infection do not alter mortality; however, patients without significant underlying disease appear to be the subgroup that will most likely benefit.

Continuation of High-Dose Vancomycin despite Nephrotoxicity

In agreement with several other studies ([3][1], [4][2]), Bosso et al. reported that in treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections, vancomycin trough concentrations of >15 mg/liter were independently associated with nephrotoxicity ([1][3]). However, how best to

Lack of Effect of Nizatidine‐Induced Elevation of Gastric pH on the Oral Bioavailability of Dapsone in Healthy Volunteers

Study Objective. To investigate the effect of histamine2 (H2)‐receptor antagonist‐induced elevation of gastric pH on oral bioavailability of a single dose of dapsone 100 mg.