Influence of piperacillin-tazobactam on pharmacokinetics of gentamicin given once daily.

The effect of piperacillin-tazobactam on the pharmacokinetics of gentamicin given once daily was studied. Healthy adult volunteers each received four drug regimens in randomized order: gentamicin 7 mg/kg i.v. once daily (1) by itself, (2) with piperacillin 4 g and tazobactam 0.5 g (both as the sodium salt) every six hours i.v., (3) with piperacillin 4 g and tazobactam 0.5 g i.v. every eight hours, and (4) with piperacillin 8 g and tazobactam 1 g by continuous i.v. infusion over 24 hours. All the gentamicin doses were infused over 30 minutes two hours after piperacillin-tazobactam. Blood samples were drawn before and at the end of each gentamicin infusion and at intervals up to 12 hours after the start of each gentamicin infusion. Samples were assayed for gentamicin concentration by an enzyme-multiplied immunoassay technique and for piperacillin and tazobactam concentrations by high-performance liquid chromatography. Six women and four men completed all four drug regimens. For the gentamicin-alone regimen, the mean +/- S.D. area under the concentration-versus-time curve was 78.06 +/- 10.28 micrograms/mL.hr, the mean +/- S.D. peak concentration (30 minutes after the end of an infusion) was 20.28 +/- 2.54 micrograms/mL, and the mean +/- S.D. half-life was 2.41 +/- 0.24 hours. The values for gentamicin alone did not differ significantly from those for gentamicin in any of the combination regimens. Coadministration of once-daily gentamicin and piperacillin-tazobactam in various i.v. infusion regimens did not affect the pharmacokinetics of once-daily gentamicin.

Pharmacoeconomic impact of once-daily aminoglycoside administration.

A retrospective cost analysis compared hospital costs of standard gentamicin dosing and once-daily regimens in 1127 patients. Hospital costs compared were drug/supply/preparation/administration (DSPA; $4.56/500 mg once-daily dose and $3.32/100 mg every 8 hrs standard dose); therapeutic drug monitoring (TDM) ($25/gentamicin level); and nephrotoxicity management. The mean length of therapy was 4.5 days with both regimens. The mean number of blood samples drawn to measure drug levels was 0.65 for once-daily dosing and 1.7 for standard dosing. Mean DSPA and TDM costs/patient for a 4.5-day course of once-daily therapy were $20.52 and $16.25, respectively ($36.77/course of therapy). In comparison, estimated mean DSPA and TDM costs for 4.5 days standard therapy were $44.82 and $42.50, respectively ($87.32/course of therapy). We observed an overall reduction in nephrotoxicity from approximately 4% to 1.2% with the once-daily program, resulting in a nephrotoxicity management cost reduction from $182 to $55/patient exposed to aminoglycosides. The once-daily program resulted in a 58% reduction in aminoglycoside-associated hospital cost and a nephrotoxicity management savings of 70%/patient.

Cost comparison of single daily i.v. doses of ceftriaxone versus continuous infusion of cefotaxime.

The costs of administering ceftriaxone 1 g in a once-daily 30-minute infusion were compared with the costs of administering cefotaxime 2 g/day (with an additional 1 g given on day 1) by continuous intravenous infusion. Time and motion studies were conducted to determine the pharmacy and nursing labor required to prepare and administer the intermittent and continuously infused antimicrobials. Mean times were multiplied by the mean New England hourly wage for pharmacy technicians, pharmacists, and nurses to determine the total labor costs of each regimen. Hospital acquisition costs of items used in preparing antimicrobial doses for administration by each method were also compared. Wholesale acquisition costs of the two drugs were used in the analysis. Labor costs were higher for the continuously infused antimicrobial because of the additional nursing time required for monitoring. Supply costs were greater for continuous infusion. Drug acquisition cost was the major component of the overall cost of therapy and was lower for continuous infusion. A cost analysis showed that continuous i.v. infusion of cefotaxime 2 g/day was less expensive from day 2 onward than intermittent daily i.v. doses of ceftriaxone 1 g.

Streamlining antimicrobial therapy for lower respiratory tract infections.

Antimicrobial streamlining is the practice of converting a broad-spectrum empirical regimen to therapy with either a single, narrow-spectrum parenteral agent or an oral agent as soon as possible. This practice results in many benefits for the patient and the hospital. When intravenous catheters can be removed early, the frequencies of catheter-associated bacteremias and phlebitis are reduced, thus making it possible to avoid incurring major costs. With the availability of newer oral agents with favorable pharmacokinetic, pharmacodynamic, and microbiological profiles, such as the fluoroquinolones, the macrolides/azalides, and the cephalosporins, the clinician has greater opportunity to employ streamlining tactics. The patient who is hospitalized with a lower respiratory tract infection (LRTI) often requires empirical antimicrobial therapy before the pathogen is identified. By day 3 of the hospital course, the pathogen is often known, the patient's condition may have stabilized, or both events may have occurred. At this point, streamlining is possible. At present, data suggest that rapid conversion from intravenous to oral antimicrobial therapy is safe and efficacious and should be considered for appropriate patients requiring hospitalization for LRTIs.

Rational vancomycin use recommendations.

The increasing occurrence of VRE will dramatically affect the management of infections in hospitalized patients, as well as increase morbidity and mortality. Vancomycin is the therapy of choice for certain gram-positive infections in patients with significant allergic histories to beta-lactam antibiotics and for infections with gram-positive microorganisms that are resistant to beta-lactam antibiotics. Conservative use of vancomycin in the future may help to avoid the further development of resistant organisms.