Drug Criteria & Outcomes-Assessing piperacillin/tazobactam (Zosyn)
By Stephen Parker, RPh
Jon Herrington, PharmD
Paul Holder, Pharm D
Scott & White Memorial Hospital
Department of Pharmacy Services
Temple, Texas
Introduction
Piperacillin/tazobactam (Zosyn) is an injectable antibacterial combination product consisting of the semi-synthetic antibiotic piperacillin and the beta-lactamase inhibitor, tazobactam sodium. This agent has a wide spectrum of in vitro antimicrobial activity against most aerobic and anaerobic gram-negative and gram-positive bacteria.
Piperacillin/tazobactam has FDA approval for the treatment of appendicitis and peritonitis, uncomplicated and complicated skin structure infections, postpartum endometriosis or pelvic inflammatory disease, community acquired pneumonia (moderate severity), and nosocomial pneumonia (moderate to severe). An assessment by the medication use evaluation subcommittee of the pharmacy and therapeutics committee of Scott & White Hospital was conducted to review indications for use of piperacillin/tazobactam, dosing, adverse effects, and outcomes.
Methods
Data were collected over a four-month period by patient care pharmacists. Orders for the drug written by all services throughout the hospital were reviewed. Evaluation included appropriateness of use, dose (with potential dose reduction based on determination of renal function), adverse events, and clinical outcomes. The patient care pharmacists also evaluated whether physicians narrowed the spectrum of antibiotic therapy by changing to piperacillin in cases where Pseudomonas aeruginosa was cultured.
Summary of data
A total of 84 charts of adult patients were reviewed throughout the hospital. The data collected are summarized in the accompanying table (see p. 2).
| Piperacillin/Tazobactam Assessment-Summary of Data | ||||
| Indication | Number of Patients | Average length of therapy with Zosyn (days) | Improvement clinical status | Febrile after 72 hours of antibiotic |
| Community-acquired pneumonia | 19 | 5.5 | 14 | 7 |
| Aspiration pneumonia | 12 | 7.8 | 10 | 3 |
| Uncomplicated UTI | 10 | 6.1 | 10 | 0 |
| Nosocomial pneumonia | 7 | 6.3 | 6 | 0 |
| Intra-abdominal | 6 | 6.3 | 4 | 1 |
| Diabetic foot injection | 4 | 5 | 4 | 0 |
| Gynecologic | 4 | 7.6 | 3 | 1 |
| Skin and soft tissue | 4 | 6.7 | 1 | 2 |
| Cholecystitis | 3 | 5 | 1 | 2 |
| Bacteremia | 5 | 8 | 3 | 2 |
| Lung abcess | 2 | 15 | 1 | 1 |
| Pyelonephritis | 1 | 5 | 1 | 0 |
| Other | 6 | 12 | 4 | 2 |
| Source: Scott & White Memorial Hospital, Department of Pharmacy Services, Temple, TX. | ||||
Results
Of the 84 total patients, data on appropriateness of dosing with respect to renal function were available on only 53 patients. Twenty-nine of those 53 patients (55%) had piperacillin/tazo bactam dosing regimens appropriately adjusted for renal dysfunction. Dosing regimens were not adjusted for renal dysfunction in 24 of the 53 patients (45%).
Aminoglycosides were utilized in conjunction with piperacillin/tazobactam in 18 of the 84 evaluable patients. In six of those 18 patients receiving both piperacillin/tazobactam and an aminoglycoside, administration was separated by less than two hours.
This regimen is of concern because beta-lactam antibiotics and aminoglycosides have the potential to inactivate each other when both are administered within a two-hour period.
Piperacillin/tazobactam was utilized in two patients for surgical prophylaxis. From the available data, it is not possible to determine whether that use was appropriate.
P. aeruginosa was isolated from cultures in eight patients. The division of infectious diseases/department of pharmacy's antibiotic streamlining team (AST) recommended narrowing antibiotic therapy to piperacillin in six of the eight cases; however, therapy was narrowed in only one of those patients. Secondary infection involving organisms requiring beta-lactam coverage was present in the two cases where recommendations to narrow coverage were not made by the AST.
Conclusions
In 34 of the 84 (40%) cases reviewed, a more narrow-spectrum, less-expensive agent could have been ordered. While piperacillin/tazobactam is FDA-approved for community-acquired pneumonia (CAP), the wide spectrum of this agent is not necessary in most cases of CAP.
Piperacillin/taxobactam should be reserved for patients with documented pseudomonal infections when co-infection with anaerobes or other potentially resistant gram-negative organisms is suspected.
While piperacillin/tazobactam is appropriate empirically when Pseudomonas is suspected, coverage should be narrowed once culture results are obtained. This is important to help prevent the development and spread of resistant organisms.
Data from this MUE suggest that ceftriaxone in combination with oral doxycycline could have been utilized in the 19 patients with CAP. Cefazolin or another narrow-spectrum antimicrobial agent could have been utilized in the 11 patients with uncomplicated urinary tract infection.
In the four patients with cellulitis, both cefazolin and nafcillin are active against the common infecting organisms (streptococci and/or staphylococci), and either would be preferred over piperacillin/tazobactam due to each agent's spectrum of activity.
[Editor's note: For more information, contact the authors at Scott & White Hospital, 2401 S. 31st St., Temple, TX 76508. Telephone: (254) 724-2111.]
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