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The stability of imipenem-cilastatin sodium (Primaxin, Merck Sharp & Dohme) in various intravenous fluids was determined after storage at 4 degrees C or 25 degrees C and after freezing. Samples of imipenem-cilastatin sodium were constituted with 100 mL of each of 17 i.v. fluids to concentrations of 2.5 mg/mL or 5.0 mg/mL of each drug component and stored in glass infusion bottles at constant room temperature (25 degrees C) or constant refrigerated temperature (4 degrees C). The concentration of each solution was determined immediately after constitution by a stability-indicating high-performance liquid chromatographic assay; the concentrations of both drugs were monitored in each i.v. fluid until the time that the concentration of either imipenem or cilastatin decreased to less than 90% of the initial concentration (t90). The exact value of t90 was determined for each solution by linear regression. The solutions were also assessed for changes in pH or color. Cilastatin sodium was more stable in all 17 i.v. fluids than imipenem. The stability of imipenem was dependent on the concentration of that drug in solution; solutions of imipenem 2.5 mg/mL were more stable than solutions of imipenem 5.0 mg/mL. The values of t90 for imipenem in solutions stored at 4 degrees C were greater than the values for solutions stored at 25 degrees C. Imipenem was most stable in 0.9% sodium chloride injection. The pH values of the solutions generally decreased during the study period.(ABSTRACT TRUNCATED AT 250 WORDS)

The chemistry, antimicrobial spectrum, mechanism of action, pharmacology and pharmacokinetics, clinical use, adverse effects, dosage and administration, place in therapy, cost-effectiveness, and formulary considerations of imipenem-cilastatin sodium are reviewed. Imipenem is the first carbapenem antibiotic of the thienamycin class to be used clinically. Imipenem has the widest spectrum of antimicrobial activity of currently available beta-lactam agents and, in contrast to other beta-lactam antibiotics, lacks cross resistance with recently introduced extended-spectrum penicillins and third-generation cephalosporins. Against gram-positive and gram-negative aerobic and anaerobic organisms, imipenem demonstrates excellent activity. Pseudomonas maltophilia, some strains of Pseudomonas cepacia, and Streptococcus faecium are resistant. Strains of methicillin-resistant staphylococci should also be considered resistant to imipenem. For clinical use imipenem is coadministered in equal parts with cilastatin. Cilastatin is a renal dehydropeptidase inhibitor that inhibits the metabolism of imipenem by renal brush-border enzymes, thus increasing imipenem concentrations in urine. Imipenem-cilastatin is administered by the intravenous route only. The adverse reaction profile of imipenem-cilastatin is similar to t that of other beta-lactam antibiotics. Recommended dosage reductions appropriate for renal impairment should be guided by periodic assessments of renal function, with close adherence to recommended dosage schedules, particularly among patients who are predisposed to seizures or receiving anticonvulsant medication. Imipenem-cilastatin performed well in both comparative and noncomparative trials of clinical efficacy and safety. For infections with multiple organisms (e.g., pelvic, intra-abdominal, or soft-tissue infections), imipenem-cilastatin may be a cost-effective and less toxic single-agent alternative to "standard" combination (e.g., aminoglycoside-penicillin plus an antianaerobic agent) therapy. However, in patients with serious pseudomonal infections (e.g., pneumonia), isolates may rapidly acquire resistance to imipenem or be replaced by resistant strains of Ps. aeruginosa when imipenem is used alone. Therefore, when the recovery of Ps. aeruginosa is anticipated or documented, treatment with imipenem-cilastatin should include an aminoglycoside to reduce the likelihood of the emergency of resistant organisms during therapy.