A meta-analysis of clinical studies of imipenem-cilastatin for empirically treating febrile neutropenic patients. 1996

N B Deaney, and H Tate
Medical Department, Merck Sharp & Dohme Limited, Hoddesdon, Hertfordshire, UK.

There are many clinical studies comparing antibiotic treatments, but the majority are too small to have sufficient power to be reasonably certain of detecting statistically a moderate treatment effect. For example, few of the 19 studies published on imipenem-cilastatin for empirically treating febrile neutropenic patients were able to show any significant treatment effect in either direction when compared with alternative regimens. We therefore undertook a meta-analysis of these studies and made 21 pairwise comparisons of a control regimen with imipenem-cilastatin. Eleven comparisons were made between imipenem-cilastatin and a beta-lactam-aminoglycoside combination, and a further 10 between the carbapenem and a beta-lactam regimen either alone or combined with a glycopeptide or other beta-lactam antibiotic. These two data sets were analysed separately. Imipenem-cilastatin demonstrated a beneficial treatment effect over that achieved by aminoglycoside containing control regimens, yielding a typical odds ratio (OR) of 0.77 (95% CI 0.61 to 0.98). A beneficial treatment effect for the carbapenem regimen was also shown against regimens that did not include an aminoglycoside, with the typical OR being 0.67 (95% CI 0.54 to 0.84). Although there was clinical heterogeneity between studies, the treatment effect itself was relatively homogenous. These results show meta-analysis to be a useful aid for interpreting the data from clinical studies that are intrinsically too small to provide conclusive results.

UI MeSH Term Description Entries
D009503 Neutropenia A decrease in the number of NEUTROPHILS found in the blood. Neutropenias
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005334 Fever An abnormal elevation of body temperature, usually as a result of a pathologic process. Pyrexia,Fevers,Pyrexias
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013845 Thienamycins Beta-lactam antibiotics that differ from PENICILLINS in having the thiazolidine sulfur atom replaced by carbon, the sulfur then becoming the first atom in the side chain. They are unstable chemically, but have a very broad antibacterial spectrum. Thienamycin and its more stable derivatives are proposed for use in combinations with enzyme inhibitors. Antibiotics, Thienamycin,Thienamycin Antibiotics
D015377 Cilastatin A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, IMIPENEM, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukotriene E4. Cilastatin Monosodium Salt,Cilastatin Sodium,MK 0791,MK-791,MK0791,MK 791,MK791,Monosodium Salt, Cilastatin,Salt, Cilastatin Monosodium,Sodium, Cilastatin
D015378 Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with CILASTATIN, a renal dipeptidase inhibitor. Imipemide,N-Formimidoylthienamycin,Imipenem Anhydrous,Imipenem, Anhydrous,MK-0787,MK0787,Anhydrous Imipenem,Anhydrous, Imipenem,MK 0787,N Formimidoylthienamycin
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes

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