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Moxalactam and piperacillin: A study of in vitro characteristics and pharmacokinetics in cancer patients

Moxalactam und Piperacillin: In vitro-Charakteristika und Pharmakokinetik bei Karzinompatienten

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Summary

We evaluated the microbiologic characteristics including MIC determinations, synergy plate assays and serum bactericidal activity for two regimens being examined as empiric antibiotic therapy for febrile granulocytopenic cancer patients. The regimens consisted of moxalactam (4 g i.v. q12h) plus piperacillin (75 mg/kg i.v. q6h) or moxalactam (as above) plus amikacin (levels adjusted to one hour post-infusion levels of 25 mg/l and troughs of 6–8 mg/l). Detailed pharmacokinetics were ascertained for the beta lactams. All drugs were active against a panel of 11 strains each ofEscherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, andStaphylococcus aureus. The pharmacokinetic profile showed serum levels sufficient to provide good antimicrobial activity throughout the dosing interval. Both regimens displayed synergistic or partially synergistic activity in the main for the test organisms; moxalactam plus piperacillin produced good results againstS. aureus andP. aeruginosa. In the serum bactericidal assays, the moxalactam-piperacillin combination produced significantly higher mean titers at both peak and trough when compared to the moxalactam-amikacin regimen. This may be because moxalactam acts as a beta lactamase inhibitor for both staphylococcal beta lactamase, as well as the Sabath-Abraham Id type beta lactamase carried byP. aeruginosa (among others). Moxalactam-piperacillin deserves extensive evaluation as empiric therapy for the febrile neutropenic cancer patients.

Zusammenfassung

Wir untersuchten die mikrobiologischen Charakteristika mit MHK-Bestimmungen, Synergismus-Plattentests und Serumbakterizidie von zwei Therapieregimen, die für die empirische Antibiotikatherapie bei granulozytopenischen Krebspatienten mit Fieber geprüft wurden. Die Therapieschemata bestanden aus Moxalactam (4 g i.v. alle 12 Stunden) plus Piperacillin (75 mg/kg i.v. alle 6 Stunden) oder Moxalactam (wie oben) plus Amikacin (Anpassung der Serumspiegel auf 25 mg/l eine Stunde nach der Infusion und Talspiegel 6–8 mg/l). Für die β-Lactam-Antibiotika wurden detaillierte pharmakokinetische Bestimmungen durchgeführt. Alle Medikamente waren gegen eine Gruppe von jeweils 11 Stämmen vonEscherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa undStaphylococcus aureus wirksam. Das pharmakokinetische Profil zeigte Serumspiegel, die für eine gute antimikrobielle Aktivität während des gesamten Dosierungsintervalls ausreichten. Beide Therapieschemata wiesen synergistische oder teilweise synergistische Aktivität für die wesentlichen Testorganismen auf. Moxalactam plus Piperacillin zeigte auch gute Ergebnisse in der Aktivität gegenS. aureus undP. aeruginosa. Im Serum-Bakterizidie-Test zeigte die Kombination Moxalactam-Piperacillin im Mittel signifikant höhere Titer zum Zeitpunkt der Spitzen- und Talspiegel als die Kombination Moxalactam-Amikacin. Möglicherweise ist dies darauf zurückzuführen, daß Moxalactam sowohl die Staphylokokken-β-Lactamase hemmt als auch die β-Lactamase vom Sabath-Abraham-Typ Id, die (unter anderen)P. aeruginosa trägt. Umfangreiche Studien zur Kombination Moxalactam-Piperacillin für die empirische Therapie bei neutropenischen Karzinompatienten mit Fieber sind gerechtfertigt.

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Authors and Affiliations

  1. Division of Infectious Diseases, University of Maryland School of Medicine, 10 South Pine Street, 21201, Baltimore, Maryland

    G. L. Drusano &  S. C. Schimpff

  2. University of Maryland Cancer Center, 22 South Greene Street, 21201, Baltimore, Maryland

    C. de Jongh, K. Newman,  J. Joshi, R. Wharton,  M. R. Moody &  S. C. Schimpff

Authors
  1. G. L. Drusano
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  2. S. C. Schimpff
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  3. C. de Jongh
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  4. K. Newman
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  5. J. Joshi
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  6. R. Wharton
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  7. M. R. Moody
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  8. S. C. Schimpff
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Drusano, G.L., Schimpff, S.C., de Jongh, C. et al. Moxalactam and piperacillin: A study of in vitro characteristics and pharmacokinetics in cancer patients. Infection 13, 20–26 (1985). https://doi.org/10.1007/BF01643616

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  • DOI: https://doi.org/10.1007/BF01643616

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