Successful High-Dosage Monotherapy of Tigecycline in a Multidrug-Resistant Klebsiella pneumoniae Pneumonia–Septicemia Model in Rats
| Autor: | Mireille van Westreenen, Hessel van der Weide, Stefan A. Boers, Wil H. F. Goessens, Rixt A. Wijma, John P. Hays, Marian T. ten Kate, Denise M. C. Vermeulen-de Jongh, Aart van der Meijden, Irma A. J. M. Bakker-Woudenberg |
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| Přispěvatelé: | Medical Microbiology & Infectious Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Microbiology (medical)
medicine.medical_specialty antibiotic resistance medicine.drug_class Klebsiella pneumoniae Antibiotics Tigecycline Biochemistry Microbiology Meropenem Article Antibiotic resistance meropenem Internal medicine medicine polycyclic compounds pneumonia Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics klebsiella pneumoniae biology business.industry septicemia lcsh:RM1-950 biochemical phenomena metabolism and nutrition medicine.disease biology.organism_classification bacterial infections and mycoses Pneumonia Regimen Infectious Diseases lcsh:Therapeutics. Pharmacology Drug of last resort tigecycline business medicine.drug |
| Zdroj: | Antibiotics, Vol 9, Iss 3, p 109 (2020) Antibiotics Antibiotics-Basel, 9(3):109. Multidisciplinary Digital Publishing Institute (MDPI) Volume 9 Issue 3 |
| ISSN: | 2079-6382 |
| Popis: | Background: Recent scientific reports on the use of high dose tigecycline monotherapy as a &ldquo drug of last resort&rdquo warrant further research into the use of this regimen for the treatment of severe multidrug-resistant, Gram-negative bacterial infections. In the current study, the therapeutic efficacy of tigecycline monotherapy was investigated and compared to meropenem monotherapy in a newly developed rat model of fatal lobar pneumonia&ndash septicemia. Methods: A Klebsiella pneumoniae producing extended-spectrum &beta lactamase (ESBL) and an isogenic variant producing K. pneumoniae carbapenemase (KPC) were used in the study. Both strains were tested for their in vitro antibiotic susceptibility and used to induce pneumonia&ndash septicemia in rats, which was characterized using disease progression parameters. Therapy with tigecycline or meropenem was initiated at the moment that rats suffered from progressive infection and was administered 12-hourly over 10 days. The pharmacokinetics of meropenem were determined in infected rats. Results: In rats with ESBL pneumonia&ndash septicemia, the minimum dosage of meropenem achieving survival of all rats was 25 mg/kg/day. However, in rats with KPC pneumonia&ndash septicemia, this meropenem dosage was unsuccessful. In contrast, all rats with KPC pneumonia&ndash septicemia were successfully cured by administration of high-dose tigecycline monotherapy of 25 mg/kg/day (i.e., the minimum tigecycline dosage achieving 100% survival of rats with ESBL pneumonia&ndash septicemia in a previous study). Conclusions: The current study supports recent literature recommending high-dose tigecycline as a last resort regimen for the treatment of severe multidrug-resistant bacterial infections. The use of ESBL- and KPC-producing K. pneumoniae strains in the current rat model of pneumonia&ndash septicemia enables further investigation, helping provide supporting data for follow-up clinical trials in patients suffering from severe multidrug-resistant bacterial respiratory infections. |
| Databáze: | OpenAIRE |
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