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Therapeutic drug monitoring-guided high dose meropenem therapy of a multidrug resistant Acinetobacter baumannii - A case report.

ABSTRACT: Background:Infections with multidrug resistant Acinetobacter baumannii in immunocompromised patients are life-threatening. Therapeutic options are rare in this context, but patients are dependent on an effective antibiotic therapy. Thus, new antibiotic strategies are deemed necessary. Case presentation:This case report recounts the therapeutic drug monitoring-guided meropenem therapy of a 32 years old patient admitted with acute exacerbation of cystic fibrosis. Veno-venous extracorporeal membrane oxygenation was initiated on the first day of admission to the intensive care unit. The patient showed insufficient serum trough levels of meropenem despite the maximum approved dose (2g every 8h) was administered which was due to augmented renal clearance. Through continuous infusion of the same cumulative dose, target levels were reached. On day 17 of admission, the patient underwent successful double-lung-transplant surgery and extracorporeal membrane oxygenation was ended. Unfortunately, the donor's lung was colonized with a multidrug resistant Acinetobacter baumannii that was positive for OXA-23 carbapenemase. Hence a combination therapy of intravenous sulbactam, tigecycline, meropenem and inhalative colistin was established, with a known minimal inhibitory concentration for meropenem of 32 mg/l. Under continuous infusion of 8 g meropenem/day, serum levels exceeded 32 mg/l over 12 days. The patient was transferred from the intensive care unit to a general ward without any signs of infection. Conclusions:Therapeutic drug monitoring-guided meropenem may be a sound new therapeutic option in eradicating multidrug resistant Acinetobacter and offer a novel therapeutic option in the field of personalized medicine.

SUBMITTER: Liebchen U

PROVIDER: S-EPMC6909205 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Therapeutic drug monitoring-guided high dose meropenem therapy of a multidrug resistant <i>Acinetobacter baumannii -</i> A case report.

Liebchen U U Paal M M Jung J J Schroeder I I Frey L L Zoller M M Scharf C C

Respiratory medicine case reports 20191112

<h4>Background</h4>Infections with multidrug resistant Acinetobacter baumannii in immunocompromised patients are life-threatening. Therapeutic options are rare in this context, but patients are dependent on an effective antibiotic therapy. Thus, new antibiotic strategies are deemed necessary.<h4>Case presentation</h4>This case report recounts the therapeutic drug monitoring-guided meropenem therapy of a 32 years old patient admitted with acute exacerbation of cystic fibrosis. Veno-venous extraco ...[more]

PMID: 31871885

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Project description:BackgroundWidespread misuse of antibiotics caused bacterial resistance increasingly become a serious threat. Bacteriophage therapy promises alternative treatment strategies for combatting drug-resistant bacterial infections. In this study, we isolated and characterized a novel, potent lytic bacteriophage against multi-drug resistant (MDR) Acinetobacter baumannii and described the lytic capability and endolysin activity of the phage to evaluate the potential in phage therapy.MethodsA novel phage, pIsf-AB02, was isolated from hospital sewage. The morphological analysis, its host range, growth characteristics, stability under various conditions, genomic restriction pattern were systematically investigated. The protein pattern of the phage was analyzed, and the endolysin activity of the phage was determined under the non-denaturing condition on SDS-PAGE. The optimal lytic titer of phage was assessed by co-culture of the phage with clinical MDR A. baumannii isolates. Finally, HeLa cells were used to examine the safety of the phage.ResultsThe morphological analysis revealed that the pIsf-AB02 phage displays morphology resembling the Myoviridae family. It can quickly destroy 56.3% (27/48) of clinical MDR A. baumannii isolates. This virulent phage could decrease the bacterial host cells (from 108 CFU/ml to 103 CFU/ml) in 30 min. The optimum stability of the phage was observed at 37 °C. pH 7 is the most suitable condition to maintain phage stability. The 15 kDa protein encoded by pIsf-AB02 was detected to have endolysin activity. pIsf-AB02 did not show cytotoxicity to HeLa cells, and it can save HeLa cells from A. baumannii infection.ConclusionIn this study, we isolated a novel lytic MDR A. baumannii bacteriophage, pIsf-AB02. This phage showed suitable stability at different temperatures and pHs, and demonstrated potent in vitro endolysin activity. pIsf-AB02 may be a good candidate as a therapeutic agent to control nosocomial infections caused by MDR A. baumannii.

Dataset Information

Therapeutic drug monitoring-guided high dose meropenem therapy of a multidrug resistant Acinetobacter baumannii - A case report.

Publications

Therapeutic drug monitoring-guided high dose meropenem therapy of a multidrug resistant <i>Acinetobacter baumannii -</i> A case report.

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