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Combined Rifampin and Sulbactam Therapy for Multidrug-Resistant Acinetobacter Baumannii Ventilator-Associated Pneumonia in Pediatric Patients.

ABSTRACT: Background:With essentially no drug available to control the infection caused by the extensively drug-resistant Acinetobacter baumannii (XDR-Ab) in infants and young children, this study explored the clinical outcomes of pediatric patients with drug-resistant XDR-Ab who were treated with rifampicin in combination with sulbactam sodium. Methods:The data for clinical outcomes, microbiological responses, and side effects were collected and evaluated for 12 critically ill infants and young children diagnosed with ventilator-associated pneumonia caused by XDR-Ab following surgical treatment for congenital heart disease in a pediatric cardiac intensive care unit. This study was approved by local institutional review board (IRB). Results:Two patients died from the complex underlining diseases. The other 10 patients were weaned off the mechanical ventilation successfully within 4-15 days after the start of treatment with rifampicin combined with sulbactam sodium and discharged home. Three cases experienced adverse side effects, including severe rash and elevated aminotransferase level. Conclusion:The combination of rifampicin and sulbactam sodium appeared to be an effective and safe therapy for severe ventilator-associated pneumonia caused by XDR-Ab in infants and young children. Side effects such as skin rashes and elevated aminotransferase levels can be reversed once rifampicin is discontinued in time. (Funded by the Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Chang-sha, China; the Departments of Anesthesiology and Pain Medicine of University of California Davis Health; and the National Institutes of Health.).

SUBMITTER: Chen J

PROVIDER: S-EPMC6901084 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Combined Rifampin and Sulbactam Therapy for Multidrug-Resistant Acinetobacter Baumannii Ventilator-Associated Pneumonia in Pediatric Patients.

Chen Jinlan J Yang Yifeng Y Xiang Kun K Li David D Liu Hong H

Journal of anesthesia and perioperative medicine 20180701 4

<h4>Background</h4>With essentially no drug available to control the infection caused by the extensively drug-resistant Acinetobacter baumannii (XDR-Ab) in infants and young children, this study explored the clinical outcomes of pediatric patients with drug-resistant XDR-Ab who were treated with rifampicin in combination with sulbactam sodium.<h4>Methods</h4>The data for clinical outcomes, microbiological responses, and side effects were collected and evaluated for 12 critically ill infants and ...[more]

PMID: 31819924

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Project description:Infection by multidrug-resistant (MDR) Acinetobacter baumannii is one of the major causes of hospital-acquired infections worldwide. The ability of A. baumannii to survive in adverse conditions as well as its extensive antimicrobial resistance make it one of the most difficult to treat pathogens associated with high mortality rates. The aim of this study was to investigate MDR A. baumannii that has spread among pediatric cancer patients in the Children's Cancer Hospital Egypt 57357. Whole-genome sequencing was used to characterize 31 MDR A. baumannii clinical isolates. Phenotypically, the isolates were MDR, with four isolates showing resistance to the last-resort antibiotic colistin. Multilocus sequence typing showed the presence of eight clonal groups, two of which were previously reported to cause outbreaks in Egypt, and one novel sequence type (ST), Oxf-ST2246. Identification of the circulating plasmids showed the presence of two plasmid lineages in the isolates, strongly governed by sequence type. A large number of antimicrobial genes with a range of resistance mechanisms were detected in the isolates, including β-lactamases and antibiotic efflux pumps. Analysis of insertion sequences (ISs) revealed the presence of ISAba1 and ISAba125 in all the samples, which amplify β-lactamase expression, causing extensive carbapenem resistance. Mutation analysis was used to decipher underlying mutations responsible for colistin resistance and revealed novel mutations in several outer membrane proteins, in addition to previously reported mutations in pmrB. Altogether, understanding the transmissibility of A. baumannii as well as its resistance and virulence mechanisms will help develop novel treatment options for better management of hospital-acquired infections. IMPORTANCE Acinetobacter baumannii represents a major health threat, in particular among immunocompromised cancer patients. The rise in carbapenem-resistant A. baumannii, and the development of resistance to the last-resort antimicrobial agent colistin, complicates the management of A. baumannii outbreaks and increases mortality rates. Here, we investigate 31 multidrug resistant A. baumannii isolates from pediatric cancer patients in Children's Cancer Hospital Egypt (CCHE) 57357 via whole-genome sequencing. Multilocus sequence typing (MLST) showed the presence of eight clonal groups including a novel sequence type. In silico detection of antimicrobial-resistant genes and virulence factors revealed a strong correlation between certain virulence genes and mortality as well as several point mutations in outer membrane proteins contributing to colistin resistance. Detection of CRISPR/Cas sequences in the majority of the samples was strongly correlated with the presence of prophage sequences and associated with failure of bacteriophage therapy. Altogether, understanding the genetic makeup of circulating A. baumannii is essential for better management of outbreaks.

Project description:Ventilator-associated pneumonia (VAP) remains an important clinical problem globally, being associated with significant morbidity and mortality. As management of VAP requires adequate and timely antibiotic administration, global emergence of antimicrobial resistance poses serious challenges over our ability to maintain this axiom. Development of antimicrobials against MDR Gram-negative pathogens has therefore emerged as a priority and some new antibiotics have been marketed or approach late stage of development. The aim of this review is to analyse new therapeutic options from the point view of potential treatment of VAP. Among recently developed antimicrobials presented herein, it is obvious that we will have promising therapeutic options against VAP caused by Enterobacteriaceae excluding those producing metallo-β-lactamases, against which only cefiderocol and aztreonam/avibactam are expected to be active. Against infections caused by carbapenem non-susceptible Pseudomonas aeruginosa, ceftolozane/tazobactam and to a lesser extend ceftazidime/avibactam may cover a proportion of current medical needs, but there still remain a considerable proportion of strains which harbor other resistance mechanisms. Murepavadin and cefiderocol hold promise against this particularly notorious pathogen. Finally, Acinetobacter baummannii remains a treatment-challenge. Eravacycline, cefiderocol and probably plazomicin seem to be the most promising agents against this difficult-to treat pathogen, but we have still a long road ahead, to see their position in clinical practice and particularly in VAP. In summary, despite persisting and increasing unmet medical needs, several newly approved and forthcoming agents hold promise for the treatment of VAP and hopefully will enrich our antimicrobial arsenal in the next few years. Targeted pharmacokinetic and clinical studies in real-life scenario of VAP are important to position these new agents in clinical practice, whereas vigilant use will ensure their longevity in our armamentarium.

Dataset Information

Combined Rifampin and Sulbactam Therapy for Multidrug-Resistant Acinetobacter Baumannii Ventilator-Associated Pneumonia in Pediatric Patients.

Publications

Combined Rifampin and Sulbactam Therapy for Multidrug-Resistant Acinetobacter Baumannii Ventilator-Associated Pneumonia in Pediatric Patients.

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