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Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

ABSTRACT: The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections.The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2.Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients).Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

SUBMITTER: Jacobs DM

PROVIDER: S-EPMC5702089 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Carbapenemase-producing Klebsiella pneumoniae (CP-Kpn) are a major concern for nosocomial infections. We previously reported an intensive care unit (ICU) outbreak of CP-Kpn. This study investigated the transmission pattern and genetic characteristic of CP-Kpn in the hospital during the outbreak period. Whole-genome sequencing was retrospectively performed on 173 CP-Kpn isolates. Pairwise single-nucleotide polymorphism (SNP) distances were calculated to determine SNP thresholds for clustering. Plasmids and mobile genome elements (MGEs) were identified through short- and long-read sequencing. Strains were classified into three groups, sequence type 11 (ST11) (86.12%), ST15 (9.83%), and other ST. An SNP threshold of 16 revealed a 66.47% clustering rate. ICU admission and meropenem use proportions were significantly higher in clustered patients than in unique patients. MGE distribution was consistent with the phylogenetic tree. Of the isolates, 53.18% were CP-Kpn with hypervirulence genes. We identified five plasmids carrying virulence genes, and four of them have not been previously reported. Clonal transmission was the main cause of CP-Kpn infections in the hospital. Multidrug resistance genes and MGE variations were correlated with clustering. Finally, four novel plasmids carrying virulence genes were identified. The findings highlight the control of CR-Kpn transmission through prevention measures to reduce nosocomial infections. IMPORTANCE In this study, we combined genomic and epidemiological analyses and defined an optimal cutoff value for SNP difference that could be used to aid investigation in tertiary hospital in China. We revealed clonal transmission was the main cause of CP-Kpn infections in the hospital and identified four novel plasmids carrying virulence genes. Our results strongly suggested that dominant CP K. pneumoniae strains lead to outbreaks and described different evolutionary patterns of plasmids carrying multidrug resistance and virulence genes.

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Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

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