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

Abstract

BackgroundThe 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.MethodsThe 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.ResultsThirty-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).ConclusionsTriple 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.

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“…The lack of an effective treatment for carbapenemase-producing K. pneumoniae is becoming a significant problem worldwide. Although polymyxin-based triple combination therapy is suggested, its clinical and microbiological success is limited [31]. Second, percutaneous drainage of the abscess is helpful for clearing the infection source.…”

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“…Therefore, meropenen prescription was continued and may contribute to the spread of infection. For sepsis, clinical symptoms frequently manifest in the absence of a positive culture resulting in diagnosis delay ( 28 ). As observed here, negative culture contributed to the wrong antibiotic prescription and was fatal to the patient.…”

NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

“…Polymyxins are the current mainstay choice of antimicrobial agents against CRE and carbapenem-resistant A. baumannii, including NDM-positive strains. The treatment of infections due to multidrug-resistant organisms (MDRO) with polymyxins has been reviewed previously (251)(252)(253), and there are many studies on the efficacy of colistin against CRE, most of which have KPC rather than NDM (254,255). In this review, we focus on treatment against NDM-positive strains only.…”