Abstract
BackgroundTo compare the efficacy and safety of double-carbapenem therapy (DCT) with other antibiotics for the treatment of multidrug resistant (MDR) Gram-negative bacterial infections.MethodsCochrane Library, PubMed, Embase and Web of Science as well as Chinese databases were searched from database establishment to February 2019. All types of studies were included if they had evaluated efficacy and safety of DCT regimens in patients with MDR Gram-negative bacterial infections. Clinical response, microbiological response, adverse events and mortality were the main outcomes. The protocol was registered with PROSPERO No. CRD42019129979.ResultsThree cohort or case-control studies consisting of 235 patients and 18 case series or case reports consisting of 90 patients were included. The clinical and microbiological responses were similar between DCT and other regimens in patients with carbapenem-resistant Enterobacteriaceae (CRE) infection. DCT achieved a lower mortality than comparators in patients with CRE infection (OR = 0.44, 95% CI = 0.24–0.82, P = 0.009). Ertapenem was the most reported antibiotic in DCT regimens in case series or case reports. Moreover, clinical and microbiological improvements were found in 59 (65.6%) and 63 (70%) in total 90 cases, respectively.ConclusionsDCT was as effective as other antibiotics in treating MDR Gram-negative bacterial infections, with similar efficacy response and lower mortality. DCT could be an alternative therapeutic option in the treatment of MDR Gram-negative bacterial infections. High-quality randomized controlled trials were required to confirm the beneficial effects of DCT.
Highlights
To compare the efficacy and safety of double-carbapenem therapy (DCT) with other antibiotics for the treatment of multidrug resistant (MDR) Gram-negative bacterial infections
Our study covered patients with MDR Gramnegative bacterial infections, and DCT was used to compare with other available antibiotics
In 2013, Giamarellou et al [26] reported that DCT successfully cured three patients with bloodstream infection and urinary tract infection caused by K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae
Summary
To compare the efficacy and safety of double-carbapenem therapy (DCT) with other antibiotics for the treatment of multidrug resistant (MDR) Gram-negative bacterial infections. Carbapenem antibiotics (including imipenem, meropenem, ertapenem and doripenem), with a broad spectrum of antibacterial activity, play an extremely important role in the field of anti-infective treatment for severe infections They are stable against most chromosomal broadspectrum beta-lactamases and cephalosporinases found in Gram-negative bacteria [1, 2]. Class A carbapenemases can effectively hydrolyze carbapenem antibiotics by binding on active-site serine These carbapenemases include the members of SME (Serratia marcescens enzyme), NMC (non-metallo enzyme carbapenemase), IMI (imipenemhydrolyzing), GES (Guiana extended spectrum) and the most important KPC (Klebsiella pneumoniae carbapenemase) beta-lactamases [8]. Class B carbapenemases include IMP (imipenemase), VIM (Verona integron-encoded MBL), SPM (Sao Paulo MBL), GIM (German imipenemase) and NDM (New Delhi MBL) groups [9, 10] They are mainly detected in P. aeruginosa and Enterobacteriaceae [11]. Most members of OXAs are not susceptible to beta-lactamase inhibitors, but may be inhibited by NaCl [12, 13]
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