A randomized controlled trial comparing the efficacy of tigecycline versus meropenem in the treatment of postoperative complicated intra-abdominal infections

Abstract

Background: The efficacy and safety of tigecycline in the treatment of complicated intra-abdominal infections (cIAIs) is potentially controversial. Here we conducted the non-inferiority study to assess the efficacy and safety of tigecycline versus meropenem in the treatment of postoperative cIAIs.Methods: Data of abdominal tumor surgery patients with postoperative cIAIs admitted to intensive care unit (ICU) between October 2017 and December 2019 were collected. A prospective, randomized controlled trial was conducted in which 56 eligible patients with cIAIs randomly received intravenous tigecycline or meropenem for 3 to 14 days. Patients and clinicians were not blinded to the group allocation.Results: The total of 56 patients were enrolled, which were divided into 2 groups, one group included 30 patients receiving meropenem and another group included 26 receiving tigecycline therapy. The 2 groups were similar at demographic and baseline clinical characteristics. Microorganisms were isolated from 46 of 56 patients (82.14%), with a total of 107 pathogens were cultured in two groups. The two groups had similar distribution of infecting microorganisms. The primary end point was the clinical response at the end-oftherapy (EOT) visit and upon discharge visit and comprehensive efficacy. The clinical success rates were 83.33%, 76.67% for meropenem versus 76.92%, 88.46% for tigecycline at the EOT visit and upon discharge visit (P>0.05), respectively. Comprehensive efficacy did not significantly differ between two groups either. There were no significant differences in 30-day and 60-day all-cause mortality between two groups (P>0.05).The univariable analysis identified that serum albumin at admission ICU, colorectal cancer on oncology type, postoperative abdominal bleeding were the risk factors for 60-day all-cause mortality. The multivariable analysis showed that postoperative abdominal bleeding were independent predictors of 60-day all-cause mortality. Gastrointestinal disorders and antibacterials-induced Fungal Infection were the most frequently reported adverse events (AEs). The incidence of AEs was similar between meropenem and tigecycline groups (P>0.05). Conclusions:Taken together, the study demonstrated that tigecycline is as effective and safe as meropenem for postoperative cIAIs in abdominal tumors patients. Tigecycline is non-inferior to meropenem.

A phase III, multicenter, double-blind, randomized clinical trial to evaluate the efficacy and safety of ceftolozane/tazobactam plus metronidazole versus meropenem in Chinese participants with complicated intra-abdominal infections

“…In the current trial, nearly 20% of baseline pathogens were ESBLpositive, compared with 7.2% in the global pivotal trial (Solomkin et al, 2015). These findings were consistent with recent trends noting a regional uptick in drug-resistant pathogens in China and underscore the regional and global need for novel antibacterial agents targeting MDR gramnegative bacteria (Jean et al, 2021, Zhang H. et al, 2018, Zhang et al, 2021, Zhang Y. et al, 2018. Notably, treatment with C/T plus metronidazole was associated with favorable clinical response against all gram-negative aerobes, including commonly isolated pathogens, such as Enterobacterales, E. coli, and K. pneumoniae.…”

“…Microbiologic response was presumed based on clinical response, because postbaseline intraabdominal cultures were not available owing to the lack of repeat intra-abdominal interventions among study participants. Because of clinical microbiologic practices at participating sites, anaerobes were not routinely isolated from cIAI specimens; however, the most commonly isolated pathogens, E. coli, K. pneumoniae, and P. aeruginosa, were consistent with the previous reports (Chen et al, 2010, Qin et al, 2017, Solomkin et al, 2015, Wang et al, 2021.…”

“…Consistent with other clinical trials assessing cIAI in China, the most commonly isolated pathogens at baseline were E.coli, K. pneumoniae, and P. aeruginosa. (Chen et al, 2010, Qin et al, 2017, Wang et al, 2021. In the current trial, nearly 20% of baseline pathogens were ESBLpositive, compared with 7.2% in the global pivotal trial (Solomkin et al, 2015).…”

“…As the incidence of ESBL-positive E.coli and K. pneumoniae isolated from patients with complicated urinary tract infections and cIAI increases, rates of these pathogenic variants in China have been reported as high as 48% and 26%, respectively (Yang et al, 2013, Zhang et al, 2019. Although the susceptibility of ESBL-positive E. coli to common antibacterial agents remained consistent between 2012 and 2014 (Zhang et al, 2017), reports of ESBL-positive K. pneumoniae isolates from cIAIs between 2015 and 2017 in China indicated increasing evidence of resistance to common antibacterial agents (ie, amikacin, imipenem, piperacillin-tazobactam, ertapenem, and cefepime) (Zhang et al, 2021). Among participants in the current trial, favorable clinical response against ESBL-positive Enterobacterales was achieved with C/T plus metronidazole, indicating C/T plus metronidazole was comparable to meropenem in this population.…”

Intra-abdominal infection after tumor surgery: tigecycline combined with β-lactam antibiotics versus tigecycline alone

“…Several clinical studies have documented the effects of tigecycline as a single agent or in combination with other antimicrobials, and only three studies involved intra-abdominal infection [ 15 – 18 , 20 – 22 ]. Cancer is the risk factor of MDR intra-abdominal infection.…”