Efficacy and safety prediction of cephalosporins antibiotics combined with metronidazole for intra-abdominal infections: a Bayesian network meta analysis / 中华消化外科杂志

ABSTRACT

Objective:To predict the efficacy and safety of cephalosporins antibiotics combined with metronidazole for intra-abdominal infections using Bayesian network meta analysis.Methods:Databases including PubMed, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database were searched for literatures from January 1990 to May 2018 with the key words of ( "intraabdominal infections" [MeSH Terms]) AND ( "Cephalosporins*" [MeSH Terms]) AND ( "randomized controlled trial" [MeSH Terms]),腹腔感染,继发性腹膜炎,腹腔脓肿,头孢. The randomized controlled trials (RCTs) about comparison of efficacy and safety between cephalosporins antibiotics combined with metronidazole versus other antibiotics for intra-abdominal infections were received and included. Experimental group included patients who received cephalosporins antibiotics combined with metronidazole for intra-abdominal infections, and control group included patients who received other antibiotics for intra-abdominal infections. The primary outcomes were the clinical cure rates, microbial clearance rate and incidence of serious adverse drug reactions. R 3.6.2 software random Bayesian model was used for meta analysis. The Markov Chain Monte Carlo was used for direct evaluation and indirect prediction. The tracing method, density plotting and leverage figure method were used to evaluate the model convergence and stability. No closed loop formed between intervention measures, so there was no need to evaluate consistency.Results:(1) Document retrieval a total of 18 available RCTs were enrolled. There were 6 792 patients, including 3 402 in the experimental group, 3 390 in the control group. (2) Results of Bayesian network meta analysis. ① The clinical cure rates of the third generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole [ odds ratio ( OR)=0.46, 0.61, 95% confidence interval( CI) as 0.26-0.81, 0.38-0.97, P<0.05]. There was no significant difference in the clinical cure rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=1.03, 95% CI as 0.59-1.80, P>0.05). ② The microbial clearance rates of the fifth generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole ( OR=0.84, 0.41, 95% CI as 0.73-0.98, 0.23-0.74, P<0.05). There was no significant difference in the microbial clearance rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=0.76, 95% CI as 0.27-1.80, P>0.05). ③ The incidence of serious adverse drug reactions was significantly lower for the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins antibiotics+ cetronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, quinolones+ metronidazole, and tigecycline than for quinolones ( OR=0.13, 0.13, 0.14, 0.13, 0.15, 0.13, 95% CI as 0.03-0.50, 0.02-0.98, 0.02-0.75, 0.02-0.59, 0.02-0.78, 0.02-0.57, P<0.05). Compared with carbapenems, the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole had no significant difference in the incidence of serious adverse drug reactions ( OR=0.96, 1.00, 1.10, 95% CI as 0.52-1.60, 0.31-3.50, 0.49-2.30, P>0.05). (3) Ranking of the efficacy and safety. ① The ranking list for clinical cure rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, synthetic penicillins, the second generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 51.73%, 35.72%, 22.57%, 31.37%, 24.98%, 32.82%, 34.69%, 29.05%, 72.36%, respectively. ② The ranking list for microbial clearance rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, the second generation cephalosporins+ metronidazole, synthetic penicillins, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 89.62%, 77.01%, 38.60%, 20.94%, 26.26%, 26.39%, 22.22%, 20.19%, 62.55%, respectively. ③ The ranking list for incidence of serious adverse drug reactions of different therapeutic regimens showed from high to low as quinolones, quinolones+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, the fourth generation cephalosporins+ metronidazole. The corresponding ranking probabilities of above regimens were 96.21%, 30.46%, 21.09%, 25.27%, 27.26%, 19.45%, 31.69%, respectively. Conclusion:In the treatment of middle- and low-risk intra-abdominal infections, it is recommended to empirically use cephalosporins+ metronidazole instead of carbapenems.