Reappraisal of the treatment duration of antibiotic regimens for acute uncomplicated cystitis in adult women: a systematic review and network meta-analysis of 61 randomised clinical trials

Background: Evidence from numerous randomised clinical trials suggest that shorter-term antimicrobial therapy is as effective as-and has other advantages over-longer-term antimicrobial regimens at achieving symptomatic cure for acute uncomplicated cystitis. Nevertheless, not all shorter regimens are adopted in clinical guidelines. This study was done to reappraise the treatment duration of each antibiotic in current guidelines for acute uncomplicated cystitis to investigate whether the regimen lengths of guideline approved antibiotics could be reduced. Methods: We systematically searched the PubMed, Embase, and Cochrane Library databases for relevant publications from inception of the databases until Dec 31, 2019. Only randomised clinical trials of women with acute uncomplicated cystitis that assessed antibiotic therapy and reported clinical or microbial response outcome values were included. A network meta-analysis was done and the quality of evidence of all of the included studies was rated. Clinical response was the primary outcome, defined as the complete disappearance of all baseline symptoms at the test-of-cure visit. Bayesian hierarchical random-effects model for dichotomous outcomes was used to compare the efficacy of each antibiotic treatment regimen directly and indirectly. This systematic review is registered in PROSPERO, CRD42018093529. Findings: Overall, 61 randomised clinical trials-which included 20 780 patients-were assessed in our systematic review. For the third-generation and fourth-generation fluoroquinolones, a 3-day regimen had similar effect to a single-dose regimen for clinical response (risk ratio [RR] 0·994 [95% credible interval 0·939-1·052] vs 1·024 [0·974-1·083]), with moderate quality of evidence. For pivmecillinam, 5-day and 7-day regimens were similar to a 3-day regimen for clinical response, with moderate quality of evidence (RR 1·041 [0·910-1·193] for the 5-day regimen and 1·095 [0·999-1·203] for the 7-day regimen). Meanwhile, for third-generation cephalosporins and amoxicillin and clavulanate, there was no difference between single-dose and 3-day regimens, but quality of evidence supporting this conclusion was low. For second-generation quinolones and co-trimoxazole, single-dose regimen was less effective than 3-day regimen in clinical response, with moderate quality of evidence. Interpretation: Treatment duration of the third-generation and fourth-generation quinolones and pivmecillinam could be shorter than the currently recommended regimens for acute uncomplicated cystitis. For other antibiotics, shorter duration of regimens could be considered, but further research is needed because of the low quality of supporting evidence. Funding: None.restrictio