Duration of treatment with third- and fourth-generation quinolones and pivmecillinam could be shorter than the currently recommended regimens and still serve to effectively manage acute uncomplicated cystitis, according to a review by researchers at the Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine and the Yonsei University College of Medicine, Seoul, South Korea.
Uncomplicated urinary tract infection (UTI), an infection in healthy people without anatomical or functional urinary tract abnormalities, occurs more frequently in women than men, with 40% to 50% of women experiencing at least one infection in their lifetime. Most uncomplicated UTI infections in women are associated with symptoms of frequency, urgency, and dysuria. In real-world practice, urine culture is not mandatory and diagnosis involves history, physical examination, and urinalysis, and clinical guidelines recommend empirical antibiotic treatment.
The International Clinical Practice Guidelines for Treatment of Acute Uncomplicated Cystitis in women were updated in 2010 and recommend a single dose of fosfomycin trometamol, a 3-day regimen of trimethoprim and sulfamethoxazole (co-trimoxazole), a 5-day regimen of nitrofurantoin, and 3-day and 7-day regimens of pivmecillinam.
Studies have suggested that shorter-term antimicrobial therapy may be just as effective or even advantageous over longer-term regimens for acute uncomplicated cystitis; however, shorter regimens are not always adopted in clinical guidelines. Therefore, a team of investigators conducted a systemic review and network meta-analysis to investigate the effectiveness of reduced duration of guideline-approved antibiotic regimens for acute uncomplicated cystitis.
In total, 61 randomised trials that included 20,780 patients were identified through a search of PubMed, Embase, and the Cochrane Library. All included clinical trials assessed antibiotic therapy in women with acute uncomplicated cystitis and reported clinical or microbial response outcomes.
Results suggest that shorter-term antimicrobial therapy is just as effective as longer-term therapy for acute uncomplicated cystitis. Although a treatment duration of 3 to 7 days is recommended for pivmecillinam, clinical responses in patients receiving 5-day and 7-day regimens were similar to those receiving a 3-day regimen, with evidence of moderate quality (risk ratio [RR] 1.041 for 5 days; 1.095 for 7 days). A similar clinical response was seen between a 3-day regimen and single dose of third-generation and fourth-generation fluoroquinolones, with evidence of moderate quality (RR 0.994 vs 1.024).
Conversely, 3-day regimens of second-generation quinolones and co-trimoxazole were associated with greater clinical response than single-dose regimens, also with evidence of moderate quality. No difference was observed in clinical response between single-dose and 3-day regimens for third-generation cephalosporins, amoxicillin, and clavulanate, but evidence quality was low or very low.
Overall, the review authors conclude, “Because antibiotic resistance has been increasing substantially worldwide, a shorter treatment duration can be beneficial in minimizing antibiotic resistance and collateral damage and reducing antibiotic-related costs and adverse effects. From this point of view, our findings are thought to be valuable.”
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.
Do Kyung Kim, Jae Heon Kim, Joo Yong Lee, Nam SuKu, Mye Sun Lee, Ju-Young Park, Jong Won Kim, Kwang Joon Kim, Kan SuCho
Infectious Disease Advisor material
The Lancet Infectious Disease abstract