Optimal dosage and duration of pivmecillinam treatment for uncomplicated lower urinary tract infections: a systematic review and meta-analysis.
OBJECTIVE
To compare the efficacy and safety of different pivmecillinam (PIV) regimes for uncomplicated lower urinary tract infections (UTIs).


METHODS
The MEDLINE, Embase, and Cochrane Library databases were searched. Randomized controlled clinical trials (RCTs) involving adults or children with symptoms suggestive of uncomplicated UTI and that compared different PIV regimes or PIV versus other antibiotics were included. Meta-analyses were conducted to obtain direct and indirect efficacy estimates. PIV regimes were categorized into high total dosage, moderate total dosage, and low total dosage. The risk of bias was evaluated using the Cochrane tool.


RESULTS
Twenty-four RCTs were identified. No difference in clinical cure was found for the high vs. moderate (short-term: risk ratio (RR) 1.01, p=0.813; long term: RR 1.09, p=0.174) or high vs. low dosage comparisons (mean difference 0, 95% confidence interval -0.44 to 0.45, p=1). For bacteriological cure, comparisons of high vs. moderate dosage (short term: RR 1.05, p=0.056; long term: RR 1.05, p=0.131) and high vs. low dosage (short term: RR 1.02, p=0.759; long term: RR 1.13, p=0.247) showed a trend in favor of the high dosage treatment. Results for relapse, re-infection, and failure were inconclusive and not statistically significant. Patients treated with high dosages were 40% (p=0.062) and 44% (p=0.293) more likely to report mild to moderate adverse events.


CONCLUSIONS
There is insufficient evidence to support the use of an optimal combination of dosage, frequency, and duration of PIV therapy for the treatment of uncomplicated lower UTI. Evidence is limited due to the high risk of bias, poor reporting, and heterogeneous study data.
UroEvidence@Deutsche Gesellschaft für Urologie, Nestorstraße 8/9 (1. Hof), 10709 Berlin, Germany.
Mariona
M
Pinart
Department of Urology and Pediatric Urology, St. Antonius Hospital, Eschweiler, Germany.
Jennifer
J
Kranz
Institute of Medical Biometry and Informatics, University Heidelberg, Heidelberg, Germany.
Katrin
K
Jensen
Institute of Medical Biometry and Informatics, University Heidelberg, Heidelberg, Germany.
Tanja
T
Proctor
Technical University of Munich, Munich, Germany.
Kurt
K
Naber
UroEvidence@Deutsche Gesellschaft für Urologie, Nestorstraße 8/9 (1. Hof), 10709 Berlin, Germany; Department of Urology, University Hospital Erlangen, Erlangen, Germany.
Frank
F
Kunath
Department of Urology, Pediatric Urology and Andrology, Justus-Liebig University, Gießen, Germany.
Florian
F
Wagenlehner
UroEvidence@Deutsche Gesellschaft für Urologie, Nestorstraße 8/9 (1. Hof), 10709 Berlin, Germany. Electronic address: schmidt@dgu.de.
Stefanie
S
Schmidt
D000561:Amdinocillin Pivoxil / Q000008:administration & dosage*; D000892:Anti-Infective Agents, Urinary / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D014552:Urinary Tract Infections / Q000188:drug therapy*
D000892:Anti-Infective Agents, Urinary; D000561:Amdinocillin Pivoxil
Antibiotics; Meta-analysis; Pivmecillinam; Urinary tract infection