{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:55:07Z","timestamp":1793130907635,"version":"4.5.0"},"reference-count":29,"publisher":"Becaris Publishing Limited","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Comp. Eff. Res."],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:p>\n                    <jats:bold>Aim:<\/jats:bold>\n                    Compared with uncomplicated urinary tract infections (UTIs), complicated UTIs (cUTIs) including acute pyelonephritis (AP) present with significant morbidity, a higher risk of treatment failure and typically require longer courses of treatment, or alternative antibiotics. The emergence of drug-resistant organisms represents a considerable challenge in the treatment of patients with cUTIs\/AP and has limited antibiotic options. Carbapenems are considered the current last line of therapy, however, carbapenem resistance represents a growing problem. Although several established and novel treatment options are available, direct comparative evidence is lacking.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Randomized controlled trials (RCTs) were identified by systematic literature review of Embase\n                    <jats:sup>\u00ae<\/jats:sup>\n                    , MEDLINE\n                    <jats:sup>\u00ae<\/jats:sup>\n                    and Cochrane databases (database inception to 15th June 2022). Relevant conference proceedings (2020\u20132022) were also reviewed. Following feasibility assessment to verify network connectivity at an overall level, outcome specific networks were prepared. Bayesian network meta-analysis (NMA) was performed (using R version 4.2.1) to determine the relative efficacy of various treatments for cUTI\/AP, including cefepime\u00a0+\u00a0enmetazobactam. Convergence was assessed by visual inspection of trace plots. The accuracy of the posterior estimates was assessed using the Monte Carlo error for each parameter. Published study results were included in the synthesis of the relative risk (RR) of efficacy end points, using a logit link with binomial likelihood distribution.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Feasibility assessment was conducted for 40 RCTs identified, to assess the viability of constructing a network of interlinked RCTs. Of those, 28 studies were included in the master NMA network. A fixed effects model (FEM) was selected due to low statistical heterogeneity, according to I\n                    <jats:sup>2<\/jats:sup>\n                    values. For composite outcome at test of cure (TOC), ceftolozane\u00a0+\u00a0tazobactam, cefepime\u00a0+\u00a0enmetazobactam, cefiderocol, levofloxacin and plazomicin demonstrated significantly higher RRs versus carbapenems. For microbiological eradication at TOC, cefepime\u00a0+\u00a0enmetazobactam, plazomicin, cefiderocol, fosfomycin, meropenem\u00a0+\u00a0vaborbactam and ceftazidime\u00a0+\u00a0avibactam demonstrated significantly higher RRs versus carbapenems. RRs for cefepime\u00a0+\u00a0enmetazobactam were also significantly higher versus several established and novel treatment options for composite outcome, microbiological eradication and clinical cure.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Against the backdrop of increasing bacterial resistance, these findings suggest that cefepime\u00a0+\u00a0enmetazobactam may represent an effective carbapenem-sparing treatment option in patients with cUTI including AP.\n                  <\/jats:p>","DOI":"10.57264\/cer-2024-0214","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T08:44:17Z","timestamp":1739954657000},"source":"Crossref","is-referenced-by-count":16,"title":["Efficacy of treatment options for complicated urinary tract infections including acute pyelonephritis: a systematic literature review and network meta-analysis"],"prefix":"10.57264","volume":"14","author":[{"given":"Florian","family":"Wagenlehner","sequence":"first","affiliation":[{"name":"Clinic of Urology, Pediatric Urology &amp; Andrology, Justus Liebig University Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica Rico","family":"Caballero","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, Hospital Clinic &amp; IDIBAPS, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikalp","family":"Maheshwari","sequence":"additional","affiliation":[{"name":"Parexel International, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayantika","family":"Biswas","sequence":"additional","affiliation":[{"name":"Parexel International, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Saini","sequence":"additional","affiliation":[{"name":"Parexel International, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Quevedo","sequence":"additional","affiliation":[{"name":"Advanz Pharma, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Polifka","sequence":"additional","affiliation":[{"name":"Advanz Pharma, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Advanz Pharma, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Cure","sequence":"additional","affiliation":[{"name":"Advanz Pharma, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"36897","reference":[{"issue":"11","key":"e_1_3_6_2_2","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1007\/s00345-019-03071-4","article-title":"Epidemiology of urological infections: a global burden","volume":"38","author":"\u00d6zt\u00fcrk R","year":"2020","unstructured":"\u00d6zt\u00fcrk R, Murt A. Epidemiology of urological infections: a global burden. World J. Urol. 38(11), 2669\u20132679 (2020).","journal-title":"World J. Urol."},{"key":"e_1_3_6_3_2","doi-asserted-by":"crossref","first-page":"888205","DOI":"10.3389\/fpubh.2022.888205","article-title":"Disease burden and long-term trends of urinary tract infections: a worldwide report","volume":"10","author":"Yang X","year":"2022","unstructured":"Yang X, Chen H, Zheng Y, Qu S, Wang H, Yi F. Disease burden and long-term trends of urinary tract infections: a worldwide report. Front. Public Health 10, 888205 (2022).","journal-title":"Front. Public Health"},{"key":"e_1_3_6_4_2","volume-title":"Complicated urinary tract infections.","author":"Sabih A","year":"2023","unstructured":"Sabih A, Leslie S. Complicated urinary tract infections. StatPearls Publishing, FL, USA (2023). 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