An open-label randomised, controlled, noninferiority clinical trial has shown that oral sitafloxacin is noninferior to intravenous (IV) ceftriaxone followed by oral cefdinir for the treatment of acute pyelonephritis and complicated urinary tract infection (cUTI).
While acute pyelonephritis develops in the lower urinary tract and spreads to the kidneys with systemic manifestations including sepsis, cUTI occurs in patients with urinary tract abnormality, urinary device, or immunocompromised conditions.1 Both acute pyelonephritis and cUTI are often associated with increased morbidity and mortality; they are also the most common cause of secondary bacteraemia.
In Thailand, the conventional antibiotic regimen for acute pyelonephritis with moderate infection is IV ceftriaxone followed by oral cephalosporin (i.e., cefdinir or cefixime).1 Meanwhile, with the availability of sitafloxacin in Thailand since 2012, it has been considered the most appropriate antibiotic choice for the treatment of acute pyelonephritis and cUTI caused by extended spectrum beta-lactamase (ESBL)-producing Escherichia coli. Thus the current study aims to compare the efficacy and safety of both treatment regimens.
This clinical trial was conducted in nine institutions across Thailand between August 2013 and September 2015.1 A total of 289 patients with acute pyelonephritis or cUTI were randomly assigned to receive either 100 mg oral sitafloxacin twice daily for 7 to 14 days, or 2 g IV ceftriaxone for 2 to 3 days followed by 100 mg oral cefdinir three times daily for another 4 to 12 days.
The most common causative pathogen isolated from the study was Escherichia coli, followed by Klebsiella pneumoniae and Proteus mirabilis.1 The intention-to-treat analysis revealed that 86.6% patients in the sitafloxacin group achieved clinical success compared to 83.3% patients in the ceftriaxone/cefdinir group; the per-protocol analysis, on the other hand, showed clinical success in 97.2% of patients receiving sitafloxacin and 99.0% of patients receiving ceftriaxone/cefdinir. This suggests a comparable clinical success rate of patients with acute pyelonephritis or cUTI in both treatment groups. In addition, the test for noninferiority showed that the primary outcomes of patients receiving sitafloxacin were noninferior to those receiving ceftriaxone/cefdinir.
The authors suggested that as oral carbapenems are not yet available in Thailand, oral sitafloxacin seems to be an appropriate treatment option for patients with acute pyelonephritis or cUTI – particularly those caused by ESBL-producing E. coli.1 The lower rate of resistance against sitafloxacin compared to ceftriaxone/cefdinir is also another factor to consider when administering oral sitafloxacin in this group of patients.
Oral sitafloxacin vs intravenous ceftriaxone followed by oral cefdinir for acute pyelonephritis and complicated urinary tract infection: a randomized controlled trial.