Sitafloxacin a promising treatment alternative for UTI

Oral sitafloxacin was just as effective and safe as levofloxacin for the treatment of complicated and uncomplicated urinary tract infections (UTIs) in adults, according to a phase III study from China.

“Complicated UTI is recurrent and refractory to treatment. Hospital-acquired UTIs are usually associated with resistant microorganisms. Hence, UTIs have produced [a] huge medical and economic burden … UTI is also one of the most common infections in China,” said the researchers.

Escherichia (E.) coli, the most frequently isolated pathogen in community-acquired uncomplicated UTIs, is highly resistant even to established antimicrobial agents*. [Infect Chemother 2018;50:67-100] Studies show that about a third of urinary isolates of E. coli are resistant to cephalosporins**, while half are not susceptible to levofloxacin or ciprofloxacin. [J Infect 2011;63:114-123]

“Therefore … a new highly active antimicrobial agent with broad coverage in clinical practice [is urgently needed] to fight UTIs, especially complicated UTIs associated with resistant bacterial isolates,” said the researchers. “[Our findings show that] sitafloxacin … can provide good clinical and microbiologic efficacy [in this setting].”

The study comprised 206 participants with acute uncomplicated and complicated UTIs and were randomized in a 1:1 ratio. Those with uncomplicated UTI received either sitafloxacin 100 mg QD or levofloxacin 500 mg QD for 3–5 days, while those with complicated UTI were given sitafloxacin 100 mg BID or levofloxacin 500 mg QD for 10–14 days. Primary efficacy endpoint was clinical cure rate at test-of-cure (TOC) visit in the per-protocol set (n=135 [uncomplicated] and 59 [complicated]). [Ann Med 2021;53:217-226]

At the TOC visit, clinical cure rates in the respective sitafloxacin and levofloxacin arms were 89 percent and 97 percent in the uncomplicated UTI cohort (p=0.066), and 82 percent and 77 percent in the complicated UTI cohort (p=0.643).

In terms of microbiologic eradication rate, in the uncomplicated UTI group, all 26 E. coli strains at baseline were eradicated following sitafloxacin use, while levofloxacin eradicated 32 of 33 E. coli isolates. These corresponded to overall bacterial eradication rates of 100 percent and 97 percent, respectively. In the complicated UTI group, the corresponding bacterial eradication rates were 93 percent and 67 percent for the respective sitafloxacin and levofloxacin arms.

Sitafloxacin-related clinical adverse event (AE) rates were similar between the uncomplicated and complicated UTI cohorts (16 percent vs 12 percent). The most common clinical AEs were pruritus and palpitation (uncomplicated UTI group) and abdominal distension (complicated UTI group).

In the uncomplicated UTI cohort, the rates of drug-related AEs were 28 percent and 18 percent in the respective sitafloxacin and levofloxacin arms. The corresponding rates among those with complicated UTI were 26 percent and 28 percent, respectively. None led to treatment cessation.

“[Our] safety analysis … suggests that oral sitafloxacin is as safe as levofloxacin. The drug-related clinical AEs … were mostly mild in severity [and] transient … These results indicate that sitafloxacin is well-tolerated in treating patients with acute uncomplicated or complicated UTI when administered by current dosing regimens,” said the researchers.

“The emerging antimicrobial resistance in the pathogens of UTIs poses a serious challenge to the efficacy of fluoroquinolone therapy. Clinicians should pay careful attention to the susceptibility testing results of local bacterial isolates when prescribing sitafloxacin,” they added.

Apart from sitafloxacin, newer fluoroquinolones (eg, finafloxacin, delafloxacin) are being developed to combat drug-resistant pathogens. “Sitafloxacin and these promising fluoroquinolones will provide more treatment options for the clinical management of UTIs in adults … It is expected to improve the outcome of patients with UTI, especially complicated UTI,” the researchers concluded.