Ceftriaxone, ciprofloxacin not inferior to cefotaxime for spontaneous bacterial peritonitis

Antibiotics, such as cefotaxime, ceftriaxone, and ciprofloxacin, demonstrate similar efficacy against spontaneous bacterial peritonitis (SBP), reports a study. Additionally, ciprofloxacin or ceftriaxone is not inferior to cefotaxime, which is the current standard for empirical therapy of community-acquired SBP.

“With the increasing prevalence of antibiotic-resistant organisms, response-guided therapy, considering the result of 48 hours ascitic polymorphonucleated (PMN) cell count on paracentesis, ensures the safety of empirical antibiotic therapy in the era of multidrug resistance,” the researchers said.

This multicentre, prospective, randomized controlled trial included 261 liver cirrhosis patients with ascites, aged 16 to 75 years, who have PMN cell count of >250/mm³. The research team conducted a follow-up paracentesis at 48 hours to determine whether patients should continue or change the assigned antibiotics. They then evaluated the resolution rates at 120 and 168 hours of treatment.

Of the patients, the majority were diagnosed as those with SBP within 48 hours of admission. Intent-to-treat (ITT) analysis revealed resolution rates at 120 hours of 67.8 percent in the cefotaxime group, 77.0 percent in the ceftriaxone group, and 73.6 percent in the ciprofloxacin group (p=0.388). [Am J Gastroenterol 2023;118:654-663]

No significant between-group difference was observed in mortality at 1 month (p=0.770). The model for end-stage liver disease score and SBP resolution were the most important factors for short-term survival, which correlated with the degree of systemic inflammation and underlying liver function, as represented by bilirubin or albumin levels, considering baseline factors only.

“These findings suggest that liver function, systemic inflammation, and treatment response are key parameters for the survival of patients with SBP,” the researchers said.

Among the three empirical therapies, cefotaxime has been studied extensively as treatment against SBP. In the early 1990s, the resolution rate after 5 days of cefotaxime was 93 percent, which was comparable to that after 10 days of the same treatment. [Hepatology 1985;5:457-462; Gastroenterology 1991;100:1737-1742]

“Hence, the American Association for the Study of Liver Diseases recommends intravenous third-generation cephalosporins such as cefotaxime as an initial treatment for SBP,” the researchers said. [Hepatology 2013;57:1651-1653; Hepatology 2021;74:1014-1048]

“In this study, the response rate was 67.8 percent with ITT analysis and 80.6 percent with per-protocol (PP) analysis at 120 hours. Although the response rates were lower than those in previous reports, on-treatment modification and extension of therapy improved the treatment response further,” they noted.

For ceftriaxone, the response rate was previously reported to be 95 percent in the early 2000s, but only 77.0 percent and 85.5 percent with ITT and PP analyses, respectively, were observed in the current study. However, the rate of ceftriaxone was the highest among the three antibiotics, and its noninferiority to cefotaxime was established.

Ciprofloxacin, on the other hand, can be administered intravenously or orally for SBP treatment. In this study, the response rates at 120 hours were 73.6 percent with ITT analysis and 85.9 percent with PP analysis. Both rates are not inferior to those of cefotaxime despite the concern of quinolone resistance. [J Hepatol 2000;33:564-569; Dig Dis Sci 2019;64:2359-2367]