Efficacy of Norfloxacin Prophylaxis to Prevent Spontaneous Bacterial Peritonitis: A Systematic Review and Meta-Analysis

Abstract

INTRODUCTION: With the emergence of multidrug-resistant organisms, the efficacy of antibiotic prophylaxis to prevent spontaneous bacterial peritonitis (SBP) has been debated. The aim of this study was to assess factors impacting effectiveness of SBP prophylaxis. METHODS: We searched PubMed, Embase, and the Cochrane Registry from inception to May 2019 to identify randomized controlled trials of patients with liver cirrhosis that assessed SBP occurrence/recurrence during antibiotic prophylaxis with the common antibiotic agents. Network meta-analysis was performed, pooling data with regard to incidence rate ratios (IRRs) of SBP, death, or extraperitoneal infections. RESULTS: Overall, 1,626 patients in 12 randomized controlled trials were included. During primary prophylaxis, the incidence rate of SBP and death in the norfloxacin-treated patients was 0.117 and 0.438 per patient-year, respectively, and IRRs of placebo vs norfloxacin were significantly higher (IRR 5.35, 95% confidence interval 1.99–14.38, P = 0.0009 for SBP and IRR 2.04, 95% confidence interval 1.20–3.44, P = 0.008 for death). The efficacy of norfloxacin to prevent SBP, but not death, decreased over time (annual percent change from 1992 to 2015 8.2%, P = 0.019), The positive treatment effect was lower in studies including patients with increased ascites protein ( P = 0.021) or exceedingly high serum bilirubin ( P = 0.012) levels. Norfloxacin was not superior to other antibiotics. The incidence rate of SBP was 2.5-fold higher in patients treated with norfloxacin as secondary compared with primary prophylaxis. No significant differences between treatment designs were observed in secondary prophylaxis. DISCUSSION: Norfloxacin remained superior to placebo in preventing SBP, yet the efficacy to prevent SBP, not death, decreased over time. Further studies to understand this phenomenon are urgently needed.

Prevention of Cirrhosis Complications: Looking for Potential Disease Modifying Agents

“…Subsequent studies showed that either norfloxacin or ciprofloxacin significantly prevented SBP occurrence in high-risk patients with low protein concentration in ascites, liver failure, and/or gastrointestinal bleeding. The benefit deriving from either norfloxacin or ciprofloxacin in either primary or secondary prophylaxis of SBP was confirmed by most meta-analyses [ 73 , 74 ]. Interestingly, norfloxacin reduced circulating bacterial products associated with improved systemic inflammatory markers and circulatory dysfunction [ 75 ].…”

Indications for medical antibiotic prophylaxis and potential targets for antimicrobial stewardship intervention: a narrative review

“…• Choice of antibiotics (taking into account emerging resistance to and adverse effects of fluoroquinolones) [109][110][111][112][113][114] AP in bite wounds…”

The search for disease-modifying agents in decompensated cirrhosis: From drug repurposing to drug discovery

“…2). In addition, based on favourable trials and meta-analyses, [38][39][40][41] norfloxacin is currently recommended by international guidelines for the primary prophylaxis of SBP in patients with ascites at high-risk (Child-Pugh score > − 9 and serum bilirubin level > − 3 mg/dl, with either impaired renal function or hyponatremia, and ascitic fluid protein lower than 15 g/L) and for secondary prophylaxis against SBP recurrence. 42 However, since norfloxacin acts effectively on bacterial translocation, which is a key initial event in the pathophysiological cascade of decompensated cirrhosis, its clinical benefit could be extended beyond the sole prevention of SBP.…”