The development of spontaneous bacterial peritonitis (SBP) represents a major prognostic landmark in the course of decompensated cirrhosis, as it is associated with high morbidity and mortality 1. Consequently, long-term antibiotic prophylaxis for the prevention of first or recurrent SBP episodes, most commonly with the fluoroquinolone norfloxacin, is recommended by international guidelines 2, 3. However, increasing evidence for growing antibiotic resistance, especially to fluoroquinolone antibiotics, along with changing patterns of bacterial pathogens of SBP has challenged this practice in recent years 4. A recent observational study even suggested an increased risk of recurrent SBP episodes in patients receiving antibiotic prophylaxis 5. Further, adverse effects of fluoroquinolone antibiotics, such as tendon rupture, impaired cardiac conduction and increased risk for Clostridium difficile enteritis, may pose significant health risks to patients 6. The present study 7 investigated a large US Veteran cohort including more than 50,000 patients with decompensated cirrhosis and provides much-needed further data on the effects of SBP development and antibiotic prophylaxis on long-term outcomes. As to be expected, the development of SBP was associated with reduced survival in the study collective. Indeed, the study found that—despite the severe negative prognostic impact of SBP itself—both primary and secondary prophylaxis were associated with higher mortality. Furthermore, antibiotic resistance increased significantly with repeated SBP episodes and with ongoing prophylaxis use. It is also interesting to note that despite documented resistance, most patients continued the same prophylactic regimen, suggesting limited translation of microbiological results into practice. These results must be interpreted with caution, as patients who received SBP prophylaxis had more advanced chronic liver disease. Therefore, the observed interaction between prophylaxis and mortality might partly reflect greater disease severity rather than a direct harmful effect of antibiotic prophylaxis. Nevertheless, the findings contribute to a growing body of evidence that long-term antibiotic prophylaxis promotes increased microbial resistance and may even adversely affect patient outcomes, underscoring the urgent need to reassess SBP prevention strategies. In this context, identification of high-risk patients to enable more precise allocation to SBP prophylaxis, along with regular reassessment according to local microbial and resistance patterns could be promising approaches. Further, alternative antibiotic substances with a more favourable risk–benefit profile could be viable alternatives to norfloxacin. However, recent randomised-controlled trials investigating the use of rifaximin or cotrimoxazole for primary prophylaxis of SBP failed to show a survival benefit in patients with decompensated cirrhosis 8, 9. It is interesting to note that these studies used different criteria to allocate patients to SBP prophylaxis (with and without considering kidney/liver function and protein content in ascites). The comparable outcomes observed in both studies suggest that a more in-depth stratification of populations at high risk for SBP could be necessary. In summary, the present study fuels the ongoing controversy over antibiotic prophylaxis strategies for SBP and highlights the need for intensified research efforts in this field. Lukas Sturm: writing – original draft. Robert Thimme: writing – review and editing. Dominik Bettinger: writing – review and editing. The authors have nothing to report. This article is linked to Silvey et al. paper. To view this article, visit https://doi.org/10.1111/apt.70498. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Sturm et al. (Mon,) studied this question.