Objective Changes in bacteriology of spontaneous bacterial peritonitis (SBP) has been documented. Reappraisal of primary SBP prophylaxis showed an increased rate of resistance in patients on primary prophylaxis with resultant discontinuation of this prophylaxis throughout the VA. We aimed to re-evaluate the risk-benefit ratio of secondary SBP prophylaxis (SecSBPPr).

Design Using validated ICD 9/10 codes, we utilized the VA Corporate Data Warehouse and the Non-VA National TriNetX database to identify patients in two different large US systems who survived their first SBP diagnosis (with confirmatory chart review from two VA centers) between 2009-2019. We evaluated the prevalence of SecSBPPr and compared outcomes between those started on SecSBPPr versus not.

Results We identified 4673 Veterans who survived their index SBP episode; 54.3% of whom were prescribed SecSBPPr. Multivariable analysis showed higher SBP recurrence risk in those on vs. off SecSBPPr (HR-1.63, p<0.001). This was accompanied by higher fluroquinolone-resistance risk in patients on SecSBPPr (OR=4.32, p=0.03). In TriNetX we identified 6708 patients who survived their index SBP episode; 48.6% were on SecSBPPr. Multivariable analysis similarly showed SecSBPPr increased the risk of SBP recurrence (HR-1.68, p<0.001). Both groups showed higher SBP recurrence trends over time in SecSBPPr patients.

Conclusion In two national data sets of >11,000 patients with SBP we found that SecSBPPr was prescribed in roughly half of patients. When initiated, SecSBPPr, compared to no prophylaxis after SBP, increased the risk of SBP recurrence in multivariable analysis by 63-68%, and this trend worsened over time. SecSBPPr should be reconsidered in cirrhosis.

• What is already known on this topic –

➢ Secondary prophylaxis to prevent recurrence of spontaneous bacterial peritonitis (SBP) has been recommended in several guidelines,

➢ Changing demographics and bacteriology could impact the effectiveness of secondary SBP prophylaxis, but a national perspective is needed.

➢ In a national Veterans cohort, primary SBP prophylaxis was associated with worse outcomes due to antibiotic resistance, which led to the VA discouraging this practice system-wide. However, the data regarding SBP prophylaxis is unclear.

• What this study adds –

➢ Almost 50% of patients with cirrhosis with SBP across 2 large US-based National cohorts (Veterans and TriNetX) evaluated from 2009-2019 were not initiated on secondary SBP prophylaxis, which gave us an opportunity to analyze the effectiveness over time in preventing recurrence.

➢ In >11,000 patients regardless of Veterans or non-Veterans, the use of secondary SBP prophylaxis worsened the rate of SBP recurrence without changes in mortality compared to those who were not on it.

➢ The SBP recurrence rate with secondary SBP prophylaxis worsened as time progressed in both cohorts and was associated with worsening antibiotic resistance.

• How this study might affect research, practice, or policy –

➢ The lack of improvement and higher SBP recurrence in patients on secondary SBP prophylaxis spanning two complementary cohorts should lead policymakers and antimicrobial stewardship professionals to re-evaluate the utility of this practice.

➢ Focusing on increasing ascites fluid culture to select patients who could benefit from secondary SBP prophylaxis may be necessary.

The authors have declared no competing interest.

Partly supported by VA Merit Review I01CX001076 and I01CX002472 to JSB and Richmond Institute for Veterans Research and VCU Wright Center CTSA UM1TR004360.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of Virginia Commonwealth University waived ethical approval for this work IRB of Richmond Veterans Affairs Medical Center gave ethical approval for this work

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