Higher Rate of Spontaneous Bacterial Peritonitis Recurrence With Secondary Spontaneous Bacterial Peritonitis Prophylaxis Compared With No Prophylaxis in 2 National Cirrhosis Cohorts

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) bacteriology has changed over time. Reappraisal of primary SBP prophylaxis showed an increased rate of resistance in patients on primary prophylaxis with resultant discontinuation of this prophylaxis throughout the Veterans Affairs (VA). We aimed to re-evaluate the risk-benefit ratio of secondary SBP prophylaxis (SecSBPPr). METHODS: Using validated International Classification of Diseases -9/10 codes, we used the VA Corporate Data Warehouse and the Non-VA National TriNetX database to identify patients in 2 different large US systems who survived their first SBP diagnosis (with chart review from 2 VA centers) between 2009 and 2019. We evaluated the prevalence of SecSBPPr and compared outcomes between those who started on SecSBPPr vs not. RESULTS: We identified 4,673 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 (hazards ratio 1.63 [1.40–1.91], P < 0.001). This was accompanied by higher fluoroquinolone resistance odds in SecSBPPr patients (odds ratio = 4.32 [1.36–15.83], P = 0.03). In TriNetX, we identified 6,708 patients who survived their index SBP episode; 48.6% were on SecSBPPr. Multivariable analysis similarly showed SecSBPPr increased SBP recurrence risk (hazards ratio 1.68 [1.33–1.80], P < 0.001). Both data sets showed higher SBP recurrence trends over time in SecSBPPr patients. Results remained consistent at 6-month and 2-year timepoints. DISCUSSION: In 2 national data sets of >11,000 patients with SBP, we found that SecSBPPr was prescribed in roughly half of patients. When initiated, SecSBPPr, compared with 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.