Editorial: Spontaneous Bacterial Peritonitis—Redrawing Empiric Therapy in the Era of Multidrug Resistance

Abbreviations

ACLF

Acute‐on‐Chronic Liver Failure

APASL

Asia‐Pacific Association for the Study of the Liver

CNNA

Culture‐negative neutrocytic ascites

CRO

Carbapenem‐Resistant Organism

EASL

European Association for the Study of the Liver

ESBL

Extended‐Spectrum Beta‐Lactamase

MDRO

Multidrug‐Resistant Organism

NNBA

Non‐Neutrocytic Bacterascites

SBP

Spontaneous Bacterial Peritonitis

In cirrhosis, spontaneous bacterial peritonitis (SBP) is a sentinel decompensating event with short‐term mortality rates comparable to variceal haemorrhage [1]. However, three decades of reliance on empiric third‐generation cephalosporins are being challenged by a shifting microbial landscape, particularly in South Asia, where multidrug‐resistant organisms (MDRO) account for over 70% of infections [1, 2]. The multicenter SBP‐INDIA study by Verma and colleagues provides essential data from this high‐resistance environment, offering a clinically relevant framework for empiric therapy and stewardship [3].

The investigators analysed 319 hospitalized adults with culture‐positive ascitic infections across 13 tertiary centers. MDRO and carbapenem‐resistant organisms (CRO) were identified in 53.6% and 24.1%, respectively, with a predominance of gram‐negative bacteria (74.6%) [3]. MDRO infection was independently associated with nosocomial or healthcare‐associated acquisition, circulatory failure, and quinolone prophylaxis patterns broadly aligned with European cohorts but considerably greater in magnitude [4]. Crucially, 30‐day survival was substantially lower with MDRO infection (53.2% vs. 73.6%), and resistance status remained an independent predictor of mortality, alongside organ failure and systemic inflammation [3].

Two findings deserve particular emphasis. First, the authors propose a risk‐based empiric regimen tailored to acquisition setting and resistance phenotype (Table 1). This aligns with EASL and APASL recommendations [5, 6] but is now anchored in region‐specific data. In environments where most nosocomial isolates are multidrug‐resistant, cephalosporin monotherapy is no longer defensible. Broader coverage is required, followed by prompt de‐escalation [7]. And second, the most provocative discovery is the outcome equivalence between SBP and non‐neutrocytic bacterascites (NNBA). Nearly one‐third of culture‐positive patients presented with an ascitic neutrophil count (ANC) < 250 cells/mm³ yet faced mortality indistinguishable from classic SBP. This challenges the long‐standing dichotomy that anchors treatment to the 250‐cell threshold [5, 6, 8] and justifies a lower clinical threshold for intervention in symptomatic, culture‐positive patients.

TABLE 1.

A risk‐stratified empiric framework for spontaneous ascitic fluid infections in hospitalized cirrhosis, adapted from the SBP‐INDIA study.

Risk stratum	Typical clinical setting	Suggested empiric regimen
Low resistance risk	Community‐acquired SBP, no recent antibiotics, no organ failure, ambulatory baseline	Third‐generation cephalosporin (e.g., ceftriaxone, cefotaxime); reassess at 48 h
Intermediate	Healthcare‐associated acquisition; quinolone prophylaxis; recent admission or invasive procedure	Piperacillin–tazobactam, or carbapenem if local ESBL prevalence is high
High resistance risk	Nosocomial acquisition; ACLF, circulatory or respiratory failure; high leukocyte count	Carbapenem ± gram‐positive cover (e.g., teicoplanin/daptomycin); add cefiderocol or β‐lactam/β‐lactamase inhibitor combinations where CRO prevalence is high

Note: Empiric choices should be refined by local antibiograms and de‐escalated promptly on the basis of culture results and clinical response.

Abbreviations: ACLF, acute‐on‐chronic liver failure; CRO, carbapenem‐resistant organism; ESBL, extended‐spectrum β‐lactamase; SBP, spontaneous bacterial peritonitis.

Nonetheless, the increasing focus on microbiological data does not diminish the clinical relevance of ANC. Pleocytosis remains a vital prognostic indicator, as evidenced by the SBP vs. Culture‐negative neutrocytic ascites (CNNA) comparison: CNNA demonstrated a significantly lower 90‐day survival than SBP (38.9% vs. 61.1%, p = 0.003). This indicates that an elevated ANC represents a severe clinical state regardless of culture status. While the study's comparative design is insightful, a consolidated analysis simultaneously incorporating SBP, CNNA, and NNBA might have further elucidated the interplay between bacterial load and host inflammatory response.

Though limited by its hospital‐based, retrospective design and missing confounders, the consistency of the resistance signals and survival gaps renders these findings significant. Nevertheless, the recommendation to treat all NNBA cases requires a tempered interpretation; antibiotic therapy should ideally be guided by overt clinical signs of infection to avoid unnecessary broad‐spectrum exposure in stable patients.

Three practice priorities emerge: individualizing empiric antibiotic therapy by risk stratification rather than utilizing ANC cutoff alone. Antimicrobial stewardship must be intensified, especially in public‐sector hospitals managing high‐acuity cirrhosis. And novel agents, including cefiderocol and newer β‐lactam/β‐lactamase inhibitor combinations, urgently require evaluation in this population [9]. In conclusion, while SBP‐INDIA necessitates a management re‐evaluation of ascitic infections in an era of critical resistance, clinical policy must balance microbiological evidence with clinical judgement and stewardship to optimize survival.

Author Contributions

Apichat Kaewdech: conceptualization, writing – original draft. Pimsiri Sripongpun: conceptualization, writing – review and editing, supervision.

Funding

The authors have nothing to report.

Linked Articles

This article is linked to Verma et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70716 and https://doi.org/10.1111/apt.70767.

Kaewdech A. and Sripongpun P., “Editorial: Spontaneous Bacterial Peritonitis—Redrawing Empiric Therapy in the Era of Multidrug Resistance,” Alimentary Pharmacology & Therapeutics 64, no. 4 (2026): 531–532, 10.1111/apt.70745.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.