Antibiotic prophylaxis to prevent spontaneous bacterial peritonitis in people with liver cirrhosis: a network meta-analysis

Komolafe, Oluyemi; Roberts, Danielle; Freeman, Suzanne C.; Wilson, Peter; Sutton, Alex J.; Cooper, Nicola J.; Pavlov, Chavdar S; Milne, EJ; Hawkins, Neil; Cowlin, Maxine; Thorburn, Douglas; Davidson, Brian R; Tsochatzis, Emmanuel; Gurusamy, Kurinchi Selvan

doi:10.1002/14651858.cd013125.pub2

Cited by 41 publications

(41 citation statements)

References 118 publications

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“…However, strict study inclusion criteria with limitation to high-quality RCTs with reported follow-up intervals and the current definition of SBP resulted in a patient collective with low heterogeneity of IRRs and allowed comparison over time with regard to IRRs of SBP and extraperitoneal infections. A recent Cochrane analysis observed no treatment effect of antibiotics over placebo but also included several other trials of low quality with high risk of bias and sparse data, which—according to the authors—made the results unreliable with inconsistent differences and high confidence intervals ( 17 ). This emphasizes the importance to select only high-quality trials with strict inclusion and exclusion criteria and similar or at least comparable follow-up periods.…”

Section: Discussionmentioning

confidence: 99%

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

Mücke

Graf

et al. 2020

Clin Transl Gastroenterol

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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.

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Section: Discussionmentioning

confidence: 99%

“…A recent Cochrane analysis including 23 studies could not find a significant benefit of antibiotic prophylaxis to prevent death or serious complications. However, many studies were of low quality, resulting in sparse data and high risk of bias ( 17 ). Thus, the type of antibiotic prophylaxis remains controversial ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

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

Mücke

Graf

et al. 2020

Clin Transl Gastroenterol

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“…Again, results suggest that only low-quality evidence supports the superiority of rifaximin over norfloxacin or other systemic antibiotics for either primary or secondary SBP prophylaxis (6,62,63) .…”

Section: Effects Of Rifaximin On Bacterial Infectionsmentioning

confidence: 94%

The Use of Rifaximin in Patients With Cirrhosis

Caraceni¹,

Vargas²,

Solà³

et al. 2021

Hepatology

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Rifaximin is an oral non-systemic antibiotic, with minimal gastrointestinal absorption and broadspectrum antibacterial activity covering both grampositive and gramnegative organisms.Rifaximin is currently worldwide used in patients with cirrhosis for preventing recurrent hepatic encephalopathy because its efficacy and safety has been proved by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which, in turn, can interfere with major events of the pathophysiological cascade

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“…42 However, because of its activity against bacterial translocation and its good safety profile, the use of rifaximin as a disease-modifying agent represents an attractive option. In addition, several observational studies and a few small-scale RCTs [47][48][49][50][51][52][53][54][55][56][57][58][59] have associated rifaximin treatment with a better control of difficult-to-treat/refractory ascites, 47,48 the reduced incidence of decompensation, all-cause hospitalisations and readmissions, SBP, variceal bleeding, and acute kidney injuryhepatorenal syndrome (AKI-HRS) with a decreased risk of renal replacement therapy. [49][50][51][52][53][54][55][56] An improvement in mortality has also been suggested in some studies.…”

Section: Key Pointmentioning

confidence: 99%

“…[49][50][51][52][53][54][55][56] An improvement in mortality has also been suggested in some studies. 48,52 However, the overall low quality of the evidence available, as highlighted by several meta-analyses, [57][58][59] precludes the possibility of reaching any definite conclusion on the global impact of rifaximin on the course of decompensated cirrhosis.…”

Section: Key Pointmentioning

confidence: 99%

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

Caraceni

Abraldes

Ginès

et al. 2021

Journal of Hepatology

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Patients with decompensated cirrhosis are currently managed through targeted strategies aimed at preventing or treating specific complications. In contrast, a disease-modifying agent should, by definition, be aimed at globally addressing 'decompensated cirrhosis'. To be defined as a disease-modifying agent in decompensated cirrhosis, interventions need to demonstrate an unequivocal benefit on the course of disease in well-designed and adequately powered randomised clinical trials with hard endpoints (i.e. patient survival). These trials also need to define the target population, dosage and timing of administration, factors guiding treatment, temporary or permanent stopping rules, transferability to daily clinical practice, cost-effectiveness, and global treatment access. By eliminating the underlying cause of cirrhosis, aetiologic treatments can still influence the course of decompensated disease by halting or slowing down disease progression or even inducing reversion to the compensated state. In contrast, there remains an unmet clinical need for disease-modifying agents which can antagonise key pathophysiological mechanisms of decompensated cirrhosis, such as portal hypertension, gut translocation, circulatory dysfunction, systemic inflammation, and immunological dysfunction. However, in the last few years, the repurposing of "old drugs" that have already been prescribed for more limited indications in hepatology or for other diseases has provided a few candidates, including human albumin, statins, and poorly absorbable oral antibiotics, which are under further evaluation in large-scale randomised clinical trials. New disease-modifying agents are also expected to be identified in the next decade through the systematic repurposing of existing drugs and the development of novel molecules which are currently undergoing pre-clinical or early clinical testing.

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Antibiotic prophylaxis to prevent spontaneous bacterial peritonitis in people with liver cirrhosis: a network meta-analysis

Abstract: Antibiotic prophylaxis to prevent spontaneous bacterial peritonitis in people with liver cirrhosis: a network meta-analysis.

Cited by 41 publications

References 118 publications

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

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

The Use of Rifaximin in Patients With Cirrhosis

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

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