Combination of GM CSF and carbapenem is superior to carbapenem monotherapy in difficult‐to‐treat spontaneous bacterial peritonitis: A randomized controlled trial

Abstract

Background: Patients with cirrhosis and treatment non-responsive spontaneous bacterial peritonitis (SBP) have high mortality. We aimed to investigate whether GM-CSF can improve SBP response rates. Patients and Methods:In this open-label RCT, 131 cirrhosis patients with difficult-totreat SBP (DTT SBP) were randomized to receive meropenem alone (1 g IV thrice daily for 5 days) (MERO Group, n = 66) or in combination with GM-CSF (1.5 mcg/Kg daily IV till resolution or till 5d) (MEROGM Group, n = 65). The primary end-point was SBP early-response (reduction in absolute neutrophil count (ANC) by >25% after 48 h).Secondary end-points included SBP resolution at day 5.Results: Patients in MEROGM group in comparison to MERO group had higher SBP early-response (60% vs. 31.8%; p = .001) and SBP resolution rates (55.4% vs. 24.2%; p = .0003). Patients in the combination arm also had better resolution of pneumonia {8/17 (47.05%) vs. 2/19 (10.5%), p = .02} and lower incidence of new-onset AKI (15.4% vs. 31.8%, p = .02), HE (18.5% vs. 34.8%, p = .04) and infections (21.5% vs. 37.9%, p = .05). In comparison to MERO group, 7-day survival was higher in MEROGM group (89.2% vs. 78.7%, p = .03), though the 28-day survival was comparable (78.4% vs. 71.2%; p = .66). None of the patients developed treatment-related severe adverse effects requiring discontinuation of therapy. Conclusions:The addition of GM-CSF to meropenem significantly improves response rates in DTT SBP patients within 48 h. Early use of GMCSF modulates host immune response, and enhances antibiotic response with higher SBP resolution. The use of GMCSF needs to be considered in combating difficult SBP in cirrhosis patients.

The impact of different antibiotic injection regimens on patients with severe infections: A meta‐analysis

“…For instance, common cold and flu symptoms can often be relieved by using antipyretics or cough suppressants alone. Moreover, some chronic conditions such as hypertension, diabetes, and thyroid issues can be managed with a single medication 41,42 . Combination therapy, on the other hand, involves multiple healthcare professionals or therapists working collaboratively to provide comprehensive treatment plans for patients 43 .…”

“…Moreover, some chronic conditions such as hypertension, diabetes, and thyroid issues can be managed with a single medication. 41 , 42 Combination therapy, on the other hand, involves multiple healthcare professionals or therapists working collaboratively to provide comprehensive treatment plans for patients. 43 This approach is typically utilized for complex diseases or issues that require knowledge and skills from various professional fields to address effectively.…”

Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23

“…Moreover, the experimental group demonstrated an improvement in the inflammatory reaction in the lungs without affecting the inflammatory levels in the blood. Another open-label RCT evaluated the effects of combining intravenous GM-CSF with Meropenem in 131 cirrhosis patients with difficult-to-treat spontaneous bacterial peritonitis (SBP) [ 112 ]. The group treated with GM-CSF had higher SBP early response and SBP resolution rates than the group treated with meropenem alone.…”

Critical Care Management of Acute-on-Chronic Liver Failure: Certainties and Unknowns

“…17,18 Treatment with GM-CSF also improved the resolution rate of severe infections (spontaneous bacterial peritonitis and pneumonia) in a single-center RCT. 19 Fungal infections are less frequent than bacterial episodes and usually complicate the course of ACLF (second infection). Invasive candidiasis/candidemia and invasive aspergillosis are the most frequent fungal infections (80 and 20%, respectively) and are associated with very poor prognosis (mortali-ty > 50%) despite adequate therapy.…”

“…17 18 Treatment with GM-CSF also improved the resolution rate of severe infections (spontaneous bacterial peritonitis and pneumonia) in a single-center RCT. 19…”