Daptomycin + Meropenem Versus Ceftazidime in the Treatment of Nosocomial Spontaneous Bacterial Peritonitis

Study Overview
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Brief Summary
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Nosocomial spontaneous bacterial peritonitis (SBP) is frequently caused by multi drug resistant bacteria. Standard treatment of SBP could be ineffective. The aim of the study is to compare daptomycin + meropenem vs ceftazidime in the treatment of nosocomial SBP.

Detailed Description
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Spontaneous bacterial peritonitis (SBP) is a well known complication in patients with liver cirrhosis and ascites. Nosocomial SBP is defined as SBP that occurs after 48 hours of hospitalization. It has been shown that patients with nosocomial SBP have a worse prognosis than patients with community-acquired SBP. It has also been shown that nosocomial SBP is frequently caused by multi drug resistant bacteria such as extended-spectrum-beta-lactamase (ESBL) producing enterobacteria or meticillin - resistant staphylococcus aureus. Currently the empirical treatment of SBP is the use of third generation cephalosporins or amoxicillin/clavulanic acid. In patients affected by nosocomial SBP these treatment could be ineffective. Up to now an empirical approach with a broader spectrum strategy (such as an association between meropenem and daptomycin) has never been compared to standard therapy in the treatment of nosocomial SBP. Thus, the aim of the study is to compare daptomycin + meropenem vs ceftazidime in the treatment of nosocomial SBP in patients with cirrhosis.

Official Title
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Daptomycin + Meropenem Versus Ceftazidime in the Treatment of Nosocomial Spontaneous Bacterial Peritonitis: an Open, Randomized, Controlled Clinical Trial

Conditions
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Cirrhosis, Ascites, Nosocomial Spontaneous Bacterial Peritonitis

Intervention / Treatment
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* Drug: Daptomycin + Meropenem
* Drug: Ceftazidime


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with liver cirrhosis and ascites Meets all criteria for nosocomial SBP as outlined below Ascitic fluid polymorphonuclear cells count >250/mm3 Onset of signs and symptoms of infection after 72 hours of hospitalization Exclusion Criteria: Hepatocellular carcinoma beyond the Milan criteria Abdominal surgery within 4 weeks Evidence of secondary peritonitis, pancreatitis or peritoneal carcinomatosis Significant heart or respiratory failure Allergy to ceftazidime, meropenem or daptomycin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daptomycin + Meropenem<br>30 patients with cirrhosis and nosocomial SBP | Drug: Daptomycin + Meropenem<br>* Daptomycin will be administered at the dose of 6 mg/kg every 24 hours and 6 mg/kg every 48 hours for an estimated creatinine clearance (CKD-EPI) of > 30 ml/min and < 30 ml/min respectively. Meropenem will be administered at the dose of 1 g t.i.d., 1 g b.i.d., 0.5 g every 24 hours for an estimated creatinine clearance of >50 ml/min, 10-50 ml/min, and < 10 ml/min respectively. The treatment will go on for 7 days. In the patients without response to treatment after 48 hours will be added a rescue therapy with fluconazole. In patients in which cultures shown a bacterial species resistant to therapy, daptomycin and meropenem will be discontinued and replaced by a therapy based on antibiotic susceptibility of isolated species.<br>|
| Active Comparator: Ceftazidime<br>30 patients with cirrhosis and nosocomial SBP | Drug: Ceftazidime<br>* Ceftazidime will be administered at the dose of 2 g t.i.d, 2 g b.i.d and 2 g at every 24 hours by intravenous infusion for an estimated creatinine clearance (CKD-EPI) of >50 ml/min, 10-50 ml/min, and < 10 ml/min respectively. The treatment will go on for 7 days. In the patients without response to treatment after 48 hours, or in which cultures shown a bacterial species resistant to therapy, ceftazidime will be discontinued and replaced by a rescue therapy with meropenem and daptomycin as provided for the experimental arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end-point of the study is the response to therapy | The response to therapy is defined as the reduction of polymorphonuclear leukocytes (PMN) count in ascitic fluid more than 25 % from baseline after 48 hours and as a PMN count in ascitic fluid less then 250/mm³ after seven days. | 48 hours and seven days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality during hospitalization |  | participants will be followed for the duration of hospital stay, an expected average of 6 weeks | 
| 30 days mortality |  | 30 days | 
| 90 days mortality |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nosocomial Spontaneous Bacterial Peritonitis, Ascites, Multi drug resistant bacteria, Albumin, Cirrhosis, Daptomycin, Meropenem, Ceftazidime, Nosocomial infection, Sepsis