Doxycycline for the Prevention of Spontaneous Bacterial Peritonitis

The utilization of doxycycline for SBP prophylaxis is a novel practice at MDMC. Therefore, an assessment of safety and efficacy is needed in order to generalize this practice. The publication of this study can potentially introduce a new alternative to guideline-directed therapies for secondary prevention of SBP. Doxycycline is non-inferior to guideline-directed therapies regarding safety and efficacy in primary and secondary prophylaxis for SBP.

Study Overview

• Status: Completed
• Conditions: Cirrhosis; Spontaneous Bacterial Peritonitis
• Intervention / Treatment: Drug: doxycycline

Detailed Description

Spontaneous bacterial peritonitis (SBP) is a common and serious complication in cirrhotic patients with a reported mortality rate of 20 to 30%.1-3 A SBP diagnosis requires abdominal paracentesis and is made in the presence of an elevated ascitic fluid absolute polymorphonuclear leukocyte (PMN) count without an evident intra-abdominal, surgically treatable source of infection.2,3 Common pathogens associated with SBP are Gram-negative colonic organisms. However, in recent years, Gram-positive pathogens have become more common, suggesting the need to evaluate SBP management.1,4-6 The recurrence rate of SBP after an initial episode has been reported to be as high as 70%.1-3 Currently, the American Association for the Study of Liver Disease (AASLD) and European Association for the Study of the Liver (EASL) guidelines recommend the use of sulfamethoxazole/trimethoprim, norfloxacin, or ciprofloxacin for the prevention of recurrent SBP. Fluoroquinolones as a class have had increased black box warnings in recent years, making ciprofloxacin fall out of favor for long-term prophylaxis.5 Sulfamethoxazole/trimethoprim is extensively metabolized by the liver and is contraindicated in marked liver impairment.8 Therefore, it is necessary to search for a prophylaxis alternative with similar efficacy and a better safety profile.

Doxycycline is a broad-spectrum antibiotic that covers Gram-positive bacteria, including Streptococcus spp., resistant strains of Staphylococcus and Enterococcus, and Gram-negative bacteria, including Enterobacteriaceae. One randomized trial in cirrhotic patients with a previous episode of SBP showed that doxycycline was associated with a reduction in inflammatory markers, such as interleukin-6 and C-reactive protein, suggesting potential benefits of doxycycline in this patient population.7 At Methodist Dallas Medical Center (MDMC) and the Liver Institute at MDMC, doxycycline has been utilized for both primary and secondary prevention of SBP. In order to compare doxycycline with guideline-directed therapies for SBP prevention in cirrhotic patients, a retrospective, cohort study was designed to review patients who meet the criteria from July 2014 to July 2018. This study aims to compare the efficacy of doxycycline with that of guideline recommended therapies for primary and secondary SBP prophylaxis, the safety of doxycycline with that of guideline recommended therapies for primary and secondary SBP prophylaxis, and identify the association between chemoprophylaxis and the risk of infections from multidrug resistant organisms (MDROs) in SBP.

• Study Type: Observational
• Enrollment (Actual): 841

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75203
      • Methodist Dallas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients hospitalized at MDMC at the Liver Institute Clinic with a diagnosis of SBP based on ascitic fluid PMN count greater than 250 cells/mm3 from July 2014 to July 2018.

Description

Inclusion Criteria:

• Patients ≥ 18 year-old with refractory ascites who are candidates for SBP prophylaxis per clinician's decision
• Patients diagnosed with cirrhosis based on clinical criteria
• Patients with a diagnosis of SBP confirmed by paracentesis

Exclusion Criteria:

• Patients who have secondary peritonitis other than SBP
• Patients who have a history of liver transplant prior to the initial episode of SBP
• Patients with incomplete medical records

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of reported SBP	Occurrence of reported SBP within 1-year of chemoprophylaxis initiation	July 2014 to July 2018

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidences of death	Incidences of death within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Incidences of Liver transplant	Incidences of liver transplant within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Incidences of bacteremia	Incidences of bacteremia within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Hospitalizations and ED visits due to AKI	Hospitalizations and ED visits due to AKI within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Hospitalizations and ED visits due to Clostridioides difficile infection	Hospitalizations and ED visits due to Clostridioides difficile infection within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Hospitalizations and ED visits due to diarrhea	Hospitalizations and ED visits due to diarrhea within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Hospitalizations and ED visits due to hyperkalemia	Hospitalizations and ED visits due to hyperkalemia within 1-year of chemoprophylaxis initiation	July 2014 to July 2018
Rate of infection with MDRO	Rate of infection with MDRO within 1-year of chemoprophylaxis initiation	July 2014 to July 2018

Collaborators and Investigators

• Sponsor: Methodist Health System
• Investigators: Principal Investigator: Jessica Rago, PharmD, Methodist Dallas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2019
• Primary Completion (Actual): August 7, 2020
• Study Completion (Actual): August 7, 2020

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: November 4, 2019
• First Posted (Actual): November 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: 061.PHA.2019.D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No