Risk of relapse and readmission among hospitalized adults with carbapenem non-susceptible gram-negative infections

Abstract

Background

Infections caused by carbapenem-nonsusceptible gram-negative (C-NS) pathogens are associated with increased mortality and high treatment costs. Identification of potentially modifiable factors that may improve patient outcomes is important for better management of C-NS GN infections.

Methods

This was a retrospective study of hospitalized adults with electronic health record evidence of complicated urinary tract infection (cUTI), bacterial pneumonia (BP), complicated intra-abdominal infection (cIAI), or bacteremia (BAC) due to C-NS GN organisms from January 2013 to March 2018. Treatment patterns and clinical characteristics during the index hospitalization were analyzed descriptively and stratified by infection site(s). The effect of patient characteristics on index infection relapse during the postdischarge period and on readmission with 30 days was modeled using logistic regression.

Results

The study included 2,862 hospitalized patients with C-NS GN infections. Index infection sites were 38.4% cUTI ± BAC, 21.5% BP ± BAC, 18.7% cUTI + BP ± BAC, 14.7% any cIAI, and 6.7% BAC only. The majority of patients (83.6%) received an antibiotic during their index hospitalization; among these, the most common classes given were penicillins (52.9%), fluoroquinolones (50.7%), and carbapenems (38.9%). During the postdischarge period, 21.7% of patients had a relapse of the index infection and 63.9% of patients were readmitted to the hospital. Factors associated with increased adjusted odds ratio (OR) for relapse or readmission included Charlson comorbidity score of ≥3 relative to 0 (relapse: OR [95% CI] = 1.34 [1.01–1.76], p = .040; readmission: OR [95% CI] 1.92 [1.50–2.46], p < .001), preindex immunocompromised status (relapse: OR [95% CI] 1.37 [1.05–1.79], p = .019; readmission: OR [95% CI] = 1.60 [1.27–2.02], p < .001), and preindex carbapenem use (relapse: OR [95% CI] = 1.35 [1.07–1.72], p = .013; readmission: OR [95% CI] = 1.25 [1.00–1.57], p = .048).

Conclusions

Adverse postdischarge outcomes were common among hospitalized patients with C-NS GN infections and were significantly associated with previous carbapenem use and patient clinical characteristics such as higher comorbidity burden and immunocompromised status. Adoption of antimicrobial stewardship and consideration of individual patient risk factors in making treatment decisions may help improve clinical outcomes.

Keywords:

• Carbapenem resistance
• gram-negative organisms
• healthcare costs
• healthcare resource utilization
• retrospective studies
• United States

Transparency

Declaration of funding

This work was supported by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA.

Declaration of financial/other relationships

Ryan Dillon and Laura Puzniak were employees of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, at the time this study was conducted. Jerry Seare and Amy Anderson are employees of Optum (Eden Prairie, MN), contracted by Merck & Co, Inc to conduct the study and provide medical writing assistance. Tanya Burton was an employee of Optum at the time this study was conducted. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

RD, TB, JS, and AJA participated in the conception and design of the study. All authors helped analyze and interpret the data, participated in critical revision of the manuscript, approved the final version for publication, and agree to be accountable for all aspects of the work.

Acknowledgements

The authors thank Eilish McCann, PhD (formerly of Merck & Co, Inc) for assistance with the conception and design of the study. Medical writing services were provided by Yvette Edmonds, PhD (Optum) and contracted by Merck Sharp & Dohme Corp.