New or recurrent infections and sepsis are leading causes of rehospitalization after sepsis.1 Although persistent immunosuppression after sepsis is considered a causative factor, patient-inherent risk factors may also contribute to increased risk of recurrent severe infections.2 The burden of infection in these patients presepsis is unknown. We analyzed the change in infection-related hospitalizations and outpatient drug prescriptions presepsis vs postsepsis.
This retrospective cohort study was based on health claims data of AOK, a statutory health insurance provider in Germany, for the years 2011 to 2015. The study was approved by the Jena University Hospital Institutional Review Board; informed consent was waived owing to deidentified patient data. This study followed followed the STROBE reporting guideline.
Inpatient sepsis cases were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, German Modification (ICD-10-GM) codes between January 1, 2013, and December 31, 2014, among AOK beneficiaries who were older than 15 years and had no sepsis in the 24 months before index hospitalization. We analyzed hospitalizations and drug prescriptions in the 12 months presepsis and postsepsis among sepsis survivors. Hospitalizations were classified as infection- or sepsis-related according to requisite ICD-10-GM hospital discharge diagnoses.3 Intensive care unit (ICU) treatment was identified by Operation and Procedure Classification System codes for intensive care complex treatment (8-980, 8-98f, 8-98d, 8-98c). We analyzed total drug prescriptions and prescriptions of anti-infectives according to Anatomic Therapeutical Chemical codes (J01, J02, J04A, J05, A07AA, P01AB). Presepsis and postsepsis outcomes were compared using a 2-sided McNemar χ2 test; statistical significance was set at α = .05. Statistical analyses were conducted using SAS Enterprise Guide, version 7.1 (SAS Institute Inc).
Among 23 million AOK beneficiaries, we identified 159 684 sepsis patients, 116 507 of whom survived hospitalization. The mean (SD) age was 73.0 (13.3) years; 52.1% were men and 47.9% were women. Among the survivors, 32.5% had severe sepsis, 27.7% were treated in an ICU, and 7.4% had no preexisting impairments. In the 12 months postsepsis, 66.8% of survivors were rehospitalized and 45.0% were rehospitalized with infection (67.4% of all rehospitalizations). Among all survivors, 11.9% were rehospitalized for recurrent sepsis, 25.9% of whom were admitted to an ICU; 56.6% of sepsis survivors received anti-infective treatment in an outpatient setting.
Although hospitalization rates increased by 3.4% from 63.4% in the 12 months presepsis to 66.8% in the 12 months postsepsis (P < .001), the proportion of patients with infection-related hospitalizations increased by 9.6% (presepsis, 35.4% vs postsepsis, 45.0%; P < .001). The proportion of patients with device-related infections nearly doubled from presepsis to postsepsis (Figure). Total outpatient drug prescriptions decreased (97.5% vs 94.1%; P < .001), but the proportion of patients with at least 1 anti-infective prescription increased by 4.0% (52.6% vs 56.6%; P < .001). The increase in hospitalization and infection-related hospitalization rates was highest in patients without preexisting medical, cognitive, or psychological impairments (hospitalization rate, from 22.5% to 54.6% [a 32.1% increase]; infection-related hospitalization rate, from 6.4% to 31.4% [a 25.0% increase]) (Table). Prescriptions of anti-infectives increased consistently across subgroups and were most prominent in the subgroup of survivors without preexisting impairments (16.7%).
This study found that infection-related hospitalizations affected 2 of every 3 sepsis survivors in Germany. Although hospitalizations among our study cohort increased by 9.6% postsepsis, more than half of these patients had already contracted infectious diseases requiring hospitalization prior to sepsis. This finding suggests that many sepsis patients are at risk for severe infections presepsis—presumably owing to preexisting immune dysfunction—and that septic insults may exacerbate their risk of developing severe infections and recurrent sepsis.4 Furthermore, patients without prior impairments and low rates of presepsis infection–related hospitalizations and drug prescriptions had these rates increase substantially postsepsis.
This study has some limitations. First, the validity of health claims diagnoses relies on coding quality. Second, subgroup comparisons should be interpreted within the context of differential mortality rates among survivors. Regardless, our findings highlight the need for preventive measures—particularly vaccinations and programs to prevent device-related infections—as well as early recognition and education regarding symptoms among all sepsis survivors and at-risk patients in the general population.
Accepted for Publication: May 22, 2022.
Published: July 8, 2022. doi:10.1001/jamanetworkopen.2022.20945
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Fleischmann-Struzek C et al. JAMA Network Open.
Corresponding Author: Carolin Fleischmann-Struzek, MD, Institute of Infectious Diseases and Infection Control, Jena University Hospital, Stoystraße 3, 07743 Jena, Germany (carolin.fleischmann@med.uni-jena.de).
Author Contributions: Dr Fleischmann-Struzek had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Fleischmann-Struzek and Ditscheid contributed equally to the study. Drs Hartog and Freytag contributed equally to the study.
Concept and design: Fleischmann-Struzek, Rose, Freytag.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Fleischmann-Struzek, Hartog, Freytag.
Critical revision of the manuscript for important intellectual content: Fleischmann-Struzek, Ditscheid, Storch, Rose, Spoden, Freytag.
Statistical analysis: Ditscheid, Rose.
Obtained funding: Fleischmann-Struzek, Hartog, Freytag.
Administrative, technical, or material support: Storch.
Supervision: Fleischmann-Struzek, Hartog, Freytag.
Conflict of Interest Disclosures: None reported.
Funding/Support: The study was funded by grant 01VSF17010 from the German Innovations Fund of the Federal Joint Committee in Germany.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.