Opioid and Stimulant Use Disorders Raise Readmission Risk After Serious Bacterial Infections

A sweeping new analysis of United States hospital data suggests that patients hospitalized with serious bacterial infections linked to injection drug use face a markedly higher risk of returning to the hospital within days of discharge when they also live with opioid use disorder, stimulant use disorder, or both. The study, published in BMC Infectious Diseases, draws on the 2022 Healthcare Cost and Utilization Project Nationwide Readmission Database and offers one of the most detailed national pictures to date of how substance use disorders shape the fragile weeks that follow treatment for injection-related infections. As overdose deaths and injection-associated infections continue to strain hospitals across the country, the findings point to a potentially powerful intervention window: the hospital stay itself.

The research team, led by investigators at Rutgers School of Public Health and Columbia University, focused on four of the most serious bacterial infections associated with injection drug use: skin and soft tissue infections, osteomyelitis, infective endocarditis, and central nervous system abscesses. These conditions represent a spectrum of severity, from painful tissue infections that may require surgical drainage to life-threatening heart valve infections and brain abscesses that demand weeks of intravenous antibiotics. All of them share a common thread in the context of the ongoing drug overdose crisis, in which contaminated injection practices introduce bacteria into the bloodstream and deep tissues, creating infections that frequently require prolonged hospitalization.

Methodologically, the study is a retrospective cohort analysis designed to produce nationally representative estimates. The researchers applied survey weights to the Nationwide Readmission Database, a federal dataset that captures readmissions across state lines and allows analysts to track patients who move between hospitals, a critical feature given that many patients with substance use disorders receive care at multiple institutions. After weighting, the analysis encompassed 392,984 index admissions of adults hospitalized with a primary diagnosis of one of the four target infections. Each admission was classified into one of four exposure groups based on ICD-10-CM diagnostic codes: neither disorder, opioid use disorder only, stimulant use disorder only, or co-occurring opioid and stimulant use disorders.

The demographic profile of the cohort underscores how deeply these infections intersect with an aging population of people who inject drugs. The mean age of hospitalized patients was 58.8 years, 57.1 percent were male, and 46.9 percent carried Medicare coverage, a striking figure for a population often assumed to be younger and uninsured. Within the cohort, 4.5 percent of admissions involved opioid use disorder alone, 3.9 percent involved stimulant use disorder alone, and 2.4 percent involved both disorders simultaneously. The overall unplanned readmission rates were 4.3 percent within seven days of discharge and 12.48 percent within thirty days, meaning roughly one in eight patients returned to the hospital within a month of being sent home.

After statistical adjustment for patient and hospital characteristics, the central finding emerged clearly: having opioid use disorder, stimulant use disorder, or both was associated with higher odds of both seven-day and thirty-day unplanned all-cause readmission compared with patients who had neither disorder. This pattern held across the short and slightly longer follow-up windows, suggesting that the elevated risk is not confined to the immediate post-discharge period but persists through the first month, when patients are typically transitioning from intravenous antibiotics in the hospital to oral regimens or outpatient infusion therapy.

Perhaps the most clinically provocative result concerns the co-occurring group. Patients diagnosed with both opioid and stimulant use disorders showed higher odds of readmission than those with opioid use disorder alone, although the authors note that this particular comparison did not reach statistical significance in their models. The direction of the effect is nonetheless consistent with a growing body of literature on polysubstance use, which suggests that people who use multiple drug classes experience compounded medical and social vulnerabilities. Stimulants such as methamphetamine and cocaine can drive frequent injection episodes, cardiovascular strain, and erratic engagement with care, while opioids contribute to overdose risk and withdrawal-related treatment disruption. When both disorders are present, the pathways back to the hospital may multiply.

The mechanisms behind these associations are likely multifactorial, and the study’s design cannot fully disentangle them. Patients with untreated opioid use disorder may leave the hospital against medical advice to avoid withdrawal, cutting short antibiotic courses for infections like endocarditis that require weeks of therapy. Others may be discharged without linkage to medications for opioid use disorder such as buprenorphine or methadone, returning to injection practices that seed new infections at old or new sites. Social factors, including housing instability, lack of transportation to follow-up appointments, and stigma within healthcare settings, can compound the pharmacological challenges. Readmissions in this population may also reflect non-infectious causes, including withdrawal, overdose, and complications of untreated chronic disease, since the study measured all-cause readmission rather than infection-specific recurrence.

For the authors, the implications point squarely toward integrating addiction treatment into inpatient infection care. Hospitalization for a serious bacterial infection represents a rare moment of sustained contact between this population and the healthcare system, often the longest period of stability a patient experiences in months. Evidence from other fields suggests that initiating medications for opioid use disorder during hospital admission, combined with warm handoffs to community-based treatment, can reduce subsequent opioid use and improve retention in care. The new findings extend the logic to infectious diseases practice, where hospitals have historically treated the infection and discharged the patient without addressing the underlying substance use disorder that produced it.

The study carries important caveats that shape how its results should be interpreted. Diagnostic codes for substance use disorders depend on clinician documentation, and undercoding is common, particularly for stimulant use disorder, which may mean some exposed patients were misclassified as unexposed and the true associations could be stronger than estimated. The all-cause readmission outcome cannot distinguish between returns driven by infection relapse and those driven by other acute events. As with any database study, residual confounding by severity of illness, social determinants of health, and treatment intensity remains possible. The authors also relied on the 2022 database year, and patterns of drug use and hospital practice continue to evolve rapidly, meaning the estimates represent a snapshot of a dynamic epidemic.

Even with those limitations, the scale of the analysis gives its central message considerable weight. Nearly 400,000 weighted hospitalizations for injection-related bacterial infections in a single year, with one in eight patients readmitted within thirty days, describes an enormous and largely preventable burden on patients, families, and the healthcare system. The finding that opioid and stimulant use disorders independently elevate short-term readmission risk reframes these disorders not as peripheral social issues but as central clinical drivers of infectious disease outcomes. As the authors conclude, embedding addiction medicine within inpatient infectious disease care, from bedside initiation of treatment to structured post-discharge linkage, could transform the hospital stay from a revolving door into a genuine turning point for one of the most vulnerable populations in American medicine.

Subject of Research: The association between opioid and stimulant use disorders and unplanned hospital readmission after injection drug use-related bacterial infections

Article Title: The impact of co-occurring opioid and stimulant use disorders on unplanned readmissions among patients hospitalized with bacterial infections

Article References: Hu, J., Blair, N., Mauro, P. M., Samples, H., Bushnell, G., Yin, M. T., & Shiau, S. (2026). The impact of co-occurring opioid and stimulant use disorders on unplanned readmissions among patients hospitalized with bacterial infections. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14321-3

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14321-3

Keywords: opioid use disorder, stimulant use disorder, bacterial infection, hospital readmission, injection drug use, infective endocarditis, osteomyelitis, polysubstance use, addiction treatment, Nationwide Readmission Database, infectious diseases, public health