Hospitalizations For Serious Infections Research Articles

Risk of Hospitalization for Serious Infection After Initiation of Ustekinumab or Other Biologics in Patients With Psoriasis or Psoriatic Arthritis.

To compare the risk of serious infections requiring hospitalization in patients with psoriasis (PsO) or psoriatic arthritis (PsA) initiating ustekinumab versus other biologics or apremilast. In this multi-database cohort study, we identified patients with PsO/PsA who initiated therapy with adalimumab, apremilast, certolizumab, etanercept, golimumab, ixekizumab, secukinumab, or ustekinumab between 2009 and 2018. The primary outcome measure was hospitalizations due to serious infections, which included bacterial, viral, or opportunistic infections. We estimated hazard ratios (HRs) comparing each study drug to ustekinumab after applying propensity score fine stratification weights for confounding control in each database. Database-specific weighted HRs were combined by meta-analysis. We identified 123,383 patients with PsO/PsA who initiated one of the study drugs. During a total of 117,744 person-years of follow-up, 1,514 serious infections occurred with a crude incidence of 1.29 per 100 person-years. After propensity score fine stratification and weighting, the incidence rates of serious infection among ustekinumab initiators ranged from 0.59 to 0.95 per 100 person-years. Compared with ustekinumab, the combined weighted HRs (95% confidence interval [95% CI]) for serious infections were 1.66 (95% CI 1.34-2.06) for adalimumab, 1.42 (95% CI 1.02-1.96) for apremilast, 1.09 (95% CI 0.68-1.75) for certolizumab, 1.39 (95% CI 1.01-1.90) for etanercept, 1.74 (95% CI 1.00-3.03) for golimumab, 2.92 (95% CI 1.80-4.72) for infliximab, 2.98 (95% CI 1.20-7.41) for ixekizumab, and 1.84 (95% CI 1.24-2.72) for secukinumab. Other biologics and apremilast were associated with a 1.4- to 3-times higher risk of hospitalization for serious infections in PsO/PsA patients when compared to ustekinumab; this finding should be considered in the safety profile of these therapies when selecting appropriate treatment regimens in patients with PsO/PsA.

Trends in Hospitalization for Serious Infections in children with Asthma in the US (2001-2014)

Asthma is associated with an increased risk of infections. However, the rate of hospitalizations for serious infections among children with asthma is not well studied. We examined trends in hospitalizations for serious infections in asthma from 2001-2014 using the National Inpatient Sample (NIS).

Improving care for individuals with serious infections who inject drugs.

Hospitalizations for serious infections requiring long-term intravenous (IV) antimicrobials related to injection drug use have risen sharply over the last decade. At our rural tertiary care center, opportunities for treatment of underlying substance use disorders were often missed during these hospital admissions. Once medically stable, home IV antimicrobial therapy has not traditionally been offered to this patient population due to theoretical concerns about misuse of long-term IV catheters, leading to discharges with suboptimal treatment regimens, lengthy hospital stays, or care that is incongruent with patient goals and preferences. A multidisciplinary group of clinicians and patients set out to redesign and improve care for this patient population through a health care innovation process, with a focus on increasing the proportion of patients who may be discharged on home IV therapy. Baseline assessment of current experience was established through retrospective chart review and extensive stakeholder analysis. The innovation process was based in design thinking and facilitated by a health care delivery improvement incubator. The components of the resulting intervention included early identification of hospitalized people who inject drugs with serious infections, a proactive psychiatry consultation service for addiction management for all patients, a multidisciplinary care conference to support decision making around treatment options for infection and substance use, and care coordination/navigation in the outpatient setting with a substance use peer recovery coach and infectious disease nurse for patients discharged on home IV antimicrobials. Patients discharged on home IV therapy followed routine outpatient parenteral antimicrobial therapy (OPAT) protocols and treatment protocols for addiction with their chosen provider. An intervention developed through a design-thinking-based health care redesign process improved patient-centered care for people with serious infections who inject drugs.

Trends in Hospitalizations for Serious Infections Among People With Opioid Use Disorder in Ontario, Canada.

ObjectivesOpioid use among people who inject drugs can lead to serious complications, including infections. We sought to study trends in rates of these complications among people with an opioid use disorder (OUD) and the sequelae of those hospitalizations.MethodsWe analyzed all inpatient hospitalizations for serious infections (infective endocarditis [IE], spinal infections, nonvertebral bone infections, and skin or soft tissue infections) among people with OUD in Ontario between 2013 and 2019. We reported the population adjusted rate of hospitalizations for serious infections annually, stratified by type of infection and prevalence of prior opioid agonist therapy and hydromorphone prescribing. We reported characteristics of hospitalizations and 30–day mortality in the most recent 2 years.ResultsAmong people with OUD there was a 167% increase in rates of IE (7.7-20.6 per million residents; P < 0.01), a 394% increase in rates of spinal infections (3.4–16.8 per million residents; P < 0.01), a 191% increase in rates of nonvertebral bone infections (8.9 to 25.9 per million residents; P < 0.01), and a 147% increase in infections of the skin or soft tissue (32.1–79.4 per million residents; P < 0.01) over 7 years in Ontario. Death in-hospital and within 30 days of discharge was highest among those with IE (11.5% and 15.9%, respectively), and lower among those with other infections (<5%).ConclusionsRates of serious infections among people with OUD are rising, placing a significant burden on patients. These findings suggest that early intervention and treatment of infections in this population are needed to prevent downstream harm.

Evaluation of Bundled Interventions for Patients With Opioid Use Disorder Experiencing Homelessness Receiving Extended Antibiotics for Severe Infection.

Hospitalizations for serious infections in patients with opioid use disorder (OUD) experiencing homelessness are common. Patients receiving 4 interventions (infectious disease consultation, addiction consultation, case management, and medications for OUD [MOUD]) had higher odds of clinical cure (unadjusted odds ratio [OR], 3.15; P = .03; adjusted OR, 3.03; P = .049) and successful retention in addiction care at 30 days (unadjusted OR, 5.46; P = .01; adjusted OR, 6.36; P = .003).

Validity of ICD‐10‐CM diagnoses to identify hospitalizations for serious infections among patients treated with biologic therapies

Identifying hospitalizations for serious infections among patients dispensed biologic therapies within healthcare databases is important for post-marketing surveillance of these drugs. We determined the positive predictive value (PPV) of an ICD-10-CM-based diagnostic coding algorithm to identify hospitalization for serious infection among patients dispensed biologic therapy within the FDA's Sentinel Distributed Database. We identified health plan members who met the following algorithm criteria: (1) hospital ICD-10-CM discharge diagnosis of serious infection between July 1, 2016 and August 31, 2018; (2) either outpatient/emergency department infection diagnosis or outpatient antimicrobial treatment within 7 days prior to hospitalization; (3) inflammatory bowel disease, psoriasis, or rheumatological diagnosis within 1 year prior to hospitalization, and (4) were dispensed outpatient biologic therapy within 90 days prior to admission. Medical records were reviewed by infectious disease clinicians to adjudicate hospitalizations for serious infection. The PPV (95% confidence interval [CI]) for confirmed events was determined after further weighting by the prevalence of the type of serious infection in the database. Among 223 selected health plan members who met the algorithm, 209 (93.7% [95% CI, 90.1%-96.9%]) were confirmed to have a hospitalization for serious infection. After weighting by the prevalence of the type of serious infection, the PPV of the ICD-10-CM algorithm identifying a hospitalization for serious infection was 80.2% (95% CI, 75.3%-84.7%). The ICD-10-CM-based algorithm for hospitalization for serious infection among patients dispensed biologic therapies within the Sentinel Distributed Database had 80% PPV for confirmed events and could be considered for use within pharmacoepidemiologic studies.

The Use of Vedolizumab in Patients With Concomitant Cirrhosis and Crohnʼs Disease

The use of vedolizumab in patients with concomitant inflammatory bowel disease (IBD) and cirrhosis has not been reported. We wish to report our center's experience with vedolizumab in 3 patients with cirrhosis and concomitant Crohn's disease (CD). From 1/2014 to present, 1542 patients with IBD were treated with vedolizumab. Three patients had cirrhosis based on liver biopsy, biochemical data, and/or imaging. The 1st patient is a 64 y/o female with a history of CD of the colon and small bowel (SB) and cirrhosis secondary to autoimmune hepatitis. She was diagnosed with CD 13 years prior and failed treatment with certolizumab and infliximab, requiring a colectomy with end ileostomy. Vedolizumab and azathioprine were started and 36 months after treatment, she is in deep remission. Prior to treatment, she had a modified model for end stage liver disease (MELD-Na) score of 8 and Child Turcott Pugh (CTP) score A5. Post-treatment, she has not required hospitalization for serious infection, and her MELD-Na and CTP are unchanged. Our 2nd case is a 57 y/o male with history of SB CD and cirrhosis due to HCV. He had a prior resection of the distal ileum and previous treatment with budesonide and 6-mercatopurine (6-MP) with persistent disease. Five years later, vedolizumab and 6-MP were started. Prior to therapy, his MELD-Na was 6 and CTP A5. Thirty-two months later, he continues on vedolizumab and is doing well with no significant infections or decompensation of his liver disease. The 3rd case is a 65 y/o male with an 11 year history of SB CD and cryptogenic cirrhosis. He was treated with steroids, infliximab, and azathioprine, however due to non-response, vedolizumab was started. Prior to treatment, his MELD-Na was 9 and CTP A6. After 5 months, the MELD-Na was 11 and CTP was A6 with no decompensation of his liver disease or significant infection. There is a paucity of data with regards to use of vedolizumab in patients with cirrhosis. The landmark studies supporting the use of vedolizumab in patients with IBD do not identify patients with cirrhosis. Recent reports suggest a favorable safety profile of vedolizumab, however patients with cirrhosis are unique as they have a predilection for opportunistic infection and hepatocellular carcinoma. Our limited study demonstrates that in patients with compensated liver disease, vedolizumab appears to be well tolerated and efficacious, however further research in patients with decompensated cirrhosis is required.

Trends in Hospitalizations for Serious Infections in Patients With Rheumatoid Arthritis in the US Between 1993 and 2013

The epidemiology of hospitalizations with infections among patients with rheumatoid arthritis (RA) is unknown, despite an increase in RA treatments that confer a risk of infection. We examined National Inpatient Sample data from 1993-2013. We identified hospitalizations among adults with RA, defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes (714.xx) in any secondary diagnosis field. We evaluated 5 infections as the primary diagnosis: pneumonia, sepsis, urinary tract infection (UTI), skin and soft tissue infections (SSTIs), and opportunistic infections (OIs). The primary outcome was the proportion of hospitalizations for each infection among all hospitalizations with a secondary diagnosis of RA. There were 792,921 hospitalizations for infection with a secondary diagnosis of RA, with the rates increasing from 90 to 206 per 100,000 persons from 1993-2013. The proportion of hospitalizations decreased for pneumonia (from 5.4% to 4.6%), UTI (from 0.4% to 0.38%), and OIs (from 0.44% to 0.26%). The proportion of hospitalizations for SSTIs increased slightly (from 2.3% to 2.5%), while hospitalizations for sepsis more than tripled (from 1.9% to 6.4%). Between 1993 and 2013, the proportion of hospitalizations for infections among RA patients appeared to decline for pneumonia and OIs, with a slight decrease in UTI, a slight increase in SSTIs, and a substantial increase in hospitalizations with sepsis. Our results are consistent with previous reports that the sensitivity of sepsis coding has increased over time.

Commentary

Commentary

Cholesterol levels and long-term rates of community-acquired sepsis.

BackgroundDyslipidemia is a risk factor for cardiovascular disease, with elevated low-density lipoprotein cholesterol (LDL-C) and decreased high-density lipoprotein cholesterol (HDL-C) recognized as risk factors for acute coronary events. Studies suggest an association between low cholesterol levels and poor outcomes in acute sepsis. We sought to determine the relationship between baseline cholesterol levels and long-term rates of sepsis.MethodsWe used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, a population-based cohort of 30,239 community-dwelling adults. The primary outcome was first sepsis event, defined as hospitalization for an infection with the presence of ≥2 systemic inflammatory response syndrome criteria (abnormal temperature, heart rate, respiratory rate, white blood cell count) during the first 28 hours of hospitalization. Cox models assessed the association between quartiles of HDL-C or LDL-C and first sepsis event, adjusted for participant demographics, health behaviors, chronic medical conditions, and biomarkers.ResultsWe included 29,690 subjects with available baseline HDL-C and LDL-C. There were 3423 hospitalizations for serious infections, with 1845 total sepsis events among 1526 individuals. Serum HDL-C quartile was not associated with long-term rates of sepsis (hazard ratio (HR) (95% CI): Q1 (HDL-C 5–40 mg/dl), 1.08 (0.91–1.28); Q2 (HDL-C 41–49 mg/dl), 1.06 (0.90–1.26); Q3 (HDL-C 50–61 mg/dl), 1.04 (0.89–1.23); Q4, reference). However, compared with the highest quartile of LDL-C, low LDL-C was associated with higher rates of sepsis (Q1 (LDL-C 3–89 mg/dl), 1.30 (1.10–1.52); Q2 (LDL-C 90–111 mg/dl), 1.24 (1.06–1.47); Q3 (LDL-C 112–135 mg/dl), 1.07 (0.91–1.26); Q4, reference).ConclusionLow LDL-C was associated with higher long-terms rates of community-acquired sepsis. HDL-C level was not associated with long-term sepsis rates.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1579-8) contains supplementary material, which is available to authorized users.

Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self-Controlled Case Series Study.

Animal studies and in vitro human studies suggest that certain opioid analgesics impair crucial immune functions. This study was undertaken to determine whether opioid use is associated with increased risk of serious infection in patients with rheumatoid arthritis (RA). We conducted a self-controlled case series analysis on a retrospective cohort of 13,796 patients with RA enrolled in Tennessee Medicaid in 1995-2009. Within-person comparisons of the risk of hospitalization for serious infection during periods of opioid use versus non-use were performed using conditional Poisson regression. Fixed confounders were accounted for by design; time-varying confounders included age and use of disease-modifying antirheumatic drugs, glucocorticoids, and proton-pump inhibitors. In additional analyses, risks associated with new opioid use, use of opioids known to have immunosuppressive properties, use of long-acting opioids, and different opioid dosages were assessed. Sensitivity analyses were performed to account for potential protopathic bias and confounding by indication. Among 1,790 patients with RA who had at least 1 hospitalization for serious infection, the adjusted incidence rate of serious infection was higher during periods of current opioid use compared to non-use, with an incidence rate ratio (IRR) of 1.39 (95% confidence interval [95% CI] 1.19-1.62). The incidence rate was also higher during periods of long-acting opioid use, immunosuppressive opioid use, and new opioid use compared to non-use (IRR 2.01 [95% CI 1.52-2.66], IRR 1.72 [95% CI 1.33-2.23], and IRR 2.38 [95% CI 1.65-3.42], respectively). Results of sensitivity analyses were consistent with the main findings. In within-person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalization for serious infection.

Initiation of Tumor Necrosis Factor-α Antagonists and the Risk of Hospitalization for Infection in Patients With Autoimmune Diseases

Although tumor necrosis factor (TNF)-α antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete. To determine whether initiation of TNF-α antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization. Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate. Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens. Study cohorts included 10,484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-α antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-α antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections. Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.