Dataset Information

Pain killers: the interplay between nonsteroidal anti-inflammatory drugs and Clostridioides difficile infection.

ABSTRACT: Clostridioides difficile is one of the leading causes of nosocomial infections worldwide. Increases in incidence, severity, and healthcare cost associated with C. difficile infection (CDI) have made this pathogen an urgent public health threat worldwide. The factors shaping the evolving epidemiology of CDI and impacting clinical outcomes of infection are not well understood, but involve tripartite interactions between the host, microbiota, and C. difficile. In addition to this, emerging data suggests an underappreciated role for environmental factors, such as diet and pharmaceutical drugs, in CDI. In this review, we discuss the role of nonsteroidal anti-inflammatory drugs (NSAIDs) and eicosanoids in CDI.

SUBMITTER: Soto Ocana J

PROVIDER: S-EPMC9058983 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pain killers: the interplay between nonsteroidal anti-inflammatory drugs and Clostridioides difficile infection.

Soto Ocaña Joshua J Bayard Nile U NU Zackular Joseph P JP

Current opinion in microbiology 20211208

Clostridioides difficile is one of the leading causes of nosocomial infections worldwide. Increases in incidence, severity, and healthcare cost associated with C. difficile infection (CDI) have made this pathogen an urgent public health threat worldwide. The factors shaping the evolving epidemiology of CDI and impacting clinical outcomes of infection are not well understood, but involve tripartite interactions between the host, microbiota, and C. difficile. In addition to this, emerging data sug ...[more]

PMID: 34894543

Similar Datasets

Project description:Clostridium difficile infection (CDI) is a major public health threat worldwide. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enhanced susceptibility to and severity of CDI; however, the mechanisms driving this phenomenon have not been elucidated. NSAIDs alter prostaglandin (PG) metabolism by inhibiting cyclooxygenase (COX) enzymes. Here, we found that treatment with the NSAID indomethacin prior to infection altered the microbiota and dramatically increased mortality and the intestinal pathology associated with CDI in mice. We demonstrated that in C. difficile-infected animals, indomethacin treatment led to PG deregulation, an altered proinflammatory transcriptional and protein profile, and perturbed epithelial cell junctions. These effects were paralleled by increased recruitment of intestinal neutrophils and CD4+ cells and also by a perturbation of the gut microbiota. Together, these data implicate NSAIDs in the disruption of protective COX-mediated PG production during CDI, resulting in altered epithelial integrity and associated immune responses.IMPORTANCEClostridium difficile infection (CDI) is a spore-forming anaerobic bacterium and leading cause of antibiotic-associated colitis. Epidemiological data suggest that use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk for CDI in humans, a potentially important observation given the widespread use of NSAIDs. Prior studies in rodent models of CDI found that NSAID exposure following infection increases the severity of CDI, but mechanisms to explain this are lacking. Here we present new data from a mouse model of antibiotic-associated CDI suggesting that brief NSAID exposure prior to CDI increases the severity of the infectious colitis. These data shed new light on potential mechanisms linking NSAID use to worsened CDI, including drug-induced disturbances to the gut microbiome and colonic epithelial integrity. Studies were limited to a single NSAID (indomethacin), so future studies are needed to assess the generalizability of our findings and to establish a direct link to the human condition.

Project description:ImportanceNonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for knee osteoarthritis. However, they are associated with uncertain long-term clinical benefit and significant toxic effects.ObjectiveTo evaluate whether discontinuing NSAIDs and engaging in a telephone-based cognitive behavioral therapy (CBT) program is noninferior to continuing NSAIDs for patients with knee osteoarthritis.Design, setting, and participantsThe Stopping NSAIDs for Arthritis Pain multicenter randomized withdrawal trial was conducted for 364 patients taking NSAIDs for knee osteoarthritis pain on most days of the week for at least 3 months between September 1, 2013, and September 30, 2018. Analysis was performed on an intent-to-treat basis.InterventionsParticipants discontinued their current NSAID and took 15 mg per day of meloxicam daily during a 2-week run-in period. Those who remained eligible were randomized in a 1:1 ratio to receive meloxicam or placebo for 4 weeks (blinded phase 1). Participants receiving meloxicam then continued this medication for 10 weeks, while those receiving placebo participated in a 10-week CBT program (unblinded phase 2).Main outcomes and measuresThe primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 4 weeks with the noninferiority margin set at 1. Secondary outcomes included the area under the curve of the pain score after 4 weeks as well as the WOMAC pain score, area under the curve of the pain score, WOMAC disability score, and global impression of change after treatment at 14 weeks.ResultsA total of 180 participants (161 men; mean [SD] age, 58. 2 [11.8] years) were randomized to receive placebo followed by CBT, and a total of 184 participants (154 men; mean [SD] age, 58.5 [10.0] years) were randomized to receive meloxicam. After adjustment for baseline pain and study site, the estimated mean difference in WOMAC pain score between the placebo and meloxicam groups after 4 weeks was 1.4 (95% CI, 0.8-2.0; noninferiority test P = .92). At week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (95% CI, 0.2-1.4; noninferiority P = .28). There was no statistically significant difference in the global impression of change (mean difference in scores, -0.2; 95% CI, -0.4 to 0.1; P = .15) or lower extremity disability (mean difference in scores, 0.9; 95% CI, -1.4 to 3.2; P = .45) between the 2 groups after 14 weeks.Conclusions and relevanceAmong patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam. However, the WOMAC pain score differences between the 2 groups were small, and there were no statistically significant differences in participants' global impression of change or function after 14 weeks.Trial registrationClinicalTrials.gov Identifier: NCT01799213.

Project description:Background and objectivesThere have been doubts about the association between nonsteroidal anti-inflammatory drug use and worsening kidney function, and whether there is a difference between risks of individual nonsteroidal anti-inflammatory drugs is presently unclear. Therefore, this study aimed to evaluate the association between nonsteroidal anti-inflammatory drug exposure and the risk of incident eGFR <60 ml/min per 1.73 m2 and compare the risks between nonsteroidal anti-inflammatory drug subtypes in the Chinese population.Design, setting, participants, & measurementsFrom 2008 to 2017, a total of 1,982,488 subjects aged 18 years or older with baseline eGFR ≥60 ml/min per 1.73 m2 were enrolled in this retrospective cohort study. Multivariable Cox proportional hazards regression adjusted for each patient's baseline characteristics was adopted to examine the association between nonsteroidal anti-inflammatory drug and incident eGFR <60 ml/min per 1.73 m2 or eGFR decline ≥30% with reference to baseline.ResultsAfter a median follow-up duration of 6.3 (interquartile range, 3.3-9.4) years, 271,848 cases (14%) of incident eGFR <60 ml/min per 1.73 m2 and 388,386 (21%) events of eGFR decline ≥30% were recorded. After adjusting for each patient's baseline characteristics, nonsteroidal anti-inflammatory drug treatment was shown to be associated with a significantly higher risk of incident eGFR <60 ml/min per 1.73 m2 (hazard ratio, 1.71; 95% confidence interval, 1.67 to 1.75) and eGFR decline ≥30% (hazard ratio, 1.93; 95% confidence interval, 1.89 to 1.96) when compared with no nonsteroidal anti-inflammatory drug, with etoricoxib exhibiting the highest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 3.12; 95% confidence interval, 2.69 to 3.62) and eGFR decline ≥30% (hazard ratio, 3.11; 95% confidence interval, 2.78 to 3.48) and ibuprofen displaying the lowest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 1.12; 95% confidence interval, 1.02 to 1.23) and eGFR decline ≥30% (hazard ratio, 1.32; 95% confidence interval, 1.23 to 1.41).ConclusionsNonsteroidal anti-inflammatory drug exposure was associated with higher risks of incident eGFR <60 ml/min per 1.73 m2 and eGFR decline ≥30%. Highest risk was observed in etoricoxib users, and lowest risk was with ibuprofen.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_04_28_CJN18501120.mp3.

Dataset Information

Pain killers: the interplay between nonsteroidal anti-inflammatory drugs and Clostridioides difficile infection.

Publications

Pain killers: the interplay between nonsteroidal anti-inflammatory drugs and Clostridioides difficile infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets