Economic impact of recurrent Clostridioides difficile infection in the USA: A systematic literature review and cost synthesis

INTRODUCTION: Up to 35% of patients with a first episode of Clostridioides difficile infection (CDI) develop recurrent CDI (rCDI), and of those, up to 65% experience multiple recurrences. A systematic literature review (SLR) was conducted to review and summarize the economic impact of rCDI in the United States of America. METHODS: English-language publications reporting real-world healthcare resource utilization (HRU) and/or direct medical costs associated with rCDI in the USA were searched in MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Library databases over the past 10 years (2012-2022), as well as in selected scientific conferences that publish research on rCDI and its economic burden over the past 3 years (2019-2022). HRU and costs identified through the SLR were synthesized to estimate annual rCDI-attributable direct medical costs to inform the economic impact of rCDI from a US third-party payer\u27s perspective. RESULTS: A total of 661 publications were retrieved, and 31 of them met all selection criteria. Substantial variability was found across these publications in terms of data source, patient population, sample size, definition of rCDI, follow-up period, outcomes reported, analytic approach, and methods to adjudicate rCDI-attributable costs. Only one study reported rCDI-attributable costs over 12 months. Synthesizing across the relevant publications using a component-based cost approach, the per-patient per-year rCDI-attributable direct medical cost was estimated to range from $67,837 to$82,268. CONCLUSIONS: While real-world studies on economic impact of rCDI in the USA suggested a high-cost burden, inconsistency in methodologies and results reporting warranted a component-based cost synthesis approach to estimate the annual medical cost burden of rCDI. Utilizing available literature, we estimated the average annual rCDI-attributable medical costs to allow for consistent economic assessments of rCDI and identify the budget impact on US payers

Clostridium Difficile Infection Risk With Important Antibiotic Classes: An Analysis of the FDA Adverse Event Reporting System

Introduction: Antibiotic use is an important risk factor for Clostridium difficile infection (CDI). Prior meta-analyses have identified antibiotics and antibiotic classes that pose the greatest risk for CDI; however, CDI epidemiology is constantly changing and contemporary analyses are needed. Objectives: The objective of this study was to evaluate the association between CDI and important antibiotic classes in recent years using the FDA Adverse Event Report System (FAERS). Methods: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CDI cases. We computed the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and CDI. An association was considered statistically significant when the lower limit of the 95%CI was greater than 1. Results: A total of 2,042,801 reports (including 5,187 CDI reports) were considered, after inclusion criteria were applied. Lincosamides (e.g., clindamycin) had the greatest proportion of CDI reports, representing 10.4% of all lincosamide reports. CDI RORs (95%CI) for the antibiotic classes were (in descending order): lincosamides 46.95 (39.49-55.82), monobactams 29.97 (14.60-61.54), penicillin combinations 20.05 (17.39-23.12), carbapenems 19.16 (15.52-23.67), cephalosporins/ monobactams/carbapenems 17.28 (14.95-19.97), cephalosporins 15.33 (12.60-18.65), tetracyclines 7.54 (5.42-10.50), macrolides 5.80 (4.48-7.51), fluoroquinolones 4.94 (4.20-5.81), and trimethoprim-sulfonamides 3.32 (2.03-5.43). Conclusion: All antibiotic classes included in the study were significantly associated with CDI. Lincosamides (e.g., clindamycin) had the highest CDI ROR among the antibiotics evaluated in this study

The Risk and Clinical Implications of Antibiotic-Associated Acute Kidney Injury: A Review of the Clinical Data for Agents with Signals from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) Database

Antibiotic-associated acute kidney injury (AA-AKI) is quite common, especially among hospitalized patients; however, little is known about risk factors or mechanisms of why AA-AKI occurs. In this review, the authors have reviewed all available literature prior to 1 June 2022, with a large number of AKI reports. Information regarding risk factors of AA-AKI, mechanisms behind AA-AKI, and treatment/management principles to decrease AA-AKI risk were collected and reviewed. Patients treated in the inpatient setting are at increased risk of AA-AKI due to common risk factors: hypovolemia, concomitant use of other nephrotoxic medications, and exacerbation of comorbid conditions. Clinicians should attempt to correct risk factors for AA-AKI, choose antibiotic therapies with decreased association of AA-AKI to protect their high-risk patients, and narrow, when clinically possible, the use of antibiotics which have decreased incidence of AKI. To treat AKI, it is still recommended to discontinue all offending nephrotoxic agents and to renally adjust all medications according to package insert recommendations to decrease patient harm

Comparative Value of Four Measures of Retention in Expert Care in Predicting Clinical Outcomes and Health Care Utilization in HIV Patients

This study compared the ability of four measures of patient retention in HIV expert care to predict clinical outcomes. This retrospective study examined Veterans Health Administration (VHA) beneficiaries with HIV (ICD-9-CM codes 042 or V08) receiving expert care (defined as HIV-1 RNA viral load and CD4 cell count tests occurring within one week of each other) at VHA facilities from October 1, 2006, to September 30, 2008. Patients were ≥18 years old and continuous VHA users for at least 24 months after entry into expert care. Retention measures included: Annual Appointments (≥2 appointments annually at least 60 days apart), Missed Appointments (missed ≥25% of appointments), Infrequent Appointments (>6 months without an appointment), and Missed or Infrequent Appointments (missed ≥25% of appointments or >6 months without an appointment). Multivariable nominal logistic regression models were used to determine associations between retention measures and outcomes. Overall, 8,845 patients met study criteria. At baseline, 64% of patients were virologically suppressed and 37% had a CD4 cell count >500 cells/mm3. At 24 months, 82% were virologically suppressed and 46% had a CD4 cell count >500 cells/mm3. During follow-up, 13% progressed to AIDS, 48% visited the emergency department (ED), 28% were hospitalized, and 0.3% died. All four retention measures were associated with virologic suppression and antiretroviral therapy initiation at 24 months follow-up. Annual Appointments correlated positively with CD4 cell count >500 cells/mm3. Missed Appointments was predictive of all primary and secondary outcomes, including CD4 cell count ≤500 cells/mm3, progression to AIDS, ED visit, and hospitalization. Missed Appointments was the only measure to predict all primary and secondary outcomes. This finding could be useful to health care providers and public health organizations as they seek ways to optimize the health of HIV patients

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota

Poorer outcomes among cancer patients diagnosed with Clostridium difficile infections in United States community hospitals

Abstract Background Cancer predisposes patients to Clostridium difficile infection (CDI) due to health care exposures and medications that disrupt the gut microbiota or reduce immune response. Despite this association, the national rate of CDI among cancer patients is unknown. Furthermore, it is unclear how CDI affects clinical outcomes in cancer. The objective of this study was to describe CDI incidence and health outcomes nationally among cancer patients in the United States (U.S.). Methods Data for this study were obtained from the U.S. National Hospital Discharge Surveys from 2001 to 2010. Eligible patients included those at least 18 years old with a discharge diagnosis of cancer (ICD-9-CM codes 140–165.X, 170–176.X, 179–189.X, 190–209.XX). CDI was identified using ICD-9-CM code 008.45. Data weights were applied to sampled patients to provide national estimates. CDI incidence was calculated as CDI discharges per 1000 total cancer discharges. The in-hospital mortality rate and hospital length of stay (LOS) were compared between cancer patients with and without CDI using bivariable analyses. Results A total of 30,244,426 cancer discharges were included for analysis. The overall incidence of CDI was 8.6 per 1000 cancer discharges. CDI incidence increased over the study period, peaking in 2008 (17.2 per 1000 cancer discharges). Compared to patients without CDI, patients with CDI had significantly higher mortality (9.4% vs. 7.5%, p < 0.0001) and longer median LOS (9 days vs. 4 days, p < 0.0001). Conclusions CDI incidence is increasing nationally among cancer patients admitted to U.S. community hospitals. CDI was associated with significantly increased mortality and hospital LOS

A cross-sectional study of national outpatient gastric acid suppressant prescribing in the United States between 2009 and 2015.

PurposeGastric acid suppressants are commonly used in the United States, and while generally well-tolerated, long-term use has been associated with infection, bone fractures, and nutrient malabsorption. The purpose of this study was to describe national trends in gastric acid suppressant use over a 7-year period.MethodsThis was a cross-sectional study using data from the National Ambulatory Medical Care Survey from 2009 to 2015. Gastric acid suppressant use was defined as any outpatient visit with a documented prescription for a proton pump inhibitor or histamine-2 receptor antagonist documented during the outpatient visit. Sample data weights were used to extrapolate to national estimates. Use was calculated as the number of prescriptions per total outpatient visits per year. Appropriateness of prescribing was assessed using FDA-approved indications listed in each visit.ResultsThese data represent 6.8 billion patient outpatient visits between 2009 and 2015, of which nearly 600 million (8.8%) had documented gastric acid suppressant use. The median (IQR) age of gastric acid suppressant users and non-gastric acid suppressant users was 62 (50-73) and 49 (25-65), respectively. Gastric acid suppressant use decreased from 9.0% in 2009 to 7.7% in 2012, and then increased to 9.7% in 2015. Proton pump inhibitor use was slightly higher in the Midwest (8.3%). Only 15.8% of gastric acid suppressant users had a documented indication.ConclusionsProton pump inhibitor use increased after 2012, and the majority of gastric acid suppressant users did not have a documented indication. Judicious gastric acid suppressant prescribing needs to be exercised, especially in the context of new safety data regarding long-term proton pump inhibitor use

National ambulatory care non-insulin antidiabetic medication prescribing trends in the United States from 2009 to 2015.

ObjectiveDespite their efficacy in lowering hemoglobin A1c, recent data suggest that sulfonylureas are associated with cardiovascular risk and hypoglycemia. The objective of this study was to determine whether prescribers decreased sulfonylurea use in favor of newer medications in the United States over seven years.Research design and methodsThis cross-sectional study utilized data from the Centers for Disease Control and Prevention's National Ambulatory Medical Care Survey. Patient visits between 2009 and 2015 were included for patients who were at least 18 years old, had a documented prescription for a non-insulin antidiabetic medication, and a diagnosis of type 2 diabetes. Sample survey data were extrapolated to national estimates using data weights. Prescribing rates were calculated as the number of visits with a documented medication class divided by the total number of visits with a prescription for any diabetes medication class, times 100%.ResultsA total of 303 million patient visits were included in this study. The median (IQR) patient age was 64 (55-73) years old and 49.8% were male. Sulfonylurea prescribing rates decreased from 43% in 2009 to 36.5% in 2015. Prescribing of GLP-1 receptor agonists increased from 2009 to 2014 (3.95% to 5.30%), but then decreased to 4.19% in 2015. SGLT-2 inhibitor prescribing began in 2013 and increased to 7.3% by 2015. Metformin prescribing remained relatively stable over the study period (range 70% to 72%).ConclusionsNational ambulatory sulfonylurea prescribing decreased from 2009 to 2015 with a corresponding increase in newer non-insulin antidiabetic agent prescribing

Comparative Effectiveness Randomized Clinical Trial Using Next-generation Microbial Sequencing to Direct Prophylactic Antibiotic Choice Before Urologic Stone Lithotripsy Using an Interprofessional Model

Background: Next-generation sequencing (NGS) methods for microbial profiling have increased sensitivity to detect urinary pathogens. Objective: To determine whether NGS microbial profiling can be used to guide antibiotic prophylaxis and reduce infection compared with the standard of care. Design, setting, and participants: A prospective randomized controlled clinical trial of patients undergoing urologic stone interventions at an academic health center from December 2019 to January 2022 was conducted. Urine was collected at the preoperative visit for standard culture and intervention NGS diagnostics. Evaluable patients were culture negative, met 2-wk follow-up, and did not cancel surgery. Of 240 individuals (control = 121, intervention = 119), 83 control and 74 intervention patients were evaluable. Intervention: Microbial findings (paired quantitative polymerase chain reaction and NGS) were sent to an infectious disease pharmacist to recommend prophylactic antimicrobial regimen. Outcome measurements and statistical analysis: The primary outcome was postoperative urinary infection within the follow-up period (Fisher’s exact test). The primary outcome was analyzed by modified intent-to-treat (mITT) and per-protocol analyses. Secondary endpoints considered included positive culture concordance, antibiotic use, and adverse events. Additional post hoc analyses investigated factors contributing to infection (univariate logistic regression). Results and limitations: The intervention significantly reduced postsurgical urinary infection risk by 7.1% (–0.73%, 15%) compared with the standard of care in the mITT analysis (1.4% vs 8.4%, p = 0.045) or by 8.5% (0.88%, 16%) compared with the per-protocol analysis (0% vs 8.5%, p = 0.032). NGS-guided treatment altered the distribution of antibiotics used (p = 0.025), and antibiotics poorly matched with NGS findings were associated with increased infection odds (odds ratio [OR] = 5.9, p = 0.046). Women were at greater odds to develop infection (OR = 10, p = 0.03) and possessed differentiated microbial profiles (p < 0.001). Conclusions: Urinary microbial NGS-guided antibiotic prophylaxis before endoscopic urologic stone lithotripsy improves antibiotic selection to reduce healthcare-associated urinary infections; however, treatment efficacy may be limited by the ability to adhere to the recommended protocol. Patient summary: We investigated whether microbial DNA sequencing could improve the selection of antibiotics before kidney stone surgery in patients not known to have any bacteria in the urine on standard culture. We found that using microbe DNA to guide antibiotic choices decreased postoperative infection rate and may encourage individualized use of available antibiotics