Microbiological characteristics, transmission routes, and mitigation measures in bronchoscope-associated investigations: Summary of Centers for Disease Control and Prevention (CDC) consultations, 2014-2022.

In this summary of US Centers for Disease Control and Prevention (CDC) consultations with state and local health departments concerning their bronchoscope-associated investigations from 2014 through 2022, bronchoscope reprocessing gaps and exposure to nonsterile water sources appeared to be the major routes of transmission of infectious pathogens, which were primarily water-associated bacteria.

Prescribing of Outpatient Antibiotics Commonly Used for Respiratory Infections Among Adults Before and During the Coronavirus Disease 2019 Pandemic in Brazil.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have impacted outpatient antibiotic prescribing in low- and middle-income countries such as Brazil. However, outpatient antibiotic prescribing in Brazil, particularly at the prescription level, is not well-described. METHODS: We used the IQVIA MIDAS database to characterize changes in prescribing rates of antibiotics commonly prescribed for respiratory infections (azithromycin, amoxicillin-clavulanate, levofloxacin/moxifloxacin, cephalexin, and ceftriaxone) among adults in Brazil overall and stratified by age and sex, comparing prepandemic (January 2019-March 2020) and pandemic periods (April 2020-December 2021) using uni- and multivariate Poisson regression models. The most common prescribing provider specialties for these antibiotics were also identified. RESULTS: In the pandemic period compared to the prepandemic period, outpatient azithromycin prescribing rates increased across all age-sex groups (incidence rate ratio [IRR] range, 1.474-3.619), with the greatest increase observed in males aged 65-74 years; meanwhile, prescribing rates for amoxicillin-clavulanate and respiratory fluoroquinolones mostly decreased, and changes in cephalosporin prescribing rates varied across age-sex groups (IRR range, 0.134-1.910). For all antibiotics, the interaction of age and sex with the pandemic in multivariable models was an independent predictor of prescribing changes comparing the pandemic versus prepandemic periods. General practitioners and gynecologists accounted for the majority of increases in azithromycin and ceftriaxone prescribing during the pandemic period. CONCLUSIONS: Substantial increases in outpatient prescribing rates for azithromycin and ceftriaxone were observed in Brazil during the pandemic with prescribing rates being disproportionally different by age and sex. General practitioners and gynecologists were the most common prescribers of azithromycin and ceftriaxone during the pandemic, identifying them as potential specialties for antimicrobial stewardship interventions.

Higher buccal mitochondrial DNA and mitochondrial common deletion number are associated with markers of neurodegeneration and inflammation in cerebrospinal fluid.

Human immunodeficiency virus (HIV) infection is potentially associated with premature aging, but demonstrating this is difficult due to a lack of reliable biomarkers. The mitochondrial (mt) DNA "common deletion" mutation (mtCDM) is a 4977-bp deletion associated with aging and neurodegenerative diseases. We examined how mtDNA and mtCDM correlate with markers of neurodegeneration and inflammation in people with and without HIV (PWH and PWOH). Data from 149 adults were combined from two projects involving PWH (n = 124) and PWOH (n = 25). We measured buccal mtDNA and mtCDM by digital droplet PCR and compared them to disease and demographic characteristics and soluble biomarkers in cerebrospinal fluid (CSF) and blood measured by immunoassay. Participants had a median age of 52 years, with 53% white and 81% men. Median mtDNA level was 1,332 copies/cell (IQR 1,201-1,493) and median mtCDM level was 0.36 copies × 102/cell (IQR 0.31-0.42); both were higher in PWH. In the best model adjusting for HIV status and demographics, higher mtDNA levels were associated with higher CSF amyloid-ß 1-42 and 8-hydroxy-2'-deoxyguanosine and higher mtCDM levels were associated with higher plasma soluble tumor necrosis factor receptor II. The differences in mtDNA markers between PWH and PWOH support potential premature aging in PWH. Our findings suggest mtDNA changes in oral tissues may reflect CNS processes, allowing the use of inexpensive and easily accessible buccal biospecimens as a screening tool for CSF inflammation and neurodegeneration. Confirmatory and mechanistic studies on mt genome alterations by HIV and ART may identify interventions to prevent or treat neurodegenerative complications.

Novel risk factors and outcomes in inflammatory bowel disease patients with Clostridioides difficile infection.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridioides difficile infection (CDI) with an increased risk of adverse outcomes including increased in-hospital mortality, IBD treatment failure, re-hospitalization, and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited. We evaluated four potentially modifiable novel risk factors [body mass index (BMI), statin use, opioid use, and antidepressant use] on CDI risk and adverse outcomes in these patients. METHODS: Using a retrospective design, variables were abstracted from records for patients with IBD and CDI from 2008 to 2013. Statistical analysis comprised descriptive statistics and univariate and multivariate logistic regression analyses. RESULTS: There were 137 patients with IBD and CDI included in this study. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe, complicated CDI, compared with 22% of patients in the underweight/normal BMI [odds ratio (OR) 2.85, p = 0.02] and 19% in the obese category (OR 3.95, p = 0.04). Statin use was associated with severe or severe, complicated CDI when controlling for age and BMI (OR 5.66, p = 0.01). There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. CONCLUSIONS: An overweight BMI and statin use were associated with severe or severe, complicated CDI in IBD patients. Further studies are needed to better understand how these factors impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of complications from CDI.

Predictors and Management of Failed Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

BACKGROUND AND GOALS: Clostridioides difficile infection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort. METHODS: A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positive C. difficile stool test during follow-up (≥2 mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT±1 month. RESULTS: Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89 y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9 mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%, P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%, P=0.01), pseudomembranes at FMT (4.3% vs. 0%, P=0.03), and poor bowel preparation (68.5% vs. 31.4%, P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy. CONCLUSIONS: Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.

Using diagnostic stewardship to reduce rates, healthcare expenditures and accurately identify cases of hospital-onset Clostridioides difficile infection.

OBJECTIVE: Lack of judicious testing can result in the incorrect diagnosis of Clostridioides difficile infection (CDI), unnecessary CDI treatment, increased costs and falsely augmented hospital-acquired infection (HAI) rates. We evaluated facility-wide interventions used at the VA San Diego Healthcare System (VASDHS) to reduce healthcare-onset, healthcare-facility-associated CDI (HO-HCFA CDI), including the use of diagnostic stewardship with test ordering criteria. DESIGN: We conducted a retrospective study to assess the effectiveness of measures implemented to reduce the rate of HO-HCFA CDI at the VASDHS from fiscal year (FY)2015 to FY2018. INTERVENTIONS: Measures executed in a stepwise fashion included a hand hygiene initiative, prompt isolation of CDI patients, enhanced terminal room cleaning, reduction of fluoroquinolone and proton-pump inhibitor use, laboratory rejection of solid stool samples, and lastly diagnostic stewardship with C. difficile toxin B gene nucleic acid amplification testing (NAAT) criteria instituted in FY2018. RESULTS: From FY2015 to FY2018, 127 cases of HO-HCFA CDI were identified. All rate-reducing initiatives resulted in decreased HO-HCFA cases (from 44 to 13; P ≤ .05). However, the number of HO-HCFA cases (34 to 13; P ≤ .05), potential false-positive testing associated with colonization and laxative use (from 11 to 4), hospital days (from 596 to 332), CDI-related hospitalization costs (from $2,780,681 to $1,534,190) and treatment cost (from $7,158 vs $1,476) decreased substantially following the introduction of diagnostic stewardship with test criteria from FY2017 to FY2018. CONCLUSIONS: Initiatives to decrease risk for CDI and diagnostic stewardship of C. difficile stool NAAT significantly reduced HO-HCFA CDI rates, detection of potential false-positives associated with laxative use, and lowered healthcare costs. Diagnostic stewardship itself had the most dramatic impact on outcomes observed and served as an effective tool in reducing HO-HCFA CDI rates.

Nontyphoid Salmonella Empyema in a Patient with Type 2 Diabetes Mellitus.

Pleuropulmonary infections caused by nontyphoid Salmonella (NTS) are rare, but may develop in immunocompromised hosts. We report the case of a 56-year-old male with uncontrolled diabetes mellitus presenting with a multiloculated empyema due to NTS involving the left oblique pulmonary fissure.

Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients. METHODS: We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results. RESULTS: We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified. CONCLUSIONS: Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

Barrett Esophagus Length, Nodularity, and Low-grade Dysplasia are Predictive of Progression to Esophageal Adenocarcinoma.

GOALS: To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review. BACKGROUND: Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned. Previous studies have reported factors predictive of progression to EAC to guide surveillance intervals, but their strength is limited by small sample size and absence of expert gastrointestinal pathologist involvement in esophageal biopsy review. STUDY: NDBE and LGD subjects were identified from a prospective registry in a tertiary care center. "Progressors" were BE subjects who developed HGD/EAC>12 months after the initial NDBE or LGD diagnosis. Cox proportional hazards model were used to identify predictors of progression. RESULTS: In total, 318 with NDBE and 301 with BE-LGD (mean age, 62.6 y, 85% male) were included. The mean follow-up was 5.3 years. The 7 NDBE and 21 LGD subjects progressed to HGD/EAC. BE length [hazards ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.29], presence of nodularity (HR, 4.98; 95% CI, 1.80-11.7), and baseline LGD (HR, 2.57; 95% CI, 1.13-6.57) were significant predictors of progression on multivariate analysis. CONCLUSIONS: In this well-defined cohort of NDBE and BE-LGD subjects, BE length, presence of LGD, and nodularity were independent predictors of progression to HGD/EAC. These factors may aid in identifying high-risk patients who may benefit from closer endoscopic surveillance/therapy.

Colon Surgery Risk With Corticosteroids Versus Immunomodulators or Biologics in Inflammatory Bowel Disease Patients With Clostridium difficile Infection.

BACKGROUND: Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), and CDI often precipitates IBD exacerbation. Because CDI cannot be distinguished clinically from an IBD exacerbation, management is difficult. We aimed to assess factors associated with adverse outcomes in IBD with CDI, including the role of escalating or de-escalating IBD therapy and CDI treatment. METHODS: Records for patients with IBD and CDI from 2008 to 2013 were abstracted for variables including IBD severity before CDI diagnosis, CDI management, subsequent IBD exacerbation, CDI recurrence, and colon surgery. Colon surgery was defined as resection of any colonic segment within 1 year after CDI diagnosis. RESULTS: We included 137 IBD patients (median age, 46 years; 55% women): 70 with ulcerative colitis (51%), 63 with Crohn's disease (46%), and 4 with indeterminate colitis (3%). Overall, 70% of CDIs were mild-moderate, 14% were severe, and 15% were severe-complicated. Clostridium difficile infection treatment choice did not vary by infection severity (P = 0.27). Corticosteroid escalation (odds ratio [OR], 5.94; 95% confidence interval [CI], 2.03-17.44) was a positive predictor of colon surgery within 1 year after CDI; older age (OR, 0.09; 95% CI, 0.01-0.44) was a negative predictor. Modifying the corticosteroid regimen did not affect CDI recurrence or risk of future IBD exacerbation. Adverse outcomes did not differ with CDI antibiotic regimens or biologic or immunomodulator regimen modification. CONCLUSIONS: Corticosteroid escalation for IBD during CDI was associated with higher risk of colon surgery. Type of CDI treatment did not influence IBD outcomes. Prospective studies are needed to further elucidate optimal management in this high-risk population.

Trends in Outcomes of Patients With Metastatic Cancer Undergoing Intubation and Mechanical Ventilation: Results of the National Hospital Discharge Survey.

Background: There has been an overall decline in intensive care unit mortality over the past 2 decades, including in patients undergoing intubation and mechanical ventilation (MV). Whether this decline extends to patients with metastatic cancer remains unknown. We analyzed the outcomes of patients with metastatic cancer undergoing intubation/MV using the National Hospital Discharge Survey (NHDS) database from 2001 to 2010. Methods: Diagnosis and procedure codes were used to identify patients with metastatic cancer who underwent intubation/MV. Demographics, diagnoses, length of stay (LOS), and discharge information were abstracted. Multivariate linear and logistic regression models with weighted analysis were conducted to study trends in outcomes. Results: During the 10-year study period, 200,350 patients with metastatic cancer and who underwent intubation/MV were identified; the mean age was 65.3 years and 46.2% were men. There was an increase in the total number of patients with metastatic cancer who underwent intubation/MV during the study period, from 36,881 in 2001-2002 to 51,003 in 2009-2010 (P<.001). The overall inpatient mortality rate was 57.3%, discharge to a care facility (DTCF) rate was 40.9% among patients alive at discharge, and mean LOS was 11.1 days. No significant trends were seen in rates of mortality, DTCF, or LOS from 2001 to 2010. Conclusions: In this national database, there was an increase in the number of patients with metastatic cancer who underwent intubation/MV. These patients had high rates of inpatient mortality and DTCF, which did not improve during the study period. Therefore, novel solutions are required to improve outcomes for these patients.

Successful Surgical Treatment of Severe Calciphylaxis Using a Bilayer Dermal Replacement Matrix.

Cutaneous calciphylaxis is a rare and often intractable disease that involves subcutaneous vascular calcification, ischemia, and subsequent necrosis. Calciphylaxis has an associated 60%-80% mortality rate with sepsis as the leading cause of death. However, despite variable success rates, the proper treatment of calciphylaxis remains controversial. In this case report, the authors present a 42-year-old female who presented with bilateral lower extremity calciphylaxis in conjunction with long-standing liver disease and acute renal failure. Cure of the patient's calciphylaxis was achieved through a surgical approach using staged debridement, placement of a dermal regenerative template (Integra Dermal Regeneration Template, Integra Lifesciences, Plainsboro, NJ), and followed by successful skin grafting. This is the first successful treatment of calciphylaxis in the literature to date using dermal regenerative template material.

Metal ions, not metal-catalyzed oxidative stress, cause clay leachate antibacterial activity.

Aqueous leachates prepared from natural antibacterial clays, arbitrarily designated CB-L, release metal ions into suspension, have a low pH (3.4-5), generate reactive oxygen species (ROS) and H2O2, and have a high oxidation-reduction potential. To isolate the role of pH in the antibacterial activity of CB clay mixtures, we exposed three different strains of Escherichia coli O157:H7 to 10% clay suspensions. The clay suspension completely killed acid-sensitive and acid-tolerant E. coli O157:H7 strains, whereas incubation in a low-pH buffer resulted in a minimal decrease in viability, demonstrating that low pH alone does not mediate antibacterial activity. The prevailing hypothesis is that metal ions participate in redox cycling and produce ROS, leading to oxidative damage to macromolecules and resulting in cellular death. However, E. coli cells showed no increase in DNA or protein oxidative lesions and a slight increase in lipid peroxidation following exposure to the antibacterial leachate. Further, supplementation with numerous ROS scavengers eliminated lipid peroxidation, but did not rescue the cells from CB-L-mediated killing. In contrast, supplementing CB-L with EDTA, a broad-spectrum metal chelator, reduced killing. Finally, CB-L was equally lethal to cells in an anoxic environment as compared to the aerobic environment. Thus, ROS were not required for lethal activity and did not contribute to toxicity of CB-L. We conclude that clay-mediated killing was not due to oxidative damage, but rather, was due to toxicity associated directly with released metal ions.

Adaptation of the neutral bacterial comet assay to assess antimicrobial-mediated DNA double-strand breaks in Escherichia coli.

This study aimed to determine the mechanism of action of a natural antibacterial clay mineral mixture, designated as CB, by investigating the induction of DNA double-strand breaks (DSBs) in Escherichia coli. To quantify DNA damage upon exposure to soluble antimicrobial compounds, we modified a bacterial neutral comet assay, which associates the general length of an electrophoresed chromosome, or comet, with the degree of DSB-associated DNA damage. To appropriately account for antimicrobial-mediated strand fragmentation, suitable control reactions consisting of exposures to water, ethanol, kanamycin, and bleomycin were developed and optimized for the assay. Bacterial exposure to the CB clay resulted in significantly longer comet lengths, compared to water and kanamycin exposures, suggesting that the induction of DNA DSBs contributes to the killing activity of this antibacterial clay mineral mixture. The comet assay protocol described herein provides a general technique for evaluating soluble antimicrobial-derived DNA damage and for comparing DNA fragmentation between experimental and control assays.