Efficacy of Noncarbapenem ß-Lactams Compared to Carbapenems for Extended-Spectrum ß-Lactamase-Producing Enterobacterales Urinary Tract Infections.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales are frequent causes of urinary tract infections (UTIs). Severe infections caused by ESBL Enterobacterales are often treated with carbapenems, but optimal treatment for less severe infections such as UTIs is unclear. METHODS: This retrospective cohort study included patients admitted to 4 hospitals in an academic healthcare system with an ESBL UTI treated with either a noncarbapenem ß-lactam (NCBL) or a carbapenem for at least 48 hours from 1 April 2014 to 30 April 2018. Those who received an NCBL were compared to those receiving a carbapenem, with a primary outcome of hospital length of stay (LOS) and secondary outcomes of clinical and microbiological response, days until transition to oral therapy, rate of relapsed infection, and rate of secondary infections with a multidrug-resistant organism. RESULTS: Characteristics were similar among patients who received carbapenems (n = 321) and NCBLs (n = 171). There was no difference in LOS for the NCBL group compared to the carbapenem group (13 days vs 15 days, P = .66). The NCBL group had higher rates of microbiologic eradication (98% vs 92%, P = .002), shorter time to transition to oral therapy (5 days vs 9 days, P < .001), shorter overall durations of therapy (7 days vs 10 days, P < .001), and lower rates of relapsed infections (5% vs 42%, P = .0003). CONCLUSIONS: Patients treated with NCBLs had similar LOS, higher rates of culture clearance, and shorter durations of antibiotic therapy compared to patients treated with carbapenems, suggesting that treatment for ESBL UTIs should not be selected solely based on phenotypic resistance.

Reductions in inpatient fluoroquinolone use and postdischarge Clostridioides difficile infection (CDI) from a systemwide antimicrobial stewardship intervention.

Objective: To determine the impact of an inpatient stewardship intervention targeting fluoroquinolone use on inpatient and postdischarge Clostridioides difficile infection (CDI). Design: We used an interrupted time series study design to evaluate the rate of hospital-onset CDI (HO-CDI), postdischarge CDI (PD-CDI) within 12 weeks, and inpatient fluoroquinolone use from 2 years prior to 1 year after a stewardship intervention. Setting: An academic healthcare system with 4 hospitals. Patients: All inpatients hospitalized between January 2017 and September 2020, excluding those discharged from locations caring for oncology, bone marrow transplant, or solid-organ transplant patients. Intervention: Introduction of electronic order sets designed to reduce inpatient fluoroquinolone prescribing. Results: Among 163,117 admissions, there were 683 cases of HO-CDI and 1,104 cases of PD-CDI. In the context of a 2% month-to-month decline starting in the preintervention period (P < .01), we observed a reduction in fluoroquinolone days of therapy per 1,000 patient days of 21% after the intervention (level change, P < .05). HO-CDI rates were stable throughout the study period. In contrast, we also detected a change in the trend of PD-CDI rates from a stable monthly rate in the preintervention period to a monthly decrease of 2.5% in the postintervention period (P < .01). Conclusions: Our systemwide intervention reduced inpatient fluoroquinolone use immediately, but not HO-CDI. However, a downward trend in PD-CDI occurred. Relying on outcome measures limited to the inpatient setting may not reflect the full impact of inpatient stewardship efforts.

The impact of an electronic medical record nudge on reducing testing for hospital-onset Clostridioides difficile infection.

OBJECTIVE: To determine the effect of an electronic medical record (EMR) nudge at reducing total and inappropriate orders testing for hospital-onset Clostridioides difficile infection (HO-CDI). DESIGN: An interrupted time series analysis of HO-CDI orders 2 years before and 2 years after the implementation of an EMR intervention designed to reduce inappropriate HO-CDI testing. Orders for C. difficile testing were considered inappropriate if the patient had received a laxative or stool softener in the previous 24 hours. SETTING: Four hospitals in an academic healthcare network. PATIENTS: All patients with a C. difficile order after hospital day 3. INTERVENTION: Orders for C. difficile testing in patients administered a laxative or stool softener in <24 hours triggered an EMR alert defaulting to cancellation of the order ("nudge"). RESULTS: Of the 17,694 HO-CDI orders, 7% were inappropriate (8% prentervention vs 6% postintervention; P < .001). Monthly HO-CDI orders decreased by 21% postintervention (level-change rate ratio [RR], 0.79; 95% confidence interval [CI], 0.73-0.86), and the rate continued to decrease (postintervention trend change RR, 0.99; 95% CI, 0.98-1.00). The intervention was not associated with a level change in inappropriate HO-CDI orders (RR, 0.80; 95% CI, 0.61-1.05), but the postintervention inappropriate order rate decreased over time (RR, 0.95; 95% CI, 0.93-0.97). CONCLUSION: An EMR nudge to minimize inappropriate ordering for C. difficile was effective at reducing HO-CDI orders, and likely contributed to decreasing the inappropriate HO-CDI order rate after the intervention.

Effects of Antiretroviral Therapy on Immune Function and Arterial Inflammation in Treatment-Naive Patients With Human Immunodeficiency Virus Infection.

IMPORTANCE: Individuals with human immunodeficiency virus (HIV) infection receiving combined antiretroviral therapy (ART) have an increased risk of myocardial infarction. Effects of ART on arterial inflammation among treatment-naive individuals with HIV are unknown. OBJECTIVE: To determine the effects of newly initiated ART on arterial inflammation and other immune/inflammatory indices in ART-naive patients with HIV infection. DESIGN, SETTING, PARTICIPANTS: Twelve treatment-naive HIV-infected individuals underwent fludeoxyglucose F 18 ([18F]-FDG) positron emission tomographic scanning for assessment of arterial inflammation, coronary computed tomographic angiography for assessment of subclinical atherosclerosis, and systemic immune and metabolic phenotyping before and 6 months after the initiation of therapy with elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (combined ART). Systemic immune and metabolic factors were also assessed in 12 prospectively recruited individuals without HIV serving as controls. The study began July 24, 2012, and was completed May 7, 2015. INTERVENTIONS: Combined ART in the HIV-infected cohort. MAIN OUTCOMES AND MEASURES: The primary outcome was change in aortic target-background ratio (TBR) on [18F]-FDG-PET with combined ART in the HIV-infected group. RESULTS: For the 12 participants with HIV infection (mean (SD) age, 35 [11] years), combined ART suppressed viral load (mean [SD] log viral load, from 4.3 [0.6] to 1.3 [0] copies/mL; P < .001), increased the CD4+ T-cell count (median [IQR], from 461 [332-663] to 687 [533-882] cells/mm3; P < .001), and markedly reduced percentages of circulating activated CD4+ T cells (human leukocyte antigen-D related [HLA-DR]+CD38+CD4+) (from 3.7 [1.8-5.0] to 1.3 [0.3-2.0]; P = .008) and CD8+ T cells (HLA-DR+CD38+CD8+) (from 18.3 [8.1-27.0] to 4.0 [1.5-7.8]; P = .008), increased the percentage of circulating classical CD14+CD16- monocytes (from 85.8 [83.7-90.8] to 91.8 [87.5-93.2]; P = .04), and reduced levels of CXCL10 (mean [SD] log CXCL10, from 2.4 [0.4] to 2.2 [0.4] pg/mL; P = .03). With combined ART, uptake of [18F]-FDG in the axillary lymph nodes, as measured by TBR, decreased from a median (IQR) of 3.7 (1.3-7.0) at baseline to 1.4 (0.9-1.9; P = .01) at study end. In contrast, no significant decrease was seen in aortic TBR in response to combined ART (mean [SD], 1.9 [0.2]; median [IQR], 2.0 [1.8-2.1] at baseline to 2.2 [0.4]; 2.1 [1.9-2.6], respectively, at study end; P = .04 by 2-way test, P = .98 for test of decrease by 1-way test). Changes in aortic TBR during combined ART were significantly associated with changes in lipoprotein-associated phospholipase A2 (n = 10; r = 0.67; P = .03). Coronary plaque increased among 3 participants with HIV infection with baseline plaque and developed de novo in 1 participant during combined ART. CONCLUSIONS AND RELEVANCE: Newly initiated combined ART in treatment-naive individuals with HIV infection had discordant effects to restore immune function without reducing arterial inflammation. Complementary strategies to reduce arterial inflammation among ART-treated HIV-infected individuals may be needed.

Aspirin Use for Primary and Secondary Prevention in Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Patients.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with increased risk of myocardial infarction (MI). The use of aspirin for primary and secondary MI prevention in HIV infection has not been extensively studied. METHODS: We performed a cross-sectional study of 4037 patients infected with HIV and 36 338 demographics-matched control patients in the Partners HealthCare System HIV cohort. We developed an algorithm to ascertain rates of nonepisodic acetylsalicylic acid (ASA) use using medication and electronic health record free text data. We assessed rates of ASA use among HIV-infected and HIV-uninfected (negative) patients with and without coronary heart disease (CHD). RESULTS: Rates of ASA use were lower among HIV-infected compared with HIV-uninfected patients (12.4% vs 15.3%, P < .001), with a relatively greater difference among patients with ≥2 CHD risk factors (22.1% vs 42.4%, P < .001). This finding was present among men and among patients in the 30-39 and 40-49 age groups. Among patients with prevalent CHD using ASA for secondary prevention, rates of ASA use were also lower among HIV-infected patients compared with HIV-uninfected patients (51.6% vs 65.4%, P < .001). CONCLUSIONS: Rates of ASA use were lower among HIV-infected patients compared with controls, with a greater relative difference among those with elevated CHD risk and those with known CHD. Further studies are needed to investigate the optimal strategies for ASA use among patients infected with HIV.

Geographic information system-based screening for TB, HIV, and syphilis (GIS-THIS): a cross-sectional study.

OBJECTIVE: To determine the feasibility and case detection rate of a geographic information systems (GIS)-based integrated community screening strategy for tuberculosis, syphilis, and human immunodeficiency virus (HIV). DESIGN: Prospective cross-sectional study of all participants presenting to geographic hot spot screenings in Wake County, North Carolina. METHODS: The residences of tuberculosis, HIV, and syphilis cases incident between 1/1/05-12/31/07 were mapped. Areas with high densities of all 3 diseases were designated "hot spots." Combined screening for tuberculosis, HIV, and syphilis were conducted at the hot spots; participants with positive tests were referred to the health department. RESULTS AND CONCLUSIONS: Participants (N = 247) reported high-risk characteristics: 67% previously incarcerated, 40% had lived in a homeless shelter, and 29% had a history of crack cocaine use. However, 34% reported never having been tested for HIV, and 41% did not recall prior tuberculin skin testing. Screening identified 3% (8/240) of participants with HIV infection, 1% (3/239) with untreated syphilis, and 15% (36/234) with latent tuberculosis infection. Of the eight persons with HIV, one was newly diagnosed and co-infected with latent tuberculosis; he was treated for latent TB and linked to an HIV provider. Two other HIV-positive persons had fallen out of care, and as a result of the study were linked back into HIV clinics. Of 27 persons with latent tuberculosis offered therapy, nine initiated and three completed treatment. GIS-based screening can effectively penetrate populations with high disease burden and poor healthcare access. Linkage to care remains challenging and will require creative interventions to impact morbidity.

Factors associated with HIV testing among public sector clinic attendees in Johannesburg, South Africa.

Uptake of VCT remains low in many sub-Saharan African countries. Men and women aged 15 and older were recruited from a family planning, STI, and VCT clinic in inner-city Johannesburg between 2004 and 2005 to take part in a cross-sectional survey on HIV testing (n = 198). Fourty-eight percent of participants reported previously testing for HIV and, of these, 86.9% reported disclosing their status to their sex partner. In multivariable analyses, individuals whose partners had been tested for HIV were more likely to have tested (AOR 2.92; 95% CI: 1.38-6.20). In addition, those who reported greater blame/shame attitudes towards people living with HIV/AIDS were less likely to have tested (AOR 0.35; 95% CI: 0.16-0.77) while those reporting more equitable attitudes towards people living with HIV/AIDS were more likely to have tested (AOR 2.87; 95% CI: 1.20-6.86). Promotion of and increased access to couples HIV testing should be made available within the South African context.

Is HIV infection a risk factor for multi-drug resistant tuberculosis? A systematic review.

BACKGROUND: Tuberculosis (TB) is an important cause of human suffering and death. Human immunodeficiency virus (HIV), multi-drug resistant TB (MDR-TB), and extensive drug resistant tuberculosis (XDR-TB) have emerged as threats to TB control. The association between MDR-TB and HIV infection has not yet been fully investigated. We conducted a systematic review and meta-analysis to summarize the evidence on the association between HIV infection and MDR-TB. METHODS AND RESULTS: Original studies providing Mycobacterium tuberculosis resistance data stratified by HIV status were identified using MEDLINE and ISI Web of Science. Crude MDR-TB prevalence ratios were calculated and analyzed by type of TB (primary or acquired), region and study period. Heterogeneity across studies was assessed, and pooled prevalence ratios were generated if appropriate. No clear association was found between MDR-TB and HIV infection across time and geographic locations. MDR-TB prevalence ratios in the 32 eligible studies, comparing MDR-TB prevalence by HIV status, ranged from 0.21 to 41.45. Assessment by geographical region or study period did not reveal noticeable patterns. The summary prevalence ratios for acquired and primary MDR-TB were 1.17 (95% CI 0.86, 1.6) and 2.72 (95% CI 2.03, 3.66), respectively. Studies eligible for review were few considering the size of the epidemics. Most studies were not adjusted for confounders and the heterogeneity across studies precluded the calculation of a meaningful overall summary measure. CONCLUSIONS: We could not demonstrate an overall association between MDR-TB and HIV or acquired MDR-TB and HIV, but our results suggest that HIV infection is associated with primary MDR-TB. Future well-designed studies and surveillance in all regions of the world are needed to better clarify the relationship between HIV infection and MDR-TB.