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In countries with high human immunodeficiency virus (HIV) prevalence, up to 30% of pregnant women are living with HIV, with fetal exposure to both HIV and antiretroviral therapy during pregnancy. In addition, pregnant women without HIV but at high risk of HIV acquisition are increasingly receiving HIV preexposure antiretroviral prophylaxis (PrEP). Investments are being made to establish and follow cohorts of children to evaluate the long-term effects of in utero HIV and antiretroviral exposure. Agreement on a key set of definitions for relevant exposures and outcomes is important both for interpreting individual study results and for comparisons across cohorts. Harmonized definitions of in utero HIV and antiretroviral drug (maternal treatment or PrEP) exposure will also facilitate improved classification of these exposures in future observational studies and clinical trials. The proposed definitions offer a uniform approach to facilitate the consistent description and estimation of effects of HIV and antiretroviral exposures on key child health outcomes. [ABSTRACT FROM AUTHOR]

Background The Centers for Medicare and Medicaid Services (CMS) implemented a core measure sepsis (SEP-1) bundle in 2015. One element was initiation of broad-spectrum antibiotics within 3 hours of diagnosis. The policy has the potential to increase antibiotic use and Clostridioides difficile infection (CDI). We evaluated the impact of SEP-1 implementation on broad-spectrum antibiotic use and CDI occurrence rates. Methods Monthly adult antibiotic data for 4 antibiotic categories (surgical prophylaxis, broad-spectrum for community-acquired infections, broad-spectrum for hospital-onset/multidrug-resistant [MDR] organisms, and anti–methicillin-resistant Staphylococcus aureus [MRSA]) from 111 hospitals participating in the Clinical Data Base Resource Manager were evaluated in periods before (October 2014–September 2015) and after (October 2015–June 2017) policy implementation. Interrupted time series analyses, using negative binomial regression, evaluated changes in antibiotic category use and CDI rates. Results At the hospital level, there was an immediate increase in the level of broad-spectrum agents for hospital-onset/MDR organisms (+2.3%, P  = .0375) as well as a long-term increase in trend (+0.4% per month, P  = .0273). There was also an immediate increase in level of overall antibiotic use (+1.4%, P  = .0293). CDI rates unexpectedly decreased at the time of SEP-1 implementation. When analyses were limited to patients with sepsis, there was a significant level increase in use of all antibiotic categories at the time of SEP-1 implementation. Conclusions SEP-1 implementation was associated with immediate and long-term increases in broad-spectrum hospital-onset/MDR organism antibiotics. Antimicrobial stewardship programs should evaluate sepsis treatment for opportunities to de-escalate broad therapy as indicated. [ABSTRACT FROM AUTHOR]

Background Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. Methods We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7–10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion. During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. Results Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval,.70–.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P =.22). Conclusions Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285. [ABSTRACT FROM AUTHOR]

Unrecognized transmission of pathogens in healthcare settings can lead to colonization and infection of both patients and healthcare personnel. The use of personal protective equipment (PPE) is an important strategy to protect healthcare personnel from contamination and to prevent the spread of pathogens to subsequent patients. However, optimal PPE use is difficult, and healthcare personnel may alter delivery of care because of the PPE. Here, we summarize recent research from the Prevention Epicenters Program on healthcare personnel contamination and improvement of the routine use of PPE as well as Ebola-specific PPE. Future efforts to optimize the use of PPE should include increasing adherence to protocols for PPE use, improving PPE design, and further research into the risks, benefits, and best practices of PPE use. [ABSTRACT FROM AUTHOR]

Background. Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods. Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results. Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged =65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions. Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States. [ABSTRACT FROM AUTHOR]

The author comments on the study by Goetghebuer et al that investigated risks of infant infection-related hospitalization in a human immunodeficiency virus (HIV)-exposed uninfected infants (HEU) cohort compared to HIV-unexposed (HU). The study established that initiation of maternal antiretroviral therapy before pregnancy reduced these risks. It notes that this study in high-income country with low HIV prevalence can not be generalized among poorer countries where most HEU children are born.

People who use drugs experience delayed HIV diagnosis, reduced entry into and retention in care, delayed initiation of antiretroviral therapy, and inferior HIV outcomes. Overcoming healthcare disparities requires evidence-based, comprehensive packages of clinical/social services, including treatment for substance use disorders.Substance use disorders (SUDs) and human immunodeficiency virus (HIV) are pervasive epidemics that synergize, resulting in negative outcomes for HIV-infected people who use drugs (PWUDs). The expanding epidemiology of substance use demands a parallel evolution of the HIV specialist—beyond HIV to diagnosis and management of comorbid SUDs. The purpose of this paper is to describe healthcare disparities for HIV-infected PWUDs along each point of a continuum of care, and to suggest evidence-based strategies for overcoming these healthcare disparities. Despite extensive dedicated resources and availability of antiretroviral therapy (ART) in the United States, PWUDs continue to experience delayed HIV diagnosis, reduced entry into and retention in HIV care, delayed initiation of ART, and inferior HIV treatment outcomes. Overcoming these healthcare disparities requires integrated packages of clinical, pharmacological, behavioral, and social services, delivered in ways that are cost-effective and convenient and include, at a minimum, screening for and treatment of underlying SUDs. [ABSTRACT FROM PUBLISHER]

Studies the risk factors for and epidemiology of Stenotrophomonas maltophilia bacteremia (SMB) in a sample of case and control allogenic bone marrow transplant patients in a Los Angeles, California, hospital. Number of patients who had undergone transplantation during the same hospitalization that SMB was detected; Evidence that severe neutropenia and severe mucositis may promote infection with SM.

Background. Guidelines recommend azithromycin or a quinolone antibiotic for treatment of Legionella pneumonia. No clinical study has compared these strategies. Methods. We performed a retrospective cohort analysis of adults hospitalized in the United States with a diagnosis of Legionella pneumonia in the Premier Perspectives database (1 July 2008-30 June 2013). Our primary outcome was hospital mortality; we additionally evaluated hospital length of stay, development of Clostridium difficile colitis, and total hospital cost. We used propensity-based matching to compare patients treated with azithromycin vs a quinolone. All analyses were repeated on a subgroup of more severely ill patients, defined as requiring intensive care unit admission or mechanical ventilation or having a predicted probability of hospital mortality in the top quartile for all patients. Results. Legionella pneumonia was diagnosed in 3152 adults across 437 hospitals. Quinolones alone were used in 28.8%, azithromycin alone was used in 34.0%, and 1.8% received both. Crude hospital mortality was similar: 6.6% (95% confidence interval [CI], 5.0%-8.2%) for quinolones vs 6.4% (95% CI, 5.0%-7.9%) for azithromycin (P = .87); after propensity matching (n = 813 in each group), mortality remained similar (6.3% [95% CI, 4.6%-7.9%] vs 6.5% [95% CI, 4.8%-8.2%], P = .84 for the whole cohort, and 14.9% [95%CI, 10.0%-19.8%] vs 18.3%[95% CI, 13.0%-23.6%], P = .36 for the more severely ill). There was no difference in hospital length of stay, development of C. difficile, or total hospital cost. Conclusions. Use of azithromycin alone or a quinolone alone for treatment of Legionella pneumonia was associated with similar hospital mortality. Few patients receive combination therapy. [ABSTRACT FROM AUTHOR]

Treatment options for Achromobacter xylosoxidans are limited. Eight cystic fibrosis patients with A. xylosoxidans were treated with 12 cefiderocol courses. Pretreatment in vitro resistance was seen in 3 of 8 cases. Clinical response occurred after 11 of 12 treatment courses. However, microbiologic relapse was observed after 11 of 12 treatment courses, notably without emergence of resistance. [ABSTRACT FROM AUTHOR]

Background Antiretroviral therapy (ART) advances, aging, and comorbidities impact hospitalizations in human immunodeficiency virus (HIV)–positive populations. We examined temporal trends and patient characteristics associated with hospitalization rates and outcomes. Methods Among patients in the University of North Carolina Center for AIDS Research HIV Clinical Cohort receiving care during 1996–2016, we estimated annual hospitalization rates, time to inpatient mortality or live discharge, and 30-day readmission risk using bivariable Poisson, Fine-Gray, and log-binomial regression models. Results The 4323 included patients (29% women, 60% African American) contributed 30 007 person-years. Overall, the hospitalization rate per 100 person-years was 34.3 (95% confidence interval [CI], 32.4–36.4) with a mean annual change of −3% (95% CI, −4% to −2%). Patients who were black (vs white), older, had HIV RNA >400 copies/mL, or had CD4 count <200 cells/μL had higher hospitalization rates (all P <.05). Thirty-day readmission risk was 18.9% (95% CI, 17.7%–20.2%), stable over time (P >.05 for both 2010–2016 and 2003–2009 vs 1996–2002), and higher among black patients, those with detectable HIV RNA, and those with lower CD4 cell counts (all P <.05). Higher inpatient mortality was associated with older age and lower CD4 cell count (both P <.05). Conclusions Hospitalization rates decreased from 1996 to 2016, but high readmissions persisted. Older patients, those of minority race/ethnicity, and those with uncontrolled HIV experienced higher rates and worse hospitalization outcomes. These findings underscore the importance of early ART and care engagement, particularly at hospital discharge. [ABSTRACT FROM AUTHOR]

Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P =.40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P =.42). Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098. [ABSTRACT FROM AUTHOR]

Background Infection with the gram-negative bacterium Burkholderia pseudomallei can result in melioidosis, a life-threatening disease that can be difficult to diagnose. Culture remains the gold standard for diagnosis but requires laboratory resources not available in many endemic regions. A lateral flow immunoassay has shown promise for POC diagnostics but suffers from low sensitivity when used on blood samples. PCR also has low sensitivity on blood, attributed to the low bacterial numbers in blood observed in melioidosis patients, even when bacteraemic. Methods A prototype i-STAT cartridge was developed to utilize the monoclonal antibody specific for the capsule of pathogenic Burkholderia species employed on the LFI. The resulting POC assay was evaluated on 414 clinical specimens from Darwin, Australia and Cambodia. Results The i-STAT assay accurately distinguished Australian blood culture positive melioidosis patients from Australian patients hospitalized with other infections (AUC = 0.91, 95% CI 0.817 - 1.0). We derived an assay cutoff with 76% sensitivity and 94% specificity that correctly classified 88% (n = 74) of the Australian patients. Interestingly, only 46% (6/13) of the culture-positive melioidosis patients in Cambodia were classified correctly. Of great importance however, the assay detected capsule from blood samples for 32% of blood culture negative melioidosis patients in both cohorts and previously undiagnosed melioidosis patients in Cambodia. In addition the assay showed high sensitivity and specificity for urine, pus and sputum. Conclusions Diagnostic tools that are not dependent upon the growth kinetics or the levels of bacteremia of B. pseudomallei represent the next-generation of diagnostics and must be pursued further. [ABSTRACT FROM AUTHOR]