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Jennifer K Parker,1 Richard Gu,1 Gregory A Estrera,1 Betsy Kirkpatrick,2 Dusten T Rose,3 Despoina AI Mavridou,1,4 Kristin E Mondy,5 Bryan W Davies1,4 1Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA; 2Austin Public Health, City of Austin, Austin, TX, USA; 3Department of Pharmacy, Ascension Seton, Dell Seton Medical Center at The University of Texas, Austin, TX, USA; 4John Ring LaMontagne Center for Infectious Diseases, The University of Texas at Austin, Austin, TX, USA; 5Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX, USACorrespondence: Bryan W Davies, Email bwdavies@utexas.eduPurpose: Carbapenem-resistant Enterobacterales (CRE) are subject to intense global monitoring in an attempt to maintain awareness of prevalent and emerging resistance mechanisms and to inform treatment and infection prevention strategies. CRE and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales are not usually examined collectively in regards to their shared pool of resistance determinants. Here, we genetically and phenotypically assess clinical isolates of CRE and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales in the growing region of Central Texas, where CRE are emergent and occurrence of non-carbapenemase-producing-CRE (non-CP-CRE) infections is increasing.Methods: CRE (n=16) and ESBL-producing Enterobacterales (n=116) isolates were acquired from a regional hospital in Central Texas between December 2018 and January 2020. Isolates were assessed genetically and phenotypically using antibiotic susceptibility testing, targeted PCR, and whole genome sequencing.Results: CRE infections are increasing in incidence in Central Texas, and Klebsiella pneumoniae is causing the majority of these infections. Moreover, K. pneumoniae sequence type (ST) 307 is commonly found among both non-CP-CRE and EBSL-producing strains. Isolates carry similar plasmids harboring the gene for the ESBL CTX-M-15 and belong to the global lineage, rather than the Texas lineage, of ST307. Antibiotic resistance profiles, sequence data, and clinical records suggest that porin mutations may promote the transition of ST307 isolates from ESBL-producing to non-CP-CRE. In addition to antibiotic resistance mechanisms, several CRE isolates harbor active colicinogenic plasmids, which might influence the competitiveness of these bacteria during patient colonization.Conclusion: K. pneumoniae of the global ST307 lineage is circulating in Central Texas and is responsible for both non-CP CRE and ESBL-producing Enterobacterales infections. Enhanced surveillance is needed to understand the possible routes for the emergence of non-CP-CRE from EBSL-producing strains.Keywords: beta-lactam, Klebsiella, colicin, genetics, carbapenemase

Introduction: It is unknown whether infectious diseases consultation improves outcomes for enterococcal bacteraemia in a multicentre healthcare system., Methods: This retrospective multicentre observational cohort study included 250 adult patients with enterococcal bacteraemia between July 2016 and December 2020. The primary endpoint was a composite of clinical failure, including persistent bacteraemia, persistent fever, and in-hospital mortality. Secondary endpoints included adherence to a treatment bundle (appropriate empiric and definitive antibiotics, appropriate planned treatment duration, obtaining repeat blood cultures and an echocardiogram)., Results: Clinical failure occurred in 35 of 155 patients (22.6%) with an infectious diseases consultation and 16 of 95 patients (16.8%) without an infectious diseases consultation (P = 0.274). Multivariate analysis identified vasopressors as the only independent predictor of the primary outcome. Infectious diseases consultation resulted in higher adherence to a treatment bundle, including echocardiogram (75.5% vs. 34.7%; P < 0.0001), repeat blood cultures (85.2% vs. 68.4%; P = 0.002), appropriate definitive antibiotics (70.5% vs. 91.6%; P < 0.0001) and appropriate planned durations of therapy (81.1% vs. 94.2%; P = 0.001). More patients in the consult group were treated with ampicillin (47.1% vs. 22.1%; P < 0.0001) and fewer were treated with vancomycin (17.4% vs. 24.2%; P = 0.068)., Conclusion: Despite finding no difference in clinical failure between groups, this study highlights important benefits of infectious diseases consultation in enterococcal bacteraemia., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

We report a case of acute, vectorborne Chagas disease, acquired locally in central Texas, USA, manifesting as Romaña's sign, which was initially mistaken for orbital cellulitis. After the infection failed to respond to antibiotics, DNA-based next generation sequencing on plasma yielded high levels of Trypanasoma cruzi; results were confirmed by PCR.

HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4(+) cell count 464 cells/mm(3), 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (≥5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions.

Our objective was to determine if the presence of metabolic complications (MC) conveyed an additional risk for left ventricular (LV) dysfunction in people with HIV. HIV⁺ and HIV⁻ men and women were categorized into four groups: (1) HIV⁺ with MC (43±7 years, n=64), (2) HIV⁺ without MC (42±7 years, n=59), (3) HIV⁻ with MC (44±8 years, n=37), or (4) HIV⁻ controls without MC (42±8 years, n=41). All participants underwent two-dimensional (2-D), Doppler, and tissue Doppler echocardiography. Overall, the prevalence of systolic dysfunction (15 vs. 4%, p=0.02) and LV hypertrophy (9 vs. 1%, p=0.03) was greater in HIV⁺ than in HIV⁻ participants. Participants with MC had a greater prevalence of LV hypertrophy (10% vs. 1%). Early mitral annular velocity during diastole was significantly (p<0.005) lower in groups with MC (HIV⁺/MC⁺: 11.6±2.3, HIV⁻/MC⁺: 12.0±2.3 vs. HIV⁺/MC⁻: 12.4±2.3, HIV⁻/MC⁻: 13.1±2.4 cm/s) and tended to be lower in groups with HIV (p=0.10). However, there was no interaction effect of HIV and MC for any systolic or diastolic variable. Regardless of HIV status, participants with MC had reduced LV diastolic function. Although both the presence of MC and HIV infection were associated with lower diastolic function, there was no additive negative effect of HIV on diastolic function beyond the effect of MC. Also, HIV was independently associated with lower systolic function. Clinical monitoring of LV function in individuals with metabolic risk factors, regardless of HIV status, is warranted.

In the combination antiretroviral therapy (cART) era, renal dysfunction remains common. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) (ClinicalTrials.gov number, NCT00146419) is a prospective observational cohort study of HIV-infected adults. At baseline, comprehensive data were collected, including cystatin C and measures of renal function. Univariate and multivariate regression analyses were performed to identify factors associated with baseline renal dysfunction [estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m(2) calculated using the simplified Modification of Diet in Renal Disease equation] and elevated cystatin C (>1.0 mg/liter) in a cross-sectional analysis. Among 670 subjects with complete data (mean age 41 years, mean CD4 cell count 530 cells/mm(3), 79% prescribed cART), the mean eGFR was 96.8 ml/min/1.73 m(2). Forty percent of subjects had renal dysfunction; 3.3% had chronic kidney disease (eGFR < 60 ml/min/1.73 m(2)). Elevated cystatin C was present in 18% of subjects. In multivariate analysis, renal dysfunction was associated with older age, non-Hispanic white race/ethnicity, higher body mass index (BMI), hypertension, higher cystatin C levels, and current prescription of ritonavir. Factors associated with elevated cystatin C included hepatitis C coinfection, hypertension, current smoking, older age, current tenofovir use, detectable plasma HIV RNA, and elevated microalbuminuria. The prevalence of chronic kidney disease (CKD) was low in this contemporary HIV cohort. However, mild to moderate renal dysfunction was common despite the widespread use of cART.

Background: As HIV-infected persons age, the relative contribution of HIV infection, combination antiretroviral therapy (cART), and the normal aging process to the frequent comorbidities is unknown., Methods: We prospectively evaluated comorbidities, cardiovascular risk, cognitive function, and anthropomorphic and laboratory parameters of HIV-infected persons aged 50 years and over in two US urban clinics. Results were compared to controls from the National Health and Nutrition Examination Survey (NHANES) matched 1:1 by age, race, gender, smoking status, and body mass index (BMI)., Results: We enrolled 122 HIV-infected persons; median age 55 years, 83% male, 57% Caucasian, 39% current smokers, mean BMI 26 kg/m2, and 92% on cART. Compared to controls, HIV-infected persons had a higher prevalence of hypertension (54% vs 38%), hypertriglyceridemia (51% vs 33%), low bone mineral density (BMD) (39% vs 0%), and lipodystrophy and greater receipt of antihypertensive and lipid-lowering medications (all Ps < .05). Groups were similar in prevalence of coronary heart disease, diabetes mellitus, chronic viral hepatitis, non-AIDS-defining malignancies and Framingham Risk and cognitive function scores., Conclusions: Older HIV-infected persons have a higher prevalence of hypertension, hypertriglyceridemia, low BMD, and lipodystrophy than matched controls, suggesting that HIV and treatment-related factors exceed "normal" aging in the development of those problems.

Background: Long-term maternal outcomes after postpartum antiretroviral therapy (ART) discontinuation are unknown., Methods: Retrospective review of pregnancies in HIV-infected women on treatment between 1997 and 2005. Women were grouped by postpartum ART use and followed until new opportunistic infection (OI), death or last clinic visit., Results: Of 172 pregnancies, postpartum ART discontinuation occurred in 123 (71.5%) women and was associated with greater parity, no partner during pregnancy, and no indication for OI prophylaxis or preconception ART in multivariate analysis (P < .05). Median follow-up was 32.5 months after delivery. There were 12 OIs and 2 deaths; 10 OIs and both deaths occurred in women who had discontinued ART., Conclusion: Postpartum ART discontinuation is common, especially among those with less advanced HIV disease, but may leave women at increased risk of long term adverse outcomes. This study highlights the need for larger longitudinal studies to determine appropriate recommendations for postpartum ART administration.

The incidence and factors associated with inappropriate use of antifungal medications were studied in a Thai tertiary care center. The incidence of inappropriate antifungal use was 74% (in 42 of 57 patients). Isolation of Candida species from urine (P = .004) was a risk factor, whereas receipt of an infectious diseases consultation (P = .004) was protective.

The use of highly active antiretroviral therapy (HAART) has resulted in sustained reductions in mortality from HIV infection. In recent years, HAART has also been associated with metabolic complications that may increase patients' cardiovascular disease risk. Recent studies have begun to support a more complex interaction between HAART, HIV infection itself, and other traditional social and immunologic factors that may predispose patients to premature cardiovascular disease. Substantial progress has been made in the development of newer antiretroviral therapies that have a better metabolic profile with respect to dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of metabolically neutral antiretroviral therapies, together with aggressive management of other modifiable coronary risk factors, may improve cardiovascular disease risk in the long term.

A total of 192 HIV-1-infected antiretroviral-naive individuals had genotyping performed in our midwest university clinic between 2003 and 2005. The overall prevalence of resistance with either a reverse transcriptase or major protease mutation was 18%. There did not seem to be a significant difference in primary resistance patterns between different modes of HIV transmission (heterosexual versus men who have sex with men), gender or between white and African-American individuals.

Background: Osteopenia and osteoporosis are frequent complications of HIV infection and/or its treatment. Alendronate is the only bisphosphonate approved for the treatment of osteoporosis in men and women. We conducted a 48-week prospective, randomized, open-label study to evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone mineral density (BMD) in patients with HIV infection., Methods: Thirty-one HIV-infected subjects with lumbar spine BMD t-scores less than -1.0 on antiretroviral therapy for a minimum of 6 months were randomized to receive (n = 15) or not to receive (n = 16) 70 mg of alendronate weekly for 48 weeks. All subjects received calcium (1000 mg daily as calcium carbonate) and vitamin D supplementation (400 IU daily). The study was powered to detect 3% changes in BMD in the lumbar spine within arms at 48 weeks., Results: Thirty-one patients were enrolled; most were male, with an average length of HIV infection of 8 years. Eighty-four percent had an HIV RNA load below 400 copies/mL, with a current median CD4+ T-cell count of 561 cells/mm3 (median nadir CD4 cell count of 167 cells/mm). At baseline, the median t-score in the lumbar spine was -1.52 and the median t-score in the hip was -1.02. Alendronate in combination with vitamin D and calcium increased lumbar spine BMD by 5.2% (95% confidence interval [CI]: 1.3-6.4) at 48 weeks compared with an increase of 1.3% (95% CI: -2.4 to 4.0) in subjects receiving vitamin D and calcium alone. One subject discontinued treatment in each arm. There were no serious adverse events., Conclusions: Alendronate, vitamin D, and calcium are safe and potentially useful in the treatment of osteopenia/osteoporosis associated with HIV infection.

Recently, a high incidence of osteopenia and osteoporosis has been observed in individuals infected with human immunodeficiency virus (HIV). This problem appears to be more frequent in patients receiving potent antiretroviral therapy. Other bone-related complications in HIV-infected individuals, including avascular necrosis of the hip and compression fracture of the lumbar spine, have also been reported. People living with HIV have significant alterations in bone metabolism, regardless of whether they are receiving potent antiretroviral therapy. The underlying mechanisms to account for these observations remain unknown, although studies are underway to examine the relationship between the bone abnormalities and other complications associated with HIV and antiretroviral therapy. HIV-infected patients with osteopenia or osteoporosis should be treated similarly to HIV-seronegative patients with appropriate use of nutritional supplements (calcium and vitamin D) and exercise. Hormone replacement and antiresorptive therapies might be also indicated.

The underlying mechanisms of several bone disorders in human immunodeficiency virus (HIV)-infected persons and any relation to antiretroviral therapy have yet to be defined. A longitudinal study was conducted to estimate the prevalence of osteopenia or osteoporosis in HIV-infected persons; to assess bone mineralization, metabolism, and histomorphometry over time; and to evaluate predisposing factors. A total of 128 patients enrolled the study, and 93 were observed for 72 weeks. "Classic" risk factors (low body mass index, history of weight loss, steroid use, and smoking) for low bone mineral density (BMD) and duration of HIV infection were strongly associated with osteopenia. There was a weak association between low BMD and receipt of treatment with protease inhibitors; this association disappeared after controlling for the above factors. Markers of bone turnover tended to be elevated in the whole cohort but were not associated with low BMD. BMD increased slightly during follow-up. Traditional risk factors and advanced HIV infection play a more significant pathogenic role in the development of osteopenia and osteoporosis associated with HIV infection than do treatment-associated factors.

This study evaluates the change in CD4(+) T cell counts among patients who achieved complete viral suppression and subsequently discontinued highly active antiretroviral therapy (HAART). We included 72 human immunodeficiency virus (HIV)-1-infected patients with plasma HIV RNA loads of <500 copies/mL for at least 3 months who then discontinued therapy for at least 12 weeks. The median CD4(+) T decay while off HAART was 16 cells/mm(3)/month (interquartile range, -6 to -34 cells/month). The mean follow-up after therapy ended was 45 weeks. The slope of the CD4(+) T cell decay was inversely correlated with the increase of CD4(+) T cells while receiving HAART, baseline virus load, CD4(+) T cell count at the time therapy was discontinued, age, and duration HIV RNA levels were undetectable. In a multiple regression analysis model, the increase of CD4(+) T cells while receiving therapy and age were independently associated with the rate of CD4(+) T cell loss.

Patients who are colonized with enteric vancomycin-resistant Enterococcus faecium (VREF) are a major reservoir for transmission of and infection with this organism. In a randomized, controlled study to assess the effectiveness of high-dose bacitracin in the eradication of enteric VREF, 12 patients who were colonized with VREF were randomized to receive placebo (n=6) or orally administered zinc bacitracin (n=6) for 10 days. Posttreatment perirectal or stool cultures indicated that after 3 weeks, VREF had been eradicated from the stool of only 2 (33%) of 6 patients in each group. Of the 8 remaining patients who were still VREF-positive at 3 weeks after treatment, 5 (62%) had later evidence of spontaneous enteric eradication at 8 weeks. Further testing of VREF isolates revealed that a significant number (n=22, 76%) were resistant to bacitracin and that patients may have been colonized with multiple different VREF strains. Although bacitracin was not effective in the enteric eradication of VREF, the high rates of spontaneous eradication suggest that other host and environmental factors are more important in achieving long-term suppression or elimination of VREF colonization.