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Background A better understanding of the risk for coronavirus disease 2019 (COVID-19) that people experiencing homelessness (PEH) face in congregate shelters versus unsheltered encampments is critical for an effective pandemic response. Methods We analyzed factors associated with current and past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among PEH in day and overnight shelters and encampments in Denver, Colorado, during June 2–July 28, 2020, and constructed multivariable logistic regression models to examine risk factors for SARS-CoV-2 RNA and seropositivity with age, race/ethnicity, testing location, testing month, and symptom status as predictor variables. Results A total of 823 participants were tested for SARS-CoV-2 RNA, and 276 individuals were tested for SARS-CoV-2 antibodies. A greater percentage of PEH at overnight shelters tested positive for SARS-CoV-2 RNA (8.6% vs 2.5%, P 60 years compared with age Conclusions Our findings support the need for continuing assessment of mitigation strategies in shelters, increasing access to individual rooms and linkage to housing options for PEH, and supporting people to remain in encampments when these options are not available.

ObjectiveThe aim of this report is to investigate the nature of the relationship between depression and condomless sex (CLS) among gay, bisexual and other men who have sex with men (GBMSM).MethodsData are from the Antiretrovirals, Sexual Transmission Risk and Attitude (ASTRA) study of people living with HIV and attending one of eight HIV outpatient clinics in England (2011–2012) and the Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) study of HIV-negative/unknown status individuals attending one of 20 genitourinary medicine clinics in England (2013–2014). This analysis included GBMSM only. For each study, the prevalence of depressive symptoms (Patient Health Questionnaire-9 score ≥10) was presented according to three categories of sex in the past 3 months (considering anal/vaginal sex with men/women and anal sex with men in separate definitions): (1) no sex, (2) condom-protected sex only and (3) CLS. Multinomial logistic regression with ‘condom-protected sex only’ as the reference group was used to adjust for age and (for ASTRA participants) time since HIV diagnosis.ResultsThere were opposing associations of depression with recent sexual behaviour: the prevalence of depression was higher among those who reported no sex and those who reported CLS, compared with those who reported condom-protected sex only. Among the 2170 HIV-positive GBMSM in ASTRA, considering anal/vaginal sex with men/women, the prevalence of depressive symptoms was 32%, 20% and 28%, respectively, among men reporting no sex (n=783), condom-protected sex only (n=551) and CLS (n=836) (global pConclusionsDepression may be linked both to lack of sexual activity and to sexual risk taking. When investigating associations between depression and CLS, it is important to separate out individuals reporting condom-protected sex only from those reporting no sex.

Background: Antiretroviral treatment (ART) reduces HIV infectiousness but the effect of early ART on sexual behaviour is unclear. Methods: We assessed, within the START randomized trial that enrolled HIV-positive adults with CD4+ cell count greater than 500 cells/μl, the effect of early (immediate) versus deferred ART on: condomless sex with HIV-serodifferent partners (CLS-D); all condomless sex (CLS); HIV transmission-risk sex (CLS-D-HIV risk, defined as CLS-D and: not on ART or started ART

Background The COVID-19 pandemic has disproportionately affected people experiencing homelessness (PEH) residing in shelters. Initial and regular testing of PEH in communities with moderate or substantial SARS-CoV-2 transmission may limit spread in shelters. We analyzed factors associated with positive SARS-CoV-2 RNA and antibody tests for PEH staying in shelters or encampments in Denver, Colorado. Methods In May 2020, Denver Public Health collaborated with local leaders to identify 4 homeless shelters and 3 outdoor encampments for voluntary, universal SARS-CoV-2 testing. At each testing event, a short questionnaire including sociodemographic factors and symptoms was administered to PEH who consented to testing. SARS-CoV-2 RNA testing by reverse transcription polymerase chain reaction (RT-PCR) was performed on nasopharyngeal swabs; antibody testing was performed on venous blood samples. PEH reporting a prior positive RT-PCR test were not retested but were eligible for antibody testing. Statistical calculations were performed with an α of 0.05; all tests were two-sided. Results From June 2–July 28, 2020, 931 PEH were approached. A total of 863 RT-PCR tests were performed at 14 testing events, and 334 antibody tests were performed at 5 testing events. Overall, 604 and 259 RT-PCR tests were conducted in 4 shelters and 3 encampments, respectively; 189 and 145 antibody tests were conducted in 3 shelters and 2 encampments, respectively. PEH tested in shelters were older, more often men, less often Native American, and less likely to report COVID-19 symptoms than those tested at encampments (Table 1). Overall, 9% of PEH tested in shelters tested positive for SARS-CoV-2 compared to 3% of PEH tested in encampments (p=0.002); 8% of men had positive RT-PCR results compared to 2% of women (p=0.03) (Table 2). PEH tested at shelters had a higher percentage of detectable SARS-CoV-2 antibodies than those tested in encampments (24% vs 8%, p=0.0002; Table 3). Neither RT-PCR nor antibody test results differed significantly by race or ethnicity. Table 1. Demographics of participants residing in encampments compared with shelters in Denver, Colorado, May-July 2020 (n=931) Table 2. Comparison of participants testing positive or negative for SARS-CoV-2 RT-PCR* by location and demographics, in Denver, Colorado, May-July 2020 Table 3. Comparison of participants testing positive or negative for antibodies against SARS-CoV-2 by location and demographics in Denver, Colorado, May-July 2020 Conclusion A greater percentage of PEH tested positive for both SARS-CoV-2 RNA and antibodies at shelters than encampments, suggesting that continued assessment of mitigation strategies in shelters should be a priority. Disclosures All Authors: No reported disclosures

We assessed attitudes to disclosure to new sexual partners and association with sexual behaviours among HIV-diagnosed gay, bisexual, and other men who have sex with men (GBMSM) in the UK Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) study in 2011-12. Among 1373 GBMSM diagnosed with HIV for ≥3 months and reporting sex in the past three months (84% on antiretroviral therapy (ART), 75% viral load (VL) ≤50c/mL), 56.3% reported higher sexual disclosure ("agree" or "tend to agree" with "I'd expect to tell a new partner I'm HIV-positive before we have sex"). GBMSM on ART with self-reported undetectable VL had lower disclosure than those on ART without self-reported undetectable VL and those not on ART. Higher sexual disclosure was associated with higher prevalence of CLS in the past three months; this was due to its association with CLS with other HIV-positive partners. Higher sexual disclosure was more common among GBMSM who had CLS with other HIV-positive partners only (72.1%) compared to those who had higher-risk CLS with HIV-serodifferent partners (55.6%), other CLS with HIV-serodifferent partners (45.9%), or condom-protected sex only (47.6%). Findings suggest mutual HIV-disclosure and HIV-serosorting were occurring in this population. Knowledge of VL status may have impacted on disclosure to sexual partners.

OBJECTIVE: HIV transmission is ongoing among men who have sex with men (MSM) in the UK. Sex without a condom (condomless sex, CLS) is the main risk factor. We investigated the prevalence of and factors associated with types of CLS. METHODS: Cross-sectional questionnaire study in UK HIV clinics in 2011/2012 (ASTRA). MSM diagnosed with HIV for ≥3 months reported on anal and vaginal sex, CLS with HIV-serodifferent partners (CLS-D) and CLS with HIV-seroconcordant (CLS-C) partners in the previous 3 months. Mutually exclusive sexual behaviours were as follows: (1) Higher HIV risk CLS-D (not on antiretroviral therapy (ART) or clinic-recorded viral load(VL) >50 c/mL), (2) Other CLS-D, (3) CLS-C without CLS-D, (4) Condom-protected sex only and (5) No anal or vaginal sex. Associations were examined of sociodemographic, HIV-related, lifestyle, and other sexual measures with the five categories of sexual behaviour. We examined the prevalence of higher HIV risk CLS-D incorporating (in addition to ART and VL) time on ART, ART non-adherence, and recent sexually transmitted infections (STIs). RESULTS: Among 2189 HIV-diagnosed MSM (87% on ART), prevalence of any CLS in the past 3 months was 38.2% (95% CI 36.2% to 40.4%) and that of any CLS-D was 16.3% (14.8%–17.9%). The five-category classification was as follows: (1) Higher HIV risk CLS-D: 4.2% (3.5% to 5.2%), (2) Other CLS-D: 12.1% (10.8% to 13.5%), (3) CLS-C without CLS-D: 21.9% (20.2% to 23.7%), (4) Condom-protected sex only: 25.4% (23.6% to 27.3%) and (5) No anal or vaginal sex: 36.4% (34.3% to 38.4%). Compared with men who reported condom-protected sex only, MSM who reported any CLS in the past 3 months had higher prevalence of STIs, chemsex-associated drug use, group sex, higher partner numbers, and lifetime hepatitis C. Prevalence of higher HIV risk CLS-D ranged from 4.2% to 7.5% according to criteria included. CONCLUSION: CLS was prevalent among HIV-diagnosed MSM, but CLS-D with higher HIV transmission risk was overall low. CLS-D is no longer the most appropriate measure of HIV transmission risk behaviour among people with diagnosed HIV; accounting for VL is important.

OBJECTIVEFor most common infections requiring hospitalization, antibiotic treatment is completed after hospital discharge. Postdischarge therapy is often unnecessarily broad spectrum and prolonged. We developed an intervention to improve antibiotic selection and shorten treatment durations.DESIGNSingle center, quasi-experimental retrospective cohort studyMETHODSPatients prescribed oral antibiotics at hospital discharge before (July 2012–June 2013) and after (October 2014–February 2015) an intervention consisting of (1) institutional guidance for oral step-down antibiotic selection and duration of therapy and (2) pharmacy audit of discharge prescriptions with real-time prescribing recommendations to providers. The primary outcomes measured were total prescribed duration of therapy and use of antibiotics with broad gram-negative activity (ie, fluoroquinolones or amoxicillin-clavulanate).RESULTSOverall, 300 cases from the preintervention period and 200 cases from the intervention period were included. Compared with the preintervention period, the use of antibiotics with broad gram-negative activity decreased during the intervention (51% vs 40%; P=.02), particularly fluoroquinolones (38% vs 25%; P=.002). The total duration of therapy decreased from a median of 10 days (interquartile range [IQR], 7–13 days) to 9 days (IQR, 6–13 days) but did not reach statistical significance (P=.13). However, the duration prescribed at discharge declined from 6 days (IQR, 4–10 days) to 5 days (IQR, 3–7 days) (P=.003). During the intervention, there was a nonsignificant increase in the overall appropriateness of discharge prescriptions from 52% to 66% (P=.15).CONCLUSIONSA multifaceted intervention to optimize antibiotic prescribing at hospital discharge was associated with less frequent use of antibiotics with broad gram-negative activity and shorter postdischarge treatment durations.Infect Control Hosp Epidemiol 2017;38:534–541

OBJECTIVESTo evaluate changes in outpatient fluoroquinolone (FQ) and nitrofurantoin (NFT) use and resistance among E. coli isolates after a change in institutional guidance to use NFT over FQs for acute uncomplicated cystitis.DESIGNRetrospective preintervention–postintervention study.SETTINGUrban, integrated healthcare system.PATIENTSAdult outpatients treated for acute cystitis.METHODSWe compared 2 time periods: January 2003–June 2007 when FQs were recommended as first-line therapy, and July 2007–December 2012, when NFT was recommended. The main outcomes were changes in FQ and NFT use and FQ- and NFT-resistant E. coli by time-series analysis.RESULTSOverall, 5,714 adults treated for acute cystitis and 11,367 outpatient E. coli isolates were included in the analysis. After the change in prescribing guidance, there was an immediate 26% (95% CI, 20%–32%) decrease in FQ use (PP=.12); these changes were sustained over the postintervention period. Oral cephalosporin use also increased during the postintervention period. There was a significant decrease in FQ-resistant E. coli of −0.4% per quarter (95% CI, −0.6% to −0.1%; P=.004) between the pre- and postintervention periods; however, a change in the trend of NFT-resistant E. coli was not observed.CONCLUSIONSIn an integrated healthcare system, a change in institutional guidance for acute uncomplicated cystitis was associated with a reduction in FQ use, which may have contributed to a stabilization in FQ-resistant E. coli. Increased nitrofurantoin use was not associated with a change in NFT resistance.Infect Control Hosp Epidemiol 2017;38:461–468

Introduction Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen. Methods/Design S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients. Both of the four-month regimens contain high-dose rifapentine instead of rifampin, with ethambutol replaced by moxifloxacin in one regimen. All drugs are administered seven days per week, and under direct observation at least five days per week. The primary outcome is tuberculosis disease-free survival at twelve months after study treatment assignment. A total of 2500 participants will be randomized; this gives 90% power to show non-inferiority with a 6.6% margin of non-inferiority. Discussion This phase 3 trial formally tests the hypothesis that augmentation of rifamycin exposures can shorten tuberculosis treatment to four months. Trial design and standardized implementation optimize the likelihood of obtaining valid results. Results of this trial may have important implications for clinical management of tuberculosis at both individual and programmatic levels. Trial registration: NCT02410772 . Registered 8 April 2015, https://www.clinicaltrials.gov/ct2/show/NCT02410772?term=02410772&rank=1

In a pilot study of 22 patients with an acute bacterial skin infection, serum levels of C-reactive protein and procalcitonin tended to be elevated at presentation and declined within 3–5 days of treatment. Further study of a biomarker-guided treatment strategy to reduce antibiotic overuse in skin infections is warranted.

OBJECTIVETo evaluate the long-term outcomes of an antimicrobial stewardship program (ASP) implemented in a hospital with low baseline antibiotic use.DESIGNQuasi-experimental, interrupted time-series study.SETTINGPublic safety net hospital with 525 beds.INTERVENTIONImplementation of a formal ASP in July 2008.METHODSWe conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008–September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005–June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1,000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset Clostridium difficile infection, and other patient-centered measures.RESULTSDuring the preintervention period, total antibacterial and antipseudomonal use were declining (−9.2 and −5.5 DOT/1,000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (−3.7 and −2.2 DOT/1,000 PD, respectively), resulting in a slope change of 5.5 DOT/1,000 PD per quarter for total antibacterial use (P=.10) and 3.3 DOT/1,000 PD per quarter for antipseudomonal use (P=.01). Antibiotic expenditures declined markedly during the stewardship period (−$295.42/1,000 PD per quarter, P=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes.CONCLUSIONIn a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures. Common ASP outcome measures have limitations.Infect Control Hosp Epidemiol 2015;00(0): 1–9

Objectives With HIV treatment prolonging survival and HIV infection now managed as a chronic illness, quality of life (QOL) is important to evaluate in persons living with HIV (PLWH). We assessed at study entry the QOL of antiretroviral-naive PLWH with CD4 counts > 500 cells/μL in the Strategic Timing of AntiRetroviral Treatment (START) clinical trial. Methods QOL was assessed with: (1) a visual analogue scale (VAS) for self-assessment of overall current health; (2) the Short-Form 12-Item Version 2 Health Survey® (SF-12V2), for which responses are summarized into eight individual QOL domains plus component summary scores for physical health [the Physical Health Component Summary (PCS)] and mental health [the Mental Health Component Summary (MCS)]. The VAS and eight domain scores were scaled from 0 to 100. Mean QOL measures were calculated overall and by demographic, clinical and behavioural factors. Results A total of 4631 participants completed the VAS and 4119 the SF-12. The mean VAS score (with standard deviation) was 80.9 ± 15.7. Mean SF-12 domain scores were lowest for vitality (66.3 ± 26.4) and mental health (68.6 ± 21.4), and highest for physical functioning (89.3 ± 23.0) and bodily pain (88.0 ± 21.4). Using multiple linear regression, PCS scores were lower (P

BACKGROUND: Recreational drug use in men who have sex with men (MSM) is of concern because it might be linked to the transmission of HIV and other sexually transmitted infections. Evidence about drug use in HIV-diagnosed MSM in the UK is limited by representativeness of the study populations. We describe patterns of drug use and associations with sexual behaviours in HIV-diagnosed MSM in the UK. METHODS: We used data from the cross-sectional ASTRA study, which recruited participants aged 18 years or older with HIV from eight HIV outpatient clinics in the UK between Feb 1, 2011, and Dec 31, 2012. We examined data for MSM, assessing the prevalence of recreational drug use and polydrug use in the previous 3 months and associations with sociodemographic and HIV-related factors. We examined the association of polydrug use with measures of condomless sex in the previous 3 months and with other sexual behaviours. FINDINGS: Our analysis included data for 2248 MSM: 2136 (95%) were gay, 1973 (89%) were white, 1904 (85%) were on antiretroviral treatment (ART), and 1682 (76%) had a viral load of 50 copies per mL or lower. 1138 (51%) used recreational drugs in the previous 3 months; 608 (27%) used nitrites, 477 (21%) used cannabis, 460 (21%) used erectile dysfunction drugs, 453 (20%) used cocaine, 280 (13%) used ketamine, 258 (12%) used 3,4-methylenedioxy-N-methylamphetamine (MDMA), 221 (10%) used gamma-hydroxybutyrate or gamma-butyrolactone, 175 (8%) used methamphetamine, and 162 (7%) used mephedrone. In the 1138 individuals who used drugs, 529 (47%) used three or more drugs and 241 (21%) used five or more. Prevalence of injection drug use was 3% (n = 68). Drug use was independently associated with younger age (p < 0·0001), not being religious (p = 0·001), having an HIV-positive stable partner (p = 0·0008), HIV-serostatus disclosure (p = 0·009), smoking (p < 0·0001), evidence of harmful alcohol drinking (p = 0·0001), and ART non-adherence (p < 0·0001). Increasing polydrug use was associated with increasing prevalence of condomless sex (prevalence range from no drug use to use of five or more drugs was 24% to 78%), condomless sex with HIV-seroconcordant partners (17% to 69%), condomless sex with HIV-serodiscordant partners (10% to 25%), and higher-HIV-risk condomless sex after taking viral load into account (4% to 16%; p ≤ 0·005 for all). Associations were similar after adjustment for sociodemographic and HIV-related factors. Methamphetamine was more strongly associated with higher-HIV-risk condomless sex than were other commonly used drugs. INTERPRETATION: Polydrug use is prevalent in HIV-diagnosed MSM and is strongly associated with condomless sex. Specialist support services for MSM with HIV who use recreational drugs might be beneficial in the reduction of harm and prevention of ongoing transmission of HIV and other sexually transmitted infections. FUNDING: National Institute for Health Research.

Objective.Hospitalizations for acute bacterial skin and skin structure infection (ABSSSI) are common. Optimizing antibiotic use for ABSSSIs requires an understanding of current management. The objective of this study was to evaluate antibiotic prescribing practices and factors affecting prescribing in a diverse group of hospitalsDesign.Multicenter, retrospective cohort study.Setting.Seven community and academic hospitals.Methods.Children and adults hospitalized between June 2010 and May 2012 for cellulitis, wound infection, or cutaneous abscess were eligible. The primary endpoint was a composite of 2 prescribing practices representing potentially avoidable antibiotic exposure: (1) use of antibiotics with a broad spectrum of activity against gram-negative bacteria or (2) treatment duration greater than 10 days.Results.A total of 533 cases were included: 320 with nonpurulent cellulitis, 44 with wound infection or purulent cellulitis, and 169 with abscess. Of 492 cases with complete prescribing data, the primary endpoint occurred in 394 (80%) cases and varied significantly across hospitals (64%–97%;P< .001). By logistic regression, independent predictors of the primary endpoint included wound infection or purulent cellulitis (odds ratio [OR], 5.12 [95% confidence interval (CI)], 1.46–17.88), head or neck involvement (OR, 2.83 [95% CI, 1.17–6.82]), adult cases (OR, 2.20 [95% CI, 1.18–4.11]), and admission to a community hospital (OR, 1.90 [95% CI, 1.05–3.44]).Conclusions.Among patients hospitalized for ABSSSI, use of antibiotics with broad gram-negative activity or treatment courses longer than 10 days were common. There may be substantial opportunity to reduce antibiotic exposure through shorter courses of therapy targeting gram-positive bacteria.Infect Control Hosp Epidemiol2014;35(10):1241–1250

BACKGROUND Among diabetics, complicated skin infections may involve gram-negative pathogens; however, the microbiology of cellulitis and cutaneous abscess is not well established. OBJECTIVE To compare the microbiology and prescribing patterns between diabetics and nondiabetics hospitalized for cellulitis or abscess. DESIGN Secondary analysis of 2 published retrospective cohorts. SETTING/PATIENTS Adults hospitalized for cellulitis or abscess, excluding infected ulcers or deep tissue infections, at 7 academic and community facilities. METHODS Microbiological findings and antibiotic use were compared among diabetics and nondiabetics. Multivariable logistic regression was performed to identify factors associated with exposure to broad gram-negative therapy, defined as receipt of at least 2 calendar days of β-lactamase inhibitors, second- to fifth-generation cephalosporins, fluoroquinolones, carbapenems, tigecycline, aminoglycosides, or colistin. RESULTS Of 770 total patients with cellulitis or abscess, 167 (22%) had diabetes mellitus. Among the 38% of cases with a positive culture, an aerobic gram-positive organism was isolated in 90% of diabetics and 92% of nondiabetics (P = 0.59); aerobic gram-negative organisms were isolated in 7% and 12%, respectively (P = 0.28). Overall, diabetics were more likely than nondiabetics to be exposed to broad gram-negative therapy (54% vs 44% of cases, P = 0.02). By logistic regression, diabetes mellitus was independently associated with exposure to broad gram-negative therapy (odds ratio: 1.66, 95% confidence interval: 1.15-2.40). CONCLUSION In cases of cellulitis or abscess associated with a positive culture, gram-negative pathogens were not more common among diabetics compared with nondiabetics. However, diabetics were overall more likely to be exposed to broad gram-negative therapy suggesting this prescribing practice may not be not warranted. Journal of Hospital Medicine 2014;9:788–794. © 2014 Society of Hospital Medicine

Background In a phase 3, randomized clinical trial (PREVENT TB) of 8053 people with latent tuberculosis infection, 12 once-weekly doses of rifapentine and isoniazid had good efficacy and tolerability. Children received higher rifapentine milligram per kilogram doses than adults. In the present pharmacokinetic study (a component of the PREVENT TB trial), rifapentine exposure was compared between children and adults. Methods Rifapentine doses in children ranged from 300 to 900 mg, and adults received 900 mg. Children who could not swallow tablets received crushed tablets. Sparse pharmacokinetic sampling was performed with 1 rifapentine concentration at 24 hours after drug administration (C24). Rifapentine area under concentration-time curve (AUC) was estimated from a nonlinear, mixed effects regression model (NLME). Results There were 80 children (age: median, 4.5 years; range, 2-11 years) and 77 adults (age: median, 40 years; all ≥18 years) in the study. The geometric mean rifapentine milligram per kilogram dose was greater in children than in adults (children, 23 mg/kg; adults, 11 mg/kg). Rifapentine geometric mean AUC and C24 were 1.3-fold greater in children (all children combined) than in adults. Children who swallowed whole tablets had 1.3-fold higher geometric mean AUC than children who received crushed tablets, and children who swallowed whole tablets had a 1.6-fold higher geometric mean AUC than adults. The higher rifapentine doses in children were well tolerated. To obtain rifapentine exposures comparable in children to adults, dosing algorithms modeled by NLME were developed. Conclusions A 2-fold greater rifapentine dose for all children resulted in a 1.3-fold higher AUC compared to adults administered a standard dose. Use of higher weight-adjusted rifapentine doses for young children are warranted to achieve systemic exposures that are associated with successful treatment of latent tuberculosis infection in adults.

Background Contemporary antiretroviral-therapy (ART) regimens have simple dosing, low toxicity, minimal side-effects, and few drug interactions. We evaluated ART regimens in an urban, safety-net, adult HIV clinic in the United States to determine proportions of patients on contemporary ART and identify opportunities to optimize ART for patients on older regimens. Methods Data including current ART regimen, HIV-1 RNA level, and age were extracted from the electronic medical record (EMR) for all patients seen in the prior 13 months. Viral suppression was defined as HIV-1 RNA < 200 copies/mL. A patient was “off-ART” if there were no fills within 270 days or ART had a stop date >90 days prior to end of the study. Unclear regimens from the EMR (n = 179) were chart reviewed. ART regimens were assigned the following designations: contemporary first-line, contemporary non-first-line, older three-drug, two-drug, salvage, or off-ART. ART was also categorized as boosted (containing cobicistat/ritonavir) vs. unboosted, by single-tablet regimen (STR) vs. multi-tablet regimen (MTR), and frequency of dosing. Correlations between ART regimen, viral suppression, and age were analyzed. Results The ART review included 1,215 individuals. Most patients (64%) were on contemporary first-line regimens; 20% were on contemporary non-first-line regimens (figure). Patients on salvage regimens had lower rates of viral suppression than those in other ART categories (80% vs. 90%, P

The lack of consistent associations between clinical outcomes and microbiological responses to therapy for some infectious diseases has raised questions about the adequacy of microbiological endpoints for tuberculosis treatment trials.To evaluate the association between symptoms and microbiological response to tuberculosis treatment.We performed a retrospective analysis of four clinical trials in which participants had culture-positive tuberculosis, standardized symptom assessment, and follow-up mycobacterial cultures. Two trials (studies 22 and 23) followed participants to identify recurrent tuberculosis; participants in studies 27 and 28 were only followed to treatment completion.This analysis included 1,978 participants; 39 (2.0%) had culture-confirmed treatment failure, and 75 (3.9%) had culture-confirmed recurrence. Productive cough was associated with indices of increased mycobacterial burden at diagnosis (acid-fast smear grade, severity of radiographic abnormalities). Fever and sweats improved rapidly with treatment, whereas productive cough decreased more slowly and was present in 20% of visits after treatment completion. During treatment, study participants with productive cough more often had concurrent culture positivity compared with those without productive cough (studies 22 and 23: adjusted odds ratio, 1.80; 95% confidence interval [CI], 1.33-2.44). Finally, symptoms during the latter part of treatment and follow-up were associated with culture-confirmed treatment failure and recurrence in studies 22 and 23 (for cough: adjusted hazard ratio, 2.07; 95% CI, 1.23-3.49; for fever: adjusted hazard ratio, 5.05; 95% CI, 2.76-9.19).There are consistent relationships between symptoms and microbiological indices of tuberculosis, including measures of mycobacterial burden at baseline, culture positivity during treatment, and time to culture-confirmed treatment failure and recurrence.

A syndrome-specific intervention to improve the management of community-acquired pneumonia in non-intensive care settings was associated with shorter treatment durations, less fluoroquinolone use, and a reduction in use of low-yield diagnostic tests., Background. Syndrome-specific interventions are a recommended approach to antibiotic stewardship, but additional data are needed to understand their potential impact. We implemented an intervention to improve the management of inpatient community-acquired pneumonia (CAP) and evaluated its effects on antibiotic and resource utilization. Methods. A stakeholder group developed and implemented a clinical practice guideline and order set for inpatient, non-intensive care unit CAP recommending a short course (5 days) of a fluoroquinolone-sparing antibiotic regimen in uncomplicated cases. Unless there was suspicion for complications or resistant pathogens, chest computed tomography (CT) and sputum cultures were discouraged. This was a retrospective preintervention postintervention study of patients hospitalized for CAP before (April 15, 2008–May 31, 2009) and after (July 1, 2011–July 31, 2012) implementation of the guideline. The primary comparison was the difference in duration of therapy during the baseline and intervention periods. Secondary outcomes included changes in use of levofloxacin, CT scans, and sputum culture. Results. One hundred sixty-six and 84 cases during the baseline and intervention periods, respectively, were included. From the baseline to intervention period, the median duration of therapy decreased from 10 to 7 days (P < .0001). Prescription of levofloxacin at discharge decreased from 60% to 27% of cases (P < .0001). Use of chest CT and sputum culture decreased from 47% to 32% of cases (P = .02) and 51% to 31% of cases (P = .03), respectively. The frequency of clinical failure between the 2 periods was similar. Conclusions. A syndrome-specific intervention for inpatient CAP was associated with shorter treatment durations and reductions in use of fluoroquinolones and low-yield diagnostic tests.

Background Infectious Diseases Society of America guidelines recommend that patients hospitalized for acute bacterial skin infections after failure of outpatient antibiotic therapy be managed as "severe" infections; however, the clinical relevance of apparent failure of outpatient therapy is not clear. Methods This was a secondary analysis of a multicenter, retrospective cohort of adults and children hospitalized for cellulitis, abscess, or wound infection. We compared clinical features, laboratory and microbiology findings, antibiotic treatment, and outcomes among patients who received outpatient antibiotics prior to admission and those who did not. Results Of 533 patients, 179 (34%) received outpatient antibiotics prior to admission. Compared with those who did not, patients who received antibiotics prior to admission less frequently had fever (18% vs 26%, P =.04) and leukocytosis (33% vs 51%, P Staphylococcus aureus was more common among those who received antibiotics prior to admission (75% vs 58%, P =.02), particularly methicillin-resistant S aureus (41% vs 27%, P =.049), whereas aerobic gram-negative bacilli were less common (3% vs 13%, P =.03). After hospitalization, clinical failure occurred with similar frequency between the 2 groups (12% vs 11%, P =.73). Conclusions Patients hospitalized with skin infections after apparently failing outpatient therapy had clinical features suggestive of less severe infection and similar outcomes compared with patients who did not receive antibiotics prior to admission. Our results suggest that inpatient treatment for patients not responding to outpatient therapy should focus on methicillin-resistant S aureus , not gram-negative pathogens.

Community-acquired pneumonia (CAP) is the most common infection leading to hospitalization in the USA. The objective of this study was to evaluate management practices for inpatient CAP in relation to Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines to identify opportunities for antibiotic and health care resource stewardship.This was a retrospective cohort study of adults hospitalized for CAP at a single institution from 15 April 2008 to 31 May 2009.Of the 209 patients with CAP who presented to Denver Health Medical Center during the study period and were hospitalized, 166 (79 %) and 43 (21 %) were admitted to a medical ward and the intensive care unit (ICU), respectively. Sixty-one (29 %) patients were candidates for outpatient therapy per IDSA/ATS guidance with a CURB-65 score of 0 or 1 and absence of hypoxemia. Sputum cultures were ordered for 110 specimens; however, an evaluable sample was obtained in only 49 (45 %) cases. Median time from antibiotic initiation to specimen collection was 11 [interquartile range (IQR) 6-19] h, and a potential pathogen was identified in only 18 (16 %) cultures. Blood cultures were routinely obtained for both non-ICU (81 %) and ICU (95 %) cases, but 15 of 36 (42 %) positive cultures were false-positive results. The most common antibiotic regimen was ceftriaxone + azithromycin (182, 87 % cases). Discordant with IDSA/ATS recommendations, oral step-down therapy consisted of a new antibiotic class in 120 (66 %), most commonly levofloxacin (101, 55 %). Treatment durations were typically longer than suggested with a median of 10 (IQR 8-12) days.In this cohort of patients hospitalized for CAP, management was frequently inconsistent with IDSA/ATS guideline recommendations, revealing potential targets to reduce unnecessary antibiotic and healthcare resource utilization.

ACADEMIC EMERGENCY MEDICINE 2012; 19:703–706 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: Due to antimicrobial resistance in Streptococcus pneumoniae, national guidelines recommend a respiratory fluoroquinolone or combination antimicrobial therapy for outpatient treatment of community-acquired pneumonia (CAP) associated with risk factors for drug-resistant S. pneumoniae (DRSP). The objectives of this study were to assess the prevalence of these risk factors and antibiotic prescribing practices in cases of outpatient CAP treated in the acute care setting. Methods: This was a retrospective cohort study of adult outpatients treated for CAP in the emergency department (ED) or urgent care center of an urban, academic medical center from May 1, 2009, through October 31, 2009, and comparison of antibiotic therapy in cases with and without DRSP risk factors. Results: Of 175 patients, 90 (51%) had at least one DRSP risk factor, most commonly asthma (n = 28, 16%), alcohol abuse (n = 24, 14%), diabetes mellitus (n = 18, 10%), chronic obstructive pulmonary disease (n = 16, 9%), age > 65 years (n = 16, 9%), and use of antibiotics within 3 months (15, 9%). Antibiotic prescriptions were similar among cases with and without DRSP risk factors: a macrolide (62% vs. 59%, respectively, p = 0.65), doxycycline (27% vs. 28%, p = 0.82), or a respiratory fluoroquinolone (9% vs. 9%, p = 0.90). Concordance with national guideline treatment recommendations was significantly lower in cases with DRSP risk factors (9% vs. 87%, p

Background Although complicated skin and soft-tissue infections (SSTIs) are among the most common infections requiring hospitalization, their clinical spectrum, management, and outcomes have not been well described. Methods We report a cohort of consecutive adult patients hospitalized for SSTI from 1 January through 31 December 2007 at an academic medical center. Cases meeting inclusion criteria were reviewed and classified as cellulitis, cutaneous abscess, or SSTI with additional complicating factors. Results In total, 322 patients were included; 66 (20%) had cellulitis, 103 (32%) had cutaneous abscess, and 153 (48%) had SSTI with additional complicating factors. Injection drug use, diabetes mellitus, and alcohol abuse were common comorbidities. Serum inflammatory markers were routinely measured and blood cultures and imaging studies were routinely performed in each group. Of 150 patients with a positive culture result for an abscess, deep tissue, or blood, Staphylococcus aureus or streptococci were identified in 145 (97%). Use of antibiotics with broad aerobic gram-negative activity (61%-80% of patients) or anaerobic activity (73%-83% of patients) was frequent in each group. The median duration of therapy for cellulitis, cutaneous abscess, and SSTI with additional complicating factors was 13 (interquartile range [IQR], 10-14), 13 (IQR, 10-16), and 14 (IQR, 11-17) days, respectively. Treatment failure, recurrence, or rehospitalization due to SSTI within 30 days occurred in 12.1%, 4.9%, and 9.2% of patients, respectively. Conclusions Hospitalizations for SSTI were common; more than half were due to cellulitis or cutaneous abscess. Frequent use of potentially unnecessary diagnostic studies, broad-spectrum antibiotic therapy, and prolonged treatment courses in these patients suggest targets for antimicrobial stewardship programs.

Rifampin has concentration-dependent activity against Mycobacterium tuberculosis . However, marked intersubject variation of rifampin concentrations occurs. In this study, we evaluated rifampin pharmacokinetics in relation to tuberculosis, geographic region, race, and single nucleotide polymorphisms of the human transporter genes SLCO1B1 , SLCO1B3 , and MDR1 . Seventy-two adults with pulmonary tuberculosis from Africa, North America, and Spain were evaluated during multidrug intensive-phase therapy, and their results were compared to those from 16 healthy controls from North America. Rifampin pharmacokinetic values were similar between tuberculosis patients and controls (geometric mean [GM] area under the concentration-time curve from 0 to 24 h [AUC 0-24 ] of 40.2 versus 40.9 μg·h/ml; P = 0.9). However, in multivariable analyses, the rifampin AUC 0-24 was significantly affected by rifampin dosage (in mg/kg of body weight), polymorphisms in the SLCO1B1 gene, and the presence of tuberculosis by geographic region. The adjusted rifampin AUC 0-24 was lowest in patients with tuberculosis from Africa compared to that in non-African patients or control subjects. The adjusted rifampin AUC 0-24 was also 36% lower among participants with SLCO1B1 genotype c.463CA than that among participants with SLCO1B1 genotype c.463CC (adjusted GM, 29.8 versus 46.7 μg·h/ml; P = 0.001). Polymorphisms in the SLCO1B1 gene associated with lower rifampin exposure were more frequent among black subjects. In conclusion, marked intersubject variation of the rifampin AUC 0-24 values was observed, but the mean values of the AUC 0-24 did not significantly vary between patients with tuberculosis and healthy controls. Lower rifampin exposure was associated with the polymorphism of the SLCO1B1 c.463C>A gene. When adjusted for the patient mg/kg dosage and transporter gene polymorphisms, rifampin exposure was lower in patients with tuberculosis, which suggests that additional absorption or metabolic processes affect rifampin exposure with tuberculosis disease.

The increase in drug-resistant tuberculosis and the global pandemic of human immunodeficiency virus infection‐related tuberculosis threaten global tuberculosis control. There are needs for improved therapy in all aspects of tuberculosis treatment: treatment of latent infection, active drug-susceptible disease, and particularly, drug-resistant disease. Fortunately, at this time of great need, the field of tuberculosis drug development has reemerged after 130 years of inactivity. I review the specific needs for new treatment regimens, the pathways of tuberculosis drug development, and the agents that are currently in clinical development. There is renewed interest in the rifamycin class; studies in the mouse model suggest that higher doses of rifampin or rifapentine may markedly improve the treatment of drug-susceptible disease. Fluoroquinolones may allow shorter treatment durations for drug-susceptible disease, though initial phase 2B trials have shown inconsistent activity. Novel drugs, such as TMC207, OPC-67683, PA824, SQ109, and PNU-100480, may improve the treatment of drug-resistant and drug-susceptible tuberculosis.

Risk for relapse was higher among persons of Asian–Pacific Islander descent., The role of microbial factors in outcomes of tuberculosis treatment has not been well studied. We performed a case–control study to evaluate the association between a Beijing strain and tuberculosis treatment outcomes. Isolates from patients with culture-positive treatment failure (n = 8) or relapse (n = 54) were compared with isolates from randomly selected controls (n = 296) by using spoligotyping. Patients with Beijing strains had a higher risk for relapse (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.0–4.0, p = 0.04) but not for treatment failure. Adjustment for factors previously associated with relapse had little effect on the association between Beijing strains and relapse. Beijing strains were strongly associated with relapse among Asian–Pacific Islanders (OR 11, 95% CI 1.1–108, p = 0.04). Active disease caused by a Beijing strain was associated with increased risk for relapse, particularly among Asian–Pacific Islanders.

Not the final published version, OBJECTIVE: To compare the HIV transmission risk among patients randomized to episodic versus continuous antiretroviral therapy. DESIGN: This was a substudy of the Strategies of Management of Antiretroviral Therapy study, in which patients were randomized to continuous versus CD4-guided episodic antiretroviral therapy. Participants were surveyed about sexual activity and needle sharing and had laboratory testing for gonorrhea, chlamydia, and syphilis. RESULTS: A total of 883 patients were enrolled in this study, the mean age of the patients was 45 years, 25% were women, and 78% were on antiretroviral therapy. At baseline, 136 participants (15.4%) had high-risk behavior (vaginal or anal sex without a condom, needle sharing, or incident bacterial sexually transmitted infection). After randomization, the proportion of participants reporting high-risk behavior was stable and did not differ by randomized arm (P = 0.39). Among participants off therapy at baseline, high-risk behavior was less common 4 months after randomization among those who were randomized to start antiretroviral therapy (P = 0.03). HIV transmission risk (high-risk behavior while HIV RNA level >1500 copies/mL) with partners perceived to be HIV uninfected was higher in the episodic therapy arm (P = 0.02). CONCLUSIONS: Patients on episodic antiretroviral therapy did not decrease high-risk behavior, and because HIV RNA levels were higher, this strategy may result in increased HIV transmission.

Because of high rates of trimethoprim-sulfamethoxazole resistance in Escherichia coli, Denver Health switched to levofloxacin as the initial therapy for urinary tract infections (UTIs) in 1999. We evaluated the effects of that switch 6 years later.Levofloxacin prescriptions per 1000 outpatient visits and levofloxacin resistance in outpatient E. coli were evaluated over time. E. coli isolated in 2005 were further characterized by specimen source and antimicrobial susceptibilities. Risk factors for levofloxacin-resistant E. coli UTI among nonpregnant adult outpatients were evaluated in a case-control study.Between 1998 and 2005, levofloxacin use increased from 3.1 to 12.7 prescriptions per 1000 visits (P.01) and resistance in outpatients increased from 1% to 9% (P.01). Although prescriptions for sulfonamide antibiotics decreased by half during the same period, E. coli resistance to trimethoprim-sulfamethoxazole increased from 26.1% to 29.6%. Levofloxacin-resistant E. coli were more likely resistant to other antibiotics than levofloxacin-susceptible isolates (90% vs 43%, P.0001). Risk factors for levofloxacin-resistant E. coli UTI were hospitalization (odds ratio for each week of hospitalization, 2.0; 95% confidence interval, 1.0-3.9) and use of levofloxacin (odds ratio, 5.6; 95% confidence interval, 2.1-27.5) within the previous year.Fluoroquinolone prescriptions increased markedly after an institutional policy change for empiric treatment of UTI, and a rapid increase in fluoroquinolone resistance among outpatient E. coli followed. Risk factors for infection with resistant E. coli were recent hospitalization and levofloxacin use. Risk factors should be considered before initiating empiric treatment with a fluoroquinolone.

Tuberculosis (TB) is one of the most common opportunistic infections among persons with HIV infection. However, there are uncertainties about both TB and HIV treatment regimens among patients with advanced immunodeficiency. On the TB treatment side, there are lingering concerns about whether patients with advanced immunodeficiency should have a more intensive regimen for TB treatment (longer duration, more frequent [daily] dosing and/or post-treatment isoniazid). The use of antiretroviral therapy among patients with TB and AIDS dramatically decreases the risk of death and other opportunistic infections. However, use of antiretroviral therapy during TB treatment is complicated by the need to coordinate the activities of the TB control program and the HIV care clinic, overlapping side-effect profiles of anti-TB and antiretroviral drugs, drug–drug interactions between the rifamycins and many antiretroviral drugs, and the occurrence of immune reconstitution inflammatory syndrome events. The combination of rifampin-based TB treatment and efavirenz-based antiretroviral therapy is clearly the best option for cotreatment of these two infections. However, there are a number of uncertainties about the optimal antiretroviral therapy if efavirenz cannot be used (because of intolerance, drug resistance, pregnancy or lack of an appropriate formulation in children). The competing risks of AIDS events and severe immune reconstitution inflammatory syndrome events raise uncertainties about the optimal timing of antiretroviral therapy during TB treatment. Despite all of these complexities, the treatment of HIV-related TB can be remarkably successful. I review these unresolved questions in the treatment of HIV-related TB and suggest studies to help resolve them.

New drugs for drug-sensitive tuberculosis (TB) could resolve many of the current challenges facing TB treatment programs. Newer fluoroquinolones have demonstrated considerable promise in murine models of TB treatment. Some, but not all, recent phase 2B clinical trials suggest that these agents could support TB treatment regimens of reduced duration. Phase 3 treatment-shortening trials based upon the addition of C8-methoxy fluoroquinolones are now underway in sub-Saharan Africa and elsewhere. Murine data have also suggested that higher-dose or higher-frequency use of currently available rifamycins (rifampin, rifapentine) could support treatment-shortening regimens. Phase 2B trials of high-dose rifampin regimens and of higher-dose/higher-frequency rifapentine-based regimens will begin soon on multiple continents. Results from these phase 2B efforts will guide the development of phase 3 trials of ultra-short TB therapies.

Background. Staphylococcus aureus bacteremia causes considerable morbidity and mortality, and strategies to improve management and outcomes of this disease are needed. Methods. Routine consultation with an infectious diseases specialist for cases of S. aureus bacteremia was mandated at our institution in May 2005. We compared the evaluation, management, and outcomes of cases before and after this policy change. All comparisons are by period (i.e., before or after initiation of the policy of routine consultation). Results. In the year before and the year after after the implementation of routine consultation, 134 and 100 cases of S. aureus bacteremia, respectively, were evaluated. Consultation rates increased from 53% of cases before to 90% of cases after the policy change (P

Objective: To evaluate the effect of episodic antiretroviral therapy on quality of life (QOL). Design: This was a substudy of the Strategies of Management of Antiretroviral Therapy study, in which patients were randomized to continuous versus CD4 cell count–guided episodic antiretroviral therapy. QOL assessments included an analog scale for current health and the Short-Form 12 Item Survey, a standard abbreviated QOL instrument. Results: A total of 1225 patients had QOL assessments over a mean follow-up time of 2.4 years. Most (76%) were on antiretroviral therapy at enrollment; the median CD4 lymphocyte count was 575 (interquartile range: 455 to 784) cells/mm 3 ; and mean current health was 75 on a scale from 0 to 100, and 50% reported very good or excellent general health. Through follow-up, whenever QOL outcomes differed, the results were inferior among patients in the episodic therapy group compared with the continuous therapy group (current health, Physical Health Component Score [both P = 0.05], general health perceptions, physical functioning, and energy [all P = 0.03]). HIV disease progression (opportunistic disease or death) was more common in the episodic therapy arm and was preceded by marked declines in QOL, but excluding participants with disease progression had minimal effect on QOL comparisons. Conclusion: CD4 count–guided episodic use of antiretroviral therapy resulted in inferior QOL compared with continuous therapy.

Background: The association between antiretroviral adherence, healthcare utilization and medical costs has not been well studied. Objective: To examine the relationship of adherence to antiretroviral medications to healthcare utilization and healthcare costs. Methods: A retrospective cohort study was conducted using data from 325 previously antiretroviral medication-naive HIV-infected individuals initiating first antiretroviral therapy from 1997 through 2003. The setting was an inner-city safety net hospital and HIV clinic in the US. Adherence was assessed using pharmacy refill data. The average wholesale price was used for prescription costs. Healthcare utilization data and medical costs were obtained from the hospital billing database, and differences according to quartile of adherence were compared using analysis of variance (ANOVA). Multivariate logistic regression was used to assess predictors of higher annual medical costs. Sensitivity analyses were used to examine alternative antiretroviral pricing schemes. The perspective was that of the healthcare provider, and costs were in year 2005 values. Results: In 325 patients followed for a mean (± SD) 3.2 (1.9) years, better adherence was associated with lower healthcare utilization but higher total medical costs. Annual non-antiretroviral medical costs were $US7612 in the highest adherence quartile versus $US10190 in the lowest adherence quartile. However, antiretroviral costs were significantly higher in the highest adherence quartile ($US17513 vs $US8690), and therefore the total annual medical costs were also significantly higher in the highest versus lowest adherence quartile ($US25125 vs $US18880). In multivariate analysis, for every 10% increase in adherence, the odds of having annual medical costs in the highest versus lowest quartile increased by 87% (odds ratio 1.87; 95% CI 1.45, 2.40). In sensitivity analyses, very low antiretroviral prices (as seen in resource-limited settings) inverted this relationship - excellent adherence was cost saving. Conclusion Better adherence to antiretroviral medication was associated with decreased healthcare utilization and associated costs; however, because of the high cost of antiretroviral therapy, total medical costs were increased. Combination antiretroviral therapy is known to be cost effective; lower antiretroviral costs may make it cost saving as well.

Treatment regimens combining moxifloxacin and rifampin for drug-susceptible tuberculosis are being studied intensively. However, rifampin induces enzymes that transport and metabolize moxifloxacin. We evaluated the effect of rifampin and the human multidrug resistance gene (MDR1) C3435T polymorphisms (P-glycoprotein) on moxifloxacin pharmacokinetic parameters. This was a single-center, sequential design study with 16 volunteers in which sampling was performed after four daily oral doses of moxifloxacin (400 mg) and again after 10 days of combined rifampin (600 mg) and moxifloxacin. After daily coadministration of rifampin, the area under the concentration-time curve from 0 to 24 h (AUC 0-24 ) for moxifloxacin decreased 27%. Average bioequivalence between moxifloxacin coadministered with rifampin and moxifloxacin alone was not demonstrated: the ratio of geometric means (RGM) of the moxifloxacin AUC 0-24 was 73.3 (90% confidence intervals [CI], 64.3, 83.5) (total P value, 0.87 for two one-sided t tests). Peak moxifloxacin concentrations, however, were equivalent: the RGM of the maximum concentration of the drug in serum was 93.6 (90% CI, 80.2, 109.3) (total P value, 0.049). Concentrations of the sulfate conjugate metabolite of moxifloxacin were increased twofold following rifampin coadministration (AUC 0-24 , 1.29 versus 2.79 μg·h/ml). Concomitant rifampin administration resulted in a 27% decrease in the mean moxifloxacin AUC 0-24 and a marked increase in the AUC 0-24 of the microbiologically inactive M1 metabolite. Additional studies are required to understand the clinical significance of the moxifloxacin-rifampin interaction.

Of 300 patients prescribed oral antibiotics at the time of hospital discharge, urinary tract infection, community-acquired pneumonia, and skin infections accounted for 181 of the treatment indications (60%). Half of the prescriptions were antibiotics with broad Gram-negative activity. Discharge prescriptions were inappropriate in 79 of 150 cases reviewed (53%).Infect Control Hosp Epidemiol 2015;00(0): 1–5

Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV).We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease.A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1).Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].).

Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis (TB) to facilitate concomitant potent antiretroviral therapy, but this approach has not been evaluated in a prospective study.To evaluate the activity of intermittent rifabutin-based therapy.Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin, isoniazid, pyrazinamide, and ethambutol (given daily, thrice-weekly, or twice-weekly per the local tuberculosis control program), followed by 4 mo of twice-weekly rifabutin plus isoniazid.Culture-positive treatment failure or relapse.A total of 169 eligible patients were enrolled. Most had advanced HIV disease; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 (interquartile range, 35-175) and 5.3 log10 copies/ml (interquartile range, 4.8-5.7), respectively. Nine (5.3%) patients had culture-positive treatment failure (n = 3) or relapse (n = 6). Eight of these nine (89%) cases had isolates with acquired rifamycin resistance. Treatment failure or relapse was associated with baseline CD4 lymphocyte count, being 12.3% (9/73; 95% confidence interval, 6.5-22.0%) among patients with CD4100 cells/mm3 versus 0% (0/65; 95% confidence interval, 0.0-4.5%) among those with higher CD4 lymphocyte counts (p0.01). One hundred thirty-seven (81%) patients received antiretroviral therapy during TB treatment. Adverse events were common, but only two patients (1%) permanently discontinued study drugs.Intermittent rifabutin-based therapy for HIV-related TB was well tolerated, but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts.

We performed a retrospective cohort study of human immunodeficiency virus (HIV)-associated Mycobacterium avium complex (MAC) infection during 1997-2004 to assess for factors associated with initial macrolide resistance. Of 52 HIV-associated sterile-site MAC isolates, 9 (17%) were initially macrolide resistant. Prior MAC treatment and prolonged MAC prophylaxis with macrolides were associated with infection with a macrolide-resistant isolate; 2 (22%) of 9 patients had limited or no prior macrolide exposure. Initial MAC isolates in HIV-infected persons should routinely be tested for macrolide resistance.

BACKGROUND There is increasing interest in the possible role of new fluoroquinolone antibiotics for treatment of tuberculosis, but widespread use of fluoroquinolones for treatment of other bacterial infections may select for resistant strains of Mycobacterium tuberculosis. METHODS We evaluated fluoroquinolone susceptibility using the proportion method (critical ciprofloxacin concentration for susceptibility testing, 2.0 mu g/mL) in isolates obtained from patients enrolled in Tuberculosis Trial Consortium clinical trials during the period of 1995-2001 and in a referral sample of isolates sent to the Centers for Disease Control and Prevention (Atlanta, GA) during the period of 1996-2000 for additional testing, often because of drug resistance. RESULTS Of the 1373 isolates from the clinical trials, 1324 (96%) were susceptible to isoniazid and rifampin; 2 (0.15%) of these isolates were also resistant to ciprofloxacin. Of the 1852 isolates from the referral sample, 603 (32.6%) were resistant to isoniazid and rifampin (i.e., multidrug resistant), 849 (45.7%) were resistant to >or=1 first-line drug but were not resistant to both isoniazid and rifampin, and 400 (21.6%) were susceptible to all first-line agents. Ciprofloxacin resistance was found in 33 (1.8%) of the referral-sample isolates. Most ciprofloxacin-resistant isolates (25 [75.8%]) were resistant to isoniazid and rifampin. CONCLUSIONS Despite widespread use of fluoroquinolones for treatment of common bacterial infections, resistance among clinical isolates of M. tuberculosis in the United States and Canada remains rare, occurring primarily among multidrug-resistant strains.

We sought to evaluate the use of human immunodeficiency virus (HIV) screening during pregnancy in a health care system using the verbal opt-out method, in which HIV screening was recommended during all pregnancies and women were given an opportunity to refuse testing.This was a retrospective cohort study of pregnancies resulting in delivery from 1998 through 2001 at Denver Health Medical Center, an urban public hospital. The main outcome measure was the proportion of documented HIV screening within 9 months before the delivery date.Of 12,221 pregnancies resulting in delivery, HIV screening was completed in 12,000 (98.2%, 95% confidence interval 97.9-98.4%). Of the 221 women not screened for HIV, only 24 (10.9% of those not screened, 0.2% of all women in the study) were documented as refusing HIV testing. Patients not screened for HIV presented late in pregnancy, a median of 1 day before delivery, compared with a median of 176 days for those who were screened (P.001).A verbal opt-out system was very effective in promoting HIV screening during pregnancy. Late presentation in pregnancy was associated with not having HIV screening performed.

The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during once-weekly continuation phase therapy in 35 patients with tuberculosis. Mean area under the plasma concentration-time curve (AUC(0-infinity)) increased significantly with dose (rifapentine AUC(0- infinity): 296, 410, and 477 microg.hour/ml at 600, 900, and 1,200 mg, respectively; p = 0.02 by linear regression). In multivariate stepwise regression analyses, AUC(0-infinity) values for rifapentine and the active 25-desacetyl metabolite were associated with drug dose and plasma albumin concentration, and were lower among men and among white individuals. Fifty-four percent of patients had total (free and protein-bound) plasma concentrations of rifapentine and of desacetyl rifapentine detected for more than 36 hours after clearance of concurrently administered isoniazid. Serious adverse effects of therapy in these study patients were infrequent (1 of 35 cases; 3%) and not linked with higher rifapentine AUC(0-infinity) or peak concentration. The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis.

Objective To estimate incidence and predictors of serious or life-threatening events that are not AIDS defining, AIDS events, and death among patients treated with highly active antiretroviral therapy (HAART) in the setting of 5 large multicenter randomized treatment trials conducted in the United States. Methods Data were analyzed from 2,947 patients enrolled from December 1996 through December 2001. All patients were to receive antiretrovirals throughout follow-up. Data collection was uniform for all main outcome measures: serious or life-threatening (grade 4) events, AIDS, and death. Results During follow-up, 675 patients experienced a grade 4 event (11.4 per 100 person-years); 332 developed an AIDS event (5.6 per 100 person-years); and 272 died (4.6 per 100 person-years). The most common grade 4 events were liver related (148 patients, 2.6 per 100 person-years). Cardiovascular events were associated with the greatest risk of death (hazard ratio = 8.64; 95% CI: 5.1 to 14.5). The first grade 4 event and the first AIDS event were associated with similar risks of death, 5.68 and 6.95, respectively. Conclusions Grade 4 events are as important as AIDS events in the era of HAART. To adequately evaluate the impact of HAART on morbidity, comorbidities and other key factors must be carefully assessed.

Human immunodeficiency virus (HIV)-related tuberculosis can be life-threatening for the individual, transmissible to others, and difficult to diagnose. We review the clinical, radiographic, and histopathologic features of HIV-related tuberculosis, and the ways in which these features are affected by the degree of immunodeficiency. At CD4 cell counts greater than 350 cells/microL, HIV-related tuberculosis has a similar presentation to tuberculosis in HIV-uninfected adults, predominantly pulmonary involvement with fibronodular and/or cavitary infiltrates. With progressive immunodeficiency, extrapulmonary involvement becomes increasingly common. Pulmonary involvement remains common at all stages of HIV disease, but the radiographic pattern is very different among persons with advanced immunodeficiency, in whom the most common abnormalities are intrathoracic adenopathy, focal lower or middle lobe infiltrates, and diffuse miliary or nodular infiltrates. The keys to the diagnosis of HIV-related tuberculosis are knowledge of the epidemiology of tuberculosis, recognition of the ways that immunodeficiency changes the clinical presentation, and an assiduous effort to obtain specimens for mycobacterial smear and culture.