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Biomedical subjects

William J Burman

Publications and source records attributed to William J Burman.

At least 19 recordsLinked to original sources

Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis.

RATIONALE: Moxifloxacin has promising preclinical activity against Mycobacterium tuberculosis, but has not been evaluated in multidrug treatment of tuberculosis in humans. OBJECTIVE: To compare the impact of moxifloxacin versus ethambutol, both in combination with isoniazid, rifampin, and pyrazinamide, on sputum culture conversion at 2 mo as a measure of the potential sterilizing activity of alternate induction regimens. METHODS: Adults with smear-positive pulmonary tuberculosis were randomized in a factorial design to receive moxifloxacin (400 mg) versus ethambutol given 5 d/wk versus 3 d/wk (after 2 wk of daily therapy). All doses were directly observed. MEASUREMENTS: The primary endpoint was sputum culture status at 2 mo of treatment. RESULTS: Of 336 patients enrolled, 277 (82%) were eligible for the efficacy analysis, 186 (67%) were male, 175 (63%) were enrolled at African sites, 206 (74%) had cavitation on chest radiograph, and 60 (22%) had HIV infection. Two-month cultures were negative in 71% of patients (99 of 139) treated with moxifloxacin versus 71% (98 of 138) treated with ethambutol (p = 0.97). Patients receiving moxifloxacin, however, more often had negative cultures after 4 wk of treatment. Patients treated with moxifloxacin more often reported nausea (22 vs. 9%, p = 0.002), but similar proportions completed study treatment (88 vs. 89%). Dosing frequency had little effect on 2-mo culture status or tolerability of therapy. CONCLUSIONS: The addition of moxifloxacin to isoniazid, rifampin, and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points.

Adult↗

Durability of adherence to antiretroviral therapy on initial and subsequent regimens.

There is uncertainty regarding the durability of adherence to antiretroviral therapy. This study is a retrospective review of previously antiretroviral naïve patients initiating therapy between 1997 and 2002. Antiretroviral adherence was calculated using prescription refill data and was analyzed over time on an initial regimen and on sequential antiretroviral regimens. Three hundred forty-four patients were included. The median lengths of the first, second, and third regimens were stable at 1.7 years, 1.2 years, and 1.5 years, respectively (p = 0.10). In multivariate analysis the factor most significantly associated with earlier initial regimen termination was poor adherence. On an initial regimen, adherence decreased over time and declined most rapidly in patients with the shortest regimens (4 to <16 months, -43% per year), followed by patients with intermediate regimen duration (16 to <28 months, -19% per year), and then patients with longer regimens (>/=28 months, -5% per year). In patients progressing to a third regimen, there was a trend toward decreasing adherence over successive regimens. In conclusion, sequential antiretroviral regimens are of similar lengths, with adherence being highly associated with first regimen duration. Adherence decreases during an initial regimen and on sequential antiretroviral regimens. Effective and durable interventions to prevent declining adherence are needed.

Adult↗

Risk-based human immunodeficiency virus (HIV) testing fails to detect the majority of HIV-infected persons in medical care Settings.

OBJECTIVES: To evaluate opportunities for earlier human immunodeficiency virus (HIV) diagnosis within a comprehensive public health care system. STUDY DESIGN: Retrospective review of newly diagnosed HIV-infected patients between September 2001 and December 2003. RESULTS: One hundred twenty of 348 (34%) newly diagnosed HIV-infected patients had medical care within our system in the 3 years before diagnosis. One hundred five of 120 (88%) patients had at least 1 prior encounter in the emergency department or urgent care center, whereas just 12 (10%) HIV diagnoses were made in these 2 sites. Only 33 (28%) patients previously presented with an HIV clinical indicator condition or sexually transmitted infection. CONCLUSIONS: Although one-third of newly diagnosed HIV-infected patients had clinical visits in the 3 years before diagnosis, few presented with clinical conditions typically associated with HIV infection. Targeted testing based on clinical presentations is not likely to result in substantially earlier HIV diagnosis. Routine screening in high prevalence settings could be more effective.

Adult↗

Selective drug taking during combination antiretroviral therapy in an unselected clinic population.

OBJECTIVES: Multidrug therapy is necessary to achieve sustained viral suppression. Discordant adherence to individual components of a multidrug regimen may lead to adverse outcomes. METHODS: Antiretroviral-naive patients initiating therapy from 1997 through 2002 were included. Adherence for each antiretroviral was determined using pharmacy refill data. Selective drug taking was defined as > or =5% difference in adherence between 2 components of an antiretroviral regimen lasting at least 60 days. RESULTS: A total of 322 of 415 patients (78%) met inclusion criteria. Selective drug taking occurred in 47 of 322 patients (15%) and on 51 of 438 regimens (12%). Factors associated with selective drug taking were lower baseline CD4 lymphocyte count (adjusted odds ratio [AOR]: 1.3, 95% CI: 1.1 to 1.6 per 100 cell/microL decrease); 3 times daily dosing schedule (AOR: 4.1, 95% CI: 1.1 to 15.5); and the presence of significant adverse drug events (AOR: 2.9, 95% CI: 1.3 to 6.4). Regimens containing a fixed-dose combination dosage form were less likely to have selective drug taking (AOR: 0.5, 95% CI: 0.2 to 0.99). Outcomes independently associated with selective drug taking included earlier progression to a new AIDS-defining illness or death (hazard ratio: 2.3, 95% CI: 1.2 to 4.5). CONCLUSIONS: Selective drug taking was relatively common among patients taking combination antiretroviral therapy. The factor most closely associated with selective drug taking was the presence of an adverse drug event. Clinical outcomes appeared worse in patients with selective drug taking.

Adult↗

Conventional and molecular epidemiology of macrolide resistance among new Mycobacterium avium complex isolates recovered from HIV-infected patients.

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.

Adult↗

Issues in the management of HIV-related tuberculosis.

This article focuses on the ways in which HIV infection and the associated immunodeficiency affect the management of active tuberculosis. Controversies in the management of HIV-related tuberculosis can be grouped into issues about tuberculosis treatment itself and issues posed by the use of combination antiretroviral therapy. The author reviews these controversies and makes recommendations for the management of HIV-related tuberculosis.

AIDS-Related Opportunistic Infections↗

Widespread emergence of methicillin resistance in community-acquired Staphylococcus aureus infections in Denver.

BACKGROUND: Increasing rates of methicillin resistance among out-patient Staphylococcus aureus infections led us to assess the epidemiology and outcome of a local outbreak. METHODS: A retrospective cohort study of outpatient skin and soft tissue infections due to S aureus in 2003. RESULTS: From 2002 to mid-2004, the percentage of outpatient S aureus isolates resistant to methicillin increased from 6 to 45%. In multivariate analysis, only male sex and age greater than 18 years were associated with methicillin resistance. Methicillin resistance was common (>15%) among isolates from patients in nearly all subgroups evaluated. Pulsed field gel electrophoresis showed isolates related to USA 300, but methicillin-resistant strains had unusually high rates of quinolone resistance. CONCLUSIONS: A single strain of methicillin-resistant S aureus is responsible for the increase in skin infections in outpatients without traditional risk factors for infection with an antibiotic-resistant strain. In areas with high rates of methicillin-resistant S aureus outpatient infections, we recommend non-beta-lactam antibiotics for initial treatment of skin and soft tissue infections.

Adolescent↗

Recurrent tuberculosis in the United States and Canada: relapse or reinfection?

Recurrence of active tuberculosis after treatment can be due to relapse of infection with the same strain or reinfection with a new strain of Mycobacterium tuberculosis. The proportion of recurrent tuberculosis cases caused by reinfection has varied widely in previous studies. We evaluated cases of recurrent tuberculosis in two prospective clinical trials: a randomized study of two regimens for the last 4 months of treatment (n = 1,075) and a study of a twice-weekly rifabutin-containing regimen for human immunodeficiency virus-infected tuberculosis (n = 169). Isolates at diagnosis and from positive cultures after treatment completion underwent genotyping using IS6110 (with secondary genotyping for isolates with less than six copies of IS6110). Of 85 patients having a positive culture after completing treatment, 6 (7.1%) were classified as false-positive cultures by a review committee blinded to treatment assignment. Of the remaining 75 cases with recurrent tuberculosis and genotyping data available, 72 (96%; 95% confidence interval, 88.8-99.2%) paired isolates had the same genotype; only 3 (4%; 95% confidence interval, 0.8-11.2%) had a different genotype and were categorized as reinfection. We conclude that recurrent tuberculosis in the United States and Canada, countries with low rates of tuberculosis, is rarely due to reinfection with a new strain of M. tuberculosis.

Adult↗

Pharmacokinetics of rifapentine at 600, 900, and 1,200 mg during once-weekly tuberculosis therapy.

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.

Adult↗

Grade 4 events are as important as AIDS events in the era of HAART.

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.

Adult↗

Conventional and molecular epidemiology of trimethoprim-sulfamethoxazole resistance among urinary Escherichia coli isolates.

BACKGROUND: Antibiotic resistance is increasing in Escherichia coli, the most common cause of urinary tract infections, but its epidemiology has not been well described. We evaluated the epidemiology of trimethoprim-sulfamethoxazole-resistant E. coli in a large, public health care system in Denver, Colorado. METHODS: Outpatients with E. coli urinary tract infections during the first 6 months of 1998 were evaluated retrospectively. A prospective study was then performed to confirm the rate of trimethoprim-sulfamethoxazole resistance. We used several strain-typing methods (pulsed-field gel electrophoresis, ribotyping, serotyping) to evaluate the molecular epidemiology of the resistance. RESULTS: The rate of trimethoprim-sulfamethoxazole resistance was similar in the retrospective (24% [161/681]) and prospective (23% [30/130]) phases of the study (P = 0.89). Almost all trimethoprim-sulfamethoxazole-resistant strains (98%) were resistant to at least one other antibiotic. Risk factors for infection with a resistant strain included age < or =3 years, Hispanic ethnicity, recent travel outside the United States, and a prior urinary tract infection. However, rates of resistance were >15% among nearly all of the subgroups. Most strains had high-level resistance (>1000 microg/mL) to trimethoprim-sulfamethoxazole. Of the 23 resistant isolates evaluated, 10 (43%) belonged to the clone A group. There was no correlation between conventional epidemiologic characteristics and the molecular mechanism of resistance or strain type. CONCLUSION: Resistance to trimethoprim-sulfamethoxazole among E. coli isolates among patients in a Denver public health care system is common, with high rates of resistance even among patients without risk factors.

Adolescent↗

Clinical and radiographic features of HIV-related tuberculosis.

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.

AIDS-Related Opportunistic Infections↗

HIV transmission risk behavior and its relation to antiretroviral treatment adherence.

BACKGROUND: Rising rates of antiretroviral drug resistance among recently infected persons are evidence of high-risk behavior among persons in HIV care. GOAL: The goal was to determine HIV transmission risk behavior among persons in HIV care and evaluate its association with treatment adherence. STUDY DESIGN: The study involved a structured interview of a random sample of patients in HIV care in an urban public clinic. Participants were categorized by transmission risk: high risk = unprotected anal/vaginal sex and/or needle sharing; low risk = protected anal/vaginal sex, unprotected and/or protected oral sex, no needle sharing; no risk = no sex or needle sharing. RESULTS: Of the 95 participants, 21 (22%) reported high-risk behavior, 36 (38%) reported low-risk behavior, and 38 (40%) reported no transmission risk in the past 3 months. Younger, more educated persons and those with an active substance abuse diagnosis were more likely to have high transmission risk (P < or = 0.05). Patients who engaged in high-risk behavior had equivalent use of antiretroviral therapy (P = 0.80) but lower adherence (P < or = 0.01) and higher median plasma viral loads (P = 0.05). CONCLUSIONS: There was a wide spectrum of transmission risk behavior among persons in HIV care. Persons reporting high-risk behavior were less adherent to antiretroviral therapy, providing a behavioral basis for transmission of drug-resistant HIV.

Adult↗

Tuberculosis in patients with HIV infection.

In the past 5 years, there have been significant advances in the understanding of the pathogenesis of TB in people infected with HIV and in the approach to diagnosis, treatment, and prevention in patients with HIV. Nucleic acid amplification tests and restriction fragment length polymorphism can contribute to the clinical management of TB patients. New guidelines are available for the treatment of active and latent TB infection in patients with HIV.

HIV Infections↗

Population pharmacokinetic modeling of pyrazinamide in children and adults with tuberculosis.

STUDY OBJECTIVE: To determine population pharmacokinetic parameters of pyrazinamide after multiple oral doses given to children and adults with tuberculosis. DESIGN: Prospective, multiple-dose population pharmacokinetic study. SETTING: Five hospitals in the United States. PATIENTS: Sixty-seven adults and 23 children with active tuberculosis. INTERVENTION: The 90 patients received multiple oral doses of pyrazinamide as part of their treatment, based on the best clinical judgment of the attending physicians and in keeping with standard clinical practices at each institution. The patients also received other antituberculosis drugs empirically or based on in vitro susceptibility data. MEASUREMENTS AND MAIN RESULTS: Serum samples were collected over 12 hours after dosing and were assayed with a validated gas chromatography assay with mass selective detection. Concentration-time data were analyzed by using population methods. Pyrazinamide concentrations increased linearly with increasing oral doses (185-3550 mg). Median maximum serum concentration values were 41.0 microg/ml with daily dosing and 66.1 microg/ml with larger, twice-weekly dosing. Incomplete (18%) or delayed (30%) absorption was more common in children than in adults (1% for each). Pharmacokinetic parameters of pyrazinamide were independent of human immunodeficiency virus status and patient demographics, except for body weight. Population elimination half-life values in pediatric and adult patients were 3.5 and 6.0 hours, respectively. Median volume of distribution (L/kg) was 32% larger in children, and median clearance (L/hr/kg) was 106% larger in children, with a resultant median half-life 43% shorter in children. CONCLUSION: Pyrazinamide concentrations and most pharmacokinetic parameters were comparable to those previously published. Apparent half-life was somewhat shorter than that in previous reports. Compared with adults, absorption of pyrazinamide in children appeared more likely to be incomplete or delayed.

Adult↗