PubMed Health⌕ Search

Biomedical subjects

R R Reves

Publications and source records attributed to R R Reves.

At least 19 recordsLinked to original sources

Outcomes of contact investigation among homeless persons with infectious tuberculosis.

SETTING: Homelessness is an important risk factor for tuberculosis (TB). Health departments often fail to identify contacts for homeless TB cases, but little else is known about the outcome of contact investigations for these cases. OBJECTIVE: To describe the outcomes of identification, tuberculin skin testing (TST), clinical evaluation and treatment for contacts of infectious homeless TB cases. DESIGN: Retrospective multicenter review of data of contact investigations conducted in 1996 by five health departments in the United States. RESULTS: Twenty-seven (8%) of 349 TB cases were homeless. Failure to identify contacts occurred in six (50%) of 12 cases residing in shelters vs. one (7%) of 15 non-shelter cases. Of 479 contacts identified, 297 (62%) were fully evaluated, 97 (20%) had only initial testing, and 85 (18%) were not evaluated. Of the 394 evaluated contacts, 13 (3%) had a prior positive TST. Of the remaining 381 contacts, six (1.6%) had active TB and 67 (17.6%) were TST-positive. Only 27 (44%) of 61 contacts completed treatment for latent TB infection. CONCLUSION: Despite the failure to identify contacts for some cases, contact investigations for homeless TB cases identified large numbers of contacts for whom evaluation and treatment were often not completed. Prospective studies with more complete documentation are needed to improve contact investigations for homeless TB cases.

Contact Tracing↗

Breaking the camel's back: multicenter clinical trials and local institutional review boards.

Clinical research has undergone remarkable and beneficial expansion in the past 25 years, but with this growth has come an unprecedented increase in workload for the human subjects protection system. Recently, a major change in federal oversight of local institutional review boards (IRBs) became evident. Although it was not announced publicly, in 1998 and 1999 federal regulatory actions against local IRBs increased threefold. Particularly notable was the marked increase in regulatory actions taken against the IRBs of academic medical centers (1 in 1997 compared with 14 in 1999). Ironically, this apparent federal crackdown began at the same time that two federal review panels called for major changes in the regulations governing local IRBs. A key factor in the current crisis in the function of local IRBs is the ascendance of multicenter clinical trials as the dominant form of clinical research. Local IRBs were not designed to handle the initial evaluation and ongoing review required by the rapidly increasing number of multicenter clinical trials. Furthermore, local IRB review of the thousands of safety reports from multicenter clinical trials monopolizes resources without promoting patient safety. Instead of rigid enforcement of outmoded regulations that do not contribute to patient safety, the responsibilities of the local IRB in the oversight of multicenter clinical trials must be systematically evaluated.

Academic Medical Centers↗

Review of false-positive cultures for Mycobacterium tuberculosis and recommendations for avoiding unnecessary treatment.

We reviewed reports of false-positive cultures for Mycobacterium tuberculosis and here propose guidelines for detecting and managing patients with possible false-positive cultures. Mechanisms of false-positive cultures included contamination of clinical devices, clerical errors, and laboratory cross-contamination. False-positive cultures were identified in 13 (93%) of the 14 studies that evaluated > or = 100 patients; the median false-positive rate was 3.1% (interquartile range, 2.2%-10.5%). Of the 236 patients with false-positive cultures reported in sufficient detail, 158 (67%) were treated, some of whom had toxicity from therapy, as well as unnecessary hospitalizations, tests, and contact investigations. Having a single positive culture was a sensitive but nonspecific criterion for detecting false-positive cultures. False-positive cultures for M. tuberculosis are not rare but are infrequently recognized by laboratory and clinical personnel. Laboratories and tuberculosis control programs should develop procedures to identify patients having only 1 positive culture. Such patients should be further evaluated for the possibility of a false-positive culture.

Culture Media↗

Long-term outcomes of treatment of Mycobacterium avium complex bacteremia using a clarithromycin-containing regimen.

OBJECTIVES: To describe the long-term outcomes of treatment of AIDS-related Mycobacterium avium complex (MAC) bacteremia using a standard clarithromycin-based regimen. DESIGN: Retrospective study of patients with MAC bacteremia diagnosed between April 1992 and April 1995. SETTING: An urban AIDS clinic SUBJECTS: One hundred seventy-six consecutive patients with MAC bacteremia. INTERVENTIONS: Clarithromycin 500 mg twice daily, ethambutol 800 or 1200 mg daily, and clofazimine 100 mg daily. MAIN OUTCOME MEASURES: Late treatment failure (defined as a positive blood culture more than 90 days after starting treatment), clarithromycin susceptibility of initial and treatment-failure isolates, DNA fingerprinting of isolates from treatment failures. RESULTS: Two out of 176 (1.1%) baseline isolates were resistant to clarithromycin. One hundred and fifty-one patients were treated for MAC bacteremia, 144 (95%) with the standard regimen. Of the 117 patients who survived > 90 days after starting therapy, 25 (21%) met the criteria for late treatment failure. Of the 22 treatment-failure isolates available for susceptibility testing, 19 (86%) were resistant to clarithromycin. Therefore, 13% of patients treated using the standard regimen (19 out of 144) had treatment failure associated with the emergence of clarithromycin resistance. Using logistic regression, non-compliance was associated with treatment failure (P = 0.02). Fourteen out of the 17 (82%) evaluable paired isolates had identical DNA fingerprint patterns, whereas three pairs showed that a different strain of MAC was present at the time of treatment failure. CONCLUSIONS: Initial resistance to clarithromycin was rare during this period. However, late treatment failure associated with the emergence of clarithromycin resistance was relatively common during long-term follow-up. Most late treatment failures represented emergence of clarithromycin resistance in the initial strain.

AIDS-Related Opportunistic Infections↗

Evaluation of a disk diffusion method for determining susceptibility of Mycobacterium avium complex to clarithromycin.

We evaluated an agar disk diffusion method for determining the susceptibility of Mycobacterium avium complex to clarithromycin. Isolates were inoculated onto the surface of a Middlebrook 7H11 plate, followed by the application of a 15-microgram clarithromycin disk. Zone sizes were read after 5-7 days of incubation. Zone sizes had a bimodal distribution; 40 isolates (10%) had no zone of inhibition, whereas the zone sizes for the remaining isolates ranged from 11 to 60 mm. Most isolates (37/40) having no zone of inhibition came from patients who had been treated previously with clarithromycin. Fifty-one isolates were also tested for clarithromycin susceptibility using a microdilution broth method. Defining susceptibility as a zone size of > 10 mm, disk diffusion test results agreed with the results by the microdilution broth method for 50 of 51 (98%) isolates tested by both methods. Agar disk diffusion is a promising method for the determination of clarithromycin susceptibility testing for M. avium complex.

Animals↗

Comparison of BACTEC 12B vs solid media for the recovery of Mycobacterium avium complex from blood cultures in AIDS patients.

We compared liquid (BACTEC 12B) and solid culture media for the diagnosis of Mycobacterium avian complex (MAC) bacteremia among 258 AIDS patients with a positive blood culture. Neither culture media alone had adequate sensitivity; BACTEC 12B detected growth earlier. Use of both liquid and solid media may improve the yield of mycobacterial blood culture.

AIDS-Related Opportunistic Infections↗

The diagnostic yield of acid-fast-bacillus smear-positive sputum specimens.

The yield of mycobacterial culture from acid-fast-bacillus smear-positive sputum specimens was 387 or 439 (88.2%). Forty-nine of 52 culture-negative specimens came from patients on treatment. We conclude that the yield of culture from smear-positive sputum specimens is very high and that only two acid-fast-bacillus smear-positive specimens are needed for the initial evaluation of pulmonary mycobacteriosis.

Bacterial Typing Techniques↗

The incidence of false-positive cultures for Mycobacterium tuberculosis.

The frequency of false-positive cultures for Mycobacterium tuberculosis due to cross-contamination has been difficult to determine because of the lack of specific strain markers. Isolates collected prospectively over 5 yr from a municipal health department laboratory underwent DNA fingerprinting using the IS6110 and pTBN12 sequences. We reviewed the clinical and laboratory records of all isolates that had matching DNA fingerprints and were processed within 42 d of each other; 8 isolates were classified as probable or definite false-positives, representing 4.0% (8/199) of the culture-positive patients. A convenience sample of 42 isolates from three other mycobacterial laboratories also underwent DNA fingerprinting, and five (12%) were found to be definite or probable false-positives. Cross-contamination during initial processing of specimens was the most common source of false-positive cultures. The source of cross-contamination for three false-positive cultures was a laboratory proficiency survey specimen containing strain H37Ra. Ten of the 13 patients were misdiagnosed as having tuberculosis, and seven received unnecessary multidrug treatment. Clinicians should be aware of the potential for false-positive cultures for M. tuberculosis, and mycobacteriology laboratories need to carefully review procedures to minimize this occurrence. DNA fingerprinting provides a valuable tool for the study of false-positive cultures.

Bacteriological Techniques↗

DNA fingerprinting with two probes decreases clustering of Mycobacterium tuberculosis.

DNA fingerprinting of Mycobacterium tuberculosis is used to study the epidemiology of tuberculosis, but the specificity of the widely used IS6110 technique has not been validated. Isolates from Denver, Colorado from December 1988 through June 1994 were fingerprinted with the IS6110 technique. Available records were reviewed for patients whose isolates were within IS6110-defined clusters, and these isolates were fingerprinted with an independent technique (pTBN12). Of 189 isolates, 86 (46%) were in IS6110-defined clusters. Clustering was inversely related to the number of copies of IS6110, ranging from 12 of 12 (100%) to 37 of 48 (77%) and 37 of 129 (29%) for isolates having one, two to five, and more than five copies (p < 0.001). Of the 86 isolates clustered with the IS6110 technique, 35 (41%) had unique pTBN12 fingerprints. Discordant results with the two fingerprinting techniques were more common among isolates having five or fewer copies of IS6110. Epidemiologic links were identified among four of 35 (11%) patients whose isolates had discordant fingerprinting results, as compared with 40 of 51 (78%) of those whose isolates matched by both IS6110 and pTBN12. DNA fingerprinting with the IS6110 technique was not a specific marker of DNA clonality, particularly among isolates having fewer than five copies of IS6110. The use of a supplemental DNA fingerprinting technique decreased clustering and improved the correlation between the transmission links predicted by molecular techniques and epidemiologic investigation.

Cluster Analysis↗

Noncompliance with directly observed therapy for tuberculosis. Epidemiology and effect on the outcome of treatment.

STUDY OBJECTIVES: To describe the epidemiology and clinical consequences of noncompliance with directly observed therapy (DOT) for treatment of tuberculosis. DESIGN: Retrospective review. SETTING: An urban tuberculosis control program that emphasizes DOT. PATIENTS: All patients treated with outpatient DOT from 1984 to 1994. MEASUREMENTS AND RESULTS: We defined noncompliance as follows: (1) missing > or = 2 consecutive weeks of DOT; (2) prolongation of treatment > 30 days due to sporadic missed doses; or (3) incarceration for presenting a threat to public health. Poor outcomes of therapy were defined as a microbiologic or clinical failure of initial therapy, relapse, or death due to tuberculosis. Fifty-two of 294 patients (18%) who received outpatient DOT fulfilled one or more criteria for noncompliance. Using multivariate logistic regression, risk factors for noncompliance were alcohol abuse (odds ratio, 3.0; 95% confidence interval, 1.2 to 7.5; p = 0.02) and homelessness (odds ratio, 3.2; 95% confidence interval, 1.5 to 7.2; p = 0.004). Noncompliant patients had poor outcomes from the initial course of therapy more often than compliant patients: 17 of 52 (32.7%) vs 8 of 242 (3.3%); relative risk was 9.9; 95% confidence interval was 4.5 to 21.7 (p < 0.001). CONCLUSIONS: In an urban tuberculosis control program, noncompliance with DOT was common and was closely associated with alcoholism and homelessness. Noncompliance was associated with a 10-fold increase in the occurrence of poor outcomes from treatment and accounted for most treatment failures. Innovative programs are needed to deal with alcoholism and homelessness in patients with tuberculosis.

Adult↗

Short-term incarceration for the management of noncompliance with tuberculosis treatment.

STUDY OBJECTIVES: To review the use of incarceration for noncompliance with tuberculosis treatment. DESIGN: Retrospective review. SETTING: An urban tuberculosis control program. PATIENTS: Patients treated for active tuberculosis. MEASUREMENTS AND RESULTS: We reviewed the legal basis and practical application of quarantine for active tuberculosis, including the use of incarceration for noncompliance. The records of patients treated at the Denver Metro Tuberculosis Clinic during 1984 to 1994 were reviewed to identify patients who were incarcerated and to evaluate the effectiveness of this intervention. Of 424 cases of tuberculosis, 20 patients (4.7%) were incarcerated for noncompliance; an additional 21 patients (5.0%) were lost to follow-up prior to completing therapy. Incarcerated patients were predominantly men who were born in the United States and had a history of homelessness and alcohol abuse. The median duration of the initial incarceration was 20 days (range, 7 to 51 days). Of the 17 patients released prior to completing therapy, 13 (76%) were compliant with outpatient, directly observed therapy after one or two short-term incarcerations (<60 days); only three patients were incarcerated for the duration of treatment. Overall, 18 of 20 incarcerated patients (90%) were successfully treated. CONCLUSIONS: Approximately 5% of the patients treated through our program were incarcerated for noncompliance; an additional 5% were unavailable for follow-up and would have been candidates for incarceration if found. Homelessness and alcoholism were closely associated with the use of incarceration. Short-term incarceration followed by outpatient, directly observed therapy was relatively successful in the management of this difficult patient population.

Adult↗

A cost-effectiveness analysis of directly observed therapy vs self-administered therapy for treatment of tuberculosis.

STUDY OBJECTIVES: To compare the costs and effectiveness of directly observed therapy (DOT) vs self-administered therapy (SAT) for the treatment of active tuberculosis. DESIGN: Decision analysis. SETTING: We used published rates for failure of therapy, relapse, and acquired multidrug resistance during the initial treatment of drug-susceptible tuberculosis cases using DOT or SAT. We estimated costs of tuberculosis treatment at an urban tuberculosis control program, a municipal hospital, and a hospital specializing in treating drug-resistant tuberculosis. OUTCOME MEASURES: The average cost per patient to cure drug-susceptible tuberculosis, including the cost of treating failures of initial treatment. RESULTS: The direct costs of initial therapy with DOT and SAT were similar ($1,206 vs $1,221 per patient, respectively), although DOT was more expensive when patient time costs were included. When the costs of relapse and failure were included in the model, DOT was less expensive than SAT, whether considering outpatient costs only ($1,405 vs $2,314 per patient treated), outpatient plus inpatient costs ($2,785 vs $10,529 per patient treated), or outpatient, inpatient, and patients' time costs ($3,999 vs $12,167 per patient treated). Threshold analysis demonstrated that DOT was less expensive than SAT through a wide range of cost estimates and clinical event rates. CONCLUSION: Despite its greater initial cost, DOT is a more cost-effective strategy than SAT because it achieves a higher cure rate after initial therapy, and thereby decreases treatment costs associated with failure of therapy and acquired drug resistance. This cost-effectiveness analysis supports the widespread implementation of DOT.

Antitubercular Agents↗

A retrospective comparison of clarithromycin versus rifampin in combination treatment for disseminated Mycobacterium avium complex disease in AIDS: clarithromycin decreases transfusion requirements.

SETTING: Urban county medical center. OBJECTIVE: To compare clinical outcomes associated with two treatment regimens for AIDS-associated disseminated Mycobacterium avium complex (DMAC). From 1989 to mid-1992, patients were treated with rifampin, ethambutol, and clofazimine; in mid-1992 clarithromycin replaced rifampin. DESIGN: A retrospective review of patients with DMAC; the main outcome measures assessed were toxicity associated with DMAC treatment, transfusions after the diagnosis of DMAC, and survival. RESULTS: 88 patients received the rifampin-based regimen and 86 were treated with the clarithromycin-based regimen. Drug-related adverse events were recorded less frequently with clarithromycin treatment (21% vs. 42%, P = 0.005), and additional antimycobacterial agents were used less often (28% vs. 44%, P = 0.04). In a multivariate logistic regression model, severe anemia at the time of DMAC diagnosis was associated with transfusion-dependence (relative risk [RR] 5.6, 95% confidence interval [CI] 2.2, 13.8, P < 0.001) and clarithromycin treatment was inversely associated with transfusion dependence (RR 0.4, 95% CI 0.1, 0.98, P = 0.04). In a multivariate Cox regression model including other factors affecting survival, clarithromycin treatment did not confer a survival advantage (P = 0.74). CONCLUSIONS: The clarithromycin-containing regimen was better tolerated and was associated with substantially lower transfusion requirements than the rifampin-based regimen; survival was not affected.

AIDS-Related Opportunistic Infections↗

Prolonged incubation of blood and bone marrow cultures in 12B bottles processed on the BACTEC 460 TB system does not increase microbial recovery.

Standard references continue to recommend testing specimens processed on the BACTEC TB System for 8 weeks, despite evidence that mycobacteria are rarely recovered beyond 5-6 weeks. To clarify this issue, we retrospectively reviewed all positive blood/bone marrow cultures processed during a 17-month period when specimens were tested for 6 weeks. We then prolonged the incubation period to 8 weeks during the subsequent 5 months. Excluding Mycobacterium genavense, only 1 of 159 mycobacterial isolates was recovered during and none were recovered beyond the 5th week of incubation and testing on the BACTEC TB System.

Bacteriological Techniques↗

Multifocal cellulitis and monoarticular arthritis as manifestations of Helicobacter cinaedi bacteremia.

Helicobacter cinaedi (formerly Campylobacter cinaedi) was first detected in the fecal flora of homosexual men. Since 1984, 11 case reports of H. cinaedi bacteremia have been published; most cases have presented as a nonspecific febrile illness in homosexual men infected with the human immunodeficiency virus (HIV). We identified seven additional cases of H. cinaedi bacteremia in two Denver hospitals within a 5-year period, which suggests that this illness is not as rare as was previously thought. Six of these cases of H. cinaedi bacteremia occurred in homosexual men who were infected with HIV. Four patients presented with the distinctive cutaneous manifestation of multifocal cellulitis, and two patients had monoarticular arthritis. Microbiological diagnosis of this infection was delayed by the slow growth of the bacterium in nonradiometric blood culture bottles. Although the patients' bacteremia was prolonged, their response to treatment was excellent. In contrast to campylobacter infections in HIV-infected patients, H. cinaedi bacteremia did not relapse after a course of effective therapy. H. cinaedi bacteremia should be suspected in HIV-infected individuals who present with an indolent febrile illness, particularly in the presence of multifocal cellulitis and/or arthritis.

AIDS-Related Opportunistic Infections↗