The case for conservative management of early HIV disease.
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Anti-HIV Agents↗
Biomedical subjects
W J Burman
Publications and source records attributed to W J Burman.
Septic shock from Mycobacterium tuberculosis after therapy for Pneumocystis carinii.
Septic shock resulting from Mycobacterium tuberculosis (TB) occurs only rarely, even among patients infected with human immunodeficiency virus. We report a case of fulminant TB sepsis in the setting of human immunodeficiency virus infection. This case illustrates the hazards of corticosteroid use as a part of empirical treatment of Pneumocystis carinii pneumonia, as well as the unique appearance of TB on chest x-ray films.
AIDS-Related Opportunistic Infections↗
Anterior uveitis and hypotony after intravenous cidofovir for the treatment of cytomegalovirus retinitis.
OBJECTIVE: This study aimed to describe the incidence and risk factors for the development of anterior uveitis in patients receiving intravenous cidofovir for the treatment of longstanding cytomegalovirus retinitis. DESIGN: The study design was a retrospective cohort. PARTICIPANTS: Eighteen patients (30 eyes) receiving parenteral cidofovir for the treatment of complicated cytomegalovirus retinitis participated. MAIN OUTCOME MEASURES: The clinical response to parenteral cidofovir; the occurrence of anterior uveitis, and the management and outcome of patients with this complication; and the effect of cidofovir on intraocular pressure measurements were measured. RESULTS: There was no progression or relapse of retinitis in patients receiving intravenous cidofovir. Eight (44%) of the 18 patients developed anterior uveitis, which occurred after a median of 4 doses of intravenous cidofovir. The median CD4+ cell count at the time of development of iritis was 101/mm3. Patients who developed uveitis had a mean increase in serum creatinine over baseline measurements (P = 0.05). The use of human immunodeficiency virus type-1 (HIV-1) protease inhibitors was not different between both groups of patients (P = 1.0). The development of anterior uveitis and visually significant hypotony necessitated withdrawal of cidofovir in only one patient. CONCLUSIONS: Anterior uveitis was a common complication after intravenous cidofovir therapy. Despite the frequency of this complication, continued treatment with intravenous cidofovir was possible in the majority of patients. Patients with anterior uveitis after intravenous cidofovir may be treated successfully with topical corticosteroid therapy and cycloplegic agents.
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↗
AIDS-related Mycobacterium kansasii infection with initial resistance to clarithromycin.
Clarithromycin is a promising drug for the treatment of Mycobacterium kansasii infection. We report a patient with AIDS and severe M. kansasii infection who had previously received a short course of clarithromycin for sinusitis. He had clinical failure of treatment using clarithromycin plus ethambutol, and the initial isolate was found to be highly resistant to clarithromycin. Nucleotide sequencing of the 23S rRNA gene of this isolate demonstrated a single base mutation at position 2058, the same as that found in clarithromycin-resistant Mycobacterium avium.
AIDS-Related Opportunistic Infections↗
Streptomyces pneumonia in a patient with human immunodeficiency virus infection: case report and review of the literature on invasive streptomyces infections.
Streptomyces species are most widely known for their production of antimicrobial substances and, apart from mycetoma, have rarely been reported as a cause of infection. We describe a patient with early human immunodeficiency virus infection who presented with fever, cough, and nodular pulmonary infiltrates. Open lung biopsy revealed necrotic tissue and a sulfur granule; aerobic bacterial cultures yielded Streptomyces species. The patient was treated successfully with clarithromycin for 6 months. We review the clinical presentation and treatment of invasive streptomyces infections.
AIDS-Related Opportunistic Infections↗
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 value of in vitro drug activity and pharmacokinetics in predicting the effectiveness of antimycobacterial therapy: a critical review.
Marked increases in case rates of drug-resistant tuberculosis and nontuberculous mycobacterial infections have brought renewed urgency to the development of new treatment regimens for mycobacterial infections. Preclinical data, such as in vitro measures of drug activity and pharmacokinetics, are used in the design of new treatment regimens. This review surveys the extensive published clinical experience concerning the treatment of drug-susceptible tuberculosis to evaluate the use of these preclinical measures in predicting clinical outcomes of antimycobacterial therapy. In vitro measures of drug activity predict the potency of a drug to prevent the emergence of resistance to other antimycobacterial drugs but do not predict the sterilizing activity of a drug or the activity of drug combinations. In vitro measures of drug activity do not allow reliable predictions of the level at which an organism should be considered resistant. Assays of drug penetration in tissues and activity against intracellular bacilli add modestly to the predictive value of in vitro measures of drug activity but still do not predict sterilizing activity. In contrast, animal models of tuberculosis have predicted relative drug potency (including sterilizing activity), the efficacy of multidrug regimens, and the duration of therapy needed. Despite pharmacokinetic parameters that would suggest the need for multiple doses per day, all of the first-line antituberculous drugs are active when given as infrequently as twice weekly. It is difficult to predict the efficacy of therapy for an intracellular pathogen that has the capacity for dormancy. Better in vitro models are needed, particularly ones that predict sterilizing activity.
Anti-Bacterial Agents↗
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↗
Evaluation of method for secondary DNA typing of Mycobacterium tuberculosis with pTBN12 in epidemiologic study of tuberculosis.
Secondary fingerprinting of Mycobacterium tuberculosis DNA with a probe containing the polymorphic GC-rich repetitive sequence present in pTBN12 has been found to have greater discriminating power than does fingerprinting with the insertion sequence IS6110 for strains carrying few copies of IS6110. To validate the use of pTBN12 fingerprinting in the molecular epidemiology of tuberculosis, M. tuberculosis isolates from 67 patients in five states in the United States and in Spain were fingerprinted with both IS6110 and pTBN12. Epidemiologic links among the 67 patients were evaluated by patient interview and/or review of medical records. The 67 isolates had 5 IS6110 fingerprint patterns with two to five copies of IS6110 and 18 pTBN12 patterns, of which 10 were shared by more than 1 isolate. Epidemiologic links are consistently found among patients whose isolates had identical pTBN12 patterns, whereas no links were found among patients whose isolates had unique pTBN12 patterns. This suggests that pTBN12 fingerprinting is a useful tool to identify epidemiologically linked tuberculosis patients whose isolates have identical IS6110 fingerprints containing fewer than six fragments.
Bacterial Typing Techniques↗
Specimen contamination in mycobacteriology laboratory detected by pseudo-outbreak of multidrug-resistant tuberculosis: analysis by routine epidemiology and confirmation by molecular technique.
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Bacteriological Techniques↗
Usefulness of the secondary probe pTBN12 in DNA fingerprinting of Mycobacterium tuberculosis.
A comparison was made between DNA fingerprints of Mycobacterium tuberculosis produced with the insertion sequence IS6110 and those produced with the polymorphic GC-rich repetitive sequence contained in the plasmid pTBN12. A total of 302 M. tuberculosis isolates from the prison system in Madrid, Spain, and the Denver Public Health Department (Denver, Colo.) were analyzed with the two probes. Both probes identified the same isolates in the same clusters when the fingerprints had six or more copies of IS6110. Analysis of isolates with unique IS6110 fingerprints demonstrated that they were unique with pTBN12. The pTBN12 probe had greater discriminating power in isolates having five or fewer copies of IS6110. Forty-seven isolates from Denver having fewer than five copies of IS6110 which were grouped in 11 clusters with identical fingerprint patterns were subdivided into 35 different patterns by pTBN12. Isolates with IS6110 fingerprints with more than six copies of IS6110 that differed from one another by only one or two hybridizing bands were analyzed with pTBN12. Most of these sets of isolates demonstrated identical patterns with pTBN12. However, some exceptions were observed, suggesting that those having nearly identical IS6110 patterns should not necessarily be included in the same cluster. Since IS6110 provides more polymorphism in the fingerprint, it is most useful in identifying isolates with unique fingerprint patterns and those in clusters in which the isolates contain six or more copies of the insertion. However, it is necessary to employ a secondary probe, such as pTBN12, to discriminate isolates with five or fewer copies of IS6110 and those with similar but not identical IS6110 patterns.
DNA Fingerprinting↗