Pacemaker wire infection with Mycobacterium tuberculosis: a case report and literature review.

Post-operative reactivation of Mycobacterium tuberculosis (TB) is a recognized complication of surgery. We report a case of reactivation TB involving pacemaker wires and review the literature on surgical site TB infections following cardiac surgery to examine the clinical features and outcomes of this rare but important presentation of TB.

A cost-effectiveness comparison of the use of antimicrobial agents for treatment or prophylaxis of travelers' diarrhea.

We conducted a decision analysis to compare the cost-effectiveness of antimicrobial agents used for treatment with their use for prophylaxis of travelers' diarrhea. Estimates of the likelihood and the cost of various outcomes were obtained from a panel of experts using the Delphi group opinion technique. Treatment with sulfamethoxazole-trimethoprim for three days was compared with daily prophylaxis with sulfamethoxazole-trimethoprim or doxycycline. The cost-effectiveness of prophylaxis with either agent (75% to 83%) was greater than that of treatment (38%). Treatment would become more cost-effective than prophylaxis when the cumulative risk of acquiring travelers' diarrhea was less than 0.05 episodes per person per week or if the effectiveness of prophylaxis fell below 35% for doxycycline and 46% for sulfamethoxazole-trimethoprim. The most important contributor to the mean cost of travelers' diarrhea in this analysis was the cost associated with a day of incapacitation due to illness. On the basis of the results of this decision analysis, we conclude that prophylaxis of travelers' diarrhea is an option that should be considered for individual situations and recommend further studies of its cost-effectiveness.

Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI.

SETTING: Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear. OBJECTIVES: To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity. DESIGN: Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV. RESULTS: Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors. CONCLUSION: The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.

Disseminated Mycobacterium genavense infection: clinical and microbiological features and response to therapy.

OBJECTIVE: Mycobacterium genavense is a newly described pathogen that causes disseminated infection in AIDS. It is difficult to detect and identify due to its slow growth and fastidious nature. There is little information available about therapy for this new pathogen. We describe clinical and laboratory features and response to therapy in four patients with advanced AIDS complicated by disseminated M. genavense infection from Denver, Colorado, USA. DESIGN AND METHODS: Retrospective analysis of four cases identified in an AIDS clinic affiliated with a municipal hospital in Denver, Colorado. Clinical samples were inoculated onto BACTEC 12B, Lowenstein-Jensen, and Middlebrook 7H11 media. RESULTS: The clinical features mimicked those of disseminated M. avium complex infection, with invasion of liver, spleen and lymph nodes with acid-fast bacilli (AFB). Acid-fast smears of blood and lymph nodes were positive; there was a modest increase in the growth index in BACTEC broth and tiny colonies appeared on Middlebrook agar. Patients were treated with combinations of antimycobacterial agents. Blood smears and cultures reverted to negative in treated patients. The best clinical response was associated with clarithromycin therapy. CONCLUSIONS: Disseminated disease due to M. genavense should be suspected among patients with the clinical presentation of disseminated M. avium complex infection and low growth index on BACTEC cultures for AFB. The diagnosis of M. genavense may be facilitated by performing acid-fast stains of samples from BACTEC bottles in such individuals. Clarithromycin therapy is associated with clinical improvement and clearance of bacteremia.

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.

Knowledge and attitudes of day care center parents and care providers regarding children infected with human immunodeficiency virus.

It was hypothesized that parents and child care providers are not prepared to accept children infected with human immunodeficiency virus (HIV), who are increasing in number, into the day care center setting. To determine their knowledge and attitudes toward HIV transmission, 219 parents in 4 day care centers and 176 care providers in 12 day care centers were given confidential questionnaires. More than 98% of respondents knew that sex and needle sharing can transmit HIV; 84% of parents and 77% of care providers knew that contact with blood can transmit HIV. There was, however, uncertainty about transmission via many common contacts in day care centers: human bites, urine, stool, tears, and vomit; kissing; sharing of food and eating utensils; and diaper changing areas. Only 43% of parents said they would allow their child to stay in the same room with a child who was infected with HIV. In a multiple logistic regression model, the unwillingness of parents to have their child stay in the same room with a child who was infected with HIV was significantly (P less than .0001) associated with black ethnicity, beliefs that such a child is likely to infect others (40%) and is dangerous to others (58%), and fear of their child being exposed to HIV (86%). Care providers' unwillingness to care for a child infected with HIV in the classroom (48%) was significantly (P less than .0001) associated with beliefs that such a child is likely to infect others (44%) and that common day care center contacts can transmit HIV (62%).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Diarrhea in children newly enrolled in day-care centers in Houston.

Diarrhea is a common illness among children in day-care centers (DCC). We hypothesized that the incidence of diarrhea was greater among children in their first 1 or 2 months after enrollment in a DCC than in any subsequent period in day care. We followed 442 children younger than 2 years of age enrolled in 13 randomly selected DCCs for the occurrence of diarrhea during a 14 1/2-month period. Parents completed standardized baseline questionnaires and research nurses visited the DCC twice weekly to record the occurrence of diarrhea and to collect stool specimens. Incidence rates, rate ratios, chi square statistics and 95% confidence intervals were calculated for crude and stratified analyses. The diarrheal incidence rate of 4.4 cases/child-year in the first 4 weeks in the centers was significantly (rate ratio, 1.6; confidence interval, 1.3 to 2.1; P less than 0.01) higher than the 2.7 cases/child-year incidence rate of diarrhea in subsequent weeks. The effects of gender, ethnicity, age, DCC size, previous DCC attendance and season were examined and did not account for the association observed between recent enrollement and risk of diarrheal illness. Rotavirus was identified in 18% of cases of diarrhea, but no association was seen with recent enrollment in DCC. A significantly higher incidence of diarrhea occurred in males compared with females (P less than 0.002) and in younger children (P less than 0.001) compared with older children. Diarrhea is common in children in DCCs and occurs significantly more frequently in children during their first 4 weeks in a DCC.

Infectious diseases and child day care.

It is estimated that more than 5.3 million children attend out-of-home child day care in the United States. This includes 2.1 million children who attend approximately 63,000 licensed child day-care centers. An additional 500,000 children receive care in 105,000 regulated day-care homes. Since the total regulated child care slots available in centers and homes are only 2.6 million, some 2.7 million additional children are likely attending unregulated family day-care homes. As a result infants and preschool children are intermingled in child care facilities that often lack adequate toilet and hand-washing facilities and are frequently staffed by individuals with little or no training in the area of infection control. Placing children in out-of-home care should not compromise their health and that of the community. The risk of infection can be lessened by teaching hygiene, supervising unregulated day-care facilities and regular antibiotic use so that bacterial resistance may be prevented.

Impact of child day care on infectious diseases in adults.

The authors review diseases that occur in day care centers and their impact on day care providers and parents. Acute infections of the gastrointestinal and respiratory tracts are the most commonly transmitted illnesses from children in day care centers to adults. The most important infections acquired by adults are those with the potential for significant clinical morbidity, such as hepatitis A, or those that generate concern, such as cytomegalovirus and parvovirus B19, because of their potential to produce congenital infections in pregnant women.

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.

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.

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.

Lack of toxicity from concomitant directly observed disulfiram and isoniazid-containing therapy for active tuberculosis.

We retrospectively evaluated the use of disulfiram among alcoholic patients being treated for active tuberculosis. There were 13 alcoholics treated with disulfiram, 105 alcoholics not on disulfiram, and 249 non-alcoholics. Rates of toxicity were higher among alcoholics than among non-alcoholics (58% vs. 32%), but there was no difference between alcoholics taking and those not taking disulfiram (61% vs. 57%). There were no neurological side effects in the disulfiram group. Disulfiram appeared to be safe when added to intermittent, directly observed isoniazid-containing tuberculosis treatment, and was useful in managing complications of alcohol abuse. However, the small number of patients on disulfiram limits the strength of this negative finding.

Results of testing for human immunodeficiency virus infection among recent contacts of infectious tuberculosis cases in the United States.

CONTEXT: Persons with recently acquired latent tuberculosis (TB) infection and human immunodeficiency virus (HIV) co-infection are at high risk of rapid progression to TB disease. OBJECTIVES: To determine the proportion of close contacts of infectious TB patients tested for HIV, and the results of HIV testing for this group. DESIGN, SETTING AND SUBJECTS: Review of health department records for all close contacts of 349 patients with culture-positive pulmonary TB aged 15 years or older reported from five study areas in the United States in 1996. MAIN OUTCOME MEASURES: Proportion of close contacts of TB patients tested for HIV, and rate of HIV infection among close contacts of TB patients. RESULTS: A total of 1169 close contacts were identified for 349 patients with active pulmonary TB. HIV test results were available for 224 (64%) TB patients and 220 (19%) close contacts. Of the TB patients tested, 164 (73%) were HIV-negative and 60 (27%) were HIV-positive. An equal proportion of close contacts of HIV-positive and -negative TB patients were tested (21% vs. 24%). Of the close contacts tested, 201 (91%) were HIV-negative and 19 (9%) were HIV-positive. Compared with close contacts of HIV-negative TB patients, close contacts of HIV-positive TB patients were more likely to be HIV-positive (53% vs. 2%; P < 0.01). This association was observed for contacts residing in the TB patient household (70% vs. none; P < 0.01), not residing in the TB patient household (20% vs. 4%; P < 0.05), 25-44 years of age (88% vs. 8%; P < 0.01), and > 44 years of age (22% vs. 2%; P < 0.05). CONCLUSIONS: HIV-positive TB patients and their close contacts may share some of the same risk factors for HIV infection. These findings suggest that the HIV status of the TB patient, in addition to established risk factors for HIV infection, may be an important consideration for prioritizing voluntary HIV counseling and testing efforts among close contacts of infectious TB patients.

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.

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.

Workplace contact investigations in the United States.

SETTING: Five state tuberculosis (TB) control programs in the United States. OBJECTIVES: To determine the prevalence of and treatment for latent TB infection (LTBI) among contacts of active TB cases identified in the workplace, and to describe TB control program policies for the initiation and conduct of workplace investigations. DESIGN: Retrospective review of health department records for all culture-positive pulmonary tuberculosis cases aged > or = 15 years reported in 1996, and their contacts. RESULTS: There were 349 cases of active TB, of whom 134 (38%) were employed. Workplace contact investigations were conducted for 42 cases, resulting in the identification of 724 contacts. The rate of LTBI was 29% overall, varying by worksite from a low of 16% to a high of 51%. LTBI estimates were higher for fully-screened contacts of smear-positive rather than of smear-negative index cases. However, fully-screened contacts of index patients with cavitary disease had lower LTBI estimates than those of index patients without cavitation. Treatment for LTBI was initiated in 45% of infected contacts. The five programs had somewhat variable policies regarding workplace contact investigations. Data on HIV co-infection and place of birth of contacts were largely missing. CONCLUSION: Factors contributing to LTBI among workplace contacts may include the presence of persons with pre-existing LTBI or a positive skin test as a result of BCG vaccination, clinical characteristics of the index case, and workplace environmental characteristics conducive to transmission. Standard guidelines for workplace investigations, written workplace investigation policies, and standard data collection practices are needed to better apportion the causes of observed infection rates in the workplace.