Dennis Kunimoto

Tuberculosis as a Primary Cause of Respiratory Failure Requiring Mechanical Ventilation

Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation (TBMV) is an uncommon occurrence. Over a 10 yr period in the province of Manitoba, Canada (population 1,091,942 in 1991), 13 patients with TBMV were identified. Non-drug-resistant M. tuberculosis was isolated from each case. The patients fell into two categories: miliary or disseminated tuberculosis (n = 7) and tuberculous pneumonia (n = 6); eight developed ARDS (adult respiratory distress syndrome) and another two probable ARDS. The hospital mortality for TBMV was compared with that for mechanically ventilated nontuberculous pneumonia and ARDS patients. Hospital mortality for patients with TBMV (69%, nine of 13) was significantly worse than hospital mortality for patients with nontuberculous pneumonia requiring mechanical ventilation (36%, 34 of 94; p < 0.025) and similar to the hospital mortality for patients with ARDS of any cause (56%, 15 of 27; p > 0.10). APACHE II scores for all groups of patients were similar. Compared with patients with tuberculous pneumonia, patients with miliary or disseminated tuberculosis were significantly more likely to develop TBMV (18.9 versus 0.8%, p < 0.0001). Despite the availability of effective antituberculous drugs, TBMV is often associated with ARDS and carries a similarly high mortality rate. Among patients with pulmonary tuberculosis, those with miliary or disseminated disease are especially prone to develop TBMV.

Pneumococcal Pneumonia: Potential for Diagnosis through a Urinary Metabolic Profile

Pneumonia, an infection of the lower respiratory tract, is caused by any of a number of different microbial organisms including bacteria, viruses, fungi, and parasites. Community-acquired pneumonia (CAP) causes a significant number of deaths worldwide, and is the sixth leading cause of death in the United States. However, the pathogen(s) responsible for CAP can be difficult to identify, often leading to delays in appropriate antimicrobial therapies. In the present study, we use nuclear magnetic resonance spectroscopy to quantitatively measure the profile of metabolites excreted in the urine of patients with pneumonia caused by Streptococcus pneumoniae and other microbes. We found that the urinary metabolomic profile for pneumococcal pneumonia was significantly different from the profiles for viral and other bacterial forms of pneumonia. These data demonstrate that urinary metabolomic profiles may be useful for the effective diagnosis of CAP.

Bacteriology of a Bear Bite Wound to a Human: Case Report

ABSTRACT Human contact with bears has become more frequent, as has the resultant bear maulings and bite injuries. We report the bacteriology of a patient bitten by a grizzly bear (Ursus arctos) from the Rocky Mountains foothills area east of Banff National Park, Alberta, Canada. The patient received field care, including metronidazole and cefazolin. Subsequent deep-wound cultures grew Serratia fonticola, Serratia marcescens, Aeromonas hydrophila, Bacillus cereus, and Enterococcus durans but no anaerobes.

Sputum isolation of Wangiella dermatitidis in patients with cystic fibrosis.

We report a case of invasive fungal pulmonary infection in a cystic fibrosis patient. Clinical deterioration coincided with isolation of Wangiella dermatitidis from her sputum, and treatment with amphotericin B followed by voriconazole resulted in clinical improvement and sterilization of the sputum. This case suggests that W. dermatitidis may be an etiologic agent of invasive pulmonary disease in the cystic fibrosis population.

An Unusual Case of Pulmonary Invasive Aspergillosis and Aspergilloma Cured with Voriconazole in a Patient with Cystic Fibrosis

The development of pulmonary aspergilloma and invasive aspergillosis is a rare complication of cystic fibrosis. We describe a 29-year-old patient with cystic fibrosis who had invasive pulmonary aspergillosis that was not cured by amphotericin B, liposomal amphotericin B, or itraconazole. This patient was subsequently successfully treated and cured with the novel antifungal agent voriconazole.

Severe Hepatotoxicity Associated with Rifampin-Pyrazinamide Preventative Therapy Requiring Transplantation in an Individual at Low Risk for Hepatotoxicity

We report a case of severe hepatotoxicity associated with rifampin-pyrazinamide preventative therapy that required liver transplantation in a closely monitored, human immunodeficiency virus-uninfected individual who had no risk for hepatotoxicity. Because hepatotoxicity associated with this treatment appears to be idiosyncratic, we recommend closer monitoring of liver enzyme levels than do the Centers for Disease Control and Prevention guidelines, as well as at least temporary interruption of treatment during any elevation of liver enzyme levels greater than the normal value.

IS1626, a new IS900-related Mycobacterium avium insertion sequence

An insertion sequence designated IS1626 was isolated and characterized from a Mycobacterium avium clinical strain. IS1626 was detected by high-stringency hybridization with the pMB22/S12 probe from IS900 of Mycobacterium paratuberculosis. IS1626 is 1418 bp in size and has a G+C content of 65 mol%. It has neither terminal inverted repeats nor flanking direct repeats. Analysis of three IS1626 insertion sites in the M. avium strain and the corresponding potential insertion sites in two IS1626-free M. avium strains indicated a consensus sequence of CATGCN(4-5)TCCTN(2)G for IS1626 insertion. In the three clones examined, IS1626 has the same orientation with respect to this target site. IS1626 has two major ORFs. ORF1179 encodes a predicted protein of 393 amino acids. ORF930, on the complementary strand of ORF1179, encodes a protein of 310 amino acids. The Shine-Dalgarno sequence for ORF930 is partially located in the flanking region, similar to other IS900-related elements. Analysis of the comparable features of insertion sequences and their variable occurrence in related organisms is useful for studying the evolution of these elements and their hosts.

The tuberculin skin test is unreliable in school children BCG-vaccinated in infancy and at low risk of tuberculosis infection.

Background: The tuberculin skin test (TST) is often used to screen for latent tuberculosis infection (LTBI) in school children, many of whom were bacille Calmette-Guérin (BCG)-vaccinated in infancy. The reliability of the TST in such children is unknown. Methods: TSTs performed in low-risk BCG-vaccinated and -nonvaccinated grade 1 and grade 6 First Nations (North American Indian) school children in the province of Alberta, Canada, were evaluated retrospectively. To further assess the specificity of the TST, BCG-vaccinated children with a positive TST (≥10 mm of induration) and no treatment of LTBI were administered a QuantiFERON-TB Gold In-Tube test (QFT-GIT, Cellestis International). Results: A total of 3996 children, 2063 (51.6%) BCG-vaccinated and 1933 (48.4%) BCG-nonvaccinated, were screened for LTBI. Vaccinated children were more likely than nonvaccinated children to be TST positive (5.7% vs. 0.2%, P < 0.001). Vaccinated children with a positive TST were more likely to have a recent past TST as compared with those with a negative TST (6.8% versus 2.8%, P = 0.01). Among 65 BCG-vaccinated TST-positive children who underwent a QFT-GIT, only 5 (7.7%; 95% CI: 2.5%, 17.0%) were QFT-GIT positive. A TST of ≥15 mm was more likely to be associated with a positive QFT-GIT than a TST of 10 to 14 mm, 16.0% (95% CI: 4.5%, 36.1%) versus 2.5% (95% CI: 0.1%, 13.2%), P = 0.047. Conclusion: The TST is unreliable in school children, BCG-vaccinated in infancy, and who are at low risk of infection. The QFT-GIT is a useful confirmatory test for LTBI in BCG-vaccinated TST-positive school children.

Relative versus absolute noncontagiousness of respiratory tuberculosis on treatment.

OBJECTIVE To assess the validity of current estimates of the noncontagiousness of sputum smear-positive respiratory tuberculosis (TB) on treatment. DESIGN A descriptive analysis of the mycobacteriologic response to treatment. SETTING A TB inpatient unit of a Canadian hospital. PATIENTS Thirty-two HIV-seronegative patients with moderate to advanced sputum smear-positive respiratory TB were treated with uninterrupted, directly observed, weight-adjusted isoniazid, rifampin, and pyrazinamide. Each patients initial isolate was drug susceptible and each patients sputum mycobacteriology was systematically followed until 3 consecutive sputum smears were negative on 3 separate days. RESULTS The time to smear conversion varied remarkably (range, 8 to 115 days; average, 46 days) and was influenced by sputum sampling frequency. Only 3 patients (9.4%) had smear conversions by 14 days and only 8 (25%) had smear conversions by 21 days, the average time it took for drug susceptibility test results to become available. During the first 21 days of treatment, the semiquantitative sputum smear score decreased rapidly and the time to detection of positive cultures doubled. Within the time to smear conversion, virtually all smear-positive specimens (98%) were culture positive and only 34% of the patients had culture conversions (ie, 3 consecutive negative cultures). CONCLUSION Current estimates of the noncontagiousness of sputum smear-positive respiratory TB on treatment (for 14 days, for 21 days, or until smear conversion) are estimates of relative noncontagiousness. They do not signal absolute noncontagiousness (culture conversion). Semiquantitative smear and time-to-detection data suggest that respiratory isolation beyond 21 days of optimal treatment should be selective.

Transmission of Mycobacterium tuberculosis Beijing Strains, Alberta, Canada, 1991–2007

Transmission of Beijing strains posed no more of a public health threat than did non-Beijing strains.