Biomedical subjects
Publications and source records attributed to S E Hoffner.
Mycobacterium tuberculosis isolates from 84 patients with pulmonary tuberculosis in Honduras were characterized by restriction fragment length polymorphism analysis. Seventy-three different IS6110 patterns were found; 63 of these were unique and 10 were shared by two to three strains each. Thus, no ongoing spread of any specific clone of bacteria could be demonstrated.
BACKGROUND: Tuberculosis is a major health problem in Central America. In Honduras, with an incidence rate of 81/100,000, it is an increasingly common cause of morbidity and hospitalization. This study was conducted to examine drug-resistant tuberculosis and prevalence of infection with atypical mycobacteria in Honduran patients with suspected pulmonary tuberculosis. METHODS: Pulmonary specimens from 235 Honduran patients with suspected tuberculosis were examined by acid-fast smears and culture. The 95 mycobacterial strains isolated were identified to species level and drug susceptibility tests were carried out. Resistant Mycobacterium tuberculosis strains were tested for susceptibility to six additional drugs. Their possible relationship was studied by DNA restriction fragment length polymorphism. RESULTS: Drug-resistant strains were found in 13 of 85 culture-verified tuberculosis patients, including 10 with isolates of multidrug-resistant bacteria. Seven of the patients with multidrug-resistant tuberculosis had smear-positive disease. Nine of them had a history of specific therapy. Two patients with drug-resistant disease were shown to be infected by identical strains. Only one of 11 HIV-positive patients had drug-resistant tuberculosis. Most resistant strains were susceptible to ciprofloxacin, amikacin, kanamycin, and pyrazinamide. Atypical mycobacteria were isolated from 10 patients with suspected tuberculosis. Seven of them were receiving antituberculosis chemotherapy and five had smear-positive samples. CONCLUSIONS: These results illustrate the importance of mycobacterial culture and subsequent species identification and in vitro susceptibility testing for identification of patients with drug-susceptible or drug-resistant tuberculosis and those infected or colonized with other mycobacteria.
Records of patients have been retrospectively examined studied during an 11-y period, from whom Mycobacterium fortuitum or M. chelonae was isolated in Sweden. Respiratory isolates were obtained from 71 patients. Clinical information was accessible in 52, chest X-ray was pathological in 51, and 42 had underlying diseases. Four skin and 4 urine isolates were observed. Two cases of osteitis and 2 bone marrow isolates of M. chelonae were found. One girl had a submandibular lymph node abscess with M. fortuitum. Of 2 HIV patients, 1 had positive blood cultures with M. fortuitum and the other positive sputum culture with M. chelonae. The broad spectrum of infections with M. fortuitum complex necessitates an integrated judgement of clinical and bacteriological data to determine the relevance of such isolates.
SETTING: There is a need for more sensitive and rapid methods for laboratory confirmation in the diagnosis of tuberculosis. OBJECTIVE: To investigate the applicability of a target rRNA amplified test system (AMTDT, Gen-Probe, CA) for rapid detection of Mycobacterium tuberculosis. DESIGN: The rRNA amplified test system was compared to standard methods for acid fast microscopy and mycobacterial culture for the demonstration of M. tuberculosis in sputum samples from 247 patients in Guinea Bissau with suspected tuberculosis. RESULTS: The highest incidence of positive samples was obtained with the AMTDT test. Out of 274 sputum samples 96 (35%) were positive by the AMTDT test, 82 (30%) were positive by culture and 38 (14%) by direct microscopy. Using culture as reference method the sensitivity of the test was 85% (after discrepancy analysis 87%), and the specificity was 86% (after discrepancy analysis 93%). CONCLUSION: The sensitivity and specificity of the AMTDT test used in this setting indicates that it may be a valuable complement for improving the laboratory diagnosis of tuberculosis.
A target amplified test system (AMTDT, Gen-Probe, San Diego, California, USA) was compared with conventional standard methods in the detection of Mycobacterium tuberculosis in sputum and other respiratory specimens from patients with suspected tuberculosis. The highest incidence of positive samples was seen with the AMTDT test. Out of 450 samples from patients with known or suspected tuberculosis, 43 (9.6%) were positive by culture, and 47 (10.4%) with AMTDT. After discrepancy analysis, 7 of the culture-negative but AMTDT-positive samples were judged to be true positive, giving the AMTDT a sensitivity of 92.0% and a specificity of 99.8%. The AMTDT test was rapid, easy to perform, sensitive, and highly specific.
Clarithromycin and rifabutin are among the most promising drugs for the therapy of infections caused by Mycobacterium avium or other atypical mycobacteria. Since synergism of combined drugs is important in order to achieve strong antimycobacterial activity, the combined inhibitory effects of antibacterial agents should also be investigated when agents are evaluated for possible use in antimycobacterial drug therapy. In the present study we examined the antimycobacterial activity of clarithromycin, rifabutin, and their combination against 51 clinical isolates of the M. avium complex from patients with acquired immune deficiency syndrome (AIDS) with disseminated mycobacteriosis. A concentration-dependent inhibition was seen for each drug. The antibacterial effect was significantly more pronounced for the combined drugs than for the agents tested separately. Synergism, against up to 88% of the strains tested, was seen for the tested drugs combined at different concentrations. All 51 M. avium strains were susceptible to the combination of 4 mg/l clarithromycin and 2 mg/l rifabutin.
Forty-nine isolates of Mycobacterium bovis from humans and animals in Sweden were analyzed by restriction fragment length polymorphism (RFLP) patterns probed by the insertion element IS6110. Most isolates had patterns indicating the presence of only one or two genomic copies of the IS6110 insertion element. This simple type of pattern was found in all human isolates. In contrast, isolates from M. bovis infections in five herds of farmed deer in Sweden showed a specific RFLP pattern with seven bands, indicating seven copies of the IS6110 sequence. In 1958, Sweden was declared free from M. bovis in cattle. However, in 1987, M. bovis was reintroduced with imported farmed deer, and since 1991, 11 outbreaks in deer herds, but not in other livestock or wildlife, have been diagnosed. Continued RFLP studies of the new Swedish M. bovis isolates can reveal possible transmission of this deer strain to other animals or humans.
Drug-resistant tuberculosis is a threat not only to the estimated 50 million people in the world carrying resistant strains, but also to the success of national TB control programmes. In Sweden, multidrug-resistant (MDR) tuberculosis comprises around 1% of the isolated strains. Isoniazid resistance is found in 7% of strains and resistance to other drugs in < 3%. Of patients with resistant TB 70% are born outside Scandinavia. Preliminary data from Estonia show that close to 20% of the strains are resistant to each of the drugs isoniazid, rifampicin and streptomycin. MDR is seen in around 16%. In a study in Ethiopia isoniazid resistance was found in 46% and MDR in 11% among treatment failures and relapse cases.
Pulmonary mycobacteriosis is usually caused by Mycobacterium tuberculosis or Mycobacterium avium complex. There are, however, other slow-growing mycobacteria that can cause pulmonary infection. Mycobacterium kansasii, Mycobacterium malmoense, Mycobacterium xenopi, Mycobacterium szulgai and Mycobacterium simiae typically infect middle-aged to elderly persons with preexisting lung disease. Differentiation of infection with these five mycobacteria from infection with Mycobacterium tuberculosis, by culture and determination of the antimicrobial susceptibility pattern of the organism are important for several reasons. All five organisms are found in water and soil. They probably infect humans from environmental habitats; human-to-human spread of infection is thought not to occur. Furthermore, isolation of the organisms in culture may represent contamination of the specimen or colonization of the patient, and not necessarily an infection. Finally, although the antituberculosis drugs-isoniazid, ethambutol, rifampin and streptomycin-have been used for treatment of infection with these five organisms, there are often differences between the antimycobacterial susceptibility patterns of Mycobacterium tuberculosis and those of the non-tuberculous mycobacteria. Thus, the optimal choice of drug therapy may differ from that used for tuberculosis.
Mycobacterium malmoense was first described in 1977 and today is second only to the Mycobacterium avium complex as a cause of atypical mycobacterial infection in Sweden. We retrospectively studied the records of 221 patients from whom M. malmoense was isolated during 1968-1989. M. malmoense was recovered from the respiratory tract of 171 patients (170 adults and one child) and from cervical lymph nodes of 36 patients (35 children and one adult). In addition, the organism was isolated from the urine of six patients, one of whom had disseminated disease and two of whom had abscesses caused by M. malmoense. A majority of the patients with pulmonary infection as well as the patient with disseminated disease had other underlying diseases.
Etest is a new concept for MIC determinations for antimicrobial agents that is based on a predefined antibiotic gradient on a plastic strip calibrated with a continuous logarithmic MIC scale covering 15 twofold dilutions. Etest was compared with a reference agar dilution method for susceptibility testing of clinical isolates of Mycobacterium chelonae and M. fortuitum. Results read after 3 days showed good agreement between MICs obtained with Etest and those obtained with the reference method within +/- 2 dilutions for 90% of all test combinations. All but one of the strains were inhibited by low concentrations of ciprofloxacin or amikacin. Susceptibility to clarithromycin, erythromycin, imipenem, rifampin, doxycycline, and fusidic acid was variable, and all strains were resistant to ceftazidime and trimethoprim. The results suggest that Etest is well suited for studies of drug resistance in rapidly growing mycobacteria.
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Isolates of Mycobacterium avium complex from five patients on longterm (3-5 yrs) anti-mycobacterial drug treatment were collected during the early and late phase of disease, and studied in vitro for their susceptibility to anti-mycobacterial drugs and drug-combinations. All isolates were resistant or moderately resistant to ethambutol, rifampicin and streptomycin when given singly; however, all strains isolated early in the disease were susceptible to the combination of ethambutol with either rifampicin or streptomycin. All late isolates had developed resistance to one or both of these combinations. Three of the patients died within a year after the last isolation of M. avium complex, and the two remaining patients still have severe chronic disease. It is concluded that the susceptibility of M. avium strains to combinations of drugs should be monitored during the course of treatment, in order to guide the selection of effective drug-combinations throughout the infection.
Sputum samples from patients with known or suspected tuberculosis were collected in Bissau, Guinea Bissau, and isolates belonging to the Mycobacterium tuberculosis complex (M. tuberculosis, M. bovis or M. africanum) were examined for their susceptibility to the 4 drugs streptomycin, isoniazid, ethambutol and rifampicin. Of 59 M. tuberculosis complex isolates only 2 were resistant to any of the drugs (isoniazid). Thus there is little resistance to these first line drugs among M. tuberculosis isolates from patients in Guinea Bissau.
Mycobacterium malmoense is an opportunistic pathogen with increasingly recognized clinical importance. It is mainly isolated in northern Europe and Great Britain, most often from patients with pulmonary infections. Conventional therapy of M. malmoense infections with antituberculosis drugs is often of limited value, and there is thus a need for improved drug regimens. The potential efficacies of new alternative drugs, such as quinolones, macrolides, amikacin, and rifabutin, are still unknown, and so is the pathogen's in vitro susceptibility to most of these drugs. In this study, we used the BACTEC system for determining the pattern of resistance of clinical M. malmoense isolates to a number of antibacterial drugs as well as their possible synergistic interactions when each of them was combined with ethambutol. The majority of the strains were resistant or moderately resistant to the drug when it was tested alone at selected concentrations. However, pronounced in vitro synergism was demonstrated for combinations of ethambutol with ciprofloxacin, amikacin, and rifampin, rendering most isolates susceptible to the combined drugs. Thus, for in vitro susceptibility testing of M. malmoense, examination of the possible synergistic effects of combined drugs also can be recommended.
Fifty-six strains of the Mycobacterium tuberculosis complex from patients in Guinea-Bissau were examined by using four biochemical tests (niacin production, nitrate reductase, pyrazinamidase, and resistance to thiophen-2-carboxylic acid hydrazide). The isolates were divided into five different biovars within a spectrum ranging from classical human M. tuberculosis to classical M. bovis.
The susceptibility of Mycobacterium kansasii to antibacterial agents alone and in combination was studied. Widespread resistance to ethambutol, ciprofloxacin and isoniazid was found when these drugs were tested separately. However, pronounced antibacterial effects were seen when ethambutol was tested in combination with ciprofloxacin, rifampicin or rifabutin, which corresponded to significantly decreased resistance to these drugs in combination.
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