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Biomedical subjects

S E Hoffner

Publications and source records attributed to S E Hoffner.

At least 55 records · Page 3Linked to original sources

A biphasic system for primary isolation of mycobacteria compared to solid medium and broth culture.

A biphasic culture system, the MB Check, was compared with conventional culture on Löwenstein-Jensen egg (LJ) solid medium and with Bactec broth culture for primary isolation of mycobacteria from clinical samples. A total of 104 mycobacterial isolates was detected from 985 samples examined by the three methods. The most sensitive primary isolation was with LJ culture and MB Check; these methods detected 93% and 87% of all positive cultures, respectively. MB Check allowed a somewhat more rapid detection than LJ culture. The presence of atypical mycobacteria was demonstrated most rapidly with the Bactec system.

Bacteriological Techniques↗

Human immunodeficiency virus type 1 enhances intracellular growth of Mycobacterium avium in human macrophages.

Disseminated Mycobacterium avium infections are common in patients with AIDS and result in a reduced life expectancy. Human monocytes/macrophages are important target cells for both human immunodeficiency virus (HIV) and M. avium. We have studied the interaction in vitro of M. avium and HIV type 1 (HIV-1) in human macrophages. Human monocytes isolated from the peripheral blood of healthy individuals were infected with HIV-1, M. avium, or both. The intracellular growth of M. avium and the replication of HIV-1 were monitored for up to 5 weeks. Intracellular mycobacterial growth was seen in all M. avium infected cell cultures and was paralleled by increased production of interleukin 1 alpha and beta. Preinfection of the macrophages with HIV-1 reduced the interleukin 1 production and accelerated the intracellular growth of M. avium. These findings may explain in part the impaired control of mycobacterial infections seen with patients with AIDS.

Cells, Cultured↗

Mycobacterium malmoense: an easily missed pathogen.

The BACTEC system (Becton Dickinson, Sparks, Md.) was compared with culture on Löwenstein-Jensen egg medium for the detection of Mycobacterium malmoense in lymph node samples from children with lymphadenitis. It was found to be significantly more sensitive and rapid. The use of the BACTEC system is thus recommended as a complement to culture on solid media for the primary isolation of atypical mycobacteria, such as M. malmoense.

Bacteriological Techniques↗

Susceptibility of mycobacteria to fusidic acid.

Fusidic acid was shown to be effective in vitro against 30 clinical isolates of Mycobacterium tuberculosis at concentrations of 32-64 mg/l, concentrations which are readily achieved in serum. All but one of 17 Mycobacterium avium complex strains were resistant to fusidic acid at concentrations up to 64 mg/l. However, synergistic effects were shown for 11 of the 17 strains when fusidic acid was combined with ethambutol. Five of the strains were fully susceptible to the combination of fusidic acid (64 mg/l) and ethambutol (4 mg/l). It is suggested that fusidic acid should be evaluated clinically as a potential supplementary drug for treatment of mycobacterial infections.

Drug Resistance, Microbial↗

Microcalorimetric studies of the initial interaction between antimycobacterial drugs and Mycobacterium avium.

To further our understanding of the mechanisms by which ethambutol potentiates the effect of other antimycobacterial drugs on mycobacteria we have studied the initial physico-chemical interaction between ethambutol and the Mycobacterium avium cell envelope using batch reaction microcalorimetry. When strains of M. avium were exposed to ethambutol an immediate endothermic reaction was recorded. When the M. avium cells were pre-treated with ethambutol this strongly affected the initial interaction between streptomycin and the bacterial cell surface. When the M. avium cells were simultaneously exposed to a combination of ethambutol and streptomycin an altered initial interaction with streptomycin was seen. These data suggest that ethambutol may potentiate the effect of other antibacterial drugs on M. avium by increasing cell wall permeability.

Antitubercular Agents↗

Serovars of Mycobacterium avium complex isolated from patients in Sweden.

The serovars of clinical isolates of Mycobacterium avium complex from 24 acquired immunodeficiency syndrome (AIDS) and 140 non-AIDS patients in Sweden were studied by using type-specific antisera. A wide distribution of serovars was seen. Serovar 6 was predominant in both groups of patients, isolated from 33 and 16% of the AIDS and non-AIDS patients, respectively. The results indicate geographical as well as disease-related differences in the distribution of M. avium complex serovars of clinical importance.

Acquired Immunodeficiency Syndrome↗

Tenosynovitis of the hand caused by Mycobacterium terrae.

Flexor tendon synovitis caused by Mycobacterium terrae resulted in considerable permanent functional impairment of the hand in six patients. Initial symptoms were subtle and uncharacteristic. Cortisone injections aggravated the condition. Surgical treatment including synovectomy was combined with antimycobacterial chemotherapy. Early diagnosis obtained by culture of synovial biopsy material to detect mycobacteria may result in an improved outcome in chronic synovitis.

Adult↗

In-vitro synergistic activity between ethambutol and fluorinated quinolones against Mycobacterium avium complex.

Ciprofloxacin, ofloxacin and norfloxacin were ineffective at clinically relevant concentrations against the Mycobacterium avium complex (MAC) in vitro as measured by radiometric respirometry. Only two of 30 clinical isolates of MAC were susceptible to any of the tested quinolones. By contrast good antibacterial activity was obtained when any of the quinolones was combined with ethambutol. The synergistic effect was most pronounced for the combination of ethambutol and ciprofloxacin, to which 76 of 100 strains were susceptible. It is suggested that the synergism is based on an enhanced penetration of the quinolones by ethambutol.

Anti-Infective Agents↗

Studies on the mechanisms of the synergistic effects of ethambutol and other antibacterial drugs on Mycobacterium avium complex.

Synergistic effects of combinations of anti-mycobacterial drugs on Mycobacterium avium complex (MAC) in vitro was studied by radiometric respirometry. Pronounced synergy was seen for several drug combinations where ethambutol was found to be the key drug in the synergistic potentiation. Microcalorimetric studies show that a very rapid physico-chemical interaction occurs between the cell-surface of MAC and ethambutol. When MAC cells were pretreated with ethambutol and then subjected to streptomycin the thermal response significantly differed from that seen with MAC cells which had not been pretreated. The typical thermal effects of the interaction of ethambutol with live and UV-killed MAC cells was not seen with heat-killed MAC cells. It is proposed that specific cell-surface protein(s) act as receptors in the initial interaction with ethambutol.

Anti-Bacterial Agents↗

Susceptibility of streptomycin-resistant Mycobacterium tuberculosis strains to amikacin.

A total of 585 Mycobacterium tuberculosis strains isolated during a three-year period in Sweden were tested for in vitro susceptibility to amikacin in comparison with streptomycin. Resistance to streptomycin was seen in 27 of the isolates (4.6%). These isolates had been obtained from 22 patients, a majority of which were non-European immigrants. All but one of the streptomycin-resistant isolates were susceptible to amikacin. None of 263 streptomycin-susceptible isolates tested was resistant to amikacin. Amikacin appears to be an alternative to streptomycin in the treatment of patients with streptomycin-resistant Mycobacterium tuberculosis.

Adolescent↗

Improved detection of Mycobacterium avium complex with the Bactec radiometric system.

A reconsideration of the laboratory methods used for primary isolation of mycobacteria other than Mycobacterium tuberculosis is needed due to the increasingly recognized importance of such mycobacterial infections in immunocompromised patients. One example of this is the severe opportunistic infections caused by Mycobacterium avium complex among AIDS patients. In this study, the Bactec radiometric system was compared to conventional culture on solid medium for the detection of M. avium complex in 3,612 selected clinical specimens, mainly of extrapulmonary origin. Of a total number of 63 M. avium complex isolates, the Bactec system detected 58 (92%), compared to 37 (59%) for conventional culture. A much more rapid detection was attained with radiometric technique than with conventional culture. The mean detection time for the cultures positive with both methods was 7.1 and 28.3 days, respectively. The Bactec radiometric system achieves a rapid and significantly more sensitive detection and seems to be an excellent complement to conventional culture in the laboratory diagnosis of infections with the M. avium complex.

Bacteriological Techniques↗

Rapid susceptibility testing of Mycobacterium tuberculosis by bioluminescence assay of mycobacterial ATP.

Mycobacterial growth was monitored by bioluminescence assay of mycobacterial ATP. Cultures of Mycobacterium tuberculosis H37Rv and of 25 clinical isolates of the same species were exposed to serial dilutions of ethambutol, isoniazid, rifampin, and streptomycin. A suppression of ATP, indicating growth inhibition, occurred for susceptible but not resistant strains within 5 to 7 days of incubation. Breakpoint concentrations between susceptibility and resistance were determined by comparing these results with those obtained by reference techniques. Full agreement was found in 99% of the assays with the resistance ratio method on Lowenstein-Jensen medium, and 98% of the assays were in full agreement with the radiometric system (BACTEC). A main advantage of the bioluminescence method is its rapidity, with results available as fast as with the radiometric system but at a lower cost and without the need for radioactive culture medium. The method provides kinetic data concerning drug effects within available in vivo drug concentrations and has great potential for both rapid routine susceptibility testing and research applications in studies of drug effects on mycobacteria.

Adenosine Triphosphate↗