Mycobacteria and the new quinolones

Leysen, D. C.; Haemers, Achiel; Pattyn, S. R.

doi:10.1128/aac.33.1.1

Cited by 148 publications

(62 citation statements)

References 54 publications

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“…38,1994 on March 21, 2019 by guest http://aac.asm.org/ Downloaded from densities in excess of 108/ml, that is, to concentrations above the threshold frequency at which genetic mutations leading to drug resistance are probably likely to begin to occur. As can be seen in Table 3, the plateau effect was shown for several fluoroquinolone-isolate combinations, which is consistent with observations of bacterial resistance to this class of drugs (17,25).…”

Section: Discussionsupporting

confidence: 77%

A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions

Skinner

Furney

Jacobs

et al. 1994

Antimicrob Agents Chemother

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Even though the macrophage is the host cell for the intracellular bacterial parasite Mycobacterium avium, macrophages have undergone only limited evaluation as models for determining the capacities of antimycobacterial drugs to inhibit the growth of M. avium within this relevant intracellular environment. In the present study, we demonstrated that a panel of M. avium isolates could actively infect homogeneous monolayers of murine bone marrow-derived macrophages. A number of established and experimental antimycobacterial drugs were then added to these cultures at a range of concentrations, and their effects on the numbers of surviving bacilli were determined 8 days later. By plotting such numbers versus drug concentrations it was then possible to clearly distinguish between compounds with bactericidal activity (such as rifabutin and PD 125354) and those with bacteriostatic effects (such as clarithromycin), even though several of these compounds had very similar MICs. In addition, an estimate of the potential therapeutic efficiency of each drug could be made by determining the concentration needed to destroy an arbitrary percentage of the inoculum (in this case, the bactericidal concentration destroying 99%o of the inoculum). Such values were considerably in excess of the MICs and may more realistically reflect the concentrations in serum required to electively reduce the bacterial burden in vivo.

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Section: Discussionsupporting

confidence: 77%

A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions

Skinner

Furney

Jacobs

et al. 1994

Antimicrob Agents Chemother

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“…Mycobacteria are naturally less susceptible to quinolones than other bacteria (Wolfson & Hooper, 1989 I. GUILLEMIN and OTHERS quinolone susceptibility patterns (Leysen et al, 1989 ;Yew et al, 1994). Indeed, we have shown previously that several mycobacterial species, such as Mycobacterium fortuitum and M. peregrinum, are less susceptible to quinolones than Escherichia coli, but are more susceptible to these drugs than other mycobacterial species such as M. smegmatis and M. tuberculosis (Guillemin et al, 1995(Guillemin et al, , 1998.…”

Section: Abbreviation : Qrdr Quinolone-resistance-determining Regionsmentioning

confidence: 99%

Purification and inhibition by quinolones of DNA gyrases from Mycobacterium avium, Mycobacterium smegmatis and Mycobacterium fortuitum bv. peregrinum

et al. 1999

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The DNA gyrases from Mycobacterium avium, Mycobacterium smegmatis and Mycobacterium fortuitum bv. peregrinum, which are species naturally resistant, moderately susceptible and susceptible to fluoroquinolones, respectively, were purified by affinity chromatography on novobiocinSepharose columns. The DNA gyrase inhibiting activities (IC 50 values) of classical quinolones and fluoroquinolones were determined from the purified enzymes and were compared to the corresponding antibacterial activities (MICs). Regarding M. fortuitum bv. peregrinum, which is nearly as susceptible as Escherichia coli, the corresponding MIC and IC 50 values of quinolones were significantly lower than those found for M. avium and M. smegmatis (e.g. for ofloxacin, MICs of 025 versus 32 and 1 µg ml N1 , and IC 50 values of 1 versus 8 and 6 µg ml N1 , respectively). Such a result could be related to the presence of Ser-83 in the quinolone-resistance-determining region of the gyrase A subunit of M. fortuitum bv. peregrinum, as found in wild-type E. coli, instead of Ala-83 in M. avium and M. smegmatis , as found in fluoroquinolone-resistant E. coli mutants. The IC 50 values of quinolones against the M. avium and M. smegmatis DNA gyrases were similar, while the corresponding MICs were 32-fold higher for M. avium when compared to M. smegmatis , suggesting that an additional mechanism, such as a low cell wall permeability or a drug efflux, could contribute to the low antibacterial potency of quinolones against M. avium.

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“…There could be scope further improve survival by better management of comorbid conditions and by improving the general health of the patient. It may be that macrolides and/or quinolones, which, during the period of this study, were found to have in vitro activity against opportunist mycobacteria [14][15][16][17][18], will result in better cure rates when added to rifampicin and ethambutol. The British Thoracic Society9s ongoing multicentre trial should answer this question by the end of 2004.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary disease caused byM. malmoensein HIV negative patients: 5‐yr follow-up of patients receiving standardised treatment

2003

Eur Respir J

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Pulmonary disease caused by M. malmoense in HIV negative patients:5-yr follow-up of patients receiving standardised treatment When two positive cultures were confirmed by the Mycobacterium Reference Units for England, Wales, Scotland or Scandinavia, the coordinating physician invited the patient9s physician to enrol the patient, who was then treated on a random basis with either rifampicin plus ethambutol or rifampicin, ethambutol and isoniazid for 2 yrs. Clinical, bacteriological and radiological progress were monitored at set intervals for 5 yrs.In over 5 yrs a total of 106 patients were recruited to the study. The mean age was 58 yrs, range 24-89 yrs. A total of 58% were male and just over half previously or at the time of the study had other lung diseases. Sputum was positive on direct smear in 58%. Cavitation was seen on the chest radiographs of 74%, the majority having cavities of o2 cm in diameter. Less than half of the patients showed bilateral disease, 26% having involvement of more than three lung zones. Disease was confined to the upper zone(s) in 30%. Other lung diseases were evident in 52%. Although clinical response was judged satisfactory at most reviews (90%), one in three patients died within 5 yrs andv5% were thought to have died primarily because of M. malmoense. There were three failures of treatment and eight relapses after the end of treatment. There was no correlation between failure of treatment/relapse and in vitro resistance. A total of 63 (59%) of patients were alive at 5 yrs, of whom 44 (42% of the total entry) were known to be cured.Pulmonary disease caused by Mycobacterium malmoense is a serious condition that is associated with high morbidity and mortality. The results of standard susceptibility tests do not correlate with the bacteriological response of the disease to chemotherapy. Rifampicin and ethambutol, with or without isoniazid, cured only 42% of patients but were better tolerated than previously described, more complex regimens of equal or lesser efficacy. There is a need for more effective regimens that will reduce mortality and failure of treatment/relapse rates, but, in addition, attention should be directed at improving management of comorbid conditions and improving the general health of the patient.

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Mycobacteria and the new quinolones

Cited by 148 publications

References 54 publications

A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions

A bone marrow-derived murine macrophage model for evaluating efficacy of antimycobacterial drugs under relevant physiological conditions

Purification and inhibition by quinolones of DNA gyrases from Mycobacterium avium, Mycobacterium smegmatis and Mycobacterium fortuitum bv. peregrinum

Pulmonary disease caused byM. malmoensein HIV negative patients: 5‐yr follow-up of patients receiving standardised treatment

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