scholarly journals Sterilizing Activities of Fluoroquinolones against Rifampin-Tolerant Populations of Mycobacterium tuberculosis

2003 ◽  
Vol 47 (2) ◽  
pp. 653-657 ◽  
Author(s):  
Yanmin Hu ◽  
Anthony R. M. Coates ◽  
Denis A. Mitchison
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bactericidal Activity ◽  
Clinical Studies ◽  
Fresh Medium ◽  
Detectable Activity ◽  
Bactericidal Activities ◽  
Serial Dilutions

ABSTRACT The bactericidal activities of ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin were tested in three models of rifampin-tolerant Mycobacterium tuberculosis persisters. Model 1 was a 100-day-old, unshaken, anaerobically adapted culture in which serial dilutions of the quinolones were incubated for 5 days and CFU counts were then done In models 2 and 3, 100 mg of rifampin/liter was added to the 100-day culture for 5 or 7 days to produce tolerant organisms that did not grow on plates; the rifampin was then washed off, fresh medium was added to allow recovery of growth on plates, and the culture was incubated for 7 days before CFU counts. In model 2, the quinolones were added after rifampin had been washed off, whereas in model 3 the quinolones were added to the cultures containing rifampin. In models 1 and 2, ciprofloxacin had the least bactericidal activity, ofloxacin and levofloxacin had greater activities, and moxifloxacin and gatifloxacin had the greatest activities. In model 3, ofloxacin had no detectable activity whereas moxifloxacin killed about log10 0.279 CFU of the persisters per ml at concentrations attainable in lesions; isoniazid had virtually no activity. These findings predict that ofloxacin will not be found to have effective sterilizing activity in clinical studies now planned whereas moxifloxacin will be able to shorten treatment.

scholarly journals Bactericidal Action of Gatifloxacin, Rifampin, and Isoniazid on Logarithmic- and Stationary-Phase Cultures of Mycobacterium tuberculosis

2005 ◽  
Vol 49 (2) ◽  
pp. 627-631 ◽  
Author(s):  
C. N. Paramasivan ◽  
S. Sulochana ◽  
G. Kubendiran ◽  
P. Venkatesan ◽  
D. A. Mitchison
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Stationary Phase ◽  
Bactericidal Activity ◽  
Bactericidal Action ◽  
Duration Of Treatment ◽  
Stationary Phase Culture ◽  
Treatment Regimens ◽  
Phase Culture ◽  
Bactericidal Activities ◽  
Strain H37rv

ABSTRACT The bactericidal activity of gatifloxacin, alone and in combination with isoniazid and rifampin, was studied on both exponential- and stationary-phase cultures of Mycobacterium tuberculosis strain H37Rv. On log-phase cultures, the bactericidal activity of gatifloxacin at 4 μg/ml was rapid and was very similar to that of isoniazid. At concentrations of 0.25 and 4 μg/ml, gatifloxacin enhanced the activity of isoniazid. Killing of the stationary-phase culture was biphasic. During the first 2 days, gatifloxacin at 4 μg/ml slightly increased the limited bactericidal activities of isoniazid and rifampin. However, no further additional bactericidal activity was found during further incubation with isoniazid alone or when gatifloxacin was added to either isoniazid or rifampin. This suggested that the stationary-phase culture contained a mixture of occasionally dividing bacilli that were killed during the first 2 days and true static persisters in the residual population that mimicked those in human lesions. In view of the failure of gatifloxacin to add to the sterilizing activity of isoniazid or rifampin during days 2 to 6 of exposure in the stationary-phase culture, it is unlikely to be a sterilizing drug that can be used to shorten the duration of treatment appreciably when it is added to present treatment regimens.

scholarly journals Early Bactericidal Activity of Moxifloxacin in Treatment of Pulmonary Tuberculosis: a Prospective, Randomized Study

2004 ◽  
Vol 48 (3) ◽  
pp. 780-782 ◽  
Author(s):  
Mathias W. R. Pletz ◽  
Andres De Roux ◽  
Andreas Roth ◽  
Karl-Heinz Neumann ◽  
Harald Mauch ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Bactericidal Activity ◽  
Randomized Study ◽  
Prospective Randomized Study ◽  
Bactericidal Activities

ABSTRACT Moxifloxacin is the most active fluoroquinolone against Mycobacterium tuberculosis in vitro. However, data about the efficacy in patients are not available. We enrolled 17 patients with tuberculosis in a prospective, randomized study. After 5 days of monotherapy with either moxifloxacin or isoniazid, we detected significant decreases in mean CFU per milliliter in sputum in both groups. The calculated early bactericidal activities for isoniazid and moxifloxacin were 0.209 and 0.273 log10 CFU per ml of sputum per day, respectively. According to the data from our study, moxifloxacin exhibits an early bactericidal activity that is comparable to that of isoniazid.

scholarly journals Bactericidal Activities of the Pyrrole Derivative BM212 against Multidrug-Resistant and Intramacrophagic Mycobacterium tuberculosis Strains

1998 ◽  
Vol 42 (11) ◽  
pp. 3035-3037 ◽  
Author(s):  
Delia Deidda ◽  
Giorgio Lampis ◽  
Rossella Fioravanti ◽  
Mariangela Biava ◽  
Giulio Cesare Porretta ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cell Line ◽  
Bactericidal Activity ◽  
Inhibitory Activity ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Lymphoma Cell Line ◽  
Pyrrole Derivative ◽  
Histiocytic Lymphoma ◽  
Bactericidal Activities

ABSTRACT The pyrrole derivative BM212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)methyl-pyrrole] was shown to possess strong inhibitory activity against bothMycobacterium tuberculosis and some nontuberculosis mycobacteria. BM212 was inhibitory to drug-resistant mycobacteria and also exerted bactericidal activity against intracellular bacilli residing in the U937 human histiocytic lymphoma cell line.

scholarly journals Acylation of SC4 dodecapeptide increases bactericidal potency against Gram-positive bacteria, including drug-resistant strains

2004 ◽  
Vol 378 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Nathan A. LOCKWOOD ◽  
Judith R. HASEMAN ◽  
Matthew V. TIRRELL ◽  
Kevin H. MAYO
Keyword(s):  
Fatty Acid ◽  
Fluorescence Spectroscopy ◽  
Bactericidal Activity ◽  
Bacterial Cell ◽  
Membrane Surface ◽  
Peptide Amphiphiles ◽  
Helical Conformation ◽  
Gram Positive ◽  
Bacterial Membranes ◽  
Bactericidal Activities

We have conjugated dodecyl and octadecyl fatty acids to the N-terminus of SC4, a potently bactericidal, helix-forming peptide 12-mer (KLFKRHLKWKII), and examined the bactericidal activities of the resultant SC4 ‘peptide-amphiphile’ molecules. SC4 peptide-amphiphiles showed up to a 30-fold increase in bactericidal activity against Gram-positive strains (Staphylococcus aureus, Streptococcus pyogenes and Bacillus anthracis), including S. aureus strains resistant to conventional antibiotics, but little or no increase in bactericidal activity against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fatty acid conjugation improved endotoxin (lipopolysaccharide) neutralization by 3- to 6-fold. Although acylation somewhat increased lysis of human erythrocytes, it did not increase lysis of endothelial cells, and the haemolytic effects occurred at concentrations 10- to 100-fold higher than those required for bacterial cell lysis. For insight into the mechanism of action of SC4 peptide-amphiphiles, CD, NMR and fluorescence spectroscopy studies were performed in micelle and liposome models of eukaryotic and bacterial cell membranes. CD indicated that SC4 peptide-amphiphiles had the strongest helical tendencies in liposomes mimicking bacterial membranes, and strong membrane integration of the SC4 peptide-amphiphiles was observed using tryptophan fluorescence spectroscopy under these conditions; results that correlated with the increased bactericidal activities of SC4 peptide-amphiphiles. NMR structural analysis in micelles demonstrated that the two-thirds of the peptide closest to the fatty acid tail exhibited a helical conformation, with the positively-charged side of the amphipathic helix interacting more with the model membrane surface. These results indicate that conjugation of a fatty acid chain to the SC4 peptide enhances membrane interactions, stabilizes helical structure in the membrane-bound state and increases bactericidal potency.

scholarly journals Activity of Medicinal Plant Extracts on Multiplication ofMycobacterium tuberculosisunder Reduced Oxygen Conditions Using Intracellular and Axenic Assays

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Purva D. Bhatter ◽  
Pooja D. Gupta ◽  
Tannaz J. Birdi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Medicinal Plant ◽  
Plant Extracts ◽  
Bactericidal Activity ◽  
Piper Nigrum ◽  
Ocimum Sanctum ◽  
Acorus Calamus ◽  
Anaerobic Conditions ◽  
Bacterial Killing ◽  
Medicinal Plant Extracts

Aim.Test the activity of selected medicinal plant extracts on multiplication ofMycobacterium tuberculosisunder reduced oxygen concentration which represents nonreplicating conditions.Material and Methods.Acetone, ethanol and aqueous extracts of the plantsAcorus calamusL. (rhizome),Ocimum sanctumL. (leaf),Piper nigrumL. (seed), andPueraria tuberosaDC. (tuber) were tested onMycobacterium tuberculosisH37Rv intracellularly using an epithelial cell (A549) infection model. The extracts found to be active intracellularly were further studied axenically under reducing oxygen concentrations.Results and Conclusions.Intracellular multiplication was inhibited ≥60% by five of the twelve extracts. Amongst these 5 extracts, in axenic culture,P. nigrum(acetone) was active under aerobic, microaerophilic, and anaerobic conditions indicating presence of multiple components acting at different levels andP. tuberosa(aqueous) showed bactericidal activity under microaerophilic and anaerobic conditions implying the influence of anaerobiosis on its efficacy.P. nigrum(aqueous) andA. calamus(aqueous and ethanol) extracts were not active under axenic conditions but only inhibited intracellular growth ofMycobacterium tuberculosis, suggesting activation of host defense mechanisms to mediate bacterial killing rather than direct bactericidal activity.

scholarly journals Penetration and bactericidal activity of cefixime in synovial fluid.

1996 ◽  
Vol 40 (5) ◽  
pp. 1198-1200 ◽  
Author(s):  
E Somekh ◽  
L Heifetz ◽  
M Dan ◽  
F Poch ◽  
H Hafeli ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Bactericidal Activity ◽  
High Performance ◽  
Oral Intake ◽  
Joint Fluid ◽  
Bacterial Isolates ◽  
Mean Values ◽  
E Coli ◽  
The Mean ◽  
Bactericidal Activities

The penetration of oral cefixime into the synovial fluids of 16 patients (mean age, 50.6 years) who underwent joint taps for rheumatic noninfectious disorders was examined. The patients were each given a single dose (400 mg) 2 to 24 h prior to the tap. Cefixime concentrations in serum and joint fluid samples were measured by high-performance liquid chromatography, and the bactericidal activities of these fluids against three isolates each of Haemophilus influenzae and Escherichia coli were examined. The highest concentrations in serum and synovial fluid were achieved 4 h following drug intake, the mean values being 2.8 and 2.03 micrograms/ml, respectively. Effective bactericidal activities (bactericidal titer, > 1:2) against E. coli and H. influenzae were demonstrated in serum and joint fluid up to 10 h following oral intake of cefixime. These results suggest that cefixime penetrates well into joint fluid, achieving levels above the MIC for E. coli lasting as long as 10 h and levels above the MIC for H. influenzae lasting up to 24 h after administration. Good bactericidal activity against susceptible bacterial isolates was observed for at least 10 h after dosing.

scholarly journals Activities of Several Novel Oxazolidinones againstMycobacterium tuberculosis in a Murine Model

1999 ◽  
Vol 43 (5) ◽  
pp. 1189-1191 ◽  
Author(s):  
M. H. Cynamon ◽  
S. P. Klemens ◽  
C. A. Sharpe ◽  
S. Chase
Keyword(s):  
Body Weight ◽  
Mycobacterium Tuberculosis ◽  
Dose Response ◽  
Murine Model ◽  
Clinical Studies ◽  
Viable Cell ◽  
Test System ◽  
Cell Counts ◽  
Dose Response Study

ABSTRACT The activities of linezolid, eperezolid, and PNU-100480 were evaluated in a murine model of tuberculosis. Approximately 107 viable Mycobacterium tuberculosis ATCC 35801 organisms were given intravenously to 4-week-old outbred CD-1 mice. In the first study, treatment was started 1 day postinfection and was given by gavage for 4 weeks. Viable cell counts were determined from homogenates of spleens and lungs. PNU-100480 was as active as isoniazid. Linezolid was somewhat less active than PNU-100480 and isoniazid. Eperezolid had little activity in this model. In the next two studies, treatment was started 1 week postinfection. A dose-response study was performed with PNU-100480 and linezolid (both at 25, 50, and 100 mg/kg of body weight). PNU-100480 was more active than linezolid, and its efficacy increased with an escalation of the dose. Subsequently, the activity of PNU-100480 alone and in combination with rifampin or isoniazid was evaluated and was compared to that of isoniazid-rifampin. The activity of PNU-100480 was similar to that of isoniazid and/or rifampin in the various combinations tested. Further evaluation of these oxazolidinones in the murine test system would be useful prior to the development of clinical studies with humans.

scholarly journals Transcriptional Inhibition of the F1F0-Type ATP Synthase Has Bactericidal Consequences on the Viability of Mycobacteria

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Matthew B. McNeil ◽  
Heath W. K. Ryburn ◽  
Liam K. Harold ◽  
Justin F. Tirados ◽  
Gregory M. Cook
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Atp Synthase ◽  
Bactericidal Activity ◽  
Mycobacterium Smegmatis ◽  
Drug Target ◽  
Potent Inhibitor ◽  
Time Dependent ◽  
Content Type ◽  
Transcriptional Inhibition ◽  
Delayed Time

ABSTRACT Bedaquiline, an inhibitor of the mycobacterial ATP synthase, has revolutionized the treatment of Mycobacterium tuberculosis infection. Although a potent inhibitor, it is characterized by poorly understood delayed time-dependent bactericidal activity. Here, we demonstrate that in contrast to bedaquiline, the transcriptional inhibition of the ATP synthase in M. tuberculosis and Mycobacterium smegmatis has rapid bactericidal activity. These results validate the mycobacterial ATP synthase as a drug target with the potential for rapid bactericidal activity.

scholarly journals Development of Macozinone for TB treatment: An Update

2020 ◽  
Vol 10 (7) ◽  
pp. 2269 ◽  
Author(s):  
Vadim Makarov ◽  
Katarína Mikušová
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Clinical Studies ◽  
Phase 1 ◽  
Tb Treatment ◽  
Drug Regimens ◽  
Further Development

Macozinone, a piperazine-benzothiazinone PBTZ169, is currently undergoing Phase 1/2 clinical studies for the treatment of tuberculosis (TB). In this review we summarize the key findings that led to the development of this compound and to identification of its target, decaprenylphospohoryl ribose oxidase DprE1, which is involved in the synthesis of the essential arabinan polymers of the cell wall in a TB pathogen, Mycobacterium tuberculosis. We present the results of the pilot clinical studies, which raise optimism regarding its further development towards more efficient TB drug regimens.

Sign in / Sign up

Export Citation Format

Share Document