scholarly journals Whole Blood Bactericidal Activity during Treatment of Pulmonary Tuberculosis

2003 ◽  
Vol 187 (2) ◽  
pp. 270-278 ◽  
Author(s):  
Robert S. Wallis ◽  
Solange A. Vinhas ◽  
John L. Johnson ◽  
Fabíola C. Ribeiro ◽  
Moisés Palaci ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bactericidal Activity ◽  
Whole Blood

BACTERICIDAL ACTIVITY OF THE BLOOD OF ACTIVELY IMMUNIZED WAX MOTH LARVAE

1962 ◽  
Vol 8 (4) ◽  
pp. 491-499 ◽  
Author(s):  
June M. Stephens
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibody Response ◽  
Bactericidal Activity ◽  
Whole Blood ◽  
Immune Serum ◽  
Shigella Dysenteriae ◽  
Immune State ◽  
The Third ◽  
Wax Moth

The blood of normal wax moth larvae is not bactericidal for Pseudomonas aeruginosa. The blood becomes moderately bactericidal when larvae are actively immunized against P. aeruginosa. This activity was measured by a modification of Nagington's technique for the estimation of typhoid antibody. Bactericidal activity appears to be the only measurable type of antibody response against P. aeruginosa. Cell-free blood was as active as whole blood; 0.02 ml of immune serum kills about 1000 organisms. The blood of normal wax moth larvae is bactericidal for Shigella dysenteriae but the blood of insects immunized against either this organism or P. aeruginosa shows no increase in activity against S. dysenteriae. A number of non-specific agents, both protein and non-protein, did not stimulate bactericidal activity in serum after their injection into normal larvae. Immune sera prepared against some strains of P. aeruginosa were not active against other strains. Storage at 37 °C or absorption with zymosan both result in blackening of immune blood and loss of bactericidal activity. Bactericidal activity is evident only during the immune state of the insect, i.e. from about 18 hours until the third day after vaccination; it develops at the same time that inhibition of melanization was observed in the blood from vaccinated larvae.

scholarly journals The Bactericidal Activity of Moxifloxacin in Patients with Pulmonary Tuberculosis

2003 ◽  
Vol 168 (11) ◽  
pp. 1342-1345 ◽  
Author(s):  
Roly D. Gosling ◽  
Leonard O. Uiso ◽  
Noel E. Sam ◽  
Emily Bongard ◽  
Esther G. Kanduma ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bactericidal Activity

scholarly journals Early Bactericidal Activity and Pharmacokinetics of the Diarylquinoline TMC207 in Treatment of Pulmonary Tuberculosis

2008 ◽  
Vol 52 (8) ◽  
pp. 2831-2835 ◽  
Author(s):  
R. Rustomjee ◽  
A. H. Diacon ◽  
J. Allen ◽  
A. Venter ◽  
C. Reddy ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bactericidal Activity ◽  
Dose Range ◽  
Study Drug ◽  
First Line ◽  
Serious Adverse Events ◽  
Once Daily ◽  
Smear Positive Pulmonary Tuberculosis

ABSTRACT Tibotec Medicinal Compound 207 (TMC207) is a novel diarylquinoline with a unique mode of action that targets mycobacterial ATP synthase. TMC207 exhibits high in vitro activity against mycobacterial strains either susceptible or resistant to all first-line and many second-line drugs, including fluoroquinolones, and has shown exceptional in vivo activity against several mycobacterial species in different animal models. In this early bactericidal activity study, 75 treatment-naïve patients with smear-positive pulmonary tuberculosis were randomized to once-daily oral TMC207 (25 mg, 100 mg, or 400 mg), 600 mg rifampin (RIF), or 300 mg isoniazid (INH) for 7 days. Sixteen-hour overnight sputum collected at baseline and on each treatment day was plated in serial dilutions on selective agar plates. The bactericidal activity was expressed as the log10 decrease in CFU/ml sputum/day. Pharmacokinetic sampling was performed on day 7 of TMC207 administration up to 24 h postdose. The decreases in log10 CFU counts (± standard deviation) from baseline to day 7 were 0.04 ± 0.46 for 25 mg TMC207 (n = 14), 0.26 ± 0.64 for 100 mg TMC207 (n = 14), 0.77 ± 0.58 for 400 mg TMC207 (n = 14), 1.88 ± 0.74 for INH (n = 11), and 1.70 ± 0.71 for RIF (n = 14). Significant bactericidal activity of 400 mg TMC207 was observed from day 4 onward and was similar in magnitude to those of INH and RIF over the same period. The pharmacokinetics of TMC207 were linear across the dose range. In summary, TMC207 demonstrated bactericidal activity with a delayed onset and was well tolerated, and no study drug-related serious adverse events occurred.

scholarly journals Impact of selective immune-cell depletion on growth of Mycobacterium tuberculosis (Mtb) in a whole-blood bactericidal activity (WBA) assay

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0216616 ◽  
Author(s):  
Gail B. Cross ◽  
Benjamin C-M Yeo ◽  
Paul Edward Hutchinson ◽  
Mark C. Tan ◽  
Rupangi Verma ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bactericidal Activity ◽  
Whole Blood ◽  
Immune Cell ◽  
Cell Depletion

The early bactericidal activity of rifabutin in patients with pulmonary tuberculosis measured by sputum viable counts: a new method of drug assessment

1993 ◽  
Vol 32 (6) ◽  
pp. 867-875 ◽  
Author(s):  
Frederick A. Sirgel ◽  
Frederik J. H. Botha ◽  
Donald P. Parkin ◽  
Bernard W. Van De Wal ◽  
Peter R. Donald ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Bactericidal Activity ◽  
New Method

scholarly journals Coadministration of Allopurinol To Increase Antimycobacterial Efficacy of Pyrazinamide as Evaluated in a Whole-Blood Bactericidal Activity Model

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Claire M. Naftalin ◽  
Rupangi Verma ◽  
Meera Gurumurthy ◽  
Qingshu Lu ◽  
Matthew Zimmerman ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Whole Blood ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Oxidase Inhibitor ◽  
Time Curve ◽  
Xanthine Oxidase Inhibitor ◽  
Content Type ◽  
Liquid Chromatography Tandem Mass ◽  
The Relationship

ABSTRACT Coadministering pyrazinamide (PZA) with the xanthine oxidase inhibitor allopurinol increases systemic levels of the active metabolite, pyrazinoic acid (POA), but the effects on bactericidal activity against tuberculosis are unknown. We randomized healthy volunteers to take a single dose of PZA (either 10 or 25 mg/kg of body weight) at the first visit and the same dose 7 days later, coadministered with allopurinol (100 mg daily; 2 days before to 1 day after the PZA dose). Blood was drawn at intervals until 48 h after each PZA dose, and drug levels were measured using liquid chromatography-tandem mass spectrometry. Whole-blood bactericidal activity (WBA) was measured by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial CFU after 72 h of incubation. Allopurinol increased the POA area under the concentration-time curve from 0 to 8 h (AUC0–8) (18.32 h · μg/ml versus 24.63 h · μg/ml for PZA alone versus PZA plus allopurinol) (P < 0.001) and its peak plasma concentration (C max) (2.81 μg/ml versus 4.00 μg/ml) (P < 0.001). There was no effect of allopurinol on mean cumulative WBA (0.01 ± 0.02 ΔlogCFU versus 0.00 ± 0.02 ΔlogCFU for PZA alone versus PZA plus allopurinol) (P = 0.49). Higher systemic POA levels were associated with greater WBA levels (P < 0.001), but the relationship was evident only at low POA concentrations. The lack of an effect of allopurinol on WBA despite a significant increase in blood POA levels suggests that host-generated POA may be less effective than POA generated inside bacteria. Coadministration of allopurinol does not appear to be a useful strategy for increasing the efficacy of PZA in clinical practice. (This study has been registered at ClinicalTrials.gov under registration no. NCT02700347.)

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