scholarly journals Moxifloxacin Pharmacokinetics/Pharmacodynamics and Optimal Dose and Susceptibility Breakpoint Identification for Treatment of Disseminated Mycobacterium avium Infection

2010 ◽  
Vol 54 (6) ◽  
pp. 2534-2539 ◽  
Author(s):  
Devyani Deshpande ◽  
Shashikant Srivastava ◽  
Claudia Meek ◽  
Richard Leff ◽  
Gerri S. Hall ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Critical Concentration ◽  
Optimal Dose ◽  
Clinical Isolates ◽  
Time Curve ◽  
Avium Infection ◽  
Mycobacterium Avium Intracellulare ◽  
Disseminated Disease ◽  
Susceptibility Breakpoint

ABSTRACT Organisms of the Mycobacterium avium-intracellulare complex (MAC) have been demonstrated to be susceptible to moxifloxacin. However, clinical data on how to utilize moxifloxacin to treat disseminated MAC are scanty. In addition, there have been no moxifloxacin pharmacokinetic-pharmacodynamic (PK/PD) studies performed for MAC infection. We utilized an in vitro PK/PD model of intracellular MAC to study moxifloxacin PK/PD for disseminated disease. Moxifloxacin doses, based on a serum half-life of 12 h, were administered, and the 0- to 24-h area under the concentration-time curve (AUC0-24) to MIC ratios associated with 1.0 log10 CFU/ml per week kill and 90% of maximal kill (EC90) were identified. The AUC0-24/MIC ratio associated with 1.0 log10 CFU/ml kill was 17.12, and that with EC90 was 391.56 (r 2 = 0.97). Next, the moxifloxacin MIC distribution in 102 clinical isolates of MAC was identified. The median MIC was 1 to 2 mg/liter. Monte Carlo simulations of 10,000 patients with disseminated MAC were performed to determine the probability that daily moxifloxacin doses of 400 and 800 mg/day would achieve or exceed 1.0 log10 CFU/ml per week kill or EC90. Doses of 400 and 800 mg/day achieved the AUC0-24/MIC ratio of 17.12 in 64% and 92% of patients, respectively. The critical concentration of moxifloxacin against MAC was identified as 0.25 mg/liter in Middlebrook media. The proposed susceptibility breakpoint means that a larger proportion of clinical isolates is resistant to moxifloxacin prior to therapy. For patients infected with susceptible isolates, however, 800 mg a day should be examined for safety and efficacy for disseminated M. avium disease.

scholarly journals In Vitro Activity of Rifamycin Derivatives against Nontuberculous Mycobacteria, Including Macrolide- and Amikacin-Resistant Clinical Isolates

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Dae Hun Kim ◽  
Su-Young Kim ◽  
Hee Jae Huh ◽  
Nam Yong Lee ◽  
Won-Jung Koh ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Therapeutic Option ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Content Type ◽  
Resistant Disease

ABSTRACT We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus, and M. kansasii. Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease.

scholarly journals In Vitro Amphotericin B Resistance in Clinical Isolates of Aspergillus terreus, with a Head-to-Head Comparison to Voriconazole

1999 ◽  
Vol 37 (7) ◽  
pp. 2343-2345 ◽  
Author(s):  
Deanna A. Sutton ◽  
Stephen E. Sanche ◽  
Sanjay G. Revankar ◽  
Annette W. Fothergill ◽  
Michael G. Rinaldi
Keyword(s):  
Amphotericin B ◽  
Aspergillus Terreus ◽  
Clinical Laboratory ◽  
Immunocompromised Host ◽  
Clinical Isolates ◽  
National Committee ◽  
High Dose ◽  
Etiologic Agents ◽  
Disseminated Disease

Amphotericin B therapy continues to be the “gold standard” in the treatment of invasive aspergillosis in the immunocompromised host. Although Aspergillus fumigatus and Aspergillus flavus constitute the major species, several reports have described invasive pulmonary or disseminated disease due to the less common Aspergillus terreus and dismal clinical outcomes with high-dose amphotericin B. We therefore evaluated 101 clinical isolates of A. terreus for their susceptibility to amphotericin B and the investigational triazole voriconazole by using the National Committee for Clinical Laboratory Standards M27-A method modified for mould testing. Forty-eight-hour MICs indicated 98 and 0% resistance to amphotericin B and voriconazole, respectively. We conclude that A. terreus should be added to the list of etiologic agents refractory to conventional amphotericin B therapy and suggest the potential clinical utility of voriconazole in aspergillosis due to this species.

scholarly journals Novel Administration of Clofazimine for the Treatment of Mycobacterium avium Infection

2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Ethan Valinetz ◽  
Helen Stankiewicz Karita ◽  
Paul S Pottinger ◽  
Rupali Jain
Keyword(s):  
Cystic Fibrosis ◽  
Lung Transplantation ◽  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Vitro Activity ◽  
The Novel ◽  
In Vitro Activity ◽  
Avium Infection ◽  
Mycobacterium Avium Infection

Abstract Clofazimine has demonstrated in vitro activity against many nontuberculous mycobacteria. We present the case of a woman with cystic fibrosis who developed disseminated macrolide-resistant Mycobacterium avium infection following lung transplantation treated in part with clofazimine. We describe the novel administration of clofazimine via gastrostomy tube.

In Vitro Biofilm Formation in Mycobacterium avium-intracellulare Complex

2020 ◽  
Author(s):  
Elena Portell-Buj ◽  
Alexandre López-Gavín ◽  
Julian González-Martín ◽  
Griselda Tudó
Keyword(s):  
Mycobacterium Avium ◽  
Biofilm Formation ◽  
Mycobacterium Avium Intracellulare

Genetic and serovar typing of clinical isolates of the Mycobacterium avium-intracellulare complex

1996 ◽  
Vol 77 (1) ◽  
pp. 71-76 ◽  
Author(s):  
K.A.L. De Smet ◽  
T.J. Hellyer ◽  
A.W. Khan ◽  
I.N. Brown ◽  
J. Ivanyi
Keyword(s):  
Mycobacterium Avium ◽  
Clinical Isolates ◽  
Mycobacterium Avium Intracellulare

scholarly journals Role of CD40 Ligand in Mycobacterium avium Infection

1999 ◽  
Vol 67 (7) ◽  
pp. 3558-3565 ◽  
Author(s):  
Tomoko Hayashi ◽  
Savita P. Rao ◽  
Pascal R. Meylan ◽  
Richard S. Kornbluth ◽  
Antonino Catanzaro
Keyword(s):  
Mycobacterium Avium ◽  
Human Monocyte ◽  
Opportunistic Pathogen ◽  
Cd40 Ligand ◽  
Inhibitory Effect ◽  
Interleukin 12 ◽  
Intracellular Growth ◽  
Cell Counts ◽  
Avium Infection

ABSTRACT Mycobacterium avium is a common opportunistic pathogen in immunocompromised patients such as those infected with human immunodeficiency virus. Although M. avium is an intracellular organism replicating predominantly in macrophages, disseminated M. avium infection is seen in AIDS patients with CD4+ cell counts of <50 cells/μl, suggesting a possible involvement of a T cell-macrophage interaction for the elimination of M. avium. To determine whether CD40-CD40 ligand (CD40L) interactions play a role in M. aviuminfection, we studied the ability of CD40L to restrict M. avium replication in human monocyte-derived macrophages (MDM) in vitro. MDM were infected with M. avium and cocultured with CD40L-transfected 293 cells for 7 days. Intracellular growth ofM. avium in these MDM was assessed by colony counting. CD40L-expressing cells inhibited growth of M. avium in MDM by 86.5% ± 4.2% compared to MDM cultured with control cells. These findings were verified by assays using purified, soluble recombinant human CD40L (CD40LT). CD40LT (5 μg/ml) inhibited intracellular growth of M. avium by 76.9% ± 18.0% compared to cells treated with medium alone. Inhibition by CD40LT was reduced by monoclonal antibodies (MAbs) against CD40 and CD40L. The inhibitory effect of CD40LT was not accompanied by enhancement of interleukin-12 (IL-12) production by M. avium-infected MDM, while CD40L-expressing cells stimulated IL-12 production by these cells. Treatment of M. avium-infected mice with MAb against murine CD40L resulted in recovery of larger numbers of organisms (0.8 to 1.0 log) from the spleens, livers, and lungs of these animals compared to infected mice which received normal immunoglobulin G. These results indicate that CD40-CD40L signaling may be an important step in host immune response against M. avium infection.

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