In Vitro Efficacy of Free and Nanoparticle Formulations of Gallium(III) meso-Tetraphenylporphyrine against Mycobacterium avium and Mycobacterium abscessus and Gallium Biodistribution in Mice

2018 ◽  
Vol 15 (3) ◽  
pp. 1215-1225 ◽  
Author(s):  
Seoung-ryoung Choi ◽  
Bradley E. Britigan ◽  
Barbara Switzer ◽  
Traci Hoke ◽  
David Moran ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Mycobacterium Abscessus

scholarly journals Effective Treatment of Mycobacterium avium subsp. hominissuis and Mycobacterium abscessus Species Infections in Macrophages, Biofilm, and Mice by Using Liposomal Ciprofloxacin

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
James D. Blanchard ◽  
Valerie Elias ◽  
David Cipolla ◽  
Igor Gonda ◽  
Luiz E. Bermudez
Keyword(s):  
Effective Treatment ◽  
Mouse Models ◽  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Number Of Individuals ◽  
Intranasal Instillation

ABSTRACT Nontuberculous mycobacteria (NTM) affect an increasing number of individuals worldwide. Infection with these organisms is more common in patients with chronic lung conditions, and treatment is challenging. Quinolones, such as ciprofloxacin, have been used to treat patients, but the results have not been encouraging. In this report, we evaluate novel formulations of liposome-encapsulated ciprofloxacin (liposomal ciprofloxacin) in vitro and in vivo. Its efficacy against Mycobacterium avium and Mycobacterium abscessus was examined in macrophages, in biofilms, and in vivo using intranasal instillation mouse models. Liposomal ciprofloxacin was significantly more active than free ciprofloxacin against both pathogens in macrophages and biofilms. When evaluated in vivo, treatment with the liposomal ciprofloxacin formulations was associated with significant decreases in the bacterial loads in the lungs of animals infected with M. avium and M. abscessus. In summary, topical delivery of liposomal ciprofloxacin in the lung at concentrations greater than those achieved in the serum can be effective in the treatment of NTM, and further evaluation is warranted.

scholarly journals In Vitro Resistance against DNA Gyrase Inhibitor SPR719 in Mycobacterium avium and Mycobacterium abscessus

2022 ◽  
Author(s):  
Wassihun Wedajo Aragaw ◽  
Nicole Cotroneo ◽  
Suzanne Stokes ◽  
Michael Pucci ◽  
Ian Critchley ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Dna Gyrase ◽  
Mycobacterium Abscessus ◽  
Drug Candidates ◽  
New Antibiotics ◽  
Novel Drug ◽  
Emergence Of Resistance

Clinical emergence of resistance to new antibiotics affects their utility. Characterization of in vitro resistance is a first step in the profiling of resistance properties of novel drug candidates.

scholarly journals Clofazimine Prevents the Regrowth of Mycobacterium abscessus and Mycobacterium avium Type Strains Exposed to Amikacin and Clarithromycin

2015 ◽  
Vol 60 (2) ◽  
pp. 1097-1105 ◽  
Author(s):  
Beatriz E. Ferro ◽  
Joseph Meletiadis ◽  
Melanie Wattenberg ◽  
Arjan de Jong ◽  
Dick van Soolingen ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Treatment Options ◽  
Mycobacterium Abscessus ◽  
Surface Model ◽  
Target Attainment ◽  
Content Type ◽  
Treatment Regimens ◽  
Combination Regimens ◽  
Type Strains

ABSTRACTMultidrug therapy is a standard practice when treating infections by nontuberculous mycobacteria (NTM), but few treatment options exist. We conducted this study to define the drug-drug interaction between clofazimine and both amikacin and clarithromycin and its contribution to NTM treatment.Mycobacterium abscessusandMycobacterium aviumtype strains were used. Time-kill assays for clofazimine alone and combined with amikacin or clarithromycin were performed at concentrations of 0.25× to 2× MIC. Pharmacodynamic interactions were assessed by response surface model of Bliss independence (RSBI) and isobolographic analysis of Loewe additivity (ISLA), calculating the percentage of statistically significant Bliss interactions and interaction indices (I), respectively. Monte Carlo simulations with predicted human lung concentrations were used to calculate target attainment rates for combination and monotherapy regimens. Clofazimine alone was bacteriostatic for both NTM. Clofazimine-amikacin was synergistic againstM. abscessus(I = 0.41; 95% confidence interval [CI], 0.29 to 0.55) andM. avium(I = 0.027; 95% CI, 0.007 to 0.048). Based on RSBI analysis, synergistic interactions of 28.4 to 29.0% and 23.2 to 56.7% were observed at 1× to 2× MIC and 0.25× to 2× MIC forM. abscessusandM. avium, respectively. Clofazimine-clarithromycin was also synergistic againstM. abscessus(I = 0.53; 95% CI, 0.35 to 0.72) andM. avium(I = 0.16; 95% CI, 0.04 to 0.35), RSBI analysis showed 23.5% and 23.3 to 53.3% at 2× MIC and 0.25× to 0.5× MIC forM. abscessusandM. avium, respectively. Clofazimine prevented the regrowth observed with amikacin or clarithromycin alone. Target attainment rates of combination regimens were >60% higher than those of monotherapy regimens forM. abscessusandM. avium. The combination of clofazimine with amikacin or clarithromycin was synergisticin vitro. This suggests a potential role for clofazimine in treatment regimens that warrants further evaluation.

scholarly journals In Vitro Activity of Bedaquiline and Delamanid against Nontuberculous Mycobacteria, Including Macrolide-Resistant Clinical Isolates

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Dae Hun Kim ◽  
Byung Woo Jhun ◽  
Seong Mi Moon ◽  
Su-Young Kim ◽  
Kyeongman Jeon ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Abscessus ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Mycobacterium Kansasii ◽  
Antimicrobial Drugs ◽  
Content Type

ABSTRACT We evaluated the in vitro activities of the antimicrobial drugs bedaquiline and delamanid against the major pathogenic nontuberculous mycobacteria (NTM). Delamanid showed high MIC values for all NTM except Mycobacterium kansasii. However, bedaquiline showed low MIC values for the major pathogenic NTM, including Mycobacterium avium complex, Mycobacterium abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. kansasii. Bedaquiline also had low MIC values with macrolide-resistant NTM strains and warrants further investigation as a potential antibiotic for NTM treatment.

scholarly journals In Vitro Antimicrobial Susceptibility of Mycobacterium abscessus in Korea

2008 ◽  
Vol 23 (1) ◽  
pp. 49 ◽  
Author(s):  
Sunghoon Park ◽  
Shinok Kim ◽  
Eun Mi Park ◽  
Hojoong Kim ◽  
O Jung Kwon ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Mycobacterium Abscessus

scholarly journals Association between 16S rRNA gene mutations and susceptibility to amikacin in Mycobacterium avium Complex and Mycobacterium abscessus clinical isolates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su-Young Kim ◽  
Dae Hun Kim ◽  
Seong Mi Moon ◽  
Ju Yeun Song ◽  
Hee Jae Huh ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Mycobacterium Avium ◽  
Inhibitory Concentration ◽  
Gene Mutations ◽  
Mycobacterium Abscessus ◽  
Clinical Isolates ◽  
Rrna Gene ◽  
High Level ◽  
Culture Conversion

AbstractWe evaluated the association between 16S rRNA gene (rrs) mutations and susceptibility in clinical isolates of amikacin-resistant nontuberculous mycobacteria (NTM) in NTM-pulmonary disease (PD) patients. Susceptibility was retested for 134 amikacin-resistant isolates (minimum inhibitory concentration [MIC] ≥ 64 µg/ml) from 86 patients. Amikacin resistance was reconfirmed in 102 NTM isolates from 62 patients with either Mycobacterium avium complex-PD (MAC-PD) (n = 54) or M. abscessus-PD (n = 8). MICs and rrs mutations were evaluated for 318 single colonies from these isolates. For the 54 MAC-PD patients, rrs mutations were present in 34 isolates (63%), comprising all 31 isolates with amikacin MICs ≥ 128 µg/ml, but only three of 23 isolates with an MIC = 64 µg/ml. For the eight M. abscessus-PD patients, all amikacin-resistant (MIC ≥ 64 µg/ml) isolates had rrs mutations. In amikacin-resistant isolates, the A1408G mutation (n = 29) was most common. Two novel mutations, C1496T and T1498A, were also identified. The culture conversion rate did not differ by amikacin MIC. Overall, all high-level and 13% (3/23) of low-level amikacin-resistant MAC isolates had rrs mutations whereas mutations were present in all amikacin-resistant M. abscessus isolates. These findings are valuable for managing MAC- and M. abscessus-PD and suggest the importance of phenotypic and genotypic susceptibility testing.

Lungenerkrankung durch nicht-tuberkulöse Mykobakterien

Pneumologie ◽  
2020 ◽  
Vol 74 (11) ◽  
pp. 773-779
Author(s):  
D. Wagner ◽  
C. Lange
Keyword(s):  
Mycobacterium Avium

ZusammenfassungDie neue ATS/ERS/ESCMID/IDSA-Leitlinie beantwortet 22 PICO-Fragen zur Behandlung von Erkrankungen der Lunge durch Mycobacterium avium-Komplex (MAC), M. kansasii, M. xenopi und M. abscessus. Allgemeines Insbesondere bei Patienten mit mikroskopischem Nachweis säurefester Stäbchen im Sputum oder kavernöser Verlaufsform sollte der Behandlungsbeginn nicht verzögert werden. Die Behandlung sollte auf einer speziesspezifischen Resistenztestung (entsprechend den CLSI-Guidelines) basieren. MAC-Lungenerkrankung Die Therapie erfolgt hier mit mindestens 3 Medikamenten inklusive einem Makrolid (eher Azithromycin als Clarithromycin) und Ethambutol. Für Patienten mit kavitärer, mit ausgeprägter nodulär-bronchiektatischer Erkrankung oder mit Makrolid-Resistenz wird zur täglichen oralen Therapie eine additive Gabe von parenteralem Amikacin oder Streptomycin empfohlen. Liposomal verkapseltes inhalatives Amikacin wird bei Therapieversagen empfohlen. Patienten mit nodulär-bronchiektatischer Erkrankungsmanifestation sollten eine orale Makrolid-basierte Therapie, die – je nach Ausmaß – 3 ×/Woche gegeben werden kann, erhalten. Als Dauer werden 12 Monate nach Konversion der Sputumkultur empfohlen. M. kansasii-Lungenerkrankung Empfohlen ist die Dreifachkombination aus Rifampicin, Ethambutol und Makrolid (oder Isoniazid ) für mindestens 12 Monate. Bei Rifampicin-Resistenz oder -unverträglichkeit wird Moxifloxacin als Ersatz empfohlen. M. xenopi-Lungenerkrankung Empfohlen ist die Dreifachkombination aus Rifampicin, Ethambutol und Makrolid (oder Moxifloxacin) für mindestens 12 Monate nach Konversion der Sputumkultur. Es wird empfohlen, bei Patienten mit kavernöser Verlaufsform zumindest parenterales Amikacin zu addieren und Experten zu konsultieren. M. abscessus-Lungenerkrankung Mindestens 3 Medikamente werden zur Therapie empfohlen. Die Substanzauswahl sollte auf einer In-vitro-Resistenztestung basieren. Makrolide sind die Grundlage, sollten aber bei Stämmen mit induzierbarer Makrolidresistenz nicht mitgerechnet werden. Zur Therapiedauer werden aufgrund fehlender Daten keine expliziten Empfehlungen ausgesprochen, eine Konsultation von Experten wird empfohlen.

Sign in / Sign up

Export Citation Format

Share Document