scholarly journals Impact of susceptibility to injectable antibiotics on the treatment outcomes of Mycobacterium abscessus pulmonary disease

2021 ◽  
Author(s):  
Youngmok Park ◽  
Yea Eun Park ◽  
Byung Woo Jhun ◽  
Jimyung Park ◽  
Nakwon Kwak ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Pulmonary Disease ◽  
Drug Susceptibility ◽  
Mycobacterium Abscessus ◽  
Beta Lactams ◽  
In Vitro Susceptibility ◽  
Referral Hospitals ◽  
Microbiological Cure ◽  
Culture Conversion

Abstract Objectives Current guidelines recommend a susceptibility-based regimen for Mycobacterium abscessus subspecies abscessus pulmonary disease (MAB-PD), but the evidence is weak. We aimed to investigate the association between treatment outcomes and in vitro drug susceptibility to injectable antibiotics in MAB-PD patients. Methods We enrolled MAB-PD patients treated with intravenous amikacin and beta-lactams for ≥4 weeks at four referral hospitals in Seoul, South Korea. Culture conversion and microbiological cure at one year were evaluated based on susceptibility to injectable antibiotics among patients treated with those antibiotics for ≥ 2 weeks. Results A total of 82 patients were analysed. The mean age was 58.7 years, and 65.9% were women. Sputum culture conversion and microbiological cure were achieved in 52.4% and 41.5% of patients, respectively. Amikacin was the most common agent to which the M. abscessus subspecies abscessus isolates were susceptible (81.7%); 9.8% and 24.0% of the isolates were resistant to cefoxitin and imipenem, respectively. The clarithromycin-inducible resistance (IR) group (n = 65) had a lower microbiological cure rate than the clarithromycin-susceptible group (35.4% vs. 64.7%). The treatment outcomes appeared to be similar regardless of in vitro susceptibility results with regard to intravenous amikacin, cefoxitin, imipenem, and moxifloxacin. In the subgroup analysis of the clarithromycin-IR group, the treatment outcomes did not differ according to antibiotic susceptibility. Conclusions We did not find evidence supporting the use of susceptibility-based treatment with intravenous amikacin and beta-lactams in patients with MAB-PD. Further research would be required.

scholarly journals In Vitro Susceptibility of Mycobacterium abscessus and Mycobacterium fortuitum Isolates to 30 Antibiotics

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yaojie Shen ◽  
Xuyang Wang ◽  
Jialin Jin ◽  
Jing Wu ◽  
Xuelian Zhang ◽  
...  
Keyword(s):  
Public Health Problem ◽  
Drug Susceptibility ◽  
Mycobacterium Abscessus ◽  
Mycobacterium Fortuitum ◽  
In Vitro Susceptibility ◽  
Antitubercular Drugs ◽  
Microdilution Method ◽  
Susceptibility Tests ◽  
Susceptibility Profiles

Objective. Nontuberculous mycobacteria (NTM) cause various diseases in humans and animals. Recently, the prevalence of NTM-related disease has been on the rise, becoming an emerging public health problem. The aim of this study was to determine the antibiotic susceptibility profiles of clinical isolates of Mycobacterium abscessus and Mycobacterium fortuitum. Methods. We performed susceptibility tests on 37 clinical NTM isolates to 30 antibiotics with the microdilution method recommended by the Clinical and Laboratory Standards Institute. Results. Both M. abscessus and M. fortuitum were highly resistant to antitubercular drugs such as isoniazid, rifampin, ethambutol, clofazimine, ethionamide, and rifabutin. M. abscessus showed the lowest resistant rates to cefoxitin (10%), azithromycin (10%), amikacin (10%), and clarithromycin (20%) and very high resistant to sulfamethoxazole, vancomycin, oxacillin, clindamycin, and all fluoroquinolones. M. fortuitum showed low resistance to tigecycline (0%), tetracycline (0%), cefmetazole (12%), imipenem (12%), linezolid (18%), and the aminoglycosides amikacin (0%), tobramycin (0%), neomycin (0%), and gentamycin (24%). Conclusion. Amikacin, cefoxitin, and azithromycin have the highest in vitro activity against M. abscessus. Isolates of M. fortuitum need to be individually evaluated for drug susceptibility before choosing an effective antimicrobial regimen for treatment of infections.

scholarly journals Mycobacterium abscessus pulmonary disease: individual patient data meta-analysis

2019 ◽  
Vol 54 (1) ◽  
pp. 1801991 ◽  
Author(s):  
Nakwon Kwak ◽  
Margareth Pretti Dalcolmo ◽  
Charles L. Daley ◽  
Geoffrey Eather ◽  
Regina Gayoso ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Pulmonary Disease ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Treatment Success ◽  
Specific Treatment ◽  
Mycobacterium Abscessus ◽  
Patient Data ◽  
The Impact ◽  
Culture Conversion

Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), caused by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense or M. abscessus subsp. bolletii, is challenging.We conducted an individual patient data meta-analysis based on studies reporting treatment outcomes for MAB-PD to clarify treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Treatment success was defined as culture conversion for ≥12 months while on treatment or sustained culture conversion without relapse until the end of treatment.Among 14 eligible studies, datasets from eight studies were provided and a total of 303 patients with MAB-PD were included in the analysis. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus subsp. abscessus and 56.7% for M. abscessus subsp. massiliense. For MAB-PD overall, the use of imipenem was associated with treatment success (adjusted odds ratio (aOR) 2.65, 95% CI 1.36–5.10). For patients with M. abscessus subsp. abscessus, the use of azithromycin (aOR 3.29, 95% CI 1.26–8.62), parenteral amikacin (aOR 1.44, 95% CI 1.05–1.99) or imipenem (aOR 7.96, 95% CI 1.52–41.6) was related to treatment success. For patients with M. abscessus subsp. massiliense, the choice among these drugs was not associated with treatment outcomes.Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin or imipenem was associated with better outcomes for patients with M. abscessus subsp. abscessus.

scholarly journals Non-Tuberculous Mycobacterial Pulmonary Disease Prevalence Status in China

2020 ◽  
Author(s):  
Chunfa Liu ◽  
Yimeng Song ◽  
Wencong He ◽  
Dongxin Liu ◽  
Ping He ◽  
...  
Keyword(s):  
Pulmonary Disease ◽  
Southern China ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Mycobacterium Abscessus ◽  
Minimal Inhibitory Concentrations ◽  
Mycobacterium Avium Intracellulare ◽  
Southeastern Region

Abstract Introduction: The information on the pulmonary disease caused by non-tuberculosis mycobacterium (NTM) in China is limited, mainly based on local or regional studies.Methods: Retrospective study involving 72 tuberculosis clusters provided sputa of enrolled presumptive cases for mycobacterial and drug-susceptibility testing in 31 provinces of Chinese mainland. Minimal inhibitory concentrations (MICs) test was used to measure the susceptibility of NTM isolates.Results: Of 4917 mycobacterial isolates cultured, 317 (6.4%, 95% confidence interval [CI], 5.8 to 7.2) isolates were confirmed as NTM, among 207 (12.1%, 95% CI, 10.6 to 13.8) isolates were detected from the southeastern region with the highest NTM prevalence. Slow growing mycobacteria (SGM) contributed 93.3% (95% CI, 76.4 to 98.8) and 56.1% (95% CI, 50.1 to 61.9) in northern and southern China, respectively. A total of 29 species were detected, the three most frequently isolated NTM belonged to Mycobacterium abscessus complex (36.0%, 95% CI, 33.3 to 38.7), Mycobacterium avium-intracellulare complex (34.1%, 95% CI, 29.1 to 39.5), Mycobacterium kansasii (9.8%, 95% CI, 8.1 to 11.4), respectively. Clarithromycin and amikacin were showed lower resistant rates to NTM in vitro. Conclusions: The southeastern region should be paid more attention to NTM pulmonary disease. More rapid growing mycobacteria (RGM) were present in southern China than the northern (P < 0.001). Considering clear correlations between in vitro activity and the in vivo outcomes of treatment, macrolides and amikacin were recommended in NTM treatment in China.

scholarly journals Molecular epidemiology, in vitro susceptibility and exoenzyme screening of Malassezia clinical isolates

2020 ◽  
Vol 69 (3) ◽  
pp. 436-442 ◽  
Author(s):  
Wei Li ◽  
Zi-Wei Zhang ◽  
Yun Luo ◽  
Ni Liang ◽  
Xiao-Xue Pi ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Synergistic Effects ◽  
Extracellular Enzyme ◽  
Drug Susceptibility ◽  
Clinical Isolates ◽  
Sequencing Analysis ◽  
In Vitro Susceptibility ◽  
Major Species ◽  
Malassezia Globosa

Introduction. Malassezia folliculitis (MF) and pityriasis versicolor (PV) are common dermatoses caused by Malassezia species. Their molecular epidemiology, drug susceptibility and exoenzymes are rarely reported in China. Aim. To investigate the molecular epidemiology, drug susceptibility and enzymatic profile of Malassezia clinical isolates. Methodology. Malassezia strains were recovered from MF and PV patients and healthy subjects (HS) and identified by sequencing analysis. The minimum inhibitory concentrations (MICs) of nine antifungals (posaconazole, voriconazole, itraconazole, fluconazole, ketoconazole, miconazole, bifonazole, terbinafine and caspofungin) and tacrolimus, the interactions between three antifungals (itraconazole, ketoconazole and terbinafine) and tacrolimus, and the extracellular enzyme profile were evaluated using broth and checkerboard microdilution and the Api-Zym system, respectively. Results. Among 392 Malassezia isolates from 729 subjects (289 MF, 218 PV and 222 HS), Malassezia furfur and Malassezia globosa accounted for 67.86 and 18.88 %, respectively. M. furfur was the major species in MF and PV patients and HS. Among 60M. furfur and 50M. globosa strains, the MICs for itraconazole, posaconazole, voriconazole and ketoconazole were <1 μg ml−1. M. furfur was more susceptible to itraconazole, terbinafine and bifonazole but tolerant to miconazole compared with M. globosa (P<0.05). Synergistic effects between terbinafine and itraconazole or between tacrolimus and itraconazole, ketoconazole or terbinafine occurred in 6, 7, 6 and 9 out of 37 strains, respectively. Phosphatases, lipases and proteases were mainly secreted in 51 isolates. Conclusions. Itraconazole, posaconazole, voriconazole and ketoconazole are theagents against which there is greatest susceptibility. Synergistic effects between terbinafine and itraconazole or tacrolimas and antifungals may be irrelevant to clinical application. Overproduction of lipases could enhance the skin inhabitation of M. furfur.

scholarly journals 1350. Clofazimine as an Oral Companion Drug for Treatment of Mycobacterium abscessus complex Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S488-S489
Author(s):  
Joy Yong ◽  
Ka Lip Chew ◽  
Paul Tambyah
Keyword(s):  
Active Agent ◽  
Liver Function Tests ◽  
Mycobacterium Abscessus ◽  
Prolonged Treatment ◽  
Attractive Alternative ◽  
In Vitro Susceptibility ◽  
Treatment Regimens ◽  
Drug Intolerance ◽  
Mycobacterium Abscessus Complex

Abstract Background Infections caused by the multi-drug-resistant Mycobacterium abscessus complex (MabsC) are challenging to treat and often require multiple antimicrobials for a prolonged treatment course and still have poor outcomes. Clofazimine, an oral anti-leprosy drug, has demonstrated good in vitro susceptibility and is being increasingly employed in treatment regimens for MabsC infections. We performed a drug-use-evaluation of clofazimine in the treatment of MabsC infections. Methods A retrospective review was performed for all patients with MabsC infections treated with clofazimine-containing regimens from January 2014 to June 2017. Results Twenty-nine patients were included. Twelve patients had pulmonary MabsC infections and seventeen had extrapulmonary infections. All isolates had clofazimine minimum-inhibitory-concentration of ≤0.5 mg/L as tested by broth microdilution. Clofazimine was prescribed at initiation of therapy in 31.0% (9/29), as a companion drug during maintenance therapy after initial intravenous therapy in 44.8% (13/29) and as part of salvage therapy due to disease progression or drug intolerance in 24.1% (7/29) of patients. Dosing of clofazimine for the pediatric patients was prescribed at 1–2 mg/kg/day while the adult patients received a range of 50–200 mg/day. Clofazimine was given for a median duration of 148.5 days (range: 14–1212) and most commonly in combination with clarithromycin (82.8%), amikacin (58.6%), and cefoxitin (24.1%). Twelve patients had documented adverse reactions attributable to clofazimine: skin hyperpigmentation (66.7%), abnormal liver function tests (16.7%), and gastrointestinal disturbance (16.7%). Table 1 describes the patients who had clofazimine ceased due to an adverse effect. Nine patients with pulmonary MabsC infections and 16 with extrapulmonary MabsC infections had documented improvement in symptoms. Conclusion Clofazimine as a companion drug in the treatment of MabsC infections was reasonably tolerated over a prolonged period of time. Its availability as an oral active agent makes it an attractive alternative to IV companion drugs and potentially improves compliance to the protracted treatment courses for patients with MabsC infections. Disclosures All authors: No reported disclosures.

In vitro susceptibility of Mycobacterium abscessus complex and feasibility of standardizing treatment regimens

2020 ◽  
Author(s):  
Ka Lip Chew ◽  
Sophie Octavia ◽  
Joelle Go ◽  
Sally Ng ◽  
Yit Er Tang ◽  
...  
Keyword(s):  
Retrospective Review ◽  
Susceptibility Testing ◽  
Mycobacterium Abscessus ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Treatment Regimens ◽  
Mycobacterium Abscessus Complex ◽  
Additional Testing

Abstract Objectives To determine the in vitro susceptibility of members of the Mycobacterium abscessus complex to routinely tested antibiotics and to an extended antibiotic panel. Methods Non-duplicate isolates for which susceptibility testing results were available were included in this study. Retrospective laboratory records were reviewed, including tigecycline susceptibility results, and testing was performed with additional drugs, including vancomycin, dalbavancin, telavancin, oritavancin, rifabutin, delafloxacin, eravacycline, clofazimine and bedaquiline using broth microdilution (Sensititre, Thermo Fisher). Results A total of 218 M. abscessus complex isolates were included for retrospective review, of which 151 were respiratory isolates. Of these 218 isolates, 211 were available for additional testing with the extended antibiotic panel. Of these, 146 were respiratory isolates. One isolate had a vancomycin MIC of 2 mg/L and MICs of all other isolates were &gt;8 mg/L. All isolates had MICs of &gt;8 mg/L for oritavancin, dalbavancin and telavancin. One isolate had a delafloxacin MIC of 4 mg/L and MICs of all other isolates were &gt;8 mg/L. The MIC50/MIC90s of rifabutin, tigecycline, eravacycline, clofazimine and bedaquiline were 16/32, 0.5/1, 0.12/0.25, 0.12/0.25 and 0.06/0.12 mg/L, respectively. Conclusions In vitro activity was demonstrated for clofazimine, bedaquiline and eravacycline, indicating potential for inclusion as standardized therapy for M. abscessus complex infections.

In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine

Parasitology ◽  
1998 ◽  
Vol 117 (6) ◽  
pp. 541-545 ◽  
Author(s):  
B. PRADINES ◽  
M. MABIKA MAMFOUMBI ◽  
D. PARZY ◽  
M. OWONO MEDANG ◽  
C. LEBEAU ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Concentration ◽  
Narrow Range ◽  
Drug Susceptibility ◽  
Drug Uptake ◽  
Cross Resistance ◽  
In Vitro Susceptibility ◽  
Positive Correlation ◽  
Common Features

The in vitro activity of artemether against 63 African isolates of Plasmodium falciparum from Libreville, Gabon was evaluated using an isotopic drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0·8 to 34·8 nm (mean IC50 5·0 nm) and the 95% confidence interval (CI95%) was 3·6–6·3 nm. In vitro decreased susceptibility or resistance were observed with artemether (14%), to chloroquine (90%), to quinine (32%). Isolate susceptibility to amodiaquine and halofantrine was high i.e. 100% and 98%, respectively. There was a significant positive correlation between responses to artemether and amodiaquine (r2=0·45, P<0·001), artemether and chloroquine (r2=0·36, P<0·001), artemether and quinine (r2=0·31, P<0·001), and artemether and halofantrine r2=0·19, P<0·01). Positive correlation between these drugs suggests in vitro cross-resistance or at least common features in drug uptake and/or mode of action or resistance.

scholarly journals Assessment and Continued Validation of the Malaria SYBR Green I-Based Fluorescence Assay for Use in Malaria Drug Screening

2007 ◽  
Vol 51 (6) ◽  
pp. 1926-1933 ◽  
Author(s):  
Jacob D. Johnson ◽  
Richard A. Dennull ◽  
Lucia Gerena ◽  
Miriam Lopez-Sanchez ◽  
Norma E. Roncal ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Culture Condition ◽  
Microtiter Plate ◽  
Growth Conditions ◽  
Drug Susceptibility ◽  
Sybr Green ◽  
Sybr Green I ◽  
Phenotypic Correlation ◽  
In Vitro Susceptibility

ABSTRACT Several new fluorescence malaria in vitro drug susceptibility microtiter plate assays that detect the presence of malarial DNA in infected erythrocytes have recently been reported, in contrast to traditional isotopic screens that involve radioactive substrate incorporation to measure in vitro malaria growth inhibition. We have assessed and further characterized the malaria SYBR Green I-based fluorescence (MSF) assay for its ability to monitor drug resistance. In order to use the MSF assay as a drug screen, all assay conditions must be thoroughly examined. In this study we expanded upon the capabilities of this assay by including antibiotics and antifolates in the drug panel and testing folic acid-free growth conditions. To do this, we evaluated a more expansive panel of antimalarials in combination with various drug assay culture conditions commonly used in drug sensitivity screening for their activity against Plasmodium falciparum strains D6 and W2. The detection and quantitation limits of the MSF assay were 0.04 to 0.08% and ∼0.5% parasitemia, respectively. The MSF assay quality was significantly robust, displaying a Z′ range of 0.73 to 0.95. The 50% inhibitory concentrations for each drug and culture condition combination were determined by using the MSF assay. Compared to the standard [3H]hypoxanthine assay, the MSF assay displayed the expected parasite drug resistance patterns with a high degree of global and phenotypic correlation (r 2 ≥ 0.9238), regardless of which culture condition combination was used. In conclusion, the MSF assay allows for reliable one-plate high-throughput, automated malaria in vitro susceptibility testing without the expense, time consumption, and hazard of other screening assays.

scholarly journals In Vitro Susceptibility Testing of GSK656 against Mycobacterium Species

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Wenzhu Dong ◽  
Shanshan Li ◽  
Shu’an Wen ◽  
Wei Jing ◽  
Jin Shi ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Binding Pocket ◽  
Trna Synthetase ◽  
Mycobacterium Abscessus ◽  
Drug Binding ◽  
Mycobacterial Species ◽  
In Vitro Susceptibility ◽  
Content Type ◽  
Sequence Variations

ABSTRACT In this study, we aimed to assess the in vitro susceptibility to GSK656 among multiple mycobacterial species and to investigate the correlation between leucyl-tRNA synthetase (LeuRS) sequence variations and in vitro susceptibility to GSK656 among mycobacterial species. A total of 187 mycobacterial isolates, comprising 105 Mycobacterium tuberculosis isolates and 82 nontuberculous mycobacteria (NTM) isolates, were randomly selected for the determination of in vitro susceptibility. For M. tuberculosis, 102 of 105 isolates had MICs of ≤0.5 mg/liter, demonstrating a MIC50 of 0.063 mg/liter and a MIC90 of 0.25 mg/liter. An epidemiological cutoff value of 0.5 mg/liter was proposed for identification of GSK656-resistant M. tuberculosis strains. For NTM, the MIC50 and MIC90 values were >8.0 mg/liter for both Mycobacterium intracellulare and Mycobacterium avium. In contrast, all Mycobacterium abscessus isolates had MICs of ≤0.25 mg/liter, yielding a MIC90 of 0.063 mg/liter. LeuRS from M. abscessus showed greater sequence similarity to M. tuberculosis LeuRS than to LeuRSs from M. avium and M. intracellulare. Sequence alignment revealed 28 residues differing between LeuRSs from M. avium and M. intracellulare and LeuRSs from M. tuberculosis and M. abscessus; among them, 15 residues were in the drug binding domain. Structure modeling revealed that several different residues were close to the tRNA-LeuRS interface or the entrance of the drug-tRNA binding pocket. In conclusion, our data demonstrate significant species diversity in in vitro susceptibility to GSK656 among various mycobacterial species. GSK656 has potent efficacy against M. tuberculosis and M. abscessus, whereas inherent resistance was noted for M. intracellulare and M. avium.

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