scholarly journals Omadacycline as a promising new agent for the treatment of infections with Mycobacterium abscessus

2019 ◽  
Vol 74 (10) ◽  
pp. 2930-2933 ◽  
Author(s):  
Hannelore I Bax ◽  
Corné P de Vogel ◽  
Johan W Mouton ◽  
Jurriaan E M de Steenwinkel
Keyword(s):  
In Vitro Study ◽  
Mycobacterium Abscessus ◽  
Concentration Effect ◽  
Strong Concentration ◽  
Treatment Regimens ◽  
Pharmacokinetic Properties ◽  
High Concentrations ◽  
Time Kill ◽  
Mycobacterial Growth

Abstract Background Despite intensive treatment regimens, the outcome of Mycobacterium abscessus infections is extremely poor and thus novel treatment regimens are needed. Although tigecycline seems to be one of the best options currently available, its long-term use is hampered by severe toxic side effects as well as the need for intravenous administration and the relatively high concentrations required for efficacy. Objectives To assess the in vitro activity of omadacycline against M. abscessus and compare it with the activity of tigecycline. Methods The concentration- and time-dependent killing capacities of omadacycline and tigecycline against M. abscessus subspecies abscessus were determined using a time–kill kinetics assay. Time–kill curves as well as concentration–effect curves were generated. Results Time–kill curves showed strong concentration-dependent antimicrobial activity for both omadacycline and tigecycline. Omadacycline showed inhibition of mycobacterial growth at 4 mg/L and mycobacterial killing at concentrations ≥16 mg/L. Tigecycline showed mycobacterial killing at concentrations ≥4 mg/L, achieving elimination at concentrations ≥16 mg/L. The concentration–effect curves after 7 days of exposure showed stasis, 1 log mycobacterial killing and 2 log mycobacterial killing at 3.3, 4.0 and 4.8 mg/L for omadacycline and 2.2, 2.7 and 3.4 mg/L for tigecycline, respectively. Conclusions The results of this in vitro study on omadacycline activity, together with its favourable (pharmacokinetic) properties, suggest that omadacycline is a potential new agent for the treatment of M. abscessus infections.

scholarly journals Auranofin Activity Exposes Thioredoxin Reductase as a Viable Drug Target in Mycobacterium abscessus

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Mike Marvin Ruth ◽  
Mara van Rossum ◽  
Valerie A. C. M. Koeken ◽  
Lian J. Pennings ◽  
Elin M. Svensson ◽  
...  
Keyword(s):  
Drug Target ◽  
Ex Vivo ◽  
Bacterial Load ◽  
Thioredoxin Reductase ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Treatment Regimens ◽  
Recommended Treatment ◽  
Time Kill

ABSTRACT Nontuberculous mycobacteria (NTM) are highly drug-resistant, opportunistic pathogens that can cause pulmonary disease. The outcomes of the currently recommended treatment regimens are poor, especially for Mycobacterium abscessus. New or repurposed drugs are direly needed. Auranofin, a gold-based antirheumatic agent, was investigated for Mycobacterium tuberculosis. Here, we test auranofin against NTM in vitro and ex vivo. We tested the susceptibility of 63 NTM isolates to auranofin using broth microdilution. Next, we assessed synergy between auranofin and antimycobacterial drugs using the checkerboard method and calculated the fractional inhibition concentration index (FICI). Using time-kill kinetics assays (TK), we assessed pharmacodynamics of auranofin alone and in combination with drug combinations showing the lowest FICIs for M. abscessus CIP 104536. A response surface analysis was used to assess synergistic interactions over time in TKs. Primary isolated macrophages were infected with M. abscessus and treated with auranofin. Finally, using KEGG Orthology, we looked for orthologues to auranofins drug target in M. tuberculosis. M. abscessus had the lowest auranofin MIC50 (2 μg/ml) among the tested NTM. The lowest average FICIs were observed between auranofin and amikacin (0.45) and linezolid (0.50). Auranofin exhibited concentration-dependent killing of M. abscessus, with >1-log killing at concentrations of >2× MIC. Only amikacin was synergistic with auranofin according to Bliss independence. Auranofin could not lower the intracellular bacterial load in macrophages. Auranofin itself may not be feasible for M. abscessus treatment, but these data point toward a promising, unutilized drug target.

scholarly journals In Vitro Study of Candida tropicalis Isolates Exhibiting Paradoxical Growth in the Presence of High Concentrations of Caspofungin

2007 ◽  
Vol 51 (12) ◽  
pp. 4474-4476 ◽  
Author(s):  
G. Sóczó ◽  
G. Kardos ◽  
I. Varga ◽  
B. Kelentey ◽  
R. Gesztelyi ◽  
...  
Keyword(s):  
Candida Tropicalis ◽  
In Vitro Study ◽  
Vitro Study ◽  
Minimum Fungicidal Concentration ◽  
Paradoxical Growth ◽  
High Concentrations ◽  
Time Kill

ABSTRACT Paradoxical growth was noted in RPMI 1640 and antibiotic medium 3 in the case of 14 and 1 of 15 Candida tropicalis strains, respectively, at a caspofungin concentration of 12.5 μg/ml using minimum fungicidal concentration tests. Time-kill assays showed that against isolates killed at lower concentrations, caspofungin at a concentration of 12.5 μg/ml was only fungistatic.

scholarly journals Antibacterial Inhibitory Effects of Punica Granatum Gel on Cariogenic Bacteria: An in vitro Study

2017 ◽  
Vol 10 (2) ◽  
pp. 152-157 ◽  
Author(s):  
Grazielle Millo ◽  
Apa Juntavee ◽  
Ariya Ratanathongkam ◽  
Natsajee Nualkaew ◽  
Peerapattana, Jomjai ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Study ◽  
Punica Granatum ◽  
Antibacterial Activities ◽  
Diffusion Method ◽  
Inhibitory Effects ◽  
Cariogenic Bacteria ◽  
Zones Of Inhibition ◽  
Time Kill

ABSTRACT Aim This study evaluated the in vitro antibacterial effects of the formulated Punica granatum (PG) gel against Streptococcus mutans, Streptococcus sanguinis, and Lactobacillus casei. Materials and methods The PG extract was dissolved in water at 500 mg/mL. High performance liquid chromatography (HPLC) was used for identification and quantification of chemical marker punicalagin. Minimum bactericidal concentration (MBC) and time-kill assay (TKA) were investigated. Antibacterial activities of the formulated PG gel, 2% chlorhexidine (CHX) gel and blank gel were tested by measuring the zones of inhibition through agar well diffusion method. Results The HPLC results showed presence of punicalagin at 2023.58 ± 25.29 μg/mL in the aqueous PG extract and at 0.234% (w/w) in the formulated PG gel. The MBC for S. mutans, S. Sanguinis, and L. casei were 250, 125, and 500 mg/mL respectively. The TKA of 500 mg/mL aqueous PG extract showed total inhibition of S. mutans, S. Sanguinis, and L. casei at 6, 1, and 24 hours contact time respectively. Agar well diffusion revealed that for S. mutans, CHX gel > PG gel > blank gel; for S. sanguinis, CHX gel = PG gel > blank gel; for L. casei, CHX gel > PG gel = blank gel. Comparison of the PG gel potency showed that S. sanguinis = S. mutans > L. casei. Conclusion The PG gel equivalent to 0.234% punicalagin (w/w) inhibited S. mutans and S. sanguinis but not L. casei within 24 hours incubation period and has the potential to be used for caries prevention. How to cite this article Millo G, Juntavee A, Ratanathongkam A, Nualkaew N, Peerapattana J, Chatchiwiwattana S. Antibacterial Inhibitory Effects of Punica Granatum Gel on Cariogenic Bacteria: An in vitro Study. Int J Clin Pediatr Dent 2017;10(2):152-157.

Leakage of Endotoxins through the Endotoxin Retentive Filter: An in vitro Study

2022 ◽  
pp. 1-9
Author(s):  
Hiroshi Nozaki ◽  
Yoshihiro Tange ◽  
Yoji Inada ◽  
Takashi Uchino ◽  
Nakanobu Azuma
Keyword(s):  
Sodium Hypochlorite ◽  
Peracetic Acid ◽  
In Vitro Study ◽  
Dialysis Fluid ◽  
High Concentration ◽  
Membrane Pores ◽  
Polyether Sulfone ◽  
Repeated Use ◽  
High Concentrations

<b><i>Introduction:</i></b> Ultrapurification of dialysis fluid has enabled highly efficient dialysis treatments. Online hemodiafiltration is one such treatment that uses a purified dialysis fluid as a supplemental fluid. In this method, an endotoxin retentive filter (ETRF) is used in the final step of dialysis fluid purification, with the aim of preventing leakage of endotoxins. Sodium hypochlorite and peracetic acid are used as disinfecting agents for the dialysis fluid pipes containing the ETRF; however, the effects of these agents on ETRF membrane pores have not been fully clarified. <b><i>Methods:</i></b> Water permeability (flux) and endotoxin permeability were assessed in 3 types of ETRFs made with different membrane materials: polyester polymer alloy (PEPA), polyether sulfone (PES), and polysulfone (PS). High-concentration sodium hypochlorite and 2 types of peracetic acid were used as disinfecting agents, and the changes in flux and the endotoxin sieving coefficient (SC) were measured. <b><i>Results:</i></b> After repeated use of high concentrations of sodium hypochlorite and peracetic acid, the PEPA and PES ETRFs did not permit passage of endotoxins, regardless of their flux. However, in the PS ETRF, the flux and endotoxin SC increased with the number of cleaning cycles. No differences were observed according to the concentration of peracetic acid disinfecting agents. <b><i>Conclusion:</i></b> PEPA and PES ETRFs completely prevent endotoxin leakage and can be disinfected at concentrations higher than the conventionally recommended concentration without affecting pore expansion. Even new PS ETRFs have low levels of endotoxin leakage, which increase after disinfection cycles using sodium hypochlorite and peracetic acid.

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.

scholarly journals Copper Supplementation in Watering Solution Reaches the Xylem But Does Not Protect Tobacco Plants Against Xylella fastidiosa Infection

Plant Disease ◽  
2020 ◽  
Vol 104 (3) ◽  
pp. 724-730 ◽  
Author(s):  
Qing Ge ◽  
Paul A. Cobine ◽  
Leonardo De La Fuente
Keyword(s):  
Biofilm Formation ◽  
Inductively Coupled Plasma ◽  
Tap Water ◽  
Xylella Fastidiosa ◽  
In Vitro Study ◽  
Optical Emission ◽  
In Planta ◽  
Inductively Coupled ◽  
High Concentrations

Xylella fastidiosa is a xylem-limited plant pathogenic bacterium that causes disease in many crops worldwide. Copper (Cu) is an antimicrobial agent widely used on X. fastidiosa hosts to control other diseases. Although the effects of Cu for control of foliar pathogens are well known, it is less studied on xylem-colonizing pathogens. Previous results from our group showed that low concentrations of CuSO4 increased biofilm formation, whereas high concentrations inhibited biofilm formation and growth in vitro. In this study, we conducted in planta experiments to determine the influence of Cu in X. fastidiosa infection using tobacco as a model. X. fastidiosa-infected and noninfected plants were watered with tap water or with water supplemented with 4 mM or 8 mM of CuSO4. Symptom progression was assessed, and sap and leaf ionome analysis was performed by inductively coupled plasma with optical emission spectroscopy. Cu uptake was confirmed by increased concentrations of Cu in the sap of plants treated with CuSO4-amended water. Leaf scorch symptoms in Cu-supplemented plants showed a trend toward more severe at later time points. Quantification of total and viable X. fastidiosa in planta indicated that CuSO4-amended treatments did not inhibit but slightly increased the growth of X. fastidiosa. Cu in sap was in the range of concentrations that promote X. fastidiosa biofilm formation according to our previous in vitro study. Based on these results, we proposed that the plant Cu homeostasis machinery controls the level of Cu in the xylem, preventing it from becoming elevated to a level that would lead to bacterial inhibition.

scholarly journals In Vitro Pharmacodynamic Properties of Three Antifungal Agents against Preformed Candida albicans Biofilms Determined by Time-Kill Studies

2002 ◽  
Vol 46 (11) ◽  
pp. 3634-3636 ◽  
Author(s):  
Gordon Ramage ◽  
Kacy VandeWalle ◽  
Stefano P. Bachmann ◽  
Brian L. Wickes ◽  
José L. López-Ribot
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Pharmacokinetic Properties ◽  
Time Kill ◽  
Candida Albicans Biofilms

ABSTRACT We have examined the in vitro activities of fluconazole, amphotericin B, and caspofungin against Candida albicans biofilms by time-kill methodology. Fluconazole was ineffective against biofilms. Killing of biofilm cells was suboptimal at therapeutic concentrations of amphotericin B. Caspofungin displayed the most effective pharmacokinetic properties, with ≥99% killing at physiological concentrations.

scholarly journals Artemisia annua and Artemisia afra extracts exhibit strong bactericidal activity against Mycobacterium tuberculosis

2020 ◽  
Author(s):  
Maria Carla Martini ◽  
Tianbi Zhang ◽  
John T. Williams ◽  
Robert B. Abramovitch ◽  
Pamela J. Weathers ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bactericidal Activity ◽  
Artemisia Annua ◽  
Multidrug Resistant ◽  
Mycobacterium Abscessus ◽  
Major Barrier ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Emergence Of Resistance

ABSTRACTEthnopharmacological relevanceEmergence of drug-resistant and multidrug-resistant Mycobacterium tuberculosis (Mtb) strains is a major barrier to tuberculosis (TB) eradication, as it leads to longer treatment regimens and in many cases treatment failure. Thus, there is an urgent need to explore new TB drugs and combinations, in order to shorten TB treatment and improve outcomes. Here, we evaluate the potential of two medicinal plants, Artemisia annua, a natural source of artemisinin (AN), and Artemisia afra, as sources of novel antitubercular agents.Aim of the studyOur goal was to measure the activity of A. annua and A. afra extracts against Mtb as potential natural and inexpensive therapies for TB treatment, or as sources of compounds that could be further developed into effective treatments.Materials and MethodsThe minimum inhibitory concentrations (MICs) of A. annua and A. afra dichloromethane extracts were determined, and concentrations above the MICs were used to evaluate their ability to kill Mtb and Mycobacterium abscessus in vitro.ResultsPrevious studies showed that A. annua and A. afra inhibit Mtb growth. Here, we show for the first time that Artemisia extracts have a strong bactericidal activity against Mtb. The killing effect of A. annua was much stronger than equivalent concentrations of pure AN, suggesting that A. annua extracts kill Mtb through a combination of AN and additional compounds. A. afra, which produces very little AN, displayed bactericidal activity against Mtb that was substantial but weaker than that of A. annua. In addition, we measured the activity of Artemisia extracts against Mycobacterium abscessus. Interestingly, we observed that while A. annua is not bactericidal, it inhibits growth of M. abscessus, highlighting the potential of this plant in combinatory therapies to treat M. abscessus infections.ConclusionOur results indicate that Artemisia extracts have an enormous potential for treatment of TB and M. abscessus infections, and that these plants contain bactericidal compounds in addition to AN. Combination of extracts with existing antibiotics may not only improve treatment outcomes but also reduce the emergence of resistance to other drugs.

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