<i>In Vitro</i>
            Susceptibility of Mycobacterium tuberculosis to Amikacin, Kanamycin, and Capreomycin

Dijkstra, Jacob A.; Laan, Tridia van der; Akkerman, Onno W.; Bolhuis, Mathieu S.; Lange, Wiel C M de; Kosterink, Jos G. W.; Werf, Tjip S. van der; Alffenaar, Jan-Willem; Soolingen, Dick van

doi:10.1128/aac.01724-17

Cited by 25 publications

(17 citation statements)

References 25 publications

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“…Experimental data demonstrate that a C max /MIC ratio of at least 10 at the site of infection is necessary to optimize bactericidal activity for amikacin, with MIC ranging from 0.5 to 2 mg/L. [4,18,19] At our center, individual MICs for amikacin are not reported. However, the critical concentration for amikacin on the Bactec MGIT 960 system, used by the Public Health Ontario Laboratory, is known to be 1.0 [20].…”

Section: Discussionmentioning

confidence: 96%

Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

Sabur

Brar

et al. 2021

BMC Infect Dis

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Background The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant toxicity. Methods Patients with MDR-TB treated at our institution receive amikacin at 8–10 mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016. Results Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9 mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12 days (IQR 5, 26). The median duration of amikacin treatment was 7.2 months (IQR 5.7, 8), and median time to sputum culture conversion was 1 month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6–24.8%); 22.2% had subjective hearing loss (95% CI 11.2–37.1%) and 31.9% subjective tinnitus (95% CI 19.1–47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8–38.6%), but only 5 patients had a GFR < 60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84–99%). Conclusions Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.

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Section: Discussionmentioning

confidence: 96%

Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

Sabur

Brar

et al. 2021

BMC Infect Dis

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“…MS14B. These compounds were isolated from Streptomyces kanamyceticus and Streptomyces capreolus, and are used as second-line drugs against multidrug-resistant tuberculosis [55]. The accurate masses of the cluster associated with Micromonospora aurantiaca MS55 correspond to possible new versions of niphimycin.…”

Section: Discussionmentioning

confidence: 99%

Diversity and Bioactive Potential of Actinobacteria Isolated from a Coastal Marine Sediment in Northern Portugal

et al. 2020

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Natural compounds have had increasing applications in the biotechnological sector, with a large fraction of these substances being channeled to the pharmaceutical industry due to their important pharmacological properties. The discovery of new bioactive molecules with novel mechanisms of action constitutes a promising solution for the design of alternative therapeutic solutions. Actinobacteria are a large group of morphologically and physiologically diverse bacteria well known for their production of biotechnologically relevant compounds. The Portuguese coast is scantly explored in terms of Actinobacteria diversity and respective bioactive potential, offering a good opportunity to find new Actinobacteria taxa and bioactive natural products. In this study, we investigated the Actinobacteria diversity associated with a sediment sample collected from the intertidal zone of a beach in northern Portugal, through a cultivation-dependent approach, and screened its antimicrobial and cytotoxic potential. A total of 52 Actinobacteria strains were recovered from the marine sediment, with the largest fraction of the isolates belonging to the genus Micromonospora. Bioactivity screening assays identified crude extracts of six Streptomyces strains active against C. albicans, exhibiting minimum inhibition concentration (MIC) values in the range of 3.90–125 μg mL−1. Twenty-five Actinobacteria crude extracts (obtained from strains of the genera Micromonospora, Streptomyces and Actinomadura) exhibited significant effects on the viability of at least one tested cancer cell line (breast ductal carcinoma T-47D and liver hepatocellular carcinoma HepG2). The Actinobacteria extracts demonstrating activity in the antimicrobial and/or cytotoxic assays were subjected to metabolomic analysis (Mass spectrometry (MS)-based dereplication and molecular networking analyses), indicating the presence of four clusters that may represent new natural products. The results obtained demonstrate the importance of bioprospecting underexplored environments, like the Portuguese coast, for enhancing the discovery of new natural products, and call attention to the relevance of preserving the natural genetic diversity of coastal environments.

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“…S2 in the supplemental material). Surprisingly, large sensitization effects between 8-and 16-fold-reduced MIC 90 values were also observed for the new TB drugs bedaquiline and delamanid, the important second-line TB drug capreomycin (42), and ampicillin (Table 1 and Fig. 3B, D, G, and I).…”

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confidence: 89%

A Protein Complex from Human Milk Enhances the Activity of Antibiotics and Drugs against Mycobacterium tuberculosis

Meikle

Mossberg

Mitra

et al. 2019

Antimicrob Agents Chemother

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Mycobacterium tuberculosis, the causative agent of human tuberculosis (TB), has surpassed HIV/AIDS as the leading cause of death from a single infectious agent. The increasing occurrence of drug-resistant strains has become a major challenge for health care systems and, in some cases, has rendered TB untreatable. However, the development of new TB drugs has been plagued with high failure rates and costs. Alternative strategies to increase the efficacy of current TB treatment regimens include host-directed therapies or agents that makeM. tuberculosismore susceptible to existing TB drugs. In this study, we show that HAMLET, an α-lactalbumin–oleic acid complex derived from human milk, has bactericidal activity againstM. tuberculosis. HAMLET consists of a micellar oleic acid core surrounded by a shell of partially denatured α-lactalbumin molecules and unloads oleic acid into cells upon contact with lipid membranes. At sublethal concentrations, HAMLET potentiated a remarkably broad array of TB drugs and antibiotics againstM. tuberculosis. For example, the minimal inhibitory concentrations of rifampin, bedaquiline, delamanid, and clarithromycin were decreased by 8- to 16-fold. HAMLET also killedM. tuberculosisand enhanced the efficacy of TB drugs inside macrophages, a natural habitat ofM. tuberculosis. Previous studies showed that HAMLET is stable after oral delivery in mice and nontoxic in humans and that it is possible to package hydrophobic compounds in the oleic acid core of HAMLET to increase their solubility and metabolic stability. The potential of HAMLET and other liprotides as drug delivery and sensitization agents in TB chemotherapy is discussed here.

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In Vitro Susceptibility of Mycobacterium tuberculosis to Amikacin, Kanamycin, and Capreomycin

Cited by 25 publications

References 25 publications

Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

Diversity and Bioactive Potential of Actinobacteria Isolated from a Coastal Marine Sediment in Northern Portugal

A Protein Complex from Human Milk Enhances the Activity of Antibiotics and Drugs against Mycobacterium tuberculosis

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