Rationale for and Efficacy of Prolonged-Interval Treatment Using Liposome-Encapsulated Amikacin in Experimental
            <i>Mycobacterium avium</i>
            Infection

Leitzke, S.; Bucke, W.E.; Börner, K.; Müller, Rainer H.; Hahn, Helmut; Ehlers, Stefan

doi:10.1128/aac.42.2.459

Cited by 53 publications

(15 citation statements)

References 19 publications

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“…Amikacin was also researched as a formulation in unilamellar liposomes (MiKasome) [ 151 ]. However, in spite of early promising results in treatments of several conditions such as urinary tract infection [ 152 ], endocarditis [ 153 ], Klebsiella pneumoniae and Mycobacterium infections [ 154 , 155 , 156 ], the development of the formulation was discontinued in the year 2000.…”

Section: Amikacinmentioning

confidence: 99%

Amikacin: Uses, Resistance, and Prospects for Inhibition

2017

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Aminoglycosides are a group of antibiotics used since the 1940s to primarily treat a broad spectrum of bacterial infections. The primary resistance mechanism against these antibiotics is enzymatic modification by aminoglycoside-modifying enzymes that are divided into acetyl-transferases, phosphotransferases, and nucleotidyltransferases. To overcome this problem, new semisynthetic aminoglycosides were developed in the 70s. The most widely used semisynthetic aminoglycoside is amikacin, which is refractory to most aminoglycoside modifying enzymes. Amikacin was synthesized by acylation with the l-(−)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A. The main amikacin resistance mechanism found in the clinics is acetylation by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], an enzyme coded for by a gene found in integrons, transposons, plasmids, and chromosomes of Gram-negative bacteria. Numerous efforts are focused on finding strategies to neutralize the action of AAC(6′)-Ib and extend the useful life of amikacin. Small molecules as well as complexes ionophore-Zn+2 or Cu+2 were found to inhibit the acetylation reaction and induced phenotypic conversion to susceptibility in bacteria harboring the aac(6′)-Ib gene. A new semisynthetic aminoglycoside, plazomicin, is in advance stage of development and will contribute to renewed interest in this kind of antibiotics.

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Section: Amikacinmentioning

confidence: 99%

Amikacin: Uses, Resistance, and Prospects for Inhibition

2017

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“…They have permeability properties similar to those of biological membranes. Liposome administration has been shown to provide delivery of antibiotics in mice infected with Mycobacterium avium (2,8,10,12,15,24,25,27) or M. tuberculosis (9,26,36) with some success.…”

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confidence: 99%

Efficacy of Microencapsulated Rifampin in Mycobacterium tuberculosis -Infected Mice

Quenelle¹,

Staas²,

Winchester³

et al. 1999

Antimicrob Agents Chemother

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Rifampin is a first-line drug useful in the treatment of tuberculosis. By using biocompatible polymeric excipients of lactide and glycolide copolymers, two microsphere formulations were developed for targeted and sustained delivery of rifampin, with minimal dosing. A small-microsphere formulation, with demonstrated ability to inhibit intracellularly replicating Mycobacterium tuberculosisH37Rv, was tested along with a large-microsphere formulation in an infected mouse model. Results revealed that by using a single treatment of the large-microsphere formulation, it was possible to achieve a significant reduction in M. tuberculosis H37Rv CFUs in the lungs of mice by 26 days postinfection. A combination of small (given as two injections on day 0 and day 7) and large (given as one injection at day 0) rifampin-loaded microsphere formulations resulted in significant reductions in CFUs in the lungs by 26 days, achieving a 1.23 log10 reduction in CFUs. By comparison, oral treatment with 5, 10, or 20 mg of rifampin/kg of body weight, administered every day, resulted in a reduction of 0.42, 1.7, or 1.8 log10units, respectively. Thus the microsphere formulations, administered in one or two doses, were able to achieve results in mice similar to those obtained with a daily drug regimen within the range of the highest clinically tolerated dosage in humans. These results demonstrate that microsphere formulations of antimycobacterial drugs such as rifampin can be used for therapy of tuberculosis with minimal dosing.

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“…A comparable technology for drug delivery is the use of liposomes. This technology has been used to deliver various drugs to treat M. avium (4,8,10,12,16,20,24,26) and M. tuberculosis infections (9,25,36). Although there have been some promising results, more studies are necessary to improve liposome technology in this area.…”

Section: Discussionmentioning

confidence: 99%

Use of Microsphere Technology for Targeted Delivery of Rifampin to Mycobacterium tuberculosis -Infected Macrophages

Barrow

Winchester

Staas

et al. 1998

Antimicrob Agents Chemother

105

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Microsphere technology was used to develop formulations of rifampin for targeted delivery to host macrophages. These formulations were prepared by using biocompatible polymeric excipients of lactide and glycolide copolymers. Release characteristics were examined in vitro and also in two monocytic cell lines, the murine J774 and the human Mono Mac 6 cell lines. Bioassay assessment of cell culture supernatants from monocyte cell lines showed release of bioactive rifampin during a 7-day experimental period. Treatment of Mycobacterium tuberculosis H37Rv-infected monocyte cell lines with rifampin-loaded microspheres resulted in a significant decrease in numbers of CFU at 7 days following initial infection, even though only 8% of the microsphere-loaded rifampin was released. The levels of rifampin released from microsphere formulations within monocytes were more effective at reducing M. tuberculosis intracellular growth than equivalent doses of rifampin given as a free drug. These results demonstrate that rifampin-loaded microspheres can be formulated for effective sustained and targeted delivery to host macrophages.

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Rationale for and Efficacy of Prolonged-Interval Treatment Using Liposome-Encapsulated Amikacin in Experimental Mycobacterium avium Infection

Cited by 53 publications

References 19 publications

Amikacin: Uses, Resistance, and Prospects for Inhibition

Amikacin: Uses, Resistance, and Prospects for Inhibition

Efficacy of Microencapsulated Rifampin in Mycobacterium tuberculosis -Infected Mice

Use of Microsphere Technology for Targeted Delivery of Rifampin to Mycobacterium tuberculosis -Infected Macrophages

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