Efficacy of ME1036 against meticillin-resistant Staphylococcus aureus and vancomycin-insensitive S. aureus in a model of haematogenous pulmonary infection

Yanagihara, Katsunori; Ohnishi, Yuriko; Morinaga, Yoshitomo; Nakamura, Shigeki; Kurihara, Shintaro; Seki, Masafumi; Izumikawa, Koichi; Kakeya, Hiroshi; Yamamoto, Yoshihiro; Yamada, Yasuaki; Kohno, Shigeru; Kamihira, Shimeru

doi:10.1016/j.ijantimicag.2008.04.030

Cited by 5 publications

(1 citation statement)

References 13 publications

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“…Our findings agree with other studies in which mice were infected intravenously with methicillin-resistant S. aureus , then administered a dose of antibiotic on a daily basis for a week. 25 , 26 , 27 However, in our study we used a single dose of S. aureus -specific lytic phage.…”

Section: Discussionmentioning

confidence: 99%

Experimental phage therapy against haematogenous multi-drug resistant <i>Staphylococcus aureus</i> pneumonia in mice

et al. 2016

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BackgroundCommunity-acquired haematogenous Staphylococcus aureus pneumonia is a rare infection, though it can be acquired nosocomially. Currently, antibiotics used against S. aureus pneumonia have shown reduced efficacy. Thus, there is need for an alternative therapy against multidrug-resistant S. aureus (MDRSA) strains in the community.ObjectiveWe sought to determine the efficacy of environmentally-obtained S. aureus lytic phage against haematogenous MDRSA pneumonia in mice.MethodsPhages and MDRSA were isolated from sewage samples collected within Nairobi County, Kenya. Isolated S. aureus bacteria were screened for resistance against ceftazidime, oxacillin, vancomycin, netilmicin, gentamicin, erythromycin, trimethroprim-sulfamethoxazole and cefuroxime. Thirty BALB/c mice aged six to eight weeks were randomly assigned into three groups: the MDRSA-infection group (n = 20), the phage-infection group (n = 5) and the non-infection group (n = 5). Mice were infected with either MDRSA or phage (108 CFU/mL) and treated after 72 hours with a single dose of clindamycin (8 mg/kg/bwt) or 108 PFU/mL of phage or a combination therapy (clindamycin and phage). The efficacy of phage, clindamycin or clindamycin with phage combination was determined using resolution of lung pathology and bacterial load in lung homogenates.ResultsThe viable MDRSA count was 0.5 ± 0.2 log10 CFU/gm in the phage-treated group, 4.4 ± 0.2 log10 CFU/gm in the clindamycin-treated group and 4.0 ± 0.2 log10 CFU/gm in the combination-treated group. The efficacy of phage therapy was significantly different from other therapeutic modes (p = 0 < 0.0001). Histology showed that the mice treated with phage did not develop pneumonia.ConclusionPhage therapy is effective against haematogenous MDRSA infection. Thus, it can be explored as an alternative treatment method.

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Section: Discussionmentioning

confidence: 99%

Experimental phage therapy against haematogenous multi-drug resistant <i>Staphylococcus aureus</i> pneumonia in mice

et al. 2016

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β‐Lactam Antibiotics

Testero

Fisher

Mobashery

2010

Burger's Medicinal Chemistry and Drug Discovery

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The β‐lactam classes of antibacterials are preeminent in the treatment of bacterial infection due to their unparalleled clinical efficacy and clinical safety. Following the discovery of the penicillins, successive β‐lactam drug discovery has added the cephalosporin, penem cephamycin, clavulanate, monobactam, nocardicin, and carbapenem subclasses. The driving force behind much of this era of discovery is the staggering ability of pathogenic bacteria to adapt previous generations of the β‐lactam by the acquisition and expression of resistance mechanisms. Although many factors contribute to β‐lactam resistance, alterations to the molecular targets of the β‐lactams (the penicillin binding proteins) and the use of enzymes (the β‐lactamases) capable of the hydrolytic deactivation of the β‐lactams are paramount. This review traces the historical development of β‐lactam drug discovery, with emphasis on the most recent progress in the medicinal chemistry, biochemistry, and microbiology of the β‐lactams leading to the discovery of new generation β‐lactam antibacterials effective against the Gram‐negative and ‐positive bacterial pathogens of current medical concern.

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Laboratory Biofilm Reactors

Kanematsu

Barry

2020

Formation and Control of Biofilm in Various Environments

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Efficacy of ME1036 against meticillin-resistant Staphylococcus aureus and vancomycin-insensitive S. aureus in a model of haematogenous pulmonary infection

Abstract: ME1036 produced >3 log10 reduction versus control against both MRSA strains: >5 log for the vancomycin-susceptible and 3.4 log for the VISA, whereas vancomycin produced <1.3 log for both strains.

Cited by 5 publications

References 13 publications

Experimental phage therapy against haematogenous multi-drug resistant <i>Staphylococcus aureus</i> pneumonia in mice

Experimental phage therapy against haematogenous multi-drug resistant <i>Staphylococcus aureus</i> pneumonia in mice

β‐Lactam Antibiotics

Laboratory Biofilm Reactors

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