Synergistic effect of linezolid with fosfomycin against Staphylococcus aureus in vitro and in an experimental Galleria mellonella model

Li, Lan; Chen, Hao; Liu, Yanyan; Xu, Shuangli; Wu, Maomao; Liu, Zhou; Qi, Caifen; Zhang, Guijun; Li, Jiabin; Huang, Xiaohui

doi:10.1016/j.jmii.2018.12.007

Cited by 17 publications

(16 citation statements)

References 32 publications

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“…These factors make G. mellonella an ideal preliminary infection model. Based on our successful application of this model to verify bacterial infection in previous studies, we used it for our in vivo experiments in the present work as well (Li et al, 2018;Lu et al, 2018;Trevijano-Contador and Zaragoza, 2018).…”

Section: Introductionmentioning

confidence: 99%

Minocycline and Fluconazole Have a Synergistic Effect Against Cryptococcus neoformans Both in vitro and in vivo

Kong

Cao

et al. 2020

Front. Microbiol.

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In recent decades, the incidence of Cryptococcus neoformans infection, which causes cryptococcosis, has consistently increased. Fluconazole (FLU) is frequently used in the treatment of this disease, mainly in the immunocompromised population, and longterm therapy usually produces drug resistance. Research on antifungal sensitizers has gained attention as a possible means of overcoming this drug resistance. Minocycline (MINO) has an inhibitory effect in vitro on FLU-resistant Candida albicans, and the combination of MINO and FLU has a synergistic effect on FLU-resistant C. albicans. A synergistic effect of MINO/FLU has been reported against C. neoformans, but this effect has not been evaluated on FLU-resistant isolates. This study aimed to investigate the interaction of MINO and FLU against FLU-resistant C. neoformans both in vitro and in vivo. We found that the combination of MINO and FLU had a synergistic effect on FLUresistant C. neoformans in vitro. For all FLU-resistant strains, the minimum inhibitory concentration (MIC) of FLU decreased significantly when used in combination with MINO, dropping from >128 µg/ml down to 4-8 µg/ml. Additionally, MINO and FLU had a synergistic effect on both susceptible and resistant C. neoformans biofilms, in which the MIC of FLU decreased from >256 µg/ml down to 4-16 µg/ml. Compared with FLU alone, the combination of MINO with FLU prolonged the survival rate of Galleria mellonella larvae infected with FLU-resistant C. neoformans, and also significantly decreased the fungal burden of infected larvae and reduced the tissue damage and destruction caused by FLU-resistant C. neoformans. These findings will contribute to the discovery of antifungal agents and may yield a new approach for the treatment of cryptococcosis caused by FLU-resistant C. neoformans.

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Section: Introductionmentioning

confidence: 99%

Minocycline and Fluconazole Have a Synergistic Effect Against Cryptococcus neoformans Both in vitro and in vivo

Kong

Cao

et al. 2020

Front. Microbiol.

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“…Fosfomycin combinations have also been evaluated against S. aureus . Cefazolin, doripenem, meropenem, moxifloxacin, and quinupristin/dalfopristin all demonstrated synergy in vitro against both methicillin‐susceptible S. aureus (MSSA) and MRSA .…”

Section: Fosfomycin In Combination With Other Antibiotics In In Vitromentioning

confidence: 99%

“…Cefazolin, doripenem, meropenem, moxifloxacin, and quinupristin/dalfopristin all demonstrated synergy in vitro against both methicillin‐susceptible S. aureus (MSSA) and MRSA . Linezolid in combination with fosfomycin has also repeatedly demonstrated synergy against MSSA and MRSA in both in vitro testing and Galleria mellonella models . In contrast to other antibiotics tested in combination with fosfomycin, vancomycin in combination has demonstrated to be indifferent to antagonistic against S. aureus .…”

Section: Fosfomycin In Combination With Other Antibiotics In In Vitromentioning

confidence: 99%

“…58,71 Fosfomycin combinations have also been evaluated against S. aureus. 67,70,[73][74][75] Cefazolin, doripenem, meropenem, moxifloxacin, and quinupristin/dalfopristin all demonstrated synergy in vitro against both methicillin-susceptible S. aureus (MSSA) and MRSA. 73,76 Linezolid in combination with fosfomycin has also repeatedly demonstrated synergy against MSSA and MRSA in both in vitro testing and Galleria mellonella models.…”

Section: Gram-positive Bacteriamentioning

confidence: 99%

“…73,76 Linezolid in combination with fosfomycin has also repeatedly demonstrated synergy against MSSA and MRSA in both in vitro testing and Galleria mellonella models. 67,[73][74][75] In contrast to other antibiotics tested in combination with fosfomycin, vancomycin in combination has demonstrated to be indifferent to antagonistic against S. aureus. 73 Similar to Enterococcus species, rifampin plus fosfomycin demonstrated synergy against MRSA in vitro, and tigecycline demonstrated synergy as well, although against fewer isolates.…”

Section: Gram-positive Bacteriamentioning

confidence: 99%

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Parenteral Fosfomycin for the Treatment of Multidrug Resistant Bacterial Infections: The Rise of the Epoxide

2019

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Fosfomycin was initially discovered in 1969 but has recently gained renewed interest for the treatment of multidrug‐resistant (MDR) bacterial infections, particularly in the United States. Its unique mechanism of action, bactericidal activity, broad spectrum of activity, and relatively safe and tolerable adverse effect profile make it a great addition to the dwindling antibiotic armamentarium. Fosfomycin contains a three‐membered epoxide ring with a direct carbon to phosphorous bond that bypasses the intermediate oxygen bond commonly present in other organophosphorous compounds; this structure makes the agent unique from other antibiotics. Despite nearly 50 years of parenteral fosfomycin use in Europe, fosfomycin has retained stable activity against most pathogens. Furthermore, fosfomycin demonstrated in vitro synergy in combination with other cell wall–active antibiotics (e.g., β‐lactams, daptomycin). These combinations may offer respite for severe infections due to MDR gram‐positive and gram‐negative bacteria. The intravenous (IV) formulation is currently under review in the United States, and apropos, this review collates more contemporary evidence (i.e., studies published between 2000 and early 2019) in anticipation of this development. The approval of IV fosfomycin provides another option for consideration in the management of MDR infections. Its unique structure will give rise to a promising epoxide epoch in the battle against MDR bacteria.

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Discovery of N,N'‐diarylurea molecules with activity against multidrug‐resistant Staphylococcus aureus

Yeo,

Jao,

Yang

et al. 2024

Archiv der Pharmazie

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The emergence and global spread of methicillin‐resistant Staphylococcus aureus (MRSA) pose a serious threat to public health, underscoring the urgent need for novel antibacterial interventions. Here, we screened 18 newly synthesized N,N’‐diarylurea derivatives to identify compounds with activity against MRSA. Our investigations led to the discovery of a small molecule, SCB‐24, which exhibited promising antimicrobial activity against MRSA USA300. Notably, SCB‐24 demonstrated high activity even in the presence of 10% fetal bovine serum and showed excellent selectivity for bacterial over mammalian cells. SCB‐24 also showed potent activity against various MRSA strains, including those resistant to second‐ and third‐line antibiotics. Importantly, the efficacy of SCB‐24 was inferior to that of vancomycin in MRSA‐infected Galleria mellonella larvae. Overall, our findings suggest that SCB‐24 has great potential as a new therapeutic for multidrug‐resistant S. aureus infections.

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Synergistic effect of linezolid with fosfomycin against Staphylococcus aureus in vitro and in an experimental Galleria mellonella model

Cited by 17 publications

References 32 publications

Minocycline and Fluconazole Have a Synergistic Effect Against Cryptococcus neoformans Both in vitro and in vivo

Minocycline and Fluconazole Have a Synergistic Effect Against Cryptococcus neoformans Both in vitro and in vivo

Parenteral Fosfomycin for the Treatment of Multidrug Resistant Bacterial Infections: The Rise of the Epoxide

Discovery of N,N'‐diarylurea molecules with activity against multidrug‐resistant Staphylococcus aureus

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