In vitro efficacy of fosfomycin-containing regimens against methicillin-resistant Staphylococcus aureus in biofilms

Tang, Hung‐Jen; Chen, Chi‐Chung; Cheng, Kuo-Chen; Toh, Han Siong; Su, Bo-An; Chiang, Shyh‐Ren; Ko, Wen Chien; Chuang, Yin-Ching

doi:10.1093/jac/dkr535

Cited by 64 publications

(67 citation statements)

References 42 publications

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“…Vancomycin plus rifampin has exhibited an in vitro synergistic effect against MRSA isolates with a high vancomycin MIC (2 g/ml) (13).However, the emergence and spread of rifampin-resistant MRSA isolates during vancomycin-rifampin combination therapy in an intensive care unit has been reported (14). Such a combination could easily induce high-level rifampin resistance (MIC Ͼ 64 g/ml) in biofilmembedded MRSA isolates, according to our in vitro study (8).…”

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confidence: 64%

“…Certainly, rifampin-resistant mutants, especially isolates with high-level resistance, could easily be selected during such combination therapy. Such diversity might also be related to the concentrations used during the experiments, as we previously mentioned (8).…”

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confidence: 89%

“…Linezolid monotherapy, as we previously reported (8), exhibited excellent inhibitory effects against biofilm-embedded MRSA. Rifampin augmented the antibacterial effect of linezolid in biofilm, as we previously found (8,12). Vancomycin plus rifampin has exhibited an in vitro synergistic effect against MRSA isolates with a high vancomycin MIC (2 g/ml) (13).However, the emergence and spread of rifampin-resistant MRSA isolates during vancomycin-rifampin combination therapy in an intensive care unit has been reported (14).…”

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confidence: 93%

“…Biofilms of individual strains were prepared in 24-well plates according to a previously described method (8) and were treated with vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, tigecycline, or rifampin alone or with rifampin-based combinations. The concentrations of most drugs were adjusted to the susceptible breakpoint concentrations (SBCs) recommended by the CLSI (9).…”

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confidence: 99%

“…Fosfomycin has long been used in combination therapies against MRSA, especially in biofilm (8,13). When used in a combination against biofilm-embedded MRSA, it possesses less mutation-inducing potential than rifampin (8).…”

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confidence: 99%

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In Vitro Efficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

Tang

Chen

Cheng

et al. 2013

Antimicrob Agents Chemother

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f To compare the in vitro antibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistant Staphylococcus aureus (MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.

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confidence: 64%

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confidence: 89%

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confidence: 93%

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confidence: 99%

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confidence: 99%

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In Vitro Efficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

Tang

Chen

Cheng

et al. 2013

Antimicrob Agents Chemother

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Fosfomycin for the Treatment of Resistant Gram‐Negative Bacterial Infections

Reffert

Smith

2014

Pharmacotherapy

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The antimicrobial agent fosfomycin was discovered in 1969, at a time when bacteria had not yet developed extended-spectrum β-lactamases or carbapenemases. Decades later, it is not uncommon for gram-negative organisms to be multidrug-resistant and even pan-resistant to available antibiotic regimens, leaving clinicians with few therapeutic alternatives. Because fosfomycin has been shown to retain activity against these virulent pathogens, there is renewed interest in its use as a therapeutic agent. Fosfomycin formulations including fosfomycin disodium and the newer tromethamine salt are less toxic than other alternatives and are attractive options for resistant gram-negative and gram-positive infections. Oral fosfomycin tromethamine is approved for urinary tract infections in the United States, and an intravenous formulation is also available outside of the United States for systemic disease. The bactericidal action of fosfomycin occurs at an earlier step in cell wall synthesis than that of β-lactam antibiotics. From an in vitro standpoint, fosfomycin generally has high activity against ESBL- and carbapenemase-producing Enterobacteriaceae; multidrug-resistant Pseudomonas aeruginosa susceptibility appears to be more dependent on the local antibiogram. Fosfomycin formulations have a large volume of distribution, penetrate biofilms, and concentrate in the urine. Both oral and intravenous fosfomycin formulations are effective for a wide range of gram-negative infections and disease severities; however, clinical studies are limited. Fosfomycin formulations are well-tolerated, and mild gastrointestinal distress is the most common adverse effect. The primary limitations of fosfomycin are the lack of established regimens for complicated infections and the lack of availability of the intravenous formulation in the United States. Further study of this promising agent seems warranted in the current climate of antibiotic resistance.

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Anti-biofilm Agents

Săndulescu

2017

Biofilm, Pilonidal Cysts and Sinuses

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In vitro efficacy of fosfomycin-containing regimens against methicillin-resistant Staphylococcus aureus in biofilms

Abstract: Fosfomycin enhanced the activities of linezolid, minocycline, vancomycin and teicoplanin. These combinatorial treatments were even better than rifampicin combination regimens, and may provide therapeutic advantages in catheter-related or prosthetic joint infections.

Cited by 64 publications

References 42 publications

In Vitro Efficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

In Vitro Efficacies and Resistance Profiles of Rifampin-Based Combination Regimens for Biofilm-Embedded Methicillin-Resistant Staphylococcus aureus

Fosfomycin for the Treatment of Resistant Gram‐Negative Bacterial Infections

Anti-biofilm Agents

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