Evaluation of linezolid or trimethoprim/sulfamethoxazole in combination with rifampicin as alternative oral treatments based on an in vitro pharmacodynamic model of staphylococcal biofilm

Haj, Cristina El; Murillo, Óscar; Ribera, Alba; Lloberas, Núria; Gómez-Junyent, Joan; Tubau, Fé; Fontova, Pere; Cabellos, Carmen; Ariza, Javier

doi:10.1016/j.ijantimicag.2018.01.014

Cited by 19 publications

(12 citation statements)

References 34 publications

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“…However, our results showed the synergistic bactericidal effect for linezolid and rifampicin combination. This is supported by the previous observation that the combination of linezolid and rifampicin resulted in 3.1-log 10 cfu/mL killing in vitro against staphylococcal biofilm (El Haj et al, 2018). Similarly, linezolid used in combination with rifampicin was more effective than their monotherapies, reducing the planktonic MRSA cells by >3.0 log 10 cfu/mL in the cage fluids of foreign-body infections (Baldoni et al, 2009).…”

Section: Discussionsupporting

confidence: 69%

Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection

Zhou

Tao

et al. 2020

Front. Microbiol.

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Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P < 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC 50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA.

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Section: Discussionsupporting

confidence: 69%

Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection

Zhou

Tao

et al. 2020

Front. Microbiol.

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“…In any case, both laboratory methods are static and do not mimic the real in vivo situation, in which the antibiotic concentrations are not constant. To overcome this problem, dynamic in vitro experiments have been designed and in vivo studies using animal models should be considered necessary [ 11 , 35 , 36 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Synergy of Linezolid with Several Antimicrobial Agents against Linezolid-Methicillin-Resistant Staphylococcal Strains

et al. 2020

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Linezolid is a synthetic oxazolydinone active against multi-resistant Gram-positive cocci that inhibits proteins synthesis by interacting with the 50S ribosomal subunit. Although linezolid-resistant strains are infrequent, several outbreaks have been recently described, associated with prolonged treatment with the antibiotic. As an alternative to monotherapy, the combination of different antibiotics is a commonly used option to prevent the selection of resistant strains. In this work, we evaluated combinations of linezolid with classic and new aminoglycosides (amikacin, gentamicin and plazomicin), carbapenems (doripenem, imipenem and meropenem) and fosfomycin on several linezolid- and methicillin-resistant strains of Staphylococcus aureus and S. epidermidis, isolated in a hospital intensive care unit in Madrid, Spain. Using checkerboard and time-kill assays, interesting synergistic effects were encountered for the combination of linezolid with imipenem in all the staphylococcal strains, and for linezolid–doripenem in S.epidermidis isolates. The combination of plazomicin seemed to also have a good synergistic or partially synergistic activity against most of the isolates. None of the combinations assayed showed an antagonistic effect.

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“…Of note, one major point pleading for the use of SXT over FQ is that MRSA strains seem to remain susceptible to SXT even after a SXT exposure [33]. However, physicians should be wary that there is a possible risk of emergence of resistance against rifampicin when prescribed in dual therapy with SXT, despite a combination therapy [34]. Nevertheless, it should be noted that those concerns are based on in vitro data and must be discussed in the light of clinical findings.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of cotrimoxazole (Sulfamethoxazole-Trimethoprim) as a salvage therapy for the treatment of bone and joint infections (BJIs)

et al. 2019

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IntroductionCotrimoxazole (Sulfamethoxazole-Trimethoprim, SXT) has interesting characteristics for the treatment of bone and joint infection (BJI): a broad spectrum of activity with adequate bone diffusion and oral and intravenous formulations. However, its efficacy and safety in BJIs are poorly documented and its use remains limited.MethodsWe conducted a retrospective study in 2 reference centers for BJIs from 2013 to 2018 among patients treated with SXT for a BJI. Data were collected from patient’s medical charts. Outcomes and adverse events were evaluated at day (D)7, D45 and D90.ResultsWe analyzed 51 patients with a mean age of 60 ± 20 (SD) years of which 76% presented with an orthopedic device infection (ODI). Gram-negative bacilli (GNB) were involved in 47% of BJIs (n = 24). Moreover, they were often polymicrobial infections (41%). Doses of SXT ranged from 800/160mg bid (61%; n = 31) to 800/160mg tid (39%; n = 20). Median SXT treatment duration was 45 days (IQR 40–45). SXT was part of a dual therapy in 84% of patients (n = 43), associated mainly with fluoroquinolones (n = 17) or rifampicin (n = 14). Outcome was favorable at D7 in 98% (n = 50), at D45 in 88.2% (n = 45) and at D90 in 78.4% (n = 40). The second agent combined with SXT was not an independent factor of favorable outcome (p = 0.97). Adverse events were reported in 8% (n = 4) of patients, with a median of 21 days (IQR 20–30) from SXT initiation and led to discontinuation (n = 3).ConclusionSXT appears to be effective for treatment of BJIs as a salvage therapy, even in GNB or polymicrobial infection, including ODI. Further data are needed to confirm SXT efficacy as an alternative oral regimen in BJIs.

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Evaluation of linezolid or trimethoprim/sulfamethoxazole in combination with rifampicin as alternative oral treatments based on an in vitro pharmacodynamic model of staphylococcal biofilm

Cited by 19 publications

References 34 publications

Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection

Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection

Synergy of Linezolid with Several Antimicrobial Agents against Linezolid-Methicillin-Resistant Staphylococcal Strains

Efficacy of cotrimoxazole (Sulfamethoxazole-Trimethoprim) as a salvage therapy for the treatment of bone and joint infections (BJIs)

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