Clinical results of linezolid in arthroplasty and trauma related infections

Ja, James; Graham, Simon Matthew; Peckham‐Cooper, Adam; Korres, Nectarios; Tsouchnica, Helen; Tsiridis, Eleftherios

doi:10.5312/wjo.v5.i2.151

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…A further limitation that needs to be considered when interpreting the results of the studies included in this review is that one main indication for the use of linezolid reported was failure of the previous treatment. Given that repeat staged prosthetic revisions and further septic surgeries following treatment of a PJI are known to lead to much worse results (Kheir et al, 2017;Khan et al, 2019) with regard to remission of an infection, the results discussed here might be low-end estimates of the potential success rate when using linezolid in PJI patients. However, this might reflect current recommendations regarding the use of linezolid as a second-line reserve therapy (Osmon et al, 2013b;Aboltins et al, 2019;Sendi and Zimmerli, 2012).…”

Section: Discussionmentioning

confidence: 99%

Clinical use of linezolid in periprosthetic joint infections – a systematic review

Theil

Schmidt-Braekling

Gosheger

et al. 2020

J. Bone Joint Infect.

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Abstract. Introduction: The most common causative organism in periprosthetic joint infections (PJIs) is Gram-positive bacteria that are increasingly drug resistant. In these cases the use of linezolid may be warranted. However, there are conflicting reports regarding its role in antibiotic treatment of PJIs. The aim of this review is to gather and analyze clinical results and treatment details on linezolid in patients with PJIs. Methods: In August 2019, a comprehensive literature search using MEDLINE (Pubmed and Ovid) and Cochrane Library was performed. A total of 504 records were screened, and a total of 16 studies including 372 patients treated with linezolid for a PJI were included in this review based on the PRISMA criteria and after quality analysis using the MINOR score and Newcastle–Ottawa scale, as well as assessing level of evidence. Pooling analysis as well as descriptive analysis was performed. Results: Based on the results from the studies included, infection control was achieved in 80 % (range 30 %–100 %) of patients after a mean follow-up period of 25 (range 2–66) months. The mean duration of treatment was 58 d intravenous and orally at a median dose of 600 mg bis in die (b.i.d.) (range 400–900 b.i.d.). A combination therapy with rifampicin was used in 53 % of patients. MRSA (methicillin-resistant Staphylococcus aureus) infections were present in 29 % and resistant CoNS (coagulase-negative Staphylococcus) in 46 %. Adverse effects occurred in 33 % of cases, mostly anemia, thrombocytopenia and gastrointestinal complaints leading to treatment discontinuation in 9 %. However, great heterogeneity was found with respect to surgical treatment, diagnosis of infection and indication for linezolid. Discussion: Linezolid is an appropriate option for treatment of resistant Gram-positive organisms in PJIs. Most commonly 600 mg b.i.d. is used, and a combination with rifampicin appears feasible although one must consider individual increases in doses in these cases. However, adverse effects are common and there are limited data for long-term use and optimal antibiotic combinations or individual doses.

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Section: Discussionmentioning

confidence: 99%

Clinical use of linezolid in periprosthetic joint infections – a systematic review

Theil

Schmidt-Braekling

Gosheger

et al. 2020

J. Bone Joint Infect.

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“…Taking these limitations into account, our work nonetheless demonstrates that combining fusidic acid with linezolid or daptomycin could be a useful therapeutic option against staphylococcal biofilm-related infections in areas and/or situations where resistance to these drugs is low (essentially, in North America [19][20][21], but not in Europe [50,51] or other regions of the world [52,53]). Linezolid and daptomycin, although recommended for short-term use, sometimes need to be use for long periods of time (Ͼ3 weeks [54][55][56][57]) in difficult situations, such as those involving biofilms, which may expose the patients to higher risks of adverse events. Synergic combinations, as those evidenced here with fusidic acid, may offer a real opportunity in this context.…”

Section: Discussionmentioning

confidence: 99%

Activities of Combinations of Antistaphylococcal Antibiotics with Fusidic Acid against Staphylococcal Biofilms in In Vitro Static and Dynamic Models

Siala

Rodríguez-Villalobos

Fernandes

et al. 2018

Antimicrob Agents Chemother

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Staphylococcal biofilms are a major cause of therapeutic failure, especially when caused by multiresistant strains. Oral fusidic acid is currently being redeveloped in the United States for skin, skin structure, and orthopedic infections, in which biofilms play a major role. The aim of this study was to examine the activity of fusidic acid alone or combined with other antistaphylococcal drugs against biofilms made by a reference strain and five clinical isolates of or in static and dynamic models (microtiter plates and a CDC reactor) exposed to clinically relevant concentrations. In microtiter plates, antibiotics alone were poorly active, with marked differences among strains. At concentrations mimicking the free-drug human maximum concentration of drug in serum (), the combination of fusidic acid with linezolid, daptomycin, or vancomycin resulted in increased activity against 4 to 5 strains, while the combination with doxycycline, rifampin, or moxifloxacin increased activity against 1 to 3 strains only. In the CDC reactor, biofilms were grown under constant flow and antibiotic concentrations decreased over time according to human elimination rates. A bactericidal effect was obtained when fusidic acid was combined with daptomycin or linezolid, but not with vancomycin. The higher tolerance of biofilms to antibiotics in the CDC reactor is probably attributable to the more complex architecture they adopt when growing under constant flow. Because biofilms grown in the CDC reactor are considered more similar to those developing , the data support further testing of combinations of fusidic acid with daptomycin or linezolid in models pertinent to chronic skin, skin structure, or orthopedic infections.

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“…Linezolid is a synthetic antibiotic possessing a novel mode of action, inhibiting bacterial protein synthesis by binding to the domain V region of 23S rRNA at an early step, and prevents the formation of N-formylmethionyl-tRNA-mRNA-70S ribosomal tertiary complex (Alicem et al, 2014). Oral administration results in 100% bio-avail-ability and thus, oral and parental administration of the drug are bioequivalent (Joel et al, 2014). However, linezolid resistant strains have been increasingly reported worldwide (Livermore et al, 2009;Lincopan et al, 2009;Almeida et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Effect of Linezolid Alone and in Combination with Other Antibiotics , on Methicillin-Resistant Staphylococcus Aureus

Yehia¹,

Said²,

Azmy³

2016

JESP

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The prevalence of methicillin-resistant Staphyloccoccus aureus (MRSA) strains has presented a new challenge in antimicrobial medication. Linezolid is a new drug with potent activity on Grampositive pathogens such as MRSA. The aim of the study was to investigate the in vitro activity of linezolid alone and in combination with imipenem, vancomycin or rifampicin to determine the most active therapy against MRSA strains. Twenty clinical MRSA strains were isolated from patients admitted to inpatient departments and outpatient clinics of Theodor Bilharz Research Institute. Standard strain MRSA ATCC 43300 was included as a control. The MICs of MRSA strains to linezolid, vancomycin, imipenem and rifampicin were evaluated using E test. Time-kill curve were used to assess the in vitro activity of linezolid (at 8x MIC) alone and in combination with imipenem (at 32x MIC), vancomycin or rifampicin (at 8x MIC). Scanning and transmission electron microscopy were performed to compare bacterial morphological alterations owing to the different combinations. Time-kill studies showed synergistic effect when linezolid combined with imipenem was tested against all the MRSA strains. Linezolid plus vancomycin or rifampicin combinations did not display any synergism or antagonism. Scanning and transmission electron microscopy observations confirmed the interactions observed in time kill experiments. Linezolid in combination with subinhibitory concentrations of imipenem can be bactericidal against MRSA strains and appears to be a promising combination for the treatment of MRSA infections. No synergistic activity was seen when the linezolid and vancomycin or rifampicin were combined. Linezolid could prevent the emergence of mutants resistant to rifampicin

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Clinical results of linezolid in arthroplasty and trauma related infections

Cited by 6 publications

References 36 publications

Clinical use of linezolid in periprosthetic joint infections – a systematic review

Clinical use of linezolid in periprosthetic joint infections – a systematic review

Activities of Combinations of Antistaphylococcal Antibiotics with Fusidic Acid against Staphylococcal Biofilms in In Vitro Static and Dynamic Models

Effect of Linezolid Alone and in Combination with Other Antibiotics , on Methicillin-Resistant Staphylococcus Aureus

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