Clinical Experience with Daptomycin for the Treatment of Patients with Osteomyelitis

Lamp, Kenneth C.; Friedrich, Lawrence V.; Mendez-Vigo, Luke; Russo, René

doi:10.1016/j.amjmed.2007.07.010

Cited by 99 publications

(73 citation statements)

References 27 publications

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“…aptomycin is being increasingly used for the treatment of complicated Gram-positive infections, such as osteomyelitis and infections of prosthetic devices caused by methicillin-resistant Staphylococcus aureus (MRSA) (1,2), but the evidence for the effectiveness of combination regimens with daptomycin has been limited. In cases of primary treatment failure with S. aureus infections, rifampin has been recommended as an adjunctive therapeutic agent (3).…”

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Relationship of In Vitro Synergy and Treatment Outcome with Daptomycin plus Rifampin in Patients with Invasive Methicillin-Resistant Staphylococcus aureus Infections

Rose

Berti

Hatch

et al. 2013

Antimicrob Agents Chemother

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We report the findings of a study examining the relationship between in vitro daptomycin-rifampin synergy and the therapeutic outcome of 12 patients with complex deep methicillin-resistant Staphylococcus aureus (MRSA) infections treated for prolonged periods with this combination. Checkerboard synergy was found in nine cases and was 100% predictive of therapeutic success; absence of synergy was found in three cases, two of which were therapeutic failures (P ‫؍‬ 0.045). No relationship was observed between synergy and outcome by time-kill assessment. Checkerboard synergy may predict clinical response to daptomycin plus rifampin for complex invasive MRSA infections requiring prolonged treatment. Daptomycin is being increasingly used for the treatment of complicated Gram-positive infections, such as osteomyelitis and infections of prosthetic devices caused by methicillin-resistant Staphylococcus aureus (MRSA) (1, 2), but the evidence for the effectiveness of combination regimens with daptomycin has been limited. In cases of primary treatment failure with S. aureus infections, rifampin has been recommended as an adjunctive therapeutic agent (3). Studies with in vitro and in vivo pharmacodynamic models of biofilm-associated infection support the use of daptomycin in combination with rifampin, where synergistic activity has been associated primarily with preventing the emergence of daptomycin-nonsusceptible strains (4-6). We have recently reported a high rate of success with daptomycin in combination with rifampin for treatment of complicated bone and joint infections (7), and in this study, we report the relationship between treatment outcome and in vitro synergy with complex deep MRSA infections.Patients with invasive MRSA infections treated with daptomycin plus rifampin between 2005 and 2008 at the University of Wisconsin Hospital and Clinics in Madison, WI, were retrospectively reviewed. Clinical and microbiologic treatment outcomes were determined using standard definitions for osteomyelitis and nonosteomyelitis infections at clinical endpoints of 1 year and 4 weeks after discontinuation of therapy, respectively (1,8), and compared to the results of in vitro synergy testing of the causative strain.The MRSA isolates from 12 patients treated with the study combination were retrieved from the hospital clinical microbiology laboratory and analyzed. Daptomycin (Cubist, Lexington, MA) and rifampin (Sigma-Aldrich, St. Louis, MO) susceptibility testing was performed by broth microdilution on all isolates (9). Antibiotic susceptibility in biofilm was also determined since most patients had infection sources that commonly involve biofilm formation. The MIC and minimum biofilm eradication concentration (MBEC) were determined using a previously described transferable solid-phase pin-lid method (10). Synergy testing was evaluated by two methods: (i) checkerboard analysis with standard definitions of fractional inhibitory concentrations (FIC) (synergy, FIC Յ 0.5; indifference, FIC of Ͼ0.5 but Յ4; antagonism, FIC Ͼ 4) (11); (ii...

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confidence: 99%

“…Clinical and microbiologic treatment outcomes were determined using standard definitions for osteomyelitis and nonosteomyelitis infections at clinical endpoints of 1 year and 4 weeks after discontinuation of therapy, respectively (1,8), and compared to the results of in vitro synergy testing of the causative strain.…”

mentioning

confidence: 99%

Relationship of In Vitro Synergy and Treatment Outcome with Daptomycin plus Rifampin in Patients with Invasive Methicillin-Resistant Staphylococcus aureus Infections

Rose

Berti

Hatch

et al. 2013

Antimicrob Agents Chemother

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“…Osteomiyelit hastalarında %63 kür elde edilmiş ve hastaların %19'unun semptom ve bulguları-nın iyileştiği gözlenmiştir [19] . Yaklaşık hastaların yarı- Daptomisin komplike CYDE'de daha kısa sürede etkin olarak bulunmuştur [20] .…”

Section: Discussionunclassified

Daptomycin Experience Between Years 2009-2013: Review of 139 Cases

Ulu¹,

Kurtaran²,

İnal³

et al. 2014

Mediterr J Infect Microb Antimicrob

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ÖZETGiriş: Daptomisin 2009 yılının ikinci yarısından itibaren ülkemizde yumuşak doku enfeksiyonları ve endokarditte kullanılmaya başlanan gram pozitif etkili bir antibakteriyel ajandır. Bu çalışmada amacımız hastanemizde daptomisinin klinik çalışmalar haricinde nasıl kullanıldığını ve kullanan hastaların özellikleri ile tedaviye cevaplarını tespit etmekti. Materyal ve Metod:Çalışmamızda 2009-2013 yılları arasında daptomisin kullanan hastalar retrospektif olarak değerlendirilmiş-tir. Hastaların demografik verileri, takip edildikleri klinikler, altta yatan hastalıklar, enfeksiyon bilgileri, üreyen mikroorganizmalar, tedavi ve klinik yanıt, yan etkiler kayıt edilmiş ve SPSS v20.0 programında analiz edilmiştir. Bulgular: Çalışmaya verilerinin tamamına erişilen 139 hasta alındı (yaş ortalaması 52.9 ± 16.4, hastaların %48.2'si erkek, %58.1'i kadın). Hastaların 52'si (%37.4) cilt ve yumuşak doku enfeksiyonu, 53'ü (%38.1) osteomiyelit, 16'sı (%11.5) protez eklem enfeksiyonu, yedisi primer kan dolaşımı enfeksiyonu (üç port enfeksiyonu, üç kateter ilişkili bakteremi ve bir laboratuvar kanıtlı bakteremi), dördü endokardit, üçü septik artrit, dördü de diğer enfeksiyonlar nedeniyle tedavi almıştır. Hastaların 107'sinde (%77) tedavi ampirik olarak başlanmıştır. Toplamda %68.6'sı gram-pozitif ve %30'u gram-negatif olmak üzere 86 mikroorganizma üre-mesi olmuştur. Hastaların sadece 10'u (%7.2) daha önce glikopeptit kullanmıştır. Tedavi sonu klinik yanıt %85.6 olarak saptanmıştır. Gram-pozitif bakteri üremesi olan hastalarda tedavi sonu klinik başarı %87,7 (50/57) olarak hesaplanmıştır, 12 hastada (%8.6) yan etki gelişmiştir. Görülen yan etkilerin yedisi muhtemel eozinofilik pnömoni iken, iki hastada CK artışı bir hastada palpablpurpura, bir hastada cilt döküntüsü ve bir hastada renal fonksiyon bozukluğu saptanmıştır.Sonuç: Daptomisinin, sıklıkla daha önceden tedavi almış, yumuşak doku enfeksiyonu ve osteomiyelit gibi komplike enfeksiyonlarda yüksek klinik başarı nedeniyle güvenle kullanılabilecek antibiyotik seçenekleri arasında olduğu görülmektedir. Gelecekte özellikle kemik eklem enfeksiyonlarında yapılacak randomize kontrollü çalışmalara ihtiyaç vardır.Anahtar kelimeler: Daptomisin, klinik başarı, osteomiyelit, yumuşak doku enfeksiyonu, bakteremi

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“…For the therapy of osteomyelitis in humans, DAP treatment regimens of 4 to 6 mg/kg once daily are currently used, although the use of a higher dose (Ͼ6 mg/kg) may improve outcome rates (15). For rats, Sakoulas et al demonstrated that the subcutaneous administration of DAP at 25 and 40 mg/kg once daily resulted in maximum drug concentrations and total drug exposures in serum that approximated those observed for humans given 4 and 6 mg/kg intravenously once daily (37).…”

Section: Discussionmentioning

confidence: 99%

Daptomycin, Fosfomycin, or Both for Treatment of Methicillin-Resistant Staphylococcus aureus Osteomyelitis in an Experimental Rat Model

Poeppl

Tobudic

Lingscheid

et al. 2011

Antimicrob Agents Chemother

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The in vivo activities of daptomycin, fosfomycin, and a combination of both antibiotics against a clinical isolate of methicillin-resistant Staphylococcus aureus (daptomycin MIC, 0.25 g/ml; fosfomycin MIC, 0.5 g/ml) were evaluated in a rat model of osteomyelitis. A total of 37 rats with experimental osteomyelitis were treated for 4 weeks with either 60 mg/kg of body weight of daptomycin subcutaneously once daily, 75 mg/kg fosfomycin intraperitoneally once daily, a combination of both drugs, or a saline placebo. After the completion of treatment, animals were euthanized, and the infected tibiae were processed for quantitative bacterial culture. Bone cultures were found to be positive for methicillin-resistant S. aureus in 9 of 9 (100%) animals of the placebo group, in 9 of 9 (100%) animals treated with daptomycin, in 1 of 10 (10%) fosfomycin-treated rats, and in 1 of 9 (22.2%) rats comprising the combination group. Results of bacterial counts in the bone samples were expressed as log 10 CFU/g of bone and analyzed by using the Mann-Whitney U test followed by Bonferroni's multiple-comparison test. Based on bacterial counts, treatment with daptomycin was significantly superior to placebo, although it remained inferior to treatment with fosfomycin. No synergistic or antagonistic effect was observed for the combination therapy. No development of resistance against daptomycin or fosfomycin was observed after the 4-week treatment period.

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Clinical Experience with Daptomycin for the Treatment of Patients with Osteomyelitis

Cited by 99 publications

References 27 publications

Relationship of In Vitro Synergy and Treatment Outcome with Daptomycin plus Rifampin in Patients with Invasive Methicillin-Resistant Staphylococcus aureus Infections

Relationship of In Vitro Synergy and Treatment Outcome with Daptomycin plus Rifampin in Patients with Invasive Methicillin-Resistant Staphylococcus aureus Infections

Daptomycin Experience Between Years 2009-2013: Review of 139 Cases

Daptomycin, Fosfomycin, or Both for Treatment of Methicillin-Resistant Staphylococcus aureus Osteomyelitis in an Experimental Rat Model

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