Raoul Herbrecht

Publications (3)15.64 Total impact

• Article: An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity.

  Louis Y A Chai, Mihai G Netea, Bee Choo Tai, Lay Wai Khin, Alieke G Vonk, Boon Wee Teo, Haran T Schlamm, Raoul Herbrecht, J Peter Donnelly, Peter F Troke, Bart-Jan Kullberg
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  ABSTRACT: OBJECTIVES: The underlying mechanism for amphotericin B-induced acute kidney injury (AKI) remains poorly understood and may be immunologically mediated. We assessed whether the development of nephrotoxicity is linked to a distinct cytokine profile in patients receiving amphotericin B deoxycholate (AmBD). PATIENTS AND METHODS: In 58 patients who received AmBD, circulating serum interleukin (IL)-6, IL-8 and IL-10 were measured at baseline, week 1 and week 2 of antifungal treatment and correlated to the development of renal impairment. The Cox proportional hazards model approach was adopted for analysis. RESULTS: The P value was 0.026 for the overall effect of IL-6 on time to development of AKI. An increasing or non-receding IL-6 trend by week 1 of AmBD treatment (followed by a decreasing or non-receding IL-6 trend from week 1 to week 2) correlated with an increased likelihood of nephrotoxicity [hazard ratio (HR) 6.93, P value 0.005 and HR 3.46, P value 0.035, respectively]. Similarly, persistently increasing IL-8 levels were linked to a 3.84-fold increased likelihood of AKI. CONCLUSIONS: In patients receiving AmBD, persistence of an elevated pro-inflammatory cytokine milieu is associated with a predisposition to drug-related kidney injury.
  Journal of Antimicrobial Chemotherapy 04/2013; · 5.07 Impact Factor
• Article: Early serum galactomannan trend as a predictor of outcome of invasive aspergillosis.

  Louis Y A Chai, Bart-Jan Kullberg, Elizabeth M Johnson, Steven Teerenstra, Lay Wai Khin, Alieke G Vonk, Johan Maertens, Olivier Lortholary, Peter J Donnelly, Haran T Schlamm, Peter F Troke, Mihai G Netea, Raoul Herbrecht
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  ABSTRACT: The monitoring and prediction of treatment responses to invasive aspergillosis (IA) are difficult. We determined whether serum galactomannan index (GMI) trends early in the course of disease may be useful in predicting eventual clinical outcomes. For the subjects recruited into the multicenter Global Aspergillosis Study, serial GMIs were measured at baseline and at weeks 1, 2, and 4 following antifungal treatment. Clinical response and survival at 12 weeks were the outcome measures. GMI trends were analyzed by using the generalized estimation equation approach. GMI cutoffs were evaluated by using receiver-operating curve analyses incorporating pre- and posttest probabilities. Of the 202 study patients diagnosed with IA, 71 (35.1%) had a baseline GMI of ≥ 0.5. Week 1 GMI was significantly lower for the eventual responders to treatment at week 12 than for the nonresponders (GMIs of 0.62 ± 0.12 and 1.15 ± 0.22, respectively; P = 0.035). A GMI reduction of >35% between baseline and week 1 predicted a probability of a satisfactory clinical response. For IA patients with pretreatment GMIs of <0.5 (n = 131; 64.9%), GMI ought to remain low during treatment, and a rising absolute GMI to >0.5 at week 2 despite antifungal treatment heralded a poor clinical outcome. Here, every 0.1-unit increase in the GMI between baseline and week 2 increased the likelihood of an unsatisfactory clinical response by 21.6% (P = 0.018). In summary, clinical outcomes may be anticipated by charting early GMI trends during the first 2 weeks of antifungal therapy. These findings have significant implications for the management of IA.
  Journal of clinical microbiology 05/2012; 50(7):2330-6. · 4.16 Impact Factor
• Source

  Available from: Mihai G Netea

  Article: Early proinflammatory cytokines and C‐reactive protein trends as predictors of outcome in invasive Aspergillosis.

  Louis A Chai, Mihai G Netea, Steven Teerenstra, Arul Earnest, Alieke G Vonk, Haran T Schlamm, Raoul Herbrecht, Peter F Troke, Bart Jan Kullberg
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  ABSTRACT: Monitoring treatment response in invasive aspergillosis is challenging, because an immunocompromised host may not exhibit reliable symptoms and clinical signs. Cytokines play a pivotal role in mediating host immune response to infection; therefore, the profiling of biomarkers may be an appropriate surrogate for disease status. We studied, in a cohort of 119 patients with invasive aspergillosis who were recruited in a multicenter clinical trial, serum interleukin (IL)-6, IL‐8, IL‐10, interferon‐γ, and C‐reactive protein (CRP) trends over the first 4 weeks of therapy and correlated these trends to clinical outcome parameters. Circulating IL‐6 and CRP levels were high at initiation of therapy and generally showed a downward trend with antifungal treatment. However, subjects with adverse outcomes exhibited a distinct lack of decline in IL‐6 and CRP levels at week 1, compared with responders (P = .02, for both IL‐6 and CRP). Nonresponders also had significantly elevated IL‐8 levels (P = .001). High initial IL‐8 and persistently elevated IL‐6, IL‐8, and CRP levels after initiation of treatment may be early predictors of adverse outcome in invasive aspergillosis. Cytokine and CRP profiles could be used for early identification of patients with a poor response to antifungal treatment who may benefit from more‐aggressive antimicrobial regimens.
  The Journal of Infectious Diseases 09/2010; 202(9):1454-62. · 6.41 Impact Factor