A multicentre pharmacoepidemiological study of therapeutic practices in invasive fungal infections in France during 1998-1999

Lortholary, Olivier; Charlemagne, Agnès; Bastides, Frédéric; Chevalier, P.; Datry, A.; Gonzalves, Marie-France; Michel, Gérard; Tilleul, P.; Veber, Benoît; Herbrecht, Raoul

doi:10.1093/jac/dkh348

Cited by 16 publications

(17 citation statements)

References 35 publications

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“…Other registries or studies have also gathered information on IMIs but have been hindered by a scope of observations limited in terms of patient type, therapies used or geographic areas [7,10,11]. In contrast, the NAAR is a registry that allows the collection and analysis of high-quality data obtained from targeted centres with substantial clinical experience and is facilitated by the use of electronic data capture and reporting software.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, changes in transplantation practices, including the sources used for stem cells, conditioning regimens and strategies to diagnose and treat IFI, have likely impacted the epidemiology and outcomes of infections [8,9]. Most recent data are limited to single-centre studies usually with a high patient volume and experience as well as a focus on allogeneic transplantation [10,11]. Few data are available on the incidence, prophylaxis and treatment of IFI in countries with a homogeneous health system and registries covering many centres with a different medical focus and specialisation.…”

Section: Introductionmentioning

confidence: 99%

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The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients

Perkhofer¹,

Lass‐Flörl²,

Hell³

et al. 2010

International Journal of Antimicrobial Agents

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A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide Austrian Aspergillus Registry. In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100000 inhabitants. Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%). In total, 34%, 30% and 36% were proven, probable and possible cases of IMI. Predominant pathogens were Aspergillus spp. (67%), followed by the zygomycetes (28%). Voriconazole was the most frequently administered agent (38%), followed by caspofungin (20%) and posaconazole (19%). Eighty patients (43%) received antifungal prophylaxis for ≥7 days, 30% of whom (24 patients) suffered from a breakthrough infection. The overall crude 12-week mortality was 34%. Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age (P>0.05). Aspergillosis remains the most commonly identified IMI amongst immunocompromised and/or immunosuppressed patients, but other moulds constitute a significant problem. Survival from IMIs appears to have improved and the main challenge is to overcome breakthrough fungal infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients

Perkhofer¹,

Lass‐Flörl²,

Hell³

et al. 2010

International Journal of Antimicrobial Agents

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“…Although interpretive breakpoints for amphotericin B have not been established, isolates of Candida for which MICs are Ͼ1 g/ml are unusual and possibly "resistant" or, at the very least, may require high doses of amphotericin B for optimal treatment (189,253,274). Application of the Etest agar-based technology to determine amphotericin B MICs in the context of a broad antifungal surveillance program has identified specific differences in the susceptibilities of the various species of Candida to this former "gold standard" antifungal agent (Table 10) (20,92,113,136,202,207,212,215,323). Although very little temporal or geographic variation in the susceptibility of Candida species to amphotericin B has been observed, it is evident that both C. glabrata and C. krusei exhibit decreased susceptibility to amphotericin B compared with C. albicans (Table 10) (113,120,202,215,216,323).…”

Section: Trends In Antifungal Susceptibility In Relation To Time Geomentioning

confidence: 99%

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

2007

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SUMMARY Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.

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“…It is estimated that the excess cost attributable to candidemia in the United States approaches $1 billion per year (46,60,111). Although much of this cost can be attributed to length of stay in hospital, the cost of antifungal therapy, especially the newer lipid formulations of amphotericin B, the echinocandins, and the extended-spectrum triazoles, is not inconsequential (41,46,60,111). Selection of the optimal antifungal therapeutic strategy is becoming increasingly complex and is often complicated further by concerns of emerging antifungal resistance (9, 41, 59).…”

Section: Clinical Importance Of Antifungal Susceptibility Testing As mentioning

confidence: 99%

Interpretive Breakpoints for Fluconazole and Candida Revisited: a Blueprint for the Future of Antifungal Susceptibility Testing

2006

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SUMMARY Developing interpretive breakpoints for any given organism-drug combination requires integration of the MIC distribution, pharmacokinetic and pharmacodynamic parameters, and the relationship between in vitro activity and outcome from both in vivo and clinical studies. Previously, the Subcommittee for Antifungal Testing of the Clinical and Laboratory Standards Institute (CLSI [formerly National Committee for Clinical Laboratory Standards]) proposed MIC interpretive breakpoints for fluconazole and Candida spp. These breakpoints were considered to be somewhat weak, because the clinical data supporting them came largely from mucosal infections and there were very few infections involving strains with elevated fluconazole MICs. We readdress the issue of fluconazole breakpoints for Candida by using published clinical and microbiologic data to provide further validation of the breakpoints proposed by the CLSI in 1997. We also address interpretive breakpoints for agar disk diffusion testing of fluconazole. The MIC distribution for fluconazole was determined with a collection of 13,338 clinical isolates. The overall MIC at which 90% of the isolates were inhibited was 8 μg/ml: 91% were susceptible (S) at a MIC of ≤8 μg/ml and 3% were resistant (R) (MIC ≥ 64 μg/ml). Similar results were obtained for 2,190 isolates from randomized clinical trials. Analysis of available data for 1,295 patient-episode-isolate events (692 represented mucosal infections and 603 represented invasive infections) from 12 published clinical studies demonstrated an overall success rate of 77%, including 85% for those episodes in which the fluconazole MIC was ≤8 μg/ml, 67% for those episodes in which the MIC was 16 to 32 μg/ml, and 42% for those episodes with resistant (MIC ≥ 64 μg/ml) isolates. Pharmacodynamic analysis demonstrated a strong relationship between MIC, fluconazole dose, and outcome. A dose/MIC ratio of ∼25 was supportive of the following susceptibility breakpoints for fluconazole and Candida spp.: S, MIC ≤ 8 μg/ml; susceptible-dose dependent (SDD), MIC = 16 to 32 μg/ml; R, MIC ≥ 64 μg/ml. The corresponding disk test breakpoints are as follows: S, ≥19 mm; SDD, 15 to 18 mm; R, ≤14 mm.

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A multicentre pharmacoepidemiological study of therapeutic practices in invasive fungal infections in France during 1998-1999

Abstract: Our results emphasize factors associated with the antifungal therapeutic decision and with the outcome of IFI.

Cited by 16 publications

References 35 publications

The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients

The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

Interpretive Breakpoints for Fluconazole and Candida Revisited: a Blueprint for the Future of Antifungal Susceptibility Testing

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