A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients

Jordanides, Niove E.; Allan, Elaine; McLintock, Lorna; Copland, Mhairi; Devaney, Maureen; Stewart, Karen; Parker, Anne; Johnson, Peter; Holyoake, Tessa L.; Jones, Brian

doi:10.1038/sj.bmt.1704768

Cited by 89 publications

(71 citation statements)

References 35 publications

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“…18,19,[26][27][28] The reported sensitivity and the NPV were moderate to high. The specificity was generally lower, but could be significantly improved by establishing the requirement of two consecutive positive PCR results as a diagnostic criterion.…”

Section: Discussionmentioning

confidence: 99%

“…Many of the published technical approaches based on real-time PCR methods are rapid and sensitive, but their detection spectrum is mostly restricted to a variety of Candida 13,14 or Aspergillus species, 15,16 or representatives of both genera. [17][18][19][20][21] Diagnostic assays permitting the detection of a wide range of fungal pathogens including fungal species of both common and emerging fungal genera are therefore required. To address the urgent clinical need, we have developed a panfungal real-time PCR assay permitting the detection of at least 80 pathogenic fungal species (European patent application 06817468.9).…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis of invasive fungal infections by a real-time panfungal PCR assay in immunocompromised pediatric patients

Landlinger¹,

Preuner²,

Bašková³

et al. 2010

Leukemia

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Invasive fungal disease (IFD) is a life-threatening event in immunocompromised patients, and there is an urgent need for reliable screening methods facilitating rapid and broad detection of pathogenic fungi. We have established a two-reaction real-time PCR assay permitting highly sensitive detection of more than 80 fungal pathogens, covering a large spectrum of moulds, yeasts and Zygomycetes. To assess the clinical potential of the assay, more than 600 consecutive specimens from 125 pediatric patients carrying a high risk of IFD were analyzed. An excellent correlation between PCR positivity and the presence of proven, probable or possible fungal infection according to the European Organization for Research and Treatment of Cancer criteria was demonstrated, as revealed by the sensitivity of the assay of 96% (95% CI: 82-99%). The negative predictive value of the panfungal PCR assay presented was 98% (95% CI: 90-100%), while the specificity and the positive predictive value were 77% (95% CI: 66-85%) and 62% (95% CI: 47-75%), respectively. The results indicate that molecular screening of patients during febrile neutropenic episodes by the assay presented could help prevent unnecessary toxicity resulting from empirical antifungal treatment in individuals who may not be at risk of imminent fungal disease. Our observations raise the possibility that rapid species identification may be required to increase the positive predictive value for impending fungus-related disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diagnosis of invasive fungal infections by a real-time panfungal PCR assay in immunocompromised pediatric patients

Landlinger¹,

Preuner²,

Bašková³

et al. 2010

Leukemia

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show abstract

“…Although the results have been variable, the authors of some of these reports have concluded that PCR contributes to establishment of the diagnosis of IFI. [15][16][17] It has also been reported that a positive PCR test precedes the clinical diagnosis of invasive aspergillosis (IA), by several days up to several weeks. 15,16 These findings raise the question of whether PCR-guided early antifungal treatment could reduce the incidence and mortality of IFI after HSCT, in an analogous way to the successful development of pre-emptive treatment of CMV.…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, noninvasive diagnostic techniques such as PCR-based assays capable of detecting DNA from Aspergillus and Candida species have been developed. [14][15][16][17][18][19] Several PCR protocols for detection of fungal DNA in blood have been used, with a wide range of sensitivity and specificity. Although the results have been variable, the authors of some of these reports have concluded that PCR contributes to establishment of the diagnosis of IFI.…”

Section: Introductionmentioning

confidence: 99%

Randomized PCR-based therapy and risk factors for invasive fungal infection following reduced-intensity conditioning and hematopoietic SCT

Blennow

Remberger

Klingspor

et al. 2010

Bone Marrow Transplant

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Invasive fungal infections (IFIs) are major complications after allogeneic hematopoietic SCT (HSCT). PCR-based assays able to detect fungal DNA have been reported to precede clinical diagnosis of IFI. We performed a prospective study to evaluate a PCR-based pre-emptive approach. Ninety-nine patients undergoing reduced-intensity conditioning (RIC) HSCT were followed with fungal PCR during the first 100 days post transplantation. Patients who tested positive were randomized to receive liposomal amphotericin B, or to no intervention. After day 100, PCR tests were performed only on clinical suspicion of IFI. A single positive PCR test was not associated with IFI, irrespective of treatment. After day 100, PCR tests for Aspergillus did not contribute to diagnosis of invasive aspergillosis (IA). The cumulative incidence rates of proven or probable IA during the first year after transplantation were 9%. GVHD grades II-IV (P ¼ 0.0014), CMV-seronegative recipient with CMVseropositive donor (Pp0.001), and conditioning with alemtuzumab (P ¼ 0.014) were significant risk factors for developing IA in a multivariate model. In this study, PCR on peripheral blood was a poor indicator of IFI early after RIC HSCT. Aspergillus PCR tests performed on clinical suspicion after day 100 were insufficiently sensitive to be diagnostically useful.

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“…Previous PCR techniques were unable to distinguish between filamentous and yeast species and required complex steps for amplification [27][28][29]. Real-time Taqman PCR is able to better characterize the fungal species, but is expensive, due in part to the requirement for a unique probe to search for a single fungal type per reaction [30].…”

Section: Polymerase Chain Reaction (Pcr)mentioning

confidence: 99%

Fungal Keratitis: Update for 2014

Stone

Tan

2014

Curr Ophthalmol Rep

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Fungal keratitis is a challenging problem worldwide, and many obstacles remain to the effective prevention, diagnosis, and therapy of this vision-threatening condition. Recent research has highlighted progress in each of these facets of the clinical approach to keratomycosis. Increased awareness of contact lens-associated fungal keratitis has prompted regulators to pay greater attention to testing of contact lens solutions under realworld conditions. Related research has also delved into the mechanisms of fungal biofilm formation and related therapeutic targets. Advances in polymerase chain reaction methodologies promise to increase the rapidity and accuracy of diagnosis, thereby decreasing the delay in instituting appropriate therapy. Antifungal pharmacologic agents remain the first line of therapy, with the newer azole antifungal voriconazole being utilized in innovative ways, such as via intrastromal injection. Large prospective studies such as the Mycotic Ulcer Treatment Trial have helped delineate optimal treatment algorithms, and variations in surgical techniques and postoperative regimens continue to be refined. Natamycin may still be more effective than other recently utilized antifungals for the treatment of Fusarium infections, but treatment failure is still a concern. Post-keratoplasty immunosuppression may benefit from the use of topical calcineurin inhibitors such as cyclosporine and tacrolimus, given their intrinsic antifungal properties. It can be argued that the prevention, diagnosis, and treatment of fungal keratitis lag behind the state of the art for bacterial keratitis, but dramatic improvements are undoubtedly on the horizon.

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A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients

Cited by 89 publications

References 35 publications

Diagnosis of invasive fungal infections by a real-time panfungal PCR assay in immunocompromised pediatric patients

Diagnosis of invasive fungal infections by a real-time panfungal PCR assay in immunocompromised pediatric patients

Randomized PCR-based therapy and risk factors for invasive fungal infection following reduced-intensity conditioning and hematopoietic SCT

Fungal Keratitis: Update for 2014

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