Outbreak of invasive aspergillosis among renal transplant recipients

Panackal, Anil A.; Dahlman, Andrea; Keil, Katharina T.; Peterson, Carol L.; Mascola, Laurene; Mirza, Sara; Phelan, Maureen; Lasker, Brent A.; Brandt, Mary E.; Carpenter, Joseph; Bell, Michael; Warnock, David W.; Hajjeh, Rana; Morgan, Juliette

doi:10.1097/01.tp.0000055983.69730.ed

Cited by 58 publications

(41 citation statements)

References 8 publications

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“…These strains also demonstrated an acquired resistance to ITZ, but no attempt was made by these investigators to further characterize the organism. Recently, in an outbreak of A. fumigatus infections among renal transplant recipients (21), the majority of the isolates recovered demonstrated an atypical, slow-sporulation phenotype (A. Panackal and M. Brandt, verbal communication). It will be necessary to document the presence of this organism among other culture collections using molecular studies in order to further assess the clinical significance of our observations.…”

Section: Discussionmentioning

confidence: 99%

Aspergillus fumigatusVariant with Decreased Susceptibility to Multiple Antifungals

Balajee

Weaver

Imhof

et al. 2004

Antimicrob Agents Chemother

107

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Isolates of Aspergillus fumigatus that demonstrate resistance to itraconazole (ITZ) have been described previously; however, the prevalence and clinical significance of ITZ resistance are not completely understood. In this study we assessed the ITZ susceptibilities of 128 A. fumigatus isolates that caused invasive infection in 82 stem cell transplant patients before and after the use of ITZ in our institution (study period, 1991 to 2000). The MICs for 10 isolates obtained from seven patients were high, >1 g/ml. The average ITZ MIC increased after institutional use of the drug began in 1995. The majority of the isolates for which MICs were high (6 of 10) and one isolate for which the MIC was low (0.06 g/ml) demonstrated an unusual phenotype, appearing as predominantly white colonies. For all seven atypical isolates, voriconazole MICs were high (>2 g/ml), and minimal effective concentrations of caspofungin were high (>4 g/ml). For two of the seven atypical isolates, amphotericin B MICs were high (>2 g/ml). The isolates appeared white due to slow sporulation; however, after prolonged incubations, the isolates sporulated with no difference in conidial color or conidiophore morphology compared with typical isolates. Randomly amplified polymorphic DNA-PCR patterns of these isolates were distinct compared with those of other A. fumigatus isolates. Sequencing of 18S rRNA genes confirmed that all were A. fumigatus; however, the mitochondrial cytochrome b gene sequences of all the atypical isolates were unique. These data suggest the potential presence of a genetically unique, poorly sporulating variant of A. fumigatus that demonstrates decreased susceptibilities to several antifungals.

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Section: Discussionmentioning

confidence: 99%

Aspergillus fumigatusVariant with Decreased Susceptibility to Multiple Antifungals

Balajee

Weaver

Imhof

et al. 2004

Antimicrob Agents Chemother

107

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“…Groups OB1, OB3, OB4, and OB5 did not yield a clear set of relationships based on Afut1 typing. Group OB1 isolates were obtained from a renal transplant unit in California (42), and group OB3 isolates were obtained from a cardiac transplant unit in New York. Isolates belonging to group OB4 were obtained from a surgical unit in a hospital in Colorado where the patients had undergone prosthetic heart valve replacement surgery (unpublished data).…”

Section: Methodsmentioning

confidence: 99%

Characterization of a Novel Gene for Strain Typing Reveals Substructuring of Aspergillus fumigatus across North America

Balajee¹,

Tay

Lasker

et al. 2007

Eukaryot Cell

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Fifty-five epidemiologically linked Aspergillus fumigatus isolates obtained from six nosocomial outbreaks of invasive aspergillosis were subtyped by sequencing the polymorphic region of the gene encoding a putative cell surface protein, Afu3g08990 (denoted as CSP). Comparative sequence analysis showed that genetic diversity was generated in the coding region of this gene by both tandem repeats and point mutations. Each unique sequence in an outbreak cluster was assigned an arbitrary number or CSP sequence type. The CSP typing method was able to identify "clonal" and genotypically distinct A. fumigatus isolates, and the results of this method were concordant with those of another discriminatory genotyping technique, the Afut1 restriction fragment length polymorphism typing method. The novel single-locus sequence typing (CSP typing) strategy appears to be a simple, rapid, discriminatory tool that can be readily shared across laboratories. In addition, we found that A. fumigatus isolates substructured into multiple clades; interestingly, one clade consisted of isolates predominantly representing invasive clinical isolates recovered from cardiac transplant patients from two different outbreak situations. We also found that the A. fumigatus isolate Af293, whose genome has been sequenced, possesses a CSP gene structure that is substantially different from those of the other A. fumigatus strains studied here, highlighting the need for further taxonomic study.Conidia of Aspergillus fumigatus become airborne easily, and subsequent inhalation of these infectious particles is believed to be the route of transmission for invasive aspergillosis. Accordingly, several nosocomial outbreaks of invasive aspergillosis have been reported with strong evidence suggesting that such infections are acquired from the environment of the hospital (10,31,35,43). The Centers for Disease Control and Prevention (CDC) recommends that in the setting of a nosocomial aspergillosis outbreak and in the presence of continuing evidence of Aspergillus infection in the hospital population, an environmental assessment should be undertaken to determine and eliminate the source of infection (51). In such nosocomial outbreak investigations, Aspergillus strain typing methods can indicate the source and/or route of infection by determining whether epidemiologically related isolates are also genetically related. Once the source is identified, corrective measures can then be undertaken to eliminate the implicated source to contain the infection. Several molecular methods have been evaluated for A. fumigatus strain typing, and these methods include randomly amplified polymorphic DNA typing (1), sequence-specific DNA primer analysis (32), polymorphic microsatellite markers (6,7,12), and analysis of hybridization profiles with a dispersed, repetitive DNA probe Afut1 (Afut1 restriction fragment length polymorphism [Afut1 RFLP]) (11,36). Although a combination of typing methods appears to have more utility in strain typing, polymorphic microsatellite markers, and Af...

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“…The national registry of U.S. Renal Data System documented that between1994 to 1997, an estimated 12% of hospitalizations for fungal infections were due to aspergillosis (1). High dose and prolonged duration of corticosteroids, graft failure requiring hemodialysis, and potent immunosuppressive therapy have been shown to be risk factors for invasive aspergillosis after renal transplantation (106,231,237). The mortality rate in renal transplant recipients with invasive aspergillosis has ranged from 75 to 80% (88,237,243).…”

Section: Renal Transplant Recipientsmentioning

confidence: 99%

AspergillusInfections in Transplant Recipients

2005

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Aspergillus infections are occurring with an increasing frequency in transplant recipients. Notable changes in the epidemiologic characteristics of this infection have occurred; these include a change in risk factors and later onset of infection. Management of invasive aspergillosis continues to be challenging, and the mortality rate, despite the use of newer antifungal agents, remains unacceptably high. Performing molecular studies to discern new targets for antifungal activity, identifying signaling pathways that may be amenable to immunologic interventions, assessing combination regimens of antifungal agents or combining antifungal agents with modulation of the host defense mechanisms, and devising diagnostic assays that can rapidly and reliably diagnose infections represent areas for future investigations that may lead to further improvement in outcomes

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Outbreak of invasive aspergillosis among renal transplant recipients

Cited by 58 publications

References 8 publications

Aspergillus fumigatusVariant with Decreased Susceptibility to Multiple Antifungals

Aspergillus fumigatusVariant with Decreased Susceptibility to Multiple Antifungals

Characterization of a Novel Gene for Strain Typing Reveals Substructuring of Aspergillus fumigatus across North America

AspergillusInfections in Transplant Recipients

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