Fatal pneumonia caused by Penicillium digitatum: a case report
© Oshikata et al.; licensee BioMed Central Ltd. 2013
Received: 14 October 2012
Accepted: 14 March 2013
Published: 23 March 2013
Penicillium species are among the most common fungi present in the environment and are usually considered non-pathogenic to humans. However, in immunocompromised hosts they can be virulent pathogens and can cause death. Penicillium digitatum is a plant pathogen that commonly causes a postharvest fungal disease of citrus called green mould; it very rarely causes systemic mycosis in humans. Here, we report a case of fatal pneumonia due to P. digitatum infection, as confirmed by repeated examination of cultured sputum.
A cavity was found in the left upper lung on routine chest X-ray in a 78-year-old undernourished male who had been diagnosed at age 66 with bronchial asthma and pulmonary emphysema. No increased sputum production was present. The presence of antigen-specific precipitating antibodies to Aspergillus flavus and P. digitatum was confirmed in the patient’s serum and also later pleural fluid by using Ouchterlony double immunodiffusion testing with A. flavus and P. digitatum antigens. The patient was treated over a period of months with itraconazole, micafungin, voriconazole, amphotericin B, and antibacterials. However, the cavity enlarged, the pleural effusion increased, and the patient began producing purulent sputum. He died from progressive renal failure. From sputum culture only one fungus was isolated repeatedly on potato-dextrose agar in large quantities. This fungus was confirmed to be P. digitatum by molecular identification. Partial sequences of the beta-tubulin gene were determined by using the primers Bt2a and Bt2b for PCR amplification and sequencing and underwent a BLAST search at the National Centre for Biotechnology Information, these results confirmed that the isolated fungus was P. digitatum.
To our knowledge, this is the first report of pulmonary infection with P. digitatum. Our patient had pulmonary emphysema and was elderly, and undernourished. These factors might have facilitated the infection. In his case, antimycotics were ineffective in treating the lung involvement. Although human infection with P. digitatum is considered rare, it appears that this organism can be very virulent and resistant to antimycotics.
KeywordsPenicillium digitatum Penicillium species Infection Immunocompromised host Pulmonary emphysema Pneumonia
Penicillium species are among the most common fungi in the environment and are usually considered non-pathogenic to humans . However, in immunocompromised hosts they can be virulent pathogens that can cause death . Penicillium digitatum is a plant pathogen that commonly causes a postharvest fungal disease of citrus called green mould ; it very rarely causes systemic mycosis in humans . Here, we report a case of fatal pneumonia due to P. digitatum infection, as confirmed by repeated examination of cultured sputum.
To extract the antigen from the sputum culture, we added 1.5 mL of Glass Beads (Biospec Product, OK, USA) to the patient’s sputum and crushed the mixture with a Mini-Beadbeater (Biospec Product, OK, USA). It was then incubated with 0.125 mol of NH4CO3 overnight at 4°C and the antigen extracted after freeze-drying of the filtrate. We diagnosed invasive pulmonary penicilliosis due to P. digitatum.
Penicillium digitatum is the most devastating pathogen of rotten citrus fruit and is responsible for 90% of production losses during post-harvest handling . Penicillium digitatum is widely distributed in soils throughout the world. People are commonly exposed to the spores of this airborne pathogen every day. Upon Ouchterlony double immunodiffusion testing, the sera of five of 770 patients with pulmonary lung disease were confirmed to have low titres of antigen-specific precipitating antibodies to P. digitatum against antigen (obtained from Greer Laboratories, Lenoir, NC). However, none of these patients had antigen-specific precipitating antibodies to P. digitatum in tests of antigen extracted from patient’ sputum culture fluid or sputum. In humans there is cross-reactivity to Aspergillus and Penicillium: most sera from patients with precipitins against Penicillium have precipitins against Aspergillus . In April 2005, our patient had precipitins against both P. digitatum and A. flavus, but we did not find any P. digitatum or A. flavus in sputum cultures or in bronchoalveolar lavage fluids. This led to a delay in diagnosis.
Penicillium species can cause opportunistic infections . Patients with Penicillium species infections have been treated successfully with itraconazole , amphotericin B [3, 9], or fluconazole . However, some patients with conditions caused by Penicillium species have died despite treatment with ketoconazole , amphotericin B , or itraconazole . Pulmonary infections with fungi, including Penicillium species, are associated with much higher mortality rates in patients with nosocomial infections or infections complicating organ failure . The minimal inhibitory concentrations of amphotericin B, itraconazole, posaconazole, ravuconazole, and voriconazole against A. flavus or Aspergillus fumigatus are lower than those against Penicillium spp. .
To our knowledge, this is the first report of pulmonary infection with P. digitatum. Our patient had pulmonary emphysema and was elderly, and undernourished. He had no known history of exposure to citrus fruit pathogens, but he was likely to have been immunocompromised. These factors might have facilitated the infection. In his case, antimycotics were ineffective in treating the lung involvement. Although human infections with P. digitatum are considered rare, it appears that this organism can be very virulent and resistant to antimycotics.
Written informed consent was obtained from the kin of the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal form.
We are grateful to Prof. Katsuhiko Kamei (Chiba University) for his guidance and invaluable advice. We declare no financial support.
- Raper KB, Thom C: Penicillium digitatum. A Manual of the Penicillia. 1968, New York: Hafner Publ. Co, 386-392.Google Scholar
- Mok T, Koehler AP, Yu MY, Ellis DH, Johnson PJ, Wickham NW: Fatal Penicillium citrinum pneumonia with pericarditis in a patient with acute leukemia. J Clin Microbiol. 1997, 35: 2654-2656.PubMedPubMed CentralGoogle Scholar
- Lyratzopoulos G, Ellis M, Nerringer R, Denning DW: Invasive infection due to Penicillium species other than P. marneffei. J Infection. 2005, 45: 184-207.View ArticleGoogle Scholar
- Ouchterlony O: Antigen-antibody reactions in gels. Acta Pathol Microbiol Scand. 1949, 26 (4): 507-515.View ArticlePubMedGoogle Scholar
- Glass NL, Donaldson GC: Development of primer sets designed for use with the PCR to amplify conserved genes from filamentous ascomycetes. Appl Environ Microbiol. 1995, 61: 1323-1330.PubMedPubMed CentralGoogle Scholar
- Holmes LG, Eckert JW: Sensitivity of Penicillium digitatum and P. italicum to postharvest citrus fungicides in California. Phytopathology. 1999, 89: 716-721. 10.1094/PHYTO.19126.96.36.1996.View ArticlePubMedGoogle Scholar
- Brouwer J: Cross-reactivity between Aspergillus fumigatus and Penicillium. Int Arch Allergy Immunol. 1996, 110: 166-173. 10.1159/000237283.View ArticlePubMedGoogle Scholar
- D’Antonio D, Violante B, Farina C, Sacco R, Angelucci D, Masciulli M, Iacone A, Romano F: Necrotizing pneumonia caused by Penicillium chrysogenum. J Clin Microbiol. 1997, 35: 3335-3337.PubMedPubMed CentralGoogle Scholar
- Gelfand MS, Cole FH, Baskin RC: Invasive pulmonary penicilliosis: successful therapy with amphotericin B. South Med J. 1990, 83: 701-704. 10.1097/00007611-199006000-00029.View ArticlePubMedGoogle Scholar
- Hsu JH, Lee MS, Dai ZK: Life-threatening airway obstruction caused by penicilliosis in a leukemic patient. Ann Hematol. 2009, 88: 393-395. 10.1007/s00277-008-0606-5.View ArticlePubMedGoogle Scholar
- Chen KY, Ko SC, Hsueh PR, Luh KT, Yang PC: Pulmonary fungal infection. Emphasis on microbiological spectra, patient outcome and prognostic factors. Chest. 2001, 120: 177-10.1378/chest.120.1.177.View ArticlePubMedGoogle Scholar
- Pfaller MA, Messer SA, Hollis RJ, Jones RN, SENTRY Participants Group: Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates and Aspergillus spp. and other filamentous fungi: report from SENTRY antimicrobial surveillance program, 2000. Antimicrob Agents Chemother. 2002, 46: 1032-1037. 10.1128/AAC.46.4.1032-1037.2002.View ArticlePubMedPubMed CentralGoogle Scholar
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