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Invasive Infections Caused by Nannizziopsis Spp. Molds in Immunocompromised Patients

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Invasive Infections Caused by Nannizziopsis Spp. Molds in Immunocompromised Patients DISPATCHES Invasive Infections Caused by Nannizziopsis spp. Molds in Immunocompromised Patients Céline Nourrisson, Magali Vidal-Roux, Escherichia coli sensitive to imipenem grew quickly in 1 Sophie Cayot, Christine Jacomet, pair of blood cultures. A second pair was positive 4 days Charlotte Bothorel, Albane Ledoux-Pilon, later, with the presence of large septate fungal hyphae Fanny Anthony-Moumouni, and arthroconidia. White and thin cottony mold colonies Olivier Lesens,1 Philippe Poirier1 grew on Sabouraud media incubated at 35°C (online Tech- nical Appendix Figure 1, https://wwwnc.cdc.gov/EID/ We report 2 new cases of invasive infections caused by article/24/3/17-0772-Techapp1.pdf). We performed best Nannizziopsis spp. molds in France. Both patients had ce- model determination and phylogenetic analyses in MEGA6 rebral abscesses and were immunocompromised. Both pa- (http://www.megasoftware.net). We identified N. obscura tients had recently spent time in Africa. by sequencing the 18S-internal transcribed spacer (ITS) 1–5.8S-ITS2 region (online Technical Appendix Figure annizziopsis spp. molds have been reported in ex- 2). The strain had low MICs for antifungals as defined by Ntremely rare cerebral and disseminated infections the European Committee on Antimicrobial Susceptibility (1,2), (Table). We describe 2 cases of Nannizziopsis in- Testing (http://www.eucast.org/): amphotericin B 0.06 µg/ fection diagnosed in France during the past 2 years. Both mL, itraconazole 0.25 µg/mL, voriconazole 0.03 µg/mL, case-patients were immunocompromised and had recently posaconazole 0.06 µg/mL, caspofungin 0.5 µg/mL, and returned from Africa. micafungin 0.015 µg/mL. We performed mycologic inves- tigations of CSF and ascites fluid a posteriori on frozen The Cases aliquots and conducted PCR assays targeting the ITS re- Case-patient 1 was a 63-year-old woman from France who gion on CSF sampled on July 15 and July 19 and on ascites had been treated for T-cell prolymphocytic leukemia di- fluid sampled on July 19. We observed positive amplifi- agnosed in December 2014. She initially received alem- cations in all samples; subsequent sequencing confirmed tuzumab, switching to bendamustine in March 2015 after the presence of DNA from N. obscura. We investigated tumor progression. That treatment failed, and idelalisib the origin of the patient’s contamination. She had made was started on July 11, 2015. The patient was hospitalized several trips to Senegal, the latest in January 2015, during 2 days later for acute renal failure with mild fever. She which an ulcerative inflammatory lesion developed on her became confused and drowsy, and cerebral computed to- left little finger. However, Grocott stain and PCR on par- mography (CT) scan showed systematized subcortical hy- affin-embedded tissue of skin biopsy were negative, and podense areas. Lumbar puncture showed neoplastic cells we attributed the lesion to the hematological malignancy. in the cerebrospinal fluid (CSF) and glucose concentration Case-patient 2 was a 52-year-old woman from within reference range. Bacteriological and fungal cultures France living in Mali, who was hospitalized in Bamako were sterile. A large volume of ascites fluid remained, in November 2016 for cough, fever, alteration of gener- despite iterative punctures with negative bacteriologi- al state, and headache. She tested seropositive for HIV cal cultures. We initiated intrathecal chemotherapy with (CD4 3/µL; HIV-1 viral load 45.300 copies/mL). Chest methotrexate/cytarabine/methylprednisolone. However, radiograph showed bilateral pneumonia, and cerebral the patient’s condition worsened, with heart failure and CT scan showed a single process on the left temporal loss of consciousness. On July 18, we took new specimens lobe. Antiretroviral therapy was initiated with a combi- of CSF, bronchial wash, ascites fluid, and blood cultures nation of efavirenz/lamivudine/tenofovir associated with and sent them for bacteriological investigation. We started isoniazid, metronidazole, amoxicillin/clavulanate, and empiric treatment with imipenem/aminoglycosides, but the trimethoprime/sulfamethoxazole. Because of worsening patient died on July 19 of septic shock. No autopsy was of her neurologic status, she was repatriated to France. At performed. Extended-spectrum β-lactamase–producing hospital admission on January 12, 2017, she had a lesion Author affiliations: Centre Hospitalier Universitaire Clermont-Ferrand, on the left middle fingernail suggestive of onychomyco- Clermont-Ferrand, France sis, hemiparesis, and paralysis of the right side of the face DOI: https://doi.org/10.3201/eid2403.170772 1These authors contributed equally to this article. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 24, No. 3, March 2018 549 DISPATCHES Table. Characteristics of Nannizziopsis spp. infection in humans* Underlying Year Age, condition or Positive (reference) y/sex Country context Species Localization samples Treatment Outcome 2017 (this 52/F France HIV, living in Nannizziopsis Brain abscess Cerebral AmpB for 1 Recovery but study) Mali sp. biopsy, CSF mo, then VCZ neurologic sequela after 2 mo 2015 (this 63/F France Leukemia, N. obscura Brain abscess Blood Not treated Death before study) recent travel culture, CSF, (death before diagnosis to Senegal ascites fluid diagnosis) 2005 (2) 38/M Germany HIV, travel to N. obscura Brain abscess Needle VCZ Recovery Nigeria aspiration of without brain lesion sequelae after 4 mo 2005 (5) 40/M United HIV N. infrequens Lung Bronchial Not treated, Recovery after States washing considered as treatment of a contaminant CMV infection 2000 (3,4) 32/M United Travel to N. hominis Lymph nodes, 3 lymph ITRA for 2 y NA States Nigeria heart, lungs, nodes spleen, kidneys 1994 (3) NA/M United HIV N. hominis Right thigh Deep muscle ITRA Death after 8 States mass mass on the mo right thigh, right groin, buttock, and lung 1982 (1) 24/M United Travel to N. obscura Abscess in right 2 biopsies of AmpB for 4 Recovery after States Africa ankle, abscess in mo 4 mo osteomyelitis tibia *AmpB, amphotericin B; CMV, cytomegalovirus; CSF, cerebrospinal fluid; ITRA, itraconazole; NA, not available; VCZ, voriconazole. associated with Broca’s aphasia. A thoracic-abdominal- containing hyphae (Figure, panels C, D), and on the fourth pelvic scan revealed a nodular lesion in the right lung (Fig- day of incubation, white mold grew on Sabouraud media ure, panel A) and multiple partly calcified pleural lesions. at 25°C and 35°C (online Technical Appendix Figure 1). Bacteriological assays, including investigation for myco- The phylogenetic analyses of the 18S-ITS1–5.8S-ITS2 re- bacteria on bronchoalveolar lavage (BAL) fluid, showed gion confirmed that the fungus belonged toNannizziopsis negative results. A Penicillium grew rapidly on myco- spp. Although the 18S region was closely related to N. logical medium, and Pneumocystis jiroveci PCR results obscura, the ITS1 region had a large insertion, suggesting were slightly positive. Cranial tomodensitometry showed the strain does not belong to the described Nannizziop- multiple gadolinium-enhancing nodules surrounded by sis species (online Technical Appendix Figure 2). Strain edema (Figure, panel B). We initiated fluconazole and MICs as defined by the European Committee on Antimi- pyrimethamine/sulfadiazine and switched antiretroviral crobial Susceptibility Testing were amphotericin B 0.25 therapy to raltegravir/abacavir/lamivudine after the on- µg/mL, itraconazole 0.03 µg/mL, voriconazole 0.125 µg/ set of acute renal insufficiency. Hemiplegia developed 15 mL, posaconazole 0.25 µg/mL, caspofungin 0.25 µg/mL, days later. A new CT scan showed stable cerebral lesions and micafungin <0.008 µg/mL. We initiated liposomal but an increase in surrounding edema. We performed a amphotericin B (5 mg/kg). On July 16, the patient became lumbar puncture and started intravenous corticotherapy. drowsy with a bilateral pyramidal syndrome and moderate CSF contained 127 leukocytes (61% lymphocytes) and reactive mydriasis. Cranial CT scan showed an increase showed hypoglycorrhachia. Investigations for toxoplas- in the abscesses and edema with brain displacement. We mosis, cryptococcosis, histoplasmosis, tuberculosis, and performed a craniotomy. One month after diagnosis, the CMV showed negative results, but ITS-targeting PCR patient’s general status had improved, with regression of results were positive on CSF. The sequence was closely the lung lesions and cerebral abscesses; her CD4 cell count related to N. obscura, but mycological cultures were ster- was 50/µL and HIV-1 load <40 copies/mL. We switched ile (online Technical Appendix Figure 2). The results of a her antifungal treatment to voriconazole. β-D-glucan assay of serum was positive (983 pg/mL; Fun- gitell, Associates of Cape Cod, Inc., http://www.acciusa. Conclusions com/clinical/fungitell/index.html) and galactomannan an- The molds of the N. vriesii complex (Chrysosporium-like ana- tigen was negative. On February 6, we performed a cerebral morph, CANV) are members of the Nannizziopsis genus (On- biopsy. Histopathologic examination showed granuloma ygenales, Eurotiomycetidae, Eurotiomycetes, Ascomycota). 550 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 24, No. 3, March 2018 Whole-Genome Analysis of M. tuberculosis, Russia CANV includes the keratinophilic species, which causes CSF cultures from both our case-patients and as- skin and fatal disseminated infections in reptiles (3,4). There cites cultures from case-patient 1 were negative, but is no documented
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