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Mixed bloodstream infection with and chrysogenum in an immunocompromised patient: case report and review of the literature E. Swoboda-Kopec1,2,Ã, M. M. Wroblewska2, A. Rokosz2 and M. Luczak1,2

1Microbiology Laboratory, Central Clinical Hospital, Warsaw and 2Department of Medical Microbiology, Medical University of Warsaw, 5 Chalubinskiego Street, 02-004 Warsaw, Poland

ÃTel/Fax: ‡48 22 628 27 39 E-mail: [email protected]

We report a case of an immunocompromised patient who developed a mixed bacterial± fungal bloodstream infection involving Staphylococcus aureus and Penicillium chryso- genum. To date, no reports of such mixed bloodstream infection have been found. Keywords Bloodstream infection, Staphylococcus aureus, Penicillium chrysogenum Accepted 26 December 2002 Clin Microbiol Infect 2003; 9: 1116±1117

A 37-year-old man was referred in March 2001 and sent for culture. The samples were processed from a regional hospital to a tertiary-care hospital in the BacT/Alert computerized system (Organon because of pyrexia of unknown origin, lasting for Teknika, Durham NC, USA), and two sets yielded 3 weeks. He presented with fever, arterial hyper- growth of microorganisms. Piperacillin combined tension, and microcytic anemia. Ten years earlier with tazobactam and ¯uconazole was empirically he suffered from renal insuf®ciency, which was administered intravenously to the patient, but, treated with regular hemodialysis due to chronic despite the treatment, he died. Autopsy examina- glomerulonephritis. Two years later, he had a tion was not done. kidney transplant and underwent immunosup- In the positive cultures, the growth of a Gram- pressive therapy, but the graft underwent a positive coccus and a was detected. The chronic rejection, and hemodialysis had to be bacterial strain was identi®ed as Staphylococcus resumed in 2000, while immunosuppressive ther- aureus with an ID 32 STAPH test (bioMerieux, apy was continued. The patient also suffered from Marcy L'Etoile, France). The strain was resistant peptic ulcer of the stomach and gastric polyposis. to G, but susceptible to methicillin. It In 1997, he had an operation because of the hemor- was susceptible to other antimicrobials included in rhage from the peptic ulcer, complicated by the ATB STAPH (bioMerieux) test. The fungal wound dehiscence. He was treated with multiple isolate obtained from the same two sets of samples blood transfusions. A year later, he underwent was identi®ed by means of standard mycologic removal of a ®brosarcoma of the left mandible, procedures (morphology of the colonies as well as but metastatic lesions were subsequently detected microscopic appearance of typical conidia) as Peni- in the ribs, resulting in pathologic fractures. He cillium chrysogenum. Susceptibility testing of the also suffered from mitral and aortic valve insuf®- mold showed sensitivity of the strain to 5-¯uoro- ciency, and had a history of hepatitis B virus cytosine (MIC < 0.5 mg/L), amphotericin B (MIC < (HBV), hepatitis C virus (HCV) and cytomegalo- 0.5 mg/L), ketoconazole (MIC < 1.0 mg/L), and virus (CMV) infection. itraconazole (MIC < 0.5 mg/L), but resistance to Echocardiographic examination revealed atrial ¯uconazole (MIC > 64.0 mg/L). ®brillation, multiple calci®cations of the mitral A diagnosis was made of a mixed bacterial± and aortic valves descending to the left ventricle, fungal bloodstream infection involving S. aureus and pulmonary hypertension. No in¯ammatory and P. chrysogenum. consolidations were detected in a chest X-ray. Five The most common opportunistic fungi are classi- sets of blood specimens were collected over 3 days ®ed within the genera Aspergillus, Penicillium,

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Mucor, Rhizopus, and Absidia [1]. Clinical condi- Manuselis GT, eds. Textbook of diagnostic microbio- tions that predispose to these infections are mainly logy. Philadelphia: WB Saunders, 2000: 709±54. immune de®ciencies due to neoplasms, organ 2. Hall WJ III. Penicillium endocarditis following open transplantation, chemotherapy, or HIV infection. heart surgery and prosthetic valve insertion. Am Heart J 1974; 87: 501±6. Penicillium spp. may occasionally cause opportu- 3. DelRossi AJ, Morse D, Spagna PM, Lemole GM. nistic infections called penicilliosis in humans [1]. Successful management of Penicillium endocarditis. They have been implicated as etiologic agents of J Thorac Cardiovasc Surg 1980; 80: 945±7. fungemia, pneumonia, peritonitis, urinary tract 4. Alvarez S. Systemic infection caused by Penicillium infections, endocarditis, and disseminated infec- decumbans in a patient with acquired immunodefi- tions, which are fatal in over 50% of cases, despite ciency syndrome. J Infect Dis 1990; 162: 283. aggressive treatment with antifungal compounds 5. Equils O, Deville JG, Shapiro AM, Sanchez CP. Peni- [2±5]. P. marnaffei recently emerged as an oppor- cillium peritonitis in an adolescent receiving chronic tunistic pathogen in patients with AIDS [6±8]. peritoneal dialysis. Ped Nephrol 1999; 13: 771±2. 6. Supparatpinyo K, Khamwan C, Boassoung V, Strains of P. chrysogenum are ubiquitous in nature, Nelson KE, Sirisanthana T. Disseminated Penicil- but very rarely cause human infections [9±11]. The lium marneffei infection in South-east Asia. Lancet fungus may also be involved in allergic conditions 1994; 334: 110±13. [12]. No reports, however, have been found to date 7. Duong TA. Infection due to Penicillium marneffei,an of a mixed bloodstream infection in humans invol- emerging pathogen: review of 155 reported cases. ving S. aureus and P. chrysogenum. Clin Infect Dis 1996; 23: 125±30. In the reviewed literature (covering the period 8. Cooper CR Jr, McGinnis MR. Pathology of Penicil- 1981±2001), only rare cases of P. chrysogenum in- lium marneffei. An emerging acquired immunodefi- fection in humans have been described [9±11]. ciency syndrome-related pathogen. Arch Path Lab Med 1997; 121: 798±804. None of them, however, involved a mixed bac- 9. Eschete ML, King JW, West BC, Oberle A. Penicil- terial±fungal etiology. Antibacterial treatment lium chrysogenum endophthalmitis. Mycopathologia administered empirically was appropriate; the 1981; 74: 125±7. S. aureus strain, isolated from the blood culture 10. D'Antonio D, Violante B, Farina C et al. Necrotizing samples, was susceptible to b-lactam , pneumonia caused by Penicillium chrysogenum. except penicillin. However, cases of penicilliosis J Clin Microbiol 1997; 35: 3335±7. are characterized by a high mortality rate, despite 11. Lopez-Martinez R, Neumann L, Gonzales-Mendoza aggressive antifungal therapy. Amphotericin B, A. Case report: cutaneous penicilliosis due to Peni- cillium chrysogenum. Mycoses 1999; 42: 347±9. with or without itraconazole, may be used suc- 12. Cooley JD, Wong WC, Jumper CA et al. An animal cessfully[13±15].Inthecasewereporthere,the model for allergic penicilliosis induced by the P. chrysogenum strain implicated in the blood- intranasal instillation of viable Penicillium chryso- stream infection was susceptible to these agents. genum conidia. Thorax 2000; 55: 489±96. Therefore, in an immunocompromised indivi- 13. Gelfand MS, Cole FH, Baskin RC. Invasive pulmo- dual, the signi®cance of the isolates of Penicillium nary penicilliosis: successful therapy with ampho- spp. needs to be thoroughly investigated, and tericin B. South Med J 1990; 83: 701±4. intravenous therapy with amphotericin B should 14. Fahhoum J, Gelfand MS. Peritonitis due to Penicil- be considered. lium sp. in a patient receiving continuous ambula- tory peritoneal dialysis. South Med J 1996; 89: 87±8. 15. Sirisanthana T, Supparatpinyo K, Perriens J, Nelson REFERENCES KE. Amphotericin B and itraconazole for treatment of disseminated Penicillium marneffei infection in 1. Smith LA, Fothergill AW, Sulton DA, Harris JL. human immunodeficiency virus-infected patients. Medically significant fungi. In: Mahon CR, Clin Infect Dis 1998; 26: 1107±10.

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