Trimethoprim/Sulfamethoxazole 치료력이 없는 환자에서 발생한 Trimethoprim/Sulfamethoxazole 내성 Pneumocystis jirovecii 폐렴 1예
A Case of Pneumonia Caused by Pneumocystis jirovecii Resistant to Trimethoprim/ Sulfamethoxazole in the Absence of Previous Drug Exposure
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폐포자충은 사람면역결핍바이러스 감염 환자에서 흔한 기회감염균이다. DHPS는 설파계열 약물의 표적이 되는 부위로 DHPS 유전자의 돌연변이는 치료와 예방 실패와 연관이 있다. 저자들은 설파계열 약물에 치료받은 경험이 없는 환자에서 DHPS 유전자 돌연변이가 있었던 폐포자충 감염 사례를 보고하고자 한다. 50세 남자가 발열, 기침, 가래, 인후통을 호소하여 내원하였다. 흉부 컴퓨터단층촬영술에서 양측 폐 전반에 걸쳐 간유리 음영이 보였고 환자는 사람면역결핍바이러스에 감염되어 있었으며 CD4+ T 세포 수는 22/ L이었다. 면역조직화학염색에서 폐포자충이 양성이었다. 환자는 TMP/SMX로 치료받았으나 증상의 호전이 없어서 clindamycin과 primaquine으로 치료 약제를 바꾼 후에 증상이 호전되었다. 분자 진단에서 mtlsurRNA 유형3이었고 DHPS 유전자 돌연변이가 55번째와 57번째 코돈에서 모두 양성이었다. 이 사례에서는 DHPS 유전자 돌연변이가 약제 노출력이 없어도 발생할 수 있기 때문에 환자를 치료할 때 유의해야 함을 시사한다.
Abstract
Pneumocystis jirovecii pneumonia is a common opportunistic infection seen in patients with human immunodeficiency virus (HIV) infection. Dihydropteroate synthase (DHPS) is a target of sulfa drugs, and mutations in DHPS gene are associated with failure in treatment and prophylaxis of P. jirovecii infections in HIV-infected patients. Here, we report a case of a patient with P. jirovecii infection, harboring DHPS gene mutations, who had not been previously treated with trimethoprim/sulfamethoxazole (TMP/SMX). A 50-yr-old man was admitted to the hospital with symptoms such as fever, cough, sputum, and sore throat. Chest computed tomography scanning revealed diffuse ground glass opacity in both the lungs, and the patient was diagnosed as having HIV infection with a CD4+ T cell count of 22/μL. Immunohistochemical test results were positive for P. jirovecii. He was treated with TMP/SMX; however, his symptoms and laboratory findings did not improve. The treatment was changed to clindamycin and primaquine, and his symptoms improved after 3 days. Molecular testing of the sample for the detection of DHPS gene mutations and the typing of mitochondrial large subunit rRNA (mtlsurRNA) revealed DHPS gene mutations at codon 55 and 57, respectively, and the case had type 3 mtlsur- RNA. This case study illustrates that DHPS mutation test results can be positive even in patients without previous exposure to TMP/SMX.
참고문헌 (17)
- Edman JC, "Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi", Nature, 334, pp.519~522 (1988)
- Stringer JR, "A new name (Pneumocystis jiroveci) for Pneumocystis from humans", Emerg Infect Dis, 8, pp.891~896 (2002)
- Kaplan JE, "Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America", MMWR Recomm Rep, 58, pp.1~207 (2009)
- Lane BR, "Dihydropteroate synthase polymorphisms in Pneumocystis carinii", J Infect Dis, 175, pp.482~485 (1997)
- Volpe F, "The multifunctional folic acid synthesis fas gene of Pneumocystis carinii appears to encode dihydropteroate synthase and hydroxymethyldihydropterin pyrophosphokinase", Gene, 112, pp.213~218 (1992)
- Walker DJ, "Drug resistance in Pneumocystis carinii: an emerging problem", Drug Resist Updat, 1, pp.201~204 (1998)
- Bellamy RJ, "HIV: treating Pneumocystis pneumonia (PCP)", BMJ Clin Evid, 2008 (2008)
- Sang Min Lee, "A Case of Pneumonia Caused by Pneumocystis jirovecii Resistant to Trimethoprim-Sulfamethoxazole", The Korean Journal of Parasitology, 53(3), pp.321~327 (2015), 대한기생충학ㆍ열대의학회
- Melanie TU, "Manual of clinical microbiology" (2011), ASM Press
- Gajdusek DC, "Pneumocystis carinii; etiologic agent of interstitial plasma cell pneumonia of premature and young infants", Pediatrics, 19, pp.543~565 (1957)
- Wilkin A, "Pneumocystis carinii pneumonia: a clinical review", Am Fam Physician, 60, pp.1699~1708 (1999)
- Fisk DT, "Pneumocystis carinii pneumonia in patients in the developing world who have acquired immunodeficiency syndrome", Clin Infect Dis, 36, pp.70~78 (2003)
- Kazanjian P, "Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis failures in AIDS patients", AIDS, 12, pp.873~878 (1998)
- Safrin S, "Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group", Ann Intern Med, 124, pp.792~802 (1996)
- Hauser PM, "Interhuman transmission as a potential key parameter for geographical variation in the prevalence of Pneumocystis jirovecii dihydropteroate synthase mutations", Clin Infect Dis, 51, pp.e28~e33 (2010)
- Beard CB, "Genetic variation in Pneumocystis carinii isolates from different geographic regions: implications for transmission", Emerg Infect Dis, 6, pp.265~272 (2000)
- Kim T, "Clinical characteristics of hospital-onset Pneumocystis pneumonia and genotypes of Pneumocystis jirovecii in a single tertiary centre in Korea", BMC Infect Dis, 15, pp.102~ (2015)