A Case of Pneumonia Caused by Pneumocystis jirovecii Resistant to Trimethoprim-Sulfamethoxazole
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A 50-year-old male visited the outpatient clinic and complained of fever, poor oral intake, and weight loss. A chest X-ray demonstrated streaky and fibrotic lesions in both lungs, and chest CT revealed multifocal peribronchial patchy ground-glass opacities with septated cystic lesions in both lungs. Cell counts in the bronchoalveolar lavage fluid revealed lymphocyte-dominant leukocytosis, and further analysis of lymphocyte subsets showed a predominance of cytotoxic T cells and few T helper cells. Video-assisted wedge resection of the left upper lobe was performed, and the histologic examination was indicative of a Pneumocystis jirovecii infection. Trimethoprim-sulfamethoxazole (TMP-SMX) was orally administered for 3 weeks; however, the patient complained of cough, and the pneumonia was aggravated in the follow-up chest X-ray and chest CT. Molecular studies demonstrated mutations at codons 55 and 57 of the dihydropteroate synthase (DHPS) gene, which is associated with the resistance to TMP-SMX. Clindamycin-primaquine was subsequently administered for 3 weeks replacing the TMP-SMX. A follow-up chest X-ray showed that the pneumonia was resolving, and the cough was also alleviated. A positive result of HIV immunoassay and elevated titer of HCV RNA indicated HIV infection as an underlying condition. This case highlights the importance of careful monitoring of patients with P. jirovecii pneumonia (PCP) during the course of treatment, and the molecular study of DHPS mutations. Additionally, altering the anti-PCP drug utilized as treatment must be considered when infection with drug-resistant P. jirovecii is suspected. To the best of our knowledge, this is the first case of TMP-SMX-resistant PCP described in Korea.
Abstract
A 50-year-old male visited the outpatient clinic and complained of fever, poor oral intake, and weight loss. A chest X-ray demonstrated streaky and fibrotic lesions in both lungs, and chest CT revealed multifocal peribronchial patchy ground-glass opacities with septated cystic lesions in both lungs. Cell counts in the bronchoalveolar lavage fluid revealed lymphocyte-dominant leukocytosis, and further analysis of lymphocyte subsets showed a predominance of cytotoxic T cells and few T helper cells. Video-assisted wedge resection of the left upper lobe was performed, and the histologic examination was indicative of a Pneumocystis jirovecii infection. Trimethoprim-sulfamethoxazole (TMP-SMX) was orally administered for 3 weeks; however, the patient complained of cough, and the pneumonia was aggravated in the follow-up chest X-ray and chest CT. Molecular studies demonstrated mutations at codons 55 and 57 of the dihydropteroate synthase (DHPS) gene, which is associated with the resistance to TMP-SMX. Clindamycin-primaquine was subsequently administered for 3 weeks replacing the TMP-SMX. A follow-up chest X-ray showed that the pneumonia was resolving, and the cough was also alleviated. A positive result of HIV immunoassay and elevated titer of HCV RNA indicated HIV infection as an underlying condition. This case highlights the importance of careful monitoring of patients with P. jirovecii pneumonia (PCP) during the course of treatment, and the molecular study of DHPS mutations. Additionally, altering the anti-PCP drug utilized as treatment must be considered when infection with drug-resistant P. jirovecii is suspected. To the best of our knowledge, this is the first case of TMP-SMX-resistant PCP described in Korea.
참고문헌 (28)
- Sepkowitz KA, "Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome", Clin Infect Dis, 34, pp.1098~1107 (2002)
- Benson CA, "Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association", Infectious Diseases Society of America, 2004, pp.53, 1~112
- Patterson JH, "Pneumocystis carinii pneumonia and altered host resistance: treatment of one patient with pentamidine isethionate", Pediatrics, 38, pp.388~397 (1966)
- Medina I, "Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone", N Engl J Med, 323, pp.776~782 (1990)
- Meshnick SR, "Drug-resistant Pneumocystis carinii", Lancet, 354, pp.1318~1319 (1999)
- Mei Q, "Failure of co-trimoxazole in Pneumocystis carinii infection and mutations in dihydropteroate synthase gene", Lancet, 351, pp.1631~1632 (1998)
- Zingale A, "Detection of Pneumocystis carinii and characterization of mutations associated with sulfa resistance in bronchoalveolar lavage samples from human immunodeficiency virus-infected subjects", J Clin Microbiol, 41, pp.2709~2712 (2003)
- Nahimana A, "Sulfa resistance and dihydropteroate synthase mutants in recurrent Pneumocystis carinii pneumonia", Emerg Infect Dis, 9, pp.864~867 (2003)
- Meneau I, "Pneumocystis jirovecii dihydropteroate synthase polymorphisms confer resistance to sulfadoxine and sulfanilamide in Saccharomyces cerevisiae", Antimicrob Agents Chemother, 48, pp.2610~2616 (2004)
- Iliades P, "Dihydropteroate synthase mutations in Pneumocystis jirovecii can affect sulfamethoxazole resistance in a Saccharomyces cerevisiae model", Antimicrob Agents Chemother, 48, pp.2617~2623 (2004)
- 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", Ann Intern Med, 124, pp.792~802 (1996)
- Helweg-Larsen J, "Effects of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of AIDS-associated P. carinii pneumonia", Lancet, 354, pp.1347~1351 (1999)
- Tasaka S, "Recent advances in the diagnosis of Pneumocystis jirovecii pneumonia in HIV-infected adults", Expert Opin Med Diagn, 7, pp.85~97 (2013)
- 김혜원, "신장 이식 환자에서 CMV duodenitis 치료 후 병발한 Pneumocystis jirovecii 폐렴 1예", Kidney Research and Clinical Practice, 27(5), pp.631~637 (2008), 대한신장학회
- Ju Young Jung, "Pneumocystis jiroveci Pneumonia Mimicking Miliary Tuberculosis in a Kidney Transplanted Patient", Tuberculosis and Respiratory Diseases, 67(2), pp.127~130 (2009), 대한결핵및호흡기학회
- Kim TY, "Pneumonia caused by fungus, Pneumocystis jirovecii and cytomegalovirus coinfection in patient with renal transplantation: a case report", J Korean Soc Transplant, 23, pp.161~165 (2009)
- Branson BM, "Detection of acute HIV infection: we can't close the window", J Infect Dis, 205, pp.521~524 (2012)
- Owen SM, "Testing for acute HIV infection: implications for treatment as prevention", Curr Opin HIV AIDS, 7, pp.125~130 (2012)
- Cohen MS, "The detection of acute HIV infection", J Infect Dis, 202(suppl 2), pp.S270~S277 (2010)
- Tyagi AK, "Study of dihydropteroate synthase (DHPS) gene mutations among isolates of Pneumocystis jirovecii", Indian J Med Res, 128, pp.734~739 (2008)
- Castro M, "Treatment and prophylaxis of Pneumocystis carinii pneumonia", Semin Respir Infect, 13, pp.296~303 (1998)
- Lane BR, "Dihydropteroate synthase polymorphisms in Pneumocystis carinii", J Infect Dis, 175, pp.482~485 (1997)
- Kazanjian P, "Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis failures in AIDS patients", AIDS, 12, pp.873~878 (1998)
- Takahashi T, "Relationship between mutations in dihydropteroate synthase of Pneumocystis carinii f. sp. hominis isolates in Japan and resistance to sulfonamide therapy", J Clin Microbiol, 38, pp.3161~3164 (2000)
- Iliades P, "Mutations in the Pneumocystis jirovecii DHPS gene confer cross-resistance to sulfa drugs", Antimicrob Agents Chemother, 49, pp.741~748 (2005)
- Iliades P, "Analysis of Pneumocystis jirovecii DHPS alleles implicated in sulfamethoxazole resistance using an Escherichia coli model system", Microb Drug Resist, 11, pp.1~8 (2005)
- Moukhlis R, "Linking Pneumocystis jirovecii sulfamethoxazole resistance to the alleles of the DHPS gene using functional complementation in Saccharomyces cerevisiae", Clin Microbiol Infect, 16, pp.501~507 (2010)
- Queener SF, "Trimethoprim resistance of dihydrofolate reductase variants from clinical isolates of Pneumocystis jirovecii", Antimicrob Agents Chemother, 57, pp.4990~4998 (2013)
