Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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A Case of Pneumonia Caused by Pneumocystis jirovecii Resistant to Trimethoprim-Sulfamethoxazole

  • Lee, Sang Min (Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center) ;
  • Cho, Yong Kyun (Division of Infection, Department of Internal Medicine, Gachon University Gil Medical Center) ;
  • Sung, Yon Mi (Department of Radiology, Gachon University Gil Medical Center) ;
  • Chung, Dong Hae (Departement of Pathology, Gachon University Gil Medical Center) ;
  • Jeong, Sung Hwan (Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center) ;
  • Park, Jeong-Woong (Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center) ;
  • Lee, Sang Pyo (Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center)
  • Received : 2014.11.20
  • Accepted : 2015.06.02
  • Published : 2015.06.30
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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.

Keywords

References

  1. Sepkowitz KA. Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome. Clin Infect Dis 2002; 34: 1098-1107. https://doi.org/10.1086/339548
  2. Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK. 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. MMWR Recomm Rep 2004; 53: 1-112.
  3. Patterson JH, Lindsey IL, Edwards ES, Logan WD Jr. Pneumocystis carinii pneumonia and altered host resistance: treatment of one patient with pentamidine isethionate. Pediatrics 1966; 38: 388-397.
  4. Medina I, Mills J, Leoung G, Hopewell PC, Lee B, Modin G, Benowitz N, Wofsy CB. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med 1990; 323: 776-782. https://doi.org/10.1056/NEJM199009203231202
  5. Meshnick SR. Drug-resistant Pneumocystis carinii. Lancet 1999; 354: 1318-1319. https://doi.org/10.1016/S0140-6736(99)00240-8
  6. Mei Q, Gurunathan S, Masur H, Kovacs JA. Failure of co-trimoxazole in Pneumocystis carinii infection and mutations in dihydropteroate synthase gene. Lancet 1998; 351: 1631-1632.
  7. Zingale A, Carrera P, Lazzarin A, Scarpellini P. 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 2003; 41: 2709-2712. https://doi.org/10.1128/JCM.41.6.2709-2712.2003
  8. Nahimana A, Rabodonirina M, Helweg-Larsen J, Meneau I, Francioli P, Bille J, Hauser PM. Sulfa resistance and dihydropteroate synthase mutants in recurrent Pneumocystis carinii pneumonia. Emerg Infect Dis 2003; 9: 864-867. https://doi.org/10.3201/eid0907.020753
  9. Meneau I, Sanglard D, Bille J, Hauser PM. Pneumocystis jirovecii dihydropteroate synthase polymorphisms confer resistance to sulfadoxine and sulfanilamide in Saccharomyces cerevisiae. Antimicrob Agents Chemother 2004; 48: 2610-2616. https://doi.org/10.1128/AAC.48.7.2610-2616.2004
  10. Iliades P, Meshnick SR, Macreadie IG. Dihydropteroate synthase mutations in Pneumocystis jirovecii can affect sulfamethoxazole resistance in a Saccharomyces cerevisiae model. Antimicrob Agents Chemother 2004; 48: 2617-2623. https://doi.org/10.1128/AAC.48.7.2617-2623.2004
  11. Safrin S, Finkelstein DM, Feinberg J, Frame P, Simpson G, Wu A, Cheung T, Soeiro R, Hojczyk P, Black JR. 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 1996; 124: 792-802. https://doi.org/10.7326/0003-4819-124-9-199605010-00003
  12. Helweg-Larsen J, Benfield TL, Eugen-Olsen J, Lundgren JD, Lundgren B. Effects of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of AIDS-associated P. carinii pneumonia. Lancet 1999; 354: 1347-1351. https://doi.org/10.1016/S0140-6736(99)03320-6
  13. Tasaka S, Tokuda H. Recent advances in the diagnosis of Pneumocystis jirovecii pneumonia in HIV-infected adults. Expert Opin Med Diagn 2013; 7: 85-97. https://doi.org/10.1517/17530059.2012.722080
  14. Kim HW, Kim MG, Woo YS, Boo CS, Jo SK, Kim HK, Jo WY, Lee KG, Kim HO, Oh CR, Kim JH. A case of Pneumocystis jirovecii pneumonia following CMV duodenitis in a kidney transplant patient. Korean J Nephrol 2008; 27: 631-637.
  15. Jung JY, Rhee KH, Koo DH, Park IN, Shim TS. Pneumocystis jirovecii pneumonia mimicking miliary tuberculosis in a kidney transplanted patient. Tubercul Respir Dis 2009; 67: 127-130. https://doi.org/10.4046/trd.2009.67.2.127
  16. Kim TY, Nam WJ, Kim SM, Shin JH, Lee KE, Kim SH, Oh DJ, Yu SH. Pneumonia caused by fungus, Pneumocystis jirovecii and cytomegalovirus coinfection in patient with renal transplantation: a case report. J Korean Soc Transplant 2009; 23: 161-165. https://doi.org/10.4285/jkstn.2009.23.2.161
  17. Branson BM, Stekler JD. Detection of acute HIV infection: we can't close the window. J Infect Dis 2012; 205: 521-524. https://doi.org/10.1093/infdis/jir793
  18. Owen SM. Testing for acute HIV infection: implications for treatment as prevention. Curr Opin HIV AIDS 2012; 7: 125-130. https://doi.org/10.1097/COH.0b013e3283506613
  19. Cohen MS, Gay CL, Busch MP, Hecht FM. The detection of acute HIV infection. J Infect Dis 2010; 202 (suppl 2): S270-S277. https://doi.org/10.1086/655651
  20. Tyagi AK, Mirdha BR, Guleria R, Mohan A, Luthra K, Singh UB. Study of dihydropteroate synthase (DHPS) gene mutations among isolates of Pneumocystis jirovecii. Indian J Med Res 2008; 128: 734-739.
  21. Castro M. Treatment and prophylaxis of Pneumocystis carinii pneumonia. Semin Respir Infect 1998; 13: 296-303.
  22. Lane BR, Ast JC, Hossler PA, Mindell DP, Bartlett MS, Smith JW, Meshnick SR. Dihydropteroate synthase polymorphisms in Pneumocystis carinii. J Infect Dis 1997; 175: 482-485. https://doi.org/10.1093/infdis/175.2.482
  23. Kazanjian P, Locke AB, Hossler PA, Lane BR, Bartlett MS, Smith JW, Cannon M, Meshnick SR. Pneumocystis carinii mutations associated with sulfa and sulfone prophylaxis failures in AIDS patients. AIDS 1998; 12: 873-878. https://doi.org/10.1097/00002030-199808000-00009
  24. Takahashi T, Hosoya N, Endo T, Nakamura T, Sakashita H, Kimura K, Ohnishi K, Nakamura Y, Iwamoto A. Relationship between mutations in dihydropteroate synthase of Pneumocystis carinii f. sp. hominis isolates in Japan and resistance to sulfonamide therapy. J Clin Microbiol 2000; 38: 3161-3164.
  25. Iliades P, Meshnick SR, Macreadie IG. Mutations in the Pneumocystis jirovecii DHPS gene confer cross-resistance to sulfa drugs. Antimicrob Agents Chemother 2005; 49: 741-748. https://doi.org/10.1128/AAC.49.2.741-748.2005
  26. Iliades P, Meshnick SR, Macreadie IG. Analysis of Pneumocystis jirovecii DHPS alleles implicated in sulfamethoxazole resistance using an Escherichia coli model system. Microb Drug Resist 2005; 11: 1-8. https://doi.org/10.1089/mdr.2005.11.1
  27. Moukhlis R, Boyer J, Lacube P, Bolognini J, Roux P, Hennequin C. Linking Pneumocystis jirovecii sulfamethoxazole resistance to the alleles of the DHPS gene using functional complementation in Saccharomyces cerevisiae. Clin Microbiol Infect 2010; 16: 501-507. https://doi.org/10.1111/j.1469-0691.2009.02833.x
  28. Queener SF, Cody V, Pace J, Torkelson P, Gangjee A. Trimethoprim resistance of dihydrofolate reductase variants from clinical isolates of Pneumocystis jirovecii. Antimicrob Agents Chemother 2013; 57: 4990-4998. https://doi.org/10.1128/AAC.01161-13

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