Atypical pneumonia has evolved in recent decades to signify lower respiratory tract diseases caused by certain respiratory pathogens. These pathogens are distinguished clinically and radiologically from typical bacterial community-acquired pneumonia (CAP). The spectrum of such infections includes zoonotic and non-zoonotic transmissions, with the latter being more common. The tendency of extrapulmonary involvement, which is true for each kind of atypical CAP, distinguishes clinically from classical CAP. Therefore, clinical syndromic diagnosis is important for raising the index of suspicion and commencing appropriate empirical antibiotic therapy and prompting further diagnostic testing. We aimed to review the literature to enhance the understanding and awareness of atypical pneumonia. We reviewed the literature for atypical pneumonia; clinical manifestations, approach to diagnosis, and management. Articles were chosen from the PubMed database, and selected studies were subjected to a thorough review. Atypical organisms that cause pneumonia are more likely to cause systemic disorders with a wide range of extrapulmonary symptoms. On the other hand, some of them are difficult to culture and dangerous to isolate. As a result, clinical syndromic diagnosis is crucial for raising the index of suspicion, commencing appropriate empirical antibiotic therapy, and promoting specific diagnostic tests.
1. Murray HW, Tuazon C. Atypical pneumonias. Med Clin North Am. 1980;64(3):507-27. doi:10.1016/S0025-7125(16)31607-8
2. Blasi F. Atypical pathogens and respiratory tract infections. Eur Respir J. 2004;24(1):171-82. doi:10.1183/09031936.04.00135703
3. Bartlett JG, Mundy LM. Community-acquired pneumonia. N Engl J Med. 1995;333(24):1618-24. doi:10.1056/NEJM199512143332408
4. Zumla A. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Lancet Infect Dis. 2010;10(5):303. doi:10.1016/S1473-3099(10)70089-X
5. Gupta SK, Sarosi GA. The role of atypical pathogens in community-acquired pneumonia. Med Clin. 2001;85(6):1349-65. doi:10.1016/S0025-7125(05)70384-9
6. Taylor-Robinson D. Infections due to species of Mycoplasma and Ureaplasma: an update. Clin Infect Dis. 1996;671-82. doi:10.1093/CLINIDS/23.4.671
7. Kannan TR, Baseman JB. ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens. Proc Natl Acad Sci. 2006;103(17):6724-9. doi:10.1073/PNAS.0510644103
8. Simmons WL, Daubenspeck JM, Osborne JD, Balish MF, Waites KB, Dybvig K. Type 1 and type 2 strains of Mycoplasma pneumoniae form different biofilms. Microbiology. 2013;159(Pt 4):737. doi:10.1099/MIC.0.064782-0
9. Foy HM, Kenny GE, Cooney MK, Allan ID. Long-term epidemiology of infections with Mycoplasma pneumoniae. J Infect Dis. 1979;139(6):681-7. doi:10.1093/INFDIS/139.6.681
10. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415-27. doi:10.1056/NEJMOA1500245
11. Qu J, Yang C, Bao F, Chen S, Gu L, Cao B. Epidemiological characterization of respiratory tract infections caused by Mycoplasma pneumoniae during epidemic and post-epidemic periods in North China, from 2011 to 2016. BMC Infect Dis. 2018;18(1):1-8. doi:10.1186/S12879-018-3250-2
12. Brown RJ, Nguipdop-Djomo P, Zhao H, Stanford E, Spiller OB, Chalker VJ. Mycoplasma pneumoniae Epidemiology in England and Wales: A National Perspective. Front Microbiol. 2016;7(FEB):157. doi:10.3389/FMICB.2016.00157
13. Spuesens EB, Fraaij PL, Visser EG, Hoogenboezem T, Hop WC, van Adrichem LN, et al. Carriage of Mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children: an observational study. PLoS Med. 2013;10(5):e1001444. doi:10.1371/JOURNAL.PMED.1001444
14. Klement E, Talkington DF, Wasserzug O, Kayouf R, Davidovitch N, Dumke R, et al. Identification of risk factors for infection in an outbreak of Mycoplasma pneumoniae respiratory tract disease. Clin Infect Dis. 2006;43(10):1239-45. doi:10.1086/508458
15. Mansel JK, Rosenow EC, Smith TF, Martin JW. Mycoplasma pneumoniae pneumonia. Chest. 1989;95(3):639-46. doi:10.1378/CHEST.95.3.639
16. Waites KB, Xiao L, Liu Y, Balish MF, Atkinson TP. Mycoplasma pneumoniae from the Respiratory Tract and Beyond. Clin Microbiol Rev. 2017;30(3):747-809. doi:10.1128/CMR.00114-16
17. Wadowsky RM, Castilla EA, Laus S, Kozy A, Atchison RW, Kingsley LA, et al. Evaluation of Chlamydia pneumoniae and Mycoplasma pneumoniae as etiologic agents of persistent cough in adolescents and adults. J Clin Microbiol. 2002;40(2):637-40. doi:10.1128/JCM.40.2.637-640.2002
18. Lieberman D, Schlaeffer F, Lieberman D, Horowitz S, Horovitz O, Porath A. Mycoplasma pneumoniae community-acquired pneumonia: a review of 101 hospitalized adult patients. Respiration. 1996;63(5):261-6. doi:10.1159/000196557
19. Cunha CB. The First Atypical Pneumonia: The History of the Discovery of Mycoplasma pneumoniae. Infect Dis Clin North Am. 2010;24(1):1-5. doi:10.1016/J.IDC.2009.10.007
20. Loomes LM, Uemura KI, Childs RA, Paulson JC, Rogers GN, Scudder PR, et al. Erythrocyte receptors for Mycoplasma pneumoniae are sialylated oligosaccharides of Ii antigen type. Nature. 1984;307(5951):560-3. doi:10.1038/307560A0
21. Daxböck F, Zedtwitz-Liebenstein K, Burgmann H, Graninger W. Severe hemolytic anemia and excessive leukocytosis masking mycoplasma pneumonia. Ann Hematol. 2001;80(3):180-2. doi:10.1007/S002770000250
22. Al-Mendalawi MD. Anemic crisis due to Mycoplasma pneumoniae complication in sickle cell patients. Saudi Med J. 2009;30(8):1105-6.
23. Tsiodras S, Kelesidis I, Kelesidis T, Stamboulis E, Giamarellou H. Central nervous system manifestations of Mycoplasma pneumoniae infections. J Infect. 2005;51(5):343-54. doi:10.1016/J.JINF.2005.07.005
24. Koskiniemi M. CNS manifestations associated with Mycoplasma pneumoniae infections: summary of cases at the University of Helsinki and review. Clin Infect Dis. 1993;17 Suppl 1(Suppl 1):S52-S7. doi:10.1093/CLINIDS/17.SUPPLEMENT_1.S52
25. Tay YK, Huff JC, Weston WL. Mycoplasma pneumoniae infection is associated with Stevens-Johnson syndrome, not erythema multiforme (von Hebra). J Am Acad Dermatol. 1996;35(5 Pt 1):757-60. doi:10.1016/S0190-9622(96)90732-X
26. Canavan TN, Mathes EF, Frieden I, Shinkai K. Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: A systematic review. J Am Acad Dermatol. 2015;72(2):239-45. doi:10.1016/J.JAAD.2014.06.026
27. Burillo A, Bouza E. Chlamydophila pneumoniae. Infect Dis Clin North Am. 2010;24(1):61-71. doi:10.1016/J.IDC.2009.10.002
28. Grayston JT, Aldous MB, Easton A, Wang SP, Kuo CC, Campbell LA, et al. Evidence that Chlamydia pneumoniae causes pneumonia and bronchitis. J Infect Dis. 1993;168(5):1231-5. doi:10.1093/INFDIS/168.5.1231
29. Kauppinen MT, Saikku P, Kujala P, Herva E, Syrjälä H. Clinical picture of community-acquired Chlamydia pneumoniae pneumonia requiring hospital treatment: a comparison between chlamydial and pneumococcal pneumonia. Thorax. 1996;51(2):185-9. doi:10.1136/THX.51.2.185
30. Bochud PY, Moser F, Erard P, Verdon F, Studer JP, Villard G, et al. Community-acquired pneumonia. A prospective outpatient study. Medicine (Baltimore). 2001;80(2):75-87. doi:10.1097/00005792-200103000-00001
31. Honeybourne D. Community-acquired pneumonia in ambulatory patients: relative importance of atypical pathogens. Int J Antimicrob Agents. 2001;18 Suppl 1(SUPPL.1):57-61. doi:10.1016/S0924-8579(01)00398-3
32. Cunha BA. Ambulatory community-acquired pneumonia: the predominance of atypical pathogens. Eur J Clin Microbiol Infect Dis. 2003;22(10):579-83. doi:10.1007/S10096-003-0996-1
33. Yu VL, Plouffe JF, Castellani-Pastoris M, Stout JE, Shousboe M, Widmer A. Distribution of Legionella species and serogroups isolated by culture in patients with sporadic community-acquired legionellosis: an international collaborative survey. J Infect Dis. 2002;186(1):127-8. doi:10.1086/341087
34. Cianciotto NP, Stamos JK, Kamp DW. Infectivity of Legionella pneumophila mip mutant for alveolar epithelial cells. Curr Microbiol. 1995;30(4):247-50. doi:10.1007/BF00293641
35. Payne NR, Horwitz MA. Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors. J Exp Med. 1987;166(5):1377-89. doi:10.1084/JEM.166.5.1377
36. Fraser DW, Tsai TR, Orenstein W, Parkin WE, Beecham HJ, Sharrar RG. Legionnaires’ disease: description of an epidemic of pneumonia. N Engl J Med. 1977;297(22):1189-97. doi:10.1056/NEJM197712012972201
37. Tsai TF, Finn DR, Plikaytis BD, Mccauley WILLIAM, Martin SM, Fraser DW. Legionnaires’ disease: clinical features of the epidemic in Philadelphia. Ann Intern Med. 1979;90(4):509-17. doi:10.7326/0003-4819-90-4-509
38. Sopena N, Sabrià-Leal M, Pedro-Botet ML, Padilla E, Dominguez J, Morera J, et al. Comparative study of the clinical presentation of Legionella pneumonia and other community-acquired pneumonia. Chest. 1998;113(5):1195-200. doi:10.1378/CHEST.113.5.1195
39. Isenman HL, Chambers ST, Pithie AD, MacDonald SL, Hegarty JM, Fenwick JL, et al. Legionnaires’ disease caused by Legionella longbeachae: Clinical features and outcomes of 107 cases from an endemic area. Respirology. 2016;21(7):1292-9. doi:10.1111/RESP.12808
40. Franco-Garcia A, Varughese TA, Lee YJ, Papanicolaou G, Rosenblum MK, Hollmann TJ, et al. Diagnosis of Extrapulmonary Legionellosis in Allogeneic Hematopoietic Cell Transplant Recipients by Direct 16S Ribosomal Ribonucleic Acid Sequencing and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Open forum Infect Dis. 2017;4(3). doi:10.1093/OFID/OFX140
41. Banderet F, Blaich A, Soleman E, Gaia V, Osthoff M. Septic arthritis due to Legionella cincinnatiensis: case report and review of the literature. Infection. 2017;45(4):551-5. doi:10.1007/S15010-016-0964-1
42. Barigou M, Cavalie L, Daviller B, Dubois D, Mantion B, Delobel P, et al. Isolation on Chocolate Agar Culture of Legionella pneumophila Isolates from Subcutaneous Abscesses in an Immunocompromised Patient. J Clin Microbiol. 2015;53(11):3683-5. doi:10.1128/JCM.01116-15
43. Han JH, Harada S, Edelstein PH, Nguyen JC, Baddour LM. Relapsing Legionella pneumophila cellulitis: a case report and review of the literature. J Infect Chemother. 2010;16(6):439-42. doi:10.1007/S10156-010-0072-6
44. Schaumann R, Pönisch W, Helbig JH, Hegenbart U, Ackermann G, Hofmann J, et al. Pericarditis after allogeneic peripheral blood stem cell transplantation caused by Legionella pneumophila (non-serogroup 1). Infection. 2001;29(1):51-3. doi:10.1007/S15010-001-0062-9
45. Ishimaru N, Suzuki H, Tokuda Y, Takano T. Severe Legionnaires’ disease with pneumonia and biopsy-confirmed myocarditis most likely caused by Legionella pneumophila serogroup 6. Intern Med. 2012;51(22):3207-12. doi:10.2169/INTERNALMEDICINE.51.7952
46. McClelland MR, Vaszar LT, Kagawa FT. Pneumonia and osteomyelitis due to Legionella longbeachae in a woman with systemic lupus erythematosus. Clin Infect Dis. 2004;38(10):e102-6. doi:10.1086/386322
47. Fernández-Cruz A, Marín M, Castelo L, Usubillaga R, Martín-Rabadán P, Bouza E, et al. Legionella micdadei, a new cause of prosthetic joint infection. J Clin Microbiol. 2011;49(9):3409-10. doi:10.1128/JCM.00770-11
48. Dorman SA, Hardin NJ, Winn Jr WC. Pyelonephritis associated with Legionella pneumophila, serogroup 4. Ann Intern Med. 1980;93(6):835-7. doi:10.7326/0003-4819-93-6-835
49. Perpoint T, Jamilloux Y, Descloux E, Ferry T, Chidiac C, Lina G, et al. PCR-confirmed Legionella non-pneumophila meningoencephalitis. Med Mal Infect. 2013;43(1):32-4. doi:10.1016/J.MEDMAL.2012.12.001
50. Arnouts PJ, Verpooten GA, De Broe ME, Ramael MR, Van Marck EA, Ysebaert DK, et al. Legionella pneumophila peritonitis in a kidney transplant patient. Scand J Infect Dis. 1991;23(1):119-22. doi:10.3109/00365549109023386
51. Fukuta Y, Yildiz-Aktas IZ, William Pasculle A, Veldkamp PJ. Legionella micdadei prosthetic valve endocarditis complicated by brain abscess: case report and review of the literature. Scand J Infect Dis. 2012;44(6):414-8. doi:10.3109/00365548.2011.645506
52. Lowry PW, Blankenship RJ, Gridley W, Troup NJ, Tompkins LS. A cluster of legionella sternal-wound infections due to postoperative topical exposure to contaminated tap water. N Engl J Med. 1991;324(2):109-13. doi:10.1056/NEJM199101103240207
53. Guy SD, Worth LJ, Thursky KA, Francis PA, Slavin MA. Legionella pneumophila lung abscess associated with immune suppression. Intern Med J. 2011;41(10):715-21. doi:10.1111/J.1445-5994.2011.02508.X
54. Charles M, Johnson E, Macyk-Davey A, Henry M, Nilsson JE, Miedzinski L, et al. Legionella micdadei brain abscess. J Clin Microbiol. 2013;51(2):701-4. doi:10.1128/JCM.02160-12
55. Yung AP, Grayson ML. Psittacosis--a review of 135 cases. Med J Aust. 1988;148(5):228-33. doi:10.5694/J.1326-5377.1988.TB99430.X
56. Hughes P, Chidley K, Cowie J. Neurological complications in psittacosis: a case report and literature review. Respir Med. 1995;89(9):637-8. doi:10.1016/0954-6111(95)90236-8
57. Samra Z, Pik A, Guidetti-Sharon A, Yona E, Weisman Y. Hepatitis in a family infected by Chlamydia psittaci. J R Soc Med. 1991;84(6):347.
58. Jeffrey RF, More IA, Carrington D, Briggs JD, Junor BJ. Acute glomerulonephritis following infection with Chlamydia psittaci. Am J Kidney Dis. 1992;20(1):94-6. doi:10.1016/S0272-6386(12)80325-8
59. Verweij PE, Meis JF, Eijk R, Melchers WJ, Galama JM. Severe human psittacosis requiring artificial ventilation: case report and review. Clin Infect Dis. 1995;20(2):440-2. doi:10.1093/CLINIDS/20.2.440
60. Macheta MP, Ackrill P, August PJ. Psittacosis, panniculitis and clofazimine. J Infect. 1994;28(1):69-71. doi:10.1016/S0163-4453(94)94223-4
61. Miyashita Y, Nakamori Y. A family outbreak of Chlamydia psittaci infection. Kansenshogaku Zasshi. 1996;70(4):377-81. doi:10.11150/KANSENSHOGAKUZASSHI1970.70.377
62. Foley JE, Nieto NC. Tularemia. Vet Microbiol. 2010;140(3-4):332-8. doi:10.1016/J.VETMIC.2009.07.017
63. Sjöstedt A. Tularemia: history, epidemiology, pathogen physiology, and clinical manifestations. Ann N Y Acad Sci. 2007;1105(1):1-29. doi:10.1196/ANNALS.1409.009
64. Weber IB, Turabelidze G, Patrick S, Griffith KS, Kugeler KJ, Mead PS. Clinical recognition and management of tularemia in Missouri: A retrospective records review of 121 cases. Clin Infect Dis. 2012;55(10):1283-90. doi:10.1093/CID/CIS706
65. Pedati C, House J, Hancock-Allen J, Colton L, Bryan K, Ortbahn D, et al. Notes from the Field: Increase in Human Cases of Tularemia--Colorado, Nebraska, South Dakota, and Wyoming, January-September 2015. MMWR Morb Mortal Wkly Rep. 2015;64(47):1317-8. doi:10.15585/MMWR.MM6447A4
66. Maurin M, Benoliel AM, Bongrand P, Raoult D. Phagolysosomal alkalinization and the bactericidal effect of antibiotics: the Coxiella burnetii paradigm. J Infect Dis. 1992;166(5):1097-102. doi:10.1093/INFDIS/166.5.1097
67. Raoult D, Marrie T. Q fever. Clin Infect Dis. 1995;20(3):489-96. doi:10.1093/CLINIDS/20.3.489
68. Hartzell JD, Wood-Morris RN, Martinez LJ, Trotta RF. Q fever: epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83(5):574-9. doi:10.4065/83.5.574
69. Dupuis G, Petite J, Péter O, Vouilloz M. An important outbreak of human Q fever in a Swiss Alpine valley. Int J Epidemiol. 1987;16(2):282-7. doi:10.1093/IJE/16.2.282
70. Woodhead MA, Macfarlane JT. Comparative clinical and laboratory features of legionella with pneumococcal and mycoplasma pneumonia. Br J Dis Chest. 1987;81(2):133-9. doi:10.1016/0007-0971(87)90130-6
71. Hammerschlag MR. Mycoplasma pneumoniae infections. Curr Opin Infect Dis. 2001;14(2):181-6. doi:10.1097/00001432-200104000-00012
72. Hindiyeh M, Carroll KC. Laboratory diagnosis of atypical pneumonia. Semin Respir Infect. 2000;15(2):101-13. doi:10.1053/SRIN.2000.9592
73. Cunha BA. Atypical pneumonia. Clinical diagnosis and empirical treatment. Postgrad Med. 1991;90(5):89-101. doi:10.1080/00325481.1991.11701073
74. Cunha BA. Atypical pneumonia: Current clinical concepts focusing on Legionnaires’ disease. Curr Opin Pulm Med. 2008;14(3):183-94. doi:10.1097/MCP.0B013E3282F79678
75. Carratalà J, Garcia-Vidal C. An update on Legionella. Curr Opin Infect Dis. 2010;23(2):152-7. doi:10.1097/QCO.0B013E328336835B
76. Pedro-Botet ML, Garcí-Cruz A, Tural C, Mateu L, Sopena N, Roure S, et al. Severe Legionnaires’ disease successfully treated with levofloxacin and azithromycin. J Chemother. 2006;18(5):559-61. doi:10.1179/JOC.2006.18.5.559
77. Woodhead M, Blasi F, Ewig S, Garau J, Huchon G, Ieven M, et al. Guidelines for the management of adult lower respiratory tract infections--full version. Clin Microbiol Infect. 2011;17 Suppl 6(Suppl 6):E1-E59. doi:10.1111/J.1469-0691.2011.03672.X
78. Yung AP, Grayson ML. Psittacosis--a review of 135 cases. Med J Aust. 1988;148(5):228-33. doi:10.5694/J.1326-5377.1988.TB99430.X
79. Gikas A, Kokkini S, Tsioutis C. Q fever: Clinical manifestations and treatment. Expert Rev Anti Infect Ther. 2010;8(5):529-39. doi:10.1586/ERI.10.29
80. Farber IM, Kudryashova MA, Galstyan LA, Shatalina SI. Current aspects of antibacterial drug administration when treating nosocomial Pneumonia. J Adv Pharm Edu Res. 2021;11(1):29-34.
Copyright © 2024 Archives of Pharmacy Practice, All rights are reserved and for all open access contents, the Creative Commons licensing terms apply.
Developed by Archives of Pharmacy Practice
