Acute Respiratory Infection Due to Mycoplasma Pneumonie: Current Status of Diagnostic Methods

Acute Respiratory Infection Due to Mycoplasma Pneumonie: Current Status of Diagnostic Methods

Table 1 Summary of studies of respiratory infections due to Mycoplasma pneumoniae in adults, published since 2003

Reference / Location / Subject age (years) / No of subjects tested / Diagnostic method(s) / No (%) of subjects infected with M. pneumoniae / Comments / Methodological problem a
[47] 2003 / Southeast Asia / 16-98 / 98 outpatients, 147 hospitalised patients / Particle agglutination test / 32 (13.1) / 26/98 (26%) in outpatients, 6/147 (4.1%) in hospitalized patients / C
[17] 2003 / Sweden / 10-84 / 177 / CFT / 17 (9.6) / C
[11] 2004 / The Netherlands / 18 / 145 / P1-based PCR, CFT, IgM-IF / 13 (9.0) / 9 definite cases and 4 probable cases
Convalescent phase serum samples 10-14 days after inclusion / …
[36] 2004 / The Netherlands / 1-88 / 159 / P1 gene-based PCR, particle agglutination and ELISA / 19 (11.9) / 7 PCR positive, all also positive in at least 1 serological test,
2-fold titer increase in IgG was defined as positive / D
[29] 2004 / Trinidad and Tobago / >2 / 132 / IgM and IgG EIA on acute phase serum / 88 (66.7) / 36/88 IgM positive / B
[10] 2005 / France / 18 / 3198 / P1-based PCR, Ag-detection by EIA / 109 (3.6) / 114 PCR positive, Ag-detection test had very low sensitivity and results were not mentioned as such. / E
[18] 2005 / Taiwan / 17-99 / 168 / IgM and IgG ELISA / 24 (14.3) / Proportion of positive results by each test not specified / C
[25] 2005 / Chile / 60-96 / 84 / P1-based PCR, 16S rRNA gene-based PCR, IgM and IgG indirect IF / 11 (13.1) / 8 positive by IFI (of which 4 by IFI alone), 7 PCR positive (of which 3 only by PCR), / …
[23]2005 / Canada / 18 / 507 / IgM and IgG ELISA / 76 (15) / Proportion of positive results by each test not specified / C
[31]2005 / Asia / 2 / 1374 / P1-based PCR, and IgM and IgG Particle agglutination test / 167 (12.2) / 129 positive by serology alone, 167 positive by serology plus PCR / …
[32]2005 / The Netherlands / 18 / 107 / PCR / 0 / PCR not described / A
[44] 2005 / The Netherlands / 18 / 105 / P1-based PCR, CFT, and Microparticle agglutination test / 10 / 10 positive by PCR, 5 by conventional methods / …
[4] 2006 / UK / 18 / 80 patients
49 controls / P1-based PCR, 16S rRNA-based PCR / 1 (1.3) / 1 PCR positive patient / …
[14] 2006 / China / 2 / 389 / P1-based PCR and particle agglutination test / 42 (10.8) / 18 positive by serology alone, 42 positive by serology and PCR / …
[41] 2006 / Denmark / 18-96 / 235 patients
113 controls / P1-based PCR and CFT / 14 (5.5) / 13 positive patients, 1 positive control
Proportion of positive results by each test not specified / …
[40] 2006 / Korea / 16 / 202 / P1-based PCR and particle agglutination test / 8 (4.0) / 5 by serology alone, 1 by serology and PCR, 2 by PCR alone / …
[7] 2007 / Chile / 17-101 / 176 / IgM and IgG indirect immunofluorescence / 3 (1.7) / Proportion of positive results by each test not specified / C
[35] 2007 / Thailand / >2 / 755 / PCR, IgM and IgG EIA / 27 (3.6) / 13 positive by seroconversion alone, 12 positive by PCR alone, 2 positive by both PCR and serology / A
[37] 2007 / India / 18 / 100 / Culture, IgM ELISA, cold agglutination test on acute phase serum / 31 (31) / 31 positive by culture, 21 positive by IgM ELISA, 34 positive by cold agglutination test / …
[3] 2008 / Australia / 18 / 885 / IgM EIA and total antibody by particle agglutination / 78 (8.8) / Proportion of positive results by each test not specified / C
[21] 2008 / Belgium / 18 / 147 / Mono and MX real-time NASBA, real-time PCR, culture, IgM and IgG EIA / 19 (12.9) / 8 positive by culture, 15 positive by PCR, 19 positive by real-time MX NASBA, 23 by mono real-time NASBA / …
[46]2008 / The Netherlands / 18 / 201 / PCR, CFT / 8 (4.0) / 7 positive by PCR, 8 positive by serology
PCR not specified / A
[24] 2008 / Chile / 18-94 / 357 / 16S r RNA gene PCR, indirect immunofluorescence / 32 (9.0) / 23 positive by PCR, 13 positive by IgM serology, and 27 by IgG serology / …
[27] 2008 / Japan / 16->80 / NS / Culture, IgM and IgG serology / 210 / 210 IgG M. pneumoniae positive, 38 culture positive / …
[9] 2009 / Egypt / 15-50 / 59 patients
20 controls / PCR, IgM and IgG EIA, culture / 25 (42.4) / 25 patients positive by PCR, 9 patients positive by culture, 29 by IgM serology and 20 positive by significant rise in IgG
2 controls positive by IgM / …

a A: no information provided about the PCR and/or serological assay used; B: single IgG titer used as part of the criteria used to define an acute infection; C: serology used as the only serodiagnostic tool; D: serological titers vary from those recommended for diagnosis of acute infections; E : 1 PCR assay used as the only diagnostic tool; F: (single) IgM titer used as the only serodiagnostic tool in some or all patients

Ag: antigen; CFT: complement fixation test; IFI: indirect immunofluorescence; IgA/G/M: Immunoglobulin A/G/M; MX: multiplex; NASBA: nucleic acid sequence-based amplification;

Table 2. Summary of studies of respiratory infections due to Mycoplasma pneumoniae in pediatric patients, published since 2003.

Reference / Location / Subject age (years) / No of subjects tested / Diagnostic method(s) / No (%) of subjects infected with M. pneumoniae / Comments / Methodological problem (s)a
[1]2003 / Germany / 1-18 / 50 / P1-based PCR, IgM and IgG serology / 16 (32) / 6 positive by PCR, 14 by serology (mainly IgM) / …
[16] 2003 / Chile / 0-14 / 106 / 16S rRNA gene-based PCR, IgM serology (2 tests) on acutephase serum, culture / 31 (29.2) / 31 positive by IgM, in 28/31 cases serology was confirmed by PCR, 19 positive by culture / …
[12] 2004 / The Netherlands / 0-16 / 168 / P1-based PCR / 4 (2.4) / E
[22] 2004 / Greece / 0.5-14 / 65 / P1-based PCR and IgM serology on acute phase serum / 18 (27.5) / 18 positive by IgM, 9 PCR positive / F
[26]2004 / USA / 0-17 / 154 / IgM and IgG serology / 21 (14) / Proportion of positive results by each test not specified / A
[28] 2004 / Japan / 0-14 / 369 / 16S rRNA gene-based PCR, CFT, culture / 69 (18.7) / 68 positive by PCR, 53 culture positive, 76 serology positive / …
[45] 2004 / Greece / 5-14 / 75 / ATPase-based PCR, IgM and IgG serology / 26 (35) / 11 positive by PCR, 21 positive by serology confirmed by 4-fold rise in IgG titre by CF-test if convalescent seum available / F
[8] 2005 / Finland / 0.3-16 / 101 / CFT and IgM and IgA serology / 27 (27) / 27 patients positive with 2 or more tests, 12 patients positive with only 1 test / …
[20] 2005 / China / 0-5 / 85 patients 185 controls / ATPase-based PCR / 6 (7.1) / All positive results were found in patients / E
[38] 2005 / India / 93 / IgM ELISA on acute phase serum / 22 (24) / All positive by single IgM determination / F
[43]2005 / Germany / 6-16 / 38 patients 42 controls / ATPase-based PCR / 4 (10.5) / All positive results were found in patients / E
[2] 2006 / Japan / 0-13 / 141 / ATPase-based PCR, and CF / 58 (41.1) / 58 PCR positive, 13 single serum positive, 27 paired serum positive / …
[19] 2006 / Finland / 0-16 / 220 / 2 IgM EIAs / 11 (5) / Not clear whether positive in acute, convalescent or both sera / F
[48] 2006 / Japan / 0-6 / 339 / P1-based PCR, passive agglutination, IgM, IgG, and IgA ELISA / 81 (23.9) / 66 PCR positive, 106 PA titers above 1:40, among PCR positive patients, 30/36 had a 4-fold increase in PA titer, 36/81 positive for IgG, 16/81 positive for IgA, and 54/81 positive for IgM / …
[15] 2007 / Korea / 0-16 / 234 / P1-based PCR, microparticle agglutination / 152 (65) / 27 by serology alone, 26 by PCR alone, 99 by both PCR and serology / …
[30] 2007 / Japan / 0-6 / 117 / 16S rRNA PCR, CFT / 17 (14.5) / 14 PCR positive / A
[34] 2007 / Japan / 0-15 / 194 / Culture, CFT, rapid test / 45 (23.2) / 14 culture positive, ImmunoCard positive in 39 paired sera and in 14 acute sera, CFT results not presented
[39] 2007 / Turkey / 5-15 / 284 / PCR, IgM ELISA on acute phase serum / NS / 33/203 PCR positive, 86/284 IgM patients, only in 13 cases positive by both PCR and IgM / F
[5] 2008 / Italy / 0-14 / 886 / P1-based PCR, IgM and IgG serology / 102 (12) / 102/886 PCR positive, 63/102 had positive IgM and/or IgG / …
[33] 2008 / Japan / 0-15 / 73 / 16S rRNA gene based PCR, IgM and IgG serology / 6 (8.2) / 6/6 PCR positive, 5/6 IgG seroconversion/significant rise, 1 additional positive by IgG serology, 2/6 Immunocard assay positive, 12 additional patients positive by Immunocard assay / …
[13] 2008 / Japan / 0-19 / 1700 / RTI-PCRb and serology / 251 (14.8) / Results serology not presented, no info on serological assay used / A
[6] 2009 / China / 0-17 / 176 / Templex Resplex Ic / 26 (14.8) / E
[42] 2009 / China / 0-5 / 475 / MX-PCR / 7 (1.5) / E

a A: no information provided about the PCR and/or serological assay used; B: single IgG titer used as part of the criteria used to define an acute infection; C : EIA used as the only serodiagnostic tool; D: serological titers vary from those recommended for diagnosis of acute infections; E : 1 PCR assay used as the only diagnostic tool; F : (single) IgM titer used as the only serodiagnostic tool in some or all patients

Ag: antigen; CFT: complement fixation test; IFI: indirect immunofluorescence; IgA/G/M: Immunoglobulin A/G/M; MX: multiplex; NASBA: nucleic acid sequence-based amplification;

b RTI-kit, Takara Bio, Kyoto, Japan, c Genaco Biomedical Products, Inc., Huntsville, AL, USA

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Reference List

1. Baer G, Engelcke G, bele-Horn M, Schaad UB, Heininger U (2003) Role of Chlamydia pneumoniae and Mycoplasma pneumoniae as causative agents of community-acquired pneumonia in hospitalised children and adolescents. Eur.J.Clin.Microbiol.Infect.Dis., 22:742-745.

2. Bamba M, Jozaki K, Sugaya N, Tamai S, Ishihara J, Kori T, Shiro H, Takeuchi Y, Cho H, Nakao A, Okano Y, Kimura K, Komiyama O, Nonoyama M, Kobayashi I, Kato T, Sunakawa K (2006) Prospective surveillance for atypical pathogens in children with community-acquired pneumonia in Japan. J.Infect.Chemother., 12:36-41.

3. Charles PG, Whitby M, Fuller AJ, Stirling R, Wright AA, Korman TM, Holmes PW, Christiansen KJ, Waterer GW, Pierce RJ, Mayall BC, Armstrong JG, Catton MG, Nimmo GR, Johnson B, Hooy M, Grayson ML (2008) The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy. Clin.Infect.Dis., 46:1513-1521.

4. Creer DD, Dilworth JP, Gillespie SH, Johnston AR, Johnston SL, Ling C, Patel S, Sanderson G, Wallace PG, McHugh TD (2006) Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care. Thorax, 61:75-79.

5. Defilippi A, Silvestri M, Tacchella A, Giacchino R, Melioli G, Di ME, Cirillo C, Di PP, Rossi GA (2008) Epidemiology and clinical features of Mycoplasma pneumoniae infection in children. Respir.Med., 102:1762-1768.

6. Deng J, Zheng Y, Zhao R, Wright PF, Stratton CW, Tang YW (2009) Culture versus polymerase chain reaction for the etiologic diagnosis of community-acquired pneumonia in antibiotic-pretreated pediatric patients. Pediatr.Infect.Dis.J., 28:53-55.

7. Diaz A, Barria P, Niederman M, Restrepo MI, Dreyse J, Fuentes G, Couble B, Saldias F (2007) Etiology of community-acquired pneumonia in hospitalized patients in chile: the increasing prevalence of respiratory viruses among classic pathogens. Chest, 131:779-787.

8. Don M, Fasoli L, Paldanius M, Vainionpaa R, Kleemola M, Raty R, Leinonen M, Korppi M, Tenore A, Canciani M (2005) Aetiology of community-acquired pneumonia: serological results of a paediatric survey. Scand.J.Infect.Dis., 37:806-812.

9. El Sayed ZM, Raafat D, El Metaal AA (2009) Relevance of serology for Mycoplasma pneumoniae diagnosis compared with PCR and culture in acute exacerbation of bronchial asthma. Am.J.Clin.Pathol., 131:74-80.

10. Gaillat J, Flahault A, deBarbeyrac B, Orfila J, Portier H, Ducroix JP, Bebear C, Mayaud C (2005) Community epidemiology of Chlamydia and Mycoplasma pneumoniae in LRTI in France over 29 months. Eur.J.Epidemiol., 20:643-651.

11. Graffelman AW, Knuistingh NA, le CS, Kroes AC, Springer MP, van den Broek PJ (2004) Pathogens involved in lower respiratory tract infections in general practice. Br.J.Gen.Pract., 54:15-19.

12. Gruteke P, Glas AS, Dierdorp M, Vreede WB, Pilon JW, Bruisten SM (2004) Practical implementation of a multiplex PCR for acute respiratory tract infections in children. J.Clin.Microbiol., 42:5596-5603.

13. Hamano-Hasegawa K, Morozumi M, Nakayama E, Chiba N, Murayama SY, Takayanagi R, Iwata S, Sunakawa K, Ubukata K (2008) Comprehensive detection of causative pathogens using real-time PCR to diagnose pediatric community-acquired pneumonia. J.Infect.Chemother., 14:424-432.

14. Huang HH, Zhang YY, Xiu QY, Zhou X, Huang SG, Lu Q, Wang DM, Wang F (2006) Community-acquired pneumonia in Shanghai, China: microbial etiology and implications for empirical therapy in a prospective study of 389 patients. Eur.J.Clin.Microbiol.Infect.Dis., 25:369-374.

15. Kim YJ, Boeckh M, Englund JA (2007) Community respiratory virus infections in immunocompromised patients: hematopoietic stem cell and solid organ transplant recipients, and individuals with human immunodeficiency virus infection. Semin.Respir.Crit Care Med., 28:222-242.

16. Kogan R, Martinez MA, Rubilar L, Paya E, Quevedo I, Puppo H, Girardi G, Castro-Rodriguez JA (2003) Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community-acquired pneumonia in children. Pediatr.Pulmonol., 35:91-98.

17. Lagerstrom F, Bader M, Foldevi M, Fredlund H, Nordin-Olsson I, Holmberg H (2003) Microbiological etiology in clinically diagnosed community-acquired pneumonia in primary care in Orebro, Sweden. Clin.Microbiol.Infect., 9:645-652.

18. Lauderdale TL, Chang FY, Ben RJ, Yin HC, Ni YH, Tsai JW, Cheng SH, Wang JT, Liu YC, Cheng YW, Chen ST, Fung CP, Chuang YC, Cheng HP, Lu DC, Liu CJ, Huang IW, Hung CL, Hsiao CF, Ho M (2005) Etiology of community acquired pneumonia among adult patients requiring hospitalization in Taiwan. Respir.Med., 99:1079-1086.

19. Lehtinen P, Jartti T, Virkki R, Vuorinen T, Leinonen M, Peltola V, Ruohola A, Ruuskanen O (2006) Bacterial coinfections in children with viral wheezing. Eur.J.Clin.Microbiol.Infect.Dis., 25:463-469.

20. Liu G, Talkington DF, Fields BS, Levine OS, Yang Y, Tondella ML (2005) Chlamydia pneumoniae and Mycoplasma pneumoniae in young children from China with community-acquired pneumonia. Diagn.Microbiol.Infect.Dis., 52:7-14.

21. Loens K, Beck T, Ursi D, Overdijk M, Sillekens P, Goossens H, Ieven M (2008) Evaluation of different nucleic acid amplification techniques for the detection of M. pneumoniae, C. pneumoniae and Legionella spp. in respiratory specimens from patients with community-acquired pneumonia. J.Microbiol.Methods, 73:257-262.

22. Maltezou HC, La-Scola B, Astra H, Constantopoulou I, Vlahou V, Kafetzis DA, Constantopoulos AG, Raoult D (2004) Mycoplasma pneumoniae and Legionella pneumophila in community-acquired lower respiratory tract infections among hospitalized children: diagnosis by real time PCR. Scand.J.Infect.Dis., 36:639-642.

23. Marrie TJ, Poulin-Costello M, Beecroft MD, Herman-Gnjidic Z (2005) Etiology of community-acquired pneumonia treated in an ambulatory setting. Respir.Med., 99:60-65.

24. Martinez MA, Ruiz M, Zunino E, Luchsinger V, Avendano LF (2008) Detection of Mycoplasma pneumoniae in adult community-acquired pneumonia by PCR and serology. J.Med.Microbiol., 57:1491-1495.

25. Martinez TM, Pino PY, Salazar BT, Jover LE, Caroca CC, Espinoza NM, Avendano CL (2005) [Diagnostic utility of the polymerase chain reaction for the diagnosis of Mycoplasma pneumoniae in elderly patients with community-acquired pneumonia]. Rev.Chilena.Infectol., 22:251-256.

26. Michelow IC, Olsen K, Lozano J, Rollins NK, Duffy LB, Ziegler T, Kauppila J, Leinonen M, McCracken GH, Jr. (2004) Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics, 113:701-707.

27. Miyashita N, Ouchi K, Kawasaki K, Oda K, Kawai Y, Shimizu H, Kobashi Y, Oka M (2008) Mycoplasma pneumoniae pneumonia in the elderly. Med.Sci.Monit., 14:CR387-CR391.

28. Morozumi M, Hasegawa K, Chiba N, Iwata S, Kawamura N, Kuroki H, Tajima T, Ubukata K (2004) Application of PCR for Mycoplasma pneumoniae detection in children with community-acquired pneumonia. J.Infect.Chemother., 10:274-279.

29. Nagalingam NA, Adesiyun AA, Swanston WH, Bartholomew M (2004) Prevalence of Mycoplasma pneumoniae and Chlamydia pneumoniae in pneumonia patients in four major hospitals in Trinidad. New Microbiol., 27:345-351.

30. Nakayama E, Hasegawa K, Morozumi M, Kobayashi R, Chiba N, Iitsuka T, Tajima T, Sunakawa K, Ubukata K (2007) Rapid optimization of antimicrobial chemotherapy given to pediatric patients with community-acquired pneumonia using PCR techniques with serology and standard culture. J.Infect.Chemother., 13:305-313.

31. Ngeow YF, Suwanjutha S, Chantarojanasriri T, Wang F, Saniel M, Alejandria M, Hsueh PR, Ping-Ing L, Park SC, Sohn JW, Aziah AM, Liu Y, Seto WH, Ngan CC, Hadiarto M, Hood A, Cheong YM (2005) An Asian study on the prevalence of atypical respiratory pathogens in community-acquired pneumonia. Int.J.Infect.Dis., 9:144-153.

32. Oosterheert JJ, van Loon AM, Schuurman R, Hoepelman AI, Hak E, Thijsen S, Nossent G, Schneider MM, Hustinx WM, Bonten MJ (2005) Impact of rapid detection of viral and atypical bacterial pathogens by real-time polymerase chain reaction for patients with lower respiratory tract infection. Clin.Infect.Dis., 41:1438-1444.

33. Otomo S, Yamamura J, Hayashi E, Nakamura T, Kakinuma H, Nakamoto Y, Takahashi H, Karasawa T (2008) Analysis of children with Chlamydophila (Chlamydia) pneumoniae and Mycoplasma pneumoniae respiratory infections by real-time PCR assay and serological tests. APMIS, 116:477-483.

34. Ozaki T, Nishimura N, Ahn J, Watanabe N, Muto T, Saito A, Koyama N, Nakane K, Funahashi K (2007) Utility of a rapid diagnosis kit for Mycoplasma pneumoniae pneumonia in children, and the antimicrobial susceptibility of the isolates. J.Infect.Chemother., 13:204-207.

35. Phares CR, Wangroongsarb P, Chantra S, Paveenkitiporn W, Tondella ML, Benson RF, Thacker WL, Fields BS, Moore MR, Fischer J, Dowell SF, Olsen SJ (2007) Epidemiology of severe pneumonia caused by Legionella longbeachae, Mycoplasma pneumoniae, and Chlamydia pneumoniae: 1-year, population-based surveillance for severe pneumonia in Thailand. Clin.Infect.Dis., 45:e147-e155.

36. Schneeberger PM, Dorigo-Zetsma JW, van der ZA, van BM, van Opstal JL (2004) Diagnosis of atypical pathogens in patients hospitalized with community-acquired respiratory infection. Scand.J.Infect.Dis., 36:269-273.

37. Shankar EM, Kumarasamy N, Balakrishnan P, Saravanan S, Solomon S, Vengatesan A, Murugavel KG, Rao UA (2007) Detection of pulmonary Mycoplasma pneumoniae infections in HIV-infected subjects using culture and serology. Int.J.Infect.Dis., 11:232-238.

38. Shenoy VD, Upadhyaya SA, Rao SP, Shobha KL (2005) Mycoplasma pneumoniae infection in children with acute respiratory infection. J.Trop.Pediatr., 51:232-235.

39. Sidal M, Kilic A, Unuvar E, Oguz F, Onel M, Agacfidan A, Aydin D, Koksalan K, Beka H (2007) Frequency of Chlamydia pneumoniae and Mycoplasma pneumoniae infections in children. J.Trop.Pediatr., 53:225-231.

40. Sohn JW, Park SC, Choi YH, Woo HJ, Cho YK, Lee JS, Sim HS, Kim MJ (2006) Atypical pathogens as etiologic agents in hospitalized patients with community-acquired pneumonia in Korea: a prospective multi-center study. J.Korean Med.Sci., 21:602-607.

41. Stralin K, Tornqvist E, Kaltoft MS, Olcen P, Holmberg H (2006) Etiologic diagnosis of adult bacterial pneumonia by culture and PCR applied to respiratory tract samples. J.Clin.Microbiol., 44:643-645.

42. Sung RY, Chan PK, Tsen T, Li AM, Lam WY, Yeung AC, Nelson EA (2009) Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays. J.Med.Virol., 81:153-159.

43. Teig N, Anders A, Schmidt C, Rieger C, Gatermann S (2005) Chlamydophila pneumoniae and Mycoplasma pneumoniae in respiratory specimens of children with chronic lung diseases. Thorax, 60:962-966.

44. Templeton KE, Scheltinga SA, van den Eeden WC, Graffelman AW, van den Broek PJ, Claas EC (2005) Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin.Infect.Dis., 41:345-351.

45. Tsolia MN, Psarras S, Bossios A, Audi H, Paldanius M, Gourgiotis D, Kallergi K, Kafetzis DA, Constantopoulos A, Papadopoulos NG (2004) Etiology of community-acquired pneumonia in hospitalized school-age children: evidence for high prevalence of viral infections. Clin.Infect.Dis., 39:681-686.

46. van de Garde EM, Endeman H, van Hemert RN, Voorn GP, Deneer VH, Leufkens HG, van den Bosch JM, Biesma DH (2008) Prior outpatient antibiotic use as predictor for microbial aetiology of community-acquired pneumonia: hospital-based study. Eur.J.Clin.Pharmacol., 64:405-410.

47. Wattanathum A, Chaoprasong C, Nunthapisud P, Chantaratchada S, Limpairojn N, Jatakanon A, Chanthadisai N (2003) Community-acquired pneumonia in southeast Asia: the microbial differences between ambulatory and hospitalized patients. Chest, 123:1512-1519.

48. Yamazaki T, Narita M, Sasaki N, Kenri T, Arakawa Y, Sasaki T (2006) Comparison of PCR for sputum samples obtained by induced cough and serological tests for diagnosis of Mycoplasma pneumoniae infection in children. Clin.Vaccine Immunol., 13:708-710.

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