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Korean J Pediatr > Volume 55(2); 2012 > Article
Youn and Lee: Mycoplasma pneumoniae pneumonia in children

Abstract

Mycoplasma pneumoniae (MP), the smallest self-replicating biological system, is a common cause of upper and lower respiratory tract infections, leading to a wide range of pulmonary and extra-pulmonary manifestations. MP pneumonia has been reported in 10 to 40% of cases of community-acquired pneumonia and shows an even higher proportion during epidemics. MP infection is endemic in larger communities of the world with cyclic epidemics every 3 to 7 years. In Korea, 3 to 4-year cycles have been observed from the mid-1980s to present. Although a variety of serologic assays and polymerase chain reaction (PCR) techniques are available for the diagnosis of MP infections, early diagnosis of MP pneumonia is limited by the lack of immunoglobulin (Ig) M antibodies and variable PCR results in the early stages of the infection. Thus, short-term paired IgM serologic tests may be mandatory for an early and definitive diagnosis. MP infection is usually a mild and self-limiting disease without specific treatment, and if needed, macrolides are generally used as a first-choice drug for children. Recently, macrolide-resistant MP strains have been reported worldwide. However, there are few reports of apparent treatment failure, such as progression of pneumonia to acute respiratory distress syndrome despite macrolide treatment. The immunopathogenesis of MP pneumonia is believed to be a hyperimmune reaction of the host to the insults from MP infection, including cytokine overproduction and immune cell activation (T cells). In this context, immunomodulatory treatment (corticosteroids or/and intravenous Ig), in addition to antibiotic treatment, might be considered for patients with severe infection.

Introduction

Mycoplasma pneumoniae (MP) is a major cause of community-acquired pneumonia in children and young adults1,2). Although more than 200 mycoplasma species have been discovered in animals and humans to date, MP is the most recognized human pathogen among them. MP infection shows a variety of clinical manifestations, ranging from asymptomatic infection to fatal pneumonia or extrapulmonary diseases. MP pneumonia has been reported in 10 to 40% of community-acquired pneumonia cases, and children are the most susceptible group to MP infection1,2). Since summer 2011, a new MP epidemic has been spreading throughout Korea. This epidemic presents some clinical and laboratory characteristics that seem to be different from those of previous epidemics, although the strain subtypes in this epidemic have not been identified yet. In this review, we briefly give an overview of the pathogenesis, epidemiology, clinical manifestations, diagnosis, and treatment of MP infection, including macrolide-resistant MP (MRMP).

Biological characteristics and immunopathogenesis

MP is an exceptionally small prokaryote, which, like viruses, can pass a filter paper. Because of the absence of a cell wall, this organism is insensitive to β-lactam antibiotics and is not stained by Gram staining. Also, MP has an extremely small genome, which makes it a fastidiously growing bacterium requiring the presence of a variety of substances, including nucleotides and sterols, for its replication both within the host and in in vitro culture systems3). MP is a mucosal extracellular pathogen - not an intracellular pathogen like viruses - and shows no cytopathic effects on other cell culture systems except to the respiratory ciliated epithelium4). It has been believed that multiplied MP agents spread to lower respiratory tract cells and induce pneumonia. In this context, the survival of MP initially depends on cytoadherence to the respiratory epithelium of the host. MP has an attachment tip in which a complex of adhesion and interactive adhesion-accessory proteins are localized. After adherence, MP may need to multiply in order to establish an infection, involving colonization and further inflammation of other tissues5). In vitro studies have shown that mycoplasma species preferentially attach to ciliated respiratory epithelial cells, and induce a cytopathic effect caused by hydrogen peroxide or other toxins (e.g., ADP-ribosylating and vacuolating cytotoxin), and by the gliding motility6,7). On the other hand, with the fastidiously growing nature of MP, the evidences of the MP agents in pathologic tissues are limited. MP are neither found beneath nor inside respiratory epithelial cells in animal models, and electronic microscopic examination of samples from patients with severe MP pneumonia, and polymerase chain reaction (PCR) assay of lung aspirate specimens from children with community-acquired pneumonia are also not effective for finding MP agents8,9).
Since MP infection, similar to other infections, is controlled by the host's immune system, and the majority of MP-infected patients recover from the disease without pneumonia, it is possible that acute lung injury in affected patients is associated with the patient's immune response. In MP infection, the innate and adaptive immune system of the host work together against insults from the infection. The mediators (proteins) from the innate immune reaction may affect the adaptive immune reaction. Toll-like receptors (TLRs) and possibly intracellular sensors, in infected cells and macrophages, that recognize MP components induce anti-pathogenic proteins and other proteins, including pro-inflammatory cytokines10,11). These proteins may affect the cells of the adaptive immune system. Lipoproteins derived from mycoplasmas, such as macrophage-activating lipopeptide 2, have been reported to induce cytokines and chemokines from macrophages through TLRs12,13). These cytokines recruit immune cells, including T cells, leading to further production of cytokines, and may be involved in the inflammatory responses toward MP infection.
Many immunological studies have revealed that various cytokines, including interleukin (IL)-2, IL-8, and IL-18; other reactive substances; and immune cells, including antigen-presenting cells and T cells, are involved in the immune reaction to MP14-16). Since it is believed that major pro-inflammatory cytokines induced by MP infection are important mediators for lung defense and lung injury, cytokine imbalance may be responsible for lung injury in this infection.
T cells may have a crucial role in the acute lung injury induced by MP infection, as well as by other viral infections such as influenza virus infection. Previous reports on these infections showed that T cell deficiency mice or T cell depressed mice with immune suppressants had less severe pneumonia with prolonged survival time and little pathologic findings compared to control mice17-19). Furthermore, some clinical characteristics of MP pneumonia also help postulate the pathogenesis of lung injury due to MP. We previously found that the severity of pneumonia was correlated with lymphocyte counts at presentation, and early immunemodulators (corticosteroids) induced rapid recovery of severe pneumonic consolidations within several days20,21).
Finally, it is unknown whether the whole MP agent itself or other substances (MP components or mediators from the host) induce immunological inflammation in lung lesions. For this issue, we introduce a new concept for the immunopathogenesis of acute lung injury in MP or influenza virus infections by using a hypothesis involving the 'protein homeostasis system' of the host2,19). Briefly, we postulated that the adaptive immune system is one among the protein homeostasis systems in vivo. B cells control proteins, except small proteins, through antibodies, and T cells control small proteins (peptides) through cytokine production or through their effect on cell-bound pathogenic proteins or through T cell receptors. During the incubation period of MP infection, substances including pathogenic proteins are produced in a focus (possibly a secondary immune organ near the primary infection sites). The substances spread and reach lung cells as main target cells, and various tissues for extrapulmonary manifestations via systemic circulation. Immune cells start to control these substances, and clinical symptoms and signs begin to appear. The pathogenic proteins bind to lower respiratory tract cells of which receptors have affinity to them, and this process induces cell injury and/or production of other proteins through signaling pathways to the nucleus of affected cells. Immune cells are recruited to the lesions to control the action of the pathogenic proteins and proteins from injured cells. Initially, nonspecific T cells and nonspecific antibodies are involved in this reaction. During this process, hyper-activated immune cells (mainly T cells) produce inflammatory cytokines and counter-inflammatory cytokines, leading to a cytokine imbalance associated with further lung cell injury. After the emergence of specific T cell clones and specific antibodies that efficiently control the pathogenic proteins, tissue injury ceases and a repair reaction begins with the immune cells.

Epidemiology

MP infection is endemic in the larger communities of the world, but epidemics, lasting several months to years, periodically occur every 3 to 7 years. In Korea, 3 to 4-year cycles of MP pneumonia have been observed from the mid-1980s to present. Pneumonia cases peak mainly in the fall or winter seasons, and epidemics last approximately 12 to 18 months22,23). Occasionally, local outbreaks have been reported in close contact settings, such as schools, military barracks, and inpatient institutions.
The epidemiological and clinical characteristics of MP infection, such as the appearance of a cyclic epidemic and lymphopenia, are similar to that of other systemic viral infections, including measles and influenza2). The susceptible population to MP, especially the young age group, would increase in number during the 3 to 4 years of the inter-epidemic period, and this age group may serve as the reservoir of the epidemics. The susceptible group would move to younger generation and most of adult generation would acquire immunity to MP over time. Seroepidemiological studies on MP infection have proven this finding: the seropositivity of immunoglobulin (Ig) G antibodies against MP is progressively greater with increasing age24), and persons >40 years old may have a seropositivity rate of near 100%. Although MP pneumonia is known to be predominant in school-aged children, in Korea, the 4 to 6 years age group was the most prevalent group, and the age of children among whom MP infection was prevalent appeared to become younger, with low frequencies of infection in the adult group in recent MP epidemics22,23).
The exact infection rate in a population during an MP epidemic is unknown. However, serologic studies suggest that during an epidemic, a significant proportion of the susceptible population (>50%) may be infected, manifesting asymptomatic or mild phenotypes, although the proportion of MP pneumonia patients may be very low.
The subtypes of MP are believed to be different in each epidemic, like in seasonal (inter-pandemic) influenza, although few studies exist for genes other than P1 gene. In a previous report, one P1 subtype of MP was found to be predominant in an epidemic; however, another P1 subtype might be predominant in other epidemics25). Recently, MRMP strains have been identified in epidemics in Far East Asian countries, including Japan, China, Korea and other countries26-29). The strains were mutated mainly in nucleic sequences of 23S rRNA or ribosomal proteins. In Korea, an investigation group found that in the 2011 epidemic, more than 50% of the isolated MP strains were MRMP strains30). Although patients infected with MRMP were reported to have the prolonged fever duration, compared to the patients infected with macrolide-sensitive strains, few cases showed treatment failure with macrolide treatment31,32). Given that MP pneumonia is a host immune-mediated and self-limited disease, the clinical implications of alternative antibiotic treatments for patients with MRMP strains require further evaluation. In addition, Narita recently proposed an interesting postulation that MRMP strains may exhibit less efficient protein synthesis because of ribosomal mutations, and that the drug resistance of MP itself does not directly lead to clinical severity33). We found that in the 2011 epidemic, the positive rate of PCR was far less than, and the initial negative rate of IgM antibody at presentation was higher than that of the 2006 to 2007 epidemic (unpublished observation).

Clinical manifestations

The most common clinical manifestation of MP infection is pneumonia. Other respiratory symptoms such as pharyngitis, otitis media, bronchitis, sinusitis, croup and bronchiolitis are also observed. The incubation period of MP pneumonia is 1 to 3 weeks. MP pneumonia patients present with acute onset of fever, sore throat, malaise, and headache; however, coryza is not usual, like that in influenza. After 3 to 7 days onset of constitutional symptoms, cough and radiographic evidence of pneumonia appear. Fever ranging from 38℃ to 39.5℃ is commonly seen. The clinical symptoms and physical findings of suspected pneumonia are often poorly correlated with the radiographic finding of pneumonia (walking pneumonia). The clinical course in untreated patients is variable, but most symptoms are resolved within 2 to 4 weeks, even in antibiotic-nonresponsive, progressive pneumonia20).
The radiographic findings of MP pneumonia are pleomorphic. Interstitial and bronchopneumonic patterns are common, and segmental and/or lobar pneumonic patterns with pleural effusions are not rare. We previously found that older children (>6 years), who have a more mature immune system, had longer duration of fever, higher C-reactive protein, and more severe pulmonary lesions and lower leukocyte counts with lymphocyte differentials than the younger group (<5 years)21).
MP infection has shown an association with asthma. The infection may precede the onset of asthma, exacerbate the asthma, or play a part in asthma chronicity in some children and adults1,34). Extrapulmonary involvement in MP infection has been identified in neurologic, dermatologic, hematologic and other immunologic disorders. Skin rash is the most frequently seen manifestation, and central nervous system complications, such as meningoencephalitis and Guillain-Barre syndrome, are rarely seen. MP is a major cause of childhood encephalitis. Immunopathogenetic mechanisms are known to be involved in the extra-pulmonary manifestations of MP35).

Diagnosis

Although a variety of serologic assays and PCR techniques have been used for the diagnosis of MP infection, methods for the early diagnosis of MP pneumonia are limited because of the lack of IgM antibodies and the variable detection rate of PCR products in the early stages of the infection1,2).
Serologic assays, including complement fixation assay, microparticle agglutination assay, enzyme-linked immunosorbent assay, and enzyme-linked immunoassay, need paired serum samples for a definitive diagnosis, showing seroconversion or a 4-fold increase in titer. The sensitivities of serologic assays for the detection of MP antibodies are known to vary36,37). We previously reported that more than 45% of patients with MP pneumonia were seroconverters whose IgM antibodies were negative in the early stage of MP infection20,21). Therefore, short-term paired IgM serologic tests may be mandatory for early and definitive diagnosis in patients with severe pneumonia2,21).
Recently, PCR assay has been applied for the early detection of MP infection. PCR is an attractive alternative test to MP culture. Several gene targets have been used, including the P1 gene and the 16S rRNA gene37). The results from PCR studies have shown variable sensitivities and specificities between children and adult groups, when compared with serologic results38,39). PCR results can be affected by the materials obtained from different sites of the respiratory tract, by the stage of disease, and by diverse technical errors. In our studies, the detection rate of PCR tests in the 2006 to 2007 epidemic was 12 to 30%21,40), but it was less than 5% in the 2011 epidemic. It is unknown whether MRMP strains are poorly colonized on the upper respiratory tract compared to other strains. In addition, MP can remain in the respiratory tract for a long time without symptoms, especially in younger children after primary infection41). Thus, PCR study alone is not sufficient for a definitive diagnosis of MP infection. Use of a combination of serologic assays and PCR may be an ideal method for the diagnosis of MP infection.

Treatment

MP infection is usually mild and self-limited, without a need for a specific treatment. Because MP has no cell wall, antibiotics such as macrolides, tetracyclines, and quinolones have been used for treating MP pneumonia. For children, only macrolides (erythromycin, clarithromycin, roxithromycin, and azithromycin) are used because of the potential side effects of alternative drugs (tetracycline and fluoroquinolones). Although earlier studies reported that antibiotic therapy for young adult patients induced more rapid resolution of fever and cough42,43), this therapy could not prevent the progression to severe pneumonia in some patients, as well as the associated extrapulmonary diseases. Patients infected with MRMP strains have prolonged fever duration; however, in general, disease progression was not observed with macrolide treatment31,32). These findings suggest that in MP infection, the substances that induce the fever and the substances that induce the pneumonia may differ in vivo. Moreover, the effects of antibiotic treatment for MP pneumonia in children are still controversial44).
Some investigators have reported that a change of antibiotics showed good outcome in MRMP-infected patients45,46). However, others have reported that patients properly treated with antibiotics showed progressive pneumonia47,48). In children and adults who were nonresponsive to antibiotics and showed progressive disease, including those with MRMP, many investigators have reported that additional corticosteroids are effective, especially in those with severe MP pneumonia20,47-51). In addition, experimental studies have also reported the beneficial effect of corticosteroids on MP infections52,53). We previously reported that the use of immune-modulators (prednisolone) for antibiotic-nonresponsive MP pneumonia patients was effective in improving clinical and radiographic findings20,21). In this 2011 epidemic, we used prednisolone (1 mg/kg) early, with a macrolide (chlarithromycin) or/and a non-macrolide antibiotic (amoxicillin/clavulanate or cefuroxime) for MP pneumonia patients who had persist fever for >48 hours after admission. The majority of the patients defervesced without disease progression within 24 to 48 hours, even in those who received only a non-macrolide antibiotic. The small group of patients who did not response to this therapy received intravenous methylprednisone (10 mg/kg for 2 to 3 days, tapering within a week) or intravenous Ig (1 g/kg/day, 1 to 2 doses), and all patients improved clinically and radiographically within several days without side effects (unpublished observation). These findings may again verify the notion that the pathogenesis of pneumonia in MP infection is immune-mediated2). Nevertheless, further controlled clinical studies for corticosteroids and candidate antibiotics (quinolones and tetracyclines) for children with MRMP infection are needed.

References

1. Atkinson TP, Balish MF, Waites KB. Epidemiology, clinical manifestations, pathogenesis and laboratory detection of Mycoplasma pneumoniae infections. FEMS Microbiol Rev 2008;32:956–973.
crossref pmid
2. Lee KY. Pediatric respiratory infections by Mycoplasma pneumoniae. Expert Rev Anti Infect Ther 2008;6:509–521.
crossref pmid
3. Razin S, Yogev D, Naot Y. Molecular biology and pathogenicity of mycoplasmas. Microbiol Mol Biol Rev 1998;62:1094–1156.
pmid pmc
4. Denny FW, Clyde WA Jr, Glezen WP. Mycoplasma pneumoniae disease: clinical spectrum, pathophysiology, epidemiology, and control. J Infect Dis 1971;123:74–92.
crossref pmid
5. Shimizu T, Kida Y, Kuwano K. Cytoadherence-dependent induction of inflammatory responses by Mycoplasma pneumoniae. Immunology 2011;133:51–61.
crossref pmid pmc
6. Techasaensiri C, Tagliabue C, Cagle M, Iranpour P, Katz K, Kannan TR, et al. Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among mycoplasma pneumoniae strains. Am J Respir Crit Care Med 2010;182:797–804.
crossref pmid pmc
7. Chang HY, Jordan JL, Krause DC. Domain analysis of protein P30 in Mycoplasma pneumoniae cytadherence and gliding motility. J Bacteriol 2011;193:1726–1733.
crossref pmid pmc
8. Rollins S, Colby T, Clayton F. Open lung biopsy in Mycoplasma pneumoniae pneumonia. Arch Pathol Lab Med 1986;110:34–41.
pmid
9. Vuori-Holopainen E, Salo E, Saxén H, Hedman K, Hyypiä T, Lahdenperä R, et al. Etiological diagnosis of childhood pneumonia by use of transthoracic needle aspiration and modern microbiological methods. Clin Infect Dis 2002;34:583–590.
crossref pmid
10. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev 2009;22:240–273.
crossref pmid pmc
11. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol 2011;30:16–34.
crossref pmid
12. Mühlradt PF, Kiess M, Meyer H, Süssmuth R, Jung G. Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at picomolar concentration. J Exp Med 1997;185:1951–1958.
crossref pmid pmc
13. Zuo LL, Wu YM, You XX. Mycoplasma lipoproteins and Toll-like receptors. J Zhejiang Univ Sci B 2009;10:67–76.
crossref pmid pmc
14. Narita M, Tanaka H, Yamada S, Abe S, Ariga T, Sakiyama Y. Significant role of interleukin-8 in pathogenesis of pulmonary disease due to Mycoplasma pneumoniae infection. Clin Diagn Lab Immunol 2001;8:1028–1030.
pmid pmc
15. Hardy RD, Jafri HS, Olsen K, Wordemann M, Hatfield J, Rogers BB, et al. Elevated cytokine and chemokine levels and prolonged pulmonary airflow resistance in a murine Mycoplasma pneumoniae pneumonia model: a microbiologic, histologic, immunologic, and respiratory plethysmographic profile. Infect Immun 2001;69:3869–3876.
crossref pmid pmc
16. Yang J, Hooper WC, Phillips DJ, Talkington DF. Cytokines in Mycoplasma pneumoniae infections. Cytokine Growth Factor Rev 2004;15:157–168.
crossref pmid
17. Denny FW, Taylor-Robinson D, Allison AC. The role of thymus-dependent immunity in Mycoplasma pulmonis infections of mice. J Med Microbiol 1972;5:327–336.
crossref pmid
18. Tanaka H, Honma S, Abe S, Tamura H. Effects of interleukin-2 and cyclosporin A on pathologic features in Mycoplasma pneumonia. Am J Respir Crit Care Med 1996;154(6 Pt 1): 1908–1912.
crossref pmid
19. Lee KY, Rhim JW, Kang JH. Hyperactive immune cells (T cells) may be responsible for acute lung injury in influenza virus infections: a need for early immune-modulators for severe cases. Med Hypotheses 2011;76:64–69.
crossref pmid
20. Lee KY, Lee HS, Hong JH, Lee MH, Lee JS, Burgner D, et al. Role of prednisolone treatment in severe Mycoplasma pneumoniae pneumonia in children. Pediatr Pulmonol 2006;41:263–268.
crossref pmid
21. Youn YS, Lee KY, Hwang JY, Rhim JW, Kang JH, Lee JS, et al. Difference of clinical features in childhood Mycoplasma pneumoniae pneumonia. BMC Pediatr 2010;10:48
crossref pmid pmc
22. Kim JW, Seo HK, Yoo EG, Park SJ, Yoon SH, Jung HY, et al. Mycoplasma pneumoniae pneumonia in Korean children, from 1979 to 2006-a meta-analysis. Korean J Pediatr 2009;52:315–323.
crossref
23. Lee SH, Noh SM, Lee KY, Lee HS, Hong JH, Lee MH, et al. Clinico-epidemiologic study of Mycoplasma pneumoniae pneumonia (1993 through 2003). Korean J Pediatr 2005;48:154–157.

24. Brunner H, Prescott B, Greenberg H, James WD, Horswood RL, Chanock RM. Unexpectedly high frequency of antibody to Mycoplasma pneumoniae in human sera as measured by sensitive techniques. J Infect Dis 1977;135:524–530.
crossref pmid
25. Sasaki T, Kenri T, Okazaki N, Iseki M, Yamashita R, Shintani M, et al. Epidemiological study of Mycoplasma pneumoniae infections in Japan based on PCR-restriction fragment length polymorphism of the P1 cytadhesin gene. J Clin Microbiol 1996;34:447–449.
pmid pmc
26. Morozumi M, Takahashi T, Ubukata K. Macrolide-resistant Mycoplasma pneumoniae: characteristics of isolates and clinical aspects of community-acquired pneumonia. J Infect Chemother 2010;16:78–86.
crossref pmid
27. Liu Y, Ye X, Zhang H, Xu X, Li W, Zhu D, et al. Characterization of macrolide resistance in Mycoplasma pneumoniae isolated from children in Shanghai, China. Diagn Microbiol Infect Dis 2010;67:355–358.
crossref pmid
28. Dumke R, von Baum H, Lück PC, Jacobs E. Occurrence of macrolide-resistant Mycoplasma pneumoniae strains in Germany. Clin Microbiol Infect 2010;16:613–616.
crossref pmid
29. Oh CE, Choi EH, Lee HJ. Detection of genetic mutations associated with macrolide resistance of Mycoplasma pneumoniae. Korean J Pediatr 2010;53:178–183.
crossref
30. Hong KB, Lee SY, Choi EH, Lee J, Ahn YM, Lee HJ. Prevalence of genetic mutations associated with macrolide resistance of Mycoplasma pneumoniae in Korea. Program and abstracts of the 2011 Autumn Meeting of the Korean Society for Pediatric Infectious Diseases 2011;2011 Nov 12; Seoul, Korean Society of Pediatric Infectious Disease. –7.
pmid
31. Suzuki S, Yamazaki T, Narita M, Okazaki N, Suzuki I, Andoh T, et al. Clinical evaluation of macrolide-resistant Mycoplasma pneumoniae. Antimicrob Agents Chemother 2006;50:709–712.
crossref pmid pmc
32. Matsubara K, Morozumi M, Okada T, Matsushima T, Komiyama O, Shoji M, et al. A comparative clinical study of macrolide-sensitive and macrolide-resistant Mycoplasma pneumoniae infections in pediatric patients. J Infect Chemother 2009;15:380–383.
crossref pmid
33. Narita M. Two unexpected phenomena in macrolide-resistant Mycoplasma pneumoniae infection in Japan and the unique biological characteristics of Mycoplasma pneumoniae. J Infect Chemother 2011;17:735–736.
crossref pmid pmc
34. Sutherland ER, Martin RJ. Asthma and atypical bacterial infection. Chest 2007;132:1962–1966.
crossref pmid
35. Narita M. Pathogenesis of extrapulmonary manifestations of Mycoplasma pneumoniae infection with special reference to pneumonia. J Infect Chemother 2010;16:162–169.
crossref pmid
36. Beersma MF, Dirven K, van Dam AP, Templeton KE, Claas EC, Goossens H. Evaluation of 12 commercial tests and the complement fixation test for Mycoplasma pneumoniae-specific immunoglobulin G (IgG) and IgM antibodies, with PCR used as the "gold standard". J Clin Microbiol 2005;43:2277–2285.
crossref pmid pmc
37. Loens K, Goossens H, Ieven M. Acute respiratory infection due to Mycoplasma pneumoniae: current status of diagnostic methods. Eur J Clin Microbiol Infect Dis 2010;29:1055–1069.
crossref pmid
38. Martínez MA, Ruiz M, Zunino E, Luchsinger V, Avendaño LF. Detection of Mycoplasma pneumoniae in adult community-acquired pneumonia by PCR and serology. J Med Microbiol 2008;57(Pt 12): 1491–1495.
crossref pmid
39. Zhang L, Zong ZY, Liu YB, Ye H, Lv XJ. PCR versus serology for diagnosing Mycoplasma pneumoniae infection: a systematic review & meta-analysis. Indian J Med Res 2011;134:270–280.
pmid
40. Youn YS, Lee KY, Hwang JY, Yim JW, Kang JH, Lee JS. Comparison of diagnostic methods and the changes of IgG subclasses in children with Mycoplasma pneumoniae pneumonia. Pediatr Allergy Respir Dis 2009;19:137–145.

41. Dorigo-Zetsma JW, Wilbrink B, van der Nat H, Bartelds AI, Heijnen ML, Dankert J. Results of molecular detection of Mycoplasma pneumoniae among patients with acute respiratory infection and in their household contacts reveals children as human reservoirs. J Infect Dis 2001;183:675–678.
crossref pmid
42. Shames JM, George RB, Holliday WB, Rasch JR, Mogabgab WJ. Comparison of antibiotics in the treatment of mycoplasmal pneumonia. Arch Intern Med 1970;125:680–684.
crossref pmid
43. McCracken GH Jr. Current status of antibiotic treatment for Mycoplasma pneumoniae infections. Pediatr Infect Dis 1986;5:167–171.
crossref pmid
44. Mulholland S, Gavranich JB, Chang AB. Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children. Cochrane Database Syst Rev 2010;(7): CD004875
pmid
45. Miyashita N, Maruyama T, Kobayashi T, Kobayashi H, Taguchi O, Kawai Y, et al. Community-acquired macrolide-resistant Mycoplasma pneumoniae pneumonia in patients more than 18 years of age. J Infect Chemother 2011;17:114–118.
crossref pmid
46. Averbuch D, Hidalgo-Grass C, Moses AE, Engelhard D, Nir-Paz R. Macrolide resistance in Mycoplasma pneumoniae, Israel, 2010. Emerg Infect Dis 2011;17:1079–1082.
crossref pmid pmc
47. Kosugi Y, Katsura H. A case of fulminant Mycoplasma pneumoniae pneumonia despite adequate antibiotic treatment. Nihon Kokyuki Gakkai Zasshi 2009;47:471–475.
pmid
48. Kim DH, Lee KY, Kim MS, Youn YS, Hwang JY, Rhim JW, et al. Corticosteroid treatment in siblings affected with severe Mycoplasma pneumoniae pneumonia. Infect Chemother 2009;41:190–195.
crossref
49. Tamura A, Matsubara K, Tanaka T, Nigami H, Yura K, Fukaya T. Methylprednisolone pulse therapy for refractory Mycoplasma pneumoniae pneumonia in children. J Infect 2008;57:223–228.
crossref pmid
50. Miyashita N, Obase Y, Ouchi K, Kawasaki K, Kawai Y, Kobashi Y, et al. Clinical features of severe Mycoplasma pneumoniae pneumonia in adults admitted to an intensive care unit. J Med Microbiol 2007;56(Pt 12): 1625–1629.
crossref pmid
51. Lu A, Wang L, Zhang X, Zhang M. Combined treatment for child refractory Mycoplasma pneumoniae pneumonia with ciprofloxacin and glucocorticoid. Pediatr Pulmonol 2011;46:1093–1097.
crossref pmid
52. Tagliabue C, Salvatore CM, Techasaensiri C, Mejias A, Torres JP, Katz K, et al. The impact of steroids given with macrolide therapy on experimental Mycoplasma pneumoniae respiratory infection. J Infect Dis 2008;198:1180–1188.
crossref pmid pmc
53. Hirao S, Wada H, Nakagaki K, Saraya T, Kurai D, Mikura S, et al. Inflammation provoked by Mycoplasma pneumoniae extract: implications for combination treatment with clarithromycin and dexamethasone. FEMS Immunol Med Microbiol 2011;62:182–189.
crossref pmid


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