今日の臨床サポート 今日の臨床サポート

著者: 櫻井隆之 NTT東日本関東病院 感染症内科部長/感染対策推進室長

監修: 具芳明 東京科学大学大学院医歯学総合研究科 統合臨床感染症学分野

著者校正/監修レビュー済:2024/09/18
参考ガイドライン:
  1. 日本呼吸器学会:成人肺炎診療ガイドライン2024
  1. 日本マイコプラズマ学会:肺炎マイコプラズマ肺炎に対する治療指針 2014
患者向け説明資料

改訂のポイント:
  1. 日本呼吸器学会の『成人肺炎診療ガイドライン2024』が発刊され、「市中肺炎(CAP)における細菌性肺炎とマイコプラズマ肺炎の鑑別」の内容を更新した。6項目中5項目以上に該当する場合は本疾患の可能性が高い。
  1. COVID-19パンデミックを経て網羅的PCRを実施できる施設が増えたため、保険収載も鑑み追記した。
  1. 抗菌薬変更のタイミングについて、48時間では判断まで短い可能性があるため、72時間に変更した。

概要・推奨   

  1. 明瞭なデータは得られないが、成人におけるマイコプラズマ肺炎において抗菌薬の投与は症状を軽減することが期待され、使用することが考慮されるべきである。ただし小児においては個別に検討することが必要である(推奨度2)
  1. マイコプラズマ肺炎における抗菌薬の選択は、耐性率などを考慮しながら、個別の症例ごとに検討することが推奨される(推奨度2)
  1. わが国においては小児を中心にマクロライド耐性マイコプラズマが急増しており、成人での感染例も存在する。マクロライドで72時間以内に解熱しない症例は治療を変更する(推奨度2)
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病態・疫学・診察 

疾患情報(疫学・病態)  
  1. マイコプラズマ肺炎はマイコプラズマ・ニューモニエ(Mycoplasma pneumoniae)により引き起こされる肺炎である。軽症であることが多く、“Walking pneumonia”とも表現される。非定型肺炎または異型肺炎の一部である。
  1. 頭痛や咽頭痛、鼻汁や関節痛、消化器症状など多彩な症状がみられる。治療後も強固な咳嗽が1カ月程度残ることが多い。
  1. 若年者の重症感のない肺炎では、COVID-19以外ではマイコプラズマを一番に考えるとよい。本疾患を疑う所見として、日本呼吸器学会「成人肺炎診療ガイドライン2024」に列挙された「市中肺炎(CAP)における細菌性肺炎とマイコプラズマ肺炎の鑑別」(下記)が参考になる。6項目のうち5項目以上に合致すれば本疾患の可能性が高く、2項目以下なら細菌性肺炎の可能性が高い。3、4項目に合致する場合は両者合併か鑑別困難と考える。かつては4項目以上の合致で非定型肺炎と診断でき、その感度は78%、特異度は93%とされていた[1][2][3]
  1. 1:年齢60歳未満
  1. 2:基礎疾患がないか、または軽微
  1. 3:強固な咳嗽
  1. 4:胸部聴診上所見が乏しい
  1. 5:迅速診断法で原因菌が同定されない
  1. 6:末梢血WBC 10,000/uL未満
  1. 感染力が強く家族内感染が多く見受けられる。すでに診断された人が身近にいるかどうかが重要である。
  1. マイコプラズマは小児疾患であるが成人にも感染する。ただしその病状は一般に軽く、肺炎に至る例は感染者の3~5%、その他は上気道炎(風邪症候群)、気管支炎などである。60歳未満が圧倒的に多いが、近年は育児を担当する60歳以上の例も珍しくない。本疾患に罹患する可能性はあるため、従前の「60歳以上ではみられない」は過去の話となった。
  1. 潜伏期間は2~3週間。発熱、頭痛などで発症し数日で強固な咳嗽が始まる。肺炎といえども軽症が多くwalking pneumoniaと呼ばれる。肺炎球菌肺炎の様なスピードはないが、ゆっくりと着実に悪化するイメージでよい。
  1. オリンピック開催年に流行するという「オリンピック病」は過去の話となり、現在は毎年流行している。秋の流行が多いが、年によって様相は異なり、一年中流行したこともある。
問診・診察のポイント  
  1. 年齢、基礎疾患の確認をする。60歳未満で基礎疾患がないかまたは軽微なことが多いためである。周囲に乳幼児がいる環境かどうかの確認も重要である。発症者からの飛沫感染が多い。

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文献 

Ishida T, Miyashita N, Nakahama C.
Clinical differentiation of atypical pneumonia using Japanese guidelines.
Respirology. 2007 Jan;12(1):104-10. doi: 10.1111/j.1440-1843.2006.00927.x.
Abstract/Text BACKGROUND AND OBJECTIVE: Atypical pneumonia occupies an important position in community-acquired pneumonia. The aim of this study was to examine whether making a diagnosis of atypical pneumonia is possible based upon the Japanese Respiratory Society guidelines.
METHODS: The data from three prospective studies were reviewed. A total of 285 patients with mycoplasmal pneumonia or chlamydial pneumonia and 515 patients with pneumococcal pneumonia or Haemophilus influenzae pneumonia were assessed to determine whether these pneumonias met the diagnostic criteria for atypical pneumonia used in the Japanese Respiratory Society guidelines. The criteria were: (i) age less than 60 years; (ii) no or only minor underlying diseases; (iii) persistent cough; (iv) limited chest auscultatory findings; (v) no sputum, or no identified aetiological agent by rapid diagnosis; and (vi) a peripheral white blood cell count below 10,000/microL.
RESULTS: All items of the criteria proved to be valid except for 'age' in patients with Chlamydophila pneumoniae pneumonia using multiple regression analysis. The sensitivity and specificity for atypical pneumonia were 77.0% and 93.0% based on four or more of the criteria respectively.
CONCLUSION: Pure atypical pneumonia can be differentiated to some degree by clinical symptoms and laboratory findings. It is important to differentiate and treat bacterial pneumonia and atypical pneumonia in regions such as Japan, where Streptococcus pneumoniae resistance to macrolides is high. Treatment covering the two types of pneumonia should be considered in elderly patients and those with underlying respiratory disease.

PMID 17207034
Miyashita N, Fukano H, Yoshida K, Niki Y, Matsushima T.
Is it possible to distinguish between atypical pneumonia and bacterial pneumonia?: evaluation of the guidelines for community-acquired pneumonia in Japan.
Respir Med. 2004 Oct;98(10):952-60. doi: 10.1016/j.rmed.2004.03.011.
Abstract/Text The Japanese Respiratory Society (JRS) published the guidelines for the management of community-acquired pneumonia in 2000. The guidelines set up nine parameters and criteria for the differential diagnosis of atypical pneumonia and bacterial pneumonia based on clinical symptoms, physical signs and laboratory data. To evaluate the performance of these guideline criteria, 91 cases of Chlamydia pneumoniae (53 cases were pure-C. pneumoniae and 38 cases were mixed-C. pneumoniae pneumonia), 103 cases of Mycoplasma pneumoniae (86 cases were pure-M. pneumoniae and 17 cases were mixed-M. pneumoniae pneumonia) and 144 cases of bacterial (Streptococcus pneumoniae and/or Haemophilus influenzae) pneumonia were analyzed. The accordance rate for a suspected atypical pneumonia with the guideline criteria was 84.8% for pure-M. pneumoniae pneumonia and 60.3% for pure-C. pneumoniae pneumonia, but only 9.0% for bacterial pneumonia, 12.1% for mixed-C. pneumoniae pneumonia and 16.6% for mixed-M. pneumoniae pneumonia. Overall, the sensitivity and specificity of the criteria in the JRS guidelines were 75.5% and 90.9%, respectively. Our results indicated that the differentiation of pneumonia in the JRS guidelines is useful for the diagnosis of M. pneumoniae pneumonia, but difficult to apply to the diagnosis of C. pneumoniae pneumonia.

PMID 15481271
日本呼吸器学会成人肺炎診療ガイドライン2024作成委員会:成人肺炎診療ガイドライン2024. 日本呼吸器学会. 2024; 28-33.
Gotoh K, Nishimura N, Ohshima Y, Arakawa Y, Hosono H, Yamamoto Y, Iwata Y, Nakane K, Funahashi K, Ozaki T.
Detection of Mycoplasma pneumoniae by loop-mediated isothermal amplification (LAMP) assay and serology in pediatric community-acquired pneumonia.
J Infect Chemother. 2012 Oct;18(5):662-7. doi: 10.1007/s10156-012-0388-5. Epub 2012 Feb 28.
Abstract/Text Rapid diagnosis of Mycoplasma pneumoniae pneumonia is required for treatment with effective antimicrobial agents without delay; however, this capacity has not yet been established in clinical practice. Recently, a novel nucleic acid amplification method termed loop-mediated isothermal amplification (LAMP) has been used to rapidly diagnose various infectious diseases. In this study, we prospectively evaluated the efficacy of the LAMP assay to rapidly diagnose M. pneumoniae pneumonia in clinical practice. Three hundred sixty-eight children (median age, 3.8 years; range, 0.1-14.3 years) admitted to our hospital between April 2009 and March 2010 for community-acquired pneumonia were enrolled in this study. We obtained throat swabs on admission to detect M. pneumoniae DNA and paired serum samples on admission and at discharge to assay M. pneumoniae antibody titers. M. pneumoniae pneumonia was diagnosed by either a positive LAMP assay or a fourfold or greater increase in antibody titer. Overall, 46 children (12.5% of the patients with pneumonia) were diagnosed with M. pneumoniae pneumonia; of these, 27 (58.7%) were aged less than 6 years. Of the aforementioned 46 children, 38 (82.6%) and 37 (80.4%) were identified by LAMP and serology, respectively. When the results of serology were taken as the standard, the sensitivity and specificity and positive and negative predictive values of the LAMP assay were 78.4%, 97.3%, 76.3%, and 97.6%, respectively. We concluded the LAMP assay may be useful for rapid diagnosis of M. pneumoniae pneumonia.

PMID 22370920
Alexander TS, Gray LD, Kraft JA, Leland DS, Nikaido MT, Willis DH.
Performance of Meridian ImmunoCard Mycoplasma test in a multicenter clinical trial.
J Clin Microbiol. 1996 May;34(5):1180-3. doi: 10.1128/jcm.34.5.1180-1183.1996.
Abstract/Text Serology is the principal laboratory method used to diagnose Mycoplasma pneumoniae infection. Meridian Diagnostics has developed the ImmunoCard Mycoplasma kit, a 10-min card-based enzyme-linked immunosorbent assay (ELISA) designed to detect immunoglobulin M (IgM) antibodies to M. pneumoniae. We compared the ImmunoCard with two M. pneumoniae IgM-specific assays (immunofluorescence assay [IFA] and ELISA) and a standard complement fixation (CF) procedure using 896 specimens submitted to clinical laboratories for M. pneumoniae serology. Equivocal results obtained by CF, IFA, or ELISA were resolved by testing with an additional method or by reviewing patient chart information. The ImmunoCard had sensitivities ranging from 74% compared with the ELISA to 96% compared with CF results with IFA. ImmunoCard specificities ranged from 85% compared with the IgM-specific ELISA to 98% compared with IgM-specific IFA results resolved with clinical chart review. We also compared the ImmunoCard results with consensus results of 694 specimens tested on at least two non-ImmunoCard methods because of the lack of a "gold standard" for M. pneumoniae serology. Overall, the ImmunoCard Mycoplasma IgM assay had 90% sensitivity, 93% specificity, and 92% agreement with the consensus results. The ImmunoCard is technically less complex and requires less equipment that the three other assays. Our results indicate that the ImmunoCard Mycoplasma IgM assay is a valid and simple procedure which can reduce technologist time (and, thus, labor cost) and turnaround time for laboratories analyzing small numbers of specimens (< 10 per batch) submitted for IgM anti-M. pneumoniae testing.

PMID 8727899
森島恒雄:小児の急性脳炎・脳症の現状. ウイルス. 2009;59(1):59-66.
Mulholland S, Gavranich JB, Gillies MB, Chang AB.
Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children.
Cochrane Database Syst Rev. 2012 Sep 12;(9):CD004875. doi: 10.1002/14651858.CD004875.pub4. Epub 2012 Sep 12.
Abstract/Text BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an important cause of community-acquired lower respiratory tract infection (LRTI) in children. Pulmonary manifestations are typically tracheobronchitis or pneumonia but M. pneumoniae is also implicated in wheezing episodes in both asthmatic and non-asthmatic individuals. Although antibiotics are used to treat LRTIs, a review of several major textbooks offers conflicting advice for using antibiotics in the management of M. pneumoniae LRTI in children.
OBJECTIVES: To determine whether antibiotics are effective in the treatment of childhood LRTI secondary to M. pneumoniae infections acquired in the community.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to February week 5, 2012) and EMBASE (1980 to March 2012).
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotics commonly used for treating M. pneumoniae (i.e. macrolide, tetracycline or quinolone classes) versus placebo, or antibiotics from any other class in the treatment of children under 18 years of age with community-acquired LRTI secondary to M. pneumoniae.
DATA COLLECTION AND ANALYSIS: The review authors independently selected trials for inclusion and assessed methodological quality. We extracted and analysed relevant data separately. We resolved disagreements by consensus.
MAIN RESULTS: A total of 1912 children were enrolled from seven studies. Data interpretation was limited by the inability to extract data that referred to children with M. pneumoniae. In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non-macrolide antibiotic. In one controlled study (of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both by polymerase chain reaction, and/or paired sera) 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month.
AUTHORS' CONCLUSIONS: There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events. There is still a need for high quality, double-blinded RCTs to assess the efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in children.

PMID 22972079
MUFSON MA, MANKO MA, KINGSTON JR, CHANOCK RM.
Eaton agent pneumonia-clinical features.
JAMA. 1961 Oct 28;178:369-74. doi: 10.1001/jama.1961.03040430005002.
Abstract/Text
PMID 14476984
Esposito S, Bosis S, Faelli N, Begliatti E, Droghetti R, Tremolati E, Porta A, Blasi F, Principi N.
Role of atypical bacteria and azithromycin therapy for children with recurrent respiratory tract infections.
Pediatr Infect Dis J. 2005 May;24(5):438-44. doi: 10.1097/01.inf.0000160949.99560.8d.
Abstract/Text BACKGROUND: The aim of this study of 352 patients, 1-14 years of age, with acute respiratory infections and a history of recurrent respiratory tract infections (RRTIs), and 208 healthy subjects was to evaluate whether Mycoplasma pneumoniae and Chlamydia pneumoniae played a role in causing acute respiratory episodes among children with RRTIs and whether specific antibiotic treatment for these bacteria could improve the acute episodes and reduce recurrences.
METHODS: The patients were blindly randomized to receive azithromycin (10 mg/kg/d for 3 days weekly, for 3 weeks) together with symptom-specific agents or symptom-specific agents alone. Acute M. pneumoniae and/or C. pneumoniae infection was diagnosed if the child had a significant antibody response in paired sera and/or if the DNA of the bacteria was detected in nasopharyngeal aspirates.
RESULTS: Atypical bacterial infections were identified for 190 patients (54.0%) and 8 healthy control subjects (3.8%; P < 0.0001). Short term (1-month) clinical success was significantly more frequent among the patients who had received azithromycin together with symptom-specific agents than among those who had received symptom-specific agents alone, but the difference was significant only for the group of patients with atypical bacteria. In contrast, long term (6-month) clinical success was significantly more frequent among the patients who had received azithromycin in addition to symptom-specific agents, regardless of whether they experienced infections with atypical bacteria or other pathogens, although positive outcomes were significantly more frequent among those with atypical bacteria.
CONCLUSIONS: Atypical bacteria seem to play a role among children with RRTIs, and prolonged azithromycin therapy can significantly improve the acute episodes and reduce the risk of recurrences.

PMID 15876944
McCracken GH Jr.
Current status of antibiotic treatment for Mycoplasma pneumoniae infections.
Pediatr Infect Dis. 1986 Jan-Feb;5(1):167-71. doi: 10.1097/00006454-198601000-00054.
Abstract/Text
PMID 3080736
Cherry JD, Welliver RC.
Mycoplasma pneumoniae infections of adults and children.
West J Med. 1976 Jul;125(1):47-55.
Abstract/Text Although the hallmark of Mycoplasma pneumoniae infection is pneumonia, the organism is also responsible for a protean array of other symptoms. With an increased awareness of the board clinical spectrum of M. pneumoniae disease and the ready availability of the cold agglutinin and M. pneumoniae complement-fixation tests, interested clinicians will note additional clinical-mycoplasmal associations in their patients.

PMID 782043
Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society.
Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
Clin Infect Dis. 2007 Mar 1;44 Suppl 2(Suppl 2):S27-72. doi: 10.1086/511159.
Abstract/Text
PMID 17278083
日本呼吸器学会成人肺炎診療ガイドライン2024作成委員会:成人肺炎診療ガイドライン2024. 日本呼吸器学会. 2024.
Shefet D, Robenshtok E, Paul M, Leibovici L.
Empirical atypical coverage for inpatients with community-acquired pneumonia: systematic review of randomized controlled trials.
Arch Intern Med. 2005 Sep 26;165(17):1992-2000. doi: 10.1001/archinte.165.17.1992.
Abstract/Text BACKGROUND: Current guidelines of empirical antibiotic treatment for inpatients with community-acquired pneumonia recommend antibiotics whose spectrum covers intracellular (atypical) pathogens. No sufficient evidence exists to support the necessity of such coverage, whereas limiting it may reduce toxic effects, resistance, and expense. Our goal was to assess the efficacy of empirical coverage of atypical pathogens in terms of mortality and clinical and bacteriological success.
METHODS: Systematic review and meta-analysis of randomized, controlled trials comparing treatment regimens with and without coverage of atypical pathogens. We searched MEDLINE, EMBASE, the Cochrane Library, and references. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using the fixed-effects model. The primary outcome assessed was all-cause mortality.
RESULTS: We included 24 trials encompassing 5015 patients. We found no studies of a drug without atypical coverage that compared it with the same drug supplemented with a drug with atypical coverage; nearly all compared a beta-lactam with a single quinolone or macrolide. There was no difference in mortality between the 2 arms (RR, 1.13 [95% CI, 0.82-1.54]). Regimens with coverage of atypical pathogens showed a trend toward clinical success and a significant advantage to bacteriological eradication. Both disappeared when evaluating methodologically high-quality studies alone. These regimens further showed a significant advantage in clinical success for Legionella pneumophila, whereas no advantage for pneumococcal pneumonia was seen. There was no difference between study arms in the frequency of total adverse events.
CONCLUSION: Empirical antibiotic coverage of atypical pathogens in hospitalized patients with community-acquired pneumonia showed no benefit of survival or clinical efficacy in this synthesis of randomized trials.

PMID 16186469
Mills GD, Oehley MR, Arrol B.
Effectiveness of beta lactam antibiotics compared with antibiotics active against atypical pathogens in non-severe community acquired pneumonia: meta-analysis.
BMJ. 2005 Feb 26;330(7489):456. doi: 10.1136/bmj.38334.591586.82. Epub 2005 Jan 31.
Abstract/Text OBJECTIVE: To systematically compare beta lactam antibiotics with antibiotics active against atypical pathogens in the management of community acquired pneumonia.
DATA SOURCES: Medline, Embase, Cochrane register of controlled trials, international conference proceedings, drug registration authorities, and pharmaceutical companies. Review methods Double blind randomised controlled monotherapy trials comparing beta lactam antibiotics with antibiotics active against atypical pathogens in adults with community acquired pneumonia. Primary outcome was failure to achieve clinical cure or improvement.
RESULTS: 18 trials totalling 6749 participants were identified, with most patients having mild to moderate community acquired pneumonia. The summary relative risk for treatment failure in all cause community acquired pneumonia showed no advantage of antibiotics active against atypical pathogens over beta lactam antibiotics (0.97, 95% confidence interval 0.87 to 1.07). Subgroup analysis was undertaken in those with a specific diagnosis involving atypical pathogens. We found a significantly lower failure rate in patients with Legionella species who were treated with antibiotics active against atypical pathogens (0.40, 0.19 to 0.85). Equivalence was seen for Mycoplasma pneumoniae (0.60, 0.31 to 1.17) and Chlamydia pneumoniae (2.32, 0.67 to 8.03).
CONCLUSIONS: Evidence is lacking that clinical outcomes are improved by using antibiotics active against atypical pathogens in all cause non-severe community acquired pneumonia. Although such antibiotics were superior in the management of patients later shown to have legionella related pneumonia, this pathogen was rarely responsible for pneumonia within the included trials. beta lactam agents should remain the antibiotics of initial choice in adults with non-severe community acquired pneumonia.

PMID 15684024
Tagliabue C, Techasaensiri C, Torres JP, Katz K, Meek C, Kannan TR, Coalson JJ, Esposito S, Principi N, Leff R, Baseman JB, Hardy RD.
Efficacy of increasing dosages of clarithromycin for treatment of experimental Mycoplasma pneumoniae pneumonia.
J Antimicrob Chemother. 2011 Oct;66(10):2323-9. doi: 10.1093/jac/dkr306. Epub 2011 Jul 25.
Abstract/Text OBJECTIVES: Mycoplasma pneumoniae respiratory infection is a common cause of acute respiratory infection in children and adults. We evaluated the efficacy of increasing dosages of clarithromycin for the optimized therapy of M. pneumoniae respiratory infection in a mouse model.
METHODS: BALB/c mice were intranasally inoculated once with M. pneumoniae or SP4 broth (control). Groups of mice were treated with increasing dosages of clarithromycin (10, 25 or 75 mg/kg/day) or placebo subcutaneously daily. Groups of mice were evaluated after 1, 2, 3, 6 and 12 days of therapy. Outcome variables included quantitative M. pneumoniae culture, histopathological score of the lungs, bronchoalveolar lavage (BAL) cytokine/chemokine/growth factor concentrations and plethysmography after aerosolized methacholine to assess airway hyperresponsiveness.
RESULTS: Elevated dosages of clarithromycin resulted in greater antimicrobial efficacy with significantly reduced M. pneumoniae quantitative cultures (P < 0.05), as well as greater improvement in markers of disease severity with significantly reduced lung histopathology scores, BAL cytokine concentrations and airway hyperresponsiveness (P < 0.05).
CONCLUSIONS: Escalated dosing of clarithromycin resulted in significantly greater therapeutic efficacy in the treatment of experimental M. pneumoniae respiratory infection.

PMID 21791441
Felmingham D.
Comparative antimicrobial susceptibility of respiratory tract pathogens.
Chemotherapy. 2004;50 Suppl 1:3-10. doi: 10.1159/000079816.
Abstract/Text Bacterial respiratory tract infections (RTIs), whether primary or subsequent to viral infection, are a frequent cause of morbidity and mortality worldwide. Treatment of these infections is most often empirical. Therefore, an antimicrobial's antibacterial spectrum must include the most likely pathogens: Streptococcus pneumoniae, the most frequent cause of community-acquired pneumonia (CAP), Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus, as well as atypicals such as Mycoplasma pneumoniae, Legionella pneumophila and Chlamydophila (Chlamydia) pneumoniae. In addition, knowledge of antimicrobial resistance among these key pathogens is imperative for physicians to choose the most appropriate therapeutic agent. The latest data from global surveillance studies indicates that high-level resistance to penicillin (MIC > or =2 mg/l) among isolates of S. pneumoniae varies widely by geographic location. Rates exceed 20% in the USA, Mexico, Japan, Saudi Arabia, Israel, Spain, France, Greece, Hungary, and the Slovak Republic. In South Africa, Hong Kong, Taiwan, and South Korea rates exceed 50%. Penicillin non-susceptibility--including isolates exhibiting high-level resistance and intermediate susceptibility (MIC 0.12-1 mg/l)--is frequently found in association with macrolide resistance, which is found at a prevalence of 70-80% in some Asian countries. Trimethoprim-sulfamethoxazole (TMP-SMX) and tetracycline resistance, either individually or combined with macrolide resistance as multiple resistance, is also associated with reduced susceptibility to penicillin. Another concern about antimicrobial resistance in respiratory tract pathogens is beta-lactamase production among isolates of H. influenzae and M. catarrhalis. However, respiratory fluoroquinolones, of which levofloxacin has been available for the longest time, currently remain active against the great majority of common bacterial respiratory pathogens, including atypicals.

PMID 15319548
Okazaki N, Narita M, Yamada S, Izumikawa K, Umetsu M, Kenri T, Sasaki Y, Arakawa Y, Sasaki T.
Characteristics of macrolide-resistant Mycoplasma pneumoniae strains isolated from patients and induced with erythromycin in vitro.
Microbiol Immunol. 2001;45(8):617-20. doi: 10.1111/j.1348-0421.2001.tb01293.x.
Abstract/Text Some patients with Mycoplasma pneumoniae infection are clinically resistant to antibiotics such as erythromycin, clarithromycin, or clindamycin. We isolated M. pneumoniae from such patients and found that one of three isolates showed a point mutation in the 23S rRNA gene. Furthermore, 141 EM-sensitive clinical isolates of M. pneumoniae were cultured in broth medium containing 100 microg/ml of erythromycin (EM). Among 11 EM-resistant strains that grew in the medium, point mutations in the 23S rRNA were found in 3 strains at A2063G, 5 strains at A2064G and 3 strains at A2064C. The relationship between the point mutation pattern of these EM-resistant strains and their resistance phenotypes to several macrolide antibiotics was investigated.

PMID 11592636
Isozumi R, Yoshimine H, Morozumi M, Ubukata K, Ariyoshi K.
Adult community-acquired pneumonia caused by macrolide resistant Mycoplasma pneumoniae.
Respirology. 2009 Nov;14(8):1206-8. doi: 10.1111/j.1440-1843.2009.01619.x. Epub 2009 Sep 1.
Abstract/Text A 28-year-old woman with community-acquired pneumonia was treated with sulbactam/ampicillin and clarithromycin, but failed to show any improvement after 4 days. The antibiotic regimen was changed to pazufloxacin and rapid clinical improvement was seen. Mycoplasma pneumoniae was identified as the causative agent, and adenine (A) to guanine (G) mutation at position 2063 in domain V of the 23S rRNA was noted in the isolate. The minimum inhibitory concentration of macrolide antibiotics, including clarithromycin, of this isolate was greatly elevated.

PMID 19732389
Girbert DN, Moellering RC Jr.,: Eliopoulos GM, et al. The Sanford Guide to Antimicrobial Therapy 2012 (42nd edition). Antimicrobial Therapy, Inc.
成田光生: 主として市中感染症で問題となる耐性菌・1 肺炎マイコプラズマ(臨床編). 臨床検査 2006;50:709-712.
Suzuki S, Yamazaki T, Narita M, Okazaki N, Suzuki I, Andoh T, Matsuoka M, Kenri T, Arakawa Y, Sasaki T.
Clinical evaluation of macrolide-resistant Mycoplasma pneumoniae.
Antimicrob Agents Chemother. 2006 Feb;50(2):709-12. doi: 10.1128/AAC.50.2.709-712.2006.
Abstract/Text Macrolide-resistant Mycoplasma pneumoniae (MR M. pneumoniae) has been isolated from clinical specimens in Japan since 2000. A comparative study was carried out to determine whether or not macrolides are effective in treating patients infected with MR M. pneumoniae. The clinical courses of 11 patients with MR M. pneumoniae infection (MR patients) treated with macrolides were compared with those of 26 patients with macrolide-susceptible M. pneumoniae infection (MS patients). The total febrile days and the number of febrile days during macrolide administration were longer in the MR patients than in the MS patients (median of 8 days versus median of 5 days [P = 0.019] and 3 days versus 1 day [P = 0.002], respectively). In addition, the MR patients were more likely than the MS patients to have had a change of the initially prescribed macrolide to another antimicrobial agent (63.6% versus 3.8%; odds ratio, 43.8; P < 0.001), which might reflect the pediatrician's judgment that the initially prescribed macrolide was not sufficiently effective in these patients. Despite the fact that the febrile period was prolonged in MR patients given macrolides, the fever resolved even when the initial prescription was not changed. These results show that macrolides are certainly less effective in MR patients.

PMID 16436730
Matsubara K, Morozumi M, Okada T, Matsushima T, Komiyama O, Shoji M, Ebihara T, Ubukata K, Sato Y, Akita H, Sunakawa K, Iwata S.
A comparative clinical study of macrolide-sensitive and macrolide-resistant Mycoplasma pneumoniae infections in pediatric patients.
J Infect Chemother. 2009 Dec;15(6):380-3. doi: 10.1007/s10156-009-0715-7.
Abstract/Text In recent years, the increased prevalence of macrolide-resistant Mycoplasma pneumoniae (MR-M. pneumoniae) has become a significant issue in Japan. We isolated 94 strains of M. pneumoniae, and determined the minimum inhibitory concentrations (MICs) of macrolides and other antimicrobial agents for these strains. We also performed a comparative clinical evaluation of macrolide efficacy for cases of MR-M. pneumoniae infections and cases of macrolide-sensitive Mycoplasma pneumoniae infections (MS-M. pneumoniae). Of the 94 isolates of M. pneumoniae, 64 (68.1%) were classified as MS-M. pneumoniae and 30 (31.9%) as MR-M. pneumoniae strains. The clinical study included an assessment of 47 pediatric cases of MS-M. pneumoniae and 22 pediatric cases of MR-M. pneumoniae. The patient demographics, such as sex, age, the period from the onset of the infection to the first examination, laboratory findings, diagnosis, and the severity of symptoms, showed no significant difference between the two study groups. However, the efficacy of macrolide treatment was 91.5% for MS-M. pneumoniae and 22.7% for MR-M. pneumoniae, a statistically significant difference (P < 0.01). Although M. pneumoniae infection is generally considered a treatable condition, the increasing prevalence of macrolide-resistant strains of M. pneumoniae has become a significant clinical issue in pediatric patients, and it is therefore necessary to give careful consideration to the appropriate antimicrobial therapy for MR-M. pneumoniae infection.

PMID 20012728
日本マイコプラズマ学会:肺炎マイコプラズマ肺炎に対する治療指針.2014.
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
櫻井隆之 : 特に申告事項無し[2025年]
監修:具芳明 : 研究費・助成金など(MSD(株),ビオメリュー・ジャパン(株))[2025年]

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