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Semin Respir Crit Care Med 2016; 37(06): 819-828
DOI: 10.1055/s-0036-1592121
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Role of Atypical Pathogens in the Etiology of Community-Acquired Pneumonia

Forest W. Arnold
1   Division of Infectious Diseases, School of Medicine, University of Louisville, Louisville, Kentucky
,
James T. Summersgill
1   Division of Infectious Diseases, School of Medicine, University of Louisville, Louisville, Kentucky
,
Julio A. Ramirez
1   Division of Infectious Diseases, School of Medicine, University of Louisville, Louisville, Kentucky
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
13. Dezember 2016 (online)

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Abstract

Atypical pneumonia has been described for over 100 years, but some of the pathogens attributed to it have been identified only in the past decades. The most common pathogens are Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila. The epidemiology and pathophysiology of these three pathogens have been studied since their discovery, and are reviewed herein to provide better insight when evaluating these patients, which hopefully translates into improved care. The incidence of atypical pathogens has been shown to be approximately 22% worldwide, but this probably varies with location. The history and physical exam of a patient with atypical pneumonia reveals how patients share many signs and symptoms with their counterpart patients who have typical pneumonias; therefore, the diagnosis primarily depends on laboratory identification, which is evolving and improving. What started out as simple, but difficult to yield cultures, has progressed to modern molecular-based testing assays. Treatment is missed if an empiric regimen includes only monotherapy with a β-lactam antimicrobial; so, many country guidelines, including the Infectious Diseases Society of America/American Thoracic Society guidelines for community-acquired pneumonia, recommend using a regimen containing either a macrolide or a fluorinated quinolone. Once an atypical pathogen has been identified, evidence trends toward favoring a quinolone, but more data are needed to confirm. The concept of using combination therapy in severe patients is also explored.

Keywords

atypical pneumonia - Mycoplasma pneumoniae - Chlamydia pneumoniae - Legionella pneumophila

Funding

None.


 

  • References

  • 1 Dingle JH. Primary atypical pneumonia. Am J Public Health Nations Health 1944; 34 (4) 347-357
    CrossrefPubMedGoogle Scholar
  • 2 Eaton MD, Meiklejohn G, van Herick W, Corey M. Studies on the etiology of primary atypical pneumonia: II. properties of the virus isolated and propagated in chick embryos. J Exp Med 1945; 82 (5) 317-328
    CrossrefPubMedGoogle Scholar
  • 3 Eaton MD, van Herick W, Meiklejohn G. Studies on the etiology of primary atypical pneumonia: III specific neutralization of the virus by human serum. J Exp Med 1945; 82 (5) 329-342
    CrossrefPubMedGoogle Scholar
  • 4 Chanock RM, Rifkind D, Kravetz HM, Kinght V, Johnson KM. Respiratory disease in volunteers infected with Eaton agent: a preliminary report. Proc Natl Acad Sci U S A 1961; 47: 887-890
    CrossrefPubMedGoogle Scholar
  • 5 Finland M, Peterson OL, Allen HE, Samper BA, Barnes MW, Stone MB. Cold agglutinins. I occurrence of cold isohemagglutinins in various conditions. J Clin Invest 1945; 24 (4) 451-457
    CrossrefPubMedGoogle Scholar
  • 6 Osterholm MT, Chin TD, Osborne DO , et al. A 1957 outbreak of Legionnaires' disease associated with a meat packing plant. Am J Epidemiol 1983; 117 (1) 60-67
    PubMedGoogle Scholar
  • 7 Stephens RS, Myers G, Eppinger M, Bavoil PM. Divergence without difference: phylogenetics and taxonomy of Chlamydia resolved. FEMS Immunol Med Microbiol 2009; 55 (2) 115-119
    CrossrefPubMedGoogle Scholar
  • 8 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 (4) 675-678
    CrossrefPubMedGoogle Scholar
  • 9 Wood PR, Hill VL, Burks ML , et al. Mycoplasma pneumoniae in children with acute and refractory asthma. Ann Allergy Asthma Immunol 2013; 110 (5) 328-334.e1
    CrossrefPubMedGoogle Scholar
  • 10 Spuesens EB, Fraaij PL, Visser EG , 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
    CrossrefPubMedGoogle Scholar
  • 11 Mogabgab WJ. Mycoplasma pneumoniae and adenovirus respiratory illnesses in military and university personnel, 1959-1966. Am Rev Respir Dis 1968; 97 (3) 345-358
    PubMedGoogle Scholar
  • 12 Centers for Disease Control and Prevention (CDC). Mycoplasma pneumoniae outbreak at a university - Georgia, 2012. MMWR Morb Mortal Wkly Rep 2013; 62 (30) 603-606
    PubMedGoogle Scholar
  • 13 Nozue T, Chikazawa H, Miyanishi S , et al. Legionella pneumonia associated with adult respiratory distress syndrome caused by Legionella pneumophila serogroup 3. Intern Med 2005; 44 (1) 73-78
    CrossrefPubMedGoogle Scholar
  • 14 Marston BJ, Plouffe JF, File Jr TM , et al; The Community-Based Pneumonia Incidence Study Group. Incidence of community-acquired pneumonia requiring hospitalization. Results of a population-based active surveillance Study in Ohio. Arch Intern Med 1997; 157 (15) 1709-1718
    CrossrefPubMedGoogle Scholar
  • 15 Viasus D, Di Yacovo S, Garcia-Vidal C , et al. Community-acquired Legionella pneumophila pneumonia: a single-center experience with 214 hospitalized sporadic cases over 15 years. Medicine (Baltimore) 2013; 92 (1) 51-60
    CrossrefPubMedGoogle Scholar
  • 16 Grayston JT. Infections caused by Chlamydia pneumoniae strain TWAR. Clin Infect Dis 1992; 15 (5) 757-761
    CrossrefPubMedGoogle Scholar
  • 17 Al-Aydie SN, Obeidat NM, Al-Younes HM. Role of Chlamydia pneumoniae in community-acquired pneumonia in hospitalized Jordanian adults. J Infect Dev Ctries 2016; 10 (3) 227-236
    CrossrefPubMedGoogle Scholar
  • 18 Cillóniz C, Ewig S, Polverino E , et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 2011; 66 (4) 340-346
    CrossrefPubMedGoogle Scholar
  • 19 Capelastegui A, España PP, Bilbao A , et al; Poblational Study of Pneumonia (PSoP) Group. Etiology of community-acquired pneumonia in a population-based study: link between etiology and patients characteristics, process-of-care, clinical evolution and outcomes. BMC Infect Dis 2012; 12: 134
    CrossrefPubMedGoogle Scholar
  • 20 Shibli F, Chazan B, Nitzan O , et al. Etiology of community-acquired pneumonia in hospitalized patients in northern Israel. Isr Med Assoc J 2010; 12 (8) 477-482
    PubMedGoogle Scholar
  • 21 Tao LL, Hu BJ, He LX , et al. Etiology and antimicrobial resistance of community-acquired pneumonia in adult patients in China. Chin Med J (Engl) 2012; 125 (17) 2967-2972
    PubMedGoogle Scholar
  • 22 Chen K, Jia R, Li L, Yang C, Shi Y. The aetiology of community associated pneumonia in children in Nanjing, China and aetiological patterns associated with age and season. BMC Public Health 2015; 15: 113
    CrossrefPubMedGoogle Scholar
  • 23 Liu Y, Chen M, Zhao T , et al. Causative agent distribution and antibiotic therapy assessment among adult patients with community acquired pneumonia in Chinese urban population. BMC Infect Dis 2009; 9: 31
    CrossrefPubMedGoogle Scholar
  • 24 Luchsinger V, Ruiz M, Zunino E , et al. Community-acquired pneumonia in Chile: the clinical relevance in the detection of viruses and atypical bacteria. Thorax 2013; 68 (11) 1000-1006
    CrossrefPubMedGoogle Scholar
  • 25 Arnold FW, Summersgill JT, Lajoie AS , et al; Community-Acquired Pneumonia Organization (CAPO) Investigators. A worldwide perspective of atypical pathogens in community-acquired pneumonia. Am J Respir Crit Care Med 2007; 175 (10) 1086-1093
    CrossrefPubMedGoogle Scholar
  • 26 Zhou Y, Zhang Y, Sheng Y, Zhang L, Shen Z, Chen Z. More complications occur in macrolide-resistant than in macrolide-sensitive Mycoplasma pneumoniae pneumonia. Antimicrob Agents Chemother 2014; 58 (2) 1034-1038
    CrossrefPubMedGoogle Scholar
  • 27 Averbuch D, Hidalgo-Grass C, Moses AE, Engelhard D, Nir-Paz R. Macrolide resistance in Mycoplasma pneumoniae, Israel, 2010. Emerg Infect Dis 2011; 17 (6) 1079-1082
    CrossrefPubMedGoogle Scholar
  • 28 Peuchant O, Ménard A, Renaudin H , et al. Increased macrolide resistance of Mycoplasma pneumoniae in France directly detected in clinical specimens by real-time PCR and melting curve analysis. J Antimicrob Chemother 2009; 64 (1) 52-58
    CrossrefPubMedGoogle Scholar
  • 29 Zheng X, Lee S, Selvarangan R , et al. Macrolide-resistant Mycoplasma pneumoniae, United States. Emerg Infect Dis 2015; 21 (8) 1470-1472
    CrossrefPubMedGoogle Scholar
  • 30 Jain S, Self WH, Wunderink RG , et al; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med 2015; 373 (5) 415-427
    CrossrefPubMedGoogle Scholar
  • 31 Masiá M, Gutiérrez F, Padilla S , et al. Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors. Clin Microbiol Infect 2007; 13 (2) 153-161
    CrossrefPubMedGoogle Scholar
  • 32 Korppi M, Don M, Valent F, Canciani M. The value of clinical features in differentiating between viral, pneumococcal and atypical bacterial pneumonia in children. Acta Paediatr 2008; 97 (7) 943-947
    CrossrefPubMedGoogle Scholar
  • 33 Fernández JA, López P, Orozco D, Merino J. Clinical study of an outbreak of Legionnaire's disease in Alcoy, Southeastern Spain. Eur J Clin Microbiol Infect Dis 2002; 21 (10) 729-735
    CrossrefPubMedGoogle Scholar
  • 34 Watts JC, Hicklin MD, Thomason BM, Callaway CS, Levine AJ. Fatal pneumonia caused by Legionella pneumophila, serogroup 3: demonstration of the bacilli in extrathoracic organs. Ann Intern Med 1980; 92 (2 Pt 1): 186-188
    CrossrefPubMedGoogle Scholar
  • 35 Evans CP, Winn Jr WC. Extrathoracic localization of Legionella pneumophila in Legionnaires' pneumonia. Am J Clin Pathol 1981; 76 (6) 813-815
    CrossrefPubMedGoogle Scholar
  • 36 Edelstein PH, Roy CR. Legionnaires' disease. In: Bennett JE, Dolin R, Blaser MJ, , eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. Philadelphia, PA: WB Saunders; 2015: 2633-2644
    Google Scholar
  • 37 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) 185-189
    CrossrefPubMedGoogle Scholar
  • 38 Borel N, Summersgill JT, Mukhopadhyay S, Miller RD, Ramirez JA, Pospischil A. Evidence for persistent Chlamydia pneumoniae infection of human coronary atheromas. Atherosclerosis 2008; 199 (1) 154-161
    CrossrefPubMedGoogle Scholar
  • 39 Waites KB, Talkington DF. Mycoplasma pneumoniae and its role as a human pathogen. Clin Microbiol Rev 2004; 17 (4) 697-728
    CrossrefPubMedGoogle Scholar
  • 40 Feeley JC, Gorman GW, Weaver RE, Mackel DC, Smith HW. Primary isolation media for Legionnaires disease bacterium. J Clin Microbiol 1978; 8 (3) 320-325
    PubMedGoogle Scholar
  • 41 Phillips E, Nash P. Culture media. In: Lennette EH, Balows A, Hausler WJ, Shadomy HJ, , eds. Manual of Clinical Microbiology. Washington, DC: American Society for Microbiology; 1985: 1051-1092
    Google Scholar
  • 42 Buesching WJ, Brust RA, Ayers LW. Enhanced primary isolation of Legionella pneumophila from clinical specimens by low-pH treatment. J Clin Microbiol 1983; 17 (6) 1153-1155
    PubMedGoogle Scholar
  • 43 Dajani AS, Clyde Jr WA, Denny FW. Experimental infection with Mycoplasma pneumonia (Eaton's Agent). J Exp Med 1965; 121 (6) 1071-1086
    CrossrefPubMedGoogle Scholar
  • 44 Roblin PM, Dumornay W, Hammerschlag MR. Use of HEp-2 cells for improved isolation and passage of Chlamydia pneumoniae . J Clin Microbiol 1992; 30 (8) 1968-1971
    PubMedGoogle Scholar
  • 45 Ieven M, Ursi D, Van Bever H, Quint W, Niesters HG, Goossens H. Detection of Mycoplasma pneumoniae by two polymerase chain reactions and role of M. pneumoniae in acute respiratory tract infections in pediatric patients. J Infect Dis 1996; 173 (6) 1445-1452
    CrossrefPubMedGoogle Scholar
  • 46 Cherry WB, Pittman B, Harris PP , et al. Detection of Legionnaires disease bacteria by direct immunofluorescent staining. J Clin Microbiol 1978; 8 (3) 329-338
    PubMedGoogle Scholar
  • 47 Edelstein PH, Beer KB, Sturge JC, Watson AJ, Goldstein LC. Clinical utility of a monoclonal direct fluorescent reagent specific for Legionella pneumophila: comparative study with other reagents. J Clin Microbiol 1985; 22 (3) 419-421
    PubMedGoogle Scholar
  • 48 Nagington J, Wreghitt TG, Tobin JO, Macrae AD. The antibody response in Legionnaires' disease. J Hyg (Lond) 1979; 83 (2) 377-381
    CrossrefPubMedGoogle Scholar
  • 49 Wang SP, Grayston JT, Alexander ER, Holmes KK. Simplified microimmunofluorescence test with trachoma-lymphogranuloma venereum (Chlamydia trachomatis) antigens for use as a screening test for antibody. J Clin Microbiol 1975; 1 (3) 250-255
    PubMedGoogle Scholar
  • 50 Ferriman D. Cold agglutinins in atypical pneumonia. Lancet 1947; 2 (6462) 34
    PubMedGoogle Scholar
  • 51 Taylor-Robinson D, Somerson NL, Turner HC, Chanock RM. Serological relationships among human mycoplasmas as shown by complement-fixation and gel diffusion. J Bacteriol 1963; 85: 1261-1273
    PubMedGoogle Scholar
  • 52 Hindiyeh M, Carroll KC. Laboratory diagnosis of atypical pneumonia. Semin Respir Infect 2000; 15 (2) 101-113
    CrossrefPubMedGoogle Scholar
  • 53 Sathapatayavongs B, Kohler RB, Wheat LJ, White A, Winn Jr WC. Rapid diagnosis of Legionnaires' disease by latex agglutination. Am Rev Respir Dis 1983; 127 (5) 559-562
    CrossrefPubMedGoogle Scholar
  • 54 Berdal BP, Farshy CE, Feeley JC. Detection of Legionella pneumonophila antigen in urine by enzyme-linked immunospecific assay. J Clin Microbiol 1979; 9 (5) 575-578
    PubMedGoogle Scholar
  • 55 Kohler RB, Zimmerman SE, Wilson E , et al. Rapid radioimmunoassay diagnosis of Legionnaires' disease: detection and partial characterization of urinary antigen. Ann Intern Med 1981; 94 (5) 601-605
    CrossrefPubMedGoogle Scholar
  • 56 Diaz MH, Winchell JM. The evolution of advanced molecular diagnostics for the detection and characterization of Mycoplasma pneumoniae . Front Microbiol 2016; 7: 232
    PubMedGoogle Scholar
  • 57 Edelstein PH. Evaluation of the Gen-Probe DNA probe for the detection of legionellae in culture. J Clin Microbiol 1986; 23 (3) 481-484
    PubMedGoogle Scholar
  • 58 Mahbubani MH, Bej AK, Miller R, Haff L, DiCesare J, Atlas RM. Detection of Legionella with polymerase chain reaction and gene probe methods. Mol Cell Probes 1990; 4 (3) 175-187
    CrossrefPubMedGoogle Scholar
  • 59 Ramirez JA, Ahkee S, Tolentino A, Miller RD, Summersgill JT. Diagnosis of Legionella pneumophila, Mycoplasma pneumoniae, or Chlamydia pneumoniae lower respiratory infection using the polymerase chain reaction on a single throat swab specimen. Diagn Microbiol Infect Dis 1996; 24 (1) 7-14
    CrossrefPubMedGoogle Scholar
  • 60 Jaulhac B, Nowicki M, Bornstein N , et al. Detection of Legionella spp. in bronchoalveolar lavage fluids by DNA amplification. J Clin Microbiol 1992; 30 (4) 920-924
    PubMedGoogle Scholar
  • 61 Jonas D, Rosenbaum A, Weyrich S, Bhakdi S. Enzyme-linked immunoassay for detection of PCR-amplified DNA of legionellae in bronchoalveolar fluid. J Clin Microbiol 1995; 33 (5) 1247-1252
    PubMedGoogle Scholar
  • 62 Koide M, Saito A. Diagnosis of Legionella pneumophila infection by polymerase chain reaction. Clin Infect Dis 1995; 21 (1) 199-201
    CrossrefPubMedGoogle Scholar
  • 63 Lindsay DS, Abraham WH, Fallon RJ. Detection of mip gene by PCR for diagnosis of Legionnaires' disease. J Clin Microbiol 1994; 32 (12) 3068-3069
    PubMedGoogle Scholar
  • 64 Bernet C, Garret M, de Barbeyrac B, Bebear C, Bonnet J. Detection of Mycoplasma pneumoniae by using the polymerase chain reaction. J Clin Microbiol 1989; 27 (11) 2492-2496
    PubMedGoogle Scholar
  • 65 Jensen JS, Søndergård-Andersen J, Uldum SA, Lind K. Detection of Mycoplasma pneumoniae in simulated clinical samples by polymerase chain reaction. Brief report. APMIS 1989; 97 (11) 1046-1048
    CrossrefPubMedGoogle Scholar
  • 66 Loens K, Ieven M, Ursi D , et al. Detection of Mycoplasma pneumoniae by real-time nucleic acid sequence-based amplification. J Clin Microbiol 2003; 41 (9) 4448-4450
    CrossrefPubMedGoogle Scholar
  • 67 Saito R, Misawa Y, Moriya K, Koike K, Ubukata K, Okamura N. Development and evaluation of a loop-mediated isothermal amplification assay for rapid detection of Mycoplasma pneumoniae . J Med Microbiol 2005; 54 (Pt 11): 1037-1041
    CrossrefPubMedGoogle Scholar
  • 68 Holland SM, Gaydos CA, Quinn TC. Detection and differentiation of Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae by DNA amplification. J Infect Dis 1990; 162 (4) 984-987
    CrossrefPubMedGoogle Scholar
  • 69 Campbell LA, Perez Melgosa M, Hamilton DJ, Kuo CC, Grayston JT. Detection of Chlamydia pneumoniae by polymerase chain reaction. J Clin Microbiol 1992; 30 (2) 434-439
    PubMedGoogle Scholar
  • 70 Gaydos CA, Quinn TC, Eiden JJ. Identification of Chlamydia pneumoniae by DNA amplification of the 16S rRNA gene. J Clin Microbiol 1992; 30 (4) 796-800
    PubMedGoogle Scholar
  • 71 Gaydos CA, Eiden JJ, Oldach D , et al. Diagnosis of Chlamydia pneumoniae infection in patients with community-acquired pneumonia by polymerase chain reaction enzyme immunoassay. Clin Infect Dis 1994; 19 (1) 157-160
    CrossrefPubMedGoogle Scholar
  • 72 Dowell SF, Peeling RW, Boman J , et al; C. pneumoniae Workshop Participants. Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada). Clin Infect Dis 2001; 33 (4) 492-503
    CrossrefPubMedGoogle Scholar
  • 73 Chernesky M, Smieja M, Schachter J , et al. Comparison of an industry-derived LCx Chlamydia pneumoniae PCR research kit to in-house assays performed in five laboratories. J Clin Microbiol 2002; 40 (7) 2357-2362
    CrossrefPubMedGoogle Scholar
  • 74 Critchley IA, Jones ME, Heinze PD , et al. In vitro activity of levofloxacin against contemporary clinical isolates of Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae from North America and Europe. Clin Microbiol Infect 2002; 8 (4) 214-221
    CrossrefPubMedGoogle Scholar
  • 75 Van Bambeke F, Tulkens PM. The role of solithromycin in the management of bacterial community-acquired pneumonia. Expert Rev Anti Infect Ther 2016; 14 (3) 311-324
    CrossrefPubMedGoogle Scholar
  • 76 Blázquez Garrido RM, Espinosa Parra FJ, Alemany Francés L , et al. Antimicrobial chemotherapy for Legionnaires disease: levofloxacin versus macrolides. Clin Infect Dis 2005; 40 (6) 800-806
    CrossrefPubMedGoogle Scholar
  • 77 Mykietiuk A, Carratalà J, Fernández-Sabé N , et al. Clinical outcomes for hospitalized patients with Legionella pneumonia in the antigenuria era: the influence of levofloxacin therapy. Clin Infect Dis 2005; 40 (6) 794-799
    CrossrefPubMedGoogle Scholar
  • 78 Sabrià M, Pedro-Botet ML, Gómez J , et al; Legionnaires Disease Therapy Group. Fluoroquinolones vs macrolides in the treatment of Legionnaires disease. Chest 2005; 128 (3) 1401-1405
    CrossrefPubMedGoogle Scholar
  • 79 Falcó V, Molina I, Juste C , et al. [Treatment for Legionnaires' disease. Macrolides or quinolones?]. Enferm Infecc Microbiol Clin 2006; 24 (6) 360-364
    CrossrefPubMedGoogle Scholar
  • 80 Haranaga S, Tateyama M, Higa F , et al. Intravenous ciprofloxacin versus erythromycin in the treatment of Legionella pneumonia. Intern Med 2007; 46 (7) 353-357
    CrossrefPubMedGoogle Scholar
  • 81 Griffin AT, Peyrani P, Wiemken T, Arnold F. Macrolides versus quinolones in Legionella pneumonia: results from the Community-Acquired Pneumonia Organization international study. Int J Tuberc Lung Dis 2010; 14 (4) 495-499
    PubMedGoogle Scholar
  • 82 Nakamura S, Yanagihara K, Izumikawa K , et al. The clinical efficacy of fluoroquinolone and macrolide combination therapy compared with single-agent therapy against community-acquired pneumonia caused by Legionella pneumophila . J Infect 2009; 59 (3) 222-224
    CrossrefPubMedGoogle Scholar
  • 83 Mandell LA, Wunderink RG, Anzueto A , et al; 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; 44 (Suppl. 02) S27-S72
    CrossrefPubMedGoogle Scholar
  • 84 Cavalié P. Evolution of antibiotic consumption from 2000–2010 in France. Bull Epidemiol Hebd [serial online] 2012; 13: 480-484 . Available at: http://www.invs.sante.fr/Publications-et-outils/BEH-Bulletin-epidemiologique-hebdomadaire/Archives/2012/BEH-n-42-43-2012 . Accessed May 10, 2016
    PubMedGoogle Scholar
  • 85 Nie W, Li B, Xiu Q. β-Lactam/macrolide dual therapy versus β-lactam monotherapy for the treatment of community-acquired pneumonia in adults: a systematic review and meta-analysis. J Antimicrob Chemother 2014; 69 (6) 1441-1446
    CrossrefPubMedGoogle Scholar
  • 86 Garin N, Genné D, Carballo S , et al. β-Lactam monotherapy vs β-lactam-macrolide combination treatment in moderately severe community-acquired pneumonia: a randomized noninferiority trial. JAMA Intern Med 2014; 174 (12) 1894-1901
    CrossrefPubMedGoogle Scholar