Semin Respir Crit Care Med 2016; 37(06): 829-838
DOI: 10.1055/s-0036-1593753
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Antibiotic Resistance in Community-Acquired Pneumonia Pathogens

Richard G. Wunderink
1   Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
,
Yudong Yin
2   Department of Infectious Disease and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
13. Dezember 2016 (online)

Abstract

The overwhelming majority of cases of community-acquired pneumonia (CAP) can be treated with the standard antibiotic regimens of a macrolide and cephalosporin or a fluoroquinolone. Despite high rates, current levels of β-lactam resistance generally do not result in treatment failure for patients with CAP when appropriate agents and doses are used. Following the introduction of the pneumococcal conjugate vaccines, the incidence of invasive pneumococcal disease declined drastically, coinciding with a decrease in penicillin resistance. Risk factors for methicillin-resistant S. aureus follow two patterns: (1) healthcare-associated risk factors and (2) pneumonia from exotoxin-producing community-acquired strains. The latter is associated with need for antibiotics which inhibit protein synthesis for optimal management. Since 2000, macrolide-resistance in M. pneumoniae has rapidly emerged worldwide, especially in Asian countries. The inability to routinely culture H. influenzae suggests that macrolide and β-lactam resistance, while present, is not a big issue. Unless risk factors for a hospital-associated strain are present, the most common Enterobacteriaceae to cause CAP, including Escherichia coli and Klebsiella, are generally susceptible to usual CAP antibiotics. Given the limited role of antibiotic resistance in CAP, a strong rationale is needed for use of antibiotics other than the standard β-lactam/macrolide or fluoroquinolone regimens.

 
  • References

  • 1 Shindo Y, Ito R, Kobayashi D , et al. Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia. Am J Respir Crit Care Med 2013; 188 (8) 985-995
  • 2 Attridge RT, Frei CR, Restrepo MI , et al. Guideline-concordant therapy and outcomes in healthcare-associated pneumonia. Eur Respir J 2011; 38 (4) 878-887
  • 3 American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171 (4) 388-416
  • 4 Griffin MR, Zhu Y, Moore MR, Whitney CG, Grijalva CG. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med 2013; 369 (2) 155-163
  • 5 Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax 2012; 67 (1) 71-79
  • 6 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
  • 7 Charles PG, Whitby M, Fuller AJ , et al; Australian CAP Study Collaboration. The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy. Clin Infect Dis 2008; 46 (10) 1513-1521
  • 8 Rice LB. Mechanisms of resistance and clinical relevance of resistance to β-lactams, glycopeptides, and fluoroquinolones. Mayo Clin Proc 2012; 87 (2) 198-208
  • 9 Jacobs MR, Koornhof HJ, Robins-Browne RM , et al. Emergence of multiply resistant pneumococci. N Engl J Med 1978; 299 (14) 735-740
  • 10 Flamm RK, Sader HS, Farrell DJ, Jones RN. Antimicrobial activity of ceftaroline tested against drug-resistant subsets of Streptococcus pneumoniae from U.S. medical centers. Antimicrob Agents Chemother 2014; 58 (4) 2468-2471
  • 11 Jones RN, Sader HS, Mendes RE, Flamm RK. Update on antimicrobial susceptibility trends among Streptococcus pneumoniae in the United States: report of ceftaroline activity from the SENTRY Antimicrobial Surveillance Program (1998-2011). Diagn Microbiol Infect Dis 2013; 75 (1) 107-109
  • 12 Wang H, Chen M, Xu Y , et al. Antimicrobial susceptibility of bacterial pathogens associated with community-acquired respiratory tract infections in Asia: report from the Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS) study, 2009-2010. Int J Antimicrob Agents 2011; 38 (5) 376-383
  • 13 Ohno A, Ishii Y, Kobayashi I, Yamaguchi K. Antibacterial activity and PK/PD of ceftriaxone against penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative ampicillin-resistant Haemophilus influenzae isolates from patients with community-acquired pneumonia. J Infect Chemother 2007; 13 (5) 296-301
  • 14 Garcia-Vidal C, Ardanuy C, Tubau F , et al. Pneumococcal pneumonia presenting with septic shock: host- and pathogen-related factors and outcomes. Thorax 2010; 65 (1) 77-81
  • 15 Moroney JF, Fiore AE, Harrison LH , et al. Clinical outcomes of bacteremic pneumococcal pneumonia in the era of antibiotic resistance. Clin Infect Dis 2001; 33 (6) 797-805
  • 16 Cillóniz C, Ewig S, Polverino E , et al. Pulmonary complications of pneumococcal community-acquired pneumonia: incidence, predictors, and outcomes. Clin Microbiol Infect 2012; 18 (11) 1134-1142
  • 17 CLSI. 2008. Performance Standards for Antimicrobial Susceptibility Testing. CLSI Document M100–S18. Clinical and Laboratory Standards Institute, Wayne, PA
  • 18 Gillespie SH. Antibiotic resistance in the absence of selective pressure. Int J Antimicrob Agents 2001; 17 (3) 171-176
  • 19 Andersson DI. The biological cost of mutational antibiotic resistance: any practical conclusions?. Curr Opin Microbiol 2006; 9 (5) 461-465
  • 20 Ríos Dueñas E, Rodríguez-Avial I, Picazo JJ. In vitro activity of ceftobiprole and seven other antimicrobial agents against invasive Streptococcus pneumoniae isolates in Spain. Eur J Clin Microbiol Infect Dis 2011; 30 (12) 1621-1625
  • 21 Isozumi R, Ito Y, Ishida T , et al; Kansai Community Acquired Pneumococcal Pneumonia Study Groupe. Genotypes and related factors reflecting macrolide resistance in pneumococcal pneumonia infections in Japan. J Clin Microbiol 2007; 45 (5) 1440-1446
  • 22 Waterer GW, Wunderink RG, Jones CB. Fatal pneumococcal pneumonia attributed to macrolide resistance and azithromycin monotherapy. Chest 2000; 118 (6) 1839-1840
  • 23 Lonks JR, Garau J, Gomez L , et al. Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae . Clin Infect Dis 2002; 35 (5) 556-564
  • 24 Yanagihara K, Izumikawa K, Higa F , et al. Efficacy of azithromycin in the treatment of community-acquired pneumonia, including patients with macrolide-resistant Streptococcus pneumoniae infection. Intern Med 2009; 48 (7) 527-535
  • 25 Kohno S, Tateda K, Kadota J , et al. Contradiction between in vitro and clinical outcome: intravenous followed by oral azithromycin therapy demonstrated clinical efficacy in macrolide-resistant pneumococcal pneumonia. J Infect Chemother 2014; 20 (3) 199-207
  • 26 Cilloniz C, Albert RK, Liapikou A , et al. The effect of macrolide resistance on the presentation and outcome of patients hospitalized for Streptococcus pneumoniae pneumonia. Am J Respir Crit Care Med 2015; 191 (11) 1265-1272
  • 27 Zarogoulidis P, Papanas N, Kioumis I, Chatzaki E, Maltezos E, Zarogoulidis K. Macrolides: from in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases. Eur J Clin Pharmacol 2012; 68 (5) 479-503
  • 28 Olsen KM, San Pedro G, Gann LP, Gubbins PO, Halinski DM, Campbell Jr GD. Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses. Antimicrob Agents Chemother 1996; 40 (11) 2582-2585
  • 29 Fuller JD, Low DE. A review of Streptococcus pneumoniae infection treatment failures associated with fluoroquinolone resistance. Clin Infect Dis 2005; 41 (1) 118-121
  • 30 Tomczyk S, Lynfield R, Schaffner W , et al. Prevention of antibiotic-nonsusceptible invasive pneumococcal disease with the 13-Valent pneumococcal conjugate vaccine. Clin Infect Dis 2016; 62 (9) 1119-1125
  • 31 Hampton LM, Farley MM, Schaffner W , et al. Prevention of antibiotic-nonsusceptible Streptococcus pneumoniae with conjugate vaccines. J Infect Dis 2012; 205 (3) 401-411
  • 32 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
  • 33 Morozumi M, Hasegawa K, Kobayashi R , et al. Emergence of macrolide-resistant Mycoplasma pneumoniae with a 23S rRNA gene mutation. Antimicrob Agents Chemother 2005; 49 (6) 2302-2306
  • 34 Cao B, Zhao CJ, Yin YD , et al. High prevalence of macrolide resistance in Mycoplasma pneumoniae isolates from adult and adolescent patients with respiratory tract infection in China. Clin Infect Dis 2010; 51 (2) 189-194
  • 35 Zheng X, Lee S, Selvarangan R , et al. Macrolide-resistant Mycoplasma pneumoniae, United States. Emerg Infect Dis 2015; 21 (8) 1470-1472
  • 36 Zhou Z, Li X, Chen X , et al. Macrolide-resistant Mycoplasma pneumoniae in adults in Zhejiang, China. Antimicrob Agents Chemother 2015; 59 (2) 1048-1051
  • 37 Yin YD, Cao B, Wang H , et al. [Survey of macrolide resistance in Mycoplasma pneumoniae in adult patients with community-acquired pneumonia in Beijing, China] [in Chinese]. Zhonghua Jie He He Hu Xi Za Zhi 2013; 36 (12) 954-958
  • 38 Miyashita N, Akaike H, Teranishi H, Ouchi K, Okimoto N. Macrolide-resistant Mycoplasma pneumoniae pneumonia in adolescents and adults: clinical findings, drug susceptibility, and therapeutic efficacy. Antimicrob Agents Chemother 2013; 57 (10) 5181-5185
  • 39 Kurata S, Taguchi H, Sasaki T, Fujioka Y, Kamiya S. Antimicrobial and immunomodulatory effect of clarithromycin on macrolide-resistant Mycoplasma pneumoniae . J Med Microbiol 2010; 59 (Pt 6): 693-701
  • 40 Burdet C, Lepeule R, Duval X , et al. Quinolones versus macrolides in the treatment of legionellosis: a systematic review and meta-analysis. J Antimicrob Chemother 2014; 69 (9) 2354-2360
  • 41 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
  • 42 Edelstein PH, Edelstein MA, Lehr KH, Ren J. In-vitro activity of levofloxacin against clinical isolates of Legionella spp, its pharmacokinetics in guinea pigs, and use in experimental Legionella pneumophila pneumonia. J Antimicrob Chemother 1996; 37 (1) 117-126
  • 43 Almahmoud I, Kay E, Schneider D, Maurin M. Mutational paths towards increased fluoroquinolone resistance in Legionella pneumophila. J Antimicrob Chemother 2009; 64 (2) 284-293
  • 44 Bruin JP, Koshkolda T, IJzerman EP , et al. Isolation of ciprofloxacin-resistant Legionella pneumophila in a patient with severe pneumonia. J Antimicrob Chemother 2014; 69 (10) 2869-2871
  • 45 Shadoud L, Almahmoud I, Jarraud S , et al. Hidden selection of bacterial resistance to fluoroquinolones in vivo: the case of Legionella pneumophila and humans. EBioMedicine 2015; 2 (9) 1179-1185
  • 46 Kutlin A, Kohlhoff S, Roblin P, Hammerschlag MR, Riska P. Emergence of resistance to rifampin and rifalazil in Chlamydophila pneumoniae and Chlamydia trachomatis . Antimicrob Agents Chemother 2005; 49 (3) 903-907
  • 47 Riska PF, Kutlin A, Ajiboye P, Cua A, Roblin PM, Hammerschlag MR. Genetic and culture-based approaches for detecting macrolide resistance in Chlamydia pneumoniae. Antimicrob Agents Chemother 2004; 48 (9) 3586-3590
  • 48 Chambers HF, Deleo FR. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 2009; 7 (9) 629-641
  • 49 Chambers HF. The changing epidemiology of Staphylococcus aureus?. Emerg Infect Dis 2001; 7 (2) 178-182
  • 50 Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005; 128 (6) 3854-3862
  • 51 Smith SB, Ruhnke GW, Weiss CH, Waterer GW, Wunderink RG. Trends in pathogens among patients hospitalized for pneumonia from 1993 to 2011. JAMA Intern Med 2014; 174 (11) 1837-1839
  • 52 Labelle AJ, Arnold H, Reichley RM, Micek ST, Kollef MH. A comparison of culture-positive and culture-negative health-care-associated pneumonia. Chest 2010; 137 (5) 1130-1137
  • 53 Self WH, Wunderink RG, Williams DJ , et al. Staphylococcus aureus community-acquired pneumonia: prevalence, clinical characteristics, and outcomes. Clin Infect Dis 2016; 63 (3) 300-309
  • 54 Mendes RE, Sader HS, Deshpande LM, Diep BA, Chambers HF, Jones RN. Characterization of baseline methicillin-resistant Staphylococcus aureus isolates recovered from phase IV clinical trial for linezolid. J Clin Microbiol 2010; 48 (2) 568-574
  • 55 Gillet Y, Issartel B, Vanhems P , et al. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 2002; 359 (9308) 753-759
  • 56 Gillet Y, Vanhems P, Lina G , et al. Factors predicting mortality in necrotizing community-acquired pneumonia caused by Staphylococcus aureus containing Panton-Valentine leukocidin. Clin Infect Dis 2007; 45 (3) 315-321
  • 57 Wunderink RG, Niederman MS, Kollef MH , et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis 2012; 54 (5) 621-629
  • 58 Sicot N, Khanafer N, Meyssonnier V , et al. Methicillin resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia--results of a prospective observational study. Clin Microbiol Infect 2013; 19 (3) E142-E148
  • 59 File Jr TM, Low DE, Eckburg PB , et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin Infect Dis 2010; 51 (12) 1395-1405
  • 60 Gadsby NJ, Russell CD, McHugh MP , et al. Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia. Clin Infect Dis 2016; 62 (7) 817-823
  • 61 Desai S, Jamieson FB, Patel SN , et al. The epidemiology of invasive Haemophilus influenzae non-serotype B disease in Ontario, Canada from 2004 to 2013. PLoS One 2015; 10 (11) e0142179
  • 62 Puig C, Calatayud L, Martí S , et al. Molecular epidemiology of nontypeable Haemophilus influenzae causing community-acquired pneumonia in adults. PLoS One 2013; 8 (12) e82515
  • 63 Resman F, Ristovski M, Forsgren A , et al. Increase of β-lactam-resistant invasive Haemophilus influenzae in Sweden, 1997 to 2010. Antimicrob Agents Chemother 2012; 56 (8) 4408-4415
  • 64 File Jr TM, Rewerska B, Vucinić-Mihailović V , et al; SOLITAIRE-IV Pneumonia Team. SOLITAIRE-IV: A randomized, double-blind, multicenter study comparing the efficacy and safety of intravenous-to-oral solithromycin to intravenous-to-oral moxifloxacin for treatment of community-acquired bacterial pneumonia. Clin Infect Dis 2016; ciw490
  • 65 Torres A, Blasi F, Peetermans WE, Viegi G, Welte T. The aetiology and antibiotic management of community-acquired pneumonia in adults in Europe: a literature review. Eur J Clin Microbiol Infect Dis 2014; 33 (7) 1065-1079
  • 66 von Baum H, Welte T, Marre R, Suttorp N, Ewig S ; CAPNETZ study group. Community-acquired pneumonia through Enterobacteriaceae and Pseudomonas aeruginosa: diagnosis, incidence and predictors. Eur Respir J 2010; 35 (3) 598-605
  • 67 Sousa D, Justo I, Domínguez A , et al. Community-acquired pneumonia in immunocompromised older patients: incidence, causative organisms and outcome. Clin Microbiol Infect 2013; 19 (2) 187-192
  • 68 Wunderink RG. Community-acquired pneumonia versus healthcare-associated pneumonia. The returning pendulum. Am J Respir Crit Care Med 2013; 188 (8) 896-898
  • 69 Rodríguez-Avial I, Ramos B, Ríos E, Cercenado E, Ordobás M, Sanz JC ; Madrid Streptococcus pneumoniae Microbiological Group. Clonal spread of levofloxacin-resistant streptococcus pneumoniae invasive isolates in Madrid, Spain, 2007 to 2009. Antimicrob Agents Chemother 2011; 55 (5) 2469-2471
  • 70 Patel SN, McGeer A, Melano R , et al; Canadian Bacterial Surveillance Network. Susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Antimicrob Agents Chemother 2011; 55 (8) 3703-3708
  • 71 Golden AR, Rosenthal M, Fultz B , et al. Characterization of MDR and XDR Streptococcus pneumoniae in Canada, 2007-13. J Antimicrob Chemother 2015; 70 (8) 2199-2202
  • 72 Adam HJ, Baxter MR, Davidson RJ , et al; Canadian Antimicrobial Resistance Alliance (CARA). Comparison of pathogens and their antimicrobial resistance patterns in paediatric, adult and elderly patients in Canadian hospitals. J Antimicrob Chemother 2013; 68 (Suppl. 01) i31-i37
  • 73 Hu F, Zhu D, Wang F, Morrissey I, Wang J, Torumkuney D. Results from the Survey of Antibiotic Resistance (SOAR) 2009-11 and 2013-14 in China. J Antimicrob Chemother 2016; 71 (Suppl. 01) i33-i43
  • 74 Pérez-Trallero E, Martín-Herrero JE, Mazón A , et al; Spanish Surveillance Group for Respiratory Pathogens. Antimicrobial resistance among respiratory pathogens in Spain: latest data and changes over 11 years (1996-1997 to 2006-2007). Antimicrob Agents Chemother 2010; 54 (7) 2953-2959
  • 75 Hong KB, Choi EH, Lee HJ , et al. Macrolide resistance of Mycoplasma pneumoniae, South Korea, 2000-2011. Emerg Infect Dis 2013; 19 (8) 1281-1284