Semin Respir Crit Care Med 2016; 37(06): 905-912
DOI: 10.1055/s-0036-1592133
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Principles of Antibiotic Management of Community-Acquired Pneumonia

Michael T. Bender
1   NewYork-Presbyterian Hospital, Weill Cornell Medicine, New York, New York
,
Michael S. Niederman
2   Department of Medicine, Weill Cornell Medical College, New York, New York
3   Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York, New York
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Publikationsverlauf

Publikationsdatum:
13. Dezember 2016 (online)

Abstract

Community-acquired pneumonia (CAP) encompasses a broad spectrum of disease severity and may require outpatient, inpatient, or intensive care management. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely offending pathogens and the severity of disease. This review summarizes key principles in starting treatment and provides recommended empiric therapy regimens for each site of care. In addition, we discuss the antimicrobial and anti-inflammatory role macrolides play in CAP, as well as specific information for managing individual CAP pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and drug-resistant Streptococcus pneumoniae. We also examine several novel antibiotics being developed for CAP and review the evidence guiding duration of therapy and current best practices for the transition of hospitalized patients from intravenous antibiotics to oral therapy.

 
  • References

  • 1 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
  • 2 Lee JS, Giesler DL, Gellad WF, Fine MJ. Antibiotic therapy for adults hospitalized with community-acquired pneumonia: a systematic review. JAMA 2016; 315 (6) 593-602
  • 3 Lee JS, Nsa W, Hausmann LR , et al. Quality of care for elderly patients hospitalized for pneumonia in the United States, 2006 to 2010. JAMA Intern Med 2014; 174 (11) 1806-1814
  • 4 Meehan TP, Fine MJ, Krumholz HM , et al. Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA 1997; 278 (23) 2080-2084
  • 5 Dedier J, Singer DE, Chang Y, Moore M, Atlas SJ. Processes of care, illness severity, and outcomes in the management of community-acquired pneumonia at academic hospitals. Arch Intern Med 2001; 161 (17) 2099-2104
  • 6 Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med 2004; 164 (6) 637-644
  • 7 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
  • 8 Simonetti A, Viasus D, Garcia-Vidal C , et al. Timing of antibiotic administration and outcomes of hospitalized patients with community-acquired and healthcare-associated pneumonia. Clin Microbiol Infect 2012; 18 (11) 1149-1155
  • 9 Waterer GW, Kessler LA, Wunderink RG. Delayed administration of antibiotics and atypical presentation in community-acquired pneumonia. Chest 2006; 130 (1) 11-15
  • 10 Lee JS, Primack BA, Mor MK , et al. Processes of care and outcomes for community-acquired pneumonia. Am J Med 2011; 124 (12) 1175.e9-1175.e17
  • 11 Kumar A, Roberts D, Wood KE , et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34 (6) 1589-1596
  • 12 Levy MM, Dellinger RP, Townsend SR , et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 2010; 36 (2) 222-231
  • 13 Kanwar M, Brar N, Khatib R, Fakih MG. Misdiagnosis of community-acquired pneumonia and inappropriate utilization of antibiotics: side effects of the 4-h antibiotic administration rule. Chest 2007; 131 (6) 1865-1869
  • 14 Welker JA, Huston M, McCue JD. Antibiotic timing and errors in diagnosing pneumonia. Arch Intern Med 2008; 168 (4) 351-356
  • 15 Polgreen PM, Chen YY, Cavanaugh JE , et al. An outbreak of severe Clostridium difficile-associated disease possibly related to inappropriate antimicrobial therapy for community-acquired pneumonia. Infect Control Hosp Epidemiol 2007; 28 (2) 212-214
  • 16 Daniel P, Rodrigo C, Mckeever TM, Woodhead M, Welham S, Lim WS ; British Thoracic Society. Time to first antibiotic and mortality in adults hospitalised with community-acquired pneumonia: a matched-propensity analysis. Thorax 2016; 71 (6) 568-570
  • 17 Read RC. Evidence-based medicine: empiric antibiotic therapy in community-acquired pneumonia. J Infect 1999; 39 (3) 171-178
  • 18 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
  • 19 Marrie TJ, Poulin-Costello M, Beecroft MD, Herman-Gnjidic Z. Etiology of community-acquired pneumonia treated in an ambulatory setting. Respir Med 2005; 99 (1) 60-65
  • 20 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
  • 21 Ramsdell J, Narsavage GL, Fink JB ; American College of Chest Physicians' Home Care Network Working Group. Management of community-acquired pneumonia in the home: an American College of Chest Physicians clinical position statement. Chest 2005; 127 (5) 1752-1763
  • 22 Vanderkooi OG, Low DE, Green K, Powis JE, McGeer A ; Toronto Invasive Bacterial Disease Network. Predicting antimicrobial resistance in invasive pneumococcal infections. Clin Infect Dis 2005; 40 (9) 1288-1297
  • 23 Campbell Jr GD, Silberman R. Drug-resistant Streptococcus pneumoniae . Clin Infect Dis 1998; 26 (5) 1188-1195
  • 24 Restrepo MI, Mortensen EM, Velez JA, Frei C, Anzueto A. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest 2008; 133 (3) 610-617
  • 25 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
  • 26 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
  • 27 Altenburg J, de Graaff CS, van der Werf TS, Boersma WG. Immunomodulatory effects of macrolide antibiotics - part 1: biological mechanisms. Respiration 2011; 81 (1) 67-74
  • 28 Postma DF, van Werkhoven CH, van Elden LJ , et al; CAP-START Study Group. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med 2015; 372 (14) 1312-1323
  • 29 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
  • 30 Sligl WI, Asadi L, Eurich DT, Tjosvold L, Marrie TJ, Majumdar SR. Macrolides and mortality in critically ill patients with community-acquired pneumonia: a systematic review and meta-analysis. Crit Care Med 2014; 42 (2) 420-432
  • 31 Baddour LM, Yu VL, Klugman KP , et al; International Pneumococcal Study Group. Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med 2004; 170 (4) 440-444
  • 32 Restrepo MI, Mortensen EM, Waterer GW, Wunderink RG, Coalson JJ, Anzueto A. Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia. Eur Respir J 2009; 33 (1) 153-159
  • 33 Brown RB, Iannini P, Gross P, Kunkel M. Impact of initial antibiotic choice on clinical outcomes in community-acquired pneumonia: analysis of a hospital claims-made database. Chest 2003; 123 (5) 1503-1511
  • 34 Corrales-Medina VF, Musher DM. Immunomodulatory agents in the treatment of community-acquired pneumonia: a systematic review. J Infect 2011; 63 (3) 187-199
  • 35 Bednar MM, Harrigan EP, Anziano RJ, Camm AJ, Ruskin JN. The QT interval. Prog Cardiovasc Dis 2001; 43 (5) (Suppl. 01) 1-45
  • 36 Rubinstein E, Kollef MH, Nathwani D. Pneumonia caused by methicillin-resistant Staphylococcus aureus . Clin Infect Dis 2008; 46 (Suppl. 05) S378-S385
  • 37 Wunderink RG. How important is methicillin-resistant Staphylococcus aureus as a cause of community-acquired pneumonia and what is best antimicrobial therapy?. Infect Dis Clin North Am 2013; 27 (1) 177-188
  • 38 Bubeck Wardenburg J, Palazzolo-Ballance AM, Otto M, Schneewind O, DeLeo FR. Panton-Valentine leukocidin is not a virulence determinant in murine models of community-associated methicillin-resistant Staphylococcus aureus disease. J Infect Dis 2008; 198 (8) 1166-1170
  • 39 Diep BA, Afasizheva A, Le HN , et al. Effects of linezolid on suppressing in vivo production of staphylococcal toxins and improving survival outcomes in a rabbit model of methicillin-resistant Staphylococcus aureus necrotizing pneumonia. J Infect Dis 2013; 208 (1) 75-82
  • 40 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
  • 41 Bernardo K, Pakulat N, Fleer S , et al. Subinhibitory concentrations of linezolid reduce Staphylococcus aureus virulence factor expression. Antimicrob Agents Chemother 2004; 48 (2) 546-555
  • 42 Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE. Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus . J Infect Dis 2007; 195 (2) 202-211
  • 43 Faris J, Mynatt RP, Hall Snyder AD, Rybak MJ. Treatment of methicillin-resistant Staphylococcal aureus (MRSA) pneumonia with ceftaroline fosamil in a patient with inhalational thermal injury. Infect Dis Ther 2015; 4 (4) 519-528
  • 44 Clavo-Sánchez AJ, Girón-González JA, López-Prieto D , et al. Multivariate analysis of risk factors for infection due to penicillin-resistant and multidrug-resistant Streptococcus pneumoniae: a multicenter study. Clin Infect Dis 1997; 24 (6) 1052-1059
  • 45 Ruhe JJ, Hasbun R. Streptococcus pneumoniae bacteremia: duration of previous antibiotic use and association with penicillin resistance. Clin Infect Dis 2003; 36 (9) 1132-1138
  • 46 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
  • 47 Yu VL, Chiou CC, Feldman C , et al; International Pneumococcal Study Group. An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis 2003; 37 (2) 230-237
  • 48 Falagas ME, Siempos II, Bliziotis IA, Panos GZ. Impact of initial discordant treatment with beta-lactam antibiotics on clinical outcomes in adults with pneumococcal pneumonia: a systematic review. Mayo Clin Proc 2006; 81 (12) 1567-1574
  • 49 File Jr TM, Segreti J, Dunbar L , et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother 1997; 41 (9) 1965-1972
  • 50 Norrby SR, Petermann W, Willcox PA, Vetter N, Salewski E. A comparative study of levofloxacin and ceftriaxone in the treatment of hospitalized patients with pneumonia. Scand J Infect Dis 1998; 30 (4) 397-404
  • 51 Anzueto A, Niederman MS, Pearle J, Restrepo MI, Heyder A, Choudhri SH ; Community-Acquired Pneumonia Recovery in the Elderly Study Group. Community-Acquired Pneumonia Recovery in the Elderly (CAPRIE): efficacy and safety of moxifloxacin therapy versus that of levofloxacin therapy. Clin Infect Dis 2006; 42 (1) 73-81
  • 52 Vardakas KZ, Siempos II, Grammatikos A, Athanassa Z, Korbila IP, Falagas ME. Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials. CMAJ 2008; 179 (12) 1269-1277
  • 53 Ruhe J, Mildvan D. Does empirical therapy with a fluoroquinolone or the combination of a β-lactam plus a macrolide result in better outcomes for patients admitted to the general ward?. Infect Dis Clin North Am 2013; 27 (1) 115-132
  • 54 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
  • 55 Spellberg B, Bartlett J, Wunderink R, Gilbert DN. Novel approaches are needed to develop tomorrow's antibacterial therapies. Am J Respir Crit Care Med 2015; 191 (2) 135-140
  • 56 Barrera CM, Mykietiuk A, Metev H , et al; SOLITAIRE-ORAL Pneumonia Team. Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL). Lancet Infect Dis 2016; 16 (4) 421-430
  • 57 van Rensburg DJ, Perng RP, Mitha IH , et al. Efficacy and safety of nemonoxacin versus levofloxacin for community-acquired pneumonia. Antimicrob Agents Chemother 2010; 54 (10) 4098-4106
  • 58 Choi D, Kim YS, Kim MJ , et al. A phase 2, multidose, double-blind, randomized, multicenter, comparative study of zabofloxacin vs moxifloxacin in the treatment of mild to moderate community-acquired pneumonia [abstract]. Presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, September 9–12, 2012, San Francisco, California, L1–L294
  • 59 Gould IM, Bal AM. New antibiotic agents in the pipeline and how they can help overcome microbial resistance. Virulence 2013; 4 (2) 185-191
  • 60 Boucher HW, Talbot GH, Benjamin Jr DK , et al; Infectious Diseases Society of America. 10 x '20 Progress—development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis 2013; 56 (12) 1685-1694
  • 61 Woodhead M, Blasi F, Ewig S , et al; Joint Taskforce of the European Respiratory Society and European Society for Clinical Microbiology and Infectious Diseases. Guidelines for the management of adult lower respiratory tract infections—full version. Clin Microbiol Infect 2011; 17 (Suppl. 06) E1-E59
  • 62 Lim WS, Baudouin SV, George RC , et al; Pneumonia Guidelines Committee of the BTS Standards of Care Committee. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009; 64 (Suppl. 03) iii1-iii55
  • 63 Li JZ, Winston LG, Moore DH, Bent S. Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Am J Med 2007; 120 (9) 783-790
  • 64 Liu C, Bayer A, Cosgrove SE , et al; Infectious Diseases Society of America. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52 (3) e18-e55
  • 65 Schuetz P, Müller B, Christ-Crain M , et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Evid Based Child Health 2013; 8 (4) 1297-1371
  • 66 Oosterheert JJ, Bonten MJ, Schneider MM , et al. Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial. BMJ 2006; 333 (7580) 1193-1195
  • 67 Ramirez JA, Srinath L, Ahkee S, Huang A, Raff MJ. Early switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community-acquired pneumonia. Arch Intern Med 1995; 155 (12) 1273-1276
  • 68 Ramirez JA, Vargas S, Ritter GW , et al. Early switch from intravenous to oral antibiotics and early hospital discharge: a prospective observational study of 200 consecutive patients with community-acquired pneumonia. Arch Intern Med 1999; 159 (20) 2449-2454
  • 69 Lodise TP, Anzueto AR, Weber DJ , et al. Assessment of time to clinical response, a proxy for discharge readiness, among hospitalized patients with community-acquired pneumonia who received either ceftaroline fosamil or ceftriaxone in two phase III FOCUS trials. Antimicrob Agents Chemother 2015; 59 (2) 1119-1126
  • 70 Carratalà J, Garcia-Vidal C, Ortega L , et al. Effect of a 3-step critical pathway to reduce duration of intravenous antibiotic therapy and length of stay in community-acquired pneumonia: a randomized controlled trial. Arch Intern Med 2012; 172 (12) 922-928
  • 71 Murray C, Shaw A, Lloyd M , et al. A multidisciplinary intervention to reduce antibiotic duration in lower respiratory tract infections. J Antimicrob Chemother 2014; 69 (2) 515-518
  • 72 Fishbane S, Niederman MS, Daly C , et al. The impact of standardized order sets and intensive clinical case management on outcomes in community-acquired pneumonia. Arch Intern Med 2007; 167 (15) 1664-1669