Abstract
Despite all published literature, controversies remain about the optimal antibiotic treatment in community-acquired pneumonia. The most debated issue is whether it is necessary to empirically start one or two antibiotics, i.e. whether or not to cover atypical agents. A review of the literature published from 2005 to present was completed, searching for new insights in antibiotic treatment in community-acquired pneumonia (CAP) focusing on monotherapy versus combined therapy. Forty-one articles were identified enrolling outpatients, and patients admitted to the ward and to the intensive care unit: 11 were meta-analyses, 8 clinical trials and 22 observational—prospective and retrospective—studies. Although controversies remain in the treatment of CAP, the use of combination therapy seems to be associated with a lower mortality in case of severe CAP that requires intensive care unit (ICU) admission, especially when a beta-lactam–macrolide association is delivered. Moreover, combination therapy is associated with better outcomes—although not always with a lower mortality—in cases of non-ICU patients with risk factors for a poor outcome, bacteraemic pneumococcal pneumonia and high suspicion of infection by atypical agents. In this setting, it appears that the best choice of treatment may be a beta-lactam–macrolide regimen.
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Abbreviations
- CAP:
-
Community-acquired pneumonia
- ICU:
-
intensive care unit
- PSI:
-
Pneumonia severity index
References
Papers of particular interest, published recently, have been highlighted as: • Of importance
Torres A, Peetermans WE, Viegi G, Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review. Thorax. 2013;68(11):1057–65.
Nair GB, Niederman MS. Community-acquired pneumonia: an unfinished battle. Med Clin N Am. 2011;95(6):1143–61.
Gattarello S, Borgatta B, Solé-Violán J, Vallés J, Vidaur L, Zaragoza R, et al. Decrease in mortality in severe community-acquired pneumococcal pneumonia: impact of improving antibiotic strategies (2000-2013). Chest. 2014;146(1):22–31.
Woodhead M, Blasi F, Ewig S, Garau J, Huchon G, Ieven M, et al. Guidelines for the management of adult lower respiratory tract infections—full version. Clin Microbiol Infect. 2011;17 Suppl 6:E1–59.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.
Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. 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 2:S27–72.
Iannini PB, Paladino JA, Lavin B, Singer ME, Schentag JJ. A case series of macrolide treatment failures in community acquired pneumonia. J Chemother. 2007;19:536–45.
Rosón B, Carratalà J, Fernández-Sabé N, Tubau F, Manresa F, Gudiol F. Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia. Arch Intern Med. 2004;164(5):502–8.
Griffin AT, Peyrani P, Wiemken TL, Ramirez JA, Arnold FW. Empiric therapy directed against MRSA in patients admitted to the intensive care unit does not improve outcomes in community-acquired pneumonia. Infection. 2013;41(2):517–23.
Pakhale S, Mulpuru S, Verheij TJ, Kochen MM, Rohde GG, Bjerre LM. Antibiotics for community-acquired pneumonia in adult outpatients. Cochrane Database Syst Rev. 2014;10:CD002109.
Skalsky K, Yahav D, Lador A, Eliakim-Raz N, Leibovici L, Paul M. Macrolides vs. quinolones for community-acquired pneumonia: meta-analysis of randomized controlled trials. Clin Microbiol Infect. 2013;19(4):370–8.
An MM, Zou Z, Shen H, Gao PH, Cao YB, Jiang YY. Moxifloxacin monotherapy versus beta-lactam-based standard therapy for community-acquired pneumonia: a meta-analysis of randomised controlled trials. Int J Antimicrob Agents. 2010;36(1):58–65.
Ye X, Sikirica V, Schein JR, Grant R, Zarotsky V, Doshi D, et al. Treatment failure rates and health care utilization and costs among patients with community-acquired pneumonia treated with levofloxacin or macrolides in an outpatient setting: a retrospective claims database analysis. Clin Ther. 2008;30(2):358–71.
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):1441–6.
Zhang L, Wang R, Falagas ME, Chen LA, Liu YN. Gemifloxacin for the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis: a meta-analysis of randomized controlled trials. Chin Med J (Engl). 2012;125(4):687–95.
Eliakim-Raz N, Robenshtok E, Shefet D, Gafter-Gvili A, Vidal L, Paul M. Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults. Cochrane Database Syst Rev. 2012;9:CD004418.
Yuan X, Liang BB, Wang R, Liu YN, Sun CG, Cai Y, et al. Treatment of community-acquired pneumonia with moxifloxacin: a meta-analysis of randomized controlled trials. J Chemother. 2012;24(5):257–67.
Asadi L, Sligl WI, Eurich DT, Colmers IN, Tjosvold L, Marrie TJ, et al. Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic review and meta-analysis. Clin Infect Dis. 2012;55(3):371–80.
Varner TR, Bookstaver PB, Rudisill CN, Albrecht H. Role of rifampin-based combination therapy for severe community-acquired Legionella pneumophila pneumonia. Ann Pharmacother. 2011;45(7-8):967–76.
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):1269–77.
Postma DF, van Werkhoven CH, van Elden LJ, Thijsen SF, Hoepelman AI, Kluytmans JA, et al. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015;372(14):1312–23.
Garin N, Genné D, Carballo S, Chuard C, Eich G, Hugli O, 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):1894–901.
Lee JH, Kim SW, Kim JH, Ryu YJ, Chang JH. High-dose levofloxacin in community-acquired pneumonia: a randomized, open-label study. Clin Drug Investig. 2012;32(9):569–76.
Torres A, Garau J, Arvis P, Carlet J, Choudhri S, Kureishi A, et al. Moxifloxacin monotherapy is effective in hospitalized patients with community-acquired pneumonia: the MOTIV study—a randomized clinical trial. Clin Infect Dis. 2008;46(10):1499–509.
Lin TY, Lin SM, Chen HC, Wang CJ, Wang YM, Chang ML, et al. An open-label, randomized comparison of levofloxacin and amoxicillin/clavulanate plus clarithromycin for the treatment of hospitalized patients with community-acquired pneumonia. Chang Gung Med J. 2007;30(4):321–32.
Xu S, Xiong S, Xu Y, Liu J, Liu H, Zhao J, et al. Efficacy and safety of intravenous moxifloxacin versus cefoperazone with azithromycin in the treatment of community acquired pneumonia. J Huazhong Univ Sci Technol Med Sci. 2006;26(4):421–4.
Portier H, Brambilla C, Garre M, Paganin F, Poubeau P, Zuck P. Moxifloxacin monotherapy compared to amoxicillin-clavulanate plus roxithromycin for nonsevere community-acquired pneumonia in adults with risk factors. Eur J Clin Microbiol Infect Dis. 2005;24(6):367–76.
Asadi L, Eurich DT, Gamble JM, Minhas-Sandhu JK, Marrie TJ, Majumdar SR. Impact of guideline-concordant antibiotics and macrolide/β-lactam combinations in 3203 patients hospitalized with pneumonia: prospective cohort study. Clin Microbiol Infect. 2013;19(3):257–64.
Rodrigo C, Mckeever TM, Woodhead M. Single versus combination antibiotic therapy in adults hospitalised with community acquired pneumonia. Thorax. 2013;68(5):493–5.
Frei CR, Jaso TC, Mortensen EM, Restrepo MI, Raut MK, Oramasionwu CU, et al. Medical resource utilization among community-acquired pneumonia patients initially treated with levofloxacin 750 mg daily versus ceftriaxone 1000 mg plus azithromycin 500 mg daily: a US-based study. Curr Med Res Opin. 2009;25(4):859–68.
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):153–9.
Bratzler DW, Ma A, Nsa W. Initial antibiotic selection and patient outcomes: observations from the National Pneumonia Project. Clin Infect Dis. 2008;47 Suppl 3:S193–201.
Bhavnani SM, Ambrose PG. Cost-effectiveness of oral gemifloxacin versus intravenous ceftriaxone followed by oral cefuroxime with/without a macrolide for the treatment of hospitalized patients with community-acquired pneumonia. Diagn Microbiol Infect Dis. 2008;60(1):59–64.
Lloyd A, Holman A, Evers T. A cost-minimisation analysis comparing moxifloxacin with levofloxacin plus ceftriaxone for the treatment of patients with community-acquired pneumonia in Germany: results from the MOTIV trial. Curr Med Res Opin. 2008;24(5):1279–84.
Lodise TP, Kwa A, Cosler L, Gupta R, Smith RP. Comparison of beta-lactam and macrolide combination therapy versus fluoroquinolone monotherapy in hospitalized Veterans Affairs patients with community-acquired pneumonia. Antimicrob Agents Chemother. 2007;51(11):3977–82.
Metersky ML, Ma A, Houck PM, Bratzler DW. Antibiotics for bacteremic pneumonia: improved outcomes with macrolides but not fluoroquinolones. Chest. 2007;131(2):466–73.
Dwyer R, Ortqvist A, Aufwerber E, Henriques Normark B, Marrie TJ, Mufson MA, et al. Addition of a macrolide to a ss-lactam in bacteremic pneumococcal pneumonia. Eur J Clin Microbiol Infect Dis. 2006;25(8):518–21.
Welte T, Petermann W, Schürmann D, Bauer TT, Reimnitz P, MOXIRAPID Study Group. Treatment with sequential intravenous or oral moxifloxacin was associated with faster clinical improvement than was standard therapy for hospitalized patients with community-acquired pneumonia who received initial parenteral therapy. Clin Infect Dis. 2005;41(12):1697–705.
Querol-Ribelles JM, Tenías JM, Querol-Borrás JM, Labrador T, Nieto A, González-Granda D, et al. Levofloxacin versus ceftriaxone plus clarithromycin in the treatment of adults with community-acquired pneumonia requiring hospitalization. Int J Antimicrob Agents. 2005;25(1):75–83.
García Vázquez E, Mensa J, Martínez JA, Marcos MA, Puig J, Ortega M, et al. Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a beta-lactam agent versus a beta-lactam agent alone. Eur J Clin Microbiol Infect Dis. 2005;24(3):190–5.
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):420–32.
Leroy O, Saux P, Bédos JP, Caulin E. Comparison of levofloxacin and cefotaxime combined with ofloxacin for ICU patients with community-acquired pneumonia who do not require vasopressors. Chest. 2005;128(1):172–83.
Adrie C, Schwebel C, Garrouste-Orgeas M, Vignoud L, Planquette B, Azoulay E, et al. Article Was Written on behalf of the Outcomerea Study Group. Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia: impact on survival and bacterial resistance. Crit Care. 2013;17(6):R265.
Wilson BZ, Anzueto A, Restrepo MI, Pugh MJ, Mortensen EM. Comparison of two guideline-concordant antimicrobial combinations in elderly patients hospitalized with severe community-acquired pneumonia. Crit Care Med. 2012;40(8):2310–4.
Rello J, Gattarello S, Souto J, Sole-Violan J, Valles J, Peredo R, et al. Community-acquired Legionella Pneumonia in the intensive care unit: Impact on survival of combined antibiotic therapy. Med Intensiva. 2013;37(5):320–6.
Martin-Loeches I, Lisboa T, Rodriguez A, Putensen C, Annane D, Garnacho-Montero J, et al. Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia. Intensive Care Med. 2010;36(4):612–20.
Rodríguez A, Mendia A, Sirvent JM, Barcenilla F, de la Torre-Prados MV, Solé-Violán J, et al. Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock. Crit Care Med. 2007;35(6):1493–8.
Harbarth S, Garbino J, Pugin J, Romand JA, Pittet D. Lack of effect of combination antibiotic therapy on mortality in patients with pneumococcal sepsis. Eur J Clin Microbiol Infect Dis. 2005;24(10):688–90.
Mortensen EM, Restrepo MI, Anzueto A, Pugh J. The impact of empiric antimicrobial therapy with a β-lactam and fluoroquinolone on mortality for patients hospitalized with severe pneumonia. Crit Care. 2005;10(1):R8.
Heffelfinger JD, Dowell SF, Jorgensen JH, Klugman KP, Mabry LR, Musher DM, et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group. Arch Intern Med. 2000;160(10):1399–408.
Grossman RF, Hsueh PR, Gillespie SH, Blasi F. Community-acquired pneumonia and tuberculosis: differential diagnosis and the use of fluoroquinolones. Int J Infect Dis. 2014;18:14–21.
Amin AN, Cerceo EA, Deitelzweig SB, Pile JC, Rosenberg DJ, Sherman BM. The hospitalist perspective on treatment of community-acquired pneumonia. Postgrad Med. 2014;126(2):18–29.
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Gattarello, S. What Is New in Antibiotic Therapy in Community-Acquired Pneumonia? An Evidence-Based Approach Focusing on Combined Therapy. Curr Infect Dis Rep 17, 45 (2015). https://doi.org/10.1007/s11908-015-0501-x
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DOI: https://doi.org/10.1007/s11908-015-0501-x