nach oben

Current Infectious Disease Reports

Erschienen in:

01.11.2018 | Respiratory Infections (F Arnold, Section Editor)

Moving Past the Routine Use of Macrolides—Reviewing the Role of Combination Therapy in Community-Acquired Pneumonia

verfasst von: Geoffrey Shumilak, Wendy I. Sligl

Erschienen in: Current Infectious Disease Reports | Ausgabe 11/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

Despite advances in diagnostic microbiology and sepsis management, community-acquired pneumonia (CAP) remains a significant cause of morbidity and mortality. Current recommendations regarding the use of beta-lactams in combination with macrolides published in clinical practice guidelines are variable and based on low-quality evidence that is frequently retrospective, observational, and heterogeneous in nature. While population-based studies have historically suggested improved clinical outcomes with the routine use of macrolide combination therapy in hospitalized patients with CAP, emerging evidence from recent randomized controlled trials has challenged this practice. In this article, we discuss the historical rationale and current evidence for combination macrolide therapy in the management of CAP.

Recent Findings

Recent randomized controlled trials have assessed the non-inferiority of beta-lactam monotherapy compared to beta-lactam/macrolide combination therapy in adult patients hospitalized with CAP. Beta-lactam monotherapy was associated with equivalent clinical outcomes in patients with mild to moderate CAP. Patients with severe CAP managed with beta-lactam monotherapy have demonstrated worse clinical outcomes when compared to patients treated with combination therapy. In addition, previous beta-lactam exposure prior to hospitalization has not been shown to negatively impact outcomes in patients managed with beta-lactam monotherapy in the hospital.

Summary

Current evidence supports the use of beta-lactam monotherapy in adult patients hospitalized with mild to moderate CAP. While existing evidence supports the use of combination therapy in patients with severe pneumonia, further large-scale randomized controlled trials are urgently needed to clarify the role of combination therapy in this population.

• Ramirez JA, Wiemken TL, Peyrani P, Arnold FW, Kelley R, Mattingly WA, et al. Adults hospitalized with pneumonia in the United States: incidence, epidemiology, and mortality. Clin Infect Dis. 2017;65(11):1806–12. https://doi.org/10.1093/cid/cix647. Prospective population-based cohort study evaluating incidence of CAP in consecutive hospitalized patients at all adult hospitals in Louisville, Kentucky. Calculation of annual population-based incidence of CAP, mortality at 1, 6, and 12 months following hospitalization, and ecological associations of CAP. CrossRefPubMed

Rui P, Kang K. National Hospital Ambulatory Medical Care Survey: 2014 Emergency department summary tables. Available from: http://www.cdc.gov/nchs/data/ahcd/nhamcs_emergency/2014_ed_web_tables.pdf.

Kochanek KD, Murphy SL, Xu JQ, Tejada-Vera B. Deaths: final for 2014. National vital statistics reports; vol 65 no4. National Center for Health Statistics: Hyattsville; 2016.

Bennett J, Dolin R, Mandell BM. Douglas and Bennett’s Principles and Practice of Infectious Diseases. Chapter 68: Acute Pneumonia. Philadelphia: Elsevier; 2015. p. 823–828.

Mandell LA, Marrie TJ, Grossman RF, Chow AW, Hyland RH, The Canadian CAP Working Group. Summary of Canadian Guidelines for the Initial Management of Community-acquired Pneumonia: an evidence-based update by the Canadian Infectious Disease Society and the Canadian Thoracic Society. Can J Infect Dis. 2000;11(5):237–48.CrossRefPubMedPubMedCentral

• Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-acquired pneumonia requiring hospitalization among U. S. adults. N Engl J Med. 2015;373:415–27. https://doi.org/10.1056/NEJMoa.1500245. Active population-based surveillance study of immunocompetent adults hospitalized with community-acquired pneumonia. In addition to conventional diagnostic testing, extensive molecular and serologic testing was employed to characterize causative pathogens and provide contemporary data on the causative agents of CAP. Despite extensive testing, found that no pathogen was detected in the majority of patients. Rhinovirus, influenza, and Streptococcus pneumoniae remained the most common identifiable causes of CAP. CrossRefPubMedPubMedCentral

McFarlane A, Sligl W. The value of macrolide-based regimens for community-acquired pneumonia. Curr Infect Dis Rep. 2015;17:50. https://doi.org/10.1007/s11908-015-0507-4.CrossRefPubMed

Schlunzen F, Zarivach R, Harms J, et al. Structural basis for the interaction of antibiotics with the peptidyl-transferase centre in eubacteria. Nature. 2001;413(6858):814–21. https://doi.org/10.1038/35101544.CrossRefPubMed

Tenson T, Lovmar M, Ehrenberg M. The mechanism of action of macrolides, lincosamides and streptogramin B reveals the nascent peptide exit path in the ribosome. J Mol Biol. 2003;330(5):1005–14.CrossRefPubMed

10.

Doern GV, Richter SS, Miller A, Miller N, Rice C, Heilmann K, et al. Antimicrobial resistance among Streptococcus pneumoniae in the United States: have we begun to turn the corner on resistance to certain antimicrobial classes? Clin Infect Dis. 2005;41(2):139–48.CrossRefPubMed

11.

Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013. https://www.cdc.gov/drugresistance/threat-report-2013/ (Accessed on April 28, 2018).

12.

Song JH, Jung SI, Ko KS, Kim NY, Son JS, Chang HH, et al. High prevalence of antimicrobial resistance among clinical Streptococcus pneumoniae isolates in Asia (an ANSORP study). Antimicrob Agents Chemother. 2004;48(6):2101–7.CrossRefPubMedPubMedCentral

13.

Zheng X, Lee S, Selvarangan R, Qin X, Tang YW, Stiles J, et al. Macrolide-resistant mycoplasma pneumoniae, United States. Emerg Infect Dis. 2015;21(8):1470–2.CrossRefPubMedPubMedCentral

14.

Kawai Y, Miyashita N, Kubo M, Akaike H, Kato A, Nishizawa Y, et al. Nationwide surveillance of macrolide-resistant mycoplasma pneumoniae infection in pediatric patients. Antimicrob Agents Chemother. 2013;57(8):4046–9.CrossRefPubMedPubMedCentral

15.

Rubin BK, Tamaoki J. Macrolide antibiotics as biological response modifiers. Curr Opin Investig Drugs. 2000;1(2):169–72.PubMed

16.

Khair OA, Devalia JL, Abdelaziz MM, Sapsford RJ, Davies RJ. Effect of erythromycin on Haemophilus influenzae endotoxininduced release of IL-6, IL-8 and sICAM-1 by cultured human bronchial epithelial cells. Eur Respir J. 1995;8(9):1451–7.PubMed

17.

Anderson R, Theron AJ, Feldman C. Membrane-stabilizing, anti-inflammatory interactions of macrolides with human neutrophils. Inflammation. 1996;20(6):693–705.CrossRefPubMed

18.

Desaki M, Okazaki H, Sunazuka T, Omura S, Yamamoto K, Takizawa H. Molecular mechanisms of anti-inflammatory action of erythromycin in human bronchial epithelial cells: possible role in the signaling pathway that regulates nuclear factor-kappa B activation. Antimicrob Agents Chemother. 2004;48(5):1581–5.CrossRefPubMedPubMedCentral

19.

Lee N, Wong C, Chan M, Yeung E, Tam W, Tsang O, et al. Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: a randomized controlled trial. Antivir Res. 2017;144:48–56.CrossRefPubMed

20.

Kovaleva A, Remmelts HHF, Rijkers GT, Hoepelman AIM, Biesma DH, Oosterheert JJ. Immunomodulatory effects of macrolides during community-acquired pneumonia: a literature review. J Antimicrob Chemother. 67(3):530–40. https://doi.org/10.1093/jac/dkr520.CrossRefPubMed

21.

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.CrossRefPubMed

22.

Lim WS, Baudouin SV, George RC, Hill AT, Jamieson C, Le Jeune I, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64 Suppl 3:iii1–55. https://doi.org/10.1136/thx.2009.121434.CrossRefPubMed

23.

Sinan E, Celia P, Bernard H, Mark W. Diagnosis and management of community and hospital acquired pneumonia in adults: summary of NICE guidance. BMJ. 2014;349:g6722. https://doi.org/10.1136/bmj.g6722.CrossRef

24.

Gleason PP, Meehan TP, Fine JM, Galusha DH, Fine MJ. Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia. Arch Intern Med. 159:1999, 2562–72.CrossRefPubMed

25.

Houck PM, MacLehose RF, Niederman MS, Lowery JK. Empiric antibiotic therapy and mortality among Medicare pneumonia inpatients in 10 western states: 1993, 1995, and 1997. Chest. 2001;119:1420–6.CrossRefPubMed

26.

Dudas V, Hopefl A, Jacobs R, Guglielmo BJ. Antimicrobial selection for hospitalized patients with presumed community-acquired pneumonia: a survey of nonteaching US community hospitals. Ann Pharmacother. 2000;34:446–52.CrossRefPubMed

27.

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;123:1503–11.CrossRefPubMed

28.

Gardiner SJ, Gavranich JB, Chang AB. Antibiotics for community-acquired lower respiratory tract infections secondary to in children. Cochrane Database Syst Rev 2015, (1):CD004875. https://doi.org/10.1002/14651858.CD004875.pub5.

29.

van Werkhoven CH, Postma DF, Oosterheert DF, Bonten MJM. Antibiotic treatment of moderate-severe community-acquired pneumonia: design and rationale of a multicenter cluster-randomized cross-over trial. Neth J Med. 2014;72(3)

30.

Weiss K, Tillotson GS. The controversy of combination vs monotherapy in the treatment of hospitalized community-acquired pneumonia. Chest. 2005;128:940–6.CrossRefPubMed

31.

File TM Jr, Marrie TJ. Does empiric therapy for atypical pathogens improve outcomes for patients with CAP? Infect Dis Clin N Am. 2013;27:99–114.CrossRef

32.

Ray W, Murray K, Hall K, Arbogast P, et al. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366:1881–90. https://doi.org/10.1056/NEJMoa1003833.CrossRefPubMedPubMedCentral

33.

Wieczorkiewicz J, Lopansri B, Cheknis A, Osmolski J, Hect D, Gerdin D, et al. Fluoroquinolone and macrolide exposure predict Clostridium difficile infection with the highly fluorquinolone and macrolide-resistant epidemic C. difficile strain BI/NAP1/027. Antimicrob Agents Chemother. 2016;60(1):418–23.CrossRefPubMed

34.

Eliakim-Raz N, Robenshtok E, Shefet D, et al. Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults. Cochrane Database Syst Rev. 2012;9:CD004418.

35.

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 Aug;55(3):371–80. https://doi.org/10.1093/cid/cis414.CrossRefPubMed

36.

•• 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. https://doi.org/10.1001/jamainternmed.2014.4887. Evaluated the non-inferiority of beta-lactam monotherapy compared with beta-lactam/macrolide combination therapy in moderately severe CAP in an open-label, multicenter, non-inferiority randomized control trial. Failed to meet primary outcome and demonstrate non-inferiority of beta-lactam monotherapy in moderately severe community-acquired pneumonia. Subgroup analyses revealed equivalent outcomes in patients with mild to moderate CAP (PSI 1-3) but worse outcomes in patients managed with beta-lactam monotherapy and severe CAP. Secondary outcomes were equivalent between the two groups. CrossRefPubMed

37.

•• Postma DF, van Werkhoven CH, van Elden LJR, et al. Antibiotic treatment strategies for community-acquired pneumonia in adults. (CAP-START). N Engl J Med. 2015;372:1312. Multi-center cluster-randomized, crossover, non-inferiority trial conducted at 7 hospitals in the Netherlands to determine if empiric therapy for CAP with beta-lactam monotherapy was non-inferior to combination beta-lactam/macrolide therapy or a respiratory fluoroquinolone. 90-day all-cause mortality was lowest in the beta-lactam monotherapy arm. Adjusted comparisons for 90-day all-cause mortality favored beta-lactam monotherapy with a 1.9% lower risk of death when compared to macrolide combination therapy. Time to oral antibiotic de-escalation, length of hospital stay, and occurrence of complications during hospital stay were not significantly different between the groups. CrossRefPubMed

38.

•• van Werkhoven CH, van de Garde EMW, Oosterheert JJ, Postma DF, Bonten MJM. Atypical coverage in community-acquired pneumonia after outpatient beta-lactam monotherapy. Respir Med. 2017;129:145–51. https://doi.org/10.1016/j.rmed.2017.06.012. Evaluation of outcomes in a subset of 179 patients from the CAP-START Trial that had previous beta-lactam exposure prior to hospitalization. Compared thirty-day mortality, hospital length of stay, and frequency of treatment escalations between patients that were continued on beta-lactam monotherapy and patients that received beta-lactams and atypical coverage. No significant differences between groups with respect to 30-day mortality and hospital length of stay were identified. CrossRefPubMed

39.

Baddour LM, Yu VL, Klugman KP, et al. Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med. 2004;170:440–4.CrossRefPubMed

40.

Arnold FW, Lopardo G, Wiemken TL, Kelley R, Peyrani P, Mattingly WA, et al. Macrolide therapy is associated with lower mortality in community-acquired bacteremic pneumonia. Respir Med. 2018;140:115–21. https://doi.org/10.1016/j.rmed.2018.05.020.CrossRefPubMed

41.

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. https://doi.org/10.1097/CCM.0b013e3182a66b9b.CrossRefPubMed

Titel: Moving Past the Routine Use of Macrolides—Reviewing the Role of Combination Therapy in Community-Acquired Pneumonia
verfasst von: Geoffrey Shumilak
Wendy I. Sligl
Publikationsdatum: 01.11.2018
Verlag: Springer US
Erschienen in: Current Infectious Disease Reports / Ausgabe 11/2018
Print ISSN: 1523-3847
Elektronische ISSN: 1534-3146
DOI: https://doi.org/10.1007/s11908-018-0651-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

23.04.2024 | Ablationstherapie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Moving Past the Routine Use of Macrolides—Reviewing the Role of Combination Therapy in Community-Acquired Pneumonia

Abstract

Purpose of Review

Recent Findings

Summary

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Hinter dieser Appendizitis steckte ein Erreger

Demenzkranke durch Antipsychotika vielfach gefährdet

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2018

Infectious Diseases and Mass Gatherings

Candida parapsilosis Vaginal Infection—a New Site of Azole Drug Resistance

Antimicrobial Therapy in Community-Acquired Pneumonia in Children

Treating HIV-Positive/Non-AIDS Patients for Community-Acquired Pneumonia with ART

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Hinter dieser Appendizitis steckte ein Erreger

Demenzkranke durch Antipsychotika vielfach gefährdet

Update Innere Medizin