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Antimicrobial Therapy in Community-Acquired Pneumonia in Children

  • Samriti Gupta
  • Rakesh Lodha
  • SK Kabra
Respiratory Infections (F Arnold, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Respiratory Infections

Abstract

Purpose of Review

Empirical antibiotic therapy remains the cornerstone of treatment in community-acquired pneumonia (CAP). However, the best option for empirical antibiotics for treatment on an ambulatory basis, as well as in those requiring hospitalization, is still unclear. This review tries to answer the question regarding the most appropriate antibiotics in different settings in children with CAP as well as duration of therapy.

Recent Findings

Recent studies have provided insights regarding use of oral antibiotics in children with mild to moderate CAP, and severe CAP with lower chest retractions but no hypoxia. In view of rapidly emerging resistance among various causative pathogens, several new drugs have been currently approved, or are under trial for CAP in children.

Summary

Current knowledge suggests that the choice of antibiotics for ambulatory treatment of CAP is oral amoxicillin with a duration of 3–5 days. Children with CAP with lower chest retractions but no hypoxia can be treated with oral amoxicillin. Severe pneumonia can be treated with intravenous antibiotics consisting of penicillin/ampicillin with or without an aminoglycoside. Several new drugs have been developed and approved for use in CAP caused by multidrug-resistant organisms, but these should be used judiciously to avoid emergence of further resistance. Future research is needed regarding the safety and efficacy of newer drugs in children.

Keywords

Acute lower respiratory tract infection Children Community-acquired pneumonia Pneumococcal 

Notes

Compliance with Ethical Standards

Conflict of Interest

Samriti Gupta, Rakesh Lodha, and S.K. Kabra declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    DeAntonio R, Yarzabal J-P, Cruz JP, Schmidt JE, Kleijnen J. Epidemiology of community-acquired pneumonia and implications for vaccination of children living in developing and newly industrialized countries: a systematic literature review. Hum Vaccin Immunother. 2016;12(9):2422–40.CrossRefGoogle Scholar
  2. 2.
    Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet Lond Engl. 2012;379(9832):2151–61.CrossRefGoogle Scholar
  3. 3.
    Walker CLF, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, et al. Global burden of childhood pneumonia and diarrhoea. Lancet Lond Engl. 2013;381(9875):1405–16.CrossRefGoogle Scholar
  4. 4.
    WHO | Pneumonia [Internet]. WHO. [cited 2018 Apr 18]. Available from: http://www.who.int/mediacentre/factsheets/fs331/en/.
  5. 5.
    Rudan I, O’Brien KL, Nair H, Liu L, Theodoratou E, Qazi S, et al. Epidemiology and etiology of childhood pneumonia in 2010: estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries. J Glob Health. 2013;3(1):010401.CrossRefGoogle Scholar
  6. 6.
    India missed 2015 child mortality target: Lancet report [Internet]. The Indian Express. 2015 [cited 2018 Apr 18]. Available from: http://indianexpress.com/article/india/india-others/india-missed-2015-child-mortality-target-says-lancet-report/.
  7. 7.
    World Health Organization, Department of Maternal N Child and Adolescent Health, World Health Organization. Revised WHO classification and treatment of pneumonia in children at health facilities: evidence summaries. [Internet]. 2014 [cited 2018 May 7]. Available from: http://apps.who.int/iris/bitstream/10665/137319/1/9789241507813_eng.pdf?ua=1.
  8. 8.
    Scott JAG, Wonodi C, Moïsi JC, Deloria-Knoll M, DeLuca AN, Karron RA, et al. The definition of pneumonia, the assessment of severity, and clinical standardization in the pneumonia etiology research for child health study. Clin Infect Dis. 2012;54(Suppl 2):S109–16.CrossRefGoogle Scholar
  9. 9.
    Mackenzie G. The definition and classification of pneumonia. Pneumonia. 2016;8:14.CrossRefGoogle Scholar
  10. 10.
    Gereige RS, Laufer PM. Pneumonia. Pediatr Rev. 2013 Oct 1;34(10):438–56.CrossRefGoogle Scholar
  11. 11.
    Rudan I, Boschi-Pinto C, Biloglav Z, Mulholland K, Campbell H. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ. 2008;86(5):408–16.CrossRefGoogle Scholar
  12. 12.
    Bradley JS, Byington CL, Shah SS, Alverson B, Carter ER, Harrison C, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25–76.CrossRefGoogle Scholar
  13. 13.
    Straus WL, Qazi SA, Kundi Z, Nomani NK, Schwartz B. Antimicrobial resistance and clinical effectiveness of co-trimoxazole versus amoxycillin for pneumonia among children in Pakistan: randomised controlled trial. Pakistan Co-trimoxazole Study Group. Lancet Lond Engl. 1998;352(9124):270–4.CrossRefGoogle Scholar
  14. 14.
    Catchup Study Group. Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan. Arch Dis Child. 2002;86(2):113–8.CrossRefGoogle Scholar
  15. 15.
    Awasthi S, Agarwal G, Singh JV, Kabra SK, Pillai RM, Singhi S, et al. Effectiveness of 3-day amoxycillin vs. 5-day co-trimoxazole in the treatment of non-severe pneumonia in children aged 2-59 months of age: a multi-centric open labeled trial. J Trop Pediatr. 2008;54(6):382–9.CrossRefGoogle Scholar
  16. 16.
    Lodha R, Kabra SK, Pandey RM. Antibiotics for community-acquired pneumonia in children. Cochrane Database Syst Rev. 2013;(6):CD004874.Google Scholar
  17. 17.
    Campbell H, Byass P, Forgie IM, O’Neill KP, Lloyd-Evans N, Greenwood BM. Trial of co-trimoxazole versus procaine penicillin with ampicillin in treatment of community-acquired pneumonia in young Gambian children. Lancet Lond Engl. 1988;2(8621):1182–4.CrossRefGoogle Scholar
  18. 18.
    Sidal M, Oğuz F, Ünüvar A, Şarbat G, Neyzi O. Trial of co-trimoxazole versus procaine penicillin G and benzathin penicillin + procaine penicillin G in the treatment of childhood pneumonia. J Trop Pediatr. 1994;40(5):301–4.CrossRefGoogle Scholar
  19. 19.
    Addo-Yobo E, Chisaka N, Hassan M, Hibberd P, Lozano JM, Jeena P, et al. Oral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study. Lancet Lond Engl. 2004;364(9440):1141–8.CrossRefGoogle Scholar
  20. 20.
    Jibril HB, Ifere OA, Odumah DU. An open, comparative evaluation of amoxycillin and amoxycillin plus clavulanic acid (‘Augmentin’) in the treatment of bacterial pneumonia in children. Curr Med Res Opin. 1989;11(9):585–92.CrossRefGoogle Scholar
  21. 21.
    Klein M. Multicenter trial of cefpodoxime proxetil vs. amoxicillin-clavulanate in acute lower respiratory tract infections in childhood. International Study Group. Pediatr Infect Dis J. 1995;14(4 Suppl):S19–22.CrossRefGoogle Scholar
  22. 22.
    Gardiner SJ, Gavranich JB, Chang AB. Antibiotics for community-acquired lower respiratory tract infections secondary to mycoplasma pneumoniae in children. Cochrane Database Syst Rev. 2015;1:CD004875.PubMedGoogle Scholar
  23. 23.
    Rasmussen ZA, Bari A, Qazi S, Rehman G, Azam I, Khan S, et al. Randomized controlled trial of standard versus double dose cotrimoxazole for childhood pneumonia in Pakistan. Bull World Health Organ. 2005;83(1):10–9.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Group BMJP. Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial. BMJ. 2004;328(7443):791.CrossRefGoogle Scholar
  25. 25.
    Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial. The Lancet. 2002;360(9336):835–41.Google Scholar
  26. 26.
    • Singh J, Sundaresan S, Manoharan A. Shet A. Serotype distribution and antimicrobial susceptibility pattern in children ≤ 5 years with invasive pneumococcal disease in India—a systematic review. Vaccine. 2017;35(35):4501–9. This article reveals the prevailing resistance of pneumococcus to penicillins in India and showed that India falls in intermediate zone of resistance. CrossRefGoogle Scholar
  27. 27.
    Greenberg D, Givon-Lavi N, Sadaka Y, Ben-Shimol S, Bar-Ziv J, Dagan R. Short-course antibiotic treatment for community-acquired alveolar pneumonia in ambulatory children: a double-blind, randomized, placebo-controlled trial. Pediatr Infect Dis J. 2014;33(2):136–42.CrossRefGoogle Scholar
  28. 28.
    Hazir T, Nisar YB, Abbasi S, Ashraf YP, Khurshid J, Tariq P, et al. Comparison of oral amoxicillin with placebo for the treatment of world health organization-defined nonsevere pneumonia in children aged 2-59 months: a multicenter, double-blind, randomized, placebo-controlled trial in Pakistan. Clin Infect Dis. 2011;52(3):293–300.CrossRefGoogle Scholar
  29. 29.
    Awasthi S, Agarwal G, Kabra SK, Singhi S, Kulkarni M, More V, et al. Does 3-day course of oral amoxycillin benefit children of non-severe pneumonia with wheeze: a multicentric randomised controlled trial. PLoS One. 2008;3(4):e1991.CrossRefGoogle Scholar
  30. 30.
    Asghar R, Banajeh S, Egas J, Hibberd P, Iqbal I, Katep-Bwalya M, et al. Chloramphenicol versus ampicillin plus gentamicin for community acquired very severe pneumonia among children aged 2-59 months in low resource settings: multicentre randomised controlled trial (SPEAR study). BMJ. 2008;336(7635):80–4.CrossRefGoogle Scholar
  31. 31.
    Duke T, Poka H, Dale F, Michael A, Mgone J, Wal T. Chloramphenicol versus benzylpenicillin and gentamicin for the treatment of severe pneumonia in children in Papua New Guinea: a randomised trial. Lancet Lond Engl. 2002;359(9305):474–80.CrossRefGoogle Scholar
  32. 32.
    Williams DJ, Hall M, Shah SS, Parikh K, Tyler A, Neuman MI, et al. Narrow vs broad-spectrum antimicrobial therapy for children hospitalized with pneumonia. Pediatrics. 2013;132(5):e1141–8.CrossRefGoogle Scholar
  33. 33.
    • Breuer O, Blich O, Cohen-Cymberknoh M, Averbuch D, Kharasch S, Shoseyov D, et al. Antibiotic treatment for children hospitalized with community-acquired pneumonia after oral therapy. Pediatr Pulmonol. 2015;50(5):495–502.CrossRefGoogle Scholar
  34. 34.
    • Williams DJ, Edwards KM, Self WH, Zhu Y, Arnold SR, McCullers JA, et al. Effectiveness of β-lactam monotherapy vs macrolide combination therapy for children hospitalized with pneumonia. JAMA Pediatr. 2017;171(12):1184–91. These articles showed the role of macrolides in children with community acquired pneumonia requiring hospitalization in combination with usual empirical antibiotic therapy. CrossRefGoogle Scholar
  35. 35.
    Dekate PS, Mathew JL, Jayashree M, Singhi SC. Acute community acquired pneumonia in emergency room. Indian J Pediatr. 2011;78(9):1127–35.CrossRefGoogle Scholar
  36. 36.
    •• Lodha R, Randev S, Kabra SK. Oral antibiotics for community acquired pneumonia with chest indrawing in children aged below five years: a systematic review. Indian Pediatr. 2016;53(6):489–95. This article documents that oral amoxicillin can be used in children with severe pneumonia having chest retractions but without hypoxia. CrossRefGoogle Scholar
  37. 37.
    Hoban DJ, Reinert RR, Bouchillon SK, Dowzicky MJ. Global in vitro activity of tigecycline and comparator agents: tigecycline evaluation and surveillance trial 2004-2013. Ann Clin Microbiol Antimicrob. 2015;14:27.CrossRefGoogle Scholar
  38. 38.
    EUCAST: Clinical breakpoints [Internet]. [cited 2018 Apr 18]. Available from: http://www.eucast.org/clinical_breakpoints/.
  39. 39.
    Yu VL, Chiou CCC, Feldman C, Ortqvist A, Rello J, Morris AJ, et al. An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis. 2003;37(2):230–7.CrossRefGoogle Scholar
  40. 40.
    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):1567–74.CrossRefGoogle Scholar
  41. 41.
    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.CrossRefGoogle Scholar
  42. 42.
    Widdowson CA, Klugman KP. Molecular mechanisms of resistance to commonly used non-betalactam drugs in Streptococcus pneumoniae. Semin Respir Infect. 1999;14(3):255–68.PubMedGoogle Scholar
  43. 43.
    Jinno S, Jacobs MR. Pneumonia due to drug-resistant Streptococcus pneumoniae. Curr Infect Dis Rep. 2012;14(3):292–9.CrossRefGoogle Scholar
  44. 44.
    Galli L, Montagnani C, Chiappini E, de Martino M. Treating paediatric community-acquired pneumonia in the era of antimicrobial resistance. Acta Paediatr Oslo Nor 1992. 2013;102(465):25–33.Google Scholar
  45. 45.
    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 N Am. 2013;27(1):177–88.CrossRefGoogle Scholar
  46. 46.
    Chavanet P. The ZEPHyR study: a randomized comparison of linezolid and vancomycin for MRSA pneumonia. Med Mal Infect. 2013;43(11–12):451–5.CrossRefGoogle Scholar
  47. 47.
    Sicot N, Khanafer N, Meyssonnier V, Dumitrescu O, Tristan A, Bes M, 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):E142–8.CrossRefGoogle Scholar
  48. 48.
    Pertel PE, Bernardo P, Fogarty C, Matthews P, Northland R, Benvenuto M, et al. Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin Infect Dis. 2008;46(8):1142–51.CrossRefGoogle Scholar
  49. 49.
    Suzuko U, Keisuke S, Hiroyuki E, OuchiKazunobu OK, Tomomichi K, et al. Japanese guidelines for the management of respiratory infectious diseases in children 2007 with focus on pneumonia. Pediatr Int. 2011;53(2):264–76.CrossRefGoogle Scholar
  50. 50.
    Cao B, Qu J-X, Yin Y-D, Eldere JV. Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance. Clin Respir J. 2015;11(4):419–29.CrossRefGoogle Scholar
  51. 51.
    Lee H, Yun KW, Lee HJ, Choi EH. Antimicrobial therapy of macrolide-resistant Mycoplasma pneumoniae pneumonia in children. Expert Rev Anti-Infect Ther. 2018;16(1):23–34.CrossRefGoogle Scholar
  52. 52.
    Ishiguro N, Koseki N, Kaiho M, Ariga T, Kikuta H, Togashi T, et al. Therapeutic efficacy of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant and macrolide-sensitive mycoplasma pneumoniae pneumonia in pediatric patients. PLoS One. 2017;12(3):e0173635.CrossRefGoogle Scholar
  53. 53.
    File TM, Low DE, Eckburg PB, Talbot GH, Friedland HD, Lee J, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftarolinefosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin Infect Dis. 2010;51(12):1395–405.CrossRefGoogle Scholar
  54. 54.
    English ML, Fredericks CE, Milanesio NA, Rohowsky N, Xu Z-Q, Jenta TRJ, et al. Cethromycin versus clarithromycin for community-acquired pneumonia: comparative efficacy and safety outcomes from two double-blinded, randomized, parallel-group, multicenter, multinational noninferiority studies. Antimicrob Agents Chemother. 2012;56(4):2037–47.CrossRefGoogle Scholar
  55. 55.
    • Barrera CM, Mykietiuk A, Metev H, Nitu MF, Karimjee N, Doreski PA, et al. 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):421–30.CrossRefGoogle Scholar
  56. 56.
    • Sun H, Ting L, Machineni S, Praestgaard J, Kuemmell A, Stein DS, et al. Randomized, open-label study of the pharmacokinetics and safety of oral and intravenous administration of omadacycline to healthy subjects. Antimicrob Agents Chemother. 2016;60(12):7431–5.PubMedPubMedCentralGoogle Scholar
  57. 57.
    • Eyal Z, Matzov D, Krupkin M, Paukner S, Riedl R, Rozenberg H, et al. A novel pleuromutilin antibacterial compound, its binding mode and selectivity mechanism. Sci Rep. 2016;6:39004.CrossRefGoogle Scholar
  58. 58.
    • Liu Y, Zhang Y, Wu J, Zhu D, Sun S, Zhao L, et al. A randomized, double-blind, multicenter phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia. J Microbiol Immunol Infect. 2017;50(6):811–20.CrossRefGoogle Scholar
  59. 59.
    • Rhee CK, Chang JH, Choi EG, Kim HK, Kwon Y-S, Kyung SY, et al. Zabofloxacin versus moxifloxacin in patients with COPD exacerbation: a multicenter, double-blind, double-dummy, randomized, controlled, phase III, non-inferiority trial. Int J Chron Obstruct Pulmon Dis. 2015;10:2265–75.CrossRefGoogle Scholar
  60. 60.
    Nannini EC, Corey GR, Stryjewski ME. Telavancin for the treatment of hospital-acquired pneumonia: findings from the ATTAIN studies. Expert Rev Anti-Infect Ther. 2012;10(8):847–54.CrossRefGoogle Scholar
  61. 61.
    Pfaller MA, Mendes RE, Sader HS, Jones RN. Telavancin activity against gram-positive bacteria isolated from respiratory tract specimens of patients with nosocomial pneumonia. J Antimicrob Chemother. 2010;65(11):2396–404.CrossRefGoogle Scholar
  62. 62.
    • Liapikou A, Cillóniz C, Torres A. Investigational drugs in phase I and phase II clinical trials for the treatment of community-acquired pneumonia. Expert OpinInvestig Drugs. 2017;26(11):1239–48. Articles 61-66 and 68 describe the various new drugs available to treat multidrug-resistant community-acquired pneumonia. However, their efficacy and safety in pediatric population still needs to be established. CrossRefGoogle Scholar
  63. 63.
    Lee Y, Hong SK, Choi S, Im W, Yong D, Lee K. In vitro activity of tedizolid against gram-positive bacteria in patients with skin and skin structure infections and hospital-acquired pneumonia: a Korean multicenter study. Ann Lab Med. 2015;35(5):523–30.CrossRefGoogle Scholar
  64. 64.
    Boucher HW, Talbot GH, Benjamin DK, Bradley J, Guidos RJ, Jones RN, et al. 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):1685–94.CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of PediatricsAll India Institute of Medical SciencesNew DelhiIndia

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