Volume : 09, Issue : 03, March – 2022

Title:

21.A CLOSER LOOK AT ANTIBIOTIC RESISTANCE IN CHILDREN

Authors :

Parveen Kausar Iqbal, Kaneez Fatima, Tahira Shaheen

Abstract :

Antibiotic resistance is a potential threat to the public wellbeing, especially in children: According to WHO surveys, death toll associated with multidrug resistant organism is 700,000 across all ages, of which around 200,000 are infants. This soaring issue has multidimensional linkages that are specific to the pediatric age group. For example, the indiscriminate abuse and misuse of antibiotics (for nascent diagnoses and indications, or at erroneous dosing) is caused by the lack of evidence based time-tested trials in paediatrics. The dynamic nature of this age group also renders another hazard which is associated with the age-dependent modifications in the drug metabolism system (cytochrome machinery) leading to weight and dose dependent efficacy. The pediatric age group has also been inflicted by the adversities of tetracycline and fluoroquinolones, and by congenital malformations which prompt frequent hospitalization involving invasive and pharmacological interventions from the time of birth. Emerging challenges for the pediatric age are MRSA, VRSA, ESBL-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae and the devastating colistin resistance. (Super-bugs). Radical measures need to be taken in order to prevent the advent of an era where a simple infection might lead to a life catastrophe.
Keywords: multidrug resistance; antibiotics; micro-organsms; superbugs; antibiotic resistance; childhood; infections; antimicrobial stewardship

Cite This Article:

Please cite this article in press Parveen Kausar Iqbal et al, A Closer Look At Antibiotic Resistance In Children., Indo Am. J. P. Sci, 2022; 09(3),.

Number of Downloads : 10

References:

1. Fight Antimicrobial Resistance: Protect Mothers and Newborns. In 4th Global Conference of Women Deliver; WHO Regional Office for Europe: Copenhagen, Denmark, 2016; Available online: http://who.int/drugresistance/activities/Women-Deliver-AMRside-event-Handout-May2016.pdf?ua=1 (accessed on 19 March 2021).
2. Cassini, A.; Högberg, L.D.; Plachouras, D.; Quattrocchi, A.; Hoxha, A.; Simonsen, G.S.; Colomb-Cotinat, M.; Kretzschmar, M.E.; Devleesschauwer, B.; Cecchini, M.; et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: A population-level modelling analysis. Lancet Infect. Dis. 2019, 19, 56–66. [CrossRef]
3. Al Jarousha, A.M.; El Jadba, A.H.; Al Afifi, A.S.; El Qouqa, I.A. Nosocomial multidrug-resistant Acinetobacter baumannii in the neonatal intensive care unit in Gaza City, Palestine. Int. J. Infect. Dis. 2009, 13, 623–628. [CrossRef]
4. Le Doare, K.; Barker, C.I.; Irwin, A.; Sharland, M. Improving antibiotic prescribing for children in the resource-poor setting. Br. J. Clin. Pharmacol. 2015, 79, 446–455. [CrossRef]
5. Okomo, U.; Akpalu, E.N.K.; Le Doare, K.; Roca, A.; Cousens, S.; Jarde, A.; Sharland, M.; Kampmann, B.; Lawn, J.E. Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: A systematic review and meta-analysis in line with the STROBE-NI reporting guidelines. Lancet Infect. Dis. 2019, 19, 1219–1234. [CrossRef]
6. Tamma, P.D.; Newland, J.G.; Pannaraj, P.S.; Metjian, T.A.; Banerjee, R.; Gerber, J.S.; Weissman, S.J.; Beekmann, S.E.; Polgreen, P.M.; Hersh, A.L. The use of intravenous colistin among children in the United States: Results from a multicenter, case series. Pediatr Infect. Dis. J. 2013, 32, 17–22. [CrossRef]
7. Naylor, N.R.; Atun, R.; Zhu, N.; Kulasabanathan, K.; Silva, S.; Chatterjee, A.; Knight, G.M.; Robotham, J.V. Estimating the burden of antimicrobial resistance: A systematic literature review. Antimicrob. Resist. Infect. Control. 2018, 7, 58. [CrossRef]
8. Travers, K.; Barza, M. Morbidity of infections caused by antimicrobial-resistant bacteria. Clin. Infect. Dis. 2002, 34, S131–S134. [CrossRef]
9. Meropol, S.B.; Haupt, A.A.; Debanne, S.M. Incidence and Outcomes of Infections Caused by Multidrug-Resistant Enterobacteriaceae in Children, 2007–2015. J. Pediatric Infect. Dis. Soc. 2018, 7, 36–45. [CrossRef]
10. Barrasa-Villar, J.I.; Aibar-Remón, C.; Prieto-Andrés, P.; Mareca-Doñate, R.; Moliner-Lahoz, J. Impact on Morbidity, Mortality, and Length of Stay of Hospital-Acquired Infections by Resistant Microorganisms. Clin. Infect. Dis. 2017, 65, 644–652. [CrossRef]
11. Johnston, K.J.; Thorpe, K.E.; Jacob, J.T.; Murphy, D.J. The incremental cost of infections associated with multidrug-resistant organisms in the inpatient hospital setting—A national estimate. Health Serv. Res. 2019, 54, 782–792. [CrossRef]
12. Mauldin, P.D.; Salgado, C.D.; Hansen, I.S.; Durup, D.T.; Bosso, J.A. Attributable hospital cost and length of stay associated with health care-associated infections caused by antibiotic-resistant gram-negative bacteria. Antimicrob. Agents Chemother. 2010, 54, 109–115. [CrossRef] [PubMed]
13. Ventola, C.L. The antibiotic resistance crisis: Part 1: Causes and threats. Pharm. Ther. 2015, 40, 277–283.
14. Davies, J.; Davies, D. Origins and evolution of antibiotic resistance. Microbiol. Mol. Biol. Rev. 2010, 74, 417–433. [CrossRef] 15. Luyt, C.E.; Bréchot, N.; Trouillet, J.L.; Chastre, J. Antibiotic stewardship in the intensive care unit. Crit. Care 2014, 18, 480. [CrossRef] [PubMed]
16. CDC Report: Antibiotic Resistance Threats in the United States. 2013. Available online: https://www.cdc.gov/drugresistance/ pdf/ar-threats-2013-508.pdf (accessed on 5 April 2021).
17. Fridkin, S.K.; Hageman, J.; McDougal, L.K.; Mohammed, J.; Jarvis, W.R.; Perl, T.M.; Tenover, F.C. Vancomycin-Intermediate Staphylococcus aureus Epidemiology Study Group. Epidemiological and microbiological characterization of infections caused by Staphylococcus aureus with reduced susceptibility to vancomycin, United States, 1997–2001. Clin. Infect. Dis. 2003, 36, 429–439. [CrossRef]
18. Long, S.W.; Olsen, R.J.; Mehta, S.C.; Palzkill, T.; Cernoch, P.L.; Perez, K.K.; Musick, W.L.; Rosato, A.E.; Musser, J.M. PBP2a mutations causing high-level Ceftaroline resistance in clinical methicillin-resistant Staphylococcus aureus isolates. Antimicrob. Agents Chemother. 2014, 58, 6668–6674. [CrossRef] [PubMed]
19. Eck, A.; Rutten, N.B.M.M.; Singendonk, M.M.J.; Rijkers, G.T.; Savelkoul, P.H.M.; Meijssen, C.B.; Crijns, C.E.; Oudshoorn, J.H.; Budding, A.E.; Vlieger, A.M. Neonatal microbiota development and the effect of early life antibiotics are determined by two distinct settler types. PLoS ONE 2020, 15, e0228133. [CrossRef] [PubMed]
20. Chong, C.Y.L.; Bloomfield, F.H.; O’Sullivan, J.M. Factors Affecting Gastrointestinal Microbiome Development in Neonates. Nutrients 2018, 10, 274. [CrossRef]
21. Goossens, H.; Ferech, M.; Vander, S.R.; Elseviers, M. ESAC Project Group. Outpatient antibiotic use in Europe and association with resistance: A cross-national database study. Lancet 2005, 365, 579–587. [CrossRef]
22. Chung, A.; Perera, R.; Brueggemann, A.B.; Elamin, A.E.; Harnden, A.; Mayon-White, R.; Smith, S.; Crook, D.W.; Mant, D. Effect of antibiotic prescribing on antibiotic resistance in individual children in primary care: Prospective cohort study. BMJ 2007, 335, 429.[CrossRef]
23. Nicolini, G.; Donà, D.; Mion, T.; Barlotta, A.; Girotto, S.; Borgia, E.; Franceschetto, G.; Scamarcia, A.; Picelli, G.; Cantarutti, L.; et al. Use of amoxicillin, amoxicillin/calvulanate and cefaclor in the Italian pediatric population. J. Pediatr. Infect. Dis. 2013, 9, 1 – 9.[CrossRef]
24. Taylor, B.; Fergusson, D.; Abbott, G.D. Antibiotics for presumed viral respiratory infections. Br. Med. J. 1977, 2, 1290–1291. [CrossRef]
25. Harnden, A.; Perera, R.; Brueggemann, A.B.; Mayon-White, R.; Crook, D.W.; Thomson, A.; Mant, D. Respiratory infections for which general practitioners consider prescribing an antibiotic: A prospective study. Arch. Dis. Child. 2007, 92, 594–597. [CrossRef]
26. Levy, E.R.; Swami, S.; Dubois, S.G.; Wendt, R.; Banerjee, R. Rates and appropriateness of antimicrobial prescribing at an academic children’s hospital, 2007–2010. Infect. Control. Hosp. Epidemiol 2012, 33, 346–353. [CrossRef] [PubMed]
27. Apisarnthanarak, A.; Bhooanusas, N.; Yaprasert, A.; Mundy, L.M. Carbapenem de-escalation therapy in a resource-limited setting. Infect. Control. Hosp. Epidemiol. 2013, 34, 1310–1313. [CrossRef] [PubMed]
28. van den Anker, J.N.; Schoemaker, R.C.; Hop, W.C.; van der Heijden, B.J.; Weber, A.; Sauer, P.J.; Neijens, H.J.; de Groot, R. Ceftazidime pharmacokinetics in preterm infants: Effects of renal function and gestational age. Clin. Pharmacol. Ther. 1995, 58, 650–659. [CrossRef]
29. Meibohm, B.; Läer, S.; Panetta, J.C.; Barrett, J.S. Population pharmacokinetic studies in pediatrics: Issues in design and analysis. AAPS J. 2005, 7, E475–E487. [CrossRef]
30. Guidance for Industry: General Considerations for Pediatric Pharmacokinetic Studies for Drugs and Biological Products. Available online: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-clinicalpharmacology-considerations-pediatric-studies-drugs-and-biological-products (accessed on 5 April 2021).
31. Manolis, E.; Osman, T.E.; Herold, R.; Koenig, F.; Tomasi, P.; Vamvakas, S.; Saint, R.A. Role of modeling and simulation in pediatric investigation plans. Paediatr. Anaesth. 2011, 21, 214–221. [CrossRef] [PubMed]
32. Bouzom, F.; Walther, B. Pharmacokinetic predictions in children by using the physiologically based pharmacokinetic modelling. Fundam. Clin. Pharmacol. 2008, 22, 579–587. [CrossRef] [PubMed]
33. Johnson, T.N.; Rostami-Hodjegan, A. Resurgence in the use of physiologically based pharmacokinetic models in pediatric clinical pharmacology: Parallel shift in incorporating the knowledge of biological elements and increased applicability to drug development and clinical practice. Paediatr. Anaesth. 2011, 21, 291–301. [CrossRef]
34. Zhao, P.; Zhang, L.; Grillo, J.A.; Liu, Q.; Bullock, J.M.; Moon, Y.J.; Song, P.; Brar, S.S.; Madabushi, R.; Wu, T.C.; et al. Applications of physiologically based pharmacokinetic (PBPK) modeling and simulation during regulatory review. Clin. Pharmacol. Ther. 2011,89, 259–267. [CrossRef]
35. American Academy of Pediatrics Committee on Infectious Diseases. The use of systemic fluoroquinolones. Pediatrics 2006, 118, 1287–1292. [CrossRef] [PubMed]
36. Bradley, J.S.; Jackson, M.A. Committee on Infectious Diseases, American Academy of Pediatrics. The use of systemic and topical fluoroquinolones. Pediatrics 2011, 128, e1034–e1045. [CrossRef] [PubMed]
37. Jackson, M.A.; Schutze, G.E. Committee on Infectious Diseases. The Use of Systemic and Topical Fluoroquinolones. Pediatrics 2016, 138, e20162706. [CrossRef]
38. Gilman, A.; Rall, T.W.; Nies, A.S.; Taylor, P. (Eds.) The Pharmacological Basis of Therapeutics, 8th ed.; Pergamon Press: New York, NY, USA, 1990; pp. 1117–1118.
39. Conchie, J.M.; Munroe, J.D.; Anderson, D.O. The incidence of staining of permanent teeth by the tetracyclines. Can. Med. Assoc. J. 1970, 103, 351–356.
40. Pickering, L.K.; Baker, C.J.; Kimberlin, D.W.; Long, S.S. Tetracyclines. In Red Book: 2009 Report of the Committee on Infectious Diseases, 28th ed.; American Academy of Pediatrics: Elk Grove Village, IL, USA, 2009; p. 739.
41. Shigeta, M.; Tanaka, G.; Komatsuzawa, H.; Sugai, M.; Suginaka, H.; Usui, T. Permeation of antimicrobial agents through Pseudomonas aeruginosa biofilms: A simple method. Chemotherapy 1997, 43, 340–345. [CrossRef]
42. Zhang, T.C.; Bishop, P.L. Evaluation of substrate and pH effects in a nitrifying biofilm. Wat. Environ. Res. 1996, 68, 1107–1115. [CrossRef]
43. Cochran, W.L.; Suh, S.J.; McFeters, G.A.; Stewart, P.S. Role of RpoS and AlgT in Pseudomonas aeruginosa biofilm resistance to hydrogen peroxide and monochloramine. J. Appl. Microbiol. 2000, 88, 546–553. [CrossRef]
44. Torretta, S.; Drago, L.; Marchisio, P.; Ibba, T.; Pignataro, L. Role of Biofilms in Children with Chronic Adenoiditis and Middle Ear Disease. J. Clin. Med. 2019, 8, 671. [CrossRef]
45. Zuliani, G.; Carron, M.; Gurrola, J.; Coleman, C.; Haupert, M.; Berk, R.; Coticchia, J. Identification of adenoid biofilms in chronic rhinosinusitis. Int. J. Pediatr. Otorhinolaryngol. 2006, 70, 1613–1617. [CrossRef]
46. Perault, A.I.; Chandler, C.E.; Rasko, D.A.; Ernst, R.K.; Wolfgang, M.C.; Cotter, P.A. Host Adaptation Predisposes Pseudomonas aeruginosa to Type VI Secretion System-Mediated Predation by the Burkholderia cepacia Complex. Cell Host Microbe. 2020, 28, 534–547. [CrossRef]
47. Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics. Available online: https://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf (accessed on 5 April 2021).
48. Herold, B.C.; Immergluck, L.C.; Maranan, M.C.; Lauderdale, D.S.; Gaskin, R.E.; Boyle-Vavra, S.; Leitch, C.D.; Daum, R.S. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA 1998, 279, 593–598. [CrossRef]
49. Sutter, D.E.; Milburn, E.; Chukwuma, U.; Dzialowy, N.; Maranich, A.M.; Hospenthal, D.R. Changing Susceptibility of Staphylococcus aureus in a US Pediatric Population. Pediatrics 2016, 137, e20153099. [CrossRef] [PubMed]
50. McNeil, J.C.; Hulten, K.G.; Kaplan, S.L.; Mason, E.O. Mupirocin resistance in Staphylococcus aureus causing recurrent skin and soft tissue infections in children. Antimicrob. Agents Chemother. 2011, 55, 2431–2433. [CrossRef] [PubMed]
51. Hiramatsu, K.; Hanaki, H.; Ino, T.; Yabuta, K.; Oguri, T.; Tenover, F.C. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J. Antimicrob. Chemother. 1997, 40, 135–136. [CrossRef]
52. Long, S.S.; Prober, C.G.; Fischer, M. (Eds.) Principles and Practice of Pediatric Infectious Diseases, 5th ed.; Staphylococcus aureus; Elsevier Saunders: Philadelphia, PA, USA, 2017; pp. 692–706.
53. Pani, A.; Colombo, F.; Agnelli, F.; Frantellizzi, V.; Baratta, F.; Pastori, D.; Scaglione, F. Off-label use of ceftaroline fosamil: A systematic review. Int. J. Antimicrob. Agents. 2019, 54, 562–571. [CrossRef]
54. Dortet, L.; Poirel, L.; Nordmann, P. Worldwide dissemination of the NDM-type carbapenemases in Gram-negative bacteria. Biomed. Res. Int. 2014, 2014, 249856. [CrossRef] [PubMed]
55. Zerr, D.M.; Miles-Jay, A.; Kronman, M.P.; Zhou, C.; Adler, A.L.; Haaland, W.; Weissman, S.J.; Elward, A.; Newland, J.G.; Zaoutis, T. Previous Antibiotic Exposure Increases Risk of Infection with Extended-Spectrum-β-Lactamase- and AmpC-Producing Escherichia coli and Klebsiella pneumoniae in Pediatric Patients. Antimicrob. Agents Chemother. 2016, 60, 4237–4243. [CrossRef] [PubMed]
56. Zerr, D.M.; Weissman, S.J.; Zhou, C.; Kronman, M.P.; Adler, A.L.; Berry, J.E.; Rayar, J.; Myers, J.; Haaland, W.L.; Burnham, C.D.; et al. The Molecular and Clinical Epidemiology of Extended-Spectrum Cephalosporin- and Carbapenem-Resistant Enterobacteriaceae at 4 US Pediatric Hospitals. J. Pediatric. Infect. Dis. Soc. 2017, 6, 366–375. [CrossRef] [PubMed]
57. Topaloglu, R.; Er, I.; Dogan, B.G.; Bilginer, Y.; Ozaltin, F.; Besbas, N.; Ozen, S.; Bakkaloglu, A.; Gur, D. Risk factors in communityacquired urinary tract infections caused by ESBL-producing bacteria in children. Pediatr. Nephrol. 2010, 25, 919–925. [CrossRef]
58. Logan, L.K.; Renschler, J.P.; Gandra, S.; Weinstein, R.A.; Laxminarayan, R. Centers for Disease Control; Prevention Epicenters Program. Carbapenem-Resistant Enterobacteriaceae in Children, United States, 1999–2012. Emerg. Infect. Dis. 2015, 21, 2014–2021. [CrossRef] [PubMed]
59. Hsu, A.J.; Tamma, P.D. Treatment of multidrug-resistant Gram-negative infections in children. Clin. Infect. Dis. 2014, 58, 1439–1448. [CrossRef] [PubMed]
60. Paterson, D.L. Resistance in gram-negative bacteria: Enterobacteriaceae. Am. J. Med. 2006, 119, S20–S70. [CrossRef]
61. Lee, C.Y.; Chen, P.Y.; Huang, F.L.; Lin, C.F. Microbiologic spectrum and susceptibility pattern of clinical isolates from the pediatric intensive care unit in a single medical center-6 years’ experience. J. Microbiol. Immunol. Infect. 2009, 42, 160–165. [PubMed]
62. Koch-Weser, J.; Sidel, V.W.; Federman, E.B.; Kanarek, P.; Finer, D.C.; Eaton, A.E. Adverse effects of sodium colistimethate. Manifestations and specific reaction rates during 317 courses of therapy. Ann. Intern. Med. 1970, 72, 857–868. [CrossRef]
63. Sarkar, S.; DeSantis, E.R.; Kuper, J. Resurgence of colistin use. Am. J. Health Syst. Pharm. 2007, 64, 2462–2466. [CrossRef]
64. Liu, Y.Y.; Wang, Y.; Walsh, T.R.; Yi, L.X.; Zhang, R.; Spencer, J.; Doi, Y.; Tian, G.; Dong, B.; Huang, X.; et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study. Lancet Infect. Dis. 2016, 16, 161–168. [CrossRef]
65. Society for Healthcare Epidemiology of America; Infectious Diseases Society of America; Pediatric Infectious Diseases Society. Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infect. Control. Hosp. Epidemiol. 2012, 33,322–327. [CrossRef]
66. EMA: Guideline on the Role of Pharmacokinetics on the Development of Medicinal Products for the Paediatric Population. Available online: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-role-pharmacokinetics-development-medicinalproducts-paediatric-population_en.pdf (accessed on 5 April 2021).
67. Ellington, M.J.; Ekelund, O.; Aarestrup, F.M.; Canton, R.; Doumith, M.; Giske, C.; Grundman, H.; Hasman, H.; Holden, M.T.G.; Hopkins, K.L.; et al. The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria: Report from the EUCAST Subcommittee. Clin. Microbiol Infect. 2017, 23, 2–22. [CrossRef]
68. US Food and Drug Administration Clinical Review. Available online: https://www.fda.gov/files/drugs/published/N200327S0 160—17-Ceftaroline-fosamil-Clinical-PREA.pdf (accessed on 22 March 2021).
69. European Medicines Agency Ceftaroline Fosamil. Available online: https://www.ema.europa.eu/en/documents/productinformation/zinforo-epar-product-information_en.pdf (accessed on 22 March 2021).
70. NDA Multi-Disciplinary Review and Evaluation–NDA 206494 Supplements 005 and 006 AVYCAZ (ceftazidime/avibactam) for injection. Available online: https://www.fda.gov/media/124307/download (accessed on 22 March 2021).
71. Larson, K.B.; Patel, Y.T.; Willavize, S.; Bradley, J.S.; Rhee, E.G.; Caro, L.; Matthew, L.; Rizk, M.L. Ceftolozane-Tazobactam Population Pharmacokinetics and Dose Selection for Further Clinical Evaluation in Pediatric Patients with Complicated Urinary Tract or Complicated Intra-abdominal Infections. Antimicrob. Agents Chemother. 2019, 63, e02578-e18. [CrossRef]
72. Roch, M.; Varela, M.C.; Taglialegna, A.; Rosato, A.E. Tedizolid is a promising antimicrobial option for the treatment of Staphylococcus aureus infections in cystic fibrosis patients. J. Antimicrob. Chemother. 2020, 75, 126–134. [CrossRef] [PubMed]
73. Gonzalez, D.; Bradley, J.S.; Blumer, J.; Yogev, R.; Watt, K.M.; James, L.P.; Palazzi, D.L.; Bhatt-Mehta, V.; Sullivan, J.E.; Zhang, L.; et al. Dalbavancin Pharmacokinetics and Safety in Children 3 Months to 11 Years of Age. Pediatr. Infect. Dis. J. 2017, 36, 645–653. [CrossRef] [PubMed]