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An Introduction to childhood Kingella Kingae infections

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What is kingella kingae bacterium,features of K. kingae,Species of Kingella,epidemiology of k. kingae,Proposed pathogenesis of K. kingae infections,Transmission of k. kingae ,Pathegenesis of k. kingae,diagnosis ,NAAT for k.kingae ,treatment of k.kingae,prevension ,osteomyelitis due to k,kingae.endocarditis due to k.kingae,Septic Arthritis due to k. kingae,Spondylodiscitis due to k. kingae, prevention of k. kingae infection

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An Introduction to childhood Kingella Kingae infections

  1. 1. An Introduction to childhood Kingella Kingae infections Prof. Dr. Saad S Al Ani Prof. of Pediatrics Senior Pediatric consultant Saad’s Kids Clinic anahbaghdad@gmail.com
  2. 2. Introduction Kingella kingae: A type of bacteria that has emerged from obscurity to become known as an important cause of invasive infections in young children 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 2
  3. 3. Kingella kingae •Fastidious •Facultative anaerobic •β-hemolytic •Appears as pairs or short chains of gram-negative coccobacilli with tapered ends •Member of the Neisseriaceae family 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 3 https://www.researchgate.net/publication/233671839_Kingella_kingae_A_Pediatric_Pathogen_of_Increasing_Importance
  4. 4. K. kingae is a recognized commensal in the oropharynx of young children particularly in ages 6 to 48 months 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 4 El Houmami N, Minodier P, Dubourg G, et al. An outbreak of Kingella kingae infections associated with hand, foot and mouth disease/herpangina virus outbreak in Marseille, France, 2013. Pediatr Infect Dis J. 2015;34(3):246–250
  5. 5. The clinical presentation of disease due to Kingella kingae is often subtle so that making the diagnosis requires a high index of suspicion. 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 5
  6. 6. Species of Kingella There are four species of Kingella: • K. kingae, the most common, is part of the bacterial flora • K. indologenes, K. denitrificans both causing endocarditis • K. oralis found in dental plaque 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 6 https://en.wikipedia.org/wiki/Kingella_kingae
  7. 7. Routine laboratory tests may be normal because the organism is difficult to culture 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 7 https://en.wikipedia.org/wiki/Kingella_kingae
  8. 8. Epidemiology • Asymptomatically carried in the posterior pharynx • Colonization: Usually starts after age 6 months Reaches a prevalence of 10% between 12 and 24 months Decreases in older children 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 8
  9. 9. Proposed pathogenesis of K. kingae infections 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 9 https://go.gale.com
  10. 10. Associated infections K. kingae invasive infections have been associated with: • Hand-foot-mouth disease • Herpes simplex virus causing stomatitis • Varicella zoster virus • Human rhinovirus 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 10 El Houmami N, Mirand A, Dubourg G, et al. Hand, foot and mouth disease and Kingella kingae infections. Pediatr Infect Dis J. 2015;34(5):547–548
  11. 11. Prerequisite for invasive disease which is commonly triggered by viral infections 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 11 El Houmami N, Minodier P, Dubourg G, et al. An outbreak of Kingella kingae infections associated with hand, foot and mouth disease/herpangina virus outbreak in Marseille, France, 2013. Pediatr Infect Dis J. 2015;34(3):246–250
  12. 12. Transmission • By close contact between young children • A recent reported increase in : Oropharyngeal carriage rates Outbreaks of invasive disease involving the skeletal system in day-care centers 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 12
  13. 13. Epidemiology (Cont.) Pharyngeal colonization plays a crucial role in the transmission of the organism through intimate contact between siblings and playmates 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 13
  14. 14. Epidemiology (Cont.) • Daycare attendance increases the risk for colonization and transmission • Clusters of invasive infection have been reported in childcare facilities 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 14
  15. 15. Epidemiology (Cont.) Invasive K. kingae disease is most frequently diagnosed in otherwise healthy children between ages 6 months and 3 yr, 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 15
  16. 16. Pathogenesis K. kingae by pili & nonpilus adhesin adherence of the organism to the pharyngeal epithelium 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 16
  17. 17. Pathogenesis (Cont.) 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 17 Gram-stain of a positive blood-culture vial from a child with K kingae bacteremia, which shows typical pairs and short chains of Gram-negative coccobacilli (gray arrows). RBCs indicates red blood cells. https://pediatrics.aappublications.org
  18. 18. Pathogenesis (Cont.) K. kingae secretes a potent Repeats-in-Toxin (RTX) toxin that exhibits deleterious activity to: – Respiratory epithelial cells – Macrophages – Synoviocytes 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 18
  19. 19. Repeats-in-Toxin (RTX) toxin Play a role in: – Disrupting the respiratory mucosa – Promoting survival of the bacterium in the bloodstream – Facilitating invasion of skeletal system tissues 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 19
  20. 20. Repeats-in-Toxin (RTX) toxin 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 20 ResearchGate
  21. 21. The frequent presentation of K. kingae disease 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 21 Upper respiratory infection Herpetic stomatitis Hand-foot-and- mouth disease Buccal aphthous ulcer suggesting that viral-induced damage to the colonized mucosal surface facilitates invasion of the bloodstream
  22. 22. Clinical presentation • Septic arthritis is the most common invasive K. kingae infection in children • followed by: Bacteremia Osteomyelitis Endocarditis 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 22
  23. 23. Clinical presentation (Cont.) K. Kingae is the most frequent etiology of skeletal system infections in children 6 months to 3 yr old in at least some countries 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 23
  24. 24. Clinical presentation (Cont.) • Invasive K. kingae infections is frequently mild (With the exception of patients with endocarditis) -body temperature <38°C - normal CRP Level - normal WBC count Are common 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 24
  25. 25. Clinical presentation (Cont.) K. kingae infections requiring a high index of clinical suspicion 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 25
  26. 26. Septic Arthritis • K. kingae –driven arthritis especially affects the large, weight-bearing joints • involvement of: -Small metacarpophalangeal -Sternoclavicular -Tarsal joints Is not unusual 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 26
  27. 27. Septic Arthritis 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 27 My Health Alberta - Alberta.ca
  28. 28. Septic Arthritis ( Cont.) • Is an acute presentation • Involvement of the hip joint resembles toxic synovitis • should be always suspected in children <4 yr old presenting with hip pain or a limp 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 28
  29. 29. Septic Arthritis ( Cont.) Synovial fluid : • <50,000 WBCs/µL in almost 25% of the patients, • The Gram stain is positive in only a small percentage of cases 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 29
  30. 30. Septic Arthritis ( Cont.) 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 30 Digital Commons @ Otterbein - Otterbein University
  31. 31. Osteomyelitis K. kingae osteomyelitis usually involves the long bones of the extremities 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 31
  32. 32. Osteomyelitis (Cont.) 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 32 Journal of Clinical Microbiology - American Society for Microbiolo Knee X-ray analyses (anteroposterior [a] and lateral views) demonstrate a round lytic lesion (arrow) circled by a well- defined sclerotic margin (dotted arrow), located in the inferior metaphysis of the femur, adjacent to the physis (arrow). The lateral view also shows a unilamellar inferoanterior periosteal reaction (arrowhead).
  33. 33. Osteomyelitis (Cont.) The calcaneus, talus, sternum, and clavicle are also frequently affected (They are rarely infected by other bacterial pathogens) 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 33
  34. 34. Osteomyelitis (Cont.) • Insidious • Diagnosed after ≥1 week in 70% of patients. 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 34
  35. 35. Osteomyelitis (Cont.) • MRI shows mild bone and soft tissue changes • Involvement of the epiphyseal cartilage appears to be specifically associated with K. kingae 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 35
  36. 36. MRI of acute osteomyelitis in long bones of children 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 36 https://www.sciencedirect.com/science/article/pii/S1877056816300998
  37. 37. Osteomyelitis (Cont.) Chronic osteomyelitis and functional orthopedic disabilities are unusual 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 37
  38. 38. Spondylodiscitis K. kingae is the 2nd most common bacterium isolated in children <4 yr old with spondylodiscitis 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 38
  39. 39. Spondylodiscitis (Cont.) • Usually Involves the lumbar intervertebral spaces • Less frequency: - thoracolumbar - thoracic - lumbosacral -cervical disks 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 39 https://www.spineuniverse.com/anatomy/lumbar-spine
  40. 40. Spondylodiscitis (Cont.) presentation Limping Refusal to sit or walk Lumbar pain Neurologic symptoms Back stiffness Abdominal complaints 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 40
  41. 41. Spondylodiscitis (Cont.) MRI studies demonstrate narrowing of the intervertebral space 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 41 https://www.researchgate.net/publication/6731419_Kingella_kingae_spondylodiscitis_in_a_child
  42. 42. Spondylodiscitis (Cont.) • Respond well to appropriate antibiotic treatment • recover without complications 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 42
  43. 43. Occult Bacteremia Usually : mild to moderate fever, symptoms suggestive of a viral upper respiratory infection 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 43
  44. 44. Occult Bacteremia (Cont.) -Mean CRP level of 2.2 mg/dL -Mean WBC count of 12,700/µL. •Children with K. kingae bacteremia respond favorably to a short course of antibiotics 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 44
  45. 45. Endocarditis •The disease may affect native as well as prosthetic valves •Typically, the left side of the heart is involved, usually the mitral valve 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 45
  46. 46. Endocarditis(Cont.) •Predisposing factors include : -cardiac malformations or -rheumatic valvular disease •Some patients have previously normal hearts 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 46
  47. 47. Endocarditis(Cont.) Fever and acute-phase reactants are elevated more in patients with endocarditis than in those with uncomplicated bacteremia 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 47
  48. 48. Echo of an infant with K. kingae endocarditis 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 48 Yackov Berkun,et al.Kingella kingae endocarditis and sepsis in an infan. European Journal of Pediatrics volume 163, pages687– 688(2004)
  49. 49. Because of the potential severity of K. kingae endocarditis, routine echocardiographic evaluation of children with isolated bacteremia is indicated 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 49
  50. 50. Despite the exquisite susceptibility of K. kingae to antibiotics, complications are common 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 50
  51. 51. Endocarditis: Complications Cardiac failure Septic shock Cerebrovascular accident (stroke) Other life-threatening complications are common • Mortality rate is high ( >10% ) 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 51
  52. 52. Diagnosis • Isolation of the bacterium • Positive nucleic acid amplification test (NAAT); polymerase chain reaction PCR) from a normally sterile site such as blood, synovial fluid, or bone tissue 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 52
  53. 53. Diagnosis (Cont.) K. kingae grows on routine bacteriologic media BUT its recovery from exudates is frequently unsuccessful 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 53 https://alchetron.com/Kingella-kingae
  54. 54. Diagnosis (Cont.) Testing bone and joint specimens by NAAT that targets specific K. kingae genes results in a 4-fold improvement in the detection of the organism 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 54
  55. 55. Treatment K. kingae is usually highly susceptible to penicillin and cephalosporins but exhibits decreased susceptibility to oxacillin 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 55
  56. 56. Treatment (Cont.) First-line therapy for skeletal infections in young children : IV 2nd or 3rd generation cephalosporin , pending culture results 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 56
  57. 57. First-line therapy (Cont.) For skeletal infections in young children : IV 2nd or 3rd generation cephalosporin , pending culture results 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 57
  58. 58. Resistant of K. kingae To • Glycopeptide antibiotics (always) • Clindamycin (majority ) 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 58
  59. 59. Skeletal infections caused by community-associated methicillin- resistant S. aureus are common, So vancomycin or clindamycin are initially administered 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 59
  60. 60. Guide switching to oral antibiotics 1. Favorable clinical response 2. Decreasing CRP levels to ≤20 µg/mL 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 60
  61. 61. Antibiotic Treatment duration Antibiotic treatment for K. kingae has ranged from: 2-3 wks for arthritis 3-6 wks for osteomyelitis 3-12 wks for spondylodiscitis 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 61
  62. 62. Most patients respond promptly to conservative treatment with appropriate antibiotics and do not require invasive surgical procedures 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 62
  63. 63. Antibiotic Treatment K. kingae 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 63
  64. 64. Bacteremia without focal infection • Initially :an IV β-lactam antibiotic • Subsequently: an oral drug once the clinical condition has improved. • In most cases: duration of therapy is 1-2 wks 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 64
  65. 65. Endocarditis Usually treated with an IV β- lactam antibiotic alone or in combination with an aminoglycoside for 4-7 wks 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 65
  66. 66. Endocarditis (Cont.) Early surgical intervention is necessary for life-threatening complications unresponsive to medical therapy 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 66
  67. 67. Prevention The risk of asymptomatic pharyngeal carriers for developing an invasive K. kingae infection is low 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 67
  68. 68. Prevention (Cont.) If cases occur , SO prophylactic antibiotic therapy to eradicate colonization in contacts and prevent further cases of disease is indicated . 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 68
  69. 69. Prophylactic antibiotic therapy Either rifampin alone, 10 mg/kg or 20 mg/kg twice daily for 2 days, Or rifampin with amoxicillin (80 mg/kg/day) for 2 days or 4 days 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 69
  70. 70. 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 70 123FreeVectors
  71. 71. References • https://www.researchgate.net/publication/233671839_Kingella_kingae_A_Pediatric_Pathogen_of_Increasing_Impo rtance • El Houmami N, Minodier P, Dubourg G, et al. An outbreak of Kingella kingae infections associated with hand, foot and mouth disease/herpangina virus outbreak in Marseille, France, 2013. Pediatr Infect Dis J. 2015;34(3):246–250 • https://en.wikipedia.org/wiki/Kingella_kingae • https://go.gale.com • El Houmami N, Mirand A, Dubourg G, et al. Hand, foot and mouth disease and Kingella kingae infections. Pediatr Infect Dis J. 2015;34(5):547–548 • https://pediatrics.aappublications.org • https://www.sciencedirect.com/science/article/pii/S1877056816300998 • https://www.spineuniverse.com/anatomy/lumbar-spine • https://www.researchgate.net/publication/6731419_Kingella_kingae_spondylodiscitis_in_a_child • Yackov Berkun,et al.Kingella kingae endocarditis and sepsis in an infan. European Journal of Pediatrics volume 163, pages687–688(2004) • Yagupsky P, Dubnov-Raz G, Gené A, Ephros M, Israeli-Spanish Kingella kingae Research Group. Differentiating Kingella kingae septic arthritis of the hip from transient synovitis in young children. J Pediatr . 2014;165:985–989. • https://alchetron.com/Kingella-kingae • Dubnov-Raz G, Ephros M, Garty BZ, et al. Invasive pediatric Kingella kingae infections: a nationwide collaborative study. Pediatr Infect Dis J. 2010;29(7):639–643 • Yagupsky P. Kingella kingae: carriage, transmission, and disease. Clin Microbiol Rev. 2015;28(1):54–79 • http://drugline.org/medic/term/kingella-kingae • https://www.researchgate.net/publication/233671839_Kingella_kingae_A_Pediatric_Pathogen_of_Increasing_Impo rtance 25/10/2020Kingella kingae infections Prof. Dr. Saad S Al Ani 71

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