Principles of antibiotic therapy in paediatrics

1. Principles of antibiotic therapy in paediatrics Dr. György Fekete

2. Antibiotics 1. What is the reason? Indication? - local infection - empiric and targeted teatment - fever + general symptoms (CRP, WBC count and smear, etc.)

3. 2. Previous microbiological investigations? - throat - urine - haemoculture - cerebrospinal fluid

4. 3. What is the potential (bacterial) cause of infection? - age (newborn, infant, toddler…) - medical procedure, hospitalisation - immune deficiency - organ damage (spleen, liver, kidney)

5. Neonatal sepsis /meningitis • Focal infection: pneumonia, RDS • Group B streptococci, E. coli, other Gram-negative rods, Listeria monocytogenes • Th: Ampicillin+ gentamicin • third generation cephalosporin instead of aminoglycoside

6. Bacterial meningitis in children, 2months to 12 yrs • S. pneumoniae, N. meningitidis, (H. influenzae type b) Therapy: - cefotaxime / ceftriaxone + vancomycine - 3. generation cephalosporines (Cefotaxime, Ceftriaxone)

7. 4. Which antibiotic will be optimal? First choice? - data of bacterial resistance - site of infection – penetration? - side effects? - bactericide effect - administration: 1x / day - not expensive

8. 5. Any combination is appropriate? - nosocomial infection - sepsis - abdominal and pelvic infections - endocarditis - empiric treatment - active tuberculosis

9. Active tuberculosis • Treatment: INH, rifampin, pyrazinamide • Ethambutol, ethionamide

10. 6. Metabolism, excretion? - kidney, liver (monitoring) - renal: aminoglycosides - liver:erythromycin, clindomycin 7. Mode of administration - iv, oral - „switch”

12. 8. Dosage ? 9. Changing of antiobiotic drug? Indications? 10. How long should we treat? - Preterm and newborn babies need antibiotic therapy of longer duration (sepsis, bacterial meningitis, etc.)

13. Antimicrobial prophylaxis Neonatal conjunctivitis • Chlamydia trachomatis • 0,5% erythromycin topically • Neisseria gonorrhoeae • 1% silver nitrate or • 0,5% erythromycin topically

14. Antimicrobial prophylaxis • Splenectomy / asplenia • Str. pneumoniae • Penicillin

15. Resistant clones of microorganisms • Str. pneumoniae • Staph. aureus • Virulent • Serious infections • Overuse of antibiotics • Viral infections • Broad spectrum antimicrobial agents

16. Antibiotic management of Staphylococcus aureus infections in US Children’s hospitals, 1999-2008 • Trends in antibiotic management for S. aureus infections, hospitalized children • The use of vancomycin, clindamycin, linezolid, trimethoprim-sulfamethoxazole, cefazolin, and oxacillin/nafcillin were examined for percentage use and days of therapy per 1000 patient- day • 64 813 patients had a discharge diagnosis for S. aureus infection • The incidence of methicillin-resistant S. aureus (MRSA) infections increased 10-fold (2 to 21 cases per 1000 admissions), methicillin- susceptible infection rate remained stable • Clindamycin showed the greatest increase: 21% in 1999 and 63% in 2008 • Importance of continuous monitoring of local S. aureus susceptibility patterns Herigon J.C et al. Pediatrics 2010, 125:1267

17. Broad - spectrum antimicrobial agents • Drastic changes in bowel flora • Bleeding disorders • Emergence of resistant organisms • Superinfections: yeasts, enterococci

18. Local (hospital) microbiological laboratory • Knowing the prevalence of antibiotic – resistant organisms in a particular community (nursery) is helpful in choosing the first-line antibiotic regimens

19. Specific therapeutic values • Vancomycin: methicillin-resistant staphylococci • Metronidazole: anaerobic infections • Ceftazidine: Pseudomonas aeruginosa • Trimethoprime+ sulfamethoxazole: shigellosis, salmonellosis, Pneumocysis carinii ( pentamidine)

24. Test of efficacy= patient’s response • No respond to seemingly appropriate therapy: reassessment is needed! • In some infections additional supportive treatment ( surgical) is necessary

25. Tonsillitis, tonsillopharyngitis • Streptococcus pyogenes : Penicillin for 10 days • Penicillin allergy: macrolid antibiotics • Non- Streptococcus origin: amoxicillin, amoxicillin+ clavulanic acid, macrolids, cephalosporin antibiotics

26. Anaerobic infections • Oropharynx, gastrointestinal tract, vagina, skin • Gram- negative nonsporulating rods: Bacteroides, Fusobacterium • Gram-positive nosporulating rods: Eubacterium, Propionibacterium

27. Anaerobic infections • Neonates: prolonged rupture of membranes, amnionitis, obstetric difficulties • Peritonitis, appendicitis • Aspiration pneumonia with lung abscess • Orofacial infections • Brain abscess

28. Periodontal infection („trench mouth”)Acute Necrotizing Ulcerative Gingivitis ( ANUG) • Periapical abscesses • Anaerobic osteomyelitis of the mandible /maxilla

29. Vincent stomatitits • Ulcers covered by brown/grey, foul-smelling exudate

31. Ludwig angina • Acute cellulitis of the sublingual and submandibular spaces • Rapid spread • Edema of the tongue and airway

32. Anaerobic infections/ treatment • Cefoxitin, amoxicillin/ clavulanate, clindamycin • Metronidazole • Cefotetan • Imipenem, merapenem • Piperacillin, tazobactam

37. CEPHALOSPORIN ANTIBIOTICS 1. generation drugs Cefazolin (Kefzol) does not cross the blood- brain barrier. No use for initial th. of sepsis / meningitis Cefalexin (Keflex. Ospexin) Cefadoxil (Duracef)

38. 2. generation drugs Cefamandol (Mandokef) Cefuroxim (Zinnat, Zinacef) Cefoxitin (Mefoxin) Cefaclor (Ceclor)

39. 3. generation drugs Cefotaxim e (Claforan) Ceftriaxone (Rocephin) Cefoperazon (Cefobid) Ceftazidim ((Fortum) Cefixim (Suprax) Ceftibuten (Cedax)

40. 4. generation drug Cefepim (Maxipime)

41. Presentation • 7-year-old boy • 3 weeks of headache refractory to acetaminophen, 1 day of altered mental status, diplopia, photophobia • Physical examination: he is difficult to arouse and is confused. He vomits once in the ED. • No skin lesions, signs of meningeal irritation, or joint swelling. Bilateral papilledema and photophobia • WBC 15.8x109/L, 85% segmented neutrophils. Lumbar puncture, CSF sent for Lyme titers, serum antibodies: positive for IgG and negative for IgM • Th: 28 days IV ceftriaxone (100 mg/kg per day) • Additional questioning:2 months prior he had erythema migrans, was diagnosed as having Lyme disease, and was treated with 21 days of cefuroxime

42. PENICILLIN Penicillin G V Streptococcus procain-penicillin Str. pneumoniae

43. METHICILLIN Oxacillin Staphylococcus aureus Nafcillin

44. AMINOPENICILLIN (ampicillin , amoxicillin) Streptococcus B Str. pneumoniae Listeria

45. AMINOPENICILLIN beta+-lactamase respiratory , inhibitor urinary tract infections (ampicillin+sulfactam, amoxicillin+clavulanic acid)

46. UREIDOPENICILLIN mezlocillin, piperacillin (+beta-lactamase inhibitor as well) piperacillin/tazobactam Severe systemic infections

47. Tetracyclines • Good effect: • Chlamydia, Mycoplasma, Actinomyces, Lyme disease, pelvic infections, urethritis, brucellosis • Contraindicated before the age of 10 yrs!

48. ANTIBIOTIC DRUGS Active ingredientProduct Amoxicillin Aktil, Augmentin + clavulanic acid Ampicillin Ospamox, Penstabil, Pentrexyl

49. Active ingredientProduct Ampicillin Unasyn +Sulbactam Azithromycin Sumamed Azlocillin Securopen

50. Active ingredientProduct Cefadroxil Duracef Ceftazidime Fortum Ceftriaxon Rocephin Cefixim Suprax