1. Antibiotics Prepared By MAGED ZAKARIA NICU Resident

2. Medically Important Bacteria

3. Penicillins They are bactericidal by interfering with bacterial cell wall synthesis Poorly penetrate into CSF unless meninges are inflammed. Destroyed by b-lactamase enzyme produced by staph, E.coli and H. influenza

4. Penicillins 2 Commonly used classes: Aminopenicillins:ampicillin and amoxicillin Ureidopenicillins:piperacillin Resistance to b-lactamase is overcomed by adding an inhibitor (sulbactam, clavulanate or tazobactam) MRSA resists penicillins by decreasing affinity of PBP. This is overcomed by using another antibiotic that acts on a different site (vancomycin)

5. Broad Spectrum Penicillins UNASYN Ampicillin + Sulbactam

6. Broad Spectrum Penicillins Augmentin Amoxacillin + Clavulanate

7. Piperacillin / Tazobactam Given by syringe pump over 30 min

8. Cephalosporins

9. Third Generation Cephalosporins The third generation cephalosporins have excellent activity against Gram–ve organisms Cephalosporins are not effective against Listeria and Enterococci. Theoretical advantages of third-generation cephalosporins Low toxicity Unnecessary measurement of serum level

10. Third Generation Cephalosporins Sulperazon Cefoperazone / Sulbactam

11. There’s a higher neonatal mortality rate with the use of Claforan compared with gentamicin Resistance develops rapidly when Claforan is used for empirical therapy So, it seems wise to restrict its use to infants with meningitis due to susceptible organisms Clark RE, Bloom BT, Spitzer AR, Gerstmann DR: empiric use of ampicillin and cefotaxime compared to ampicillin and gentamicinis associated with an increased risk of death for neonates at risk for sepsis. Pediatrics 117:67-74, 2006

12. Ceftriaxone

13. Ceftriaxone

14. Fourth Generation Cephalosporins Given by syringe pump over 30 min or IM Cefepime

15. Carbapenems (Imipenem and Meropenem) The broadest spectrum antibiotics. MRSA and enterococci are not susceptible

16. Imipenem

17. Meropenem Dose In Sepsis: 20 mg/kg/dose IVI over 30 min Q12h Dose In Meningitis And Pseudomonas Infection: 40 mg/kg/dose IVI over 30 min Q8h

18. Glycopeptides Include Vancomycin and Teicoplanin. They are bactericidal against Gram +ve bacteria including S. aureus, CONS, Pneumococci and enterococci especially for infections associated with medical devices

19. Vancomycin

20. Teicoplanin

21. Aminoglycosides Include gentamycin, tobramycin and amikacin Side effects include nephrotoxicity and ototoxicity This is decreased by use of once-daily dose plus monitoring of serum level Toxicity is increased by use of other nephrotoxic drugs e.g. lasix and vancomycin, hypokalemia, hypovolemia and hypomagnesemia

22. Gentamicin

23. Amikacin AMIKIN Given by syringe pump over 30 min IM route is associated with variable absorption especially in VLBW Dose and dosing interval vary according to PMA and postnatal age

24. Macrolides Include erythromycin, clarithromycin and azithromycin Effective in atypical pneumonia caused by mycoplasma, chlamydia and legionella They are enzyme inhibitors so they may increase the level of theophylline

25. Azithromycin

26. Clindamycin Protein synthesis inhibitor Effective against gram +ve aerobes and anerobes No significant activity against gram –ve bacteria Pseudomembranous colitis is rare in pediatric practice

27. Metronidazole Given by syringe pump over 60 min

28. Rifampin 10-20 mg/kg/dose Q24h PO 5-10 mg/kg/dose Q12h over 30 min IVI

29. Linezolid A protein synthesis inhibitor (Bacteriostatic) It’s directed primarily against gram +ve organisms

30. Linezolid Thrombocytopenia occurs in 2% of patients who were on the drug for > 2 wks

31. Ciprofloxacin

32. Ciprofloxacin

33. Applied Knowledge

34. Empirical vs. Specific Antibiotic Therapy Specific antibiotic depends on isolation of the micro-organism from a sterile body site. While empirical antibiotic therapy depends on clinical diagnosis before or even without identification of the pathogen

35. Empirical vs. Specific Antibiotic Therapy In the neonatal period, the causative pathogens are typically acquired perinatally as well as the flora of the nursery. Important Pathogens Causing EOS: 1. GBS 2. E. coli 3. Listeria All these pathogens can cause meningitis so if meningitis can’t be excluded, the emperical antibiotic should be able to cross the BBB.

36. Empirical vs. Specific Antibiotic Therapy Staph. aureus and coagulase-negative staph. are major risks for infections associated with indwelling medical devices e.g. venous catheters, ventriculo-peritoneal shunt, etc .. Removal or replacement of the colonized device may be required for cure.

37. Choice of a Suitable Antibiotic Consider two factors The Neonate: PMA and Postnatal age, renal and hepatic function and severity of infection. The likely organism and its antibacterial sensitivity The final choice should depend on microbiological advice if possible Knowledge of prevalent organisms and their current sensitivity is of great help in antibacterial choice before bacteriological confirmation.

38. Choice of a Suitable Antibiotic Early-onset Sepsis (GBS - E.coli - Listeria) Ampicillin + Gentamicin Late-onset Sepsis CONS - MRSA:Vancomycin Pseudomonas:Fortum – Tazocin – Gentamicin Enterobacter:Maxipime – Meronem Klebsiella:Claforan – Meronem - Gentamicin

39. Antibiotic Combinations ß-lactam antibiotics are synergistic with aminoglycosides as penicillins alter the permeability of bacterial cells to facilitate the entry of aminoglycosides to intracellular target sites. Although this combination is used clinically, these drugs should never be placed in the same infusion fluid, because on prolonged contact, the positively charged aminoglycosides form an inactive complex with the negatively charged penicillins.

40. Antibiotic Combinations Examples Unasyn + Garamycin Tazocin + Amikin

41. Antibiotic Combinations Combine antibiotics to extend their antimicrobial spectrum Penicillin + Third generation Cephalosprin Meronem + Vancomycin Penicillin + Aminoglycoside + Flagyl or Dalacin-C

42. When to Change Antibiotics Clinically deteriorating. Increasing Hematologic Sepsis Score. Rising CRP titer. According to C&S results.

44. Hypothermia (15%)

45. Jaundice (35%)

46. Hepatomegaly (33%)

47. Splenomegaly

48. Respiratory distress (33%)

49. Apnea (22%)

50. Cyanosis (24%)

51. Refusal of feeding (28%)

52. Poor Suckling

53. Vomiting (25%)

54. Abdominal Distension (17%)

56. Neutrophil Values Suggestive of Infection

57. C-Reactive Protein An acute phase reactant elevated in the presence of inflammation or infection with a response time of 6-8 hours. CRP is quite useful in ruling out more than predicting a possible sepsis. The usefulness of CBC and CRP is markedly improved with serial measurement

58. Switching From A Parenteral To An Oral Form The ongoing parenteral administration of antibiotics should be reviewed regularly. In older children it may be possible to switch to an oral antibiotic. In neonates and infants this should be done more cautiously because of the relatively high incidence of bacteremia and the possibility of variable oral absorption.

59. When to Stop Antibiotics Hematologic Sepsis Score ≤ 2 2 consecutive negative CRP Clinically free. No indwelling medical devices Negative cultures !