Antibiotics and Neonatal Sepsis


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Antibiotics and Neonatal Sepsis

  1. 1. Antibiotics<br />Prepared By<br />MAGED ZAKARIA<br />NICU Resident<br />
  2. 2. Medically Important Bacteria<br />
  3. 3. Penicillins<br />They are bactericidal by interfering with bacterial cell wall synthesis<br />Poorly penetrate into CSF unless meninges are inflammed.<br />Destroyed by b-lactamase enzyme produced by staph, E.coli and H. influenza <br />
  4. 4. Penicillins<br />2 Commonly used classes:<br />Aminopenicillins:ampicillin and amoxicillin<br />Ureidopenicillins:piperacillin<br />Resistance to b-lactamase is overcomed by adding an inhibitor (sulbactam, clavulanate or tazobactam)<br />MRSA resists penicillins by decreasing affinity of PBP. This is overcomed by using another antibiotic that acts on a different site (vancomycin)<br />
  5. 5. Broad Spectrum Penicillins<br />UNASYN<br />Ampicillin + Sulbactam<br />
  6. 6. Broad Spectrum Penicillins<br />Augmentin<br />Amoxacillin + Clavulanate<br />
  7. 7. Piperacillin / Tazobactam<br />Given by syringe pump over 30 min<br />
  8. 8. Cephalosporins<br />
  9. 9. Third Generation Cephalosporins<br />The third generation cephalosporins have excellent activity against Gram–ve organisms<br />Cephalosporins are not effective against Listeria and Enterococci.<br />Theoretical advantages of third-generation cephalosporins<br />Low toxicity<br />Unnecessary measurement of serum level<br />
  10. 10. Third Generation Cephalosporins<br />Sulperazon<br />Cefoperazone / Sulbactam<br />
  11. 11. There’s a higher neonatal mortality rate with the use of Claforan compared with gentamicin<br />Resistance develops rapidly when Claforan is used for empirical therapy<br />So, it seems wise to restrict its use to infants with meningitis due to susceptible organisms<br />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<br />
  12. 12. Ceftriaxone<br />
  13. 13. Ceftriaxone<br />
  14. 14. Fourth Generation Cephalosporins<br />Given by syringe pump over 30 min or IM<br />Cefepime<br />
  15. 15. Carbapenems (Imipenem and Meropenem)<br />The broadest spectrum antibiotics.<br />MRSA and enterococci are not susceptible<br />
  16. 16. Imipenem<br />
  17. 17. Meropenem<br />Dose In Sepsis: 20 mg/kg/dose IVI over 30 min Q12h<br />Dose In Meningitis And Pseudomonas Infection: 40 mg/kg/dose IVI over 30 min Q8h <br />
  18. 18. Glycopeptides<br />Include Vancomycin and Teicoplanin.<br />They are bactericidal against Gram +ve bacteria including S. aureus, CONS, Pneumococci and enterococci especially for infections associated with medical devices<br />
  19. 19. Vancomycin<br />
  20. 20. Teicoplanin<br />
  21. 21. Aminoglycosides<br />Include gentamycin, tobramycin and amikacin<br />Side effects include nephrotoxicity and ototoxicity<br />This is decreased by use of once-daily dose plus monitoring of serum level <br />Toxicity is increased by use of other nephrotoxic drugs e.g. lasix and vancomycin, hypokalemia, hypovolemia and hypomagnesemia<br />
  22. 22. Gentamicin<br />
  23. 23. Amikacin<br />AMIKIN<br />Given by syringe pump over 30 min<br />IM route is associated with variable absorption especially in VLBW<br />Dose and dosing interval vary according to PMA and postnatal age<br />
  24. 24. Macrolides<br />Include erythromycin, clarithromycin and azithromycin<br />Effective in atypical pneumonia caused by mycoplasma, chlamydia and legionella<br />They are enzyme inhibitors so they may increase the level of theophylline<br />
  25. 25. Azithromycin<br />
  26. 26. Clindamycin<br />Protein synthesis inhibitor<br />Effective against gram +ve aerobes and anerobes<br />No significant activity against gram –ve bacteria<br />Pseudomembranous colitis is rare in pediatric practice <br />
  27. 27. Metronidazole<br />Given by syringe pump over 60 min<br />
  28. 28. Rifampin<br />10-20 mg/kg/dose Q24h PO<br />5-10 mg/kg/dose Q12h over 30 min IVI<br />
  29. 29. Linezolid<br />A protein synthesis inhibitor (Bacteriostatic)<br />It’s directed primarily against gram +ve organisms<br />
  30. 30. Linezolid<br />Thrombocytopenia occurs in 2% of patients who were on the drug for &gt; 2 wks<br />
  31. 31. Ciprofloxacin<br />
  32. 32. Ciprofloxacin<br />
  33. 33. Applied Knowledge<br />
  34. 34. Empirical vs. Specific Antibiotic Therapy<br />Specific antibiotic depends on isolation of the micro-organism from a sterile body site.<br />While empirical antibiotic therapy depends on clinical diagnosis before or even without identification of the pathogen<br />
  35. 35. Empirical vs. Specific Antibiotic Therapy<br />In the neonatal period, the causative pathogens are typically acquired perinatally as well as the flora of the nursery. <br />Important Pathogens Causing EOS:<br /> 1. GBS 2. E. coli 3. Listeria<br />All these pathogens can cause meningitis so if meningitis can’t be excluded, the emperical antibiotic should be able to cross the BBB.<br />
  36. 36. Empirical vs. Specific Antibiotic Therapy<br />Staph. aureus and coagulase-negative staph. are major risks for infections associated with indwelling medical devices e.g. venous catheters, ventriculo-peritoneal shunt, etc ..<br />Removal or replacement of the colonized device may be required for cure.<br />
  37. 37. Choice of a Suitable Antibiotic<br />Consider two factors<br />The Neonate: PMA and Postnatal age, renal and hepatic function and severity of infection.<br />The likely organism and its antibacterial sensitivity<br />The final choice should depend on microbiological advice if possible<br />Knowledge of prevalent organisms and their current sensitivity is of great help in antibacterial choice before bacteriological confirmation.<br />
  38. 38. Choice of a Suitable Antibiotic<br />Early-onset Sepsis (GBS - E.coli - Listeria)<br />Ampicillin + Gentamicin<br />Late-onset Sepsis<br />CONS - MRSA:Vancomycin<br />Pseudomonas:Fortum – Tazocin – Gentamicin<br />Enterobacter:Maxipime – Meronem<br />Klebsiella:Claforan – Meronem - Gentamicin<br />
  39. 39. Antibiotic Combinations<br />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. <br />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.<br />
  40. 40. Antibiotic Combinations<br />Examples<br />Unasyn + Garamycin<br />Tazocin + Amikin<br />
  41. 41. Antibiotic Combinations<br />Combine antibiotics to extend their antimicrobial spectrum<br />Penicillin + Third generation Cephalosprin<br />Meronem + Vancomycin<br />Penicillin + Aminoglycoside + Flagyl or Dalacin-C<br />
  42. 42. When to Change Antibiotics<br />Clinically deteriorating.<br />Increasing Hematologic Sepsis Score.<br />Rising CRP titer.<br />According to C&S results.<br />
  43. 43. Clinical Signs Suggesting Sepsis<br /><ul><li>Hyperthermia (51%)
  44. 44. Hypothermia (15%)
  45. 45. Jaundice (35%)
  46. 46. Hepatomegaly (33%)
  47. 47. Splenomegaly
  48. 48. Respiratory distress (33%)
  49. 49. Apnea (22%)
  50. 50. Cyanosis (24%)
  51. 51. Refusal of feeding (28%)
  52. 52. Poor Suckling
  53. 53. Vomiting (25%)
  54. 54. Abdominal Distension (17%)
  55. 55. Diarrhea (11%)</li></li></ul><li>Hematologic Sepsis Score<br />Manroe BL, Weinberg AG, et al. The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J Pediatr. 1979; 95: 89-98.<br />Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a hematologic scoring system. J Pediatr. 1988; 112: 761-767.<br />Seebach JD, Morant R, et al. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J ClinPathol. 1997; 107: 582-591.<br />Zipursky A, Palko J, et al. The hematology of bacterial infections in premature infants. Pediatrics. 1976; 57: 839-853.<br />
  56. 56. Neutrophil Values Suggestive of Infection<br />
  57. 57. C-Reactive Protein<br />An acute phase reactant elevated in the presence of inflammation or infection with a response time of 6-8 hours.<br />CRP is quite useful in ruling out more than predicting a possible sepsis.<br />The usefulness of CBC and CRP is markedly improved with serial measurement<br />
  58. 58. Switching From A Parenteral To An Oral Form<br />The ongoing parenteral administration of antibiotics should be reviewed regularly.<br />In older children it may be possible to switch to an oral antibiotic. <br />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.<br />
  59. 59. When to Stop Antibiotics<br />Hematologic Sepsis Score ≤ 2<br />2 consecutive negative CRP<br />Clinically free.<br />No indwelling medical devices<br />Negative cultures !<br />