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Antibiotics and Neonatal Sepsis
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Antibiotics and Neonatal Sepsis

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Antibiotics and Neonatal Sepsis Antibiotics and Neonatal Sepsis Presentation Transcript

  • Antibiotics
    Prepared By
    MAGED ZAKARIA
    NICU Resident
  • Medically Important Bacteria
  • 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
  • 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)
  • Broad Spectrum Penicillins
    UNASYN
    Ampicillin + Sulbactam
  • Broad Spectrum Penicillins
    Augmentin
    Amoxacillin + Clavulanate
  • Piperacillin / Tazobactam
    Given by syringe pump over 30 min
  • Cephalosporins
  • 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
  • Third Generation Cephalosporins
    Sulperazon
    Cefoperazone / Sulbactam
  • 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
  • Ceftriaxone
  • Ceftriaxone
  • Fourth Generation Cephalosporins
    Given by syringe pump over 30 min or IM
    Cefepime
  • Carbapenems (Imipenem and Meropenem)
    The broadest spectrum antibiotics.
    MRSA and enterococci are not susceptible
  • Imipenem
  • 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
  • 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
  • Vancomycin
  • Teicoplanin
  • 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
  • Gentamicin
  • 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
  • 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
  • Azithromycin
  • 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
  • Metronidazole
    Given by syringe pump over 60 min
  • Rifampin
    10-20 mg/kg/dose Q24h PO
    5-10 mg/kg/dose Q12h over 30 min IVI
  • Linezolid
    A protein synthesis inhibitor (Bacteriostatic)
    It’s directed primarily against gram +ve organisms
  • Linezolid
    Thrombocytopenia occurs in 2% of patients who were on the drug for > 2 wks
  • Ciprofloxacin
  • Ciprofloxacin
  • Applied Knowledge
  • 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
  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • Antibiotic Combinations
    Examples
    Unasyn + Garamycin
    Tazocin + Amikin
  • Antibiotic Combinations
    Combine antibiotics to extend their antimicrobial spectrum
    Penicillin + Third generation Cephalosprin
    Meronem + Vancomycin
    Penicillin + Aminoglycoside + Flagyl or Dalacin-C
  • When to Change Antibiotics
    Clinically deteriorating.
    Increasing Hematologic Sepsis Score.
    Rising CRP titer.
    According to C&S results.
  • Clinical Signs Suggesting Sepsis
    • Hyperthermia (51%)
    • Hypothermia (15%)
    • Jaundice (35%)
    • Hepatomegaly (33%)
    • Splenomegaly
    • Respiratory distress (33%)
    • Apnea (22%)
    • Cyanosis (24%)
    • Refusal of feeding (28%)
    • Poor Suckling
    • Vomiting (25%)
    • Abdominal Distension (17%)
    • Diarrhea (11%)
  • Hematologic Sepsis Score
    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.
    Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a hematologic scoring system. J Pediatr. 1988; 112: 761-767.
    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.
    Zipursky A, Palko J, et al. The hematology of bacterial infections in premature infants. Pediatrics. 1976; 57: 839-853.
  • Neutrophil Values Suggestive of Infection
  • 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
  • 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.
  • When to Stop Antibiotics
    Hematologic Sepsis Score ≤ 2
    2 consecutive negative CRP
    Clinically free.
    No indwelling medical devices
    Negative cultures !