Empiric antibiotic therapy Prof Ruth Nduati Department of Paediatrics and Child health University of nairobi

Evidence based treatment of infections to prevent anti microbial resistance Evidence based treatment (culture result) Empiric treatment

Why empiric therapy? Assessment- gathering data Diagnosis - hypothesis History Physical examination Diagnosis - hypothesis Management – testing hypothesis Empiric treatment Laboratory Investigations , Imaging

Infections are common Antimicrobial resistance is a problem Genuine resistance Inappropriate selection Inadequate dosing Amount duration

Identification of specific organisms Microbial resistance Many variables Sample collection Sample handling Culture – media Resistance panel Over calling resistance

Steps in selecting the empiric protocol Effect modifiers Where did acquire the infection? Is there an infection? Diagnosis Likely organism at the community? No recent antibiotic use Recent antibiotic use in hospital? Length of admission < />5 days in hospital SEVERITY OF ILLNESS Does the child have co-morbid conditions – malnutrition, cardiac disease, neutropenia

Selecting an empiric protocol Infection Common Pathogen Patient/ Infection factors Initial empiric therapy Community acquired pneumonia (CAP) S. Pneumoniae H. Influenza Mycoplasma Pneumoniae Chlamydia Pneumoniae Out-patient otherwise healthy Azithromycin or Clarithromycin or Doxycyclin (>7yrs) Out-patient with co-morbidities or recent antibiotic use Amoxycillin or Amoxycillin Clavulate or Cefuroxime (2nd Gen) plus Azithromycin / Clarithromycin Inpatient non ICU In patient ICU

Selecting an empiric protocol Infection Common Pathogen Patient/ Infection factors Initial empiric therapy Community acquired pneumonia (CAP) S. Pneumoniae H. Influenza Mycoplasma Pneumoniae Chlamydia Pneumoniae Inpatient non ICU Levofloxacin or Moxifloxacin Ceftriaxone or Cefotaxime or Ampicillin plus Azithromycin / Clarithromycin In patient ICU Ceftriaxone or Cefotaxime or Ampicillin/sulbactam

Health care associated Pneumonia Causative organisms Duration of Hospital stay Initial empiric therapy S. Pneumoniae H. Influenza Staph aureus MSSA E. Coli Klebsiella pneumoniae Early onset ( within 5 days of hospitalization) and no recent antibiotic exposure Ceftriaxone or Ampicillin/sulbactam

Health care associated Pneumonia Causative organisms Duration of Hospital stay Initial empiric therapy S. Pneumoniae H. Influenza Staph aureus MSSA E. Coli Klebsiella pneumoniae Staph aureus (MRSA) Enterobacter species Proteus species Serratia Pseudomonas aeroginosa Late onset ( within 5 days of hospitalization) and or recent antibiotic exposure Cefepine or ceftazidine or meropenem, or Pipreracillin tazobactam plus Gentamycin or Amikacin Vancomycin or Linezolid

Doses of many antibiotic vary with age of child

Age and weight adjusted dosing Drug Route < 2Kg > 2 Kg < 7 days 8-28 days Amikacin I/V, I/M 15mgevery 48 hours 15mgevery 24-48 hours 15mgevery 24 hours 15mg every 12-24 Meropenem 20mg 12hourly 20mg 8 hourly Ceftriaxone 50mg every 24 hours Cefalosporins and Penicillins generally don’t need age adjusted dosing

Selection and Dosing of many antibiotic varies with severity of illness

Assess for danger signs Example IMCI danger sign list Inability to drink or breastfeed Vomiting everything History of convulsions in current illness Lethargy or altered consciousness Seizures now Other Features of septic shock – cold extremities, cap refill, petichae, multi-organ dysfunction Oxygen saturation

- DAIDS Tables Standardized approach to grading severity of disease. Tables developed to support multi-cente clinical trials Useful tool for decision making Grade adverse event/symptom/sign into 5 categories Grade 1 mild event Grade 2 moderate event Grade 3 severe event Grade 4 potentially life-threatening event Grade 5 death

Example of severity of infection adjustments Drug Route Dose/Kg/Day Mild /moderate infection Severe infection Comment Amikacin IV,IM 15-22.5mg in 3 doses Meropenem IV 30-60mg in 3 doses Higher dose 120mg in 3 doses for treatment of meningitis

Example of severity of infection adjustments Drug Dose/Kg/Day Mild /moderate infection Severe infection Comment Ceftriaxone (Extended spectrum) IV/IM 50-75mg once daily 100 mg 1-2 doses Large dose – meningitis & penicillin resistant pneumococcal pneumonia Amoxycillin (PO) 25-50mg in 3 doses 80-100mg PO as step down for invasive infection High dose in AOM

Example of severity of infection adjustments Drug Dose/Kg/Day Mild /moderate infection Severe infection Comment Cefuroxime (2nd generation) IV/IM 75-100mg in 3 doses 100-200mg in 3-4 doses Less active against penicillin resistant pneumococcal pneumonia ORAL 20-30mg 2 doses daily Limited activity against pneumococcus

Careful selection of empiric treatment protocol is key to preventing anti microbial resistance DISEASE Specific treatment