COMMON ANTIBIOTICS USE

IN PEDIATRICS
15/5/62
PRINCIPLE

  Diagnosis : site
  Common pathogen
  Organism susceptibility
  Host
  Side effects
  Empirical or Definite therapy
  Broad as necessary, narrow as possible
  Follow clinical response
FACTORS INFLUENCING CLINICAL OUTCOME

Host

Bug Drug
HOST FACTOR

  Immune status
  Underlying disease
  Renal failure
  Liver and biliary disease
  Asplenia
  Burn
  Edema
  Risk : catheter, line, hospitalization
  Allergy
  Age
RENAL FAILURE

  Avoid nephrotoxic drugs

  Adjust dose in most antimicrobials
SIGNIFICANT SIDE EFFECTS

  Diarrhea : clindamycin, most antibiotics

  Aplastic anemia : chloramphenicol
  Hearing loss : aminoglycosides, vancomycin
  Seizure : penicillin, cephalosporin, imipenem, metronidazole
  Acute tubular necrosis : aminoglycosides, vancomycin
  Acute interstitial nephritis : penicillin
  Electrolyte abnormalities : Amphotericin B
  Kernicterus : ceftriaxone, sulfamethoxazole
  Arthropathy : fluoroquinolone
  Tooth discoloration and enamel hypoplasia : tetracyclin
  Gray baby in newborn : chloramphenicol
PATHOGEN FACTOR

  Site of infection
  Susceptibility
ANTIBIOTICS RESISTANCE

  Decrease permeability of bacterial membrane

  Target modification : binding proteins
  Production of drug-inactivated enzyme : beta-lactamase
  Metabolic bypass
  Efflux pump
ANTIMICROBIALS FACTOR

  Spectrum
  Antimicrobial activity :
  static & cidal
  Pharmacokinetics
  Pharmacodynamics
  Drug interaction
PHARMACOKINETICS

  Absorption : oral bioavailability

  Distribution : volume of distribution(Vd)
  Metabolism
  Elimination
  Renal clearance
  Nonrenal clearance : biliary tree, intestine
PHARMACODYNAMICS

  Concentration-dependent killing agents

  Time-dependent killing agents
Time-Dependent Killing agents Concentration-Dependent Killing agents

  Penicillins   Aminoglycosides
  Cephalosporins   Fluoroquinolones
  Macrolides

  Methods to maximize exposure

  Continuous infusion
  Prolonged infusion
  Given more frequently
TIME-DEPENDENT KILLING AGENTS
DURATION OF ANTIMICROBIALS

  Pathophysiology of disease
  Site of infection
  Mechanism of action of drug
  Response to antimicrobials
BACTERIAL TARGETS FOR ANTIMICROBIALS
 INHIBIT CELL WALL SYNTHESIS

  Penicillins
  Cephalosporins
  Carbapenems
  Monobactam
  Glycopeptides
Penicillin Spectrum
Natural penicillin Penicillin G, Penicillin V, Gram positive cocci : Streptococci., Enterococci
Procaine Penicllin Gram positive bacilli : Listeria monocytogenes, C.diphtheria
Gram negative cocci : N.meningitides, N.gonorrhea, Eikenella corrodens
Anaerobe : Clostridium spp., ยกเว้น Bacteroides fragilis
Spirochette : Leptospira interrogans, Treponema pallidum

Aminopenicillin Ampicillin, amoxicillin Gram positive cocci,Enterococci group,L.monocytogenes,

Some Gram negative bacilli : H.influenzae, M.catarrhalis, E.coli, Shigella
spp.Salmonella spp., P.mirabillis
Penillinase- Oxacillin, Cloxacillin, dicloxacillin, Methicillin-susceptible Staphylococcus aureus,
resistant methicillin Methicillin-susceptible coagulase negative staphylococcus
penicillins Streptococci,
Most anaerobic gram positive cocci
Carboxypenicillins Ticarcillin P.Aeruginosa (combine with Aminoglycosides)
Enterobacter, Serratia, Klesiella, B.fragillis, Acinetobacter
Ureidopenicillins Piperacillin P.Aeruginosa (combine with Aminoglycosides)
Enterobacter, Serratia, Klesiella, B.fragillis, Acinetobacter
β-lactam/β- Amoxillin/clavulanate Gram positive cocci(+Enterococci), MSSA, anaerobe,
lactamase (Augmentin®)
inhibitors Ampicillin/sulbactam(Unasyn®)
Ticarcillin/clavulanate(Tiimentin®) P.Aeruginosa
Piperacillin/tazobactam(Tazocin®) P.Aeruginosa
 Cephalosporin Parenteral Oral Spectrum

1st generation Cefazolin Cephalexin Gram positive cocci :S.aureus, Steptococci,

Susceptible S.pneumoniae,
Some gram negative bacilli

2nd generation Cefuroxime Cefuroxime, Gram positive cocci : S.aureus, Streptococci, S.pneumoniae
cefprozil Gram negative bacilli : H.influenzae, M.catarrhalis,
N.menigitidis, N.gonorrhea, E.coli, P.mirabilis, Klebsielaa spp.

3rd generation Cefotaxime Cefdinir(Omnicef®) Gram positive

(Claforan®), Cefditoren(Meiact®) Gram negative bacilli
ceftriaxone Cefixime(Cefspan®)
ไม่ cover Enterococci
(cef3®, Ceftibuten(Cedax®)
Rocephin®)

3rd generation Ceftazidime Decrease activity against staphylococcus

Antipseudomonal (cef4®), Enhance activity against P.aeruginosa
effect cefoperazone
ไม่ cover Enterococci

4th generation Cefepime Gram positive cocci

cefpirome Gram negative bacilli,ESBL-E.coli, K.pneumonia
P.aeruginosa
ไม่ cover Enterococci
ANTIBIOTICS RESISTANCE (BETA LACTAM)

  decreased permeability of bacterial membranes

  Altered target sites ( penicillin binding protein)
  Promotion of antibiotic efflux
  Enzymatic alteration ( gram negative and stappylococi : betalactamase)
BETALACTAMASE INHIBITOR

  Clavulanic acid : plasmid betalactamase

  Penicillanic acid sulfone (sulbactam and tazobactam) : chromosomal
betalactamase
ORAL CEPHALOSPORIN

  1st generation : cefprozil and cephalexin (can’t Tx H. influenza and M. catarrhalis

  2nd generation : cefuroxime and cefaclor (cover H. influenza and M.catarrhalis)
  3rd generation
  ceftibuten and cefixime (cefspan)
  cefdinir and cefodoxime proxetil
  4 th generation (advance generation) : PISP (penicillin intermediate resistant S.
pneumonia)
  cefditoren pivoxil
 INHIBIT PROTEIN SYNTHESIS

  Aminoglycosides
  Macrolides
  erythromycin : S. pneumonia, M.catarrhalis
  azithromycin : S.pneumonia, M.catarrhalis, H.influenza

  Clindamycin
COMMON ANTIBIOTICS USE
COMMON ANTIBIOTICS USE

  Respiratory tract infection

  pharyngitis
  acute otitis media
  rhinosinusitis
  pneumonia
  Infectious diarrhea
GROUP A STREPTOCOCCUS PHARYNGITIS

  Sudden onset of sore throat, age 5-15 years, fever, headache, nausea,
vomiting, abdominal pain, tonsillopharyngeal inflammation, patchy
tonsillopharyngeal exudates, palatal petechiae, anterior cervical adenitis
and scarlatiniform rash

  Lab :
  Throat swab culture ( standard method), sensitivity 90-95, false negative
  rapid streptococcal antigen test , sensitivity 60-70, specificity 95%
 GROUP A STREPTOCOCCUS PHARYNGITIS
Antimicrobials Route Dose Duration(Day)
No penicillin allergy Penicillin V Oral เด็กเล็ก 250 mg/kg/dose x 2-3 times/day 10
เด็กโต 250 mg/kg/dose x 4 times/day
หรือ 500 mg/kg/dose x 2 times/day

Amoxicilin Oral 50mg/kg/day divided in 1-2 times 10

(Max 1,000mg/day)
Benzathine penicillin G IM < 27 kg : 600,000 unit Single dose
≥ 27 kg : 1,200,000 unit
Penicillin allergy, Cephalexin Oral 20 mg/kg/dose x 2 times/day 10
Not severe (Max 500 mg/dose)

Severe penicillin Clindamycin Oral 7 mg/kg/dose x 3 times/day 10

allergy (Max 300 mg/dose)
Azithromycin Oral 12 mg/kg/dose x 1 time/day 5
(Max 500 mg/dose)
Clarithromycin Oral 7.5 mg/kg/dose x 2 times/day 10
(Max 250 mg/dose)
 ACUTE OTITIS MEDIA
Pathogen

  Virus   Acute otitis media (AOM) : sudden

onset/ effusion of middle ear (TM
  Bacteria bulging, decrease movement,
  S.pneumoniae effusion behind TM, otorrhea)/sign
  H.influenza (nontypable) and symptom ( redness at TM or
  M.catarrhalis othalgia)
  otits media with effusion (OME) : no
clinical and sign of infection
  Chronic serous otitis media (CSOM)
: otorrhea 2-6 weeks, TM rupture
Risk factors for Resistant S.pneumoniae infection

  Age ≤ 2 years old

  Attendance at day-care center
  Siblings of children attending at day-care center
  Prior AOM within past 6 months
  Receipt of antibiotics within last 3 months
  Not vaccinated with PCV
UNCOMPLICATED AOM
 INITIAL OR DELAYED ANTIBIOTIC TREATMENT OF AOM
Antimicrobials Route Dose Duration(Day)
No penicillin allergy Amoxicillin Oral 80-90 mg/kg/day in 2 divided doses ≤ 2 years old, severe
symptoms : 10 days
Amoxicillin/clavulanate* Oral 90 mg/kg/day of amoxicillin in 2
divided doses 2-5 years old,
Penicillin allergy, Cefdinir Oral 14 mg/kg/day in 1-2 divided doses Mild to moderate
Not severe : 7 days
Cefuroxime Oral 30 mg/kg/day in 2 divided doses
≥ 6 years old,
mild to moderate
Cefpodoxime Oral 10 mg/kg/day in 2 divided doses
: 5-7 days
Ceftriaxone IM, IV 50 mg/kg/day OD 1-3

Severe penicillin Azithromycin Oral 10 mg/kg/day OD in 1st day then 5 5 days

allergy (type I mg/kg/day in 2nd -5th day
hypersensitivity)

* May be considered in patients who have received amoxicillin in previous 30 days and have the otitis-conjunctivitis syndrome
ANTIBIOTIC TREATMENT AFTER 48-72 HR OF
FAILURE OF INITIAL ANTIBIOTIC TREATMENT
Antimicrobial Route Dose Duration
First line Amoxicillin/clavulate oral 90 mg/kg/day of amoxicillin in 2 Evaluate after 48-
divided doses 72hr
Ceftriaxone IM, IV 50 mg/kg/day OD 3 days
Alternative Clindamycin IV 20 mg/kg/day in 3 divided doses
Ceftriaxone plus
clindamycin
**พิจารณา tympanocentesis,
consult specialist
ACUTE BACTERIAL RHINOSINUSITIS

  Clinical Rhinosinusitis (bacterial)   2-10% Bacteria

  Persistent symptoms > 10 days   S.pneumoniae
  Severe symptoms :   H.influenza (nontypable)
  T≥39̊C
  M.catarrhalis
  purulent nasal discharge > 3-4
consecutive days   S.aureus
  Worsening symptoms
 S Antimicrobials Route Dose Duration(Day)
No penicillin allergy Amoxicillin/clavulanate Oral 45 mg/kg/day of amoxicillin in 2 10-14
1st line divided doses
2nd line Amoxicillin/clavulanate Oral 90 mg/kg/day of amoxicillin in 2
divided doses
Ceftriaxone IV 50-75 mg/kg/day OD

Cefotaxime IV 100 mg/kg/day in 3-4 divided doses

Penicillin allergy, Clindamycin 30-40 mg/kg/day in 2 divided doses

Not severe plus cefpodoxime 10 mg/kg/day in 2 divided doses
Or cefixime 8 mg/kg/day in 2 divided doses

Severe penicillin Levofloxacin Oral, IV 10-20 mg/kg/day in 1-2 doses

allergy (Max 500mg/day)
Moxifloxacin IV 400 mg/day
PNEUMONIA

  Fever Age group

  Respiratory distress   < 1 month : group B strep, E.coli
  age group
  1-3 month :
  Virus : RSV, parainfluenza virus
  Bacteria : S.pneumonia, H.influenza,
Chlamydia trachomatis, B.pertussis, S.
aureus
  3 mo-5yr :
  virus : rhinovirus, adenovirus, RSV
  Bacteria : S. pneumonia, H. influenza
  5yr-15 yr : S. pneumonia, Chlamydophila
pneumoniae
 OUTPATIENT
Antimicrobials Dose
No penicillin allergy

1st line Amoxicillin 90 mg/kg/day in 2 divided doses

(Max 4 g/day)
Alternative Amoxicillin/clavulanate 90 mg/kg/day of amoxicillin in 2 divided doses
(Max 4 g/day of amoxicillin)
Penicillin allergy, Cefpodoxime 10 mg/kg/day in 2 divided doses
Not severe

Cefuroxime 30 mg/kg/day in 2 divided doses

Severe penicillin allergy Levofloxacin 10-20 mg/kg/day OD (Max 500 mg)

* ถ้าอายุ > 7 ปี ให้ doxycycline 2-4 mg/kg/day แทนได้

 INPATIENT
Fully immunized with PCV and Hib
vaccine,
Minimal local resistance in invasive
pneumococcal strains
Not fully immunized PCV and Hib
vaccine,
Significant local resistance in
invasive pneumococcal strains,
Severe pneumonia
Suspected CA-MRSA
1st line Alternative
Ampicillin 150-200 mg/kg/day IV in 4 Ceftriaxone 50-100 mg/kg/day IV q 12-
divided doses 24 hr
Penicillin G 200,000-250,000 unit/kg/day IV Cefotaxime 150 mg/kg/day IV in 3-4
in 4-6 divided doses divided doses
Ceftriaxone 50-100 mg/kg/day IV q 12-24 Levofloxacin 10-20 mg/kg/day oral/IV
hr OD
Cefotaxime 150 mg/kg/day IV in 3-4 Ampicillin 300-400 mg/kg/day IV q 6 hr
divided doses
Add vancomycin 40-60 mg/kg/day IV q6hr
Or clindamycin 40 mg/kg/day IV q6hr
ATYPICAL PNEUMONIA

1st line Azithromycin 10 mg/kg/day(Max 500 mg) in 1st day

Then 5 mg/kg/day(Max 250 mg) in 2nd-5th day
Alternative Clarithromycin 15 mg/kg/day in 2 divided doses(Max 1 g/day)
Erythromycin 40 mg/kg/day in 4 divided doses
Doxycycline 2-4 mg/kg/day in 2 divided doses
เมือA อายุ > 7 ปี
INFLUENZA VIRUS

  Oseltamivir
  BW < 15 kg : 30 mg oral q 12 hr
  BW 15-23 kg : 45 mg oral q 12 hr
  BW 23-40 kg : 60 mg oral q 12 hr
  > 40 kg : 75 mg oral q 12 hr
INFECTIOUS DIARRHEA

  Shigella species, salmonella ( indication for Tx : infants < 3 months old, patient
with malignancy, chronic GI disease, severe colitis, hemoglobiopthies, HIV
infection or immunocompromised patients), Enterotoxigenic E.coli, Vibrio cholera
  Antibiotics
  Norfloxacin or ciprofloxacin
  TMP/SMX
  Oral 3rd generation cephalosporin