Principles of antibiotic therapy in paediatrics
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Principles of antibiotic therapy in paediatrics
Dr. György FeketeDr. György Fekete
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AntibioticsAntibiotics
1.1. What is the reason? Indication?What is the reason? Indication?
- local infection- local infection
- empiric and targeted teatment- empiric and targeted teatment
- fever + general symptoms - fever + general symptoms (CRP, (CRP, WBC count and WBC count and smear, etc.)smear, etc.)
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2. Previous microbiological 2. Previous microbiological investigations?investigations?
- throat- throat
- urine- urine
- haemoculture- haemoculture
- cerebrospinal fluid- cerebrospinal fluid
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3. What is the potential (bacterial) 3. What is the potential (bacterial) cause of infection?cause of infection?
- age (newborn, infant, - age (newborn, infant, toddler…)toddler…)
- medical procedure, - medical procedure, hospitalisationhospitalisation
- immune deficiency- immune deficiency
- organ damage (spleen, liver, - organ damage (spleen, liver, kidney) kidney)
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Neonatal sepsis /meningitisNeonatal sepsis /meningitis
Focal infection: pneumonia, RDSFocal infection: pneumonia, RDS Group B streptococci, E. coli, other Gram-Group B streptococci, E. coli, other Gram-
negative rods, Listeria monocytogenesnegative rods, Listeria monocytogenes Th: Ampicillin+ gentamicin Th: Ampicillin+ gentamicin third generation cephalosporin instead of third generation cephalosporin instead of
aminoglycosideaminoglycoside
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Bacterial meningitis in children, Bacterial meningitis in children, 2months to 12 yrs2months to 12 yrs
S. pneumoniae, N. meningitidis, S. pneumoniae, N. meningitidis, (H. influenzae type b)(H. influenzae type b)
Therapy: - cefotaxime / ceftriaxone + Therapy: - cefotaxime / ceftriaxone + vancomycinevancomycine
- 3. generation - 3. generation cephalosporines cephalosporines
(Cefotaxime, (Cefotaxime, Ceftriaxone)Ceftriaxone)
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4.4. Which antibiotic will be Which antibiotic will be optimal? First choice?optimal? First choice?
- data of bacterial resistance- data of bacterial resistance
- site of infection – - site of infection – penetration?penetration?
- side effects?- side effects?
- bactericide effect- bactericide effect
- administration: 1x / day- administration: 1x / day
- not expensive- not expensive
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5.5. Any combination is Any combination is appropriate?appropriate?
- nosocomial infection- nosocomial infection
- sepsis- sepsis
- abdominal and pelvic - abdominal and pelvic infectionsinfections
- endocarditis- endocarditis
- empiric treatment- empiric treatment
- active tuberculosis- active tuberculosis
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Active tuberculosisActive tuberculosis
Treatment: INH, rifampin, pyrazinamideTreatment: INH, rifampin, pyrazinamide Ethambutol, ethionamideEthambutol, ethionamide
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6.6. Metabolism, excretion?Metabolism, excretion?
- kidney, liver (monitoring)- kidney, liver (monitoring)
- renal: aminoglycosides- renal: aminoglycosides
- liver:erythromycin, - liver:erythromycin, clindomycinclindomycin
7.7. Mode of administrationMode of administration
- iv, oral- iv, oral
- „switch”- „switch”
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8.8. Dosage ? Dosage ?
9.9. Changing of antiobiotic drug? Changing of antiobiotic drug? Indications?Indications?
10.10. How long should we treat?How long should we treat?
- Preterm and newborn babies need - Preterm and newborn babies need antibiotic therapy of longer duration antibiotic therapy of longer duration (sepsis, bacterial meningitis, etc.)(sepsis, bacterial meningitis, etc.)
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Antimicrobial prophylaxisAntimicrobial prophylaxis
Neonatal conjunctivitisNeonatal conjunctivitis Chlamydia trachomatisChlamydia trachomatis
– 0,5% erythromycin topically0,5% erythromycin topically Neisseria gonorrhoeaeNeisseria gonorrhoeae
– 1% silver nitrate or1% silver nitrate or– 0,5% erythromycin topically0,5% erythromycin topically
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Antimicrobial prophylaxisAntimicrobial prophylaxis
Splenectomy / aspleniaSplenectomy / asplenia Str. pneumoniaeStr. pneumoniae PenicillinPenicillin
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Resistant clones of Resistant clones of microorganismsmicroorganisms
Str. pneumoniaeStr. pneumoniae Staph. aureusStaph. aureus VirulentVirulent Serious infectionsSerious infections Overuse of antibioticsOveruse of antibiotics
– Viral infectionsViral infections– Broad spectrum antimicrobial agentsBroad spectrum antimicrobial agents
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Antibiotic management of Staphylococcus aureus Antibiotic management of Staphylococcus aureus
infections in US Children’s hospitals, 1999-2008infections in US Children’s hospitals, 1999-2008 Trends in antibiotic management for S. aureus infections, hospitalized Trends in antibiotic management for S. aureus infections, hospitalized
childrenchildren The use of vancomycin, clindamycin, linezolid, trimethoprim-The use of vancomycin, clindamycin, linezolid, trimethoprim-
sulfamethoxazole, cefazolin, and oxacillin/nafcillin were examined for sulfamethoxazole, cefazolin, and oxacillin/nafcillin were examined for percentage use and days of therapy per 1000 patient- daypercentage use and days of therapy per 1000 patient- day
64 813 patients had a discharge diagnosis for S. aureus infection64 813 patients had a discharge diagnosis for S. aureus infection The incidence of methicillin-resistant S. aureus (MRSA) infections The incidence of methicillin-resistant S. aureus (MRSA) infections
increased 10-fold (2 to 21 cases per 1000 admissions), methicillin- increased 10-fold (2 to 21 cases per 1000 admissions), methicillin- susceptible infection rate remained stablesusceptible infection rate remained stable
Clindamycin showed the greatest increase: 21% in 1999 and 63% in Clindamycin showed the greatest increase: 21% in 1999 and 63% in 20082008
Importance of continuous monitoring of local S. aureus susceptibility Importance of continuous monitoring of local S. aureus susceptibility patternspatterns
Herigon J.C et al. Pediatrics 2010, 125:1267Herigon J.C et al. Pediatrics 2010, 125:1267
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Broad - spectrum antimicrobial Broad - spectrum antimicrobial agentsagents
Drastic changes in bowel floraDrastic changes in bowel flora Bleeding disordersBleeding disorders Emergence of resistant organismsEmergence of resistant organisms Superinfections: yeasts, enterococciSuperinfections: yeasts, enterococci
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Local (hospital) microbiological Local (hospital) microbiological laboratorylaboratory
Knowing the prevalence of antibiotic – Knowing the prevalence of antibiotic – resistant organisms in a particular resistant organisms in a particular community (nursery) is helpful in choosing community (nursery) is helpful in choosing the first-line antibiotic regimensthe first-line antibiotic regimens
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Specific therapeutic valuesSpecific therapeutic values
VancomycinVancomycin: methicillin-resistant : methicillin-resistant staphylococcistaphylococci
MetronidazoleMetronidazole: anaerobic infections: anaerobic infections CeftazidineCeftazidine: Pseudomonas aeruginosa: Pseudomonas aeruginosa Trimethoprime+ sulfamethoxazole:Trimethoprime+ sulfamethoxazole:
shigellosis, salmonellosis, Pneumocysis shigellosis, salmonellosis, Pneumocysis carinii ( carinii ( pentamidinepentamidine))
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ThroatThroat
No. No. ofof samplessamples::920920
positivepositive:: 18%18%
negativenegative:: 82%82%
DistributionDistribution::
GroupGroup S.pyogenesS.pyogenes+C,F,G :+C,F,G :38%38%
S.aureusS.aureus:: 38%38%
OtherOther:: 24%24%
No No repeatedrepeated examinationexamination is is indicatedindicated duringduringantibioticantibiotic therapytherapy!!
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Ear
No. No. ofof samplessamples: 311: 311
positivepositive: 47%: 47%
negativenegative: 53%: 53%
DistributionDistribution::
•• S.pneumoniaeS.pneumoniae 40%40%
•• H.influenzaeH.influenzae 20%20%
•• PseudomonasPseudomonas 8%8%
•• S.pyogenesS.pyogenes 6%6%
•• OtherOther 26% 26%
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UrineUrine
No. No. ofof samplessamples::17961796
positivepositive:: 28%28%
negativenegative:: 60%60%
NotNot validvalid:: 12%12%
DistributionDistribution::
E.coliE.coli 47%47%
KlebsiellaKlebsiella spsp.. 15%15%
ProteusProteus spsp.. 10%10%
EnterococcusEnterococcus 9%9%
Coag.neg.StaCoag.neg.Sta.. 3%3%
OtherOther 16%16%
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Hemoculture
No. of samples: 970
positive: 18%
negative: 82%
Distribution:
Sta.coag.negSta.coag.neg:: 53%53%
KlebsKlebs.,.,EnterobEnterob.:.: 12%12%
PseudomonasPseudomonas spsp.:.:8%8%
E.coli:E.coli: 5%5%
Group B-.Strept: 4%
α,β hem.Str. 4%
Fungi: 3%
Other: 11%
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Test of efficacy= patient’s Test of efficacy= patient’s responseresponse
No respond to seemingly appropriate No respond to seemingly appropriate therapy: reassessment is needed!therapy: reassessment is needed!
In some infections additional supportive In some infections additional supportive treatment ( surgical) is necessarytreatment ( surgical) is necessary
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Tonsillitis, tonsillopharyngitisTonsillitis, tonsillopharyngitis
Streptococcus pyogenes : Penicillin for 10 Streptococcus pyogenes : Penicillin for 10 daysdays
Penicillin allergy: macrolid antibioticsPenicillin allergy: macrolid antibiotics Non- Streptococcus origin: amoxicillin, Non- Streptococcus origin: amoxicillin,
amoxicillin+ clavulanic acid, macrolids, amoxicillin+ clavulanic acid, macrolids, cephalosporin antibioticscephalosporin antibiotics
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Anaerobic infectionsAnaerobic infections
Oropharynx, gastrointestinal tract, vagina, Oropharynx, gastrointestinal tract, vagina, skinskin
Gram- negative nonsporulating rods: Gram- negative nonsporulating rods: Bacteroides, FusobacteriumBacteroides, Fusobacterium
Gram-positive nosporulating rods: Gram-positive nosporulating rods: Eubacterium, PropionibacteriumEubacterium, Propionibacterium
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Anaerobic infectionsAnaerobic infections
Neonates: prolonged rupture of membranes, Neonates: prolonged rupture of membranes, amnionitis, obstetric difficultiesamnionitis, obstetric difficulties
Peritonitis, appendicitisPeritonitis, appendicitis Aspiration pneumonia with lung abscessAspiration pneumonia with lung abscess Orofacial infectionsOrofacial infections Brain abscessBrain abscess
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Periodontal infection („trench mouth”)Periodontal infection („trench mouth”)Acute Necrotizing Ulcerative Gingivitis Acute Necrotizing Ulcerative Gingivitis
( ANUG)( ANUG) Periapical abscessesPeriapical abscesses Anaerobic osteomyelitis of the mandible Anaerobic osteomyelitis of the mandible
/maxilla/maxilla
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Vincent stomatititsVincent stomatitits
Ulcers covered by brown/grey, foul-Ulcers covered by brown/grey, foul-smelling exudatesmelling exudate
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Ludwig anginaLudwig angina
Acute cellulitis of the sublingual and Acute cellulitis of the sublingual and submandibular spacessubmandibular spaces
Rapid spreadRapid spread Edema of the tongue and airwayEdema of the tongue and airway
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Anaerobic infections/ treatmentAnaerobic infections/ treatment
Cefoxitin, amoxicillin/ clavulanate, Cefoxitin, amoxicillin/ clavulanate, clindamycinclindamycin
MetronidazoleMetronidazole Cefotetan Cefotetan Imipenem, merapenemImipenem, merapenem Piperacillin, tazobactamPiperacillin, tazobactam
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CEPHALOSPORIN ANTIBIOTICSCEPHALOSPORIN ANTIBIOTICS
1.1. generation drugsgeneration drugs
CefazolinCefazolin (Kefzol) (Kefzol) does not does not cross the cross the blood- brain barrier. No use for blood- brain barrier. No use for initial th. of initial th. of sepsis / meningitissepsis / meningitis
CefalexinCefalexin (Keflex. Ospexin)(Keflex. Ospexin)
CefadoxilCefadoxil (Duracef)(Duracef)
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2. generation drugs2. generation drugs
CefamandolCefamandol (Mandokef)(Mandokef)
CefuroximCefuroxim (Zinnat, Zinacef)(Zinnat, Zinacef)
CefoxitinCefoxitin (Mefoxin)(Mefoxin)
CefaclorCefaclor (Ceclor)(Ceclor)
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3. 3. generation drugsgeneration drugs
CefotaximCefotaxim ee (Claforan)(Claforan)
CeftriaxoneCeftriaxone (Rocephin)(Rocephin)
CefoperazonCefoperazon (Cefobid)(Cefobid)
CeftazidimCeftazidim ((Fortum)((Fortum)
CefiximCefixim (Suprax)(Suprax)
CeftibutenCeftibuten (Cedax) (Cedax)
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4.4. generation druggeneration drug
CefepimCefepim (Maxipime)(Maxipime)
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PresentationPresentation 7-year-old boy7-year-old boy 3 weeks of headache refractory to acetaminophen, 1 day of altered 3 weeks of headache refractory to acetaminophen, 1 day of altered
mental status, diplopia, photophobiamental status, diplopia, photophobia Physical examination: he is difficult to arouse and is confused. He Physical examination: he is difficult to arouse and is confused. He
vomits once in the ED.vomits once in the ED. No skin lesions, signs of meningeal irritation, or joint swelling. No skin lesions, signs of meningeal irritation, or joint swelling.
Bilateral papilledema and photophobiaBilateral papilledema and photophobia WBC 15.8x10WBC 15.8x1099/L, 85% segmented neutrophils. Lumbar /L, 85% segmented neutrophils. Lumbar puncture, puncture,
CSF sent for Lyme titers, serum antibodies: positive for CSF sent for Lyme titers, serum antibodies: positive for IgG and negative for IgMIgG and negative for IgM
Th: 28 days IV ceftriaxone (100 mg/kg per day)Th: 28 days IV ceftriaxone (100 mg/kg per day) Additional questioning:2 months prior he had erythema migrans, was Additional questioning:2 months prior he had erythema migrans, was
diagnosed as having Lyme disease, and was treated with 21 days of diagnosed as having Lyme disease, and was treated with 21 days of cefuroxime cefuroxime
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PENICILLINPENICILLIN
Penicillin G VPenicillin G VStreptococcusStreptococcus
procain-penicillinprocain-penicillin Str. Str. pneumoniaepneumoniae
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METHICILLINMETHICILLIN
OxacillinOxacillin
Staphylococcus Staphylococcus aureusaureus
NafcillinNafcillin
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AMINOPENICILLINAMINOPENICILLIN
(ampicillin , amoxicillin) (ampicillin , amoxicillin) Streptococcus BStreptococcus B
Str. Str. pneumoniaepneumoniae
ListeriaListeria
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AMINOPENICILLINAMINOPENICILLIN
beta+-lactamasebeta+-lactamase respiratory , respiratory , inhibitorinhibitor
urinary tract urinary tract infectionsinfections
(ampicillin+sulfactam,(ampicillin+sulfactam,amoxicillin+clavulanic acid)amoxicillin+clavulanic acid)
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UREIDOPENICILLINUREIDOPENICILLIN
mezlocillin, piperacillinmezlocillin, piperacillin
(+beta-lactamase inhibitor as well)(+beta-lactamase inhibitor as well)
piperacillin/tazobactampiperacillin/tazobactam
Severe systemic infectionsSevere systemic infections
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TetracyclinesTetracyclines
Good effect:Good effect: Chlamydia, Mycoplasma, Actinomyces, Chlamydia, Mycoplasma, Actinomyces,
Lyme disease, pelvic infections, urethritis, Lyme disease, pelvic infections, urethritis, brucellosisbrucellosis
Contraindicated before the age of Contraindicated before the age of 10 yrs!10 yrs!
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ANTIBIOTIC DRUGSANTIBIOTIC DRUGS
Active ingredientActive ingredient ProductProduct
AmoxicillinAmoxicillin Aktil, AugmentinAktil, Augmentin
+ clavulanic acid+ clavulanic acid
AmpicillinAmpicillin Ospamox,Ospamox,Penstabil,Penstabil,
PentrexylPentrexyl
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Active ingredientActive ingredient ProductProduct
AmpicillinAmpicillin UnasynUnasyn
+Sulbactam+Sulbactam
AzithromycinAzithromycin SumamedSumamed
AzlocillinAzlocillin SecuropenSecuropen
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Active ingredientActive ingredient ProductProduct
CefadroxilCefadroxil DuracefDuracef
CeftazidimeCeftazidime FortumFortum
CeftriaxonCeftriaxon RocephinRocephin
CefiximCefixim SupraxSuprax
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Active ingredientActive ingredient ProductProduct
CefepimeCefepime MaxipimeMaxipime
CeftibutenCeftibuten CedaxCedax
CefoperazonCefoperazon CefobidCefobid
CefotaximCefotaxim ClaforanClaforan
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Active ingredientActive ingredient ProductProduct
CefuroximCefuroxim Zinacef, ZinnatZinacef, Zinnat
ClarithromycinClarithromycin KlacidKlacid
ClindamycinClindamycin Dalacin CDalacin C
CiprofloxacinCiprofloxacin Ciprobay, Cifran,Ciprobay, Cifran,SupplinSupplin
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Active ingredientActive ingredient ProductProduct
ImipenemImipenem TienamTienam+ cilostatin+ cilostatin
JosamycinJosamycin WilprafenWilprafen
MeropenemMeropenem MeronemMeronem
MetronidazolMetronidazol KlionKlion
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Active ingredientActive ingredient ProductProduct
MezlocillinMezlocillin BaypenBaypen
NetilmicinNetilmicin NetromycineNetromycine
PenicillinPenicillin Maripen, Maripen, Ospen,Ospen,
VegacillinVegacillin
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Active ingredientActive ingredient ProductProduct
SulfamethoxazolSulfamethoxazol Sumetrolim, Sumetrolim,
+trimethoprim+trimethoprim Bactrim, Bactrim, CotrimelCotrimel
TeicoplaninTeicoplanin Targocid Targocid
TobramycinTobramycin Brulamycin Brulamycin
VancomycinVancomycin Vancocyn Vancocyn