Principles of antibiotic therapy in paediatrics

Dr. György FeketeDr. György Fekete

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.)

2. Previous microbiological 2. Previous microbiological investigations?investigations?

- throat- throat

- urine- urine

- haemoculture- haemoculture

- cerebrospinal fluid- cerebrospinal fluid

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)

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

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)

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

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

Active tuberculosisActive tuberculosis

Treatment: INH, rifampin, pyrazinamideTreatment: INH, rifampin, pyrazinamide Ethambutol, ethionamideEthambutol, ethionamide

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”

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.)

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

Antimicrobial prophylaxisAntimicrobial prophylaxis

Splenectomy / aspleniaSplenectomy / asplenia Str. pneumoniaeStr. pneumoniae PenicillinPenicillin

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

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

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

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

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))

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!!

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%

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%

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%

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

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

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

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

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

Vincent stomatititsVincent stomatitits

Ulcers covered by brown/grey, foul-Ulcers covered by brown/grey, foul-smelling exudatesmelling exudate

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

Anaerobic infections/ treatmentAnaerobic infections/ treatment

Cefoxitin, amoxicillin/ clavulanate, Cefoxitin, amoxicillin/ clavulanate, clindamycinclindamycin

MetronidazoleMetronidazole Cefotetan Cefotetan Imipenem, merapenemImipenem, merapenem Piperacillin, tazobactamPiperacillin, tazobactam

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)

2. generation drugs2. generation drugs

CefamandolCefamandol (Mandokef)(Mandokef)

CefuroximCefuroxim (Zinnat, Zinacef)(Zinnat, Zinacef)

CefoxitinCefoxitin (Mefoxin)(Mefoxin)

CefaclorCefaclor (Ceclor)(Ceclor)

3. 3. generation drugsgeneration drugs

CefotaximCefotaxim ee (Claforan)(Claforan)

CeftriaxoneCeftriaxone (Rocephin)(Rocephin)

CefoperazonCefoperazon (Cefobid)(Cefobid)

CeftazidimCeftazidim ((Fortum)((Fortum)

CefiximCefixim (Suprax)(Suprax)

CeftibutenCeftibuten (Cedax) (Cedax)

4.4. generation druggeneration drug

CefepimCefepim (Maxipime)(Maxipime)

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

PENICILLINPENICILLIN

Penicillin G VPenicillin G VStreptococcusStreptococcus

procain-penicillinprocain-penicillin Str. Str. pneumoniaepneumoniae

METHICILLINMETHICILLIN

OxacillinOxacillin

Staphylococcus Staphylococcus aureusaureus

NafcillinNafcillin

AMINOPENICILLINAMINOPENICILLIN

(ampicillin , amoxicillin) (ampicillin , amoxicillin) Streptococcus BStreptococcus B

Str. Str. pneumoniaepneumoniae

ListeriaListeria

AMINOPENICILLINAMINOPENICILLIN

beta+-lactamasebeta+-lactamase respiratory , respiratory , inhibitorinhibitor

urinary tract urinary tract infectionsinfections

(ampicillin+sulfactam,(ampicillin+sulfactam,amoxicillin+clavulanic acid)amoxicillin+clavulanic acid)

UREIDOPENICILLINUREIDOPENICILLIN

mezlocillin, piperacillinmezlocillin, piperacillin

(+beta-lactamase inhibitor as well)(+beta-lactamase inhibitor as well)

piperacillin/tazobactampiperacillin/tazobactam

Severe systemic infectionsSevere systemic infections

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!

ANTIBIOTIC DRUGSANTIBIOTIC DRUGS

Active ingredientActive ingredient ProductProduct

AmoxicillinAmoxicillin Aktil, AugmentinAktil, Augmentin

+ clavulanic acid+ clavulanic acid

AmpicillinAmpicillin Ospamox,Ospamox,Penstabil,Penstabil,

PentrexylPentrexyl

Active ingredientActive ingredient ProductProduct

AmpicillinAmpicillin UnasynUnasyn

+Sulbactam+Sulbactam

AzithromycinAzithromycin SumamedSumamed

AzlocillinAzlocillin SecuropenSecuropen

Active ingredientActive ingredient ProductProduct

CefadroxilCefadroxil DuracefDuracef

CeftazidimeCeftazidime FortumFortum

CeftriaxonCeftriaxon RocephinRocephin

CefiximCefixim SupraxSuprax

Active ingredientActive ingredient ProductProduct

CefepimeCefepime MaxipimeMaxipime

CeftibutenCeftibuten CedaxCedax

CefoperazonCefoperazon CefobidCefobid

CefotaximCefotaxim ClaforanClaforan

Active ingredientActive ingredient ProductProduct

CefuroximCefuroxim Zinacef, ZinnatZinacef, Zinnat

ClarithromycinClarithromycin KlacidKlacid

ClindamycinClindamycin Dalacin CDalacin C

CiprofloxacinCiprofloxacin Ciprobay, Cifran,Ciprobay, Cifran,SupplinSupplin

Active ingredientActive ingredient ProductProduct

ImipenemImipenem TienamTienam+ cilostatin+ cilostatin

JosamycinJosamycin WilprafenWilprafen

MeropenemMeropenem MeronemMeronem

MetronidazolMetronidazol KlionKlion

Active ingredientActive ingredient ProductProduct

MezlocillinMezlocillin BaypenBaypen

NetilmicinNetilmicin NetromycineNetromycine

PenicillinPenicillin Maripen, Maripen, Ospen,Ospen,

VegacillinVegacillin

Active ingredientActive ingredient ProductProduct

SulfamethoxazolSulfamethoxazol Sumetrolim, Sumetrolim,

+trimethoprim+trimethoprim Bactrim, Bactrim, CotrimelCotrimel

TeicoplaninTeicoplanin Targocid Targocid

TobramycinTobramycin Brulamycin Brulamycin

VancomycinVancomycin Vancocyn Vancocyn