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Principles of antibiotic therapy in paediatrics. Dr. György Fekete. Special pediatric considerations. Immunology Pharmacokinetics Overuse of antibiotics Mistake: fever = antibiotic therapy Except: neutropenia!. Antimicrobial Programme. Reduction of healthcare associated infections
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Principles of antibiotic therapy in paediatrics Dr. György Fekete
Special pediatric considerations • Immunology • Pharmacokinetics • Overuse of antibiotics • Mistake: fever = antibiotic therapy • Except: neutropenia!
AntimicrobialProgramme Reduction of healthcareassociatedinfections Slowingthedevelopment of antimicrobialresistance Right Drug, RightDose, Right Time, Right Duration
Antibiotics 1. What is the reason? Indication? - local infection (skin, pneumonia, UTI, etc.) - empiric and targeted teatment - fever + general symptoms (CRP, WBC count and smear, procalcitonin, etc.)
Donot start antibioticswithoutevidence of bacterialinfection! History of allergies – atopicallergy Penicillin hypersensitivity: 1 – 10%, anaphylacticreactions < 0.05% 0.5 – 6.5% of patientsallergictopenicillins: alsoallergictocephalosporins Start prompt effectivetreatmentwithinonehour of diagnosis: severesepsis, lifethreateninginfections
Toprescribe antibioticswhicharelikelyto be bactericidaltothepathogenatthe site of infection inadequatedosis + adequateduration fortheshortestdurationlikelyto be effective
Precisedocumentation Clinicalindication Dose and route of administration Drugchart + clinicalnotes Review/ stop dateorduration Allsensitivityresults Consultationwithmicrobiologist
2. Previous microbiological investigations? - Gram staining - throat - urine - haemoculture - cerebrospinal fluid - pleural, synovial fluid - rapid tests (Str.pyogenes, S. pneumoniae, H. influenzae antigens)
3. What is the potential (bacterial) cause of infection? - age (newborn, infant, toddler…) - medical procedure, hospitalisation - immune deficiency - organ damage (spleen, liver, kidney)
Localizing symptoms Skin Upper respiratory Lower respiratory Genitourinary Gastrointestinal CNS Skeletal Cardiovascular Hepatic
Skin: Sta. aureus, Str. pyogenes • Deep infections: anaerobic, Gram negative • Tonsillopharyngitis 15-20%: Str. pyogenes • Differential dg:infectious mononucleosis • Cystic fibrosis: pulmonary infection, Pseudomonas aeruginosa • Diabetes mellitus: Sta.aureus
Neonatal sepsis /meningitis Focalinfection: pneumonia, RDS Group B streptococci, E. coli, otherGram-negativerods, Listeriamonocytogenes, S. aureus Th: Ampicillin+ cefotaxim Thirdgenerationcephalosporininstead of aminoglycoside
Bacterialmeningitisinchildren, 2 monthsto 12 yrs Str. pneumoniae, N. meningitidis (B,C) (H. influenzaetype b) Therapy: 1 – 3 months: - cefotaxime / ceftriaxone + ampicillin +vancomycin >3 months:cefotaxime/ceftriaxone +vancomycin
Bacterialmeningitis Empirictherapy: < 3 months: IV Cefotaxime + IVAmoxicillin > 3 months: IV Ceftriaxone Neisseriameningitidis: Ivcefotaxime 7 days (+ IV Vancomycin) Group B Streptococcus: IV Cefotaxime 14 days Gramnegativeinfections: IV cefotaxime 21 days
Listeriamonocytogenes: IV amoxicillin 21 days + Gentamicininthefirst7 days
4. Which antibiotic will be optimal? First choice? - data of bacterial resistance (enterococci are resistant to cephalosporins) - site of infection – penetration? - side effects? - bactericide effect - administration: 1x / day - not expensive
Resistant clones of microorganisms • Str. pneumoniae • Staph. aureus • Virulent • Serious infections • Overuse of antibiotics • Viral infections • Broad spectrum antimicrobial agents
5. Any combination is appropriate? - nosocomial infection - sepsis (focal infection is not known,granulocytopenia) - abdominal and pelvic infections - endocarditis - empiric treatment - active tuberculosis
Susceptibility testing It is the opportunity to avoid broader spectrum (and more expensive) antibiotics when a more narrowly active (and cheaper) drug is effective!
No combination therapy is necessary in cases of „non-hospital” infections • Exception: the doctor can not decide whether pneumonia is „typical” or „atypical” • Therapy: beta- lactam+ macrolid antiobiotics • Atypical pneumonia syndrome: Legionella, Chlamydia trachomatis (psittaci, pneumoniae), Mycoplasma pneumoniae
Active tuberculosis Treatment: INH, rifampin, pyrazinamide Ethambutol, ethionamide
6. Metabolism, excretion? - kidney, liver (monitoring) - renal: aminoglycosides - liver: erythromycin, clindamycin, ceftriaxon - maternal antiobiotic treatment during breast – feeding (chloramphenicol, tetracyclin,sulfonamids,metronidasol) 7. Mode of administration - iv, oral - „switch”
Iv. administration (initial 2 weeks) Sepsis, meningitis Endocarditis Liver abscess Osteomyelitis Septic arthritis Empyema Cavitating pneumonia
Long-termhypotension Hemorrhagicdiathesis Severeornecrotisingsofttissueinfections Intracranialabscesses Intra – abdominalsepsis Exacerbation of cysticfibrosis Severeinfectionsduringchemotherapy-relatedneutropenia
Switchingfrom IV tooraladministration Clinicalimprovement The patient is medicallystable
8. Dosage ? Body surface, body weight Special doses in neonates 9. Changing of antiobiotic drug? Indications? 10. How long should we treat? - Preterm and newborn babies need antibiotic therapy of longer duration (sepsis, bacterial meningitis, etc.)
Optimal duration of antibiotic therapy Streptococcal tonsillopharyngitis: penicillin/ 10days Acute osteomyelitis: 4-6 weeks UTI: 7- 14 days (multiresistant Gram negative bacteria: 4-6 weeks)
Antimicrobial prophylaxis Neonatalconjunctivitis • Chlamydia trachomatis • 0.5% erythromycintopically • Neisseriagonorrhoeae • 1% silvernitrateor • 0.5% erythromycintopically
Antimicrobial prophylaxis Splenectomy / asplenia Str. pneumoniae Penicillin
Antimicrobial prophylaxis Prevention of early-onset B group Streptococcus infection Maternal screening (26-28. gestational week) Iv. ampicillin, or clindamycin, erythromycin
Antimicrobial prophylaxis • Rheumatic fever • Long-term Penicillin prophylaxis • Recurrent UTI ( vesio-ureteral reflux, etc.) • Bacterial endocarditis
Broad - spectrum antimicrobial agents Drastic changes in bowel flora Bleeding disorders Emergence of resistant organisms Superinfections: yeasts, enterococci
Cellulitis (phlegmone) Inflammation of the subcutaneous connective tissue – may lead to abscess Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae (<2 yrs) Therapy: IV penicillin+ clindamycin, flucloxacillin
Erysipelas Group A Streptococcus, Staph. aureus Therapy: phenoxymethylpenicillin Staph. aureus: PO flucloxacillin (beta –lactamantibiotic of thepnicillinclass)
Tonsillitis, tonsillopharyngitis Streptococcus pyogenes : Penicillin for 10 days Penicillin allergy: macrolid antibiotics Non- Streptococcus origin: amoxicillin, amoxicillin+ clavulanic acid, macrolids, cephalosporin antibiotics
Epiglottitis Emergency! 2-7 yrs Haemophilus influenzae type B (vaccination) Sudden onset of fever Dysphagia, muffled voice, cyanosis, stridor, inspir. retractions Progression to total airway obstruction Th: endotracheal intubation, ceftriaxone iv. Manipulate as little as possible!
Pediatric pulmonary diseases 50% of deaths under age of 1 yr 20% of all hospitalisations under age of 15 yrs 7% of children: chronic disorder of the lower respiratory system
Most common diseases Viral upper respiratory infections Otitis media Pneumonia Asthma Cystic fibrosis
Symptoms Dyspnea, tachypnea, hyperpnea Cough Chest pain Rales(crackles), rhonchi Wheezing Retractions Fever
Bacterial pneumonia Risks: aspiration, immunodeficiency, tracheoesophageal fistula, cleft palate, CF, congestive heart failure, splenectomia,etc. Fever, cough, dyspnea, meningismus, abdominal pain, otitis media Laboratory findings: elevated WBC, CRP Chest X-ray Age-specific bacteria Complications: empyema, sepsis, abscesses
Diagnostic measures History (parents, child) Inspection (flaring of alae nasi) Auscultation (take a deep breath: blow out a candle) Respiratory rate (younger than 1 year: 25-35/min, sleeping) Imaging techniques Arterial blood gas analysis Pulse oximetry, capnography Pulmonary function testing Laryngoscopy, bronchoscopy
Uncomplicatedcommunityacquiredpneumonia <5 years : PO amoxicillin (+macrolideif no response) 5 – 18 yrs: PO amoxicillin + POclarithromycin
Hospitalacquiredpneumonia IV ceftazidime (+IVgentamicininPseudomonasaerug. infection) IV Vancomycin + IVAztreonam
Urinarytractinfections Children <3 monthswithpossible UTI infection: IV Cefotaxime+ IV Amoxicillin Acutepyelonephritis > 3 months: IV Ceftriaxone, 72 hrs, thenreview. Step down to PO cefalexin
Specific therapeutic values Vancomycin: methicillin-resistantstaphylococci Metronidazole: anaerobicinfections Ceftazidine: Pseudomonasaeruginosa Trimethoprime+ sulfamethoxazole:shigellosis, salmonellosis, Pneumocysiscarinii ( pentamidine)