Principles of antibiotic therapy in paediatrics Dr. György Fekete

1. What is the reason? Indication? Antibiotics 1. What is the reason? Indication? - local infection - empiric and targeted teatment - fever + general symptoms (CRP, WBC count and smear, etc.)

2. Previous microbiological investigations? - throat - urine - haemoculture - cerebrospinal fluid

3. What is the potential (bacterial) cause of infection? - age (newborn, infant, toddler…) - medical procedure, hospitalisation - immune deficiency - organ damage (spleen, liver, kidney)

Neonatal sepsis /meningitis Focal infection: pneumonia, RDS Group B streptococci, E. coli, other Gram-negative rods, Listeria monocytogenes Th: Ampicillin+ gentamicin third generation cephalosporin instead of aminoglycoside

Bacterial meningitis in children, 2months to 12 yrs S. pneumoniae, N. meningitidis, (H. influenzae type b) Therapy: - cefotaxime / ceftriaxone + vancomycine - 3. generation cephalosporines (Cefotaxime, Ceftriaxone)

4. Which antibiotic will be optimal? First choice? - data of bacterial resistance - site of infection – penetration? - side effects? - bactericide effect - administration: 1x / day - not expensive

5. Any combination is appropriate? - nosocomial infection - sepsis - abdominal and pelvic infections - endocarditis - empiric treatment - active tuberculosis

Active tuberculosis Treatment: INH, rifampin, pyrazinamide Ethambutol, ethionamide

6. Metabolism, excretion? - kidney, liver (monitoring) - renal: aminoglycosides - liver:erythromycin, clindomycin 7. Mode of administration - iv, oral - „switch”

8. Dosage ? 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.)

Antimicrobial prophylaxis Neonatal conjunctivitis Chlamydia trachomatis 0,5% erythromycin topically Neisseria gonorrhoeae 1% silver nitrate or

Antimicrobial prophylaxis Splenectomy / asplenia Str. pneumoniae Penicillin

Resistant clones of microorganisms Str. pneumoniae Staph. aureus Virulent Serious infections Overuse of antibiotics Viral infections Broad spectrum antimicrobial agents

Antibiotic management of Staphylococcus aureus infections in US Children’s hospitals, 1999-2008 Trends in antibiotic management for S. aureus infections, hospitalized children The use of vancomycin, clindamycin, linezolid, trimethoprim-sulfamethoxazole, cefazolin, and oxacillin/nafcillin were examined for percentage use and days of therapy per 1000 patient- day 64 813 patients had a discharge diagnosis for S. aureus infection The incidence of methicillin-resistant S. aureus (MRSA) infections increased 10-fold (2 to 21 cases per 1000 admissions), methicillin- susceptible infection rate remained stable Clindamycin showed the greatest increase: 21% in 1999 and 63% in 2008 Importance of continuous monitoring of local S. aureus susceptibility patterns Herigon J.C et al. Pediatrics 2010, 125:1267

Broad - spectrum antimicrobial agents Drastic changes in bowel flora Bleeding disorders Emergence of resistant organisms Superinfections: yeasts, enterococci

Local (hospital) microbiological laboratory Knowing the prevalence of antibiotic – resistant organisms in a particular community (nursery) is helpful in choosing the first-line antibiotic regimens

Specific therapeutic values Vancomycin: methicillin-resistant staphylococci Metronidazole: anaerobic infections Ceftazidine: Pseudomonas aeruginosa Trimethoprime+ sulfamethoxazole: shigellosis, salmonellosis, Pneumocysis carinii ( pentamidine)

Test of efficacy= patient’s response No respond to seemingly appropriate therapy: reassessment is needed! In some infections additional supportive treatment ( surgical) is necessary

Tonsillitis, tonsillopharyngitis Streptococcus pyogenes : Penicillin for 10 days Penicillin allergy: macrolid antibiotics Non- Streptococcus origin: amoxicillin, amoxicillin+ clavulanic acid, macrolids, cephalosporin antibiotics

Anaerobic infections Oropharynx, gastrointestinal tract, vagina, skin Gram- negative nonsporulating rods: Bacteroides, Fusobacterium Gram-positive nosporulating rods: Eubacterium, Propionibacterium

Anaerobic infections Neonates: prolonged rupture of membranes, amnionitis, obstetric difficulties Peritonitis, appendicitis Aspiration pneumonia with lung abscess Orofacial infections Brain abscess

Periodontal infection („trench mouth”) Acute Necrotizing Ulcerative Gingivitis ( ANUG) Periapical abscesses Anaerobic osteomyelitis of the mandible /maxilla

Vincent stomatitits Ulcers covered by brown/grey, foul-smelling exudate

Ludwig angina Acute cellulitis of the sublingual and submandibular spaces Rapid spread Edema of the tongue and airway

Anaerobic infections/ treatment Cefoxitin, amoxicillin/ clavulanate, clindamycin Metronidazole Cefotetan Imipenem, merapenem Piperacillin, tazobactam

CEPHALOSPORIN ANTIBIOTICS 1. generation drugs Cefazolin (Kefzol) does not cross the blood- brain barrier. No use for initial th. of sepsis / meningitis Cefalexin (Keflex. Ospexin) Cefadoxil (Duracef)

2. generation drugs Cefamandol (Mandokef) Cefuroxim (Zinnat, Zinacef) Cefoxitin (Mefoxin) Cefaclor (Ceclor)

3. generation drugs Cefotaxim e (Claforan) Ceftriaxone (Rocephin) Cefoperazon (Cefobid) Ceftazidim ((Fortum) Cefixim (Suprax) Ceftibuten (Cedax)

4. generation drug Cefepim (Maxipime)

Presentation 7-year-old boy 3 weeks of headache refractory to acetaminophen, 1 day of altered mental status, diplopia, photophobia Physical examination: he is difficult to arouse and is confused. He vomits once in the ED. No skin lesions, signs of meningeal irritation, or joint swelling. Bilateral papilledema and photophobia WBC 15.8x109/L, 85% segmented neutrophils. Lumbar puncture, CSF sent for Lyme titers, serum antibodies: positive for IgG and negative for IgM Th: 28 days IV ceftriaxone (100 mg/kg per day) Additional questioning:2 months prior he had erythema migrans, was diagnosed as having Lyme disease, and was treated with 21 days of cefuroxime

PENICILLIN Penicillin G V Streptococcus procain-penicillin Str. pneumoniae

METHICILLIN Oxacillin Staphylococcus aureus Nafcillin

AMINOPENICILLIN (ampicillin , amoxicillin) Streptococcus B Str. pneumoniae Listeria

amoxicillin+clavulanic acid) AMINOPENICILLIN beta+-lactamase respiratory , inhibitor urinary tract infections (ampicillin+sulfactam, amoxicillin+clavulanic acid)

UREIDOPENICILLIN mezlocillin, piperacillin (+beta-lactamase inhibitor as well) piperacillin/tazobactam Severe systemic infections

Tetracyclines Contraindicated before the age of 10 yrs! Good effect: Chlamydia, Mycoplasma, Actinomyces, Lyme disease, pelvic infections, urethritis, brucellosis Contraindicated before the age of 10 yrs!

ANTIBIOTIC DRUGS Active ingredient Product Amoxicillin Aktil, Augmentin + clavulanic acid Ampicillin Ospamox, Penstabil, Pentrexyl

Active ingredient Product Ampicillin Unasyn +Sulbactam Azithromycin Sumamed Azlocillin Securopen

Active ingredient Product Cefadroxil Duracef Ceftazidime Fortum Ceftriaxon Rocephin Cefixim Suprax

Active ingredient Product Cefepime Maxipime Ceftibuten Cedax Cefoperazon Cefobid Cefotaxim Claforan

Active ingredient Product Cefuroxim Zinacef, Zinnat Clarithromycin Klacid Clindamycin Dalacin C Ciprofloxacin Ciprobay, Cifran, Supplin

Active ingredient Product Imipenem Tienam + cilostatin Josamycin Wilprafen Meropenem Meronem Metronidazol Klion

Active ingredient Product Mezlocillin Baypen Netilmicin Netromycine Penicillin Maripen, Ospen, Vegacillin

Active ingredient Product Sulfamethoxazol Sumetrolim, +trimethoprim Bactrim, Cotrimel Teicoplanin Targocid Tobramycin Brulamycin Vancomycin Vancocyn