Einheit für pädiatrische Infektiologie Antibiotics - what, why, when and how?

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1 Einheit für pädiatrische Infektiologie Antibiotics - what, why, when and how? Andrea Duppenthaler

2 Limping patient local pain swelling tenderness warmth fever acute Osteomyelitis

3 What to expect? Arnold et al, Pediatrics 2012,130;4:e821

4 acute Osteomyelitis Diagnostic work up age? exposition? underlying diseases? antibiotic pre-treatmen? Neonate: GBS, E. coli Infants: gram-neg s, S.aureus, Streptococci Children/Adolescents: S. aureus

5 acute Osteomyelitis Diagnostic work up - culture blood - culture aspiration - material for PCR? - serology? empiric treatment?

6 β - Lactam Penicilline Penicillin G/V Cephalosporine Cefuroxim Axetil II Makrolid Clarithromycin Azithromycin Lincosamid Clindamycin Amoxicillin Cefaclor II Erythromycin Oxazolidin Flucloxacillin Co - Amoxicillin Piperacillin Pip/Tazobactam Nitrofurantoin Phosphor-acid Fosfomycin Imidazole Metronidazol Polymyxin Colistin Cefpodoxim Ceftibuten Ceftriaxon Cefepime Lipopeptid Daptomycin Monobactam Aztreonam Quinolones Ciprofloxacin Moxifloxacin Norfloxacin III III III IV Carbapenem Meropenem Imipenem Ertapenem Sulfonamid Cotrimoxazol Aminoglycosides Amikacin Gentamycin Streptomycin Tobramycin Linezolid Glycopeptide Vancomycin Teicoplanin Steroid-Antibitics Fusidinsäure Rifamycin Rifampicin Tetrazykline Doxycyclin Minocyclin

7 mode of action Feigin&Cherry, Textbook Ped infect Dis7th edt

8 growth of bacteria log CFU normal growth Makrolids TMP/SMX bacteriostatic bactericidal β - Lactams t

9 Atyp.Organisms (Mykoplasma, Chlamydien) Pseudomonas ESBL Gram positiv Gram negativ Enterobacteriacea Haemophilus Moraxella Neisseria Enterococci Streptckocci A,B,C,G,Pneumo Staphylococcus aureus MRSA bactericidal bacterio static Aminopenicllin Aminopenicillin with β - Lactam Broadspektrumpenicillin Ceph I Ceph II Ceph III Ceph IV (iv) Carbapenem (iv) Glycopeptides Aminoglykosides (iv, inhalativ) Quinolones Makrolids TMP/SMX Clindamycin Tetracyklin

10 acute hematogenous osteomyelitis Treatment options: bactericidal vs. bacteriostatic? age > 4j: S. aureus, age < 4j S. aureus, gram-neg s, Streptococci

11 tonsils: S. pyogenes lymphnodes: S. pyogenes S. aureus urinary tract: E. coli Klebsiella spp. Enterococcus spp. Ô ENT: S. pneumoniae M. catarrhalis H. influenzae pulmonary: S. pneumoniae M. catarrhalis H. influenzae musculoskeletal: S. aureus GBS, GAS K. kingae (Enterobacteriaceae) skin: S. pyogenes S. aureus (MRSA) Sepsis CH E. coli S. pneumoniae S. aureus N. meningitidis Indikation für Antibiotika im Hinblick auf Resistenzentwicklung A. Duppenthaler

12 Feigin&Cherry, Textbook Ped infect Dis7th edt

13 Bone penetration antibacterial substance dependent on: serum level molecular size protein binding blood flow local ph

14 Pharmakodynamics Feigin&Cherry, Textbook Ped infect Dis7th edt

15 Bioavailability and Bone Penetration Roberts K, 2014 sites.utexas

16 Choice of antibacterial substance spectrum bactericidal vs bacteriostatic distribution/penetration bioavailability: good for: TMP-SMX, Clindamycin, Linezolid, Quinolones, Metronidazole, Rifampicin

17 Treatment Osteomyelitis high burden of bacteria concentration above MIC at the site of infection for a sufficient time periode iv! high dosage, right interval bone - turnover slow length of treatment (3-4 weeks)

18 Treatment Osteomyelitis Initially parenteral Proposal PIGS:

19 Antimicrobial resistance = Survival strategy of bacteria! intrinsic vs. acquired - driven by antibiotic exposure - subinhibitory drug leves survival of the fittest - transfer to other bacteria

20 Antimicrobial resistance BMC Biology :123

21 Take Home Message Diagnostic work - up before treatment start broad, step down not only spectrum matters: pharmakokinetics and dynamics high burden of bacteria: - high concentration (iv > oral) - adequate doses - interval as short as possible

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