Katharina Kreitmeyri,II,VI, Ulrich Von Bothi,VI, Alenka Pecarii, Johannes P. Bordeiii
Katharina KreitmeyrI,II,VI, Ulrich von BothI,VI, Alenka PecarII, Johannes P. BordeIII, Rafael MikolajczykIV,V,VI, Johannes HuebnerI,III,VI
Pediatric Antibiotic Stewardship: Successful Interventions to Reduce Broad-Spectrum Antibiotic Use on General Pediatric Wards
Keywords: Pediatric Antibiotic Stewardship; Quality of Care, days of therapy (DoT); Antimicrobial Stewardship Program (ASP); Dosing Accuracy; Patient Safety
Acknowledgments: This work was supported by AOK Bayern - Die Gesundheitskasse. On behalf of all authors, the corresponding author states that there is no conflict of interest.
______
I Division of Pediatric Infectious Diseases, Dr. von Hauner Children's Hospital, , LMU Munich, Lindwurmstr. 4, 80337 Munich, Germany
II Hospital Pharmacy, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
III Division of Infectious Diseases, University Medical Center, Hugstetter Str. 55, 79106 Freiburg i. Br, Germany
IV Epidemiological and Statistical Methods Research Group, Helmholtz-Center for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany
V Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
VI German Center for Infection Research (DZIF)
*Corresponding Author:
Katharina Kreitmeyr ()
Division of Pediatric Infectious Diseases, Dr. von Hauner Children's Hospital, LMU Munich, Lindwurmstr. 4, 80337 Munich, Germany
Electronic Supplementary Material
Tab. S1 Local Empiric Antibiotic Guideline, AntibiotiKARTE
Check before EVERY antibiotic therapy: / Is an antibiotic really necessary? Prescribe antibiotics only when a clear clinical benefit is expected.Does the patient have any allergies or signs of renal insufficiency?
ALWAYS take microbiological culture BEFORE starting any antibiotic therapy!
Evaluate daily: Is it possible to
- stop - switch IV to PO
- escalate/deescalate - define total lengths of therapy
- optimize dosing according to local guidelines?
Infection / Empiric Antibiotic Therapy
Fever of Unknown Origin (FUO)
< 3 months / Ampicillin 50 mg/kg tds IV
PLUS Cefotaxime 50 mg/kg tds IV
> 3 months / Ceftriaxone1 80 mg/kg od IV (max. 4 g)
Fever in Neutropenia (FIN)
Piperacillin/Tazobactam2 100 mg/kg tds IV (max. 4 g/dose)
if suspicion of MRSA or CVC-infection: ADD Vancomycin3 15 mg/kg tds IV (max. 650 mg/dose)
Septic Shock
Meropenem 20 mg/kg tds IV (max. 1 g/dose)
CNS Infections
Meningoencephalitis / Aciclovir <1 a: 20 mg/kg tds IV, >1 a: 10 mg/kg tds IV (max. 850 mg/dose)
PLUS >1 Mo.: Ceftriaxone1 80 mg/kg od IV (max. 4 g)
Meningitis < 3 months / Ampicillin <1 Mo.: 100 mg/kg tds IV, >1 Mo.: 100 mg/kg qds IV
PLUS Cefotaxime 50 mg/kg qds IV
Meningitis > 3 months / Ceftriaxone1 80 mg/kg od IV (max. 4 g)
Pneumonia
Newborn / Ampicillin 50 mg/kg tds IV
PLUS Cefotaxime 50 mg/kg tds IV
Community acquired (CAP)
4 weeks – 6 months / Cefuroxime 40 mg/kg tds IV
Community acquired (CAP)
> 6 months / Ampicillin 50 mg/kg tds IV (max. 2 g/dose) or
Amoxicillin 30 mg/kg tds PO (max. 1.5 g/dose)
Atypical / Clarithromycin 7.5 mg/kg bd PO (max. 500 mg/dose)
Nosocomial / Piperacillin/Tazobactam2 100 mg/ kg tds IV (max. 4 g/dose)
Multidrug-Resistant Bacteria
History of ESBL colonisation / Meropenem 15 mg/kg tds IV (max. 1 g/dose)
History of MRSA colonisation / include Vancomycin³ 15 mg /kg tds IV (max. 650 mg/dose) as part of empiric therapy
ENT Infections
Tonsillitis /
pharyngitis / Antibiotics are not the first choice!
ONLY perform rapid strep test if min. 3 out of the following symptoms present: exudative, fever, painful cervical lymphadenopathy, no cough.
ONLY in case of proven group A streptococcal infection:
Penicillin V 30,000 IU/kg tds PO (max. 2 Mio. IU/dose) for 7d
Epiglottitis / tracheitis / >1 Mo.: Ceftriaxone1 50 mg/kg od IV (max. 4 g)
Acute otitis media / acute sinusitis / Antibiotics are not the first choice!
Carefully evaluate using an antibiotic, because of high probability of viral origin and spontaneous recovery. First-line treatment: Analgesia, nasal decongestant. Re-evaluation after 24–48 h, if persistence of symptoms or child deteriorates: Amoxicillin 30 mg/kg tds PO (max. 1.5 g/dose)
Malignant otitis externa / Ceftazidime 50 mg/kg tds IV (max. 1.5 g/dose)
PLUS Ciprofloxacin 15 mg /kg bd IV (max. 750 mg/dose)
Urinary Tract Infections
Cystitis / Amoxicillin/Clavulanic acid 20/5 mg/kg tds PO (max. 1000/250 mg/dose)
Pyelonephritis < 3 months / Ampicillin <1 Mo.: 100 mg/kg tds IV, >1 Mo.: 100 mg/kg qds IV
PLUS Cefotaxime 50 mg/kg qds IV
Pyelonephritis > 3 months / Piperacillin/Tazobactam2 100 mg/ kg tds IV (max. 4 g/dose)
Gastrointestinal Tract
Peritonitis / Piperacillin/Tazobactam2 100 mg/kg tds IV (max. 4 g/dose)
Skin, Soft Tissue and other Infections
Osteomyelitis /
septic arthritis / Cefuroxime 50 mg/kg tds IV (max. 1.5 g/dose)
Lymphadenitis / Amoxicillin/Clavulanic acid 20/5 mg/kg tds PO (max. 1000/250 mg/dose)
Cellulitis / impetigo / Amoxicillin/Clavulanic acid 20/5 mg/kg tds PO (max. 1000/250 mg/dose)
Cellulitis serious (with fever / fast progress) / Ampicillin/Sulbactam4 50 mg/kg tds IV (max. 4 g/dose)
PLUS Flucloxacillin 50 mg/kg qds IV (max. 2 g/dose)
(for penicillin allergy, >1 Mo.: Clindamycin 10 mg/kg qds IV)
Preseptal cellulitis / Ampicillin/Sulbactam4 50 mg/kg tds IV (max. 4 g/dose) or
amoxicillin/Clavulanic acid 20/5 mg/kg tds PO (max. 1000/250 mg/dose)
Postseptal / periorbital cellulitis / >1 Mo.: Ceftriaxone1 80 mg/kg od IV (max. 4 g)
PLUS Flucloxacillin 50 mg/kg qds IV (max. 2 g/dose)
Bites
(animals / human) / Amoxicillin/Clavulanic acid 20/5 mg/kg tds PO (max. 1000/250 mg/dose).
Check need for rabies and tetanus prophylaxis!
1 Do not mix Ceftriaxone with total parenteral nutrition (TPN) / calcium-containing products; don’t use in case of hyperbilirubinemia
2 Dosing recommendations expressed as piperacillin content
3 Therapeutic Drug Monitoring recommended
4 Dosing recommendations expressed as ampicillin content
od: once daily, bd: twice daily, tds: three times daily, qds: four times daily
Tab. S2 Antibiotic Dosing Recommendations at Dr. von Hauner Children’s Hospital
Substance / Route of administration / Single dose [mg/kg] / Daily dose [mg/kg*d] / Dosing interval q [h] / Maximum daily doseAmoxicillin / PO / 30 / 90 / 8 / 6 g/d
Amoxicillin/Clavulansäure / PO / 20/5 / 60/15 / 8 / 2,625/375 mg/d
Ampicillin / IV / 50 / 150 / 8 / 6 g/d
Ampicillin_Meningitis / IV / 100 / 300 / 8 / 15 g/d
Ampicillin/Sulbactam / IV / 50 / 150 / 8 / 12 g/d
Azithromycin / PO/IV / 10 / 10 / 24 / 0,5 g/d
Cefazolin / IV / 30 / 90 / 8 / 8 (-12) g/d
Cefotaxim / IV / 33 / 100 / 8 / 8 g/d
Cefotaxim_Meningitis / IV / 50 / 200 / 6 / 12 g/d
CefPOdoxim / PO / 5 / 10 / 12 / 400 mg/d
Ceftazidim / IV / 50 / 150 / 8 / 6, CF: 9 g/d
Ceftriaxon / IV / 50 / 50 / 24 / 2 g/d
Ceftriaxon_Meningitis / IV / 80 / 80 / 24 / 4 g/d
Cefuroxim / PO / 15 / 30 / 12 / 1 g/d
Cefuroxim / IV / 40 / 120 / 8 / 4,5 g/d
Cefuroxim_Osteomyelitis / IV / 50 / 150 / 8 / 6 g/d
Ciprofloxacin / PO/IV / 15 / 30 / 12 / 1,5 g/d
Clarithromycin / PO / 7,5 / 15 / 12 / 1 g/d
Clindamycin / PO/IV / 10 / 40 / 6 / 1.8 (-2.7) g/d
Cotrimoxazol / PO / 3 / 6 / 12 / 320 mg/d
Flucloxacillin / PO / 33 / 100 / 8 / 8 g/d
Flucloxacillin / IV / 50 / 200 / 6 / 12 g/d
Meropenem / IV / 20 / 60 / 8 / 3 g/d
Meropenem_Meningitis / IV / 40 / 120 / 8 / 6 g/d
Metronidazol / PO/IV / 10 / 30 / 8 / 2 g/d
Moxifloxacin / IV / 10 / 10 / 24 / 400 mg/d
Penicillin G / IV / 75,000 IE / 300,000 IE / 6 / 24 Mio IE/d
Penicillin V / PO / 30,000 IE / 90,000 IE / 8 / 6 Mio IE/d
PipTaz / IV / 100 / 300 / 8 / 12 (-18) g/d
Rifampicin / PO / 10 / 20 / 12 / 600-900 mg/d
References
Dt. Gesellschaft für Pädiatrische Infektiologie, DGPI Handbuch - Infektionen bei Kindern und Jugendlichen, Stuttgart: Thieme Verlag. 2013 (6th ed.)
Tschudy MK, Arcara, K.M. The Harriet Lane Handbook. Philadelphia: Elsevier Mosby. 2012 (19th ed.)
Aronoff GR, Bennett W.M., Berns J.S., et al. Drug Prescribing in Renal Failure. Philadelphia: American College Of Physicians. 2007 (5th ed.)
British National Formulary (BNF) for children. London: Pharmaceutical Press. 2014
Schmid I. Ambulanzmanual Pädiatrie von A-Z. Heidelberg: Springer-Verlag Berlin. 2014 (4th ed.)
Bradley J, Nelson, J. Nelson's Pediatric Antimicrobial Therapy. Elk Grove Village: American Academy of Pediatrics. 2014 (20th ed.)
Taketomo CK, Hodding, J.H., Kraus, D.M. Pediatric & Neonatal Dosage Handbook. Lexi-Comp, Inc. 2012 (19th ed.)
Tab. S3 Restricted Antibiotics Requiring Special Authorization at Dr. von Hauner Children’s Hospital
Cefepime / Ertapenem / RifabutinCeftaroline / Fosfomycin / Streptomycin
Ceftobiprole / Levofloxacin / Sulbactam
Ceftolozane/tazobactam / Linezolid / Sulfadiazine
Dapsone / Mezlocillin / Teicoplanin
Daptomycin / Nitrofurantoin / Tigecycline
Tab. S4 Comparison of Average Antibiotic Use Density Expressed as Doses per 1,000 Patient-Days (PD) during Pre-Intervention and Post-Intervention Period
pre-intervention period / post-intervention period / DifferencePD / 4,510 / PD / 4,456
Substance / doses total / doses/1,000 PD / % / doses total / doses/1,000 PD / % / doses/1000 PD / %
J01C Penicillins / 2156 / 478.0 / 38.8 / 2496 / 560.1 / 47.8 / 82.1 / 17.2
J01CR05 Piperacillin + BLI / 1404 / 311.3 / 25.3 / 1384 / 310.6 / 26.5 / -0.7 / -0.2
J01CR01-2 Other penicillins + BLI / 231 / 51.2 / 4.2 / 399 / 89.5 / 7.6 / 38.3 / 74.8
J01CF Beta-lactamase resistant penicillins / 12 / 2.7 / 0.2 / 62 / 13.9 / 1.2 / 11.3 / 422.9
J01CA Penicillins with extended spectrum / 463 / 102.7 / 8.3 / 574 / 128.8 / 11.0 / 26.2 / 25.5
J01CE Beta-lactamase sensitive penicillins / 46 / 10.2 / 0.8 / 77 / 17.3 / 1.5 / 7.1 / 69.4
J01D Cephalosporins / 1780 / 394.7 / 32.0 / 1130 / 253.6 / 21.6 / -141.1 / -35.7
J01DB 1st-generation cephalosporins / 78 / 17.3 / 1.4 / 4 / 0.9 / 0.1 / -16.4 / -94.8
J01DC 2nd-generation cephalosporins / 1228 / 272.3 / 22.1 / 778 / 174.6 / 14.9 / -97.7 / -35.9
J01DD 3rd-generation cephalosporins / 474 / 105.1 / 8.5 / 348 / 78.1 / 6.7 / -27.0 / -25.7
J01M Fluoroquinolones / 256 / 56.8 / 4.6 / 101 / 22.7 / 1.9 / -34.1 / -60.1
Ciprofloxacin / 202 / 44.8 / 3.6 / 88 / 19.7 / 1.7 / -25.0 / -55.9
Levofloxacin / - / - / - / 6 / 1.3 / 0.1 / 1.3 / -
Moxifloxacin / 54 / 12.0 / 1.0 / 7 / 1.6 / 0.1 / -10.4 / -86.9
J01XB Nitroimidazoles (Metronidazol) / 331 / 73.4 / 6.0 / 151 / 33.9 / 2.9 / -39.5 / -53.8
J01FA Macrolides / 170 / 37.7 / 3.1 / 243 / 54.5 / 4.7 / 16.8 / 44.7
J01XA Glycopeptides / 262 / 58.1 / 4.7 / 357 / 80.1 / 6.8 / 22.0 / 2.1
Vancomycin / 248 / 55.0 / 4.5 / 357 / 80.1 / 6.8 / 25.1 / 45.7
Teicoplanin / 14 / 3.1 / 0.3 / - / - / - / -3.1 / -
J01DH Carbapenems / 209 / 46.3 / 3.8 / 402 / 90.2 / 7.7 / 43.9 / 94.7
J01FF Lincosamides (Clindamycin) / 219 / 48.6 / 3.9 / 241 / 54.1 / 4.6 / 5.5 / 11.4
Others / 107 / 23.7 / 1.9 / 93 / 20.9 / 1.8 / -2.9 / -12.0
J01G Aminoglycosides / 40 / 8.9 / 0.7 / 10 / 2.2 / 0.2 / -6.6 / -74.7
J01XB Polymyxine (Colistin) / 30 / 6.7 / 0.5 / - / - / - / -6.7 / -
Total / 5560 / 1232.8 / 100.0 / 5224 / 1172.4 / 100.0 / -60.5 / -4.9
5