![Page 1: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/1.jpg)
Antibiotics – back to basics
Petra Schelstraete
Kinderinfectieziekten UZ Gent
LOK groep 01/12/2012
![Page 2: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/2.jpg)
To be discussed
• History
• Basic principles of AB therapy and AB/host/infective organism interaction
• AB classes + use
![Page 3: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/3.jpg)
Antibiotics: Introduction
• Antibiotics = a natural substance produced by a micro-organism to kill another
• Anti-infectives/Anti-microbrial = any agent (natural or synthetic) that kills pathogens (microbes)
• Antibiotics exploit the differences between bacterial and human cells: drug is more toxic to the infecting organism than to the host
![Page 4: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/4.jpg)
Antibiotics: History
• Alexander Fleming observed antibiosis against bacteria by a fungus of the genus Penicillium in 1928
• Florey and Chain succeeded in purifying the first penicillin in 1942
• Chain, Florey and Fleming: Nobel Prize in Medicine in 1945
![Page 5: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/5.jpg)
![Page 6: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/6.jpg)
Antibiotics: History
![Page 7: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/7.jpg)
Bacteria
![Page 8: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/8.jpg)
Gram-positieve kokken
Staphylococcus aureus
Staphylococcus epidermidis en andere coagulase-negatieve stafylokokken
Staphylococcus saprophyticus
Streptococcus pyogenes (groep A, β-hemolytisch) en groepen C en G
Streptococcus agalactiae (groep B, β-hemolytisch)
Streptococcus viridans
Streptococcus bovis groep D
Peptostreptococcus (anaërobe streptokok)
Streptococcus pneumoniae (pneumokok)
Enterococcus species groep D
Gram-positieve staafjes
Aërobe Bacillus anthracis
Corynebacterium diphtheriae
Listeria monocytogenes
Anaërobe Clostridium difficile (pseudomembraneuze colitis)
Clostridium perfringens (welchii)
Clostridium tetani
Gram-negatieve kokken
Neisseria gonorrhoeae (gonokok)
Neisseria meningitidis (meningokok)
Moraxella catarrhalis
Gram-negatieve staafjes
Aërobe
Enterobacteriën
Citrobacter species
Enterobacter species
Escherichia coli
Klebsiella pneumoniaeProteus mirabilis (indol-negatief)Providencia rettgeri, Morganella morganii, Proteus vulgaris en Providencia stuartii
Salmonella Typhi en andere salmonellae
Serratia species
Shigella species
Yersinia enterocolitica
Andere Gram-negatieve staafjes
Acinetobacter speciesBordetella pertussis (kinkhoest)Brucella (brucellose)Calymmatobacterium granulomatisFrancisella tularensis (tularemie)Gardnerella vaginalisHaemophilus ducreyi (ulcus molle)Haemophilus influenzaeLegionella pneumophilaPseudomonas aeruginosaVibrio cholerae
Anaërobe
Bacteroides fragilis en non-fragilis
Fusobacteriën
Prevotella
Porphyromonas
![Page 9: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/9.jpg)
AB effect: micro-organism and host
• Micro-organism: – Bactericidal/bacteriostatic effect
• Host : side effects – Diarrhea, dental staining
– Toxic/related to dose: eg AG and nefrotoxicity
– Toxic/not related to dose: eg hepatitis
– Allergic: eg anaphylaxis in penicillin allergic patients
– Effect on natural ecosystem : eg intestinal flora
![Page 10: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/10.jpg)
AB effect: sensitive vs resistant organism
• Resistance: the inability to kill or inhibit the organism with clinically achievable drug concentrations
• Resistance may be innate (naturally resistant)
• Resistance may be acquired - mutation - acquisition of foreign DNA
• Resistance and MIC
![Page 11: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/11.jpg)
Antimicrobial resistance: contributing factors
• inadequate levels of antibiotics at the site of
infection
• too low dosage of AB
• too short duration of treatment
• overwhelming numbers of organisms
• overuse / misuse of antibiotics
![Page 12: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/12.jpg)
Famous resistant bugs
• MRSA
• VISA/VRSA
• VRE
• ESBL
![Page 13: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/13.jpg)
AB effect: PK/PD
• Pharmacokinetics: what the body does to the drug
• Pharmacodynamics: what the drug does to the body.
![Page 14: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/14.jpg)
GI Absorption
Blood
Renal
excretion
Pharmacokinetics
Extracellular
compartment
of tissues
Oral ingestion
![Page 15: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/15.jpg)
Drug Pharmacokinetics in blood Se
rum
An
tib
ioti
c C
on
cen
trat
ion
0
2
4
6
8
10
0 1 2 3 4 5 6 7 8
Time (hours)
(mcg
/mL)
9 10 11 12
Dose Dose
![Page 16: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/16.jpg)
Effecten anti-infectieus middel: farmakokinetiek- farmacodynamiek
• Relatie antibioticum tot MIC
MIC
conc
tijd
Piekconcentratie/MIC
Duur concentratie boven MIC (time above MIC)
![Page 17: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/17.jpg)
Concentratie-afhankelijke AB
• Piekconc/MIC zo hoog mogelijk: volledige dagdosis in 1 gift (bv. aminoglycosiden)
MIC
conc
tijd
![Page 18: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/18.jpg)
Tijds afhankelijke AB
• ‘time above MIC’ zo lang mogelijk: dagdosis opdelen in frequente giften (bv. betalactam AB)
MIC
conc
tijd
![Page 19: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/19.jpg)
Antibiotic groups
• Beta lactam antibiotics
– Penicillins
– Cephaolsporins
– Carbapenems
– monobactams
• Aminoglycosides
• Macrolides/lincomycins
• Sulfonamides
• Fluoroquinolones
• Glycopeptides
• Tetracyclins
• Oxazolidinones
• Tuberculostatics
• Urinary antiseptics
![Page 20: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/20.jpg)
Classification of antibiotics • Chemical origin
– Natural/semisynthetic/synthetic
• Spectrum of activity – Broad vs narrow spectrum
• Biological activity – Bactericidal/bacteriostatic
• Pharmacodynamic properties – Time vs concentration dependent killing of bacteria
• Mechanism of action
![Page 21: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/21.jpg)
Mechanisms of action
![Page 22: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/22.jpg)
AB that inhibit cell wall synthesis
• Beta lactam antibiotics
– Penicillins
– Cephalosporins
– Carbapenems
– Monobactams
• Glycopeptides
BACTERICIDAL
![Page 23: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/23.jpg)
Small spectrum penicillins
– Beta lactamase (penicillinase) sensitive
• peni V, peni G, benzathinepenicilline
• Good activity to streptococci , no gram neg (only Neisseria), some anaerobic activity (peni G)
• Tonsillitis, pneumonia, meningococcal meningitis
– Beta lactamase (penicillinase) insensitive/antistaphylococcal penicillins
• (Flu)(cl)oxacillin
• Good gram pos activity
• Infections of skin, bone
![Page 24: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/24.jpg)
Broad spectrum penicillins (1)
• Aminopenicillins
– Amoxicillin, ampicillin
• Gram pos (excl S. aur), some gram neg (beta lactamase neg), some anaerobic activity
• Respiratory tract infections (ENT+Lung)
– Amoxicillin + clavulanic acid
• Good gram pos (incl S. aur) and gram neg and anaerobic activity
• Respiratory infections, abdominal infections
![Page 25: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/25.jpg)
Broad spectrum penicillins (2)
• Carboxypenicillins
– Temocillin
– good gram neg activity (excl P. aeruginosa), no gram pos, no anaerobic activity
• Acylureidopenicillins/antipseudomonas pencillins
– Piperacilline+tazobactam
– good gram pos and gram neg (incl P. aeruginosa) and anaerobic activity
– Hospital infections lung, abdomen
![Page 26: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/26.jpg)
Cephalosporins (1)
• 1st generation – Mainly gram pos, some gram neg and anaerobic
• 2nd generation – Weaker gram pos, better gram neg, some anaerob
• 3rd generation – Excellent gram neg, some gram pos and anaerob
• 4th generation – Excellent gram neg, good gram pos, some
anaerob
![Page 27: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/27.jpg)
Cephalosporins (2)
• 1st generation: Cefadroxil, cefazoline
– Tonsillitis, peri-operative prophylaxis
• 2nd generation: Cefaclor, cefuroxime
– Respiratory tract infections
• 3rd generation: Cefotaxim, Ceftriaxone, Ceftazidim
– Sepsis
– Cave only ceftazidim active to P. aeruginosa
• 4th generation: cefepime
– severe hospital infections
![Page 28: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/28.jpg)
carbapenems
• Imipenem, meropenem
• Good gram neg, gram pos and anaerobic activity
• NO: MRSA, MRSE, S. maltophilia, B. cepacia
• Life threatening polymicrobial infections
• CAVE: imipenem and convulsions
• CAVE: carbapenems and secondary yeast infections
![Page 29: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/29.jpg)
monobactams
• Aztreonam
• Good gram neg (also P. aeruginosa), no gram pos,no anaerobic activity
![Page 30: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/30.jpg)
glycopeptides
• Vancomycin, teicoplanin
• good gram pos, some anaerobe activity
• Infections caused by MRSA, ampi R enterococcen, methi R CNS
• Cave red man syndrome
![Page 31: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/31.jpg)
Mechanisms of action
![Page 32: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/32.jpg)
Inhibition of protein synthesis
• Macrolides, lincosamides
• Aminoglycosides
• Tetracyclins
• Fluoroquinolones
BACTERIOSTATIC (ML,LC)
BACTERICIDAL (AG, TC, FQ)
![Page 33: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/33.jpg)
macrolides
• Azithromycin, clarithromycin, erythromycin, roxithromycin
• Gram pos and atypical organisms ( Mycoplasma
Chlamydia, Legionella), some gram neg and anaerobic activity
• Respiratory infections caused by atypical organisms and B. pertussis
![Page 34: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/34.jpg)
lincomycins
• clindamycin
• Gram pos and anaerobic activity
• Bone infections
• CAVE: pseudomembranous colitis
![Page 35: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/35.jpg)
aminoglycosides
• Amikacin, gentamycin, tobramycin
• Excellent gram neg, some gram pos (no streptococci), Mycobacteria
• Severe hospital infections: sepsis, endocarditis, pyelonephritis, pneumonia
• Synergistic action with beta lactam AB
• CAVE never monotherapy!
• Toxicity:
– Kidney: reversible
– Middle ear: irreversible
• ODD: less nefrotoxicity
![Page 36: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/36.jpg)
fluoroquinolones
• Ciprofloxacin, (levofloxacin, norfloxacin, ofloxacin)
• Good gram neg and atypical, some gram pos and anaerobic activity
• Cystic fibrosis, urinary tract infection caused by P. aeruginosa
• Toxic effect on cartilago: not confirmed in human studies
![Page 37: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/37.jpg)
Mechanisms of action
![Page 38: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/38.jpg)
Inhibition of metabolic pathways
• Trimethoprim/Sulfomethoxazole
• Inhibition of folic acid synthesis
• Bacteriostatic, combination bactericidal
• gram neg and gram pos activity
• Urinary tract infections, Pneumocystis jiroveci, respiratory infections
![Page 39: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/39.jpg)
sulfonamides
• Bacteriostatic/ combination bactericidal
• Inhibition of bacterial folic acid synthesis
![Page 40: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/40.jpg)
![Page 41: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/41.jpg)
Most appropriate AB therapy: THE CHOICE
• Micro-organisms must be sensitive
• AB must be able to reach site of infection
– PK/PD dynamics
• MIC/MBC
• Time dependent vs concentration dependent killing
• Minimal side effects
• Minimising risk of development of resistance
![Page 42: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/42.jpg)
How to avoid/overcome AB resistance
• AB:
–Alter structure of AB (cephalosporins) –Add beta lactamase inhitor
• High dosage of AB “dead bugs dot not mutate”
• Restrictive use of AB –Guidelines – Switch to smaller spectrum AB according to
microbiological results • Hygienic measures to avoid transfer of
organisms
![Page 43: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/43.jpg)
![Page 44: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/44.jpg)
![Page 45: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/45.jpg)
Bactericidal vs bacteriostatic
![Page 46: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/46.jpg)
Beta lactamases
• Production of beta lactamase most important resistance mechanism to beta lactam antibiotics
• Beta lactamase production in both gram negative (e.g. E. coli, K. pneumoniae, P. mirabilis) and gram positive bacteria (S. aureus, B. fragilis)
• Can be overcome by addition of beta lactamase inhibitor to antibiotic (e.g. clavulanic acid, tazobactam)
![Page 47: Antibiotics back to basics zorgaanbod/Kinderziekten... · 2015. 12. 14. · Cephalosporins (2) •1st generation: Cefadroxil, cefazoline –Tonsillitis, peri-operative prophylaxis](https://reader036.vdocuments.us/reader036/viewer/2022071110/5fe4fd727c65f11c08552562/html5/thumbnails/47.jpg)
What additional bugs do they cover?
• S. aureus
• H. influenzae
• Neisseria sp.
• Bacteroides fragilis
• E. coli and Klebsiella
• Not better for Pseudomonas or Enterobacter