Professional Documents
Culture Documents
Drug
Infection
Host Bacteria
Host defence
Improving the probability of
positive outcomes
• Window of opportunity
– Early recognition and treatment of infection
– Selection of appropriate antibiotic
(e.g. through in vitro susceptibility determination)
– Optimization of DOSE using
Pharmacodynamic principles
• Sepsis
SIRS + suspected or confirmed infection
Key Message 1
• Diagnose sepsis early and give antibiotics
promptly to reduce mortality from sepsis
Antibiotics
Actions
Bactericidal
Kills bacteria, reduces bacterial load
Bacteriostatic
Inhibit growth and reproduction of bacteria
All antibiotics require the immune system to work
properly
Bactericidal appropriate in poor immunity
Bacteriostatic require intact immune system
ß-Lactams
Β-Lactam
Thiazolidine Ring
Ring
ß-Lactams
ß-Lactams
Penicillin
Narrow Spectrum
Cephalosporin •Benzylpenicillin (Penicillin G)
•Cefalexin •Phenoxymethylpenicillin (Pen V)
•Cefuroxime •Flucloxacillin
•Cefotaxime Broad Spectrum
•Ceftriaxone •Amoxicillin/Co-amoxiclav
•Ampicillin
Carbapenem •Piperacillin with Tazobactam
•Meropenem (Tazocin)
•Imipenem
•Doripenem
•Ertapenem
Mechanisms of Action
Osmotic
Pressure
Cell Membrane
Osmotic
Pressure
Cell membrane
Rupture
Spectrum of Activity
• Very wide
• Gram positive and negative bacteria
• Anaerobes
• Spectrum of activity depends on the agent
and/or its group
Adverse Effects
•ß-Lactamase
•Other mechanisms are of less importance
•Augmentin
Important Points
•Semisynthetic derivatives:
•Amikacin (from Kanamycin)
•Netilmicin (from Sisomicin)
30S Ribosomal Unit Blockage by
Aminoglycosides
• Inactivation by Aminoglycoside
modifying enzymes
– This is the most important mechanism
Important Points
14
Erythromycin Telithromycin
15 14
Clarithromycin
Azithromycin
Mechanism of Action
• Bacteriostatic- usually
• Inhibit bacterial RNA-dependent
protein synthesis
– Bind reversibly to the 23S ribosomal
RNA of the 50S ribosomal subunits
• Block translocation reaction of the
polypeptide chain elongation
Spectrum of Activity
• Gram-Positive Aerobes:
– Activity: Clarithromycin>Erythromycin>Azithromycin
• MSSA
• S. pneumoniae
• Beta haemolytic streptococci and viridans streptococci
• Gram-Negative Aerobes:
– Activity: Azithromycin>Clarithromycin>Erythromycin
• H. influenzae, M. catarrhalis, Neisseria sp.
• NO activity against Enterobacteriaceae
• Anaerobes: upper airway anaerobes
• Atypical Bacteria
Mechanisms of Resistance -
Microlides
• Intra-cellular organisms
– Chlamydia
– Gonococcus
Summary
• Bacteriostatic
• ALL hepatic elimination
• Gastrointestinal Sideeffects (up to 33 %)
(especially Erythromycin)
• Nausea
• Vomiting
• Diarrhoea
• Dyspepsia
• Best used in atypical pneumonia
• Excellent tissue and cellular penetration
– Very useful in susceptible intracellular infections
Fluoroquinolones
Fluoroquinolones
Quinolone pharmacore
Mechanism of Action
• Prevent:
• Relaxation of supercoiled DNA before
replication
• DNA recombination
• DNA repair
Spectrum of Activity
• Gram-positive
• Gram-Negative (Enterobacteriaceae H.
influenzae, Neisseria sp. Pseudomonas
aeruginosa)
– Ciprofloxacin is most active
• Atypical bacteria: all have excellent activity
Summary
• Wide range of activity against Gram positive and
negative bacteria.
• Sepsis from Intra-abdominal and Renal Sources
– Coliforms (Gram negative bacilli)
• UTI
– E. coli
• Very good tissue penetration
• Excellent oral bioavailability
• High risk for C.difficile
Tetracyclines
•Doxycycline
•Long acting
Mechanism of Action
• Atypical organisms
– Mycoplasmas
– Chlamydiae
– Rickettsiae
– Protozoa
Adverse Effects
• Oesophageal ulceration
• Photosensitivity reaction
• Incorporate into foetal and children bone
and teeth
Vancomycin
Mechanism of Action
• Antibiotic
• Amoebicide
• Anti-protozoal
– Trichomonas Vaginalis
Mechanisms of Action
• Molecular reduction
– Nitroso intermediates
– Sulfamides
• Melatbolised
– Bacterial DNA de-stabilised
Spectrum of Activity & Uses
• Anaerobes
– Bacterial Vaginosis
– Pelvic Inflammatory Disease
– C. Diff
Bio-Availability
• Oral
• Intra-venous
– Expensive
• Rectal
– Cheap
Summary
Any Questions?
Chlamydia Trachomatis
• Obligate, intracellular bacterium
• Rigid cell wall but NO peptidoglycan layer
• Cervicitis
• Slapingitis
• Pelvic Inflammatory Disease
• Neonate - mucopurulent conjunctivitis
• Reiter's syndrome(urethritis, uveitis, arthritis)
• Lymphogranuloma Venereum
Chlamydia Trachomatis
• Diagnosis
– Giemsa stain
• Inclusion bodies in epithelial cells
• Gram stain of no value
– ELISA - antigens in exudates or urine
– Immunofouresence
– PCR
– Culture
Chlamydia Trachomatis
• Life Cycle
Elementary Body
Cell
Binary Fission
Daughter
Elementary Bodies
Chlamydia Trachomatis
• Treatment
– Tetracyclines (Doxicycline)
– Erythromycin
– Azythromycin
PK/PD Principles in
Antibiotic Prescribing And
Prescribing in Organ Failure
SAHD May 17, 2013
Peter Gayo Munthali
Consultant Microbiologist
UHCW
Honorary Associate Clinical Professor
University of Warwick
Pharmacokinetics - Beta-
Lactams
• Absorption
– PO forms have variable absorption
– Food can delay rate and extent of absorption
• Distribution
– Widely to tissues & fluids
– CSF penetration:
IV – limited unless inflamed meninges