Download Free Medical Antibiotics PowerPoint Presentation

Antibiotics PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Pharmacology, which is titled "Antibiotics", to know about six classes of commonly used antibiotics (Beta lactams, Aminoglycosides, Fluoroquinolones, Macrolides, Tetracyclines, Glycopeptides, and Metronidazole). Also, know about the mechanism of action of each antibiotic class, the clinical use of each class of antibiotic, and possible major side effects.

Tags : Pharmacology, Antibiotics, classification, Beta lactams, Aminoglycosides, Fluoroquinolones, Macrolides, Tetracyclines, Glycopeptides, Metronidazole, clinical use, side effects

Published on : Jul 18, 2021 | Views : 3297 | Downloads : 5

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Antibiotics MR. H GEE MD, FRCOG Hon. Assoc. Clinical Professor University of Warwick
Slide 2-

Objectives By the end of this lecture you should be able to: Classify commonly used antibiotics into six major antibiotic classes of; Beta lactams Aminoglycosides Fluoroquinolones Macrolides Tetracyclines Glycopeptides Metronidazole Understand the mechanism of action of each antibiotic class. Understand clinical use of each class of antibiotic Possible major side effects.
Slide 3-

There are Three in this Relationship Drug Bacteria Resistance Pharmacodynamics(PD) Infection Host defence Toxicity Pharmacokinetics (PK) Host
Slide 4-

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 Use optimized dosing that would allow for the minimization of selecting further resistance
Slide 5-

Early recognition of infection (Sepsis) Systemic inflammatory response syndrome (SIRS) (Bone et al Crit Care med 1989.;17 :389) Systemic activation of the immune response  2 of the following in response to an insult: T > 38 .C or < 36.C HR > 90 bpm RR > 20 bpm WBC > 12 000 cells/mm3 Sepsis SIRS + suspected or confirmed infection
Slide 6-

Key Message 1 Diagnose sepsis early and give antibiotics promptly to reduce mortality from sepsis
Slide 7-

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
Slide 8-

ß-Lactams Β-Lactam Ring Thiazolidine Ring
Slide 9-

ß-Lactams ß-Lactams Penicillin Narrow Spectrum Benzylpenicillin (Penicillin G) Phenoxymethylpenicillin (Pen V) Flucloxacillin Broad Spectrum Amoxicillin/Co-amoxiclav Ampicillin Piperacillin with Tazobactam (Tazocin) Cephalosporin Cefalexin Cefuroxime Cefotaxime Ceftriaxone Carbapenem Meropenem Imipenem Doripenem Ertapenem
Slide 10-

Mechanisms of Action Anti Cell Wall Activity Bactericidal
Slide 11-

Beta Lactams Against Bacterial Cell Wall Cell wall Osmotic Pressure Antibiotic against cell wall Osmotic Pressure Cell membrane Rupture Cell Membrane
Slide 12-

Spectrum of Activity Very wide Gram positive and negative bacteria Anaerobes Spectrum of activity depends on the agent and/or its group
Slide 13-

Adverse Effects Penicillin hypersensitivity – 0.4% to 10 % Mild: rash Severe: anaphylaxis & death There is cross-reactivity among all Penicillins Penicillins and cephalosporins ~5-15%
Slide 14-

Resistance to ß-Lactams ß-Lactamase Other mechanisms are of less importance Augmentin
Slide 15-

Important Points Beta lactams need frequent dosing for successful therapeutic outcome Missing doses will lead to treatment failure Beta lactams are the safest antibiotics in renal and hepatic failure Adjustments to dose may still be required in severe failure
Slide 16-

Summary Cell wall antibiotics Bactericidal Wide spectrum of use Antibiotics of choice in many infections Limitations Allergy Resistance due to betalactamase Very safe in most cases No monitoring required
Slide 17-

Aminoglycosides Inhibit bacterial protein synthesis by irreversibly binding to 30S ribosomal unit Naturally occurring: Streptomycin Neomycin Kanamycin Tobramycin Gentamicin Semisynthetic derivatives: Amikacin (from Kanamycin) Netilmicin (from Sisomicin)
Slide 18-

30S Ribosomal Unit Blockage by Aminoglycosides Causes mRNA decoding errors
Slide 19-

Spectrum of Activity Gram-Negative Aerobes Enterobacteriaceae; E. coli, Proteus sp., Enterobacter sp. Pseudomonas aeruginosa Gram-Positive Aerobes (Usually in combination with ß-lactams) S. aureus and coagulase-negative staphylococci Viridans streptococci Enterococcus sp. (gentamicin)
Slide 20-

Adverse Effects Nephrotoxicity Direct proximal tubular damage - reversible if caught early Risk factors: High troughs, prolonged duration of therapy, underlying renal dysfunction, concomitant nephrotoxins Ototoxicity 8th cranial nerve damage – irreversible vestibular and auditory toxicity Vestibular: dizziness, vertigo, ataxia Auditory: tinnitus, decreased hearing Risk factors: as for nephrotoxicity Neuromuscular paralysis Can occur after rapid IV infusion especially with; Myasthenia gravis Concurrent use of succinylcholine during anaesthesia
Slide 21-

Prevention of Toxicity Levels need to be monitored to prevent toxicity due to high serum levels To be avoided where risk factors for renal damage exist Dehydration Renal toxic drugs
Slide 22-

Mechanisms of Resistance Inactivation by Aminoglycoside modifying enzymes This is the most important mechanism
Slide 23-

Important Points Aminoglycosides should be given as a large single dose for a successful therapeutic outcome Multiple small doses will lead to treatment failure and likely to lead to renal toxicity Aminoglycosides are toxic drugs and require monitoring Avoid use in renal failure but safe in liver failure Avoid concomitant use with other renal toxic drugs Check renal clearance, frequency according to renal function
Slide 24-

Summary Restricted to aerobes Toxic, needs level monitoring Best used in Gram negative bloodstream infections Good for UTIs Limited or no penetration Lungs Joints and bone CSF Abscesses
Slide 25-

Macrolides
Slide 26-

Macrolides Erythromycin Telithromycin Clarithromycin Lactone Ring Azithromycin 15 14 14 14
Slide 27-

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
Slide 28-

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
Slide 29-

Mechanisms of Resistance - Microlides Altered target sites Methylation of ribosomes preventing antibiotic binding Cross-resistance occurs between all macrolides
Slide 30-

Clinical Use Cellulitis/Skin and soft tissue Beta haemolytic streptococci Staphylococcus aureus Intra-cellular organisms Chlamydia Gonococcus
Slide 31-

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
Slide 32-

Fluoroquinolones
Slide 33-

Fluoroquinolones Quinolone pharmacore
Slide 34-

Mechanism of Action Prevent: Relaxation of supercoiled DNA before replication DNA recombination DNA repair
Slide 35-

Spectrum of Activity Gram-positive Gram-Negative (Enterobacteriaceae H. influenzae, Neisseria sp. Pseudomonas aeruginosa) Ciprofloxacin is most active Atypical bacteria: all have excellent activity
Slide 36-

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
Slide 37-

Tetracyclines Hydronaphthacene nucleus containing four fused rings Tetracycline Short acting Doxycycline Long acting
Slide 38-

Mechanism of Action Inhibit protein synthesis Bind reversibly to bacterial 30S ribosomal subunits Prevents polypeptide synthesis Bacteriostatic
Slide 39-

Spectrum of Activity All have similar activities Gram positives aerobic cocci and rods Staphylococci Streptococci Gram negative aerobic bacteria Atypical organisms Mycoplasmas Chlamydiae Rickettsiae Protozoa
Slide 40-

Adverse Effects Oesophageal ulceration Photosensitivity reaction Incorporate into foetal and children bone and teeth Avoid in pregnancy and children
Slide 41-

Summary Very good tissue penetration Use usually limited to; Skin and soft tissue infections Chlamydia
Slide 42-

Glycopeptides Vancomycin Teicoplanin Vancomycin
Slide 43-

Mechanism of Action Inhibit peptidoglycan synthesis in the bacterial cell wall Prevents cross linkage of peptidoglycan chains
Slide 44-

Summary Large molecule Only active against Gram positive bacteria Second choice in all its uses except; MRSA C.difficile
Slide 45-

Metronidazole Antibiotic Amoebicide Anti-protozoal Trichomonas Vaginalis
Slide 46-

Mechanisms of Action Molecular reduction Nitroso intermediates Sulfamides Melatbolised Bacterial DNA de-stabilised
Slide 47-

Spectrum of Activity & Uses Anaerobes Bacterial Vaginosis Pelvic Inflammatory Disease C. Diff
Slide 48-

Bio-Availability Oral Intra-venous Expensive Rectal Cheap
Slide 49-

Summary Wide spectrum of activity Anaerobes In combination
Slide 50-

Use of Pharmacokinetics in Treatment Beta lactams Good/variable (Dependant on individual antibiotic) Soft tissue Bone and joints Lungs CSF Poor Abscesses Examples of good Tissue Penetrators Tetracyclines Macrolides Quinolones Clindamycin Aminoglycosides Good Circulating organisms Poor Soft tissue Bone and joints Abscesses Lungs CSF
Slide 51-

Key Message 2 When selecting an antibiotic consider the following; Where is the infection? Which antibiotics will reach the site of infection Match the two and select your antibiotic
Slide 52-

Key Message 3 Always check the impact of an antibiotic on other drugs that a patient is on Consult BNF or equivalent
Slide 53-

PHEW!!! Any Questions?
Slide 54-

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
Slide 55-

Chlamydia Trachomatis Diagnosis Giemsa stain Inclusion bodies in epithelial cells Gram stain of no value ELISA - antigens in exudates or urine Immunofouresence PCR Culture
Slide 56-

Chlamydia Trachomatis Life Cycle Elementary Body Cell Reticulate Body Binary Fission Daughter Elementary Bodies Release from Cell
Slide 57-

Chlamydia Trachomatis Treatment Tetracyclines (Doxicycline) Erythromycin Azythromycin
Slide 58-

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
Slide 59-

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 Metabolism & Excretion Primarily renal elimination Some have a proportion of drug eliminated via the liver ALL -lactams have short elimination half-lives
Slide 60-

Clinical Use - Beta- Lactams Cellulitis/Skin and soft tissues Commonest causes Beta haemolytic streptococci Staphylococcus aureus Which Antibiotics? Benzylpenicillin (Streptococci only) Flucloxacillin (Staphylococcus aureus and streptococci) Other beta lactams can be used but spectrum too wide
Slide 61-

Clinical Use - Beta- Lactams UTI Commonest cause E. coli Which antibiotics Cephalexin Co-Amoxiclav Secondary choice, better non beta lactam alternatives exist Nitrofurantoin Trimethoprim
Slide 62-

Clinical Use - Beta- Lactams Sepsis from Intra-abdominal and Renal Sources Commonest causes Coliforms (Gram negative bacilli) Which antibiotics? Co-Amoxiclav Tazocin Meropenem/imipenem/ertapenem (ESBL suspected)
Slide 63-

Pharmacokinetics - Aminoglycosides All have similar pharmacologic properties Gastrointestinal absorption: unpredictable but always negligible Distribution Hydrophilic: widely distributes into body fluids but very poorly into; CSF Vitreous fluid of the eye Biliary tract Prostate Tracheobronchial secretions Adipose tissue Elimination 85-95% eliminated unchanged via kidney t1/2 dependent on renal function In normal renal function t1/2 is 2-3 hours
Slide 64-

Clinical Use 1 - Aminoglycosides Sepsis from Intra-abdominal and Renal Sources Commonest causes Coliforms (Gram negative bacilli) Which antibiotics? Gentamicin/Amikacin (with beta lactam and or metronidazole)
Slide 65-

Clinical Use 2 - Aminoglycosides UTI Very effective in UTI as 85-95% of the drug is eliminated unchanged via kidney Commonest cause E. coli Which antibiotics Gentamicin Secondary choice, better alternatives exist Nitrofurantoin Trimethoprim Beta lactams
Slide 66-

Pharmacokinetics 1- Microlides Erythromycin ( Oral: absorption 15% - 45%) Short t1/2 (1.4 hr) Acid labile Absorption (Oral) Erythromycin: variable absorption of 15% - 45% Clarithromycin: 55% Azithromycin: 38% Half Life (T1/2) Erythromycin 1.4 Hours Clarithromycin (250mg and 500mg 12hrly) 3-4 & 5-7 hours respectively Azithromycin 68hours Improved tolerability Excellent tissue and intracellular concentrations Tissue levels can be 10-100 times higher than those in serum Poor penetration into brain and CSF Cross the placenta and excreted in breast milk
Slide 67-

Pharmacokinetics 2 - Microlides Metabolism & Elimination ALL hepatic elimination
Slide 68-

Adverse Effects - Microlides Gastrointestinal (up to 33 %) (especially Erythromycin) Nausea Vomiting Diarrhoea Dyspepsia Thrombophlebitis: IV Erythromycin & Azithromycin QTc prolongation, ventricular arrhythmias Other: ototoxicity with high dose erythromycin in renal impairment
Slide 69-

ppt slide no 69 content not found
Slide 70-

Pharmacokinetics - Fuoroquinolones Absorption Good bioavailability Oral bioavailability 60-95% Divalent and trivalent cations (Zinc, Iron, Calcium, Aluminum, Magnesium) and antacids reduce GI absorption Distribution Extensive tissue distribution but poor CSF penetration Metabolism and Elimination Combination of renal and hepatic routes
Slide 71-

Adverse Effects - Fluoroquinolones Cardiac Prolongation QTc interval Assumed to be class effect Articular Damage Cartilage damage Induced in animals with large doses
Slide 72-

Resistance - Fluoroquinolones Altered target sites due to point mutations. The more mutations, the higher the resistance to Fluoroquinolones Most important and most common Altered cell wall permeability Efflux pumps Cross-resistance occurs between fluoroquinolones
Slide 73-

Clinical Use 1- Fluoroquinolones Sepsis from Intra-abdominal and Renal Sources Commonest causes Coliforms (Gram negative bacilli) Which antibiotics? Ciprofloxacin High risk for C.difficile, safer alternatives should be used
Slide 74-

Clinical Use 2 - Fluoroquinolones UTI Commonest cause E. coli Which antibiotics Ciprofloxacin High risk for C.difficile, safer alternatives should be used
Slide 75-

Pharmacokinetics - Tetracyclines Incompletely absorbed from GI, improved by fasting Metabolised by the liver and concentrated in bile (3-5X higher than serum levels) Excretion primarily in the urine except doxycycline ( 60% biliary tract into faeces,40% in urine) Tissue penetration is excellent but poor CSF penetration Incorporate into foetal and children bone and teeth
Slide 76-

Resistance - Tetracyclines Efflux Alteration of ribosomal target site Production of drug modifying enzymes
Slide 77-

Clinical Use - Tetracyclines Cellulitis/Skin and soft tissues/ Bone and Joint Infections Commonest causes Beta haemolytic streptococci Staphylococcus aureus Which Antibiotics? Doxycycline
Slide 78-

Pharmacodynamics
Slide 79-

Drug Absorption Curve
Slide 80-

Key Message 4&5 Aminoglycosides are toxic drugs and require monitoring Avoid use in renal failure but safe in liver failure Avoid concomitant use with other renal toxic drugs Check renal clearance, frequency according to renal function Beta lactams are the safest antibiotics in renal and hepatic failure Adjustments to dose may still be required in severe failure