Lecture 4.1 - Introduction to Antibiotics and Antimicrobials PDF

Antimicrobials - classification: ◦Antibacterial, antifungal, antiviral and antiprotozoal agents ◦Antibacterial agents can be classified: ‣ Bactericidal (kill off straight away) or bacteriostatic (stop them from replicating) ‣ Spectrum - 'broad' (act against both gram...

Antimicrobials - classification: ◦Antibacterial, antifungal, antiviral and antiprotozoal agents ◦Antibacterial agents can be classified: ‣ Bactericidal (kill off straight away) or bacteriostatic (stop them from replicating) ‣ Spectrum - 'broad' (act against both gram positive and negative, and both aerobic and anaerobic) vs 'narrow' (more specific) ‣ Target site (mechanism of action) ‣ Chemical structure (antibacterial class) Ideal features of antimicrobial agents: ◦Selectively toxic ◦Few adverse effects ◦Reach site of infection ◦Oral/IV formulation ◦Long half-life (infrequent dosing) ◦No interference with other drugs Classes of antibacterials and their mechanims of action: ◦Bacterial cell - prokaryote Mechanisms of resistance: ◦Drug inactivating enzymes (denature, kill or destroy the bacteria) ‣ E.g. beta-lactamases, aminoglycoside enzymes ◦Altered target ‣ Target has lowered affinity for antibacterial e.g. resistance to methicillin, macrolides and trimethoprim ◦Altered uptake ‣ Decreases permeability ‣ Or increases efflux ◦Biofilm mode of growth (made out of polysaccharides) ‣ Hence why it’s hard to treat infections on joint replacements Genetic mechanisms of resistance:  Measuring antibiotic activity: Disc sensitivity testing: ◦Sensitive ◦Intermediate ◦Resistant Antibiotic sensitivity by Etest: ◦Minimum inhibitory concentration (MIC) as mg/L Automated antibiotic sensitivity testing: ◦Minimum inhibitory concentration (MIC) as mg/L Considerations for antibiotic therapy: ◦Severity/cause of infection - antibiotics are ineffective against viral infections. ◦Consider patient's medical history, other drugs and allergy to antibiotics ◦Taking samples (e.g. swab, blood, urine sample, tissue or bone sample) before start of antibiotic therapy ◦Broad spectrum antibiotics should be used if there is an urgency and the causative organism has not been identified - kills a lot of bacteria ◦Route of administration taking tablets is easier than intravenous routes. ◦Dose of antibiotics ◦Longevity of therapy ◦Combination therapy ◦Prophylaxis Selection of antibiotics for treatment: ◦Empirical therapy initially ◦Isolate and identify the organism ◦Determine its sensitivity ◦Treat with an appropriate antibiotic Beta-lactams:  Penicillins: ◦Penicillin - mainly active against streptococci ◦Amoxicillin - also some activity against Gram-negatives ◦Flucloxacillin - active against staphylococci and streptococci (used a lot in cellulitis) ◦Beta-lactamase inhibitor combinations ‣ Amoxicillin/clavulanate (all of the above + anaerobes + gram-negative bacteria) Amoxicillin is able to carry on its task as clavulanate breaks down bacteria ‣ Piperacillin/tazobactam (as above + gram negative, including Pseudomonas species) Cephalosporins: ◦Broad-spectrum but no anaerobe activity ◦Cetriaxone has good activity in the CSF ◦Concern over association with C.difficile ◦Ceftazidime + avibactam and ceftlozane + tazobactam used for multidrug resistant Gram negative infections Carbapenems: ◦Carbapenems: imipenem, meropenum and ertapenem ‣ Very broad spectrum (including anaerobes) ‣ Active against most (not all) gram negatives ‣ Generally safe in penicillin allergy ◦Imipenem + relebactam ‣ Serious gram negative infections (including anaerobes) ◦Meropenem + vaborbactam ‣ Complicated gram negative UTI Glycopeptides: ◦Vancomycin: ‣ Active against most gram positive (not gram negative) ‣ Some enterococci resistant (VRE) ‣ Resistance in staphs rare ‣ Not absorbed (oral for C.difficile only) ‣ Therapeutic drug monitoring (TDM) required (narrow therapeutic window) ◦Teicoplanin: ‣ Similar activity to vancomycin ‣ Easier to administer ◦Dalbavancin and telavancin: ‣ Acute gram positive skin infections ‣ MRSA pneumonia Tetracyclines: ◦Tetracycline and doxycycline: ‣ Similar spectrum, both oral only. ‣ Broad-spectrum but specific use in penicillin allergy, usually for gram positive ‣ Active in atypical pathogens in pneumonia (useful in older patients with chest infections)  ‣ Active against chlamydia and some protozoa ‣ Should not be given to children