Lecture 21- Principles Of Antimicrobial Therapeutics II Flashcards
(12 cards)
Combination of antibiotics
Achieve synergism; e.g. B-lactam + aminoglycoside (gentamicin) for endocarditis
-slow down emergence of resistance e.g. sulphonamide + trimethoprim
-infections requiring prolonged treatment; e.g. multi-drug therapy for HIV/ TB
- mixed infections; e.g. peritonitis, leg ulcers in diabetic pts (mixture of anaerobes, aerobes, G+ve + G-ve organisms)
Antibacterial drug interactions
Additive/indifferent- combined effects = sum of independent effects
Synergistic- combined effects > sum of independent effects
Antagonistic- combined effects < sum of independent effects
Antibacterial drug interactions
Interactions= hard to predict;
- vary within species and strains
- occur over a narrow range of conc/ drug ratios
Method of detection;
- checkerboard
- killing curve
Testing of antibiotic interactions
Activity of one drug = enhances that of a second drug synergy
Drugs may interfere with each other- Antagonism
Penicillins + Bacteriostatic drugs; tetracyclines = antagonistic, since penicillins require actively growing cells + static drugs prevent cell growth
Aminoglycosides = synergistic when used in combination with penicillins
Synergism in antibiotic combinations
Sequential inhibition of successive steps in metabolism; sulphonamide-trimethoprim
Sequential inhibition of protein synthesis; syncercid
Facilitation of drug entry of one antibiotic by another; beta-lacam-aminoglycoside
Inhibition of inactivating enzymes; ampicillin- clavulanic acid
Prevention of emergence of resistant populations; triple therapy for TB
Treatment of systemic fungal infections; candidiasis, cryptococcosis; with amphotericin + flucytosine
Antagonism of antibiotic combinations
Inhibition of bactericidal activity such as treatment of meningitis - bacteriostatic drug prevents bactericidal activity of another
Completion for drug binding sites; e.g. macrolides-chloramphenicol combinations
Inhibition of cell wall permeability mechanisms e.g. chloramphenicol-Aminoglycoside combinations
Induction of b-lactamases by b-lactam drugs
Limitations of antimicrobial therapy
Disruption of normal flora;
- opportunistic infections may result from loss of normal flora
Adverse side effects with some agents;
- penicillin allergy
- hypersensitivity to some other antibiotics
- ototoxicity and nephrotoxicity
- bone marrow suppression
- tooth colour discolouration
Emergence of resistant bacteria
Antibiotic drug resistance
Major health challenge
Due to largely inappropriate use of antibiotics in hospital and community
- treating people with viral infections with antibiotics; common cold, flu, viral pneumonia etc
- using broad spectrum rather than narrow spectrum antibiotics
- using new special antibiotics to treat infections when an older antibiotic would be effective
Use of antibiotics to improve growth and production in animals
Types of antibiotic resistance
*Natural resistance= particularly microbes are inherently resistant to particular agents
- multi drug efflux pumps in pseudomonas aeruginosa
- Aminoglycoside resistance in strict anaerobes
- inability of penicillin G to penetrate gram - bacteria cell wall
*Acquired resistance involves bacteria becoming resistant to a drug that was previously effective=
- multi-drug resistance in mycobacterium tuberculosis
- fluroquinolone resistance in staphylococcus aureus + penicillin resistance in streptococcus pneumoniae
- acquired resistance occurs in response to exposure of bacteria to antibiotics
Mechanisms of antibiotic resistance
*Antibiotic modification- bacteria avoids the antibiotics deleterious effects by inactivating the antibiotic; production of B-lactamases
*Prevention of antibiotic entry into the cell of gram - bacteria=
- porins are transmembrane proteins that allow for the diffusion of antibiotics through their highly impermeable outer membrane
*Active efflux of antibiotic- bacteria can actively pump out the antibiotic from the cell;
- energy dependent on efflux of tetracyclines widely seen in enterobacteriae
*Alteration of drug target= bacteria can also evade antibiotic action through the alteration
*Bypassing drugs action= bacteria can bypass the deleterious effect of the drug while not stopping the production of the original sensitive target; alternative PBP produced by MRSA in addition to the normal PBP
Major antibiotic resistance problems
Hospital;
- methicillin resistant s.aureus - hospital and community required
- vancomycin resistant enterococci
- multi resistant gram - bacteria
Community;
- community acquired MRSA
- penicillin resistant streptococcus pneumoniae
- multi drug resistant mycobacterium tuberculosis
Reducing antibiotic resistance
Hospitals;
- improved infection control
- implement and enforce hospital policies for prescribing antibiotics
- use narrow spectrum antibiotics where possible
- older classes where possible
- hold new antibiotics in reserve and only use when absolutely essential
- combined therapy where appropiate
- vaccines where available
Community;
- education of docs and pts- no antibiotics for simple viral infection
- use older classes of antibiotics where possible
- vaccines where possible
- combined therapy for TB
