Antimicrobial Chemotherapy Flashcards
What are antibiotics only active against?
Bacteria
What is a bactericidal?
Antimicrobial that kills bacteria
E.g penicillin
What does an organism that is sensitive mean?
If it is inhibited or killed by the antimicrobial available AT SITE OF INFECTION
What is MBC?
Minimal bactericidal concentration - (needed to kill given organism)
What is a bacteriostatic?
Antimicrobial that inhibits growth of bacteria
What does it mean if an organism is resistant?
If it is not killed or inhibited by antimicrobial available at site of infection
What is MIC?
Minimal inhibitory concentration - of antibodies=microbial needed to inhibit growth in given organism.
What are the routes of administration of antibiotics?
Topical - cream, applied to skin
Systemic - pills, taken internally, orally or parenterally
Parenteral - needle - IV or IM (intramuscularly)
Antibiotics cause inhibition of:
Cell wall synthesis
Protein synthesis
Nucleic acid synthesis
What can we do about side effects and toxicity?
Consider dose and duration
Side effects
Allergic reactions - commonly associated with penicillin and cephalosporins
Immediate hypersensitivity - anaphylactic shock
Delayed hypersensitivity
Gastrointestinal - nausea, vomiting
Thrush
Renal toxicity
Neurological toxicity - e.g optic neuropathy (losing sight)
haematological toxicity - toxic effect on bone marrow
Minimising adverse reactions
Antibiotics/ antimicrobial should be used only when indicated and in minimum dose. With the duration Jesse Cary to just achieve efficacy.
What patient characteristics need to be taken into account when prescribing antibiotics?
Age
Renal function
Liver function
Pregnancy
Prophylaxis
Administration of antibiotics to prevent future occurrence of infection
Indication for antimicrobial:
Prophylaxis
Therapy
Drug related considerations
Antibiotic should be effective against known/ likely causative organism
Choice is based on results of sensitivity of tests, if not - educated test.
Mono therapy or combination of antimicrobial?
More than one mixed together
Effects: additive - same effect as singular one
Antagonistic - less effect as singular one
Synergistic - more effect than singular one
Most common combination?
Penicillin and gentamicin.
Susceptibility testing
Simplest way to measure MIC (min inhibitory concentration) is with the
E TEST
What is an E test used for?
To determine the Minimum inhibitory concentration of one antibiotic against one organism
Which antibiotics are involved in cell wall synthesis inhibition
Penicillin
Cephalosporin
- both beta-lactams.
What do beta-lactams do?
Inhibit cell-wall synthesis
What are vancomycin and teicoplanin?
Glycopeptides
Work on inhibiting cell wall synthesis before beta-lactams
Only act on gram-positive organisms
What is dangerous about vancomycin?
It is toxic
What do glyopeptides work on?
Gram positive bacteria only
What antimicrobials are used in protein synthesis inhibition?
Aminoglycosides - e.g gentamicin
Macrolides& tetracyclines
Oxazolinones - linezolid
Cyclic lipopeptide - daptomycin
What is gentamicin?
An aminoglycoside,
Used in inhibition of protein synthesis
Especially useful in gram negative bacteria
Can be dangerous - very toxic
What is linezolid?
Eg of oxazolinone - inhibits protein synthesis
Works on MRSA
What is daptomycin?
A cyclic lipopeptide
Works on gram positive, especially MRSA.
Inhibition of protein synthesis
What antibiotics are used in nuclei acid synthesis inhibition?
Trimethoprim
sulphamethoxazole
Fluroquniolones - ciprofloxacin
What is ciprofloxacin?
A fluroquinolone
Effective in gram-negative bacteria
Cannot be used in children as it interferes with cartilage growth
Why can ciprofloxacin not be used in children?
As it interferes with cartilage growth
What types of antibiotic resistance are there?
Intrinsic/ inherent
Acquired
What are the two types of acquired inhibition?
Spontaneous mutation to bacterial DNA during replication
Spread of resistant gene (by plasmids or transposons)
What are the main antibiotic resistances?
Beta-lactam resistance
Glycopeptide resistance
What are the 2 types of beta-lactam resistance?
B lactamase production - bacterial enzymes which cleave ring of antibiotic, making it inactive.
Alteration of PBP at target site -
What is staph-aureus resistant to ?
Pencillins
What is fluclozacillin?
Modified pencillin which is resistant to actions of beta- lactamase
What is used to treat staph-aureus and why?
Flucloxacillin, as produces beta-lactamases which prevents usage of pencillin.
What are ESBLs and CPES?
Worrying problems for the future.
Resistant to everything.
What is MRSA?
Methicillin resistant staph aureus
What is MRSA resistant to?
All penicillins and cephalosporins
Explain alteration of PBPs as a beta-lactam resistant strategy
Alters protein structure so beta-lactam can no longer bind to stop it.
What is ESBLs?
Some gram-negative organisms have these (extended spectrum B - lactamases) which are resistant to all b-lactam agents.
Glycopeptide resistance
Only resistant to gram-positive bacteria
Vancomycin ad teicoplanin
Vancomycin resistance
In enterococci (gram-positive)
VRE vancomycin resistant enetrococci
Have appeared recently, not common.
What is VRE?
Vancomycin resistant enterococci
Appeared recently
Clinically worrying
What is Clostridium dificile?
Anaerobic, gram-positive, bacillus
Causes gastro-intestinal side-effects.
Can lead to pseudomembranous colitis
Detected in stool
Treatment = oral vancomycin or oral metronidazole
What are the differnt types of allergic reactions?
Immediate hypersensitivity - anaphylactic shock
Delayed hypersensitivity - Stevens-Johnson syndrome, rashes
What is CDI?
Clostridium dificile infection.- important side effect or antibiotic therapy.
What can minimise CDI?
Restricted prescribing of broad spectrum antibiotic according to local protocols.
What is thrush?
Over-growth of resistant organisms
Brought about by broad-spectrum antimicrobials.
E.g overgrowth of yeast Candida albicans
Oral/ vaginal candidiasis
Liver toxicity
Transient elevation of liver enzymes
Severe hepatitis
Drugs associated with liver toxicity?
Tetracycline
Anti-TB drugs - isoniazid, rifampicin
Flucloxacillin
Common side effects?
Allergic reactions Liver toxicity Renal toxicity Neurological toxicity Haematological toxicity
Renal?
Kidneys
Renal/ nephrotoxicity
Most commonly seen with aminoglycoside group e.g gentamicin
Or Vancomycin
Usually reversible
Neurological toxicity
Ototoxicity
Optic neuropathy
Peripheral
What is ototoxicty?
Ear toxicity
what side effect is associated with anti TB drugs
Optic neuropathy - optic nerve damage
Peripheral neuropathy - damage to peripheral nerves
Example of haematological toxicity?
New MRSA agent LINEZOLID (bone marrow suppressor) (could lower platelet counts)
Prevention of adverse reactions?
Only when necessary and instructed
Minimum dose and duration that achieves efficacy
Care for which groups needs to be given?
Extreme ages
Pregnant women
Those with renal or liver problems
What antimicrobials should be monitored to ensure maximum efficacy and minimum toxicity?
Those with a low therapeutic margin (difference between effective and toxic dose is small)
What two situations would antimicrobials be necessary?
Prophylaxis or treatment
What drug related considerations need to be acknowledged when giving antimicrobials?
Spectrum of antimicrobial agent
Mono therapy vs combination therapy
What are the possible outcomes of combination therapy?
Additive
Antagonistic
Synergistic - great effect together
What is the most common example of combination therapy that leads to a synergistic effect?
Pencillin and gentamicin against streptococcal infective endocarditis
Penicillin breaks down wall
Gentamicin can now reaches ribosomes
Combination of a cidal and static drug will most-likely result in
Antagonistic effects
Examples of commonly used bacteriostatic drugs
Macrolides
Tetracyclines
Trimethoprim
Examples of bactericidal drugs
B-lactams
Aminoglycosides
Glycopeptides
Quinolones
Are anti-virals static or cidal?
Virustatic
Which two commonly used antimicrobials have a low therapeutic index and can be toxic?
VANCOMYCIN AND GENTAMYCIN
What is the standard duration of therapy and what are the exceptions?
7 days
Longer for osteomyelitis or endocarditis
Staph aureus - 14 days
Urinary tract infection cystitis - 3 days of trimethoprim
What are the two main reasons for monitoring serum levels of an antimicrobial ?
Ensure therapeutic levels have been achieved.
Ensure levels have not risen to toxicity.
Sensitivity/ susceptibility testing
Automated - gives an indication of MIC
E test- strip of gradient to compare against
What are the classes of anti-fungal drugs?
Polyenes
Azoles
Allylamines
Echinocandins
What is amophotericin B?
Used intro-venously for serious yeast infections.
It is TOXIC
(Anti-fungal drug)
What is nystatin?
An anti-fungal drug
Used to treat serious fungal infections
Topically/ orally routed
What treats a yeast infection?
Fluconazole
Type of anti-fungal drug - azole
What drug is used to fight fungal infection of skin and nails?
Terbinafine
Type of allylamine
What are echinocandins used for?
Serious Candida and aspergillus infections (anti-fungal drug)
What are the different classes of anti-viral drugs?
Anti herpes drugs
Anti HIV drugs
Drugs for chronic Hep B and C
Drugs for viral respiratory infections
Anti-viral resistance
At its very early stages
Genotypes analysis - sequencing of part of genome
What anti-viral drug is used to treat herpes simplex and varicella zoster?
Aciclovir
What does ZIDOVUDINE treat?
HIV
