11.1 Antimicrobials Flashcards
What is meant by multi-drug resistance?
Non-susceptibility to at least one agent in three or more antimicrobial categories
What is meant by extensively drug resistant?
Non-susceptibility to at least one agent in all but two or fewer antimicrobial categories
What is meant by pan drug resistant?
Non-susceptibility to all agents in all antimicrobial categories
What are the key points of antimicrobial stewardship?
Appropriate use of antimicrobials
Optimal clinical outcomes
Minimize toxicity and other adverse events
Reduce the costs of health care for infections
Limit the selection for antimicrobial resistant strains.
What are the persuasive interventions of antibiotic stewardship?
Education Consensus Opinion leaders Reminders Audit Feedback
What are the restrictive interventions of stewardship intention?
Restricted susceptibility reporting
Formulary restriction
Prior authorisation
Automatic stop orders
What are the structural interventions of antibiotic stewardship?
Computerised records
Rapid lab test
Expert systems
Quality monitoring
What is used to guide antibiotic choice?
History/presenting complaint
Follow local guidelines
Why should local guidelines by used over NICE guidelines when prescribing antibiotics?
as regional sensitivity/resistance is a thing
Before treating an infection with antimicrobials, what should be done?
microbiological samples obtained pertinent to the suspected infection; this will allow laboratory testing for
sensitivity and resistance, thus allow you to give more focused treatment
What is considered in antibiotic guidelines?
Which pathogens are most likely causative for a given infection type
What are the characteristics of these pathogens, i.e. Gram +ve vs. Gram –ve, Anaerobic vs. Aerobic?
Does it reach the site of infection?
What must a clinician consider before prescribing an antibiotic advised by the local guidelines?
Is the drug available in the right formulation?
What is the half-life/dosing frequency?
Does it interact with other drugs?
Are there toxicity concerns?
Does the antibiotic require therapeutic drug monitoring?
Does your patient have an allergy to the drug?
What antimicrobials affect cell wall synthesis?
Penicillins
Vancomycin
Cephalosporins
What antibiotics affect folic acid metabolism?
Trimethoprim
Sulfonamides
What antibiotics affect protein synthesis (30s inhibitors)
Tetracyclines
Gentamicin
Streptomycin
Nitrofurans
What antibiotics affect protein synthesis (50s inhibitors)
Erythromycin (Macrolides)
What is the mechanism of action of beta lac tam antibiotics?
Interfere with the synthesis of the bacterial cell wall peptidoglycan
Generally bactericidal
1. Antibiotic binds to penicillin-binding protein on bacteria
2. Inhibit the transpeptidation enzyme (responsible for linking the peptidoglycan chains to form rigid cell walls)
3. Disruption of bacterial cell wall structure.
What are the three main sub groups of beta lactams?
Penicillin
Cephalosporins
Carbapenems
What are common examples of penicillins?
Phenoxymethylpenicillin (Penicillin V)
Flucloxacillin (Beta lactamase resistant)
Amoxicillin (Broad spectrum)
Co-amoxiclav
What is the role of clavulanic acid?
Beta-lactamase inhibitor. Inhibits beta-lactamase breaking down beta-lactate antibiotic molecular structure
What combination of drugs is co-amoxiclav?
Amoxicillin
Clavulanic acid
What cautions should be taken before administering penicillin?
Individual sensitivity testing often required, particularly in secondary care
What are the clinical applications of penicillins?
Bacterial meningitis Bone and joint infections Skin and soft tissue infections Otitis media Pneumonia UTIs STIs
What are examples of cephalosporins?
Cefalexin
Ceftriaxone
Cefuroxime
Cefotaxime
What must be considered before presribingcephalosporins in secondary care?
Individual sensitivity testing
What are the clinical applications of cephalosporins?
Septicaemia Pneumonia Meningitis Biliary tract infections UTIs (especially in pregnancy or in patients unresponsive to other drugs) Sinusitis
What antibacterial affect bacterial protein synthesis?
Tetracyclines Aminoglycosides Macrolides Oxazolidinones Lincosamides Nitrofurans
What is the mechanism of action of tetracyclines?
Following uptake into susceptible organisms by active transport, tetracyclines act by inhibiting protein synthesis
Bind to bacterial ribosomes, preventing binding of tRNA to it, thus preventing the initiation of protein synthesis
Bacteriostatic
What are common examples of tetracyclines?
Doxycycline
Tetracycline
What are the clinical applications of tetracyclines?
Respiratory tract infections (particularly atypical organisms)
Acne
Chlamydia
Lyme disease
Why shouldn’t tetracyclines be given to children under 12, pregnant and breastfeeding women?
As causes staining of developing teeth
What is the mechanism of action of macrolides?
Inhibit bacterial protein synthesis by an effect on ribosomal translocation Bactericidal/bacteriostatic
What are common examples of macrolides?
Erythromycin
Clarithromycin
Azithromycin
What are the clinical applications of macrolides?
The antimicrobial spectrum of macrolides is very similar to that of penicillin
Also active against atypical respiratory pathogens
Give an example of a nitrofuran?
Nitrofurantoin
What is the mechanism of action of nitrofurantoin?
Works by being reduced to multiple reactive intermediates by nitrofuran reductase inside the bacterial cell
These intermediates then attack ribosomal and DNA proteins within the bacteria, as well as inhibit the Citric acid cycle
Why is nitrofurantoin one of the first line agents in treating urinary tract infections?
Up to 50% of an oral dose Nitrofurantoin is excreted in the urine in unchanged form
This allows Nitrofurantoin to concentrate within urine, leading to more effective levels within the bladder than in other tissue compartments
What is the mechanism of action of quinolones?
Inhibit topoisomerase II (a bacterial DNA gyrase), the
enzyme that produces a negative supercoil in DNA and
thus permits transcription or replication
What are common examples of quinolones?
Ciprofloxacin
Levofloxacin
What are the clinical applications of quinolones?
Very good cover of Gram negative organisms, as well as atypical organisms and Gram positives Clinical applications: Complicated UTIs Pseudomonas aeruginosa cover Gonorrhoea
What are the important ADR of quinolones?
Tendinitis +/- rupture
Aortic dissection
Central nervous system effects (inc. Convulsions)
What is the mechanism of action of trimethoprim?
Folate antagonist: Reversible inhibitor of dihydrofolate reductase, which is responsible for the production of Tetrahydrofolic acid necessary for the biosynthesis of bacterial nucleic acids and proteins
Binds with a much stronger affinity to bacterial dihydrofolate reductase than human
Bacteriostatic/bactericidal
What are the clinical applications of trimethoprim?
UTIs
When are trimethoprim contraindicated?
In pregnancy, has tetragenic effects on fetus
What organisms is metronidazole effective against?
Protozoa and anaerobic bacteria
What advice must be given to a patient taking metronidazole?
Has disulfiram-like action, advise patients to avoid using alcohol when on the antibiotic as would get severe hangover.
What are the most commonly used antivirals?
Aciclovir (DNA Polymerase Inhibitors)
Oseltamivir (Neuraminidase Inhibitors)
What is the mechanism of action of acyclovir?
Activated predominantly in infected cells as it is phosphorylated and activated by viral enzyme thymidine. When active, acyclovir inhibits the viral DNA polymerase.
What are the clinical applications of acyclovir?
Herpes simplex infections (genital herpes, encephalitis) Varicella zoster (chicken pox, shingles)
When is acyclovir advised to treat herpes simplex virus?
Predominantly to treat serotype HSV-2 (genital infections. Not used to treat HSV-1/ herpes labialis in healthy patients. May be used prescribed orally in HSV-1 depending on severity, frequency and persistence of the lesions, and if the patients are immunocompromised
What is the routine treatment of genital herpes?
First episode:
Oral Aciclovir within 5 days of the start of the episode or while new lesions are forming
Recurrent episodes:
Episodic antiviral treatment – if attacks are infrequent (<6/year)
Either 800mg TDS for 2 days or 200mg 5x/day for 5 days. Consider self-initiated treatment, to allow for early start
Suppressive antiviral treatment – if attacks are more frequent (≥6/year) OR causing psychological distress OR affecting the person’s social life
400mg BD OR 200mg QDS. If breakthrough recurrences occur, the dosage should be increased. Continue treatment for max. 1 year, after which it should be stopped to assess recurrence
What are notable sites for CYP450 enzymes?
Liver Small intestine Lungs Placenta Kidneys
What are the most significant CYP enzymes?
CYP3A4
CYP2DP
Why should metronidazole not be prescribed alongside warfarin?
Warfarin is an anticoagulant that is metabolised by CYP2C9
Metronidazole is a CYP2C9 inhibitor
Inhibiting the enzyme will slow down warfarin metabolism and cause warfarin overdose.
What medications should not be prescribed alongside macrolides and why?
Macrolides inhibit CYP3A4, and should not be prescribed alongside drugs that are metabolised by this enzyme such as verapamil (CCB) and simvastatin. If prescribed together would cause CCB overdose (orthostatic hypotension) and statin overdose (myopathy and rhabdomyolysis on rare occasions)
Describe the enterohepatic circulation
Begins with drug absorption across the intestine into the portal circulation, followed by uptake into the
hepatocytes. Next, drug and or conjugated metabolites
are secreted into the bile and returned to the intestine,
where drug can be reabsorbed into the circulation
How do oral antibiotics reduce the absorption rates of certain drugs?
Oral antibiotics can eliminate gut flora and lessen the enzymes involved in the metabolism of drugs in bile. Reduce absorption rates of drugs that are absorptive due via secondary absorption in bile due to the enterohepatic circulation. For example antibiotics, NSAIDs, hormones, opiods, digoxin, warfarin.
What advice should be given to females on the contraceptive pill when taking antibiotics?
Oral antibiotics can lower the rates of enterohepatic recycling and cause lower blood concentrations of oestrogen and progesterone in patients on oral contraceptives. Increases the risk of becoming pregnant. Should use additional barrier contraceptive methods whilst on antibiotics.
