Y3 Antibiotics Flashcards
What two groups of bacteria are penicillins active against?
Staphylococci and Streptococci
gram-positive
How do penicillins work?
Inhibit the enzyme responsible for synthesising the bacterial cell wall (X-linking of peptidoglycan)
What is the active group on penicillins?
Beta-lactam ring
How do bacteria become resistant to antibiotics?
By synthesising the enzyme beta-lactamase
What are some of the simplest forms of penicillin?
Benzyl-penicillin and Phenoxymethypenicillin
What are BenPen and Phenoxymethypenicillin (penicillin V) used to treat usually?
STREP INFECTIONS: Pneumonia (in combination with macrolide)
Tonsilitis
Endocarditis
SSTIs +fluclox
CLOSTRIDIAL INFECTIONS:
Tetanus
MENINGOCOCCAL INFECTIONS:
Meningitis and septicaemia
Which penicillins have anti-pseudomonad properties?
TAZOCIN: tazobactam and piperacillin
What particular agent does tazocin have good action against?
Pseudomonas Aeruginosa
Why is tazobactam a useful addition? What agents does tazocin thus cover that other penicillins do not?
It is a beta-lactamase inhibitor and so fewer organisms are resistant to tazocin.
Staph. Aureus and gram-negative anaerobes
What sorts of infections is tazocin particularly useful in?
HCAIs (usually quite multi-resistant organisms:
- HAP
- Hospital acquire UTI
- Intra-abdominal sepsis
- SSTI
What are some adverse effects of tazocin?
Abx associated colitis
What are some examples of broad spectrum penicillins?
Amoxicillin and Co-amoxiclav
What makes amoxicillin more useful against gram-negative bacteria?
It has an amino chain attached to its beta-lactam ring
What can we do to make amoxicillin even more broad spectrum?
Add clavulanic acid to make co-amoxiclav
- Clavulanic acid is an example of a beta lactase inhibitor
What is one of the main uses of amoxicillin and why?
Empirical treatment for pneumonia? Covers the common gram positive causes: Strep Pneumoniae and the common gram negative causes: haemophilus influenzae
What are some of the less common uses for amoxicillin?
Empirical treatment for UTIs (usually trimethoprim and nitrofurantoin)
Part of treatment for an HCAI or intrabdominal sepsis
Part of treatment for H. pylori associated peptic ulcers
What are some penicillinase resistant antibiotics? How do they achieve this?
Flucloxacillin
Addition of an acyl group make them resistant to many lactase enzymes
What organism is flucloxacillin particularly useful against?
Staphylococcus aureus (NOT ALL STRANDS) MRSA is resistant to fluclox.
What sorts of infections is flucloxacillin particularly good at treating?
SSTIs
We can use it in combination with BenPen if particularly severe but can often cover alone
What are some of the less common infections that flucloxacillin can be used for?
Osteomyelitis and septic arthritis and endocarditis
How do cephalosporins and carbapenems work?
With a beta-lactam ring
How are cephalosporins and carbapenems different from penicillin?
Side groups (dihydrothiazine ring - cephs) and (hydroxyethyl ring - penems) make them less resistant to beta-lactamases
Are cephalosporins and carbapenems typical narrow or broad spectrum?
Broad. The newer ones even more so
What are some examples of cephalosporins?
Cefalexin, cefotaxime, cephradine
What are some examples of carbapenems?
Meropenem and ertapenem
What are some of the more common uses of cephalosporins?
2nd and 3rd line treatment for UTIs and LRTIs
What sorts of infections are cephalosporins and carbapenems used for?
Cephalosporins and carbapenems are usually reserved for very severe or very complicated infections because they have such broad spectrum activity.
They are able to cover most infections
How does trimethoprim work?
it inhibits folate synthesis and thus stops bacteria from being able to replicate DNA
Is trimethoprim broad or narrow spectrum?
BROAD. Especially against gram negative enterobacteria e.g. E.coli
What can we add to trimethoprim to make it even broader spectrum? How does this work?
A sulphonamide (sulphamethoxazole). Another type of folate inhibitor but it works in a different way and so their effects can be additive. CO-TRIMOXAZOLE
What are some common uses of trimethoprim?
First line for UTI. 200mg PO BD.
Alternative are nitrofurantoin and piperacillinam
What is a common use for co-trimoxazole?
Pneumocystis pneumonia in people with immunosuppression e.g. HIV
What are some of the contra-indications for trimethoprim?
FIRST trimester of pregnancy (neural tube defects)
How does nitrofurantoin work?
It is metabolised by bacteria and the active form Nitrofuran is produced which damages bacterial DNA
What organisms is nitrofurantoin useful against?
Gram positive and gram negative agents that commonly cause UTI
What organisms is nitrofurantoin less useful against?
Ones that have reduced activity of nitrofuran reductase
What is the most common reason for using nitrofurantoin?
Uncomplicated UTI
What are some of the contraindications of nitrofurantoin?
Do not use in pregnancy at all or in the first 3 months of life.
How do tetracyclines work?
They inhibit protein synthesis by binding to 30s sub-units and are hence bacteriostatic
What are some examples of tetracyclines?
Doxycycline and Lymecycline
Are tetracyclines broad or narrow spectrum?
Relatively broad
How do bacteria develop resistant to tetracyclines?
Develop an efflux pump to pump them out
What are some of the adverse effects of tetracyclines?
GI symptoms but they are some of the lowest risk for C Diff
What are some of the most common uses for tetracyclines?
Acne Vulgaris: particularly when there are inflamed papule caused by propionibacterium acnes
LRTI including infective exacerbation of COPD and atypical pneumonias
Chlamydial infection including PIFD
Typhoid, Anthrax, malaria and lyme disease
What are some of the contraindications for tetracylines?
Bind teeth and bones during development so do not give during pregnancy
How do aminoglycosides work?
Similarly to tetracyclines - they bind irreversibly to 30S subunits and hence inhibit protein synthesis
Are aminoglycosides bactericidal or bacteriostatic?
Bactericidal - they have other mechanisms of action which are largely not-understood. It is likely one of these which causes them to be bactericidal
What are some examples of aminoglycosides?
Gentamicin and Streptomycin
Which organisms are aminoglycosides useful against?
Gram negative aerobic bacteria (neisseria meningitides and gonorrhoea and campylococci, staphylococci and mycobacteria
How do aminoglycosides enter the bacterium cell?
Via OXYGEN-dependent channels (hence anaerobes innately resistant)
How do some aerobes develop resistance against aminoglycosides?
Changing the permeability of their membranes
How can we attempt to overcome aerobe resistance to aminoglycosides?
If we give them with penicillins then penicillins can help to weaken the cell membrane and again improve the permeability
What are some contraindications of aminoglycosides?
They are nephrotoxic and ototoxic
Through what route to we give aminoglycosides?
Always IV. They do not cross lipid membranes and so cannot be given orally.
What are some of the most common uses for aminoglycosides?
Severe sepsis (usually when the source has been identified Pyelonephritis and complicated UTIs Biliary and other intra-abdominal sepsis Endocarditis
How do Macrolides work?
They inhibit protein synthesis by binding to the 50S sub-unit
What are some examples of macrolides?
Erythromycin, Clarithromycin, Azithromycin
Are macrocodes bacteriostatic or bactericidal?
Bacteriostatic
Are macrocodes broad or narrow spectrum? Which ones are broadest?
Relatively broad
Clarithromycin and azithromycin have an even broader spectrum towards gram-negatives particularly heamophilus influenzae
How do bacteria become resistant to macrolides?
Ribosome mutations
What are some adverse effects? Which macrolides are most likely to cause them?
C. difficile overgrowth colitis.
Erythromycin is the most common abx to cause this
Can also cause ototoxicity and cholestatic jaundice
Prolong QT interval
What are macrolides most commonly used for?
LRTI (Clarithromycin when penicillin is contraindicated due to allergy)
SSTI (when penicillin is CId because of allergy)
Severe pneumonia (added to penicillin to cover atypical e.g. legionella or mycoplasma)
Eradication of H.pylori (part of triple therapy with PPI and amoxicillin)
How do quinolones work?
Inhibit DNA synthesis
What are some examples of quinolones?
Ciprofloxacin, Levofloxacin
Which organisms are quinolones most effective against?
Gram negative bacteria
Which quinolone has a broader spectrum?
Levofloxacin - better effect against gram positives and so can be used for LRTIs.
Commonly used after tazocin in HAP
How do organisms develop resistance against quinolones?
Decreasing permeability or increasing efflux to reduce the intra-cellular concentration
What are some of the most common uses of quinolones?
UTI
Severe GI infection (shigella or campylobacter)
LRTI
Cipro is one of the only abx with use against pseudomonas aeruginosa
What are some adverse effects of quinolones?
Can cause C.diff with hyper-virulent 027 strain
How do glycopeptides work?
Inhibits growth and X-linking of peptidoglycan
Which strains of bacteria are glycopeptides effective against?
Gram positives
What is the most common example of a glycopeptide?
Vancomycin
What are some of the most common adverse effects of vancomycin?
Thrombophlebitis at infusion site and in extreme cases Red-Man Syndrome (widespread anaphylaxis)
Nephrotoxic and ototoxic
What are some of the most common uses of vancomycin?
Endocarditis (when severe or if MRSA)
Treatment for abx associated colitis due to C.diff (125mg PO for 10-14 days)
What is an examples of an anaerobic anti microbial?
metronidazole
How does metronidazole work?
Enters bacterium via passive diffusion and produce a NITROSO free radical during its metabolism. This binds to DNA and reduces synthesis
Which organisms are resistant to metronidazole?
Aerobes - they cannot metabolise it and so are innately resistant
What are some adverse effects of metronidazole? What are some warnings to give when prescribing?
GI upset as well as peripheral optic neuropathy, seizures and encephalopathy
DO NOT DRINK WITH ALCOHOL because enzyme acetylaldehyde dehydrogenase is inhibited (profuse vomiting, flushing and nausea)
What are some contra-indications for giving metronidazole?
Liver disease (they are metabolised by the CYP450 system)
What is metronidazole commonly used for?
Antibiotic associated colitis with c. diff
Oral infections (dental abscess or aspiration pneumonia)
Surgical and gynaecological infections
Protozoal infections including dysentry and giardiasis
