Antibiotics Flashcards
What are the inhibitors of cell wall?
Beta lactams which are penicillins, cephalosporins, carbepenems and monobactams
Glycopeptides
What are the antibiotics classes active against ribosomes?
30S - Tetracyclines - Aminoglycosides 50S - Macrolides - Lincosamides - Chloramphenicol - Fusidic acid - Lineozlid
What are the antibiotics choices for MRSA
Vancomycin
Linezolid
Fusidic acid and rifampicin
Pristinomycin (a macrolide and a depsipeptin)
What is the main side effect limiting chloramphenicols systemic use?
Aplastic anaemia in 1 in 30000
What antibiotics block folic acid synthesis?
Trimethoprim
Sulphonamides
What is the mechanism of action of fluroquinolones?
DNA gyrase inhibitor. Gyrase in gram negatives and topoisomerase 4 in gram positives are required to maintain the DNA in the double helix structure.
What are the mechanisms bacteria use to develop resistance?
Chromosomal mutation
Plasmids
Tansposons (free DNA)
Bacteriophange
What are the ESCAPPM organism and what are their significance?
Enterobacter Serratia Citrobacter Acinetobacter Providentia Proteus vulgaris Morganella morganii These bacteria have chromosomally encoded beta lactamse which is inducible with treatment with a cephalosporin
What is ESBL? Which bacteria most commonly carry this resistance?
Extended spectrum b-lactamase
This inactivates all cephalosporins and penicillins
Usually seen in E.Coli and Klebsiella - aka UTIs
What are the mechanisms of resistance?
Antibiotic inactivation
Alteration of target site
Decreased antibiotic permeability
Active efflux
What are the narrow spectrum pencillins? And what do they cover?
Benzylpenicillin Benzathine Procaine Phenoxymethyl Gram pos cocci
What do the moderate spectrum penicillins cover than the narrow do not?
Wider gram neg - E.coli, haemophilus and enteroccoci
What penicillins cover pseudomonas?
The very broad spectrum - piptaz and timentin
Which generations of cephalosporins have more gram negative cover?
The later generations mostly from 3rd gen (ceftriaxone and cefotaxime) onwards
Pseudomonas is only covered by ceftazidine (3rd gen) and cefepime (4th gen)
What are the 1st generation cephalosporins?
Cephalexin
Caphazolin
Cephalothin
What bacteria do cephalosporins have no effect against?
MRSA
Listeria
Enterococci
What are the carbapenems and what are their mechanisms of action?
Meropenem
Imipenem
Ertapenem
A beta lactam they bind to penicillin binding sites and disrupt cell wall synthesis. They are resistant to most beta lactamases.
What antibiotics are active against ESBL producting bacteria?
Meropenem
cotrimoxazole
Ertapenem
What are carbepenems not active against?
MRSA Stenotrophomonas VRE Burkholderia Atypical bugs - legionella myooplasma
What is the problematic side effect of imipenem?
Seizures especially with decreased renal function
What class is vancomycin and what is its mechanism of action?
Glycopeptide along with teicoplanin
Inhibits cell wall synthesis by binding to precurser units - no beta lactam ring
What is spectrum of activity of glycopeptides?
MRSA MSSA Enterococci (not VRE) Pneumococcus Does not have any significant gram neg cover
What is the mechanism of resistance in VRE?
Transferred via plasmids
There is an alteration in the binding site
What are the treatment options for enterococcus?
Naturally resistant to all cephalosporins
Amoxicillin or ampicillin
Vancomycin
*for serious infections often paired with an aminoglycoside for synergy
What is the mechanism of action and the types of aminoglycosides?
They bind with the 30S ribosomal subunit in the cell which inhibits protein synthesis
What is the effect of low oxygen environments on aminoglycosides?
Aminoglycosides act on the intracellular ribosomal subunit. It takes 2 steps to gain intracellular access - a porin then electron transport. This last step is dependant on a number of factors including O2. Anaerobic bacteria are intrinsically resistant and low O2 environments like an abscess also prevent adequate uptake.
What is the aminmoglycoside with the least side effects?
Tobamycin
What are the macrolides and what is their mechanism of action?
Azithromycin Clarithromycin Erythromycin Roxithromycin Bacteriostatic, reversibly bind to 50S ribosome preventing protein synthesis
What is the spectrum of macrolides?
Atypicals (legionella, mycoplasma, chlamydia) Gram + cocci Some gram - cocci and anaerobes Nontuberculous mycobacteria eg MAC Pertussis Haemophilus
What are the adverse effects of macrolides
GI upset esp erythromycin
Ototoxicity
Hepatotoxicity
Prolong QTc
What are the tetracyclines and what is their mechanism of action?
Doxycycline
Minocycline
Tigecycline
Bind to 30S ribosome, prevent protein formation
What is the spectrum of tetracyclines?
Gram + and - coverage
Atypicals
Rickettsia and spirochates
Some protozoa eg malaria
Some nontuberculous mycobaceria
Minocycline can be active against bacteria that are resistant to other tetracyclines
Tigecycline is very broad including MRSA, VRE, anaerobes but not psuedomonas
What is the oral anti-pseudomonal drug, what class is it and what is its mechanism of action?
Ciprofloxacin a fluroquinolone. Other drugs in this class are moxifloxacin, norfloxicin. It is a DNA gyrase inhibitor which destabilises the DNA helix structure. In gram + it acts on topoisomerase 4 which has the same action
What is the spectrum of fluroquinlones?
Very broad spectrum.
Ciprofloxicin - Gram - including pseudomonas, haemophilus, legionella and some mycobacteria
Norfloxacin - same as cipro but only for mucosal infections
Moxifloxacin - Gram + and -, anaerobes, atypicals, some mycobacterium. Not good for pseudomonas
What is the main role for moxifloxacin?
Very broad spectrum esp gram +. Used for severe penicillin allergies
What are the side effects of fluroquinolones
GI upset C. Diff Photosensitivty CNS effects Cartilage effects - Achilles tendon rupture or tendonitis QTc prolongation Drug interactions
What is clindamycin and what is its mechanism of action?
It is a lincosamide along with lincomycin.
It is bacteriostatic and binds to the 50S subunit of the ribosome inhibiting protein synthesis
What is the spectrum of lincosamides?
Gram positive cocci including MRSA
Anaerobes
Toxoplasma
No useful gram neg coverage
What is the primary role for monobactams?
Aztreonam
Only gram neg coverage
Good for ESCAPPM, pseudomonas
What are the rifamycins and what are their mechanism of action?
Rifampicin and rifabutin
Inhibits RNA polymerase
What is the main mechanism of resistance to rifampicin?
Only a single gene mutation is required to alter the binding site leading to resistance.
What is the spectrum of rifamycins?
Gram +
Mycobacterial species
Can be used in combination with fusidic acid for MRSA
What colour does the urine change to if treated with rifamycins?
A pink/red colour
What class does metronidazole belong to and what is its mechanism of action?
A Nitroimidazole along with tinidazole.
It binds to bacterial DNA disrupting its structure and preventing neucleic acid synthesis
What is the spectrum of action of nitroimidazoles?
Anaerobes - gram +, - and protozoa
Notably good for c.diff
What is in bactrim?
Trimethoprim and sulfamethoxazole
What is the mechanism of action of chloramphenicol and what is it active against?
Binds to and inhibits 50S subunit of the ribosome inhibiting bacterial protein synthesis
It is a broad spectrum with activity against gram pos and neg as well as rickettsia and chlamydia
What is the role of linezolid?
Vancomycin resistant MRSA
VRE
What is the mechanism of action of daptomycin? What is its role?
Binds to cell membranes causing depolarisation. This inhibits protein, DNA and RNA synthesis leading to cell death.
It is primarily used for antibiotic resistant gram positive bacteria including VRE
What are the side effects of bactrim?
Hyperkalaemia Hypersensitivity GI upset Skin sensitivity Bone marrow suppression
What clinical infection can daptomycin not be used for?
Pneumonia - no penetrance
