Antimicrobial agents 110821 Flashcards
name some beta lactam antibiotics
penicillins
cephalosporins
carbapenems
How do beta lactams work
bactericidal. Inhibit cell wall synthesis by being a substrate to penicillin binding protein
Why might beta lactams not be effective
if the cell wall has already been formed or if the bacteria does not have a peptidoglycan cell wall e.g. mycoplasma, clamydia
Describe how penicillin works
works against Gram +ve streptococci, clostridia
broken down by beta lactamases which are produced by staph aureus etc
Describe amoxicillin
Broad spectrum to enterococci and gram -ve
Flucloxacillin
effective against STAPH AUREUS as it is NOT broken down by beta lactamase produced by SA
Piperacillin
broad spectrum (pseudomonas, non-enteric gram -ve, broken down by beta lactamase
Clavulanic acid and tazobactam
beta lactamase inhibitors,
Name some examples of Cephalosporins
Ceforoxime, ceftriaxone, ceftazidime
What is the significance of the generations of cephalosporins
Increasing activity against gram negative bacilli
ceftazidime vs. ceftriaxone vs. cefotaxime
ceftriaxone (associated with c. diff, treat meningitis, no cover against pseudomonas); ceftazidime (activity against pseudomonas), cefotaxime (paediatric ceftriaxone)
Do cephalosporins work against ESBL producing organisms
No they don’t - use carbapenems
what are Carbapenems used for
Stable against ESBL producing organisms
Examples of CARBAPENEMS
Meropenem, imipenem, ertapenum
What are examples of beta lactams
penicillins, cephalosporins, carbapenems, monobactams
Key features of beta lactams
o Relatively non-toxic
o Renally excreted so decrease dose if renal impairment
o Short T1/2 (many are type 2 drugs so aim to maximise the time > MIC)
o Will not cross BBB
o Cross allergenic – penicillin has 10% cross reactivity with cephalosporins and carbapenems
Glycopeptides
Active against gram +ve, large molecules so unable to penetrate gram -ve.
Slowly bactericidal
nephrotoxic
Important uses of glycopeptides
MRSA, c dif
Why must you monitor glycopeptides
nephrotoxic
Examples of glycopeptides
Vancomycin
Teicoplanin
Telavancin
Give examples of antibiotics that inhibit protein synthesis
aminoglycosides, tetracyclines, macrolides, cloramphenicol, oxazolidinones
Aminoglycosides, examples, MOA
• Aminoglycosides – gentamicin, amikacin, tobramycin
o Bind to amino-acyl site of 30s ribosome subunit
o Rapid, concentration-dependent bactericidal
o Require specific transport mechanisms to enter
Accounts for some intrinsic resistance
o Ototoxic and nephrotoxic – monitor levels
o Gentamicin and tobramycin are particularly active against pseudomonas aeruginosa
o Synergistic combination with beta lactams
Endocarditis treatment, pneumonia
o No activity against anaerobes
Tetracyclines
o Broad spectrum, activity against intracellular pathogens – chlamydia, rickettsia, mycoplasma
o Bacteriostatic (stops bacteria from reproducing)
o Widespread resistance now
o Deposited in growing bone
Don’t give to children, pregnant women
o SE: photosensitivity rash (summer effect)
Particularly doxycycline
Which protein synthesis inhibitor should you NOT give to children and pregnant women
Tetracyclines as it deposits in growing bone
Macrolides
o Bacteriostatic
o Useful agent for treating mild staphylococcal or streptococcal infections in pen-allergic patients
o Active against campylobacter species, legionella, pneumophilia
o Newer agents include clarithromycin and azithromycin due to a better half-life
o Little activity against gram -ve bacteria (membrane)
o Useful to inhibit toxins produced by bacteria
Cloramphenicol
o Bacteriostatic
o Broad antibacterial activity
o Rarely used apart from eye preparations
Risk of aplastic anaemia
Risk of grey-baby syndrome in neonates because of inability to metabolise the drug
Oxazolidinoes
o Highly active against gram +ve (MRSA & VRE)
o Not active against most gram -ve
o Expensive, may cause thrombocytopenia & optic neuritis; should only be used with micro/ID approval
o Binds to 23S component of 50s subunit prevents formation of a functional 70s initiation complex
Which antibiotics inhibit DNA synthesis
Quinolones and nitromidazoles
Nitromidazoles
o Under anaerobic conditions, an active intermediate is produced which causes DNA strand breakage
o Rapidly bactericidal
o Active against anaerobic bacteria and protozoa (Giardia)
o Nitrofurans are related compounds (nitrofurantoin is good for cystitis and lower UTIs)
Quinolones
o Act on alpha unit of DNA gyrase, bactericidal
o Broad antibacterial activity versus gram -ve (pseudomonas aeruginosa)
o Newer agents (levofloxacin, moxifloxin) better against gram +ve and intracellular bacteria (Chlamydia spp.)
o Well absorbed after PO administration (good bioavailability)
o Use for UTI, pneumonia, atypical pneumonia, bacterial gastroenteritis
o Lower your seizure threshold, also causes achilles tendonitis
Rifamycin
• Rifamycins – rifampicin and rifabutin
o Inhibits protein synthesis by binding to DNA-dependent RNA polymerase, inhibiting initiation
o Bactericidal
o Active against mycobacteria and chlamydia
o Interactions with other drugs metabolised in the liver (OCP) and so need to monitor LFTs
o Turns secretions orange (urine and contacts) – can check compliance
o Rifampicin resistance (never used as a single):
Resistance due to chromosomal mutation
Causes single amino acid change in beta subunit of RNA polymerase which fails to bind rifampicin
Inhibitors of folate metabolism include
• Sulphonamides
o Resistance is common
o Combination of sulphamethoxazole + trimethoprim (co-trimoxazole) is important in treating pneumocystis jiroveci pneumonia (PCP – HIV-defining disease)
• Diaminopyrimidines – trimethoprim
o Used as treatment for community acquired UTIs
How does MRSA and strep pneumoniae have resistance to flucloxacillin
target modification
How do ESBLs have resistance
enzyme modification/iniactivation
