Antimicrobial agents 110821 Flashcards by Sijia Yao

name some beta lactam antibiotics

penicillins
cephalosporins
carbapenems

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How do beta lactams work

bactericidal. Inhibit cell wall synthesis by being a substrate to penicillin binding protein

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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

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Describe how penicillin works

works against Gram +ve streptococci, clostridia

broken down by beta lactamases which are produced by staph aureus etc

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Describe amoxicillin

Broad spectrum to enterococci and gram -ve

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Flucloxacillin

effective against STAPH AUREUS as it is NOT broken down by beta lactamase produced by SA

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Piperacillin

broad spectrum (pseudomonas, non-enteric gram -ve, broken down by beta lactamase

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Clavulanic acid and tazobactam

beta lactamase inhibitors,

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Name some examples of Cephalosporins

Ceforoxime, ceftriaxone, ceftazidime

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What is the significance of the generations of cephalosporins

Increasing activity against gram negative bacilli

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ceftazidime vs. ceftriaxone vs. cefotaxime

ceftriaxone (associated with c. diff, treat meningitis, no cover against pseudomonas); ceftazidime (activity against pseudomonas), cefotaxime (paediatric ceftriaxone)

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Do cephalosporins work against ESBL producing organisms

No they don’t - use carbapenems

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what are Carbapenems used for

Stable against ESBL producing organisms

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Examples of CARBAPENEMS

Meropenem, imipenem, ertapenum

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What are examples of beta lactams

penicillins, cephalosporins, carbapenems, monobactams

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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