antibiotics

Question 1

MIC?

Answer 1

Determined Minimum Inhibitory capacity (MIC) – concentration under standard conditions at which no visible growth of bacteria in broth or on plate
Disc diffusion methods – zone of inhibition around antibiotic impregnated disc

Interpretation susceptibility by MIC breakpoint/ zone diameter

Question 2

pharmacodynamics determinanrts of outcomes?

Answer 2

Different parameters best predict response to therapy for different classes of antibiotics
Time>MIC
β-lactams, vancomycin, macrolides
Cmax/MIC ratio
Aminoglycosides
AUC24h/ MIC ratio
Fluoroquinolones

Question 3

describe gram positives and negative bacteria

Answer 3

Question 4

when touse penicillins?

Answer 4

Benzylpenicillin – iv only
Streptococci (not Enterococci), Neisseria meningitidis, some anaerobes

Penicillin V – po
Streptococci (not Enterococci), some anaerobes

Flucloxacillin (penicillinase stable)
Staphylococcus aureus, Streptococci (not Enterococci), some anaerobes

Amoxicillin/ Ampicillin
As benzylpenicillin + limited Enterobacteriaceae activity, Haemophilus influenzae, Enterococci, Listeria

Piperacillin – antipseudomonal penicillin
As amoxicillin + enhanced Enterobacteriaceae activity, Pseudomonas

Question 5

b lactamase inhibitos?

Answer 5

Amoxicillin + clavulanic acid (Augmentin)
Active against Staphylococcus aureus (MSSA)
Enhanced activity Enterobacteriaceae and anaerobes

Piperacillin + tazobactam (Tazocin)
Similar Augmentin + Pseudomonas cover

Question 6

cephalosporin?

Answer 6

1st generation
Cefradine, Cefalexin
Staphylococcus aureus (MSSA), streptococci (not enterococci), limited enterobacteriaceae cover
2nd generation
Cefuroxime
Increased spectrum and potency vs enterobacteriaceae
3rd generation
Cefotaxime, Ceftriaxone, Ceftazidime
Further increase spectrum and potency vs enterobacteriaceae
Ceftazidime only – Pseudomonas
Reduced activity gram-positives

Question 7

carbapenems?

Answer 7

Meropenem and Imipenem

Very broad spectrum
Enterobacteriaceae – including multi-drug resistant
Pseudomonas
Staphylococci (MSSA), streptococci
Anaerobes

Question 8

b lactam ADR?

Answer 8

Other GI upset
Reduced seizure threshold
Neutropenia
Liver enzyme abnormalities
Interstitial nephritis

Question 9

glycopeptides activity?

Answer 9

Active most gram-positive cocci and bacilli – including MRSA.
Some enterococci are resistant
Not clinically useful against gram-negative infections
Clostridial species inc C. difficile

Question 10

glycopeptides clinical use?

Answer 10

IV for serious infections with:
Known or suspected infection with multi-resistant gram-positive bacteria (eg MRSA)
β-lactam allergy and known or suspected infection with gram-positive bacteria
Skin and soft tissue infection
Joint and bone infection
Infections of prosthetic devices – eg central lines, joint prosthesis
Endocarditis

Question 11

glycopeptide ADR?

Answer 11

Nephrotoxicity
Ototoxicity
Red man syndrome
Allergy
Cytopenias

Question 12

aminoglycosides?

Answer 12

Streptomycin
Gentamicin
Amikacin
Tobramycin

Bind 30s subunit of ribosomes → conformational change → interrupts translation and translocation of mRNA

Gram negative bacilli – including Pseudomonas
Staphylococci (not used as monotherapy)

Intrinsic resistance in Streptococci and anaerobes
but …..
Synergistic killing combined with cell wall active agents (eg β-lactam) against Streptococci

Question 13

aminoglycoside ADR?

Answer 13

Associated with significant toxicity with a narrow therapeutic index – drug levels required
Nephrotoxic
Ototoxic
Neuromuscular blockade
Allergy uncommon

Bactericidal
Concentration dependent killing
Single daily dosing as effective most indications
Adverse events reduced single daily dosing
Post-antibiotic effect

Cross blood brain barrier poorly
Low concentrations in bronchial secretions
Very high concentrations in urine

Question 14

fluroquinolones?

Answer 14

Ciprofloxacin
Levofloxacin
Moxifloxacin
Gatifloxacin etc

Inhibit activity of DNA gyrase and topoisomerase IV → Inhibit bacterial DNA synthesis
Bactericidal
Excellent oral bioavailability

Ciprofloxacin
Most potent vs aerobic gram negative
Includes Pseudomonas (only clinically useful oral antibiotic)
Staphylococci (resistance relatively common)
Atypical bacteria (Legionella, mycoplasma etc)
Limited activity vs Streptococci
Levofloxacin
Enhanced activity streptococci and anaerobes

Ciprofloxacin
Pseudomonal infection if oral therapy appropriate
Complicated UTI, prostatitis
Abdominal infections
Often no longer first line in UK hospital policies – attempts to control C. difficile
Levofloxacin
Pneumonia (β-lactam allergy)
Legionaire’s disease

Question 15

fluroquinolones ADR?

Answer 15

Antibiotic associated diarrhoea
Tendon rupture
Central nervous system side effects – includes seizures
Use not advised in children (exceptions eg CF) and pregnancy – risk arthropathy

Question 16

macrolides and lincosamides?

Answer 16

Bind 50s ribosomal subunit – inhibit bacterial protein synthesis
Macrolides: erythromycin, clarithromycin, azithromycin etc
Staphylococci and Streptococci
Moraxella, Haemophilus (unreliable)
“Atypical pathogens”
Lincosamides: clindamycin
Staphylococci, Streptococci and anaerobes

Clinical usage:
Empirical treatment pneumonia (combination with β-lactam)
Chlamydia and non-gonococcal urethritis
Skin and soft tissue infections – β-lactam allergy

Question 17

macrolidess and lincosamiedes ADR?

Answer 17

Adverse events:
GI upset
Antibiotic associated diarrhoea (esp clindamycin)
Other side effects infrequent

Question 18

fusidic acid?

Answer 18

Fusidic acid
Inhibits protein synthesis
Staphylococcus aureus – as combination treatment

Question 19

other antibiotics?

Answer 19

Nitrofurantoin
only for UTI treatment
Trimethoprim
inhibitor folate metabolism
Predominantly UTI treatment
Metronidazole
Broad anaerobic cover
Free radical production – DNA and protein damage

Question 21

newerantibioitcs?

Answer 21

Linezolid
Inhibits protein synthesis
Gram positive bacteria including MRSA, VRE
Daptomycin
Alters integrity of bacterial cell membrane
Gram positive bacteria including MRSA
Tigecycline
Related to tetracyclines – reduced resistance
Broad spectrum including MRSA, VRE, some resistant gram-negatives – not Pseudomonas