Anti-infectives Flashcards

1
Q

Name THREE aminoglycosides and describe their MOA

A

Gentamicin
Amikacin (designed as a poor substrate for inactivating enzymes to overcome gent/tob resistance)
Tobramycin
Streptomycin (Anti-tuberculosis)
Paromomycin (SAS - oral, acts only in GIT)

Inhibit protein synthesis by irreversibly binding to the 30S ribosomal subunit and causing cell membrane damage. Concentration-dependent bactericidal effect.

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2
Q

What are some precautions around aminoglycosides and how are they metabolised/excreted?

A
  • Neuromuscular disease
  • History of ototoxicity
  • Renally cleared therefore caution in impairment (accumulation leading to increased toxicity)
  • Reserve use in pregnancy unless severe infection
  • Do not give with penicillins in same bag/line they are physically incompatible
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3
Q

Aminoglycosides are bactericidal and work synergistically with agents that interfere with cell wall synthesis; describe their spectrum, in particular which agent has the broadest spectrum?

A

Active against aerobic gram negative organisms (and some gram positive), including Pseudomonas Aeruginosa. They have minimal action on anaerobes.

Amikacin has the broadest spectrum, with activity against Mycobacterium spp. and Nocardia spp. - usually reserved for organisms resistant to gentamicin and tobramycin

Treat Pseudomonal infections with aminoglycoside + broad-spectrum anti-pseudomonal penicillin/cephalosporin/carbapenem

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4
Q

When should I start monitoring aminoglycoside (Gent in particular) plasma levels? How I do this? What is range?

A

Treatment <48 hours? Normal renal function? Don’t bother

Treatment >48 hours? Daily dosing? Monitor drug concentration and SeCr every 3-5 days in stable patients, more frequently if unstable. Patients with CF require specialist input

How? Calculate AUC, need two blood levels. 30mins post dose and one more 6-14 hours later.

Multiple daily dosing? Monitor trough levels. Target for gent <1mg/L

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5
Q

What should I monitor in patients on aminoglycosides? (5 things)

A
  • Renal function
  • Plasma concentrations
  • Hearing loss (cochlear)
  • Balance, dizziness, tinnitus (vestibular)
  • Hydration status
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6
Q

Gentamicin dose in

  • Adult
  • Endocarditis
  • Surgical prophylaxis

Should I use IBW?

A

Adult
Use the higher dose for young adults and the lower one for the elderly.
CrCl >60 mL/minute, IM/IV 5–7 mg/kg once daily.
CrCl 30–60 mL/minute, IM/IV 4–5 mg/kg once daily.
CrCl <30 mL/minute, seek specialist advice.

Endocarditis
IV, 1 mg/kg every 8 hours (with other agents). This dose is not used for empirical treatment.

Surgical prophylaxis
Adult, IV 2–5 mg/kg to be completed before skin incision. The higher dose may be used for certain indications, eg cardiac, vascular, lower limb amputation.

Yes, use IBW if pt is >20% above their IBW

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7
Q

Aminoglycosides are polycations and therefore highly polar. Do they cross the blood brain barrier? What is their half life?

A

They don’t cross the BBB. Half life is 2-3 hours with virtually all of the dose being excreted unchanged renally.

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8
Q

Do I need to worry about drug interactions with aminoglycosides?

A

Yeah, caution is necessary with other nephrotoxins (first generation cephalosporins apparently!) especially in existing impairment and/or reduced urine volume.

Also be careful with neuromuscular blockers and magnesium sulfate parenterally as they increase risk of paralysis

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9
Q

Carbapenems are broad spectrum beta-lactam antibiotics designed to deal with gram-negative organisms resistant to penicillins, name THREE and tell me how they work?

A

Ertapenem
Imipenem (sometimes given with cilastatin to prevent renal inactivation by dehydropeptidase 1)
Meropenem

Bind to penicillin-binding proteins, much like penicillins. Usually bactericidal.

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10
Q

Carbapenems have the broadest spectrum of all antibacterial classes with good activity against G-ve, G+ve and anaerobes. They are resistant to ESBLs but not metallo-beta-lactamases (carbapenemases). What organisms are they inactive against?

A

MRSA, Enterococcus Faecium, Stenotrophomonas Maltophilia.

Stenotrophomonas in particular is intrinsically resistant and may emerge as an opportunistic infection

Ertapenem is inactive against P. Aeruginosa and Acinetobacter

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11
Q

Meropenem can be used to treat meningitis, why can’t I use the other two?
Also what should I monitor in someone on a carbapenem?

A

Imipenem and ertapenem both carry an increased risk of seizure. While we’re on it, carbapenems can significantly decrease valproate levels and precipitate seizures, so avoid use or convert to IV valproate and monitor carefully.

Monitor renal function, FBC and LFTs long term.

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12
Q

What is the dose frequency for:

Ertapenem
Imipenem
Meropenem

A

Ertapenem - Once Daily
Imipenem - Every six hours
Meropenem - Every eight hours

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