Antimicrobial dosing in special populations

Antimicrobial dosing in special populations

Antimicrobial dosing in special populations

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Renal Impairment - Kidney-Friendly Dosing

  • Principle: Prevent drug toxicity for agents cleared by the kidneys. Adjust dose, extend interval, or both.

  • Action: Calculate Creatinine Clearance (CrCl) to estimate Glomerular Filtration Rate (GFR).

    • Formula (Cockcroft-Gault): $CrCl = \frac{(140 - Age) \times Weight (kg)}{72 \times SCr (mg/dL)} \times (0.85 \text{ if female})$
  • Commonly Requiring Adjustment:

    • Penicillins (except nafcillin/oxacillin)
    • Cephalosporins (except ceftriaxone)
    • Vancomycin, Aminoglycosides (e.g., Gentamicin)
    • Fluoroquinolones (except moxifloxacin)

Exam Favorite: Several antimicrobials are hepatically cleared and do not require renal dose adjustments. Key examples include Ceftriaxone, Doxycycline, Azithromycin, Clindamycin, and Metronidazole.

Hepatic Impairment - Liver-Safe Choices

  • Guiding principle: Select antimicrobials with minimal hepatic metabolism and low intrinsic hepatotoxicity. While the Child-Pugh score offers a general guide, drug-specific recommendations are paramount.

  • Generally Safe Agents (Primarily Renal Excretion):

    • Penicillins: Most are well-tolerated (e.g., Piperacillin-Tazobactam).
    • Cephalosporins: Most generations are safe.
      • Caution: Ceftriaxone (significant biliary excretion).
    • Aminoglycosides: Gentamicin, Tobramycin.
    • Vancomycin.
    • Fluoroquinolones: Ciprofloxacin, Levofloxacin.
    • Carbapenems: Meropenem, Ertapenem.

⭐ Amoxicillin-clavulanate is a notorious cause of drug-induced liver injury (DILI). The injury pattern is typically cholestatic hepatitis, which can manifest weeks after the course is completed and is linked to the clavulanate component.

Obesity Dosing - Weighty Matters

Obesity alters drug pharmacokinetics, particularly the volume of distribution (Vd). Dosing adjustments are critical to ensure efficacy and avoid toxicity.

  • Dosing Weight Strategy:
Drug TypeVd in AdiposeRecommended Dosing WeightExamples
HydrophilicLowIdeal (IBW) or Adjusted (AdjBW)β-lactams, Aminoglycosides, Vancomycin, Daptomycin
LipophilicHighTotal Body Weight (TBW)Fluoroquinolones, Macrolides, Rifampin, Tetracyclines
-   Use Adjusted Body Weight (AdjBW) for many hydrophilic drugs.
-   $AdjBW = IBW + 0.4 * (TBW - IBW)$

High-Yield: Aminoglycosides dosed on Total Body Weight (TBW) in obese patients can lead to supratherapeutic levels and ↑ risk of nephrotoxicity and ototoxicity. Always use an adjusted or ideal body weight for them.

Obesity and Pharmacokinetic Changes Affecting Drug Dosing

Other Populations - Cradle to Grave

Factors for antimicrobial dosing in special populations

  • Pediatrics (Neonate/Infant):

    • Dosing is weight-based (mg/kg).
    • Immature renal/hepatic function → ↓ clearance, ↑ half-life.
    • Avoid: Tetracyclines (bone/teeth), Fluoroquinolones (cartilage), Ceftriaxone & Sulfonamides (kernicterus risk).
  • Geriatrics:

    • ↓ Renal clearance is primary concern; adjust dose for CrCl.
    • Altered body composition (↑ fat, ↓ water) affects volume of distribution.
    • High risk of drug interactions from polypharmacy.
  • Pregnancy:

    • Physiologic ↑ in GFR & volume of distribution may require dose increases.
    • Most drugs cross the placenta.
    • Safe: Penicillins, Cephalosporins.
    • Avoid: Tetracyclines, Fluoroquinolones.

⭐ Chloramphenicol in neonates can cause "Gray Baby Syndrome" (cardiovascular collapse) due to deficient glucuronidation.

High‑Yield Points - ⚡ Biggest Takeaways

  • Renal failure requires dose reduction for drugs like vancomycin and aminoglycosides.
  • Hepatic dysfunction affects liver-metabolized agents like metronidazole and macrolides.
  • In obesity, lipophilic drugs (e.g., fluoroquinolones) may need higher, weight-based doses.
  • Pregnancy alters pharmacokinetics; avoid teratogens like tetracyclines and fluoroquinolones.
  • Neonates and the elderly have reduced clearance, mandating careful dose adjustments.
  • Aminoglycosides use concentration-dependent killing, allowing once-daily dosing.

Practice Questions: Antimicrobial dosing in special populations

Test your understanding with these related questions

A 13-year-old boy presents to his pediatrician with a 1-day history of frothy brown urine. He says that he believes he had strep throat some weeks ago, but he was not treated with antibiotics as his parents were worried about him experiencing harmful side effects. His blood pressure is 148/96 mm Hg, heart rate is 84/min, and respiratory rate is 15/min. Laboratory analysis is notable for elevated serum creatinine, hematuria with RBC casts, and elevated urine protein without frank proteinuria. His antistreptolysin O titer is elevated, and he is subsequently diagnosed with post-streptococcal glomerulonephritis (PSGN). His mother is distraught regarding the diagnosis and is wondering if this could have been prevented if he had received antibiotics. Which of the following is the most appropriate response?

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Flashcards: Antimicrobial dosing in special populations

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Fluoroquinolones are _____ due to them causing cartilage damage to the fetus

TAP TO REVEAL ANSWER

Fluoroquinolones are _____ due to them causing cartilage damage to the fetus

teratogenic

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Antimicrobial dosing in special populations | Antimicrobials - OnCourse NEET-PG