What is the appropriate Tobramycin dosing for a 63‑year‑old, 63‑kg man with a Pseudomonas foot infection and impaired renal function (serum creatinine 148 µmol/L)?

Tobramycin Dosing for Pseudomonas Foot Infection in a 63-Year-Old Man with Renal Impairment

For this 63-year-old, 63-kg man with a serum creatinine of 148 µmol/L (approximately 1.67 mg/dL), tobramycin should be dosed at 5–7 mg/kg once daily (315–441 mg daily), with the dosing interval extended based on his estimated creatinine clearance of approximately 40–45 mL/min, requiring administration every 36–48 hours rather than every 24 hours. 1

Calculating the Appropriate Dose and Interval

Initial Dose Calculation

• The standard once-daily tobramycin dose for Pseudomonas infections is 5–7 mg/kg, which for this 63-kg patient equals 315–441 mg per dose. 2, 1
• For severe Pseudomonas infections, target peak serum concentrations of 25–35 µg/mL are recommended, which the 5–7 mg/kg dose achieves with once-daily administration. 2
• Once-daily aminoglycoside dosing is equally efficacious and less toxic than three-times-daily dosing for Pseudomonas infections, making it the preferred approach even in renal impairment. 3, 4

Adjusting for Renal Impairment

• With a serum creatinine of 148 µmol/L (1.67 mg/dL) and estimated creatinine clearance of 40–45 mL/min using the Cockcroft-Gault equation, this patient has moderate renal impairment requiring interval extension rather than dose reduction. 1
• The FDA label specifies that for patients with renal impairment, the milligram dose should be maintained at the full amount (5–7 mg/kg) but the dosing frequency reduced to every 36–48 hours to preserve the concentration-dependent bactericidal effect while allowing adequate drug clearance. 1
• A practical approach is to administer 350–400 mg (approximately 6 mg/kg) every 36–48 hours, with the exact interval determined by therapeutic drug monitoring. 1, 5

Combination Therapy Requirement

Tobramycin should NOT be used as monotherapy for this Pseudomonas foot infection; it must be combined with an antipseudomonal β-lactam such as piperacillin-tazobactam 3.375 g IV every 6–8 hours (adjusted for renal function), ceftazidime 2 g IV every 12 hours, or cefepime 2 g IV every 12 hours. 2

• Combination therapy with a β-lactam plus aminoglycoside is mandatory for severe Pseudomonas infections to prevent treatment failure and resistance development. 2
• Monotherapy with aminoglycosides for Pseudomonas infections leads to resistance emergence in 30–50% of cases, making combination therapy essential. 2

Therapeutic Drug Monitoring Strategy

Essential Monitoring Parameters

• Obtain a trough level immediately before the second dose (at 36–48 hours), targeting a trough concentration <1–2 mg/L to minimize nephrotoxicity and ototoxicity. 1, 6, 5
• If the trough is >2 mg/L, extend the dosing interval further (e.g., from every 36 hours to every 48 hours). 5
• Peak levels are not routinely necessary with once-daily dosing unless there is concern about inadequate exposure, in which case a peak 1 hour post-infusion should be 25–35 µg/mL. 2, 1

Renal and Auditory Monitoring

• Measure serum creatinine every 2–3 days to detect early aminoglycoside-induced nephrotoxicity, which occurs in 43% of tobramycin-treated patients with prolonged courses. 7, 5
• Baseline and weekly audiometry are recommended for courses exceeding 10 days, as auditory toxicity occurs in 25% of tobramycin-treated patients with extended therapy. 7
• Nephrotoxicity risk increases with treatment duration beyond 10 days, concurrent use of other nephrotoxic agents (NSAIDs, vancomycin), and high-dose furosemide, all of which should be avoided or minimized. 5

Treatment Duration

The standard duration for Pseudomonas foot infections is 10–14 days, with the exact duration determined by clinical response, source control (debridement), and whether osteomyelitis is present. 2, 8

• If osteomyelitis is documented, extend treatment to 4–6 weeks with appropriate surgical debridement. 8
• For soft tissue infection without bone involvement, 10–14 days is adequate if the patient demonstrates clinical improvement and adequate source control. 2

Critical Pitfalls to Avoid

Dosing Errors

• Never reduce the milligram dose per kilogram in renal impairment—maintain 5–7 mg/kg but extend the interval. Dose reduction compromises the concentration-dependent killing of Pseudomonas and promotes resistance. 1
• Do not use the traditional three-times-daily dosing nomogram (1 mg/kg every 8 hours), as once-daily dosing is superior in efficacy and safety. 3, 4
• Avoid using gentamicin instead of tobramycin for Pseudomonas infections, as tobramycin has lower nephrotoxicity and superior antipseudomonal activity. 2, 7

Monitoring Failures

• Do not rely solely on serum creatinine to assess renal function in elderly patients—this 63-year-old man likely has a GFR lower than his creatinine suggests due to age-related muscle mass loss. 9
• Never extend tobramycin monotherapy beyond 7–10 days without infectious disease consultation, as prolonged aminoglycoside courses carry substantial toxicity risk. 1, 5

Combination Therapy Omissions

• Do not assume that high-dose tobramycin alone is adequate—the β-lactam component is essential for synergy and resistance prevention. 2
• If the patient has a severe β-lactam allergy, substitute aztreonam 2 g IV every 8 hours as the antipseudomonal β-lactam partner. 2

Practical Dosing Regimen Summary

For this 63-kg patient with SCr 148 µmol/L:

• Tobramycin 350–400 mg (approximately 6 mg/kg) IV infused over 30–60 minutes every 36–48 hours
• PLUS piperacillin-tazobactam 3.375 g IV every 8 hours (or alternative antipseudomonal β-lactam adjusted for CrCl 40–45 mL/min)
• Check trough tobramycin level before the second dose, targeting <1–2 mg/L
• Monitor serum creatinine every 2–3 days
• Duration: 10–14 days for soft tissue infection, longer if osteomyelitis is present
• Obtain baseline audiometry if treatment will exceed 10 days 1, 7, 5