What is the role of aminoglycosides (e.g. gentamicin, tobramycin) in the treatment of peritonitis?

Aminoglycosides for Peritonitis

Aminoglycosides (gentamicin, tobramycin) are FDA-approved for treating intra-abdominal infections including peritonitis, but current guidelines recommend reserving them for specific situations rather than routine first-line empiric therapy due to toxicity concerns and superior alternatives. 1

Role in Different Types of Peritonitis

Spontaneous Bacterial Peritonitis (SBP)

• Third-generation cephalosporins (cefotaxime 2g IV every 8 hours) are the established first-line treatment, NOT aminoglycosides. 2
• Aminoglycosides are not mentioned in current SBP management guidelines and should be avoided given the availability of safer, equally effective alternatives. 2

Secondary/Complicated Intra-Abdominal Infections (Adults)

• Aminoglycosides are NOT recommended for routine empiric treatment of community-acquired intra-abdominal infections. 3
• Reserve aminoglycosides for two specific scenarios: (1) patients with documented beta-lactam allergies, or (2) combination therapy for suspected multidrug-resistant (MDR) gram-negative bacteria when used WITH beta-lactams. 3
• The 2017 WSES guidelines explicitly state that aminoglycosides should be avoided for routine use due to toxic side effects (nephrotoxicity and ototoxicity). 3
• Aminoglycosides fail to achieve adequate tissue penetration into pancreatic tissue at standard IV doses, making them unsuitable for pancreatic infections. 3
• Aminoglycosides lack anaerobic coverage and MUST be combined with metronidazole if used. 3

Pediatric Peritonitis

• Aminoglycoside-containing regimens have been used successfully for decades in children with complicated intra-abdominal infections, contrasting sharply with adult practice. 3
• The classic three-drug regimen of gentamicin + ampicillin + clindamycin (or metronidazole) remains a commonly used option in pediatric patients. 3
• However, even in children, broader-spectrum single agents (carbapenems, piperacillin-tazobactam) are now preferred for perforated appendicitis with peritonitis. 3

FDA-Approved Indications and Dosing

Approved Uses

• Tobramycin and gentamicin are FDA-approved for intra-abdominal infections including peritonitis caused by susceptible E. coli, Klebsiella spp., and Enterobacter spp. 1
• Coverage includes Pseudomonas aeruginosa, which is critical for healthcare-associated peritonitis. 1

Dosing for Adults with Normal Renal Function

• Serious infections: 3 mg/kg/day divided into three equal doses of 1 mg/kg every 8 hours. 1
• Life-threatening infections: Up to 5 mg/kg/day in 3-4 divided doses, reduced to 3 mg/kg/day as soon as clinically indicated. 1
• Once-daily dosing (5-7 mg/kg daily) is recommended for patients with preserved renal function to optimize peak concentrations. 4
• Dosage should not exceed 5 mg/kg/day unless serum concentrations are monitored. 1

Critical Toxicity Concerns

Nephrotoxicity

• Aminoglycosides cause acute kidney injury including acute renal failure, with risk factors including high trough levels, peak concentrations >12 mcg/mL, prolonged therapy, and concurrent nephrotoxic drugs. 1
• Monitor serum tobramycin/gentamicin levels and renal function in ALL patients during treatment. 1
• Reduce dose or discontinue if renal impairment occurs. 1

Ototoxicity

• Aminoglycosides cause irreversible auditory and vestibular toxicity that may continue progressing after drug discontinuation. 1
• Risk factors include high serum concentrations, prolonged therapy, renal impairment, and concurrent ototoxic drugs. 1
• Discontinue immediately if ototoxicity occurs. 1

Neuromuscular Blockade

• Monitor for neuromuscular blockade, particularly in patients with myasthenia gravis or those receiving neuromuscular blocking agents. 1

Therapeutic Drug Monitoring

• Therapeutic drug monitoring is essential to minimize toxicity, primarily ensuring trough concentrations are sufficiently low to prevent renal toxicity. 4
• Target peak concentrations of approximately 3 μg/mL and trough concentrations <1 μg/mL when using divided dosing. 3
• In sepsis and septic shock, initiate with a full, high-end loading dose due to increased volume of distribution. 4

Clinical Algorithm for Use

Step 1: Determine peritonitis type

• SBP → Use cefotaxime, NOT aminoglycosides 2
• Secondary peritonitis in adults → Proceed to Step 2
• Pediatric peritonitis → Consider gentamicin-based regimen as alternative to carbapenems 3

Step 2: Assess for specific indications in adults

• Beta-lactam allergy? → Consider aminoglycoside + metronidazole 3
• Suspected MDR gram-negative bacteria? → Consider aminoglycoside + beta-lactam combination 3
• Neither condition? → Use alternative agents (carbapenems, piperacillin-tazobactam, cephalosporin + metronidazole) 3

Step 3: If aminoglycoside selected, assess renal function

• Normal renal function → Once-daily dosing 5-7 mg/kg 4
• Impaired renal function → Extended interval dosing with monitoring 4, 1

Step 4: Mandatory monitoring

• Baseline and serial renal function tests 1
• Serum drug levels (peak and trough) 4, 1
• Auditory and vestibular function assessment 1

Common Pitfalls to Avoid

• Do not use aminoglycosides as monotherapy—they lack anaerobic coverage essential for peritonitis. 3
• Do not use aminoglycosides for routine community-acquired peritonitis in adults—toxicity risk outweighs benefits when safer alternatives exist. 3
• Do not assume pediatric and adult dosing strategies are interchangeable—aminoglycosides remain more acceptable in pediatric practice. 3
• Do not continue therapy without monitoring—nephrotoxicity and ototoxicity can be irreversible. 1
• Do not use for pancreatic infections—inadequate tissue penetration at standard doses. 3