What antibiotic treatment is indicated for impaired renal function and septicemia?

From the Guidelines

Antibiotic Treatment for Impaired Renal Function and Septicemia For patients with impaired renal function and septicemia, antibiotic treatment should be initiated promptly with a broad-spectrum regimen, such as intravenous piperacillin-tazobactam (4.5g every 8 hours) or ceftriaxone (2g every 12 hours), in combination with an aminoglycoside, such as gentamicin (5-7 mg/kg every 24 hours) 1.

• The choice of empiric antimicrobial therapy depends on complex issues related to the patient’s history, clinical status, and local epidemiologic factors, including the nature of the clinical syndrome/site of infection, concomitant underlying diseases, chronic organ failures, medications, indwelling devices, the presence of immunosuppression or other form of immunocompromise, recent known infection or colonization with specific pathogens, and the receipt of antimicrobials within the previous three months 1.
• Patients with impaired renal function may require dose adjustments, such as ceftriaxone (1g every 24 hours) or gentamicin (3-5 mg/kg every 48 hours), to minimize the risk of nephrotoxicity 1.
• The duration of treatment should be tailored to the individual patient's response, but typically ranges from 7-14 days 1.
• Vancomycin is another antibiotic whose efficacy is at least partially concentration-dependent, and dosing to a trough target of 15-20 mg/L is recommended to maximize the probability of achieving appropriate pharmacodynamic targets, improve tissue penetration, and optimize clinical outcomes 1.
• For β-lactams, the key pharmacodynamics correlate to microbiologic and clinical response is the time that the plasma concentration of the drug is above the pathogen MIC relative to the dosing interval (T > MIC), and a minimum T > MIC of 60% is generally sufficient to allow a good clinical response in mild to moderate illness 1.

From the FDA Drug Label

In patients with impaired renal function, gentamicin is cleared from the body more slowly than in patients with normal renal function. The more severe the impairment, the slower the clearance. Dosage must be adjusted Results of these tests may serve as guides for adjusting dosage in patients with renal impairment (see DOSAGE AND ADMINISTRATION)

The antibiotic treatment indicated for impaired renal function is gentamicin (IV), but the dosage must be adjusted according to the degree of renal impairment. For septicemia, gentamicin can be used, but the dosage adjustment is crucial in patients with impaired renal function to avoid potential nephrotoxicity 2.

• Key considerations:
  • Dosage adjustment is necessary in patients with impaired renal function
  • The degree of renal impairment affects the clearance of gentamicin
  • Monitoring of serum creatinine level and endogenous creatinine clearance rate is recommended to guide dosage adjustment

From the Research

Antibiotic Treatment for Impaired Renal Function and Septicemia

• The choice of antimicrobials should be performed according to the local pathogen patterns of resistance 3.
• Individual antimicrobial optimization is essential to achieve adequate concentrations of antimicrobials, to reduce adverse effects, and to ensure successful outcomes, as well as preventing the emergence of multidrug-resistant pathogens 3.
• The loading dose is the administration of an initial higher dose of antimicrobials, regardless of the presence of organ dysfunction, and further doses should be implemented according to pharmacokinetics/pharmacodynamics of antimicrobials and should be adjusted according to the presence of renal or liver dysfunction 3.
• For patients with impaired renal function, the antibiotic treatment should be adjusted to prevent accumulation of the drug and its toxic effects 4.
• In patients with septicemia, combination therapy with an anti-pseudomonal beta-lactam and a fluoroquinolone or an aminoglycoside are recommended to provide the necessary spectrum of activity and to prevent the emergence of resistant organisms 5.
• Appropriate beta-lactam antibiotics recommended for the treatment of severe septicemia, either as monotherapy or as combination therapy, are the 4th generation cephalosporin cefepime, the carbapenems imipenem and meropenem, and the acylamino-beta-lactamase inhibitor combination piperacillin-tazobactam 5.

Considerations for Antibiotic Treatment

• Rapid identification of pathogen resistance profile and real-time measurement of drug concentrations with regimen adjustment on MIC are essential for individualized antibiotic management in critically ill patients 4.
• The duration of antibiotic treatment should be reviewed at regular intervals to allow effective de-escalation and administration of short courses of antimicrobials for most patients 3.
• Antimicrobial stewardship frameworks, leadership, focus on the optimal duration of treatments, de-escalation, and novel diagnostic stewardship approaches will help to improve the process of care and overall quality of care 3.