What is the appropriate antibiotic regimen for treating infections caused by gram-negative bacilli, including both fermenters (e.g. Escherichia coli, Klebsiella pneumoniae) and non-fermenters (e.g. Pseudomonas aeruginosa)?

From the Guidelines

The most appropriate antibiotic regimen for treating infections caused by gram-negative bacilli, including both fermenters and non-fermenters, is an antipseudomonal beta-lactam such as piperacillin-tazobactam, cefepime, or meropenem, with or without an aminoglycoside, depending on the severity of the infection and the risk of multidrug-resistant pathogens 1.

Key Considerations

• For community-acquired infections with suspected fermenters like E. coli or Klebsiella, a third-generation cephalosporin or fluoroquinolone may be appropriate.
• For healthcare-associated infections or when dealing with non-fermenters like Pseudomonas, an antipseudomonal beta-lactam is recommended.
• Combination therapy may be necessary for severe infections or suspected resistant organisms, with the addition of an aminoglycoside or fluoroquinolone.
• Treatment duration typically ranges from 7-14 days, with longer courses for complicated infections.
• Dosing adjustments are necessary for patients with renal impairment.

Risk Factors for Multidrug-Resistant Pathogens

• Antibiotic therapy in the previous 90 days
• Hospital stay of more than 5 days prior to suspected infection
• Renal replacement therapy requirement during infection
• Septic shock
• ARDS

Recommendations

• Empirical combined therapy is indicated in the presence of at least one risk factor for multidrug-resistant bacteria or non-fermenting Gram-negative bacilli.
• After pathogen identification and susceptibility testing, combined therapy may not be necessary, and de-escalation to the narrowest effective antibiotic is recommended to reduce resistance development and adverse effects 1.

From the FDA Drug Label

Meropenem for injection is indicated for the treatment of complicated skin and skin structure infections (cSSSI) due to ... Pseudomonas aeruginosa, Escherichia coli, ... Meropenem for injection is indicated for the treatment of complicated appendicitis and peritonitis caused by ... Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, ... Piperacillin and tazobactam has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections: Aerobic bacteria Gram-positive bacteria ... Gram-negative bacteria Acinetobacter baumannii Escherichia coli Haemophilus influenzae (excluding beta-lactamase negative, ampicillin-resistant isolates) Klebsiella pneumoniae Pseudomonas aeruginosa (given in combination with an aminoglycoside to which the isolate is susceptible)

The appropriate antibiotic regimen for treating infections caused by gram-negative bacilli, including both fermenters (e.g. Escherichia coli, Klebsiella pneumoniae) and non-fermenters (e.g. Pseudomonas aeruginosa), may include:

• Meropenem (2)
• Piperacillin-tazobactam (3), which can be effective against Pseudomonas aeruginosa when given in combination with an aminoglycoside. Key considerations:
• The choice of antibiotic should be based on the specific type of infection, the severity of the infection, and the susceptibility of the causative organism to the antibiotic.
• It is essential to follow the recommended dosage and administration guidelines for the chosen antibiotic.
• In some cases, combination therapy may be necessary to ensure adequate coverage against gram-negative bacilli.

From the Research

Antibiotic Regimens for Gram-Negative Bacilli

The choice of antibiotic regimen for treating infections caused by gram-negative bacilli, including both fermenters and non-fermenters, depends on various factors such as the severity of the infection, the causative pathogen, and its antibiotic resistance profile.

• For infections caused by fermenters like Escherichia coli and Klebsiella pneumoniae, a regular dose of 12/1.5 g/24 h of piperacillin-tazobactam is sufficient in > 90% of the critically ill population to treat infections with MICs ≤ 8 mg/L 4.
• For infections caused by non-fermenters like Pseudomonas aeruginosa with an MIC of 16 mg/L, there is a fine line between therapeutic and toxic exposure, and dosing guided by renal function and therapeutic drug monitoring could enhance target attainment 4.
• Inappropriate initial antimicrobial therapy is associated with adverse outcomes in antibiotic-resistant gram-negative bacteremia, particularly in patients with a high-risk source of bacteremia 5.
• A 7-day course of antibiotic therapy is noninferior to 14 days for uncomplicated gram-negative bacteremia in patients who are afebrile and hemodynamically stable for at least 48 hours 6.

Key Considerations

• The rate of antibiotic resistance among gram-negative bacilli has accelerated dramatically in recent years, making it essential to choose the appropriate antibiotic regimen 7.
• The source of the infection, causative pathogen, and its antibiotic resistance profile should be considered when selecting an antibiotic regimen.
• Dosing regimens should be guided by renal function and therapeutic drug monitoring to enhance target attainment and minimize the risk of toxicity.

Antibiotic Resistance

• The increasing incidence of infections due to antibiotic-resistant gram-negative bacilli is a significant concern, and inappropriate initial antimicrobial therapy can lead to adverse outcomes 7, 5.
• The development of antibiotic resistance is a complex issue, and strategies to slow its spread include optimizing antibiotic use, improving infection control practices, and developing new antibiotics 7.