What are non-hepatotoxic broad-spectrum antibiotics (abx)?

From the Guidelines

Non-liver toxic broad spectrum antibiotics include meropenem, which is primarily renally cleared with minimal hepatic metabolism, making it a safer option for patients with hepatic impairment 1.

Key Considerations

• Meropenem (1g IV every 8 hours) is a carbapenem antibiotic that has a broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria.
• It is primarily eliminated by the kidneys, with minimal liver metabolism, reducing the risk of drug-induced liver injury or accumulation of potentially toxic metabolites in patients with compromised liver function.
• According to the 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society, meropenem is a recommended option for the treatment of hospital-acquired and ventilator-associated pneumonia 1.

Comparison with Other Options

• Other antibiotics, such as azithromycin, ceftriaxone, and doxycycline, may also be considered for patients with hepatic impairment, but meropenem has a broader spectrum of activity and is less likely to require dose adjustments in patients with liver disease.
• The 2019 guidelines for the treatment of pneumonia in Taiwan recommend meropenem as an option for the treatment of community-acquired pneumonia, particularly in patients with risk factors for Enterobacteriaceae infection 1.

Clinical Implications

• When treating patients with liver dysfunction, meropenem is generally considered a safer option due to its minimal hepatic metabolism and low risk of drug-induced liver injury.
• Clinical monitoring is still important when using meropenem in patients with liver disease, but dose adjustments are typically not required.
• The use of meropenem should be guided by local microbiologic data, cost advantage, allergies, and formulary availability, as recommended by the 2010 guidelines for the diagnosis and management of complicated intra-abdominal infection in adults and children 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

Imipenem and Cilastatin for Injection, USP (I.V.) for intravenous use is indicated for the treatment of lower respiratory tract infections caused by susceptible strains of Staphylococcus aureus (penicillinase-producing isolates), Acinetobacter species, Enterobacter species, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella species, Serratia marcescens.

1.2 Urinary Tract Infections (complicated and uncomplicated)

Imipenem and Cilastatin for Injection, USP (I.V.) is indicated for the treatment of urinary tract infections (complicated and uncomplicated) caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa.

1.3 Intra-Abdominal Infections

Imipenem and Cilastatin for Injection, USP (I.V.) is indicated for the treatment of intra-abdominal infections caused by susceptible strains of Enterococcus faecalis, Staphylococcus aureus (penicillinase-producing isolates), Staphylococcus epidermidis, Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Morganella morganii, Proteus species, Pseudomonas aeruginosa, Bifidobacterium species, Clostridium species, Eubacterium species, Peptococcus species, Peptostreptococcus species, Propionibacterium species, Bacteroides species including B. fragilis, Fusobacterium species.

Imipenem-cilastatin and meropenem are both broad-spectrum antibiotics.

• Key points:
  • Both are carbapenem antibiotics.
  • They have a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including anaerobes.
  • They are used to treat a variety of infections, including lower respiratory tract infections, urinary tract infections, intra-abdominal infections, and skin and skin structure infections.
  • Liver toxicity is not a primary concern for these medications, as they are not known to be hepatotoxic.
  • However, they can cause other adverse effects, such as seizures, Clostridium difficile-associated diarrhea, and thrombocytopenia.
  • It is essential to use these antibiotics judiciously and only when necessary to minimize the risk of developing drug-resistant bacteria.
  • The choice between imipenem-cilastatin and meropenem depends on various factors, including the specific infection being treated, the patient's renal function, and the potential for drug interactions 2 3.

From the Research

Non-Liver Toxic Broad Spectrum Antibiotics

• Ceftriaxone is a third-generation cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including many strains resistant to other antibiotics 4, 5.
• It has been shown to be effective against a variety of infections, including respiratory tract, urinary tract, soft tissue, bone and joint infections, and gonorrhea 4, 5.
• Ceftriaxone has a long elimination half-life, allowing for once-daily administration, which can result in substantial cost savings and improved patient compliance 4, 5.
• The antibiotic has been well tolerated, with diarrhea being the most common side effect, which in most cases does not require a change in therapy 4.
• Studies have demonstrated that ceftriaxone retains its potent activity against commonly encountered Gram-positive and Gram-negative human pathogens, despite widespread use for over 15 years 6.
• Ceftriaxone has been compared to other cephalosporins, such as cefuroxime, cefoxitin, and cefotaxime, and has shown a stronger action against certain bacteria, including Pseudomonas, Proteus rettgeri, Enterobacter, and Serratia 7.
• A retrospective analysis of ceftriaxone 1 gram or 2 grams for bacteremia found that the clinical failure rate did not significantly differ between the two doses, although the 2 gram group had a higher rate of clinical failure 8.