What alternative antibiotic can be used to treat gram-negative bacteria in a patient with a hypersensitivity reaction to penicillin (Penicillin allergy)?

From the Guidelines

For patients with penicillin allergies who need treatment for gram-negative bacterial infections, aztreonam is a recommended option, as it has no cross-reactivity with penicillin allergies and specifically targets gram-negative bacteria, unless there is a history of ceftazidime allergy, as suggested by the 2022 practice parameter update 1. When considering treatment options for gram-negative bacterial infections in patients with penicillin allergies, several factors must be taken into account, including the severity of the allergy, the site and severity of the infection, local resistance patterns, and patient-specific factors such as renal function and pregnancy status.

• Aztreonam is particularly valuable in this context because it does not cross-react with penicillin allergies, making it a safe choice for patients with a history of penicillin allergy, except for those with a confirmed allergy to ceftazidime 1.
• Other options may include fluoroquinolones, such as ciprofloxacin or levofloxacin, which are often recommended as first-line alternatives for gram-negative infections in patients with penicillin allergies, as noted in guidelines for the management of community-acquired pneumonia 1.
• Aminoglycosides, such as gentamicin, tobramycin, or amikacin, can also be effective, but their use must be carefully considered due to potential toxicity, especially in patients with renal impairment.
• The choice of antibiotic should always prioritize the patient's safety and the efficacy of the treatment, taking into account the most recent and highest quality evidence available, such as the 2022 practice parameter update on drug allergy 1, which provides guidance on the use of aztreonam in patients with penicillin or cephalosporin allergies.

From the FDA Drug Label

Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to cefepime for injection occurs, discontinue the drug BEFORE THERAPY WITH FORTAZ IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFTAZIDIME, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBACTERIAL DRUGS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.

Cefepime or Ceftazidime can be used for gram-negative bacteria, but caution is advised in patients with a penicillin allergy due to the risk of cross-hypersensitivity 2, 2, 3.

• Key considerations:
  • Cross-hypersensitivity: may occur in up to 10% of patients with a history of penicillin allergy
  • Allergic reactions: discontinue the drug if an allergic reaction occurs
  • Caution: exercise caution when giving these products to penicillin-sensitive patients

From the Research

Antibiotic Options for Gram-Negative Bacteria in Patients with Penicillin Allergy

• For patients with a penicillin allergy, alternative antibiotics are necessary to treat gram-negative bacterial infections.
• According to 4, several antibiotics have been approved for the treatment of multidrug-resistant (MDR) Gram-negative infections, including:
  • β-lactam/β-lactamase inhibitor combinations
  • Eravacycline
  • Plazomicin
  • Cefiderocol
• These antibiotics offer potential treatment options for patients with penicillin allergies, as they do not contain penicillin and have shown efficacy against gram-negative bacteria.
• However, it is essential to consider the patient's specific allergy and medical history when selecting an antibiotic, as well as the potential for resistance and side effects.

Pharmacologic Optimization of Antibiotics

• Pharmacologic dose optimization is crucial for managing gram-negative infections, especially in high-risk patient populations 5.
• Therapeutic drug monitoring and nomogram-based dosing may be necessary to optimize antibiotic exposure and prevent resistance.
• The choice of antibiotic and dosing strategy should be individualized based on the patient's renal function, severity of illness, and other factors.

Treatment Challenges and Strategies

• Gram-negative bacterial infections can be challenging to treat due to the outer membrane's permeability barrier, which limits the effectiveness of many antibiotics 6.
• Potentiator molecules that disrupt this barrier may provide a strategy to render multi-drug resistant pathogens susceptible to a broader range of antibiotics.
• However, the use of potentiator molecules is still in the experimental stage, and more research is needed to determine their safety and efficacy.

Penicillin Allergy Assessment

• A pharmacist-led penicillin allergy assessment can help reduce empiric fluoroquinolone use and improve guideline-preferred antibiotic use 7.
• Accurate assessment and documentation of penicillin allergies are essential to ensure that patients receive appropriate antibiotic therapy and minimize the risk of adverse reactions.