Is Ceftazidime (Ceftazidime) + Avibactam (Avibactam) effective for treating Neisseria meningitidis (N. meningitidis) meningitis?

From the Guidelines

Ceftazidime-avibactam is not recommended as first-line therapy for meningococcal encephalitis. The preferred treatment for meningococcal infections, including meningitis and encephalitis, is high-dose intravenous penicillin G or ceftriaxone for 7-10 days, as recommended by the UK Joint Specialist Societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults 1. For penicillin-allergic patients, chloramphenicol or a fluoroquinolone may be used as alternatives. Ceftazidime-avibactam is a combination antibiotic primarily designed for treating multidrug-resistant gram-negative infections, particularly those producing certain beta-lactamases. While ceftazidime alone has some activity against Neisseria meningitidis (the causative organism of meningococcal infections), the addition of avibactam provides no additional benefit against this organism as N. meningitidis does not typically produce the beta-lactamases that avibactam inhibits, as noted in the ESCMID guideline for the treatment of infections caused by multidrug-resistant gram-negative bacilli 1. Furthermore, ceftazidime-avibactam is significantly more expensive than standard therapies and has not been well-studied for CNS infections. Treatment should be initiated immediately after obtaining blood cultures, as meningococcal infections can progress rapidly and have high mortality rates if not promptly treated, highlighting the importance of following established guidelines such as those from the ESCMID 1.

Some key points to consider in the treatment of meningococcal encephalitis include:

• The importance of prompt treatment with effective antibiotics to reduce morbidity and mortality
• The use of high-dose intravenous penicillin G or ceftriaxone as first-line therapy
• The consideration of alternative antibiotics, such as chloramphenicol or a fluoroquinolone, for penicillin-allergic patients
• The limited role of ceftazidime-avibactam in the treatment of meningococcal infections, due to its primary indication for multidrug-resistant gram-negative infections.

From the FDA Drug Label

Ceftazidime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: ... Neisseria meningitidis Therapeutic concentrations of ceftazidime are achieved in the following body tissues and fluids... Cerebrospinal fluid 2 g q8hr IV 5 120 min 9. 8 (inflamed meninges)

Ceftazidime may be effective against Neisseria meningitidis, the causative agent of meningococcal encephalitis. Therapeutic concentrations of ceftazidime are achieved in the cerebrospinal fluid, which is the site of infection in meningitis. However, the FDA label does not explicitly state that ceftazidime is indicated for the treatment of meningococcal encephalitis. Therefore, the use of ceftazidime for this indication should be approached with caution and considered on a case-by-case basis 2.

From the Research

Ceftazidime-Avibactam for Meningococcal Encephalitis

• There is limited information available on the use of ceftazidime-avibactam for meningococcal encephalitis specifically 3, 4, 5, 6, 7.
• However, ceftazidime-avibactam has been shown to be effective against Gram-negative bacterial infections, including those caused by Enterobacteriaceae and Pseudomonas aeruginosa 6, 7.
• In the treatment of severe infections, ceftazidime-avibactam has been used in combination with other antibiotics, such as aztreonam, and has shown promise in treating metallo-beta-lactamases-producing Enterobacterales 5.
• The use of ceftazidime-avibactam for meningococcal infections is not well-studied, but other antibiotics such as ciprofloxacin, rifampin, and penicillin have been shown to be effective in eradicating Neisseria meningitidis 4.
• Ceftazidime-avibactam may be considered as a potential treatment option for meningococcal encephalitis, but more research is needed to determine its efficacy and safety in this specific context 6, 7.

Mechanism of Action and Pharmacology

• Ceftazidime-avibactam is a combination of a third-generation cephalosporin and a non-β-lactam β-lactamase inhibitor, which works by inhibiting the activity of β-lactamases and allowing ceftazidime to reach its target 6, 7.
• The pharmacokinetic and pharmacodynamic properties of ceftazidime-avibactam make it a potential option for the treatment of severe infections, including those caused by Gram-negative bacteria 5, 6, 7.

Clinical Efficacy and Safety

• Ceftazidime-avibactam has been shown to be effective in the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and hospital-acquired pneumonia, including ventilator-associated pneumonia 7.
• The safety and tolerability profile of ceftazidime-avibactam is generally consistent with that of ceftazidime alone and other injectable cephalosporins 7.