Pharmacokinetics of cefamandole and ampicillin in experimental meningitis

Insights

Cefamandole and ampicillin penetration into rabbit cerebrospinal fluid increased during meningitis. However, cefamandole levels only exceeded the inhibitory concentration for Haemophilus influenzae at the highest dose.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Neuroscience

Background:

  • Cerebrospinal fluid (CSF) penetration is crucial for antibiotics treating central nervous system infections.
  • Cefamandole and ampicillin are commonly used antibiotics, but their efficacy in meningitis depends on CSF concentrations.

Purpose of the Study:

  • To evaluate the penetration of cefamandole and ampicillin into the CSF of rabbits with and without pneumococcal meningitis.
  • To determine if meningitis affects antibiotic concentrations in the CSF and serum.

Main Methods:

  • Rabbits were administered varying intramuscular doses of cefamandole (25-150 mg/kg) and ampicillin (200-300 mg/kg).
  • CSF and serum antibiotic concentrations were measured in normal rabbits and those with experimentally induced pneumococcal meningitis (24 and 48 hours post-infection).

Main Results:

  • In normal rabbits, only high-dose cefamandole (150 mg/kg) and ampicillin achieved detectable CSF concentrations.
  • Meningitis significantly increased cefamandole and ampicillin penetration into the CSF after 24 hours.
  • Cefamandole CSF levels exceeded the inhibitory concentration for Haemophilus influenzae only at the 150 mg/kg dose.
  • Serum concentrations of both antibiotics were lower (32-38%) in rabbits with meningitis compared to normal rabbits.

Conclusions:

  • Meningitis enhances cefamandole and ampicillin penetration into rabbit CSF, but therapeutic levels, especially for cefamandole against H. influenzae, may not always be achieved.
  • Reduced serum concentrations in infected animals warrant further investigation regarding dosing strategies.

Related Concept Videos

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations01:15

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations

Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
Estimation of k and VD of Aminoglycosides01:20

Estimation of k and VD of Aminoglycosides

Aminoglycosides are a class of antibiotics used to treat various bacterial infections. Clinicians must determine the elimination rate constant (k) and volume of distribution (VD) to optimize therapeutic efficacy and minimize toxicity. The k value represents the rate at which the drug is removed from the body, and the VD reflects the degree to which the drug distributes into body tissues. Accurately estimating these parameters allows healthcare professionals to tailor drug dosing to individual...
Pharmacodynamic Models: Overview01:27

Pharmacodynamic Models: Overview

Pharmacodynamic (PD) responses describe the interaction between a drug and its biological target, culminating in a physiological effect. These responses can be classified into different types: continuous variables, such as blood glucose levels; categorical outcomes, like survival rates; and time-to-event metrics, such as disease progression. Understanding and modeling PD responses are critical for optimizing drug efficacy and safety.PD models describe the relationship between drug concentration...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Viral Meningitis01:18

Viral Meningitis

Viral meningitis is the most common form of meningitis and is often referred to as aseptic meningitis to indicate the absence of bacterial involvement. It is generally milder than bacterial meningitis, with symptoms including fever, headache, stiff neck, drowsiness, nausea, photophobia, and vomiting. Rarely, more severe manifestations or death may occur. Common causative agents include enteroviruses, particularly coxsackie A and B viruses and echoviruses, all members of the Enterovirus genus...
Bacterial Meningitis II: Pathophysiology01:26

Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...