A compilation of meropenem tissue distribution data

Abstract

Meropenem body fluid and tissue concentration data from both published studies and samples obtained during efficacy evaluation have been compiled and presented according to a consistent format to facilitate comparison. The concentration data have been compared with the mode MIC data available for the pathogens isolated during the clinical evaluation of meropenem. These data support the widespread and rapid penetration of meropenem into the interstitial fluid of those tissues not protected by a tight epithelial barrier. Furthermore, they suggest that the proposed dosages of meropenem 500 mg or 1 g tds would provide an adequate duration of cover at tissue sites for the treatment of a range of commonly occurring pathogens. A higher dosage of 40 mg/kg or 2 g in adults given tds would be recommended for meningitis based on the penetration of meropenem into CSF. Overall, the tissue and body fluid data presented confirm the expectation, based on the plasma concentrations and theoretical arguments, that meropenem is rapidly and readily distributed into the interstitial fluid, thereby producing concentrations in tissues likely to be clinically effective. This is consistent with the available clinical data on the therapeutic efficacy of meropenem.

Safety of Imipenem/Cilastatin in Neurocritical Care Patients

“…Like other b-lactam antibiotics, imipenem has some penetration into the CSF, and greater permeability with meningeal inflammation [2].…”

Bone marrow aplasia and meropenem in a paediatric patient

“…A dose of 40 mg/kg/8 h in children with bacterial meningitis produces concentrations in the CSF of between 0·9 and 6·5 mg/l, which far exceed the minimum inhibitory concentration (MIC 90 ) of the microorganisms that most commonly cause community‐acquired meningitis. This is the recommended dose, with a maximum of 2 g/8 h (Hutchinson et al , 1995). Meropenem penetrates the CSF well when the haematoencephalic barrier is inflamed.…”

Meropenem, a New Carbapenem Antibiotic

“…No specific protein-binding studies have been reported in the literature, but the manufacturer reports the protein binding of meropenem to be approximately 2%.8, 92 The agent appears to be widely distributed in various body tissues and fluids (Table 4). 12' 66* [95][96][97][98][99][100][101][102] Penetration into the cerebrospinal fluid (CSF) results in drug concentrations ranging from below 1% of simultaneous plasma concentrations in patients with intact uninflamed meninges, to 52% of simultaneous plasma concentrations after administration of single intravenous doses of 20-40 mgkg to adults and children with inflamed meninges.95 Penetration into the CSF is, as may be expected, related to the size of the dose; patients with acute bacterial meningitis receiving 20-mg/kg doses achieved meropenem CSF concentrations of 0.1-2.8 mg/L, and 40-mgkg doses resulted in concentrations ranging from 0.33-6.5 m g L g 5 One case report of an adult receiving 6 g/day observed mean Cmin and C,,, of 0.5 mg/L and 1.6 mg/L, respectively. lo3 Although its penetration into the CSF varies considerably among individuals, guinea pig models of bacterial meningitis showed the drug to be effective in the treatment of infections due to penicillin-sensitive S. pneumoniae, E. coli, P aencginosa, L. monocytogenes, N. meningitidis, and H. influenzae.lo4 Consistent with both pharmacokinetic data and animal models, the agent also is effective i n the treatment of meningitis in clinical studies in humans.…”