Imipenem/cilastatin treatment of bacterial meningitis in children

Wong, Victor K.; Wright, Harry T.; Ross, Lawrence A.; Mason, Wilbert H.; Inderlied, Clark B.; Kim, Kwang Sik

doi:10.1097/00006454-199102000-00009

Cited by 186 publications

(42 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the only series in which imipenem-cilastatin was used to treat meningitis, seizures occurred during therapy in 10 of 21 children (48%), of whom 3 had had seizures before receiving the drug. Thus, 7 of 18 children with no history of seizures (39%) had seizures during imipenem-cilastatin therapy (28). Four of 47 retrospective controls (8.5%) not receiving imipenem-cilastatin in that study had seizures after the start of antimicrobial therapy.…”

Section: Discussionmentioning

confidence: 85%

“…The carbapenem class of antimicrobial agents is highly active against the major bacterial pathogens causing meningitis, but in the first clinical trial of such an agent, the use of imipenem-cilastatin was terminated because of an excess of seizures in those receiving the drug (28). Meropenem, a carbapenem structurally related to imipenem, is stable to the majority of ␤-lactamases (23) and is active in vitro against a broad range of gram-negative and gram-positive aerobic and anaerobic bacteria, with several-fold-greater activity than that of imipenem against H. influenzae and N. meningitidis (4).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem Meningitis Study Group

Klugman

Dagan

1995

Antimicrob Agents Chemother

159

View full text Add to dashboard Cite

Broad-spectrum cephalosporins are drugs of choice for the treatment of meningitis in communities which can afford them. The emergence of cephalosporin-resistant pneumococci demands the clinical trial of alternate agents. Carbapenems are active against the bacteria causing meningitis, but the use of imipenem-cilastatin was frustrated by drug-associated seizures. The safety and efficacy of meropenem, a new carbapenem, were compared to those of cefotaxime in a prospective randomized trial of 190 children with bacterial meningitis. Seizures occurred within 24 h before antibiotic therapy in 16 of 98 patients (16%) randomized to receive meropenem and in 6 of 92 patients (7%) randomized to receive cefotaxime. In patients without seizures before therapy, seizures occurred during therapy in 5 of 82 patients (6%) receiving meropenem and in 1 of 86 patients (1%) receiving cefotaxime (95% confidence interval: ؊0.7%, 10.6%). None were thought to be drug related. Twenty-four meropenem-treated patients (24%) and 11 cefotaxime-treated patients (12%) had neurological abnormalities before therapy. In patients without pretherapy neurological abnormalities, these abnormalities were present after treatment in 4 of 74 meropenem-treated patients (5%) and in 2 of 81 cefotaxime-treated patients (2%) (95% confidence interval: ؊3.2%, 9.1%). Of 75 meropenem-treated and 64 cefotaxime-treated patients with pretherapy positive cerebrospinal-fluid cultures, 68 and 59, respectively, had repeat lumbar punctures. Bacterial eradication was found to be 100% in both groups. Our data suggest that meropenem may be a carbapenem agent that is well tolerated and effective in the treatment of bacterial meningitis.

show abstract

Section: Discussionmentioning

confidence: 85%

mentioning

confidence: 99%

Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem Meningitis Study Group

Klugman

Dagan

1995

Antimicrob Agents Chemother

159

View full text Add to dashboard Cite

show abstract

“…In their article, the authors complain of the lack of adequate antibiotic susceptibility interpretation criteria for and clinical experience in treating systemic infections caused by S. pneumoniae with antibiotics, other than penicillin, and of the lack of data that correlate clinical outcome Considering the cefotaxime concentrations achieved in CSF, about 4 ,g/ml in the acute phase of purulent meningitis (7), the minimal concentrations (0.5 to 1 p,g/ml) in the CSF of children with bacterial meningitis reported by Ellmen et al (3), and the clinical outcome of the case described above, it seems that a breakpoint for cefotaxime of 2 ,g/ml is too high, although until now, the published cases of S. pneumoniae resistant to cefotaxime isolated from CSF reported MICs of >2 ,ug/ml (2,4,6 points, and clearly the clinical outcome of treatment needs to be correlated with in vitro susceptibility predictions.…”

mentioning

confidence: 87%

“…Additional clinical details regarding this patient that might explain the delayed sterilization of the spinal fluid in this child, such as treatment with corticosteroids or the presence of an underlying disease, would be helpful. Although imipenem-cilastatin therapy did sterilize the CSF in 3 days, there is little experience with this antimicrobial agent, and there are reports of excessive seizures in children with meningitis who receive this drug (6). Currently, vancomycin alone or combined with rifampin is considered the next best agent(s) for treating S. pneumoniae meningitis due to cefotaxime-resistant strains (3,5).…”

mentioning

confidence: 99%

Cefotaxime breakpoint for Streptococcus pneumoniae

Cantón

1993

Antimicrob Agents Chemother

View full text Add to dashboard Cite

“…Epileptic seizures have been observed for up to 33% of children treated with imipenem i.v. for bacterial meningitis (263). After intraventricular injection in rats, cefazolin, imipenem, and aztreonam were most potent in inducing epileptic seizures (49).…”

Section: ␤-Lactam Antibioticsmentioning

confidence: 99%

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

2010

View full text Add to dashboard Cite

SUMMARY The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable.

show abstract

Imipenem/cilastatin treatment of bacterial meningitis in children

Cited by 186 publications

References 0 publications

Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem Meningitis Study Group

Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem Meningitis Study Group

Cefotaxime breakpoint for Streptococcus pneumoniae

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

Contact Info

Product

Resources

About