Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carbapenems differ from the penicillins (penams) in having an unsaturated bond between C2 and C3 and a carbon atom replacing sulphur at position 1 of the thiazolidine ring. The various carbapenems differ primarily in the configuration of the side chains at C2 and C6. Carbapenems include the thienamycins, olivanic acids, carpetimycins, asparenomycins, pluracidomycins, and other natural and semi-synthetic compounds. Carbapenems vary in their stability and resistance to beta-lactamases, ability to inhibit and to induce beta-lactamases, and in-vitro spectra of activity. Many are highly unstable in solution. Some are degraded by mammalian dehydropeptidases in vivo. The hydroxyethyl side chain in the alpha or trans-configuration at C6 in thienamycin provides striking resistance to beta-lactamases, but this compound is highly unstable in concentrated solution and the solid state. The N-formimidoyl derivative of thienamycin (imipenem) is more stable in solution and has broad-spectrum activity against aerobic and anaerobic bacteria. However, imipenem is not stable to renal dehydropeptidases and its degradation products are nephrotoxic in certain animals. It is thus administered with the dehydropeptidase inhibitor cilastatin. High serum levels of imipenem (especially in patients with renal failure and central nervous system disease) have been associated with seizures. The drug is therefore not appropriate for meningitis. Meropenem is a new carbapenem which has the same side chain as imipenem at C6. Its unique side chain at C2 assures a broad spectrum of activity which includes Pseudomonas aeruginosa and other aerobic and anaerobic organisms. Only Ps. (Xanthomonas) maltophilia is generally resistant. This species is resistant also to imipenem.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The carbapenems: new broad spectrum beta-lactam antibiotics. 268 Nov 23

The parenteral carbapenem meropenem is relatively stable to inactivation by human renal dehydropeptidase (DHP-1) and does not require concomitant administration of a DHP-1 inhibitor such as cilastatin. It has a broad spectrum of antibacterial activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic pathogens being highly susceptible to the drug. Meropenem has shown clinical and bacteriological efficacy in the treatment of a wide range of serious infections in adults and children which is at least comparable with that of currently available treatment options. Its clinical and bacteriological efficacy is similar to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus metronidazole in the treatment of intraabdominal infections; cefotaxime or ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime with or without an aminoglycoside, in lower respiratory tract infections; and imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections. Satisfactory clinical and bacteriological response rates have also been achieved in patients with skin and skin structure infections, obstetric and gynaecological infections or septicaemia, and in immunocompromised patients with febrile episodes. Preliminary findings also indicate efficacy in the treatment of respiratory tract infections in patients with cystic fibrosis. The tolerability profile of meropenem is generally similar to that of comparator agents, although it is associated with a lower incidence of adverse gastrointestinal effects (nausea and vomiting) than imipenem/cilastatin. Importantly, the incidence of seizures in patients with meningitis is not increased following administration of meropenem. Thus, meropenem is an effective broad spectrum antibacterial drug for the treatment of a wide range of infections including polymicrobial infections in both adults and children, with comparable efficacy to imipenem/cilastatin and various other treatment regimens. Meropenem is likely to be of greatest value as empiric monotherapy in the treatment of serious infections for those caused by multiply-resistant pathogens. Further clinical experience is necessary, however, to ultimately define its place in therapy.
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PMID:Meropenem. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. 758 92

The carbapenem class of antibacterial agents is highly effective in vitro against the bacterial pathogens causing meningitis. Both imipenem and meropenem penetrate into the cerebrospinal fluid of children with inflamed meninges in the acute phase of meningitis. The wider clinical use of imipenem/cilastatin for the treatment of meningitis has been limited by the high incidence of seizures (up to 33%) in patients not having seizures prior to drug therapy. However, imipenem/cilastatin has been successfully used for the treatment of pneumococcal meningitis following failure of treatment with third-generation cephalosporins. The bacteriological and clinical efficacy of meropenem appears similar to that of cefotaxime in the management of meningitis in children and there was no significant propensity of either meropenem or cefotaxime to cause seizures. Meropenem has also been usefully employed to treat multi-resistant Pseudomonas aeruginosa meningitis. These data suggest that meropenem should be further investigated for use in the treatment of meningitis.
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PMID:Carbapenem treatment of meningitis. 765 3

Meropenem and imipenem/cilastatin were compared in an open, randomised prospective multicentre study in the treatment of acute exacerbations of severe chronic obstructive pulmonary disease in hospitalised patients. One-hundred-and-seventy-three patients were enrolled; 164 were evaluable for clinical efficacy and 98 for bacteriological efficacy, with 144 pathogens isolated. The predominant pathogens were Haemophilus influenzae (n = 30), Streptococcus pneumoniae (18), Staphylococcus aureus (12), Pseudomonas aeruginosa (11), Moraxella catarrhalis (8), other Gram-negative bacteria (Neisseria, Klebsiella, Proteus, and Enterobacter spp.) (53) and other Gram-positive bacteria (12). A single bacterial pathogen was identified in 61 patients, whereas two bacterial pathogens were isolated in 31 patients and three in six patients. The clinical response at the end of treatment was very high in both groups with a satisfactory outcome (cured or improved) in 97.6% of the meropenem patients and in 96.3% of the imipenem/cilastatin patients; at follow-up the rates were 89.1% and 89.8%, respectively. The bacterial success (eradication or presumed eradication) was 88.2% in the meropenem group and 89.4% in the comparator group. Nausea or vomiting were reported more frequently in patients treated with imipenem/cilastatin, whereas in the meropenem group an increase in aminotransferases was reported. One patient treated with imipenem/cilastatin was withdrawn from the study due to seizures. Meropenem and imipenem/cilastatin were highly effective for the treatment of severe bacterial exacerbations of chronic bronchitis but meropenem was better tolerated.
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PMID:Treatment of acute bacterial exacerbations of chronic obstructive pulmonary disease in hospitalised patients--a comparison of meropenem and imipenem/cilastatin. COPD Study Group. 854 88

Third-generation cephalosporins are presently the agents of choice for the empirical antimicrobial therapy of bacterial meningitis. However, a number of factors associated with these agents, namely the development of resistance by pneumococci, limited activity against some Enterobacteriaceae and Pseudomonas spp., and the possible adverse effects of their bacteriolytic mode of action, indicate that newer classes of antimicrobial agents be evaluated for the treatment of bacterial meningitis. Meropenem is a carbapenem antibiotic which is highly active against the major bacterial pathogens causing meningitis, and penetrates well into the cerebrospinal fluid. Two prospective randomised studies in 56 adult bacterial meningitis patients have compared meropenem 40 mg/kg 8-hourly, up to a maximum of 6 g/day (n = 28) with cephalosporin treatment, i.e. cefotaxime (n = 17) or ceftriaxone (n = 11). Patients were assessed by neurological examination, Glasgow Coma Score and Herson-Todd score. Clinical cure was observed in all 23 evaluable patients treated with meropenem (100%) and with 17 of the 22 evaluable cephalosporin-treated patients (77%). All pre-treatment isolates were eradicated except one isolate of Staphylococcus aureus in a cefotaxime-treated patient. Neurological sequelae were noted in three meropenem and four cephalosporin-treated patients. No patients in either treatment group experienced seizures after the start of therapy. This was despite the fact that a patient in each group had experienced seizures before therapy, several had underlying CNS disorders, and that doses of 6 g/day of meropenem were given. Hearing impairment was recorded in 11 meropenem and nine cephalosporin treated patients. Three patients in the meropenem group and one in the cephalosporin group died during treatment for reasons unrelated to study therapy. Overall, the results of this study indicate that meropenem is an effective and well-tolerated antibiotic for the treatment of bacterial meningitis in adults.
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PMID:A randomised comparison of meropenem with cefotaxime or ceftriaxone for the treatment of bacterial meningitis in adults. Meropenem Meningitis Study Group. 854 2

In this multicentre, randomised study of 170 children hospitalised with bacterial infections, meropenem (10 to 20 mg/kg every 8 h) was found to be as effective and as well tolerated as cefotaxime (100 to 150 mg/kg/day), with or without amikacin or metronidazole. Most drug-related adverse events were mild and self-limiting. Neither regimen was associated with seizures. The overall incidence of clinically significant laboratory changes was similar in the two treatment groups. Satisfactory clinical responses were obtained in 94/96 (98%) patients treated with meropenem monotherapy and 43/46 (93%) children treated with cefotaxime regimens, while satisfactory bacteriological responses were obtained in 25/28 (89%) and 9/10 (90%) patients, respectively. Meropenem monotherapy appears to be a well-tolerated and effective drug for paediatric infections.
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PMID:Safety and efficacy of meropenem in hospitalised children: randomised comparison with cefotaxime, alone and combined with metronidazole or amikacin. Meropenem Paediatric Study Group. 854 3

Meropenem is the second carbapenem antibiotic available in the United States. It has a broad spectrum of activity that includes moderate activity against gram-positive bacteria and excellent gram-negative aerobic and anaerobic activity. Meropenem has enhanced gram-negative activity relative to imipenem-cilastatin and often retains activity against strains resistant to third-generation cephalosporins and imipenem-cilastatin. The drug penetrates well into most body fluids and tissues, including cerebrospinal fluid. It is also stable against renal dehydropeptidase hydrolysis and does not require coadministration of a dehydropeptidase inhibitor. Meropenem showed excellent efficacy in clinical studies involving seriously ill patients with intraabdominal, central nervous system, lower respiratory tract, skin and soft tissue, urinary tract, and febrile neutropenic infections. It appears well tolerated and, relative to imipenem-cilastatin, may have reduced potential for causing seizures and other central nervous system toxicities. Although it has many favorable qualities and some potential advantages relative to other broad-spectrum agents, additional trials and clinical experience are necessary to define its optimal place in clinical practice.
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PMID:Meropenem, a new carbapenem antibiotic. 925 May 44

The choice of an antibiotic for the treatment of a serious paediatric infection is generally a difficult problem. The arrival of Carbapenem resulted an important advance in the field of medicine due to its broad-spectrum, low incidence of resistances and good safety profile. Among Carbapenems, Meropenem introduction represents a progress because of its pharmacokinetics characteristics and blood-brain barrier penetration. Meropenem dosage depends on the patient weight, and the way of administration is potentially easier. Meropenem has been compared with the most used paediatric antimicrobial in controlled and randomised clinical trials, showing a high efficacy in the treatment of several infections (respiratory, urinary, intraabdominal, dermatological, septicemia) and in neutropenic and cystic fibrosis patients aged between one month and twelve years old. Meropenem is specially useful in the bacterial meningitis treatment because it penetrates into the cerebrospinal fluid of patients with inflamed meninges and reaches therapeutic concentrations, and because appearance of seizures is low. Adverse reactions produced by Meropenem show a poor incidence and its severity is usually mild. With regard to this characteristics, it can be concluded that Meropenem is an antimicrobial which efficacy and safety profiles guarantee its use in the treatment of severe paediatric infections.
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PMID:[Clinical pharmacology and indications of meropenem in severe pediatric infection]. 941 68

Three broad-spectrum antibiotics are reviewed, each from a different class. Meropenem is closely related to imipenem and was recently approved for use in children. Its advantages over imipenem include greater activity against gram-negative bacteria and lack of association with seizures. Cefepime is a fourth generation cephalosporin with the gram-positive activity of cefotaxime and the gram-negative spectrum of ceftazidime. Trovafloxacin is a fluoroquinolone with an exceptionally broad antibacterial spectrum. Meropenem is approved for use in children, cefepime is approved for use in adults only, and trovafloxacin is still undergoing clinical trials. These agents should be reserved for treatment of serious infections, especially those in immunocompromised patients or polymicrobial infections.
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PMID:New antibiotics. 952 36

Serious infections in children represent unique challenges for the treating physician. For the pediatric patient, considerations of drug toxicity are especially critical to avoid potential long-term complications of therapy. There are several advantages associated with using single, broad-spectrum, empiric antibiotic therapy, including reduced potential for drug-mediated toxicity or drug interactions and facilitation of home therapy. Of the antibiotics available for monotherapy, the carbapenems have the broadest spectrum of activity. However, a major obstacle toward the use of the carbapenems in pediatrics has been the risk of seizures occurring during therapy with imipenem/cilastatin. In clinical studies of meningitis and other infections in children, no drug-related seizures were reported when treated with the carbapenem meropenem. Meropenem monotherapy has been shown to be similar to ceftriaxone- and cefotaxime-based single or multiple antibiotic regimens, in terms of clinical and microbiologic efficacy and tolerability. Thus, meropenem represents a favorable treatment choice for the seriously ill child, either as empiric monotherapy or as definitive therapy of polymicrobial or nosocomial infections.
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PMID:Selecting therapy for serious infections in children: maximizing safety and efficacy. 963 16


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