PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Meropenem”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed1997

[In vivo pharmacokinetic of amikacin and its pharmacodynamic in combination with cefepime, cefpirome and meropenem in an in vitro/ex vivo micropig model].

Three female Yucatan micropigs were included and received a single dose of amikacin (15 mg/kg) by short infusion (30 min) combined either with a single dose of cefepime or cefpirome (30 mg/kg/12 h) or meropenem (7 mg/kg/8 h). The beta-lactams were administered either by intravenous intermittent injection or by continuous infusion. The mean elimination half-life and clearance value of amikacin were 1.88 h and 2.15 ml/min.kg-1 respectively. These pharmacokinetic parameters were similar to those obtained in man (t1/2 = 2,42 h et Cl = 1,61 ml/min kg-1). Furthermore, they were not affected by coadministration of cefepime, cefpirome and to meropenem. While resistant to cefepime, cefpirome and amikacin, Klebsiella pneumoniae producing ESBL was susceptible to combination of these cephalosporins with amikacin in an in vitro/ex vivo micropig model. For the six dosage regimens used in this study, the killing activities were similar and resulted in at least 4 log decrease at 6 h after drug exposure. For antimicrobial combination consisting of bolus dosing of amikacin plus continuous infusion of cefepime or cefpirome, the 12 h serum bactericidal titers (SBTs) were 1:8 for cefepime and 1:2 for cefpirome dosage regimen. When each drug administered intermittently, the 12 h SBTs were 1:4 for cefepime and 1:2 for cefpirome. The 8 h SBTs for dosing schedule containing meropenem combined with amikacin were 1:4 and 1:16 after 30 min short infusion and continuous infusion respectively. In conclusion, our study showed that the micropig model is a reliable model for pharmacokinetic investigation of amikacin. It was concluded that beta-lactam antibiotics tested with amikacin may be coadministered by using the standard recommended dosing regimen of amikacin. Continuous infusion of beta-lactams combined with once dosing of amikacin seems to be as or more effective than intermittent injection of each drug.

Amikacin↗
PubMed1997

[Penetration of meropenem in gram-negative bacilli. Differences in activity with imipenem].

The outer membrane of gramnegative bacteria cell-wall contain channels formed by proteins known as porins, which facilitate the penetration of molecules into the cell. Imipenem and meropenem possess an important intrinsic activity against most gramnegative bacteria due to their high affinity for the penicillin-binding proteins PBP-2 and/or PBP-3. Meropenem is slightly more active against certain species of Enterobacteriaceae, Pseudomonas aeruginosa and nonfermenters bacilli. In this sense the differences in the activity between the two carbapenems may be attributable to differences in their affinity for PBPs, differences in their resistance to beta-lactamases hydrolysis, or to the differences in the capacity to employ certain porin channels. OprF is the main porin channel involved in the beta-lactam penetration of bacteria, though OprC and OprD2 may also contribute to the penetration of carbapenems into P. aeruginosa. However, evidences suggest that although impenem requires the presence of OprD2, meropenem may use other pathways for penetration. In Escherichia coli both carbapenems use ompF and ompC, and no specific porin channels have been detected. Only in the case of Enterobacter cloacae may exceptions exists among Enterobacteriaceae.

Bacterial Outer Membrane Proteins↗
PubMed1997

[Meropenem: microbiologic perspective].

Meropenem is a beta-lactamic carbapenem derived from thienamycin and is structurally characterized by the presence of a beta-methyl group in position C1 which confers stability to the molecule versus renal dehydropeptidase 1 (DHP-1), thereby making the coadministration of an enzyme inhibitor unnecessary. Its esterochemical configuration of the lateral chain in C2 (dimethyl carbomoilpyrrolidenethium) increases the activity versus gram negative bacteria (enterobacteria and pseudomonas) and moreover, may explain the reduction in the proconvulsive effect observed in imipenem/cilastatin. Meropenem has great bactericide power and has a very wide spectrum of activity depending on it low molecular weight and zwiterionic structure, stability versus almost all the clinically important beta-lactamases and high affinity for the PBPs. It covers gram positive aerobes (Staphylococcus aureus, coagulase negative staphylococci, streptococci including Streptococcus pneumoniae resistant to penicillin, Enterococcus faecalis, Rhodococcus equi, Listeria monocytogenes) and gram negative bacteria (enterobacteria, P. aeruginosa, Acinetobacter, Aeromonas, Plesiomonas, Vibrio, Haemophilus influenzae, Neisseria, Moraxella) and anaerobes (Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Clostridium, Peptostreptococcus, and Propionibacterium acnes), being more active than imipenem versus gram negatives: P. aeruginosa (2-4-fold), enterobacteria (2-32-fold) and H. influenzae (4-8-fold) and less active versus the gram positives (enterococci, streptococci and staphylococci). Meropenem has no activity on Enterococcus faecium, S. aureus resistant to methycillin, Stenotrophomonas maltophilia and other genera producers of chromosomic methalo-beta-lactamases (carbapenemases). Resistance may be due to impermeability given the loss of the OprD porin (OprD2 in enterobacteria and P. aeruginosa) loss of different membrane proteins (Proteus mirabilis, Proteus rettgeri, Enterobacter cloacae, Enterobacter aerogenes), modifications of the PBPs (gram positive) and the production of carbapenemases (chromosomic methalo-beta-lactamases).

Bacteria, Aerobic↗
PubMed1997

[Meropenem: pharmacologic advantages of clinical interest].

The pharmacokinetic profile of meropenem is similar to that of imipenem/cilastatin. It differs in resistance to hydrolysis by the methaloenzyme, dehydropeptidase I, and therefore does not require the combination of cilastatin, being administered alone. Similar to other beta-lactamic drugs, it is mainly distributed in the extravascular space (apparent Vd, 21 I) with an half life of elimination of approximately one hour. A low proportion binds to plasma proteins (< 20%). The tissue concentrations are maintained for prolonged periods at values greater than the MIC of most pathogens. In LCR and aqueous humor it has limited penetration. Nonetheless, the levels achieved in patients with meningitis (40 mg/kg/8 h) range between 0.9 and 6.5 micrograms/ml, greater than the MIC of most pathogens associated with this disease. The renal clearance of meropenem surpasses that of creatinine, thereby indicating excretion by glomerular filtration and tubular secretion. The doses in patients with renal insufficiency should be reduced according to creatinine clearance. Modification of the dosage is not necessary in patients with hepatic failure. Administered at a doses of 1 g/8 hours meropenem presented a value of (AUICo infinity) 60-90 micrograms/h/ml. The (AUIC)24 = 125 ensures that the serum concentrations are maintained above 3 micrograms/ml during a period greater than 80% of the dosage interval.

Age Factors↗
PubMed1997

[Tolerance and safety of carbapenems: the use of meropenem].

The purpose of this article is to review the safety and tolerance of two carbapenems (imipenem/cilastatin and meropenem) in order to establish their possible use in different clinical settings. The tolerance and safety profile of both carbapemens in intravenous and intramuscular formulation is good. With imipenem/cilastatin, nausea and vomiting can constitute a practical problem requiring prolonged times of perfusion and high dilutions. The possibility of administering meropenem in intravenous infusion or bolus injection with lower volumes of fluid, without increasing the incidence of these adverse reactions, may have practical advantages in special situations. The possible neurotoxicity of the imipenem/cilastatin presents limitations of the use in high risk circumstances such as meningitis, previous alterations of CNS, renal insufficiency and concomitant administration of other drugs with neurotoxic profiles and when high doses of administration are needed. The meropenem, by the contrary, can be used in patients with infections of the CNS and other risk factors, at high doses, without increased risk of seizures.

Animals↗
PubMed1998

[Comparative activity of meropenem and other antibiotics against the pathogens of nosocomial infections].

Comparative activity of meropenem and other antibacterial drugs against isolates from intensive care and reanimation units of various profiles was estimated. It was shown that the recommendations for the combined therapy with the 3rd generation cephalosporins and aminoglycosides should be revised, since none of the isolates resistant to ceftazidime or cefotaxime was susceptible to gentamicin or tobramycin. At present the most promising agents of empirical therapy are carbapenems (meropenem and imipenem). However, the resistance of methicillin resistant staphylococci and Enterococcus faecium to carbapenems and the intrinsic resistance of some gram-negative bacteria to carbapenems are indicative of the necessity of microbiological diagnosis, especially when the treatment with meropenem fails.

Anti-Bacterial Agents↗
PubMed1998

[Effectiveness of the new carbapenem antibiotic, meropenem, in adult patients with mucoviscidosis].

Clinical efficacy of meropenem (meronem, Zeneca), a new carbapenem, was studied in the treatment of 4 adult patients with mucoviscidosis. The drug was administered as intravenous infusions 3 times a day in a daily dose of 60 mg/kg body weight for 10 days. A positive clinical effect was observed in 3 patients and in 1 patient stabilization of the clinical state was recorded. A significant decrease in the titre of the Pseudomonas aeruginosa colonies in 2 patients and that of the P. aeruginosa mucosa colonies in 3 patients was bacteriologically confirmed. Good tolerance and no side effects of meropenem in the doses used were stated. The study showed that meropenem may be recommended for the treatment of adult patients with mucoviscidosis.

Adult↗
PubMed1998

Effects of imipenem and meropenem on serum sensitivity and surface hydrophobicity of Klebsiella pneumoniae.

Serum sensitivity and surface hydrophobicity of two Klebsiella pneumoniae strains (internal strain No. 378 and 3259) exposed to imipenem (CAS 64221-86-9) and meropenem (CAS 96036-03-2) at subinhibitory concentrations (sub-MICs; 1/4, 1/8 and 1/16 of the MICs) were evaluated. Carbapenems at all sub-MICs tested (with the exception of 1/16 of the MICs in strain 378) decreased susceptibility of bacteria to serum bactericidal activity. All sub-MICs of the antibiotics tested also reduced the bacterial surface hydrophobicity. The surface hydrophobicity of strain 3259 was most effectively decreased after the exposure to imipenem and meropenem at 1/4 of the MICs (to 3% or 5.2% of the control values). The highest decrease of hydrophobicity in strain 378 was found after exposure to imipenem and meropenem at 1/16 of the MICs (19.2% or 32.3%).

Blood Bactericidal Activity↗
PubMed1996

The development and performance of a radioimmunoassay for the analysis of ZM 213,689, the major metabolite of meropenem--a carbapenem antibiotic--in plasma and urine.

The development of a radioimmunoassay for the analysis of ZM 213,689, the major metabolite of meropenem found in the plasma and urine of rat, dog and humans, is described. The assay is rapid in order to minimise the effect of degradation of meropenem to ZM 213,689 in biological samples and has a working range of 0.08-3.5 mg l-1 (RSD < or = 15%). The antibody was specific for ZM 213,689 with cross-reactivity to meropenem of only 0.4%. The synthesis of the immunogen and radiotracer involved a novel approach due to the multifunctional nature of ZM 213,689.

Animals↗
PubMed1997

Comparative in vitro pharmacodynamics of BO-2727, meropenem and imipenem against Gram-positive and Gram-negative bacteria.

OBJECTIVE: To investigate and compare the in vitro pharmacodynamics of three carbapenems: imipenem, meropenem and BO-2727. METHODS: The following studies were performed: (1) comparative studies of the rate of killing of the three carbapenems of reference strains of Gram-positive and Gram-negative bacteria at a concentration corresponding to the 1-h serum level following 500 mg intravenously in humans; (2) comparative studies of the rate of killing of BO-2727, meropenem and imipenem at different antibiotic concentrations of reference strains of Gram-positive and Gram-negative bacteria; (3) comparative studies of the rate of killing of BO-2727, meropenem and imipenem of bacteria which are phenotypically tolerant; (4) studies of the postantibiotic effect of BO-2727 using viable counts and optical density; (5) studies of the postantibiotic sub-MIC effect (PA SME) of BO-2727 using optical density. RESULTS: No difference in killing rate was noted between the three carbapenems, and there was no concentration-dependent killing of the Gram-negative strains after 6 h. A pronounced paradoxical effect was seen against Staphylococcus aureus. All three antibiotics were able to kill phenotypically tolerant bacteria. Only very short or no postantibiotic effect of BO-2727 was found against the investigated strains. Very long PA SMEs were noted for the Gram-negative strains, although there was a pronounced variation for the different strains of Pseudomonas aeruginosa. CONCLUSION: There was no significant difference between the studied carbapenems in their pharmacodynamic properties. All three antibiotics acted similarly to other beta-lactam antibiotics.

Journal Article↗
PubMed1993

In vitro activities of meropenem, PD 127391, PD 131628, ceftazidime, chloramphenicol, co-trimoxazole, and ciprofloxacin against Pseudomonas cepacia.

In a study of 110 Pseudomonas cepacia isolates from patients without cystic fibrosis, the in vitro potencies of three new compounds, meropenem, PD 127391, and PD 131628, were comparable to those of ceftazidime and ciprofloxacin and exceeded those of chloramphenicol and co-trimoxazole. The MICs of ceftazidime, ciprofloxacin, meropenem, and the PD compounds for 90% of strains tested were < or = 4 micrograms/ml, whereas they were 32 micrograms/ml for chloramphenicol and co-trimoxazole. Data for 20 isolates from patients with cystic fibrosis indicated that the isolates were less susceptible to all seven antibiotics tested, with the most active compounds being meropenem and PD 127391.

Anti-Bacterial Agents↗
PubMed2004

Comparison in a rat thigh abscess model of imipenem, meropenem and cefoperazone-sulbactam against Acinetobacter baumannii strains in terms of bactericidal efficacy and resistance selection.

BACKGROUND: We compared imipenem, meropenem and cefoperazone-sulbactam against hospital originated A. baumannii strains in terms of bactericidal efficacy and selection of resistant mutants during treatment in a rat thigh abscess model. METHODS: A total of 18 strains were inoculated in 54 animals (one strain for three animals). Randomly selected 10 among these 18 strains were inoculated in another 10 rats as the control group. Imipenem, meropenem and cefoperazone-sulbactam were the antibiotics compared. After four days of treatment, Wistar albino rats (200 to 250 g) were sacrificed and the abscess materials were processed for mean colony counts and for the presence of resistant mutants. RESULTS: The mean CFUs per gram (mean +/- (std. deviation) [x10(4)]) of the abscess were: 9,14 (25,24), 2,11 (3,78), 1,20 (1,70) in the imipenem (n = 17), meropenem (n = 18) and cefoperazone-sulbactam (n = 17) groups, respectively. The differences were not significant. On the other hand, no resistant mutant was detected in abscess materials. CONCLUSION: This study indicated; first, cefoperazone-sulbactam is comparable to carbapenems in bactericidal efficacy in this particular abscess model and second, emergence of resistance due to spontaneous mutations is not at least a frequent phenomenon among A. baumannii.

Journal Article↗
PubMed1997

A comparative study of the in vitro activity of meropenem and representatives of the major classes of broad-spectrum antibiotics.

OBJECTIVE: To compare the in vitro activity of meropenem with that of other agents with a broad-spectrum of antibacterial activity, and which may therefore be candidates for empirical use. The agents tested were imipenem, third-generation and newer cephalosporins, penicillins combined with a beta-lactamase inhibitor, ciprofloxacin and amino-glycosides. METHODS: Using agar dilution methods, all agents were tested against 900 clinical isolates (many of which were multiresistant), including Gram-positive aerobes, nutritionally fastidious aerobes, Enterobacteriaceae, non-fermenters and anaerobes, collected from 17 UK hospitals during 1994. In addition, some agents were tested against strains expressing defined beta-lactamases, including extended-spectrum beta-lactamases. RESULTS: The potency and spectrum of the carbapenems, unequalled against aerobes and anaerobes, were undoubtedly influenced by their stability to serine beta-lactamases. Meropenem and imipenem exhibited essentially the same spectrum of activity but imipenem was often less potent, notably against Gram-negative aerobes, including Pseudomonas aeruginosa and Burkholderia cepacia. Conversely, the activity of the third-generation (MIC90s 0.016--64 mg/L) and, to some extent, the newer cephalosporins (MIC90s 0.06--8 mg/L) and the augmented penicillins (MIC90s 1 to >128 mg/L) was unreliable against many genera of Enterobacteriaceae because of chromosomally mediated enzymes or the, now commonplace, plasmid-mediated beta-lactamases. Ciprofloxacin had modest activity (MIC90s 1--64 mg/L) against Gram-positive aerobes, was potent against nutritionally fastidious species, had again variable activity against the Enterobacteriaceae (MIC90s 0.008--4 mg/L) and was inactive against many strains of Pseudomonas, Burkholderia and Acinetobacter, resulting in MIC90s of 4 to >128 mg/L. The aminoglycosides were impressive only against the Enterobacteriaceae, with amikacin alone active (MIC90s 2--8 mg/L) against the 11 species tested. CONCLUSIONS: This study demonstrates that it is difficult on grounds of spectrum to differentiate third-generation cephalosporins, and that neither cefepime nor cefpirome materially enhance utility. The study suggests also that, judged on activity in vitro, meropenem or imipenem are the only monotherapy options for empirical antibacterial therapy of polymicrobic infections or when local epidemiology indicates the predominance of multiresistant Enterobacteriaceae. Instability to current and emerging beta-lactamases is progressively compromising the use of all other beta-lactam compounds.

Journal Article↗
PubMed2004

[Meropenem as empirical therapy in moderate to severe infections in hospitalized children aged 3 to 12 months and 1 to 14 years].

The objective of this study was to evaluate the clinical efficacy, dose and tolerability of treatment with meropenem in children with moderate to severe infections. An observational, multicenter, prospective study of 258 children was conducted. Two cohorts (81 under the age of 1 year, and 177 aged 1 to 14 years) were followed up at 48 hours, at the end of treatment, and 1 week later. Nosocomial infections were present in 37.5% of the children aged 1 to 14 years, and in 79.7% of those younger than 1 year of age (p < 0.001). A total of 79% received 20 mg/kg/8 h of meropenem; 43.8% received combination treatment with antifungal agents, glycopeptides or both. At 48 hours, 77.4% showed a clinical improvement; 74.2% were clinically cured at the end of treatment, and 77.5% at 1 week after the end of treatment. The clinical outcome was similar in both groups. Eradication or negative control cultures were found in 76.8%, with no difference between the two age groups. No major adverse events were reported, except for one case of pancytopenia after 2 days of treatment in a patient with a transplanted liver.

Adolescent↗
PubMed1993

Antimicrobial activity of the new carbapenem biapenem compared to imipenem, meropenem and other broad-spectrum beta-lactam drugs.

The in vitro activity of biapenem was compared to that of imipenem, meropenem and other broad-spectrum beta-lactams. A total of 716 isolates from recent cases of clinical septicemia and an additional 137 stock strains possessing known beta-lactamases or other well-characterized resistance mechanisms were tested. The minimal concentrations inhibiting 90% of strains (MIC90) of Enterobacteriaceae species were for biapenem 0.03 to 1 mg/l and for imipenem 0.25 to 2 mg/l. No member of the Enterobacteriaceae was found to be resistant to biapenem. Biapenem and meropenem were the most active drugs against Pseudomonas aeruginosa, with an MIC90 of 1 mg/l. Biapenem was more active than ceftazidime against most gram-negative and gram-positive bacteria tested. Biapenem was as potent as imipenem against anaerobic bacteria (including Bacteroides fragilis), with an MIC90 of 0.25 mg/l. High MICs of biapenem were demonstrated for Xanthomonas maltophilia, oxacillin-resistant Staphylococcus spp. and Enterococcus spp. These species have demonstrated resistance to other carbapenems and to most of the newer cephalosporins. The results of this study, coupled with previously documented favorable qualities of biapenem, endorse further investigation of this broad-spectrum antibacterial agent for clinical use.

Anti-Bacterial Agents↗
PubMed1999

Meropenem alone and in combination with vancomycin in experimental meningitis caused by a penicillin-resistant pneumococcal strain.

In a rabbit model of meningitis caused by a pneumococcus highly resistant to penicillin (MIC, 4 microg/ml), meropenem, a broad-spectrum carbapenem, was bactericidal (-0.48+/-0.14 deltalog10 cfu/ml h) and slightly superior to ceftriaxone (-0.34+/-0.23 deltalog10 cfu/ml x h) and vancomycin (-0.39+/-0.19 deltalog10 cfu/ml x h). Although the combination of vancomycin with ceftriaxone was significantly more active than ceftriaxone alone (-0.55+/-0.19 deltalog10 cfu/ml x h), only an insignificant gain was observed by the addition of vancomycin to meropenem (-0.55+/-0.28 deltalog10 cfu/ml x h).

Animals↗
PubMed1992

Interpretive criteria and quality control guidelines for lomefloxacin and meropenem in susceptibility tests of Haemophilus influenzae using Haemophilus test medium.

Lomefloxacin and meropenem were tested in a multilaboratory study to establish susceptibility testing interpretive criteria and quality control (QC) guidelines for Haemophilus influenzae using Haemophilus test medium (HTM). Interpretive criteria were established by using triplicate testing of 102 representative H. influenzae strains. Only a susceptible category was proposed for lomefloxacin (greater than or equal to 22 mm and less than or equal to 2 micrograms/ml) and meropenem (greater than or equal to 13 mm and less than or equal to 4 micrograms/ml) due to the lack of resistant isolates. QC range for H. Influenzae ATCC 49247 were established using multiple HTM agar and broth base lots, three disk lots for each drug, and a number of test replicates consistent with the National Committee for Clinical Laboratory Standards M23-T guideline.

Anti-Infective Agents↗