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PubMed2005

Meropenem in the treatment of febrile neutropenic children.

The aim of this retrospective study was to evaluate the clinical effectiveness of meropenem in immunocompromised children. Between January 1998 and December 2002 in the hemato-oncological units of our hospital meropenem was used in 87 febrile events diagnosed in 55 patients, and 328 bacterial cultures were evaluated. Microorganisms were detected and identified in 64 of the 328 hemocultures; there was a predominance of gram-positive strains (67%). In 49.4% the infection was documented microbiologically. In 16 additional cases the infection was proven clinically and 32.2% of the episodes were considered to be fever of unknown origin. The success rate of the meropenem therapy-excluding the proven fungal or coagulase-negative Staphylococcus infections--was 72.9% and for the whole cohort 49.4%. The results demonstrate that meropenem is effective and well-tolerated when used for the treatment of neutropenic cancer children.

Adolescent↗

PubMed1994

Outer membrane permeability of Serratia marcescens to meropenem and imipenem.

The penetration rates of meropenem and imipenem through the outer membrane (OM) of Serratia marcescens was evaluated by the method of Zimmermann and Rosselet. To this aim, two strains of the specie were transformed with the pMON-01 plasmid DNA that carries the bla S gene from Xanthomonas maltophilia encoding for the L-1 beta-lactamase. The permeability of the transformants to cephaloridine was not affected by the presence of the plasmid. Imipenem was shown to penetrate the OM of the transformants at a rate 4- to 5-fold higher than that of meropenem and close to that of cephaloridine. Meropenem appeared more active than imipenem in inhibiting the targets as inferred from the calculated concentrations of antibiotic in the cell periplasm in the presence of MIC. The calculation of the target access index (TAI) indicated that a 20- to 50-fold decrease in permeability or increase in beta-lactamase activity would be required to significantly increase the MICs of imipenem or meropenem for these strains.

Cell Membrane Permeability↗

PubMed1999

Penetration and decay of meropenem into the human aqueous humor and vitreous.

The aim of this study was to determine the penetration of intravenously administered meropenem into the human aqueous humor and vitreous. Thirty patients about to undergo cataract surgery and fourteen patients about to undergo vitrectomy received a 2 g dose of meropenem before surgery. Specimens of aqueous humor or vitreous and blood were obtained intraoperatively and analyzed by high performance liquid chromatography (HPLC). The study was designed as a non-randomized prospective trial. Thirty min to 12 hr after administration, mean aqueous humor levels of 13.4 and 1.1 mg/l and vitreous levels between 8.94 and 1.08 mg/l were found, respectively. The peak concentrations are distinctly above the in vitro measured minimum inhibitory concentration of meropenem for 90% (MIC90) of almost all relevant gram-positive and gram-negative organisms, including Pseudomonas aeruginosa and Enterobacteriaceae. With regard to its broad spectrum, high antibacterial activity, and good penetration into ocular fluids, meropenem seems to be an alternative to currently used systemic drugs. Its usefulness in perioperative prophylaxis, as initial therapy after perforating or penetrating injuries, or in the therapy of bacterial endophthalmitis has yet to be proved.

Aqueous Humor↗

PubMed1995

Comparison of the activity of meropenem with that of other agents in the treatment of intraabdominal, obstetric/gynecologic, and skin and soft tissue.

Meropenem, a new carbapenem with improved stability in the presence of human dehydropeptidase-I[1], was evaluated in three prospective, multicenter, randomized, controlled clinical trials in North America. We compared the in vitro activity of meropenem and conventional antimicrobial agents for the treatment of intraabdominal, obstetric/gynecologic, and skin or soft tissue infections as well as the responses of pathogens to all of these agents. The trials of the drug for intraabdominal infection were double blind, and those for the obstetric/gynecologic and soft tissue infections were open labeled. Overall, MICs of meropenem for pathogens were lower, and the pathogen response rates were at least comparable to those for the following comparative agents: clindamycin plus tobramycin (for intraabdominal infections); clindamycin plus gentamicin (for obstetric/gynecologic infections); and imipenem and cilastatin (for skin or soft tissue infections). Meropenem has high in vitro potency and covers a broad spectrum of anaerobic and aerobic pathogens.

Abdomen↗

PubMed1997

Tissue penetration of Meropenem in patients undergoing gynecologic surgery.

The purpose of this study was to assess the tissue-penetrating ability of a new beta-lactam antibiotic, meropenem, in 64 patients undergoing elective gynecologic surgery. Patients received a single 500-mg dose intravenously before surgery. Plasma and tissue concentrations of meropenem were highest at approximately 1 hour, and good tissue penetration was seen in the variety of specimens evaluated. The median plasma concentration at approximately 1 hour was 13.3 micrograms/mL. The median fluid and tissue concentrations at approximately 1 hour were as follows: cervix, 8.5 micrograms/g; endometrium, 2.3 micrograms/g; fallopian tube, 1.9 micrograms/g; myometrium, 3.6 micrograms/g; ovary, 2.3 micrograms/g; and uterus, 2.3 micrograms/g. These tissue concentrations exceed the MICs of meropenem for 90% of typical pathogens associated with gynecologic infections. Meropenem readily penetrates gynecologic tissue. A single 500-mg dose provides adequate tissue concentrations for treatment of gynecologic infections caused by susceptible pathogens.

Adult↗

PubMed1997

A multicenter study comparing intravenous meropenem with clindamycin plus gentamicin for the treatment of acute gynecologic and obstetric pelvic infections in hospitalized women.

We conducted a multicenter trial to compare the efficacy and safety of meropenem with the efficacy and safety of clindamycin plus gentamicin in the treatment of 515 hospitalized patients with acute gynecologic and obstetric pelvic infections. At the end of treatment, the rates of satisfactory clinical and bacteriologic response were high (88%) in both treatment groups: the rates of response were 90% for the meropenem group and 86% for the clindamycin/gentamicin group. No serious adverse events occurred. The most frequently reported drug-related adverse clinical events in the meropenem group were nausea and injection-site reactions (> 1% of patients), and the most common drug-related laboratory abnormality was thrombocythemia. Similar patterns of adverse events occurred in the clindamycin/gentamicin group; however, the incidence of diarrhea and eosinophilia was higher in this group. In summary, this trial demonstrated that meropenem is an effective and safe alternative to the combination of clindamycin plus gentamicin for the treatment of women with acute gynecologic and obstetric pelvic infections.

Adolescent↗

PubMed1989

The growth-inhibitory properties of meropenem against anaerobes of clinical importance.

The in-vitro activity of meropenem against anaerobic bacteria was assessed by an agar dilution procedure. MICs were measured for 449 clinical isolates and reference strains. Meropenem showed excellent activity against both Gram-negative anaerobes, including Bacteroides fragilis (MIC90 0.25 mg/l), and Gram-positive anaerobes. The MIC90 for Clostridium perfringens was 0.01 mg/l. Meropenem had comparable activity to imipenem against Gram-negative anaerobes but was more active than imipenem against clostridia, including C. difficile (MIC90 2 mg/l compared with 8 mg/l). Meropenem was more active against anaerobes than was cefoxitin, metronidazole or clindamycin.

Anti-Bacterial Agents↗

PubMed1989

Antibacterial activity of meropenem against gram-negative bacteria with a permeability defect and against staphylococci.

Meropenem, like imipenem, showed a good affinity for high molecular weight PBPs of Escherichia coli and Pseudomonas aeruginosa and had a better affinity for PBP3 than imipenem. Meropenem, like imipenem, also remained almost fully active against permeability mutants of enterobacteria lacking in confirmed or putative porins. This good permeation of the carbapenems may relate to their zwitterionic character. In-vitro, mutants and clinical isolates of P. aeruginosa, for which the MIC of imipenem was greater than or equal to 4 mg/l, were always more sensitive to meropenem. Methicillin resistant staphylococci were sensitive neither to imipenem nor to meropenem.

Bacterial Proteins↗

PubMed1989

In-vitro activity of meropenem, a new carbapenem, against multiresistant Pseudomonas aeruginosa compared with that of other antipseudomonal antimicrobials.

The novel carbapenem meropenem, which is stable to dehydropeptadase action, was studied in vitro against 173 nosocomial isolates of Pseudomonas aeruginosa derived from pus, expectorated sputum, bronchial secretions, urine or blood of infected patients. Susceptibilities to meropenem, imipenem, ceftazidime, cefotaxime, piperacillin, gentamicin, amikacin and ciprofloxacin were determined by the agar dilution technique with an inoculum of 10(4) cfu/spot. The proportion of sensitive isolates with MICs below the breakpoint was highest for meropenem (91% less than or equal to 8 mg/l); the proportion of sensitive isolates for the remaining antibacterials was as follows: ciprofloxacin 87% less than or equal to 2 mg/l; imipenem 85% less than or equal to 8 mg/l; ceftazidime 77.5% less than or equal to 16 mg/l; piperacillin 60% less than or equal to 64 mg/l; amikacin 44% less than or equal to 8 mg/l; gentamicin 34% less than or equal to 4 mg/l and cefotaxime 15% less than or equal to 16 mg/l. Strains moderately resistant to imipenem (MIC 16-32 mg/l) were mostly sensitive to meropenem, but highly resistant strains (MIC 128-256 mg/l) were invariably resistant (MIC greater than 128 mg/l) to the new carbapenem.

Anti-Bacterial Agents↗

PubMed1990

Antibacterial effect of meropenem and imipenem on Proteus mirabilis.

Phase-contrast microscopy, killing-curves and turbidimetric growth-curves were used in a comparative study of the antibacterial effects of a new carbapenem, meropenem (SM 7338) and imipenem on five strains of Proteus mirabilis. Despite the low MIC (0.2 mg/l) of imipenem for the five strains included in our study, the MBC remained relatively high (4.4 mg/l). During the first few hours of incubation, imipenem induced large lemon-shaped cells while the turbidity increased without substantial changes in culture viability. Later, most of the cell-wall deficient bacteria generated small spheroplasts until the antibiotic concentration exceeded 32 times the MIC. The MIC of meropenem was lower (0.03 mg/l) with an MBC (0.08 mg/l) very close to the MIC. Meropenem also induced large bodies but these cell-wall deficient bacteria did not generate small round bodies as observed with imipenem. In conclusion, imipenem produced in strains of Pr. mirabilis an amdinocillin-like change in cell morphology, responsible for the discrepancies observed between MIC and MBC. This effect was not observed with meropenem.

Imipenem↗

PubMed1992

In-vitro activity of new carbapenem antibiotics: comparative studies with meropenem, L-627 and imipenem against pathogenic Nocardia spp.

MICs of two new carbapenems, meropenem and L-627, and imipenem were determined against 98 strains of the Nocardia asteroides group (i.e. N. asteroides sensu stricto, Nocardia farcinica and Nocardia nova), 46 strains of Nocardia brasiliensis and 17 strains of Nocardia otitidiscaviarum. Meropenem and L-627 were less active against the N. asteroides group than imipenem. Among the three species of the N. asteroides group, N. nova was the most sensitive to all the carbapenems. Meropenem was more active than imipenem against both N. brasiliensis and N. otitidiscaviarum with MIC50 values of 28.3-53.3 mg/L. L-627 was less active than meropenem.

Carbapenems↗

PubMed1993

Activity of meropenem and other antimicrobial agents against uncommon gram-negative organisms.

The in-vitro activity of meropenem and other antimicrobial agents was tested by agar dilution against 113 uncommon Gram-negative pathogens. Both meropenem and ceftriaxone showed the most activity against the test isolates. The potency of meropenem was greater than imipenem against Pasteurella multocida, Eikenella corrodens, Haemophilus parainfluenzae, Moraxella spp., Kingella spp., and Actinobacillus actinomycetemcomitans. Further work is necessary to assess the in-vivo activity of meropenem against these Gram-negative isolates.

Anti-Bacterial Agents↗

PubMed1993

The entry of meropenem into human macrophages and its immunomodulating activity.

The uptake of meropenem by human macrophages and its consequences upon subsequent phagocytosis and killing of intracellular staphylococci has been studied. The cellular to extracellular concentration ratios (C/E) of meropenem were always high (range 3-12) at extracellular concentrations ranging from 0.125 to 1 mg/L. The uptake was not energy-dependent, being similar when viable and formalin-killed cells were used and was influenced neither by environmental temperature nor by the addition of a metabolic inhibitor. Meropenem at half the MIC caused a significant enhancement of phagocytosis and a reduction in the survival of intracellular Staphylococcus aureus. Pre-exposure of either staphylococci or macrophages to sub-MIC concentrations of meropenem led to an increase in uptake of bacteria and intracellular bactericidal activity by macrophages.

Adjuvants, Immunologic↗

PubMed1995

The comparative inhibitory and bactericidal activities of meropenem and imipenem against Acinetobacter spp. and Enterobacteriaceae resistant to second generation cephalosporins.

The inhibitory and bactericidal activities of meropenem and imipenem were compared using Acinetobacter spp. and Enterobacteriaceae resistant to second generation cephalosporins. The inhibitory activity of both agents was similar for Acinetobacter spp. but meropenem was more active against the Enterobacteriaceae. Bactericidal activities were compared employing time-kill curves which indicated meropenem was more bactericidal than imipenem against Enterobacteriaceae at pharmacologically achievable concentrations while imipenem was more bactericidal than meropenem against Acinetobacter spp.

Acinetobacter↗

PubMed1995

The pharmacokinetics of meropenem in surgical patients with moderate or severe infections.

The pharmacokinetics of meropenem were studied in a group of 11 surgical patients (four male, seven female; mean age 63 years; mean weight 72 kg) all of whom had moderate or severe infection and who received a mean dose of 14.5 mg/kg +/- 2.7 meropenem 8-hourly iv for a minimum of 4 days. Venous blood samples were collected at timed intervals after the first dose on day 1 and the second dose on the fourth or fifth day of therapy. Serum meropenem concentrations were assayed by HPLC and fitted to a two compartment pharmacokinetic model. The mean pharmacokinetic parameters (+/- standard deviation) on day 1 were T1/2 84.6 +/- 24.1 min, Vdss 0.22 +/- 0.06 L/kg, AUC 6028 +/- 1983.2 mg.min/L, Cltot 188 +/- 67 mL/min and MRT 89.1 +/- 67.8 min. On the fourth or fifth days of therapy the values were T1/2 79.9 +/- 18.2 min, Vdss 0.17 +/- 0.8 L/kg, AUC 6000.7 +/- 2417 mg.min/L, Cltot 190 +/- 60 mL/min and MRT 67.8 +/- 30.4 min. Although the T1/2, Vdss and MRT decreased from day 1 to day 4 or 5 these changes were not statistically significant (Student's t-test, P > 0.05). Total clearance of meropenem was linearly related to creatinine clearance or patient age on the first day of therapy. Although the T1/2 and MRT were longer and the Cltot lower than those reported for young healthy volunteers, they were similar to those found in elderly volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

A comparison of the pharmacokinetics of meropenem after administration by intravenous injection over 5 min and intravenous infusion over 30 min.

The pharmacokinetics of meropenem were determined in healthy volunteers after intravenous injection over 5 min or iv infusion over 30 min. Five volunteers received meropenem 500 mg and six volunteers received 1000 mg. For both doses, administration over 5 rather than 30 min doubled the plasma concentrations observed at the end of the dosing period. Comparison of the other data derived from the two modes of administration indicated that rapid administration of meropenem did not appreciably alter its disposition pharmacokinetics. Plasma clearance, renal clearance, non-renal clearance, terminal half-life and volume of distribution were unchanged. Within 1 h of dosing, the plasma concentrations were very similar indicating that dosing over either time period would result in similar antimicrobial cover and thus should not affect efficacy. There were no changes in tolerability of meropenem associated with more rapid administration.

Adolescent↗

PubMed1998

Comparative pharmacodynamics of meropenem using an in-vitro model to simulate once, twice and three times daily dosing in humans.

An in-vitro pharmacokinetic model was used to study the antibacterial activity of meropenem. Strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were exposed to meropenem concentrations likely to be produced in an adult by rapid iv infusion of 3 g once a day (q24h regimen), 1.5 g twice a day (ql2h regimen) or 1 g three times a day (q8h regimen). Each of these three dosing regimens produced a rapid reduction in viable bacterial count over the first 16 h after dosing. There were no differences in the pattern of reduction in viable count with the q24h, q12h or q8h regimens with any of the three bacterial strains tested over the first 16 h. However, reduction in viable counts was poorer at 24 h with the q24h than q12h or q8h regimens. A simulation lasting 48 h of the q24h dosing regimen indicated a reduction in bacterial count below the limit of detection from the model with E. coli but not with P. aeruginosa or S. aureus. The time for which the meropenem concentration was higher than the MIC for the bacteria correlated best with the reduction in viable bacterial count at 24 h. The AUC for the bacterial time-kill curve, which may be a better measure of antibacterial efficacy, was not related to the length of time for which the concentration was above the MIC or the peak concentration/MIC ratio. The antibacterial effect of the conventional q8h dosing simulation was indistinguishable from that given by the q12h simulation, and both the q8h and q12h regimens offered minor advantages over a q24h regimen. Dosing of meropenem 12 hourly or 24 hourly in humans should be investigated.

Adult↗

PubMed2000

Use of meropenem 3 g once daily for outpatient treatment of infective exacerbations of bronchiectasis.

Meropenem administered as a single iv 3 g dose once every 24 h was used to treat nine ambulatory patients with infective exacerbations of bronchiectasis. Serum meropenem concentrations were measured before dosing and at 30 min after each 30 min infusion. Mean pre-dose concentrations were <0.1 mg/L and mean post-dose concentrations 93.9 +/- 29.5 mg/L (95% confidence interval (CI) 86. 2-101.6, n = 59). A pathogen was cultured from sputum in six patients and eradicated (<100 cfu/g sputum) in all but one by day 6 of therapy. Previous work on animals has shown that a bacteriostatic effect is seen with meropenem when t > MIC is greater than 20-30% of the dose interval. In these nine patients, this could be achieved and was associated with successful outcome for pathogens for which MICs are </= 0.5 mg/L. Therefore, once-a-day meropenem therapy may be a useful option for outpatient treatment for isolates for which MICs are </= 0.5 mg/L.

Aged↗