Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT02153 (Meropenem)
 588 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Meropenem and comparative antibiotics were evaluated in five models of infection. All antibiotics were administered parenterally; imipenem was used in combination with cilastatin but meropenem and other agents were given alone. Generalized infections in mice caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Serratia marcescens, Proteus mirabilis or Pseudomonas aeruginosa all responded to low doses of meropenem or imipenem. Immunocompromised mice infected with Ps. aeruginosa responded to slightly higher doses of meropenem or gentamicin but required four to seven times the dose of other agents. Those given a greater challenge of Ps. aeruginosa were treated most successfully by meropenem. Treatment with meropenem, imipenem or ceftazidime caused significant reductions of E. coli in the urinary bladder and kidneys of mice challenged per urethram. Infection with Ps. (Xanthomonas) maltophilia localized to the subcutaneous neck tissue of guinea pigs was also treated successfully. Lung infections caused by Ps. aeruginosa in guinea pigs were treated effectively by meropenem, imipenem, and ceftazidime at the dose of 10 mg/kg but only meropenem eradicated bacteria from all the tissues examined. These results demonstrate that meropenem has excellent antibacterial activity in vivo in both normal and immunocompromised animals and in some models of infection is superior to imipenem.
 ...
PMID:Therapeutic activity of meropenem in experimental infections. 268 Nov 26

Infection remains the major cause of morbidity and mortality for cancer patients who become granulocytopenic as a result of chemotherapy. Treatment is instituted at the first sign of infection and before the identification of the causative pathogen (empiric treatment). For many years, standard empiric treatment has been combination therapy with beta-lactams and aminoglycosides. The advent of new broad spectrum antibiotics, such as ceftazidime, has introduced the possibility of empiric monotherapy. However, ceftazidime has only modest activity against infections due to Gram-positive organisms, which presently account for at least 50% of infections in neutropenic patients, and resistance to ceftazidime in Gram-negative organisms has been documented. Meropenem is a new carbapenem with a broad antibacterial spectrum with greater in vitro activity than ceftazidime against staphylococci, streptococci and many Gram-negative bacteria. A comparative study of intravenous meropenem (1 g 8-hourly) and ceftazidime (2 g 8-hourly) in the empiric treatment of febrile neutropenic patients with haematological malignancies has been conducted. In an open, randomised trial of the treatment of 338 febrile episodes, all patients survived to 72 hours on both treatments, and meropenem was found to be at least as clinically effective as ceftazidime in eradicating both Gram-positive and Gram-negative infections. Early modification of treatment (48-72 hours) was required for approximately 40% of patients but occurred less frequently in patients treated with meropenem than with ceftazidime. Tolerability of both treatments was good. Meropenem should be compared with standard combination therapy in a large randomised trial before adopting it as empiric monotherapy for febrile neutropenic patients.
 ...
PMID:Empiric monotherapy in neutropenia: a realistic goal? 765 1

The in vitro activity of meropenem, a new carbapenem, and the combination effect with netilmicin, tobramycin, gentamicin, and teicoplanin against Pseudomonas spp. and enterococci was studied. Meropenem showed very good in vitro activity against Pseudomonas aeruginosa (MIC90 2 mg/l) and good to moderate activity against Pseudomonas putida (MIC90 4 mg/l) and Enterococcus faecalis (MIC90 8 mg/l). Aminoglycosides were highly active against P. putida (MIC90 0.5 mg/l), but showed only moderate activity against P. aeruginosa. The synergistic effect of meropenem was shown in combination with teicoplanin against E. faecalis (40%). No Pseudomonas strains were inhibited by the synergistic effect of meropenem with aminoglycosides. No antagonism occurred with any of the combinations.
Infection
PMID:Combination effect of meropenem with aminoglycosides and teicoplanin on Pseudomonas and enterococci. 800 95

The efficacy of meropenem was compared to that of the combination of tobramycin plus clindamycin (T/C) in a multiinstitutional clinical trial of treatment for patients suffering intraabdominal infection. Among the 177 patients enrolled and randomized, 127 were clinically evaluable and 86 were microbiologically evaluable. Analysis of data on an intent-to-treat basis for all randomized patients and on the basis of a successful outcome (absence of any infection) for clinically evaluable patients failed to detect any difference in efficacy between the two treatments. Infection was cleared in 92% of meropenem- and 89% of T/C-treated clinically evaluable patients. Eradication of pathogens also was similar in the two treatment groups. Overall, adverse drug experiences were comparable between the two treatment groups, with the exception of an increase in serum creatinine level (which occurred more frequently in patients receiving T/C). Meropenem appears to be efficacious for the treatment of intraabdominal infections.
 ...
PMID:Meropenem versus tobramycin plus clindamycin for treatment of intraabdominal infections: results of a prospective, randomized, double-blind clinical trial. 852 41

Meropenem and comparator antibiotics, including ceftriaxone, ceftazidime, benzyl penicillin and a combination of ampicillin plus gentamicin, were evaluated in a model of bacterial meningitis in the guinea-pig. The model is an acute infection in which challenge with each organism, if untreated, causes an increase in numbers of white blood cells, elevation of protein concentrations and 6-8 log10 cfu/mL of bacteria in the CSF. Infections caused by Haemophilus influenzae, Neisseria meningitidis, three strains of Streptococcus pneumoniae (two penicillin-resistant), Escherichia coli, Pseudomonas aeruginosa and Listeria monocytogenes all responded to meropenem, which was as active as the comparator agents in all studies, and was more active in most. Of particular note were the results seen against S. pneumoniae (penicillin-resistant) infections, in which meropenem was significantly more effective than ceftriaxone. Also notable were results from the P. aeruginosa infection where meropenem, at low doses, was more effective than ceftazidime. Activity against L. monocytogenes was equivalent to that produced by treatment with the combination of ampicillin plus gentamicin, even when treatment was delayed. These results show that, in an animal model, meropenem penetrates into CSF in concentrations sufficient to produce significant reductions in the numbers of common and less common pathogens.
 ...
PMID:Efficacy of meropenem in experimental meningitis. 854 1

Meropenem was compared with imipenem/cilastatin for the treatment of serious bacterial infections in a randomized, prospective multicentre study. Both study drugs were given intravenously 1 g every 8 h and no other antimicrobial agents were permitted concomitantly. Of the 204 patients enrolled, the treatment of 177 was evaluable for clinical efficacy and 115 for bacteriological efficacy. In the clinically evaluable treatment population, 75 (83%) of the 90 patients in the meropenem group and 78 (90%) of the 87 in the imipenem/cilastatin group had a single site of infection whereas the remainder had two or more sites of infection. Infections of the lower respiratory tract and peritoneal cavity predominated accounting for 95 and 75 cases respectively. Other infections included skin and soft tissue infections, complicated urinary tract infections, bacteraemia and a case of meningitis treated with meropenem and one of mediastinitis treated with imipenem/cilastatin. One hundred and nineteen (67%) patients were in an intensive care unit, 105 (59%) were receiving assisted ventilation and 93 (53%) of the patients had failed previous antibiotic therapy. One hundred and ten organisms were identified as pathogens in the meropenem group and 109 in the imipenem/cilastatin group. Overall, treatment with meropenem was clinically successful in 68 (76%) of 90 cases and imipenem/cilastatin in 67 (77%) of 87 cases and the corresponding eradication rates of bacteria were 85 of 110 (77%) and 90 of 109 (83%) respectively. Superinfections due to resistant bacteria occurred in two patients treated with meropenem and three cases given imipenem/cilastatin. No statistically significant differences in the clinical or bacteriological outcome were observed between the treatment groups for any of the infection sites analysed. Both drugs were well tolerated with adverse events considered to be related to therapy being recorded for 10 (9%) of 106 patients treated with meropenem and 12 (12%) of 98 of those who had been given imipenem/cilastatin. Empirical monotherapy with meropenem was therefore as effective and as well tolerated as that with imipenem/cilastatin for the treatment of serious bacterial infections.
 ...
PMID:Intravenous meropenem versus imipenem/cilastatin in the treatment of serious bacterial infections in hospitalized patients. Meropenem Serious Infection Study Group. 888 26

In a nonblind, randomised, parallel-group study, initial empirical monotherapy with meropenem 1 g intravenously every 8 h was compared to an identical dosage of imipenem/cilastatin for the treatment of 66 febrile episodes in 61 adult neutropenic patients. 25/31 episodes treated with meropenem and 24/30 imipenem/cilastatin-treated episodes were still receiving unmodified therapy at 72 h (primary endpoint); this difference was not statistically significant. By the end of the treatment courses, 18/31 meropenem-treated episodes had responded clinically (cured or improved) compared with 18/30 episodes treated with imipenem/cilastatin. Another ten episodes initially treated with meropenem and six episodes treated with imipenem/cilastatia were cured after an additional antimicrobial agent had been administered (cured with modification). Satisfactory bacteriological responses (eradication plus presumed eradication) at the end of unmodified therapy was 9/11 in the meropenem group and 14/16 in the comparator group. Both regimes were well tolerated; however, there were more reports of nausea and/or vomiting in the impenem/cilastatin group (7/33 vs. 2/33 in the meropenem group). The carbapenems meropenem and imipenem/cilastatin appear to be suitable agents for empirical monotherapy of febrile episodes in neutropenic patients. Meropenem may be better tolerated than imipenem/cilastatin, allowing optimal dosing in this patient population.
Infection
PMID:Empirical monotherapy with meropenem versus imipenem/cilastatin for febrile episodes in neutropenic patients. 900 99

Infection remains the major cause of morbidity and mortality for cancer patients who become granulocytopenic. Combinations of beta-lactams plus aminoglycosides have been the standard empiric therapy for febrile granulocytopenic patients, especially those with profound long-lasting granulocytopenia. The advent of new broad-spectrum cephalosporins and carbapenems has favoured the possibility of empiric monotherapy. Meropenem is a parenteral carbapenem antibiotic stable to renal dehydropeptidase-I which has excellent bactericidal activity against almost all clinically significant aerobic and anaerobic organisms. Meropenem hasta an antibacterial spectrum similar to that of imipenem but it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae, Haemophilus influenzae, Proteus spp, Morganella spp and Providencia spp. Recently, the efficacy, safety, and tolerance of meropenem monotherapy for the empirical treatment of fever in granulocytopenic cancer patients have been compared in two large prospective randomized multicenter trials. The Meropenem Study Group compared monotherapy with meropenem versus ceftazidime and the EORTC conducted a comparative study of meropenem monotherapy versus the combination of ceftazidime plus amikacin. In both groups, success rates were similar by type of infection and infection-related mortality was low. Related adverse events were also similar in both groups. These studies confirm that monotherapy with meropenem is as effective as ceftazidime-containing regimens for the empiric treatment of fever in granulocytopenic patients.
 ...
PMID:[Monotherapy with meropenem in febrile granulocytopenic patients]. 941 73

Infections remain the major cause of morbidity and mortality among neutropenic cancer patients. The current study addresses the question whether monotherapy with the new broad-spectrum carbapenem meropenem exhibits efficacy comparable to that of the standard combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Seventy-one patients with hematological malignancies (55%) or solid tumors (45%), neutropenia < 500/microliter, and fever > 38.5 degrees C were randomly assigned to either meropenem (1 g every 8 h) or ceftazidime (2 g every 8 h) and amikacin (15 mg/kg/day) intravenously. Meropenem (n = 34) and ceftazidime/amikacin (n = 37) were equivalent with respect to the clinical response at 72 h (62% versus 68%) (p > 0.05) and at the end of unmodified therapy (59% versus 62%). Gram-positive bacteremia responded poorly in the meropenem and ceftazidime/amikacin group (29% versus 25%), whereas all gram-negative bacteremias responded except for one in the meropenem group caused by Pseudomonas aeruginosa. All patients survived to 72 h. One patient in each group died of gram-positive sepsis resistant to study medication. No significant side effects occurred in any regimen. This study suggests that meropenem monotherapy might be as effective as combination therapy with ceftazidime and amikacin for the empirical treatment of febrile neutropenic patients.
 ...
PMID:Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. 954 Jul 61

Eighty three patients with neutropenia and cancer were randomised to receive either 1 g meropenem tds or amikacin 15 mg/kg single dose daily plus ceftazidime 2 g tds. No prophylactic antibiotics were allowed before entry to the trial. Seventy seven patients were available for analysis. Infection was microbiologically or clinically documented in 53 episodes (69%). The overall success rate without adjustment was 49% in monotherapy, 37.5% in the combination group. These rates were increased to 65% and 56%, respectively when secondary infection episodes requiring a different class of chemotherapy were taken into account. Median duration for defervescence was 3 days in successfully treated patients in both groups. Only minor reversible side effects were noted in both treatment arms. Meropenem monotherapy seemed as effective and safe as amikacin plus ceftazidime for the empirical treatment of neutropenic cancer patients with fever.
 ...
PMID:Comparison of meropenem with amikacin plus ceftazidime in the empirical treatment of febrile neutropenia: a prospective randomised multicentre trial in patients without previous prophylactic antibiotics. Meropenem Study Group of Turkey. 1056


1 2 Next >>