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PubMed1990

Quality control criteria for testing the susceptibility of anaerobic bacteria to meropenem.

Reference values for quality control of in vitro susceptibility tests with meropenem against anaerobic bacteria were determined in a multilaboratory study by the approved National Committee for Clinical Laboratory Standards agar dilution method for the four quality control strains. The study protocol also included the evaluation of microdilution testing, medium additives, and multiple lots of media. The recommended MIC control ranges for three of the control organisms are as follows: Bacteroides fragilis ATCC 25285, 0.06 to 0.125 micrograms/ml; Bacteroides thetaiotaomicron ATCC 29741, 0.125 to 0.5 micrograms/ml; and Eubacterium lentum ATCC 43055, 0.125 to 0.5 micrograms/ml. The modal MIC for Clostridium perfringens ATCC 13124 was at or below the lowest concentration of meropenem tested, and no values are recommended.

Bacteria, Anaerobic↗

PubMedDate not supplied

In vitro effects of meropenem and imipenem/cilastatin on some functions of human natural effector cells.

Meropenem, a new carbapenem antibiotic, was assessed to evaluate its effects on some functional parameters of human polymorphonuclear (PMN) and natural killer (NK) cells in comparison with imipenem/cilastatin. Both drugs significantly inhibited PMN phagocytosis and chemotaxis at concentrations of 2,000 and 4,000 microg/ml. They affected PMN microbicidal activity, evaluated against Candida albicans, only at 4,000 microg/ml. A study of the effects of both drugs on peripheral NK populations and the human NK line (NK-92) showed that even at 4,000 microg/ml there was no effect on antitumor activity. These data indicate that meropenem can reduce some PMN antimicrobial functions only at very high concentrations like imipenem/cilastatin, whereas no concentration influenced NK activity.

Candida↗

PubMed2003

Use of Monte Carlo simulation to design an optimized pharmacodynamic dosing strategy for meropenem.

Prolonging the infusion of meropenem over 3 hours increases the percentage of the dosing interval that drug concentrations remain above the minimum inhibitory concentration (MIC), thereby maximizing the pharmacodynamics of this agent and adhering to drug stability constraints. Monte Carlo simulation was employed to determine pharmacodynamic target attainment rates for several prolonged infusion (PI) meropenem dosage regimens as compared with the traditional 30-minute infusion (TI) against Enterobacteriaceae, Acinetobacter species, and Pseudomonas aeruginosa populations. Percent time above the MIC (%T>MIC) exposures for 1000 mg TI q8h, 2000 mg TI q8h, 500 mg PI q8h, 1000 mg PI q12h, 1000 mg PI q8h, 2000 mg PI q12h, and 2000 mg PI q8h were simulated for 10,000 subjects. Variability in pharmacokinetic parameters and MIC distributions were derived from studies in healthy volunteers and the MYSTIC surveillance program, respectively. The probabilities of attaining bacteriostatic (30% T>MIC) and bactericidal (50% T>MIC) exposures were high for all dosage regimens against populations of Enterobacteriaceae. Against Acinetobacter species and Pseudomonas aeruginosa, the 2000-mg PI q8h dosage regimen provided the highest target attainment rates. For mild to moderate infections caused by Enterobacteriaceae, prolonged infusion regimens of 500 mg PI q8h and 1000 mg PI q12h would provide equivalent target attainment rates to the traditional 30-minute infusion while requiring less drug over 24 hours. For more serious infections presumably caused by Acinetobacter species or Pseudomonas aeruginosa, a dose of 2000 mg PI q8h is recommended because of its high bactericidal target attainment rate against these pathogens. Further study of these dosage recommendations in clinical trials is suggested.

Acinetobacter Infections↗

PubMed2001

Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.

Infection remains the major cause of morbidity and mortality in immunocompromised children with malignancy. In addition, the economic impact of antibiotic treatment should always be evaluated, especially in developing countries. In our center between January 1998 and January 1999, 73 children with hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)]; 9 children with solid tumors (rhabdomyosarcoma, neuroblastoma) had 87 febrile neutropenic episodes (related to chemotherapy). These children were randomized prospectively into three treatment groups. The first group (n: 28) received cefepime plus netilmicin, while the second group (n: 29) was treated with ceftazidime plus amikacin and the third (n: 30) with meropenem as monotherapy. The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin, which is the standard therapy for febrile neutropenia. Microbiologically documented infections were 29.9%, clinically documented infections were 9.2% and 60.9% of the febrile neutropenic episodes were considered to be FUO. Gram-positive microorganisms were the most commonly isolated agents from blood cultures [MRSA (Methicillin Resistant Staphylococcus aureus) in 6 patients and MSSA (Methicillin Sensitive Staphylococcus aureus) in 4 patients]. The success rates were 78.5%, 79.3% and 73.3 % for the 1st, 2nd and 3rd groups respectively. In 4 patients (4.5%) fever responded only to amphotericin-B therapy. There was no statistically significant difference between the three treatment regimens with respect to efficacy, safety and tolerance (chi2 test, p>0.05), but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost, the monotherapy regimen was the most expensive. The main determining factors for the choice of treatment of febrile neutropenic children, especially in a developing country, are cost, presence of indwelling catheter and the bacterial flora of the unit, as well as efficacy.

Adolescent↗

PubMed1995

Stability of a 1 beta-methylcarbapenem antibiotic, meropenem (SM-7338) in aqueous solution.

The stability and the degradation products of 1 beta-methylcarbapenem, meropenem in aqueous solution were investigated. In pH 4-8 dilute solution, pseudo-first-order degradation was observed, and good stability of meropenem in aqueous solution was demonstrated by the effect of 1 beta-methyl group against hydrolysis of beta-lactam ring. As degradation products, the beta-lactam hydrolyzed product and the dimer product resulting from intermolecular aminolysis of beta-lactam ring by the amine of the second molecule were described.

Anti-Infective Agents↗

PubMed2004

Empiric treatment of multidrug-resistant Burkholderia cepacia lung exacerbation in a patient with cystic fibrosis: application of pharmacodynamic concepts to meropenem therapy.

A 31-year-old man with cystic fibrosis was diagnosed with multidrug-resistant Burkholderia cepacia pneumonia. Meropenem 2000 mg every 8 hours was administered as a 3-hour infusion to maximize pharmacodynamic exposure; oral minocycline 100 mg twice/day was also given. Blood samples were collected to confirm meropenem concentrations. Concentrations above the mimimum inhibitory concentration (MIC) of 8 microg/ml were achieved for 52% of the dosing interval, which is greater than what is required for a bactericidal effect. The patient's condition improved, he was discharged, and completed a 3-week course of the antibiotic regimen. After 6 months, he had remained at his baseline level of health. This case demonstrates that pharmacodynamic principles can be used to design an antibiotic dosing regimen that can achieve optimal exposures when the MIC is above that considered susceptible to conventional dosing strategies.

Adult↗

PubMed2004

Meropenem administered as a prolonged infusion to treat serious gram-negative central nervous system infections.

The treatment of gram-negative infection of the central nervous system (CNS) presents a clinical challenge due to antibiotic resistance and difficulties with penetration into the cerebrospinal fluid (CSF). Two patients with gram-negative CNS infections were treated successfully with high-dose, prolonged infusions of meropenem. The CSF meropenem concentrations exceeded the minimum inhibitory concentration of the pathogen for virtually the entire dosing interval in both cases. Our experience demonstrates that dosage modification to maximize pharmacodynamic targets and bactericidal activity may be practically applied to optimize antibiotic treatment for difficult-to-treat CNS infections.

Adult↗

PubMed2006

A comparison of the in vitro antimicrobial activity of liposomes containing meropenem and gentamicin.

The antimicrobial activity of eight cationic, two neutral and three anionic liposome compositions containing meropenem and gentamicin was tested in vitro in broth and serum medium. The cationic formulations showed better antibacterial efficacy against both Gram-positive and Gram-negative bacteria than the anionic and neutral ones, regardless of the encapsulated drug. The most effective formulations were the cationic PC/DOPE/DOTAP 3:4:3 and PC/Chol/DOTAP 3:4:3, as the MICs with meropenem were 2 to 4 times lower than those of the free drug.

Anti-Bacterial Agents↗

PubMed1999

[Analysis of secretion into the saliva of cefoxitin (Mefoxin), imipenem (Tienam) and meropenem (Meronem)].

The salivary excretion of cefoxitin (Mefoxin), a second-generation beta-lactam antibiotic of the cefalosporin group, which shows enhanced anti-anaerobic effect was investigated in oral surgery patients. In animal experiments the saliva levels of imipenem (Tienam) and meropenem (Meronem), which also belong to the betalactam carbapenem group were studied. The antibiotics were administered parenterally in single therapeutic doses, then blood samples were taken first after half an hour then hourly, and mixed saliva was collected for 6 hours. Cefoxitin was found to reach top level in the 1st hour, then this level decreased rapidly, and in the 4th hour it was no longer measurable. Out of the carbapenems imipenem showed highest level in the 2nd hour and in the 4th hour its concentration in the saliva was minimal. Meropenem reached a higher level in the saliva (1,5-2 times higher than the serum level) in the 2nd hour after administration, which persisted even in the 6th hour. The experimental results justify the administration of these antibiotics in dentistry and oral surgery.

Adult↗

PubMed2000

Detection of emerging resistance patterns within longitudinal surveillance systems: data sensitivity and microbial susceptibility. MYSTIC Advisory Board. Meropenem Yearly Susceptibility Test Information Collection.

Communicating information from antimicrobial resistance surveillance study data to microbiologists and physicians can be challenging. Large amounts of data, commonly reaching millions of MICs or zone diameter endpoints, must be analysed and condensed to easily-read tables or figures. Furthermore, data must not be prejudged relative to susceptibility categories, because of the diverse nature of interpretive criteria available internationally. An attempt must be made to present results of all surveillance studies in a mode that can be reinterpreted for immediate use in different geographical areas, or used to compare future data with relative ease and high accuracy. Such data displays require peer-reviewed journals to permit greater numbers of more complex tables to present results. The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) study is a year-on-year global surveillance programme in medical centres where meropenem is available for use. We have developed a presentation strategy that expands the long-term clinical value of MYSTIC results. In addition to statistical parameters, tables of cumulative percentages or numbers of strains inhibited at each tested antimicrobial concentration will be presented. Alternative figures (Finland-o-grams) could also be used, but these generally lack precise extractable rates and require more journal space. Regardless of study design, promotion of this presentation philosophy enhances any surveillance study's value to each reader or user and facilitates application to locally appropriate interpretations. The widespread use of these analysis and presentation principles as benchmarks by various resistance studies and networks is strongly encouraged, particularly by investigations across international boundaries.

Anti-Bacterial Agents↗

PubMed2001

Rapid antibiotic drug monitoring: meropenem and ceftazidime determination in serum and bronchial secretions by high-performance liquid chromatography-integrated sample preparation.

A sensitive and rapid HPLC assay for the determination of the beta-lactam antibiotics ceftazidime and meropenem in serum and bronchial secretions is described. HPLC-integrated sample preparation allows direct injection of serum samples without any pretreatment. Sputum samples need only a simple homogenisation and volume measurement but no liquefying reagents are necessary. The inline extraction technique is realized by automatically switching from the extraction column to the analytical column. After the matrix passed the extraction column, the retained analyte is quantitatively transferred to the analytical column where separation by isocratic HPLC is performed. Ceftazidime and meropenem are detected according to their absorption maxima at 258 and 296 nm, respectively. The detection limit of both antibiotics is estimated to be better than 0.5 microg/ml in serum as well as in sputum samples. The described procedure allows determination of the antibiotics within 30-45 min, thereby facilitating drug monitoring in clinical routine.

Bronchi↗

PubMedDate not supplied

[In vitro antibacterial activity and beta-lactamase stability of meropenem].

The comparative activity of meropenem with that of imipenem, cefotaxime, ceftriaxone and ceftazidime against 856 gram-negative bacilli was studied studied by an agar dilution method. Meropenem and imipenem were high active against tested strains. Resistance to third generation cephalosporins was high for most microorganisms tested. For rapid detection of metallo-beta-lactamase (MBL)-producing gram-negative bacilli a simple disk diffusion test was used. EDTA, FeCl2 and CuCl2 were evaluated as IMP-1 inhibitors. The method is helpful for screening of IMP-1 producers in daily clinical activity.

Anti-Bacterial Agents↗

PubMed2005

An outbreak of SHV-5 producing Klebsiella pneumoniae in a neonatal intensive care unit; meropenem failed to avoid fecal colonization.

An outbreak of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae (ESBL-Kp) in a neonatal intensive care unit prompted a prospective surveillance study between 12th September and 6th October 2003. Surveillance was carried out by obtaining stool samples twice a week. The DNA relatedness of the isolates was shown by random amplified polymorphic DNA comparison (ERIC-PCR). ESBL production was identified by clavulanate synergy, isoelectric focusing, PCR and sequence analysis. During the study period, 49 neonates were hospitalized in the neonatal intensive care unit (NICU). In the first 20-day period, five neonates were infected with ESBL-Kp. The first patient treated with third generation cephalosporin and the second patient treated with meropenem died. While all three infected survivors were clinically improving, the digestive tracts were being colonized by SHV-5 producing Klebsiella. In the next period of the study, five neonates were colonized by ESBL-Kp as well. Univariate comparison of risk factors between colonized and non-colonized neonates was not significant. A total of 24 colonally related ESBL-Kp have been recovered from clinical materials and stool samples. This study demonstrated that parenterally applied meropenem, though successful in treating the systemic illness, might fail to protect the digestive tract from colonization of ESBL-Kp.

Anti-Bacterial Agents↗

PubMed2006

Colistin, meropenem and rifampin in a combination therapy for multi-drug-resistant Acinetobacter baumannii multifocal infection. A case report.

A 16 year-old girl underwent a multifocal (lungs, skin, soft tissues) infection due to multiresistant Acinetobacter baumannii after a car crash. To treat such a severe disease we used a combination therapy of colistin (2 millions Units twice/day), rifampicin (600 mg/day), meropenem (1 g 3 times a day) after a synergistic activity test was performed (checkerboard method on Mueller-Hinton broth and 5x10(5) cfu/mL inoculum). After 24 days, when a significant clinical improvement was gained, the 3-drugs combination therapy was replaced with i.v. levofloxacin 500 mg twice/day but, after 10 days of quinolones therapy, fever started again and the same multidrug resistant (MDR) A. baumannii was isolated from the skin grafts, central venous catheter tip and bronchial alveolar lavage. A combination therapy with colistin and meropenem was therefore started and definitive defervescence was obtained after 10 days. This therapy was continued for 70 days even if the patient was apyretic because A. baumannii was still present in the skin secretions. After 109 days of hospitalization in our intensive care unit, the patient was transferred to a rehabilitative unit. This case shows how useful is, in selected cases, rediscovering old antibiotic drugs, specially when they are adopted as a combination therapy, and highlights the importance of the clinical microbiological laboratory as it may help clinicians in choosing the best drugs combination.

Accidents, Traffic↗

PubMed1995

[Multicenter comparative study of meropenem, a new carbapenemic preparation, administered intramuscularly. Treatment of respiratory and urinary infections in hospitalized patients]l.

263 hospitalized patients were enrolled in a multicentre study to assess efficacy and safety of i. m. meropenem, compared to ceftazidime, in the treatment of lower respiratory tract infections and urinary infections as well. Meropenem, administered at a dose of 500 mg tid, was therapeutically equivalent to the reference agent (1000 mg tid in RTI's and 500 mg tid in UTI's) in both indications. The two treatments were well tolerated, without any serious local or systemic side effect.

Adult↗

PubMed1996

[In vitro study of the bacteriostatic and bactericidal activity of meropenem against strains of Pseudomonas aeruginosa multiresistant to antibiotics].

Meropenem is a new dehydropeptidase stable carbapenem which has an in vitro bacteriostatic activity superior to imipenem against Pseudomonas aeruginosa. Minimal inhibitory concentrations of meropenem (MEM) and imipenem (IPM) were determined on twelve strains: two were genetically characterized reference strains and ten isolated from patients. Killing curves were performed for MEM used at 1,2 and 4 fold the MIC and 32 mg/l; survivors were counted at baseline and after 5 and 24 hours of incubation by spiral plating. Five strains were susceptible to MEM and IPM; five were intermediate and two resistant to MEM; these seven strains were resistant to IPM. A weak bactericidal effect was obtained after 5 h at each concentration. Only one strain achieved a 3 log 10 reduction after 5 h at 2 x MIC. A regrowth of all the strains tested was observed after 24 h.

Dose-Response Relationship, Drug↗

PubMed1997

[Meropenem in the treatment of surgical intra-abdominal infections].

Intraabdominal infections are severe with a high morbidity and mortality which may be produced by multiple causes: perforation of the empty viscera, intestinal inflammatory processes, vascular pictures, abdominal traumatisms as a consequence of surgery. From a microbiologic point of view, different types of gram positive and gram negative aerobes such as anaerobe microorganisms or fungi may be isolated as causes. Polymicrobial infections are usually observed. The main treatment policy is to correctly eliminate the causing foci of the bacterial contamination whether surgically of by percutaneous drainage. Parallelly, it is essential for the surgeon to use appropriate antibiotic treatment. Meropenem, a carbapenem, has a wide spectrum antibacterial activity which cover gram positive and gram negative aerobes in addition to anaerobes leading to scarce adverse reactions. All the above leads meropenem to be a very effective alternative in both the treatment of these infections as monotherapy and for initiating empiric therapy.

Abdomen↗

PubMed1997

[Successful meropenem therapy of recurrent multiple brain abscess].

Authors describe the history of a 37-year-old man suffering from multiple purulent brain abscess. The multiple brain abscess evolved primarily from a gluteal abscess to the lung, and secondarily from the lung to the brain by hematogenous spreading of the bacteria. The identification of the pathogene/s was unsuccessful despite numerous bacteriological examination. Despite many regimens of empiric antibacterial therapy the brain abscesses progressed, neurologic state of the patient deteriorated. At long last, the patient was given chloramphenicol. After that, he had no more fever, his consciousness cleared, no more epileptic convulsion occurred and the cell number of the cerebrospinal fluid became normal. The patient was thought to be cured and was sent home. Two months later fever occurred again and it was accompanied by excrutiating headache, increasing disorientation, so the patient was admitted to the hospital. The occurrence of a new brain abscess and purulent meningitis indicated the relapse of the disease. It was again unsuccessful to identify the pathogene/s therefore the authors treated the patient with many empiric antibiotic regimen, all of which-including chloramphenicol too--proved to be uneffective. As all the therapeutic regimens usually used in the treatment of purulent brain abscess were uneffective--including the combinations which have the widest antibacterial spectrum, authors gave meropenem as ultimum refugium. Some days later the fever came to an end, his consciousness cleared, the brain pressure and the cerebrospinal fluid became normal. The patient had no serious complaints in the course of the four years follow up, his residual neurologic symptoms regressed. On the base of this case history, authors suppose that meropenem--which has already proved to have a very wide antibacterial spectrum and to be very effective in the therapy of many kinds of serious bacterial infections--could also become a promising new therapeutic alternative in the treatment of purulent brain abscess.

Adult↗