meropenem mechanism of action
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Streptococcus agalactiae The trial was conducted in the United States, South Africa, Canada, and Brazil. If you are taking any of these drugs: Divalproex or valproic acid. Meropenem has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)]. The dry powder should be stored at controlled room temperature 20º to 25ºC (68º to 77ºF) [see USP]. [8] For ß-lactams, including meropenem, prolonged intravenous administration is associated with lower mortality than bolus intravenous infusion in persons with whose infections are severe, or caused by bacteria that are less sensitive to meropenem, such as Pseudomonas aeruginosa.[8][9]. Mechanism of Action. Five patients were found to be bacteriologically not cured, 3 in the comparator group (1 relapse and 2 patients with cerebral abscesses) and 2 in the Meropenem group (1 relapse and 1 with continued growth of Pseudomonas aeruginosa). Of the total number of subjects in clinical studies of Meropenem, approximately 1100 (30%) were 65 years of age and older, while 400 (11%) were 75 years and older. Increasing the dose of valproic acid or divalproex sodium may not be sufficient to overcome this interaction. Freshly prepared solutions of Meropenem for injection should be used. Porphyromonas asaccharolytica Moraxella catarrhalis [15][16], O=C3N2\C(=C(\S[C@H]1C[C@@H](C(=O)N(C)C)NC1)[C@H](C)[C@@H]2[C@H]3[C@H](O)C)C(=O)O, InChI=1S/C17H25N3O5S/c1-7-12-11(8(2)21)16(23)20(12)13(17(24)25)14(7)26-9-5-10(18-6-9)15(22)19(3)4/h7-12,18,21H,5-6H2,1-4H3,(H,24,25)/t7-,8-,9+,10+,11-,12-/m1/s1, World Health Organization's List of Essential Medicines, "Press Announcements - FDA approves new antibacterial drug", "Meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration", "Clinical outcomes of prolonged infusion (extended infusion or continuous infusion) versus intermittent bolus of meropenem in severe infection: A meta-analysis", "Pancytopenýa and Sepsýs due to Meropenem: A Case Report", "Meropenem side effects - from FDA reports", "Meropenem in critical care - uncovering the truths behind weaning failure", "New molecule knocks out superbugs' immunity to antibiotics", "Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo", https://en.wikipedia.org/w/index.php?title=Meropenem&oldid=991775996, World Health Organization essential medicines, Drugboxes which contain changes to watched fields, Wikipedia medicine articles ready to translate, Creative Commons Attribution-ShareAlike License, This page was last edited on 1 December 2020, at 19:34. Table 10: Efficacy rates by Pathogen in the Clinically Evaluable Population with Bacterial Meningitis. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University.. Probenecid competes with Meropenem for active tubular secretion and thus inhibits the renal excretion of Meropenem. However, as their use increases and expands into new patient populations, the rate of seizures with these agents may increase. In fertility studies, intravenous Meropenem was administered to male rats beginning 11 weeks before mating and throughout mating and to female rats from 2 weeks before mating through Gestation Day 7 at doses of 240, 500, and 1000 mg/kg/day. Compatibility of Meropenem for injection with other drugs has not been established. The most common adverse events occurring in greater than 5% of the patients were: headache (7.8%), nausea (7.8%), constipation (7.0%), diarrhea (7.0%), anemia (5.5%), and pain (5.1%). There was no evidence of mutagenic potential found in any of these tests. [1] It is on the World Health Organization's List of Essential Medicines. Its structural formula is: Meropenem for injection is a white to pale yellow crystalline powder. Enterococcus faecalis (vancomycin-susceptible isolates only) ... -Meningitis - meropenem-If Pseudomonas is known or suspected - NOT ertapenem. The following adverse reactions have been identified during post-approval use of Meropenem. They inhibit bacterial cell wall synthesis by binding to one or more penicillin-binding proteins (PBP's) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls. Local adverse events that were reported with Meropenem were as follows: Systemic adverse events that were reported with Meropenem occurring in greater than 1.0% of the patients were diarrhea (4.8%), nausea/vomiting (3.6%), headache (2.3%), rash (1.9%), sepsis (1.6%), constipation (1.4%), apnea (1.3%), shock (1.2%), and pruritus (1.2%). Prescribing Meropenem in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. In general, resistance arises due to mutations in penicillin-binding proteins, production of metallo-β-lactamases, or resistance to diffusion across the bacterial outer membrane. If superinfection does occur during therapy, appropriate measures should be taken. These reactions are more likely to occur in individuals with a history of sensitivity to multiple allergens. [10] Many of these adverse effects were observed in severely ill individuals already taking many medications including vancomycin. Mechanism of Action. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. Several cases of severe hypokalemia have been reported. Solutions prepared for infusion (Meropenem for injection concentrations ranging from 1 mg/mL to 20 mg/mL) re-constituted with Dextrose Injection 5% should be used immediately. Additional systemic adverse events that were reported with Meropenem and occurring in less than or equal to 1.0% but greater than 0.1% of the patients are listed below within each body system in order of decreasing frequency: Bleeding events were seen as follows: gastrointestinal hemorrhage (0.5%), melena (0.3%), epistaxis (0.2%), hemoperitoneum (0.2%). Mechanism of Action: Meropenem is a structural analog of impipenem that is resistant to cleavage by renal dehydropeptidase I. Fecal elimination represents only approximately 2% of the dose. The elimination half-life for Meropenem was approximately 1.5 hours in pediatric patients of age 3 months to 2 years. Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death. [1] Use in pregnancy appears to be safe. The NOAEL value was considered to be 1000 mg/kg/day (approximately 3.2 times the MRHD based on body surface area comparisons). Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. During clinical investigations, 2904 immunocompetent adult patients were treated for non-CNS infections with the overall seizure rate being 0.7% (based on 20 patients with this adverse event). When treating complicated skin and skin structure infections caused by P.aeruginosa, a dose of 1 gram every 8 hours is recommended. Severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalized exanthematous pustulosis (AGEP) have been reported in patients receiving Meropenem [see Adverse Reactions (6.2) ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Chemistry and Mechanism of Action Meropenem. There is one metabolite of Meropenem that is microbiologically inactive. Meropenem is a carbapenem antibiotic for parenteral use that exerts its action by interfering with bacterial wall synthesis. The values represent the number of patients clinically cured/number of clinically evaluable patients at the post-treatment follow-up visit, with the percent cure in parentheses (Fully Evaluable analysis set). Clostridium perfringens Meropenem for injection is indicated for the treatment of complicated appendicitis and peritonitis caused by viridans group streptococci, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus species . 2 g IV every 8 hours is recommended by clinical practice guidelines as a treatment option for empiric or documented meningitis. Meropenem has a niche in its spectrum of coverage. Before initiating therapy with Meropenem, it is important to inquire about previous hypersensitivity reactions to penicillins, cephalosporins, other β-lactams, and other allergens. Consider symptomatic treatments. The carbapenem class of antibiotics have in common a carbon atom substituted for sulfur at position 1 and an unsaturated bond between C2 and C3 of the familiar penicillin nucleus (Figure 1). Following intravenous doses of 500 mg, mean plasma concentrations of Meropenem usually decline to approximately 1 mcg/mL at 6 hours after administration. Doses of 1 gram may also be administered as an intravenous bolus injection (5 mL to 20 mL) over approximately 3 minutes to 5 minutes. For patients with varying degrees of renal impairment, the incidence of heart failure, kidney failure, seizure and shock reported with Meropenem, increased in patients with moderately severe renal impairment (creatinine clearance 10 to 26 mL/min) [see Dosage and Administration (2.2), Warnings and Precautions (5.9), Use in Specific Populations (8.5), (8.6), Clinical Pharmacology (12.3)]. A 5-minute intravenous bolus injection of Meropenem for injection in healthy volunteers results in mean peak plasma concentrations of approximately 45 mcg/mL (range 18 to 65) for the 500 mg dose and 112 mcg/mL (range 83 to 140) for the 1 gram dose. 12 & 16, Chuangye Rd., Xinshi Dist., Tainan City 74144, Taiwan for With respect to hearing loss, 263 of the 271 evaluable patients had at least one hearing test performed post-therapy. [3] The World Health Organization classifies meropenem as critically important for human medicine.[4]. It inhibits bacterial cell wall synthesis like other β-lactam antibiotics. Approximate Average Concentration (mg/mL), Table 6: Meropenem Pharmacokinetic Parameters in Patients Less Than 3 Months of Age, GA less than 32 weeks PNA less than 2 weeks, GA less than 32 weeks PNA 2 weeks or older, GA 32 weeks or older PNA less than 2 weeks, GA 32 weeks or older PNA 2 weeks or older, Escherichia coli and Pseudomonas aeruginosa, Campylobacter jejuni Citrobacter freundii, Degree of Hearing Loss (in one or both ears), We comply with the HONcode standard for trustworthy health information -, Savior Lifetec Corporation Tainin Branch Injection Plant. If signs and symptoms suggestive of these reactions appear, Meropenem should be withdrawn immediately and an alternative treatment should be considered. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Four hundred forty-six patients (397 pediatric patients 3 months to less than 17 years of age) were enrolled in 4 separate clinical trials and randomized to treatment with Meropenem (n=225) at a dose of 40 mg/kg every 8 hours or a comparator drug, i.e., cefotaxime (n=187) or ceftriaxone (n=34), at the approved dosing regimens. Table 11: Hearing Loss at Post-Therapy in the Evaluable Population Treated with Meropenem. Meropenem is an antibacterial drug [see Microbiology (12.4)].
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