meropenem mechanism of action

[1] Serious side effects include Clostridium difficile infection, seizures, and allergic reactions including anaphylaxis. Probenecid competes with Meropenem for active tubular secretion, resulting in increased plasma concentrations of Meropenem. 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. When treating complicated skin and skin structure infections caused by P.aeruginosa, a dose of 1 gram every 8 hours is recommended. The overall spectrum is similar to that of imipenem, although meropenem is more active against Enterobacteriaceae and less active against Gram-positive bacteria. What is the mechanisms of action of carbapenems? It works against extended-spectrum β-lactamases, but may be more susceptible to metallo-β-lactamases. Meropenem is a substrate of OAT1 and OAT3 transporters in the proximal tubule of the kidney, and probenecid is an inhibitor of these drug transporters. Peptostreptococcus species. The following Table shows the degree of hearing loss between the Meropenem-treated patients and the comparator-treated patients. [1] It is on the World Health Organization's List of Essential Medicines. 12.4 Microbiology. [7], As with other ß-lactams antibiotics, the effectiveness of treatment depends on the amount of time during the dosing interval that the meropenem concentration is above the minimum inhibitory concentration for the bacteria causing the infection. Savior Lifetec Corporation 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). Its strongest affinities are toward PBPs 2, 3 and 4 of Escherichia coli a… This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Eggerthella lenta, Fusobacterium species Meropenem and its metabolite are readily dialyzable and effectively removed by hemodialysis; however, no information is available on the use of hemodialysis to treat overdosage. At this dosage, no adverse pharmacological effects or increased safety risks have been observed. Consider symptomatic treatments. Meropenem prevents bacteria from forming the walls that surround them. Each 500 mg Meropenem for injection vial will deliver 500 mg Meropenem and 45.1 mg of sodium as sodium carbonate (1.96 mEq) [see Dosage and Administration (2.4)]. The values represent the number of patients clinically cured/number of clinically evaluable patients, with the percent cure in parentheses. In the seriously ill patient population, it was not possible to determine the relationship between observed adverse events and therapy with Meropenem. Meropenem for injection has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis. It is similar to impenem and cilastin . Dosage adjustment is necessary in patients with creatinine clearance 50 mL/min or less [see Dosage and Administration (2.2), Warnings and Precautions (5.8), Clinical Pharmacology (12.3)]. Klebsiella pneumoniae The trial was conducted in the United States, South Africa, Canada, and Brazil. Intentional overdosing of Meropenem is unlikely, although accidental overdosing might occur if large doses are given to patients with reduced renal function. It inhibits bacterial cell wall synthesis like other β-lactam antibiotics. The adverse reactions seen in these patients that were reported and their rates of occurrence are as follows: Adverse Laboratory Changes in Pediatric Patients: Laboratory changes seen in the pediatric studies, including the meningitis studies, were similar to those reported in the adult studies. Table 8: Clinical Efficacy Rate by Pathogen for Clinically Evaluable Population, Staphylococcus aureus, methicillin susceptible. Urinary concentrations of Meropenem in excess of 10 mcg/mL are maintained for up to 5 hours after a 500 mg dose. 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%). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In a peri-postnatal study in rats described in the published literature 2, intravenous Meropenem was administered to dams from Gestation Day 17 until Lactation Day 21 at doses of 240, 500, and 1000 mg/kg/day. Meropenem is an antibacterial drug [see Microbiology (12.4)]. Streptococcus agalactiae DrugBank Meropenem Anhydrous is the anhydrous form of meropenem, a broad-spectrum carbapenem with antibacterial properties, synthetic Meropenem inhibits cell wall synthesis in gram-positive and gram-negative bacteria. Use of Meropenem in pediatric patients 3 months of age and older with bacterial meningitis is supported by evidence from adequate and well-controlled studies in the pediatric population [see Indications and Usage (1.3), Dosage and Administration (2.3), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.3)]. However, as their use increases and expands into new patient populations, the rate of seizures with these agents may increase. If superinfection does occur during therapy, appropriate measures should be taken. 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) ]. Freshly prepared solutions of Meropenem for injection should be used. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid. Blood and Lymphatic System Disorders: agranulocytosis, neutropenia, and leukopenia; a positive direct or indirect Coombs test, and hemolytic anemia. Bacteroides uniformis Streptococcus pyogenes To reduce the development of drug-resistant bacteria and maintain the effectiveness of Meropenem for injection and other antibacterial drugs, Meropenem for injection should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. 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). [2] It was approved for medical use in the United States in 1996. Clostridium perfringens Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. There are several mechanisms of resistance to carbapenems: 1) decreased permeability of the outer membrane of gram-negative bacteria (due to diminished production of porins) causing reduced bacterial uptake, 2) reduced affinity of the target PBPs, 3) increased expression of efflux pump components, and 4) production of antibacterial drug-destroying enzymes (carbapenemases, metallo-β-lactamases). Meropenem penetrates the cell wall of most gram-positive and gram-negative bacteria to bind penicillin-binding-protein (PBP) targets. [3] The World Health Organization classifies meropenem as critically important for human medicine.[4]. From: Side Effects of … If you are allergic to meropenem; any part of meropenem; or any other drugs, foods, or substances. Subscribe to newsletters for the latest medication news, new drug approvals, alerts and updates. Peak tissue time: 1 hr after infusion. (See dosing Table below.). Pediatric Patients (Neonates and Infants less than 3 months of Age): Meropenem was studied in 200 neonates and infants less than 3 months of age. Meropenem for injection is indicated for the treatment of complicated skin and skin structure infections (cSSSI) due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis (vancomycin-susceptible isolates only), Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus species . The walls are necessary to protect bacteria from their environment and to keep the contents of the bacterial cell together. Two hundred and sixty one (261) patients randomized to Meropenem and 287 patients randomized to imipenem-cilastatin were clinically evaluable. 3. Table 5: Meropenem Concentrations in Selected Tissues (Highest Concentrations Reported). The following in vitro data are available, but their clinical significance is unknown. The recommended dose of Meropenem for injection is 500 mg given every 8 hours for skin and skin structure infections and 1 gram given every 8 hours for intra-abdominal infections. The clinical efficacy rates by pathogen are provided in Table 8. Proteus mirabilis The background risk of major birth defects and miscarriage for the indicated population is unknown. When treating cSSSI caused by P. aeruginosa, a dose of 20 mg/kg (or 1 gram for pediatric patients weighing over 50 kg) every 8 hours is recommended. Neisseria meningitidis The following adverse reaction frequencies were derived from the clinical trials in the 2904 patients treated with Meropenem. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. Its molecular formula is C22H24N3O7SNa and MW is 497.50.The chemical structure is: Bloodstream Infections. The safety and effectiveness of Meropenem have been established for pediatric patients 3 months of age and older with complicated skin and skin structure infections and bacterial meningitis, and for pediatric patients of all ages with complicated intra-abdominal infections. Bacteroides fragilis In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Meropenem, from the carbapenem class, is effective against most gram-positive, gram-negative, anaerobic, and even extended beta-lactamase–producing bacteria and has good CSF penetration. ... -Meningitis - meropenem-If Pseudomonas is known or suspected - NOT ertapenem. 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%). provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. To compare and contrast imipenem and meropenem in terms of in vitro activity, pharmacokinetics, clinical efficacy and adverse effects. The following adverse reactions have been identified during post-approval use of Meropenem. The concomitant use of Meropenem and valproic acid or divalproex sodium is generally not recommended. Meropenem is a carbapenem antibiotic for parenteral use that exerts its action by interfering with bacterial wall synthesis. Three controlled clinical studies of complicated intra-abdominal infections were performed in Europe; Meropenem was compared with imipenem (two trials) and cefotaxime/metronidazole (one trial). [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]. Dosage should be reduced in patients with creatinine clearance of 50 mL/min or less. A similar trend was also seen in the cUTI trial. It is active against Gram-positive and Gram-negative bacteria. Meropenem is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. The NOAEL value was considered to be 1000 mg/kg/day (approximately 3.2 times the MRHD based on body surface area comparisons). Mechanism of Action: Cause rapid bacterial cell death by covalently binding to penicillin-binding proteins (PBPs) involved in the biosynthesis of mucopeptides in bacterial cell walls. 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. Mechanism of Action. Meropenem, sold under the brandname Merrem among others, is a broad-spectrum antibiotic used to treat a variety of bacterial infections. The study was open-label, uncontrolled, 98% of the infants received concomitant medications, and the majority of adverse events were reported in neonates less than 32 weeks gestational age and critically ill at baseline, making it difficult to assess the relationship of the adverse events to Meropenem. Single dose clear glass vials of Meropenem for injection containing 500 mg or 1 gram (as the trihydrate blended with anhydrous sodium carbonate for re-constitution) of sterile Meropenem powder. For meropenem, doripenem, and ertapenem, the seizure rate for each agent is reported as less than 1%. Mechanism Of Action. Worldwide post-marketing adverse reactions not otherwise listed in the Adverse Reactions from Clinical Trials section of this prescribing information and reported as possibly, probably, or definitely drug related are listed within each body system in order of decreasing severity. Re-constitute injection vials (500 mg and 1 gram) with sterile Water for Injection (see Table 4 below). It inhibits bacterial cell wall synthesis like other β-lactam antibiotics. 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. The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Data sources include IBM Watson Micromedex (updated 2 Nov 2020), Cerner Multum™ (updated 2 Nov 2020), ASHP (updated 23 Oct 2020) and others. The bactericidal activity … If an allergic reaction to Meropenem occurs, discontinue the drug immediately. No information is available on the effects of Meropenem on the breast-fed child or on milk production. Haemophilus influenzae In vitro tests show Meropenem to act synergistically with aminoglycoside antibacterial drugs against some isolates of Pseudomonas aeruginosa. Dosing must be adjusted for altered kidney function and for haemofiltration. It inhibits cell wall synthesis by binding to several penicillin-binding proteins, resulting in defective cell walls & osmotically unstable organisms susceptible to cell lysis. In patients with renal impairment, thrombocytopenia has been observed but no clinical bleeding reported [see Dosage and Administration (2.2), Adverse Reactions (6.1), Use In Specific Populations (8.5), (8.6), Clinical Pharmacology (12.3)]. At enrollment, approximately 37% of the patients had underlying diabetes, 12% had underlying peripheral vascular disease and 67% had a surgical intervention. Meropenem is hemodialyzable. One controlled clinical study of complicated intra-abdominal infection was performed in the United States where Meropenem was compared with clindamycin/tobramycin. Adverse events with an incidence of greater than 1%, and not listed above, include: pharyngitis, accidental injury, gastrointestinal disorder, hypoglycemia, peripheral vascular disorder, and pneumonia. Meropenem is an injectable carbapenem antibiotic. Table 1: Recommended Meropenem for Injection Dosage Schedule for Adult Patients with Renal Impairment, Recommended dose (500 mg cSSSI and 1 gram Intra-abdominal). Pasteurella multocida Meropenem readily penetrates the cell wall of most gram-positive and gram-negative bacteria to bind penicillin-binding-protein (PBP) targets. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. Medically reviewed by Doripenem has high affinity for PBP2 and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli [9]. Gram-positive bacteria A 55-year-old, 102kg Caucasian male, with a history of seizures andmultiple sclerosis, complicated by quadriplegia and dysphagia, wastransferred to Veteran Affairs Medical Centre in Long Beach,California, for the treatment of urosepsis, Clostridium difficile colitis and aspiration pneumonia (sputum samples had tested positive for Klebsiella spp and Pseudomonas spp). The largest dose of Meropenem administered in clinical trials has been 2 grams given intravenously every 8 hours. Meropenem for injection is a sterile, pyrogen-free, synthetic, carbapenem antibacterial for intravenous administration. The measured renal clearance and the effect of probenecid show that Meropenem undergoes both filtration and tubular secretion. The bactericidal action of meropenem results from the inhibition of cell wall synthesis. The study included 510 patients randomized to Meropenem and 527 patients randomized to imipenem-cilastatin. A 2014 study looked at cross-reaction between carbapenems and … Meropenem is soluble in 5% monobasic potassium phosphate solution, sparingly soluble in water, very slightly soluble in hydrated ethanol, and practically insoluble in acetone or ether.

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