The medical need for compounds with broad-spectrum activity, rapid bactericidal action, limited resistance-promoting properties and good tolerability has been met with carbapenem compounds. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. Pharmacokinetic studies with Meropenem in patients with renal impairment have shown that the plasma clearance of Meropenem correlates with creatinine clearance. [1] Serious side effects include Clostridium difficile infection, seizures, and allergic reactions including anaphylaxis. Meropenem for injection is indicated for the treatment of bacterial meningitis caused by Haemophilus influenzae, and Neisseria meningitidis and penicillin-susceptible isolates of Streptococcus pneumoniae. Meropenem for injection is a sterile, pyrogen-free, synthetic, carbapenem antibacterial for intravenous administration. The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. 2 g IV every 8 hours is recommended by clinical practice guidelines as a treatment option for empiric or documented meningitis. The pharmacokinetics of Meropenem, in pediatric patients 2 years of age or older, are similar to those in adults. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: agranulocytosis, neutropenia, and leukopenia; a positive direct or indirect Coombs test, and hemolytic anemia. 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 . Neisseria meningitidis and penicillin-susceptible isolates of Streptococcus pneumoniae. Meropenem for injection is supplied in 20 mL and 30 mL injection vials containing sufficient Meropenem to deliver 500 mg or 1 gram for intravenous administration, respectively. The types of systemic and local adverse events seen in these patients are similar to the adults, with the most common adverse reactions reported as possibly, probably, or definitely related to Meropenem and their rates of occurrence as follows: In the meningitis studies, the rates of seizure activity during therapy were comparable between patients with no CNS abnormalities who received Meropenem and those who received comparator agents (either cefotaxime or ceftriaxone). Porphyromonas asaccharolytica [1] It is more resistant to breakdown by β-lactamase producing bacteria. Bacteroides ureolyticus He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. However, there is no information on the usefulness of hemodialysis to treat overdosage [see Overdosage (10)]. The solution varies from colorless to yellow depending on the concentration. Its molecular formula is C22H24N3O7SNa and MW is 497.50.The chemical structure is: The bactericidal activity of meropenem results from the inhibition of cell wall synthesis. Meropenem is bactericidal except against Listeria monocytogenes, where it is bacteriostatic. 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). Review the mechanism of action of ZERBAXA® (ceftolozane and tazobactam), which demonstrated in vitro activity in the presence of certain mechanisms of resistance. Escherichia coli There are insufficient human data to establish whether there is a drug-associated risk of major birth defects or miscarriages with Meropenem in pregnant women. The study evaluated Meropenem at doses of 500 mg administered intravenously every 8 hours and imipenem-cilastatin at doses of 500 mg administered intravenously every 8 hours. Meropenem is the only carbapenem approved for meningitis, for which it can be used as alternative therapy. Gram-positive bacteria Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Meropenem, and may range in severity from mild diarrhea to fatal colitis. 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. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Case reports in the literature have shown that co-administration of carbapenems, including Meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The meropenem component of VABOMERE is a penem antibacterial drug. Meropenem penetrates the cell wall of most gram-positive and gram-negative bacteria to bind penicillin-binding-protein (PBP) targets. Discard unused portion, For Intravenous Use Only The concomitant use of Meropenem and valproic acid or divalproex sodium is generally not recommended. This inactivates the PBPs, leading to a weakened cell wall, which eventually ruptures because of osmotic pressure forces [8]. Increasing the dose of valproic acid or divalproex sodium may not be sufficient to overcome this interaction. For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: http://www.fda.gov/STIC. In vitro tests show Meropenem to act synergistically with aminoglycoside antibacterial drugs against some isolates of Pseudomonas aeruginosa. In contrast to other beta-lactams, it is highly resistant to degradation by β-lactamases or cephalosporinases. Using strict evaluability criteria and microbiologic eradication and clinical cures at follow-up which occurred 7 or more days after completion of therapy, the presumptive microbiologic eradication/clinical cure rates and statistical findings are provided in Table 9: Table 9: Presumptive Microbiologic Eradication and Clinical Cure Rates at Test-of-Cure Visit in the Evaluable Population with Complicated Intra-Abdominal Infection. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University.. There is inadequate information regarding the use of Meropenem for injection in patients on hemodialysis or peritoneal dialysis. Over time, however, problems such as resistance development and selection of resistant organisms have become apparent. Repeated evaluation of the patient is essential. 1 gram Injection Vial (NDC 6800-447-58) and packaged in cartons of 10 vials (NDC 68001-447-57). If focal tremors, myoclonus, or seizures occur, evaluate neurologically, placed on anti-convulsant therapy if not already instituted, and re-examine the dosage of Meropenem to determine whether it should be decreased or discontinued. 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. Bactericidal concentrations (defined as a 3 log 10 reduction in cell counts within 12 hours to 24 hours) are typically 1to 2 times the bacteriostatic concentrations of Meropenem, with the exception of Listeria monocytogenes, against which lethal activity is not observed. 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)]. 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. Adult patients with complicated skin and skin structure infections including complicated cellulitis, complex abscesses, perirectal abscesses, and skin infections requiring intravenous antimicrobials, hospitalization, and surgical intervention were enrolled in a randomized, multi-center, international, double-blind trial. 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). If you are allergic to meropenem; any part of meropenem; or any other drugs, foods, or substances. Adverse laboratory changes that were reported and occurring in greater than 0.2% of the patients were as follows: Hepatic: increased alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactose dehydrogenase (LDH), and bilirubin, Hematologic: increased platelets, increased eosinophils, decreased platelets, decreased hemoglobin, decreased hematocrit, decreased white blood cell (WBC), shortened prothrombin time and shortened partial thromboplastin time, leukocytosis, hypokalemia, Renal: increased creatinine and increased blood urea nitrogen (BUN), Complicated Skin and Skin Structure Infections. If administration of Meropenem is necessary, then supplemental anti-convulsant therapy should be considered [see Warnings and Precautions (5.4)]. Absorption. Use of Meropenem in pediatric patients less than 3 months of age with intra-abdominal infections is supported by evidence from adequate and well-controlled studies in adults with additional data from a pediatric pharmacokinetic and safety study [see Indications and Usage (1.2), Dosage and Administration (2.3), Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14.2)]. [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. This condition frequently occurs in patients with hematological malignancies and cancer patients receiving anticancer drugs that suppress bone marrow formation. Table 3: Recommended Meropenem for Injection Dosage Schedule for Pediatric Patients Less than 3 Months of Age with Complicated Intra-abdominal Infections and Normal Renal Function, Infants less than 32 weeks GA and PNA less than 2 weeks, Infants less than 32 weeks GA and PNA 2 weeks and older, Infants 32 weeks and older GA and PNA less than 2 weeks, Infants 32 weeks and older GA and PNA 2 weeks and older. It is active against Gram-positive and Gram-negative bacteria. Doripenem, like other β-lactam antibiotics, reacts with penicillin-binding proteins (PBPs) to form stable acyl-enzymes. 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. The proportion of patients who discontinued study treatment due to an adverse event was similar for both treatment groups (Meropenem, 2.5% and imipenem-cilastatin, 2.7%). If you are taking probenecid. The percentage of time of a dosing interval that unbound plasma concentration of Meropenem exceeds the Meropenem minimum inhibitory concentration (MIC) against the infecting organism has been shown to best correlate with efficacy in animal and in vitro models of infection. A further 28% is recovered as the microbiologically inactive metabolite. Staphylococcus aureus (methicillin-susceptible isolates only) All Meropenem-treated patients with seizures had pre-existing contributing factors. Approximately 70% (50% - 75%) of the dose is excreted unchanged within 12 hours. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Last updated on Sep 1, 2020. 12.4 Microbiology. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. What is the mechanisms of action of carbapenems? Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. Streptococcus pyogenes Bacteria cannot survive without a cell wall. Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. 12 & 16, Chuangye Rd., Xinshi Dist., Tainan City 74144, Taiwan for Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. Mechanism of Action. Dosage should be reduced in patients with creatinine clearance of 50 mL/min or less. Bloodstream Infections. Contents are Sterile, amoxicillin, Keflex, doxycycline, triamcinolone, metronidazole, azithromycin, ciprofloxacin, clindamycin, Augmentin, Flagyl. Prevotella melaninogenica Imipenem was the first carbapenem antibiotic selected for development more than two dec… Meropenem for injection should be given as intravenous infusion over 30 minutes. If superinfection does occur during therapy, appropriate measures should be taken. Mechanism of Action. At enrollment, approximately 37% of the patients had underlying diabetes, 12% had underlying peripheral vascular disease and 67% had a surgical intervention. [3] The World Health Organization classifies meropenem as critically important for human medicine.[4]. Citrobacter koseri Table 7: Success Rates at Test-of-Cure Visit for Clinically Evaluable Population with Complicated Skin and Skin Structure Infections. [1] Those who are allergic to other β-lactam antibiotics are more likely to be allergic to meropenem as well. To compare and contrast imipenem and meropenem in terms of in vitro activity, pharmacokinetics, clinical efficacy and adverse effects. Clostridium difficile [10] Unlike imipenem, it is stable to dehydropeptidase-1, so can be given without cilastatin. [1] It is in the carbapenem family of medications. Doripenem has high affinity for PBP2 and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli [9]. For meropenem, doripenem, and ertapenem, the seizure rate for each agent is reported as less than 1%. However, the efficacy of Meropenem in treating clinical infections caused by these bacteria have not been established in adequate and well-controlled clinical trials. A 2014 study looked at cross-reaction between carbapenems and … Peptostreptococcus species. A pharmacokinetic study with Meropenem in elderly patients with renal impairment showed a reduction in plasma clearance of Meropenem that correlates with age-associated reduction in creatinine clearance. [5] Meropenem is frequently given in the treatment of febrile neutropenia. The bactericidal activity of Meropenem results from the inhibition of cell wall synthesis. There was no evidence of impaired fertility at doses up to 1000 mg/kg/day (on the basis of body surface area comparison, approximately 3.2 times to the MRHD of 1 gram every 8 hours). In rats administered intravenous Meropenem in late pregnancy and during the lactation period, there were no adverse effects on offspring at doses equivalent to approximately 3.2 times the MRHD based on body surface area comparison (see Data). Meropenem for injection has been found to be effective in eliminating concurrent bacteremia in association with bacterial meningitis. The background risk of major birth defects and miscarriage for the indicated population is unknown. 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). [2] It was approved for medical use in the United States in 1996. There was no evidence of mutagenic potential found in any of these tests. The bactericidal activity of meropenem results from the inhibition of cell wallsynthesis. Peak tissue time: 1 hr after infusion. 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)]. Campylobacter jejuni Citrobacter freundii The following are discussed in greater detail in other sections of labeling: Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Solutions prepared for infusion (Meropenem for injection concentrations ranging from 1 mg/mL to 20 mg/mL) re-constituted with Sodium Chloride Injection 0.9% may be stored for 1 hour at up to 25°C (77°F) or 15 hours at up to 5°C (41°F). Dosage adjustment is recommended in patients with advanced age and/or adult patients with creatinine clearance of 50 mL/min or less [see Dosage and Administration (2.2)]. Table 11: Hearing Loss at Post-Therapy in the Evaluable Population Treated with Meropenem. The types of systemic and local adverse events seen in these patients are similar to the adults, with the most common adverse events reported as possibly, probably, or definitely related to Meropenem and their rates of occurrence as follows: Pediatric Patients with Bacterial Meningitis: Meropenem was studied in 321 pediatric patients (3 months to less than 17 years of age) with meningitis at a dosage of 40 mg/kg every 8 hours. Tell your doctor about the allergy and what signs you had. If you are taking any of these drugs: Divalproex or valproic acid. Meropenem has been reported to be excreted in human milk. Mechanism of Action. [13][14] Meropenem, like other carbapenems, is a potent inducer of multidrug resistance in bacteria. MEDLINE search from 1975 to 1997 and follow-up of references. Mechanism of Action Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death. Freshly prepared solutions of Meropenem for injection should be used. [6], Meropenem is administered intravenously as a white crystalline powder to be dissolved in 5% monobasic potassium phosphate solution. There are numerous reports of seizure activity associated with imipenem-cilastatin, with seizure rates ranging from 3-33%. For pediatric patients (with normal renal function) less than 3 months of age, with complicated intra-abdominal infections, the Meropenem for injection dose is based on gestational age (GA) and postnatal age (PNA). Additionally, in a study of 511 patients with complicated skin and skin structure infections, 93 (18%) were 65 years of age and older, while 38 (7%) were 75 years and older. Meropenem for injection (I.V.) Bacteroides uniformis In a study of complicated skin and skin structure infections, the adverse reactions were similar to those listed above. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. In the seriously ill patient population, it was not possible to determine the relationship between observed adverse events and therapy with Meropenem. β-Lactams were among the first antimicrobial agents available for the therapy of infectious diseases. Administration of a carbapenem (imipenem, meropenem, and perhaps ertapenem) alone or with other antibiotics was associated with a significantly lower ... Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects View in Chinese … the beta-lactam ring. There were no adverse effects in the dams and no adverse effects in the first generation offspring (including developmental, behavioral, and functional assessments and reproductive parameters) except that female offspring exhibited lowered body weights which continued during gestation and nursing of the second generation offspring. Meropenem administered to pregnant rats during organogenesis (Gestation Day 6 to Gestation Day 17) in intravenous doses of 240, 500, and 750 mg/kg/day was associated with mild maternal weight loss at all doses, but did not produce malformations or fetal toxicity. It is (4R,5S,6S)-3- [[(3S,5S)-5-(Dimethylcarbamoyl)-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxilic acid trihydrate. In 2017 the FDA granted approval for the combination of meropenem and vaborbactam to treat adults with complicated urinary tract infections. Data sources include IBM Watson Micromedex (updated 2 Nov 2020), Cerner Multum™ (updated 2 Nov 2020), ASHP (updated 23 Oct 2020) and others. At least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Meropenem against isolates of similar genus or organism group. Meropenem readily penetrates the cell wall of most Gram-positive and Gram-negative bacteria to reach penicillin-binding-protein (PBP) targets. 12.4 Microbiology. 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. At the end of a 30-minute intravenous infusion of a single dose of Meropenem for injection in healthy volunteers, mean peak plasma concentrations of Meropenem are approximately 23 mcg/mL (range 14 to 26) for the 500 mg dose and 49 mcg/mL (range 39-58) for the 1 gram dose. A pharmacokinetic study with Meropenem in elderly patients has shown a reduction in the plasma clearance of Meropenem that correlates with age-associated reduction in creatinine clearance [see Clinical Pharmacology (12.3)]. The dry powder should be stored at controlled room temperature 20º to 25ºC (68º to 77ºF) [see USP]. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with β-lactams. 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. When treating complicated skin and skin structure infections caused by P.aeruginosa, a dose of 1 gram every 8 hours is recommended. In the Meropenem treated group, 12/15 patients with seizures had late onset seizures (defined as occurring on day 3 or later) versus 7/20 in the comparator arm. The success rates in the clinically evaluable patients at the follow-up visit were 86% (225/261) in the Meropenem arm and 83% (238/287) in imipenem-cilastatin arm. Compatibility of Meropenem for injection with other drugs has not been established. Serratia marcescens, Bacteroides ovatus Streptococcus pyogenes, Streptococcus agalactiae, Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis, and Peptostreptococcus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, and Peptostreptococcus. Carbapenems Mechanism of Action-inhibitors of cell wall synthesis by binding to and inhibiting PBP-2 -Penetrates very well into cell wall -Time dependent Bactericidal.