Ertapenem is a 1-beta-methyl carbapenem and broad-spectrum beta-lactam antibiotic with the bactericidal property. Ertapenem binds to penicillin-binding proteins (PBPs) located on the bacterial cell wall, in particular PBPs 2 and 3, thereby inhibiting the final transpeptidation step in the synthesis of peptidoglycan, an essential component of the bacterial cell wall. Inhibition results in a weakening and subsequent lysis of the cell wall leading to cell death of Gram-positive and Gram-negative aerobic and anaerobic pathogens. This agent is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases.
Ertapenem is a broad-spectrum carbapenem antibiotic used primarily for the treatment of aerobic gram-negative bacterial infections. Ertapenem, like other carbapenems, is associated with transient and asymptomatic elevations in serum enzymes. The carbapenems have also been linked to rare instances of clinically apparent, acute cholestatic liver injury.
Ertapenem is meropenem in which one of the two methyl groups attached to the amide nitrogen is replaced by hydrogen while the other is replaced by a 3-carboxyphenyl group. The sodium salt is used for the treatment of moderate to severe susceptible infections including intra-abdominal and acute gynecological infections, pneumonia, and infections of the skin and of the urinary tract. It has a role as an antibacterial drug. It is a carbapenemcarboxylic acid and a pyrrolidinecarboxamide. It is the conjugate acid of an ertapenem(1-).
Mechanism of Action
The bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin-binding proteins (PBPs). In Escherichia coli, it has a strong affinity toward PBPs 1a, 1b, 2, 3, 4, and 5 with a preference for PBPs 2 and 3. Ertapenem is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases, and extended-spectrum beta-lactamases. Ertapenem is hydrolyzed by Metallo-beta-lactamases.
Antimicrobials are the most frequently implicated class of drugs in drug-induced seizure, with beta-lactams being the class of antimicrobials most often implicated. The seizure-inducing potential of the carbapenem subclass may be directly related to their beta-lactam ring structure. Data on individual carbapenems and seizure activity are scarce. To evaluate the available evidence on the association between carbapenem agents and seizure activity, /investigators/ conducted a literature search of the MEDLINE (1966-May 2010), EMBASE (1974-May 2010), and International Pharmaceutical Abstracts (1970-May 2010) databases. Reference citations from the retrieved articles were also reviewed. Mechanistically, the seizure propensity of the beta-lactams is related to their binding to gamma-aminobutyric acid (GABA) receptors. There are numerous reports of seizure activity associated with imipenem-cilastatin, with seizure rates ranging from 3-33%. For meropenem, doripenem, and ertapenem, the seizure rate for each agent is reported as less than 1%. However, as their use increases and expands into new patient populations, the rate of seizures with these agents may increase. High-dose therapy, especially in patients with renal dysfunction, preexisting central nervous system abnormalities, or a seizure history increases the likelihood of seizure activity. …
Indications of Ertapenem
For the treatment the following moderate to severe infections caused by susceptible isolates of the designated microorganisms:
- (1) complicated intra-abdominal infections due to Escherichia coli, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus species, Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis,
- (2) complicated skin and skin structure infections, including diabetic foot infections without osteomyelitis due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus agalactiae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumonia, Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species, Porphyromonas asaccharolytica, or Prevotella bivia,
- (3) community-acquired pneumonia due to Streptococcus pneumoniae (penicillin-susceptible isolates only) including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates only), or Moraxella catarrhalis,
- (4) complicated urinary tract infections including pyelonephritis due to Escherichia coli, including cases with concurrent bacteremia, or Klebsiella pneumoniae,
- (5) acute pelvic infections including postpartum endometritis, septic abortion, and post-surgical gynecologic infections due to Streptococcus agalactiae, Escherichia coli, Bacteroides fragilis, Porphyromonas asaccharolytica, Peptostreptococcus species, or Prevotella bivia.
Treatment of the following infections when caused by bacteria known or very likely to be susceptible to ertapenem and when parenteral therapy is required:
- intra-abdominal infections;
- community-acquired pneumonia;
- acute gynecological infections;
- diabetic foot infections of the skin and soft tissue.
- PreventionInvanz is indicated in adults for the prophylaxis of surgical site infection following elective colorectal surgery.
- Consideration should be given to official guidance on the appropriate use of antibacterial agents.
- Intraabdominal Infection
- Pelvic Infections
- Pneumonia
- Pyelonephritis
- Urinary Tract Infection
- Skin or Soft Tissue Infection
- Infection Prophylaxis
- Gynecological infection
- Moderate, severe Community-Acquired Pneumonia (CAP)
- Moderate, severe Complicated Intra-Abdominal Infections
- Moderate, severe Complicated Skin and Soft Tissue Infection
- Moderate, severe Complicated Urinary Tract Infection
- Moderate, severe Diabetic Foot Infection
- Moderate, severe Postpartum Endomyometritis
- Moderate, severe Septic Abortion
Therapeutic Uses
- beta-Lactams; Anti-Bacterial Agents
- Ertapenem sodium is indicated for the treatment of adult patients and pediatric patients (3 months of age and older) with moderate to severe infections caused by susceptible isolates of the designated microorganisms.
- Ertapenem sodium is indicated for the treatment of complicated intra-abdominal infections due to Escherichia coli, Clostridium clostridioforme, Eubacterium centum, Peptostreptococcus species, Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis.
- Ertapenem sodium is indicated for the treatment of complicated skin and skin structure infections, including diabetic foot infections without osteomyelitis due to Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus agalactiae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumonia, Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species, Porphyromonas saccharolytic, or Prevotella Livia. Ertapenem sodium has not been studied in diabetic foot infections with concomitant osteomyelitis.
- Ertapenem sodium is indicated for the treatment of community-acquired pneumonia due to Streptococcus pneumoniae (penicillin-susceptible isolates only) including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates only), or Moraxella catarrhalis.
- Ertapenem sodium is indicated for the treatment of complicated urinary tract infections including pyelonephritis due to Escherichia coli, including cases with concurrent bacteremia, or Klebsiella pneumonia.
- Ertapenem sodium is indicated for the treatment of acute pelvic infections including postpartum endometritis, septic abortion, and post-surgical gynecological infections due to Streptococcus agalactiae, Escherichia coli, Bacteroides fragilis, Porphyromonas saccharolytic, Peptostreptococcus species, or Prevotella Livia.
- Ertapenem sodium is indicated for the prevention of surgical site infection following elective colorectal surgery.
Contraindications of Ertapenem
Ertapenem is contraindicated in patients with known hypersensitivity to ertapenem, other carbapenems, or any ingredient in the formulation; history of anaphylactic reaction to beta-lactams. Patients with known hypersensitivity to local anesthetics of the amide-type should not receive ertapenem sodium reconstituted with lidocaine hydrochloride for IM injection.
- diarrhea from infection with Clostridium difficile bacteria
- lesion of the brain
- decreased kidney function
- severe renal impairment
- seizures
- chronic kidney disease stage 4 (severe)
- chronic kidney disease stage 5 (failure)
- Allergies to Betalactams and Carbapenems
Dosage of Ertapenem
- Strengths: 1 g
Intraabdominal Infection
- 1 g IV or IM once a day for 5 to 14 days
Pelvic Infections
- 1 g IV or IM once a day for 3 to 10 days
Pneumonia
- 1 g IV or IM once a day
- The total duration of therapy: 10 to 14 days
Pyelonephritis
- 1 g IV or IM once a day
- The total duration of therapy: 10 to 14 days
Urinary Tract Infection
- 1 g IV or IM once a day
- The total duration of therapy: 10 to 14 days
Skin or Soft Tissue Infection
- 1 g IV or IM once a day for 7 to 14 days
Infection Prophylaxis
- 1 g IV once as a single dose, 1 hour before surgical incision
Pediatric Dose
Intraabdominal Infection
- 3 months to 12 years: 15 mg/kg IV or IM twice a day
- Maximum dose: 1 g/day
- 13 years or older: 1 g IV or IM once a day
- Duration of therapy: 5 to 14 days
Pelvic Infections
- 3 months to 12 years: 15 mg/kg IV or IM twice a day
- Maximum dose: 1 g/day
- 13 years or older: 1 g IV or IM once a day
- Duration of therapy: 3 to 10 days
Pneumonia
- 3 months to 12 years: 15 mg/kg IV or IM twice a day
- Maximum dose: 1 g/day
- 13 years or older: 1 g IV or IM once a day
- The total duration of therapy: 10 to 14 days
Pyelonephritis
- 3 months to 12 years: 15 mg/kg IV or IM twice a day
- Maximum dose: 1 g/day
- 13 years or older: 1 g IV or IM once a day
- The total duration of therapy: 10 to 14 days
Urinary Tract Infection
- 3 months to 12 years: 15 mg/kg IV or IM twice a day
- Maximum dose: 1 g/day
- 13 years or older: 1 g IV or IM once a day
- The total duration of therapy: 10 to 14 days
Skin or Soft Tissue Infection
- 3 months to 12 years: 15 mg/kg IV or IM twice a day
- Maximum dose: 1 g/day
- 13 years or older: 1 g IV or IM once a day
- Duration of therapy: 7 to 14 day
Side Effects of Ertapenem
The Most Common
- severe stomach pain, diarrhea that is watery or bloody;
- tremors, twitching, or rigid (very stiff) muscles
- a seizure (convulsions);
- unusual changes in your mood or behavior.
- Nausea – vomiting
- diarrhea
- constipation
- headache
- dizziness
- stomach pain
- fever
- cough
- confusion
- difficulty falling asleep or staying asleep
- redness or irritation at the injection site
- swelling, redness, burning, itching, or irritation of the vagina
- swelling of the hands, feet, ankles, or lower legs
Common
- pain, redness, or mild swelling where the injection was given.
- severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)
- hives
- rash
- itching
- difficulty breathing or swallowing
- seizures
- unusual tiredness or weakness
- pale skin
- fast or irregular heartbeat
- shortness of breath
- chest pain
Drugs Interactions Of Ertapenem
- amifampridine
- BCG
- bupropion
- cholera vaccine, live
- divalproex sodium
- entecavir
- estradiol
- ethinyl estradiol
- evening primrose
- fluphenazine
- ginkgo
- indium oxyquinoline in-111
- iohexol
- iopamidol
- lindane topical
- metrizamide
- mycophenolate mofetil
- mycophenolic acid
- pemetrexed
- polyethylene glycol 3350 with electrolytes
- probenecid
- tramadol
- typhoid vaccine, live
- valproic acid
- How should this medicine be used?
Pregnancy Category
This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus.
- AU TGA pregnancy category – B3
- US FDA pregnancy category – Not assigned.
Animal studies have revealed evidence of slightly decreased fetal weight and effects on vertebral ossification. While no maternal or embryofetal effects were observed in pregnant rats administered IV doses up to 700 mg/kg/day (about 1.2 times the maximum recommended human dose based on AUC) during organogenesis, slight decreases in average fetal weight and an associated decrease in the average number of ossified sacrocaudal vertebrae were observed in pregnant mice administered IV doses up to 700 mg/kg/day (about 3 times the MRHD based on body surface area comparison) during organogenesis. This drug crossed the placental barrier in rats. There are no controlled data in human pregnancy.
AU TGA pregnancy category B3
Drugs have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
US FDA pregnancy category Not Assigned
The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.
Ertapenem injection comes as a powder to be mixed with liquid to be injected intravenously (into a vein) or intramuscularly (into a muscle). It is infused (injected slowly) intravenously over a period of at least 30 minutes once or twice a day for up to 14 days. It is also may be given once or twice a day intramuscularly for up to 7 days. The length of treatment depends on the type of infection being treated. Your doctor will tell you how long to use ertapenem injection. After your condition improves, your doctor may switch you to another antibiotic that you can take by mouth to complete your treatment.
You may receive an ertapenem injection in a hospital, or you may use the medication at home. If you will be using ertapenem injection at home, use it at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or another healthcare provider to explain any part you do not understand. Use ertapenem injection exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.
If you will be using ertapenem injection at home, your health care provider will show you how to use the medication. Be sure that you understand these directions, and ask your healthcare provider if you have any questions. Ask your healthcare provider what to do if you have any problems infusing ertapenem injection.
You should begin to feel better during the first few days of treatment with ertapenem injection. If your symptoms do not improve or if they get worse, call your doctor.
Use ertapenem injection until you finish the prescription, even if you feel better. If you stop using ertapenem injection too soon or if you skip doses, your infection may not be completely treated and the bacteria may become resistant to antibiotics.
Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient.
What special precautions should I follow?
Before taking ertapenem injection,
- tell your doctor and pharmacist if you are allergic to ertapenem; other carbapenem antibiotics such as imipenem/cilastatin (Primaxin), doripenem (Doribax), or meropenem (Merrem); local anesthetics such as bupivacaine (Marcaine), etidocaine (Durant), lidocaine, mepivacaine (Carbocaine, Prilocaine), or prilocaine (Citanest); cephalosporins such as cefaclor (Ceclor), cefadroxil (Duricef), or cephalexin (Keflex), other beta-lactam antibiotics such as penicillin or amoxicillin (Amoxil, Trimox, Wymox), any other medications, or any of the ingredients in ertapenem injection. Ask your pharmacist or check the manufacturer’s patient information for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: probenecid (Probalan) or valproic acid (Depakene, Depakote). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you have or have ever brain lesions, seizures, or kidney disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using ertapenem injection, call your doctor.
References