Carbapenem

Aka: Carbapenem, Penem Antibiotic

advertisement

II. Indications

  1. Bacterial Coverage
    1. Gram Positive Bacteria
      1. Streptococcus
      2. Staphylococcus aureus (MSSA)
    2. Gram Negative Bacteria
      1. Enterobacteriaceae
      2. Listeria
    3. Anaerobic Bacteria
      1. Enterococcus
      2. Bacteroides
      3. Pseudomonas
  2. Conditions
    1. ESBL Aerobic Gram Negative Rods
    2. Multi-drug allergy patients (e.g. Penicillin and Cephalosporin allergies) with susceptible infections
    3. Carbapenems are best reserved for critically ill patients with Severe or Complicated Infections
      1. Skin and Soft Tissue Infections
      2. Respiratory tract infections
      3. Intraabdominal infections
      4. Urogenital infections
      5. Endocarditis
      6. Sepsis
      7. Meningitis
      8. Anthrax (off-label use of Meropenem)

III. Mechanism

  1. Broad-spectrum, beta lactam Antibiotics with bactericidal activity
    1. Carbapenems have the broadest spectrum of activity of any of the beta lactam Antibiotics (Penicillins, Cephalosporins)
  2. Structure
    1. Fused beta lactam ring (provides for beta lactamase resistance)
  3. Attaches to Penicillin binding Proteins (PRBs) on Bacterial cell wall (similar to other beta lactams)
    1. Interferes with peptidoglycan synthesis (key component of the Bacterial cell wall)
    2. Results in a weak Bacterial cell wall and Bacterial cell lysis
  4. Carbapenems are stable against most beta lactamases
    1. AmpC Beta lactamases
    2. Extended Spectrum Beta Lactamases
  5. Carbapenems are a major cause of Antibiotic Resistance (related to broadest spectrum of activity)
    1. Serine Carbapenemases (e.g. Klebsiella producing Carbapenemases)
    2. Metallo Beta-Lactamases
    3. Oxacillinases (OXA-48)

IV. Pharmacokinetics

  1. All Carbapenems have poor oral absorption and are administered via Parenteral Route
  2. Renal excretion (unchanged in urine)

V. Adverse Effects

  1. Gastrointestinal Effects (Diarrhea, Nausea or Vomiting)
    1. More common with Imipenem-Cilastin
  2. Skin Rash (including injection site reactions)
  3. Pruritus
  4. Liver Function Test abnormalities
    1. Serum Aminotransferase increase is common
      1. Transient mild-moderate increases
      2. Most common with Imipenem-Cilastin
    2. Cholestatic liver injury is rare
  5. Antibiotic Drug Resistance
  6. Clostridioides difficile
  7. Seizures
    1. Higher risk in elderly, underlying CNS disorders or Epilepsy, impaired Renal Function or high doses
    2. Also seen with Imipenem-Cilastin (Primaxin) when combined with Ganciclovir
    3. Carbapenems are associated with a higher risk of Seizure than other beta lactams
  8. Thrombocytopenia
    1. May oocur with Meropenem (Merrem) in patients with renal dysfunction

VI. Drug Interactions

  1. Valproic Acid
    1. Significant decrease in Valproic Acid levels

VII. Medications: Imipenem-Cilastin (Primaxin)

  1. Unknown safety in pregnancy and Lactation
  2. Background
    1. Imipenem alone is rapidly inactivated by renal DHP-1
    2. Cilastin is added to Imipenem to prolong its half life by slowing renal excretion
  3. Dosing
    1. Infuse over 20-30 minutes (over 40 to 60 minutes if dose >500 mg or Nausea occurs)
    2. Adult
      1. High dose (intermediately sensitive Bacteria)
        1. CrlCl >=90 ml/min: 1000 mg IV/IM every 6 hours
        2. CrCl 60-90 ml/min: 750 mg IV/IM every 8 hours
      2. Low dose (suscepible Bacteria, empiric Febrile Neutropenia coverage)
        1. CrlCl >=90 ml/min: 500 mg every 6 hours or 1000 mg every 8 hours IV/IM
        2. CrCl 60-90 ml/min: 500 mg IV/IM every 6 hours
    3. Child (3 months and older)
      1. Avoid in renal Impairment if weight <30 kg
      2. Dose: 15 to 25 mg/kg IV every 6 hours (maximum: 4 g/day)
    4. Infant (birth to 3 months)
      1. Avoid in renal Impairment
      2. Age <1 week: 25 mg/kg every 12 hours
      3. Age 1 to 4 weeks: 25 mg/kg every 8 hours
      4. Age 1 to 3 months: 25 mg/kg every 6 hours
  4. Indications: Complicated Infections
    1. Avoid in Meningitis and other CNS Infections
    2. Sepsis
    3. Pneumonia
    4. Endocarditis
    5. Intraabdominal Infections
    6. Bone and joint infections
    7. Pelvic or gynecologic infections
    8. Urinary Tract Infections
    9. Skin and Soft Tissue Infections
    10. Empiric Febrile Neutropenia coverage (not FDA approved)

VIII. Medications: Meropenem (Merrem)

  1. Unknown safety in pregnancy and Lactation
  2. Dosing
    1. Adult (and child weighing >50 kg)
      1. High Dose: 2000 mg IV every 8 hours
        1. Indicated in Meningitis (not FDA approved)
      2. Medium Dose: 1000 mg IV every 8 hours
        1. Indicated in complicated intra-abdominal and Pseudomonas infections
        2. Also used in Hospital Acquired Pneumonia, complicated UTI, Malignant Otitis Externa (not FDA approved)
      3. Low Dose: 500 mg IV every 8 hours
        1. Indicated in Skin and Soft Tissue Infections
      4. Adjust dose in impaired Renal Function
        1. CrCl 10 to 25 ml/min: Give indicated dose every 12 hours
        2. CrCl 26 to 50 ml/min: Give 50% of indicated dose every 12 hours
        3. CrCl <10 ml/min: Give 50% of indicated dose every 24 hours
    2. Child over age 3 months (and weight<50 kg)
      1. High Dose: 40 mg/kg IV every 8 hours
        1. Indicated in Meningitis
      2. Medium Dose: 20 mg/kg IV every 8 hours
        1. Indicated in complicated intra-abdominal and Pseudomonas infections
      3. Low Dose: 10 mg/kg IV every 8 hours
        1. Indicated in Skin and Soft Tissue Infections
    3. Infant age 2 weeks to 3 months (for complicated intra-abdominal infection)
      1. Gestational age <32 weeks: 20 mg/kg IV every 8 hours
      2. Gestational age >32 weeks: 30 mg/kg IV every 8 hours
    4. Infant age <2 weeks (for complicated intra-abdominal infection)
      1. Gestational age <32 weeks: 20 mg/kg IV every 12 hours
      2. Gestational age >32 weeks: 20 mg/kg IV every 8 hours

IX. Medications: Ertapenem (Invanz)

  1. Administration
    1. Administer IV doses over 30 minutes (and do not combine with dextrose solutions)
    2. Dilute IM doses with Lidocaine (if not allergic)
  2. Dosing
    1. FDA approved duration up to 14 days IV and up to 7 days IM
    2. Adult (and age >12 years)
      1. Dose: 1 g IM/IV every 24 hours (or 1 hour prior to surgical incision)
      2. Renal Dosing
        1. CrCl <30 ml/min: 500 mg IV every 24 hours
        2. Hemodialysis: 500 mg IV every 24 hours
          1. Give additional 150 mg after Dialysis if dose within 6 hours prior to Dialysis
    3. Child (3 months to 12 years)
      1. Dose: 15 mg/kg IV or IM every 12 hours (max total daily dose: 1 gram/day)
  3. Indications: Complicated Infections
    1. Avoid in Pseudomonas and Acinetobacter infections (inactive)
    2. Community Acquired Pneumonia
    3. Diabetic Foot Infections
    4. Intraabdominal and Pelvis Infections
    5. Skin and Soft Tissue Infections
    6. Urinary Tract Infections
  4. Safety
    1. Unknown safety in pregnancy
    2. Safe in Lactation

X. Medications: Doripenem (Doribax)

  1. Adult Dosing
    1. Standard Dose: 500 mg IV every 8 hours for 5 to 14 days
    2. Renal Dosing
      1. CrCl 30-50 ml/min: 250 mg IV every 8 hours
      2. CrCl 10-30 ml/min: 250 mg IV every 12 hours
  2. Indications
    1. Avoid in Bacterial Pneumonia (increased mortality)
    2. Primarily used in severe aerobic Gram-Negative Bacterial infections (esp. Pyelonephritis and intraabdominal infections)
    3. May have greater Pseudomonas activity than other Carbapenems
  3. Safety
    1. Pregnancy Category B
    2. Unknown safety in Lactation

XI. Medications: Combinations

  1. Recarbio (Imipenem-Cilastin AND Relebactam)
    1. Indicated in complicated UTI or intra-abdominal infections where other options have been exhausted
    2. Unknown safety in pregnancy and Lactation
    3. Adult dosing
      1. CrCl >=90 ml/min: 1.25 g IV every 6 hours administered over 30 minutes
      2. CrCl 60 to 89 ml/min: 1 g IV every 6 hours administered over 30 minutes
      3. CrCl 30 to 59 ml/min: 0.75 g IV every 6 hours administered over 30 minutes
      4. CrCl 15 to 29 ml/min: 0.5 g IV every 6 hours administered over 30 minutes
      5. CrCl <15 ml/min: Avoid unless Hemodialysis planned for within 48 hours
        1. Administer after Hemodialysis
  2. Vabomere (Meropenem AND Vaborbactam)
    1. Indicated in complicated UTI where other options have been exhausted
    2. Adult dosing
      1. CrCl >=50 ml/min: 4 g IV every 8 hours administered over 3 hours
      2. CrCl 30 to 49 ml/min: 2 g IV every 8 hours administered over 3 hours
      3. CrCl 15 to 29 ml/min: 2 g IV every 12 hours administered over 3 hours
      4. CrCl <15 ml/min: 1 g IV every 12 hours administered over 3 hours
        1. Administer after Hemodialysis

XII. References

  1. LiverTox (2017), accessed online 1/2/2023
    1. https://www.ncbi.nlm.nih.gov/books/NBK548705/
  2. Hamilton (2020) Tarascon Pharmacopeia
  3. (2012) Presc Lett, Resource #231205, Comparison of Carbapenem Antibiotics
  4. Zhanel (2007) Drugs: 67(7): 1027-52 [PubMed]

Images: Related links to external sites (from Bing)

These images are a random sampling from a Bing search on the term "Carbapenem." Click on the image (or right click) to open the source website in a new browser window. Search Bing for all related images

Related Studies

Related Topics in Pharmacology

advertisement