Carbapenem

• Carbapenems are a class of broad-spectrum antibiotics used for the treatment of severe bacterial infections.
• They are considered the most potent β-lactam antibiotics available and are often reserved for serious infections caused by multidrug-resistant bacteria.
• Carbapenems exhibit a broad spectrum of activity against a wide range of bacteria, including both Gram-positive and Gram-negative bacteria.
• Similar to penicillins and cephalosporins, carbapenems are members of the beta lactam class of antibiotics, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis.
• However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins.
• Furthermore, carbapenems are typically unaffected by emerging antibiotic resistance, even to other beta-lactams.

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Carbapenems structure

Carbapenems

Mechanism of Action

• Carbapenems belong to the β-lactam class of antibiotics, which also includes penicillins and cephalosporins.
• They exert their bactericidal effect by inhibiting bacterial cell wall synthesis.
• Specifically, carbapenems bind to penicillin-binding proteins (PBPs), which are enzymes involved in the cross-linking of peptidoglycan chains in the bacterial cell wall.
• This binding prevents the formation of a structurally stable cell wall, leading to cell lysis and bacterial death.

Spectrum of Activity

• Carbapenems have a broad spectrum of activity against various bacteria, including both Gram-positive and Gram-negative organisms.
• They are particularly effective against multidrug-resistant bacteria, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Carbapenems are often considered the treatment of choice for serious infections caused by these resistant organisms.

Other: Carbapenems generally exhibit good activity against anaerobes such as Bacteroides fragilis. Like other beta lactam antibiotics, they lack activity against atypical bacteria, which do not have a cell wall and are thus not affected by cell wall synthesis inhibitors.

Clinical Uses

Carbapenems are primarily used for the treatment of severe infections caused by susceptible bacteria.

They are commonly employed in the following clinical scenarios:

• Intra-Abdominal Infections: Carbapenems are frequently used as empiric therapy for intra-abdominal infections, including peritonitis and abscesses.
• Pneumonia: In certain cases of severe hospital-acquired or ventilator-associated pneumonia, carbapenems may be used as part of combination therapy.
• Urinary Tract Infections: Carbapenems are considered a treatment option for complicated urinary tract infections caused by multidrug-resistant organisms.
• Bacterial Meningitis: In some cases of bacterial meningitis, particularly those caused by drug-resistant organisms, carbapenems may be used as part of combination therapy.

Adverse Effects

• Carbapenems are generally well-tolerated; however, like any medication, they can cause adverse effects.

Some common adverse effects associated with carbapenems include: Gastrointestinal Disturbances: Nausea, vomiting, and diarrhea may occur with carbapenem use. Hypersensitivity Reactions: Rarely, carbapenems can cause allergic reactions, ranging from mild rashes to severe anaphylaxis. Individuals with a known hypersensitivity to carbapenems or other β-lactam antibiotics should avoid their use. Central Nervous System Effects: In rare cases, carbapenems may cause adverse effects on the central nervous system, such as seizures or encephalopathy. This is more likely to occur in individuals with pre-existing central nervous system disorders or high doses of carbapenems.

• It's important to discuss potential adverse effects and any known allergies with a healthcare professional before initiating carbapenem therapy.

Examples of Carbapenems

• Some examples of carbapenems commonly used in clinical practice include:
• Imipenem
• Meropenem
• Ertapenem
• Doripenem
• These are the major carbapenems available; however, their availability may vary depending on the country or region.
• Each carbapenem may have differences in spectrum of activity, dosing regimens, and specific considerations, so the choice of the appropriate agent depends on the specific clinical situation and susceptibility testing.

Contraindications

• While carbapenems are generally safe and effective antibiotics, there are certain contraindications to consider. Contraindications are specific circumstances or conditions in which the use of a particular medication is not recommended due to potential risks.

Here are some common contraindications for carbapenems:

Hypersensitivity or Allergy:

• Individuals who have a known hypersensitivity or allergy to carbapenems or other β-lactam antibiotics should avoid their use.
• Allergic reactions can range from mild skin rashes to severe anaphylaxis, a life-threatening allergic reaction.

Severe Hypersensitivity to β-Lactam Antibiotics:

• Individuals with a history of severe hypersensitivity reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, to β-lactam antibiotics should avoid carbapenems.

• Furthermore, carbapenems are also contraindicated in patients who are taking valproic acid for seizures, as it has been shown to decrease valproic acid concentrations by as much as 90%.

See Also

• Antibiotics
• β-Lactam Antibiotics
• Gram-Positive Bacteria
• Gram-Negative Bacteria

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