What are Carbapenems? A Guide to Last-Resort Antibiotics

October 6, 2025 •

5 min read

Originally discovered in 1976, carbapenems are a potent class of broad-spectrum beta-lactam antibiotics that were developed from the naturally derived compound thienamycin. They are often reserved as 'last-line' agents for serious, multidrug-resistant infections that have failed to respond to other treatments.

Quick Summary

Carbapenems are potent, broad-spectrum beta-lactam antibiotics that inhibit bacterial cell wall synthesis. They treat serious infections, particularly those caused by multidrug-resistant bacteria, but face increasing resistance threats.

Key Points

Broad-Spectrum Antibiotics: Carbapenems are highly effective against a wide array of Gram-positive, Gram-negative, and anaerobic bacteria.
Last-Resort Treatment: They are often reserved for severe infections caused by multi-drug resistant organisms, including those producing Extended-Spectrum Beta-Lactamases (ESBLs).
Inhibit Cell Wall Synthesis: The mechanism involves binding to penicillin-binding proteins (PBPs), which disrupts the bacteria's cell wall formation, causing cell death.
Potential for Seizures: Imipenem, in particular, carries a notable risk of causing seizures, especially in patients with pre-existing CNS disorders or kidney problems.
Rising Resistance: The emergence of carbapenemase-producing bacteria (CRE) is a major public health threat that compromises the effectiveness of this antibiotic class.
Intravenous Administration: Due to poor oral bioavailability, most carbapenems must be administered via injection.

The Mechanism of Action: How Carbapenems Work

As members of the beta-lactam family of antibiotics, carbapenems work by disrupting the synthesis of the bacterial cell wall. All bacteria have an outer layer called a cell wall that protects them from the outside world. Carbapenems inhibit the transpeptidases, or penicillin-binding proteins (PBPs), that are responsible for linking the peptidoglycan chains that form the cell wall. By irreversibly binding to these proteins, the antibiotic prevents the bacteria from building and repairing its cell wall. Without a structurally sound cell wall, the bacterial cell is unable to withstand internal pressure and bursts (a process known as lysis), leading to cell death. This mechanism classifies carbapenems as bactericidal, meaning they kill bacteria directly.

Unlike many other beta-lactam antibiotics, carbapenems have a unique chemical structure that provides excellent stability against most beta-lactamase enzymes produced by bacteria to inactivate antibiotics. However, some bacteria have developed specific carbapenemase enzymes that can still break down this class of drugs, leading to resistance.

Types and Characteristics of Carbapenems

There are several types of carbapenems in clinical use, each with slightly different properties and spectrums of activity. The main types include:

Imipenem: The first carbapenem approved for clinical use, imipenem is always administered in combination with cilastatin. Cilastatin is a dehydropeptidase inhibitor that prevents the breakdown of imipenem by renal enzymes, which would otherwise reduce its effectiveness and increase the risk of nephrotoxicity. It has good activity against Gram-positive bacteria.
Meropenem: Unlike imipenem, meropenem is stable against the renal dehydropeptidase enzyme and does not require a co-administered inhibitor like cilastatin. It is particularly noted for its ability to penetrate the cerebrospinal fluid, making it a valuable treatment for meningitis. It is also highly effective against Gram-negative bacteria, including Pseudomonas aeruginosa.
Ertapenem: This carbapenem has a longer half-life, allowing for once-daily dosing, which is a significant advantage for hospital and outpatient settings. However, it has a narrower spectrum than meropenem or imipenem, notably lacking activity against Pseudomonas aeruginosa and Acinetobacter species.
Doripenem: Similar to meropenem and imipenem, doripenem is active against Pseudomonas aeruginosa and is used for hospital-acquired infections. Some studies suggest it has enhanced activity against Pseudomonas aeruginosa compared to imipenem and meropenem.

Clinical Uses for Carbapenems

Due to their broad-spectrum activity and high potency, carbapenems are reserved for treating severe, complicated, or multi-drug resistant bacterial infections where other antibiotics have failed or are likely to be ineffective. Their primary uses include:

Complicated intra-abdominal infections: Carbapenems are effective against many anaerobic and Gram-negative bacteria commonly found in these infections.
Hospital-acquired pneumonia (HAP) and Ventilator-associated pneumonia (VAP): Especially when resistant pathogens like Pseudomonas aeruginosa or Extended-Spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae are suspected.
Complicated urinary tract infections (UTIs): For cases where resistance to other antibiotic classes is a concern.
Bacterial meningitis: Meropenem is specifically indicated for this condition due to its excellent central nervous system penetration.
Sepsis: Used as an empiric therapy in critically ill patients with suspected serious infections.

Common and Severe Side Effects

While generally well-tolerated, carbapenems are not without potential side effects. The most common adverse effects include gastrointestinal issues, skin reactions, and infusion-related problems. More serious, but less frequent, side effects can also occur.

Common side effects:

Nausea and vomiting
Diarrhea
Injection site reactions (pain, redness, swelling, thrombophlebitis)
Headache
Rash and itching

Severe side effects and risks:

Seizures and CNS toxicity: Carbapenems, especially imipenem, can cause seizures, particularly in patients with pre-existing CNS disorders, renal insufficiency, or high doses. This risk is a significant consideration when prescribing these potent antibiotics.
Clostridioides difficile infection (CDI): As broad-spectrum antibiotics, carbapenems can disrupt the normal gut flora, increasing the risk of C. difficile-associated diarrhea or colitis.
Allergic reactions: Serious and sometimes fatal allergic reactions, including anaphylaxis, can occur. Patients with a history of penicillin allergy should be treated with caution due to the risk of cross-reactivity.
Drug interactions: Carbapenems can decrease the blood levels of the anti-seizure medication valproic acid, potentially leading to a loss of seizure control.

Comparing Different Carbapenems


Feature	Imipenem/Cilastatin	Meropenem	Ertapenem
Spectrum of Activity	Very broad, including Gram-positive, Gram-negative, and anaerobes. Good Gram-positive coverage.	Very broad, similar to imipenem but often with greater activity against Gram-negative organisms, including P. aeruginosa.	Broad spectrum against Gram-positive, Gram-negative, and anaerobes, but lacks activity against P. aeruginosa and Acinetobacter.
Renal Stability	Unstable; requires co-administration with cilastatin to prevent degradation by renal dehydropeptidase-1 (DHP-1).	Stable against DHP-1; does not require co-administration with cilastatin.	Stable against DHP-1; does not require co-administration with cilastatin.
CNS Penetration	Excellent penetration into CSF when meninges are inflamed, but carries a higher seizure risk.	Excellent penetration into CSF, considered safer for meningitis due to lower seizure risk.	Good penetration, but not used for meningitis due to lack of specific approval and safety data.
Dosing Frequency	Typically administered every 6 to 8 hours.	Typically administered every 8 hours.	Once-daily dosing is a key advantage.

The Threat of Carbapenem Resistance

The emergence of resistance is a growing and serious concern with carbapenems. As a “last-resort” class of antibiotics, their efficacy is critical for treating severe infections. The most worrying development is the rise of Carbapenem-Resistant Enterobacteriaceae (CRE). These are bacteria, such as Klebsiella pneumoniae and E. coli, that produce enzymes called carbapenemases, which are able to hydrolyze and inactivate carbapenems.

Resistance can also occur through other mechanisms, including the production of efflux pumps that actively push the antibiotic out of the bacterial cell, and mutations that alter the outer membrane proteins (porins) required for carbapenem entry into Gram-negative bacteria. The spread of CRE and other resistant pathogens highlights the urgent need for stringent antimicrobial stewardship programs, which aim to optimize antibiotic use to slow the development of resistance. Efforts include limiting carbapenem use to only necessary cases and ensuring appropriate prescribing and de-escalation strategies. The Infectious Diseases Society of America (IDSA) provides comprehensive guidelines on managing these challenging infections, emphasizing the importance of accurate susceptibility testing.

Conclusion

Carbapenems represent a vital and potent class of broad-spectrum antibiotics, reserved for serious bacterial infections, particularly those caused by multi-drug resistant organisms. Their mechanism of action, which involves inhibiting bacterial cell wall synthesis, provides reliable bactericidal activity. However, clinicians must carefully weigh their use due to potential side effects, including neurological risks, and the urgent need to preserve their effectiveness in the face of rising antimicrobial resistance. Continued responsible use and the development of new treatments are essential to ensuring that carbapenems remain a viable option for those who need them most. For further information, the National Institutes of Health offers detailed articles on this class of antibiotics.

Frequently Asked Questions

Carbapenems are used to treat serious bacterial infections such as complicated intra-abdominal infections, pneumonia (including hospital-acquired and ventilator-associated), sepsis, bacterial meningitis, and complicated urinary tract infections, especially when multi-drug resistant bacteria are involved.

The main difference is that imipenem requires co-administration with cilastatin to prevent its inactivation by a renal enzyme, whereas meropenem is stable against this enzyme and does not need cilastatin. Meropenem is also often preferred for treating meningitis due to a lower seizure risk.

Carbapenems are considered among the most potent beta-lactam antibiotics due to their broad spectrum and stability against many bacterial enzymes. They are often referred to as 'last-resort' agents for difficult-to-treat infections caused by resistant bacteria.

The vast majority of carbapenems have very poor absorption from the gastrointestinal tract and must therefore be administered parenterally, via intravenous (IV) or intramuscular (IM) injection, to be effective.

Carbapenem resistance occurs when bacteria develop mechanisms to inactivate carbapenems. The most significant threat is the production of carbapenemase enzymes, which break down the antibiotic, leaving limited treatment options.

The most common side effects include gastrointestinal issues like nausea and diarrhea, injection site reactions, and skin rashes. More serious, but less common, side effects include seizures and severe allergic reactions.

Patients with a history of severe penicillin allergies are generally advised against taking carbapenems due to the potential for cross-reactivity. While the risk may be low for some patients with milder allergies, a careful assessment is necessary.