Understanding What Are the Last Resort Antibiotics

October 7, 2025 •

3 min read

According to the Centers for Disease Control and Prevention, antibiotic-resistant bacteria cause approximately 2.8 million infections and lead to over 35,000 deaths annually in the United States alone. This growing public health crisis has made it necessary to rely on a special class of powerful drugs known as what are the last resort antibiotics.

Quick Summary

These are potent antimicrobial drugs used when standard treatments fail against multidrug-resistant bacteria. They combat serious infections but carry significant risks and are reserved for critical cases to preserve their effectiveness. This guide explains key examples and the global challenge of resistance.

Key Points

Reserved for Extreme Cases: Last resort antibiotics are powerful drugs reserved for life-threatening infections where other treatments have failed, primarily against multidrug-resistant bacteria.
Broad-Spectrum Carbapenems: Antibiotics like meropenem are used as a final option against a wide range of bacteria, but resistance, such as CRE, is an alarming and growing problem.
Resurgence of Polymyxins: Older drugs like colistin have been brought back for extremely resistant Gram-negative infections, despite known toxic side effects like kidney damage.
Fighting Resistant Gram-Positive Bacteria: Vancomycin, linezolid, and daptomycin are critical last resort drugs for Gram-positive pathogens like MRSA and VRE, though resistance to these has also emerged.
Antimicrobial Stewardship is Vital: To preserve the effectiveness of these precious medications, strict control over their use through antimicrobial stewardship programs is necessary to slow the development of resistance.
Serious Side Effects: The use of last resort antibiotics often involves significant risks of adverse effects, including damage to kidneys and nerves, which must be carefully weighed against the severity of the infection.

What Are Last Resort Antibiotics?

Last resort antibiotics are potent antimicrobial medications held in reserve for treating severe infections caused by multidrug-resistant organisms, often called "superbugs." These drugs are used only when other antibiotics have failed, due to the serious nature of the infections they treat and the need to prevent further resistance. The emergence of resistance to these final options is a significant global health threat.

The Role of Last Resort Antibiotics in Combating Superbugs

Antimicrobial resistance (AMR) is a natural process where bacteria evolve to withstand antibiotics, often accelerated by improper antibiotic use. Bacteria can develop resistance through genetic changes, and their rapid reproduction allows resistant strains to spread quickly. Last resort antibiotics are the final defense against these resistant bacteria, used for infections like Carbapenem-Resistant Enterobacterales (CRE), Methicillin-Resistant Staphylococcus aureus (MRSA), and Vancomycin-Resistant Enterococci (VRE).

Key Classes of Last Resort Antibiotics

Carbapenems

Carbapenems, such as meropenem and imipenem, are broad-spectrum beta-lactam antibiotics used for serious, multi-drug resistant bacterial infections when standard antibiotics are ineffective. They work by inhibiting bacterial cell wall synthesis. However, resistance to carbapenems is increasing due to enzymes like carbapenemases produced by bacteria such as CRE.

Polymyxins (Colistin)

Polymyxins, including Colistin and Polymyxin B, are used as a last line of defense against extensively drug-resistant (XDR) Gram-negative bacterial infections. Their use was limited in the past due to toxicity concerns but has increased due to the lack of alternatives. They disrupt the bacterial cell membrane, causing cell death. Resistance is growing, partly due to the mcr-1 gene. Polymyxins are associated with significant side effects, including kidney and nerve damage.

Vancomycin

Vancomycin is a glycopeptide antibiotic primarily used for severe Gram-positive infections like MRSA and VRE. It prevents bacteria from building cell walls. Resistance has emerged in some S. aureus (VRSA) and Enterococci (VRE) strains. Side effects can include kidney damage, hearing loss, and a reaction called 'red man syndrome'.

Linezolid

Linezolid is an oxazolidinone antibiotic effective against Gram-positive bacteria, including VRE and MRSA, particularly for hard-to-treat infections. It inhibits bacterial protein synthesis. Long-term use can lead to side effects like blood disorders and nerve damage. Resistance is currently low but is being monitored.

Daptomycin

Daptomycin is a lipopeptide antibiotic used for serious Gram-positive infections, such as complicated skin infections and bloodstream infections, when other options like vancomycin are no longer effective. It works by disrupting the bacterial cell membrane. Resistance to daptomycin has been reported and can involve changes in the cell membrane.

The Critical Need for Antimicrobial Stewardship

Careful use of last resort antibiotics is essential to maintain their effectiveness. Antimicrobial stewardship programs, which promote appropriate antibiotic prescribing, are crucial. The World Health Organization (WHO) places these drugs in a "Reserve" category, for specific patients and microbes. Responsible antibiotic use and ongoing research for new treatments are necessary to combat bacterial evolution.

Comparison of Key Last Resort Antibiotics


Antibiotic Class	Examples	Target Bacteria	Key Risks & Side Effects	Resistance Concerns
Carbapenems	Meropenem, Imipenem	Broad-spectrum Gram-positive and Gram-negative	GI upset, seizures, hypersensitivity	Increasing global prevalence of Carbapenemase-producing Enterobacterales (CRE)
Polymyxins	Colistin (Polymyxin E), Polymyxin B	Gram-negative bacteria (e.g., Pseudomonas, Acinetobacter)	Nephrotoxicity, Neurotoxicity	Emergence of plasmid-mediated resistance (mcr-1 gene)
Glycopeptides	Vancomycin	Gram-positive bacteria (e.g., MRSA, VRE)	Nephrotoxicity, Ototoxicity, Red man syndrome	Rising incidence of Vancomycin-Resistant Enterococci (VRE) and intermediate susceptibility in S. aureus
Oxazolidinones	Linezolid	Gram-positive bacteria (e.g., MRSA, VRE)	Myelosuppression, Neuropathy (with long-term use)	Acquisition of resistance genes like cfr and optrA
Lipopeptides	Daptomycin	Gram-positive bacteria (e.g., MRSA, VRE)	GI upset, Muscular pain, Peripheral neuropathy	Membrane remodeling changes that reduce antibiotic binding

Conclusion

Last resort antibiotics are vital for treating severe, multidrug-resistant infections and highlight the growing issue of antimicrobial resistance. Careful use through stewardship programs is critical to preserve their effectiveness. As resistance continues to emerge, ongoing research for new treatments and responsible prescribing are essential to combat superbugs. Learn more about the World Health Organization's efforts to combat AMR.

This article is for informational purposes only and does not constitute medical advice. Consult a healthcare professional for diagnosis and treatment.

Frequently Asked Questions

They are considered last resort because they are potent, broad-spectrum drugs reserved for infections that have become resistant to other, more common antibiotics. This practice helps to preserve their effectiveness by limiting their use to only the most critical cases, slowing the emergence of resistance.

Antimicrobial resistance (AMR) is when microorganisms evolve to defeat the drugs designed to kill them. Last resort antibiotics are used when AMR has rendered all other treatments ineffective, making their continued efficacy crucial for treating dangerous superbugs.

These antibiotics are generally associated with a higher risk of serious side effects compared to standard antibiotics. The potential adverse effects, such as nephrotoxicity (kidney damage) or neurotoxicity (nerve damage), are often significant but are deemed acceptable when a patient faces a life-threatening, drug-resistant infection.

Common examples include carbapenems (like meropenem), polymyxins (like colistin), vancomycin, linezolid, and daptomycin. Each of these classes targets specific types of bacteria and infections.

Resistance to last resort antibiotics is a major concern because it means there may be no effective treatment left for an infection. Overuse accelerates this process, which is why these drugs are used so cautiously.

In cases where a bacterium becomes resistant to all available treatments, it is considered pan-drug resistant. This can lead to untreatable, life-threatening infections. Such scenarios underscore the urgency of developing new antibiotics and practicing good antimicrobial stewardship.

Efforts to combat resistance include implementing strict antimicrobial stewardship programs, investing in research and development of new drugs and diagnostic tests, and educating the public and healthcare professionals on responsible antibiotic use.