Understanding Multidrug-Resistant Organisms (MDROs)

Every year, over a million people worldwide die from infections caused by bacteria that no longer respond to standard antibiotics. These bacteria are known as multidrug-resistant organisms (MDROs), and they represent one of the most serious threats to modern healthcare. Whether it’s a wound that won’t heal, a urinary tract infection that keeps coming back, or a case of pneumonia that doesn’t improve with treatment – MDROs can be behind it. Understanding what MDROs are, which ones are most common, and how drug resistance is classified is essential for anyone working in or studying healthcare and public health.

What are multidrug-resistant organisms? 🔗

For epidemiologic purposes, MDROs are defined as microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents. In simpler terms, these are germs – mainly bacteria – that have developed the ability to survive exposure to multiple types of antibiotics. When a germ is resistant to an antibiotic, it means that certain treatments will not work or may be less effective, making these infections hard to treat.

Antimicrobial agents are drugs designed to kill or inhibit the growth of microorganisms. When bacteria evolve mechanisms to withstand these drugs, they become resistant. When they resist multiple classes of such drugs simultaneously, they earn the label “multidrug-resistant.”

MDROs are found mainly in hospitals and long-term care facilities, where they often affect people who are older or very ill. However, certain MDROs have also been increasingly found in community settings, making this a concern that extends well beyond hospital walls.

How do MDROs develop? 🔗

MDROs develop when antibiotics are taken longer than necessary or when they are not needed. Over time, repeated antibiotic exposure allows bacteria that already carry resistance genes to survive and multiply. The more antibiotics are used – especially when misused – the greater the chances that resistant strains emerge and spread.

The misuse and overuse of antimicrobials in humans, animals, and plants are the main drivers in the development of drug-resistant pathogens. This includes inappropriate prescribing by healthcare providers, patients not completing their prescribed courses, and the widespread use of antibiotics in agriculture.

How do MDROs spread? 🔗

Most MDRO infections spread through direct contact with an infected person’s bodily fluids, such as blood, wound drainage, urine, stool, or sputum. They can also spread through contact with contaminated equipment or surfaces. In healthcare facilities, the hands of healthcare workers are the most common way MDROs travel from patient to patient. Shared objects like bed rails, IV poles, and catheters can also serve as vehicles for transmission.

Common multidrug-resistant organisms 🔗

Common MDROs include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci species (VRE), carbapenemase-producing Enterobacteriaceae, and Gram-negative bacteria that produce extended-spectrum beta-lactamases (ESBLs). Each of these poses unique challenges in clinical settings, but all share the characteristic of severely limiting treatment options.

Methicillin-resistant Staphylococcus aureus (MRSA) 🔗

MRSA is perhaps the most widely recognized MDRO. It is a type of Staphylococcus aureus bacterium that has become resistant to methicillin and many related antibiotics. MRSA accounts for up to 80% of bacterial MDR infections. In community settings, MRSA commonly causes skin infections, but in hospitals it can lead to serious bloodstream infections, pneumonia, and surgical site infections.

Deaths due to MRSA increased the most globally among all resistant pathogens, directly causing an estimated 130,000 deaths in 2021 – more than doubling from 57,200 in 1990. This trend makes MRSA one of the most closely monitored MDROs worldwide.

Vancomycin-resistant Enterococci (VRE) 🔗

VRE are strains of Enterococci that have become resistant to vancomycin, an antibiotic commonly used to treat serious bacterial infections. Enterococcus faecalis and Enterococcus faecium are the two species most frequently involved. While Enterococci are normally found in the human gastrointestinal tract and don’t usually cause illness, they can become dangerous in immunocompromised patients.

Vancomycin resistance has been reported as an independent predictor of death from enterococcal bloodstream infections. VRE is primarily acquired in healthcare settings and spreads through person-to-person contact or contaminated environments. Patients with prolonged antibiotic use, indwelling medical devices, or long hospital stays are at the highest risk.

Multidrug-resistant tuberculosis (MDR-TB) 🔗

MDR-TB is caused by strains of Mycobacterium tuberculosis that resist at least the two most potent first-line anti-TB drugs: isoniazid and rifampicin. MDR tuberculosis is increasingly common and particularly worrisome because many strains resist all known antitubercular drugs. MDR-TB requires much longer treatment – often 9 to 20 months – using second-line drugs that tend to be more expensive and cause more side effects.

TB transmission occurs primarily through inhaling respiratory droplets from infected individuals, and the risk is highest in crowded settings with poor ventilation.

Other notable MDROs 🔗

Beyond MRSA, VRE, and MDR-TB, several other organisms demand attention. Notable species include MDR Escherichia coli and Klebsiella pneumoniae, Acinetobacter baumannii (some strains of which resist all antimicrobial agents), and organisms like Stenotrophomonas maltophilia that are intrinsically resistant to the broadest-spectrum antimicrobials.

Carbapenem-resistant Enterobacteriaceae (CRE) have become a major concern because carbapenems are often considered “last resort” antibiotics. Among Gram-negative pathogens, resistance to carbapenems and fluoroquinolones has been increasing significantly. Additionally, Candida auris, a multidrug-resistant fungus, has emerged as a global threat in healthcare facilities due to its ability to persist on surfaces and its high mortality rate in invasive infections.

Classification of drug resistance: MDR, XDR, and PDR 🔗

Not all drug resistance is the same. To bring consistency to how resistance is described around the world, an international group of experts from the European Centre for Disease Prevention and Control (ECDC) and the CDC proposed a standardized classification system in 2012. This framework defines three levels of resistance: MDR, XDR, and PDR.

Multidrug resistance (MDR) 🔗

MDR is defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories. In practical terms, if a bacterium cannot be killed or inhibited by drugs from at least three different antibiotic classes, it qualifies as MDR. This is the broadest and most commonly encountered category of resistance.

For example, a strain of E. coli that resists penicillins, fluoroquinolones, and aminoglycosides would be classified as MDR. While treatment is more complicated with MDR organisms, clinicians typically still have some therapeutic options available.

Extensive drug resistance (XDR) 🔗

XDR is defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories – meaning the bacterial isolate remains susceptible to only one or two drug classes. This is a more severe level of resistance that leaves healthcare providers with very few treatment choices.

XDR organisms often require use of relatively toxic drugs, high doses, or drug combinations that carry a greater risk of side effects. For instance, treating an XDR Acinetobacter baumannii infection may require the use of colistin – an older antibiotic known for significant kidney toxicity – because nearly every other antibiotic class has been rendered ineffective.

Pandrug resistance (PDR) 🔗

PDR is defined as non-susceptibility to all agents in all antimicrobial categories. This is the most extreme form of resistance. A PDR organism leaves clinicians with zero approved antibiotic options. While truly pandrug-resistant infections are rare, they do occur and represent the worst-case scenario in infectious disease management.

Bacteria that are PDR carry the most absolute type of resistance possible, implying that there are no approved antimicrobial agents with activity against these strains. When a PDR infection occurs, treatment must rely on experimental therapies, combination approaches, or supportive care.

Understanding the hierarchy 🔗

These three categories exist on a spectrum. MDR is the starting level of significant resistance, XDR represents a severe escalation where only one or two drug classes still work, and PDR is the ultimate endpoint where nothing works. PDR is a subset of XDR in this classification hierarchy.

It’s worth noting that these definitions have been criticized for limited usefulness in clinical practice because they weigh all antibiotics equally, regardless of their real-world effectiveness, pharmacokinetic properties, and toxicity. To address this, a newer concept called difficult-to-treat resistance (DTR) has been proposed. DTR focuses specifically on resistance to all first-line, lower-toxicity agents – such as beta-lactams and fluoroquinolones – rather than simply counting the number of resistant drug classes.

The global impact of MDROs 🔗

The consequences of MDRO infections extend far beyond individual patients. Bacterial AMR was directly responsible for an estimated 1.27 million global deaths in 2019 and contributed to 4.95 million deaths. A comprehensive analysis published in The Lancet found that between 2025 and 2050, AMR is estimated to lead directly to more than 39 million deaths and be associated with a broader 169 million deaths if current trends continue.

Increased lengths of stay, costs, and mortality have been associated with MDRO infections. Patients with resistant infections spend more time in hospitals, require more expensive treatments, and face higher chances of complications and death compared to those with susceptible infections.

AMR puts many of the gains of modern medicine at risk, making infections harder to treat and making other medical procedures – such as surgery, caesarean sections, and cancer chemotherapy – much riskier.

Prevention and control of MDROs 🔗

Preventing the emergence and spread of MDROs requires action at multiple levels. In healthcare settings, the CDC recommends a combination of hand hygiene, contact precautions, environmental cleaning, and antimicrobial stewardship programmes.

Antimicrobial stewardship involves ensuring that antibiotics are prescribed only when necessary, that the right drug is chosen for the right infection, and that courses are completed appropriately. When people use antibiotics they don’t need, the body may develop resistance, and then antibiotics may not work when they are truly needed.

Infection prevention and control (IPC) measures are equally critical. These include proper hand washing, isolation of infected patients, use of personal protective equipment by healthcare workers, and thorough disinfection of surfaces and medical equipment. Improved access to healthcare and antibiotics could save a total of 92 million lives between 2025 and 2050.

Surveillance and reporting systems help track resistant organisms across facilities and regions. As of year-end 2024, 127 countries and 3 territories have joined the WHO’s Global Antimicrobial Resistance and Use Surveillance System (GLASS) , enabling better monitoring of resistance trends globally.

What do you think? With MDROs posing an ever-growing threat to global health, how can individuals – not just healthcare workers – contribute to slowing the spread of antimicrobial resistance? And should governments prioritise funding for new antibiotic development or for stronger infection prevention programmes?

References

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC8713071/
2. https://epi.utah.gov/mdro/
3. https://www.cec.health.nsw.gov.au/keep-patients-safe/infection-prevention-and-control/multi-drug-resistant-organism-and-emerging-pathogens
4. https://doh.wa.gov/public-health-provider-resources/healthcare-professions-and-facilities/healthcare-associated-infections/antimicrobial-resistance-and-antimicrobial-stewardship/mdro-toolkit
5. https://www.sciencedirect.com/science/article/pii/S1198743X14616323
6. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01867-1/fulltext
7. https://www.cdc.gov/infection-control/hcp/mdro-management/background.html