Antimicrobial resistance is one of the most urgent public health threats of our time, affecting millions of people worldwide and making once-treatable infections increasingly difficult to manage. Understanding how to identify resistant infections early and accurately is essential for protecting both individual health and community wellbeing.

Introduction: Who Should Undergo Testing and When

Anyone who develops an infection may need diagnostic testing to determine whether their illness is caused by germs that have developed resistance to standard treatments. Antimicrobial resistance happens when bacteria, viruses, fungi and parasites change in ways that make the medicines designed to kill them no longer work effectively. These germs survive despite treatment and continue to grow and spread, making infections harder to treat.^[1]

You should seek diagnostic testing when you have an infection that doesn’t improve with usual treatment, when your symptoms worsen despite taking prescribed medications, or when your healthcare provider suspects you may have been exposed to resistant germs. This is particularly important if you have recently been hospitalized, live in a crowded setting, have a weakened immune system, or take antibiotics frequently. People who work in healthcare settings or have close contact with others who have had resistant infections should also be vigilant about seeking proper diagnosis when they feel unwell.^[3]

Certain groups face higher risk of infections caused by resistant organisms. Newborn babies, especially those born prematurely, adults over age 65, people experiencing homelessness, those living in crowded conditions, individuals with compromised immune systems, and people who take antibiotics long-term all have greater vulnerability to these dangerous infections. For these individuals, diagnostic testing becomes even more critical to ensure appropriate treatment is started quickly.^[3]

Early and accurate diagnosis matters because antimicrobial-resistant infections can lead to severe outcomes if not properly identified and treated. Delays in finding the right medication can result in extended illness, longer hospital stays, increased risk of death, and severe medication side effects when healthcare providers must try multiple treatments before finding one that works. More than 2.8 million antimicrobial-resistant infections occur each year in the United States alone, and more than 35,000 people die as a result.^[6]

Diagnostic Methods for Identifying Resistant Infections

Healthcare providers use several types of diagnostic tests to determine whether an infection involves resistant microorganisms. The most fundamental approach involves collecting samples from the infected area or body fluid and sending them to a laboratory for detailed analysis. These samples might include blood, urine, tissue, wound swabs, sputum, or other bodily fluids depending on where the infection is located.^[25]

Laboratory testing serves as the cornerstone of diagnosing antimicrobial resistance. When a sample arrives at the lab, technicians first work to grow and identify the specific germ causing the infection. This process, called culture, involves placing the sample in special growth media that allows bacteria or fungi to multiply. Once enough organisms have grown, laboratory scientists can identify the exact species present. This identification step is crucial because different types of bacteria and fungi have different patterns of resistance.^[4]

After identifying the organism, the laboratory performs what’s called antimicrobial susceptibility testing. This testing exposes the cultured germs to various antibiotics or antifungals to see which medications can effectively kill them or stop their growth. Technicians observe how the organisms respond to different concentrations of various drugs. The results tell healthcare providers which medications will likely work and which ones the germs have become resistant to. This information is critical for choosing the most effective treatment.^[4]

Blood tests play an important role in diagnosing many types of infections. When bacteria or fungi enter the bloodstream, a condition called bacteremia or fungemia, blood cultures can detect these organisms. Healthcare providers draw blood samples and send them to the laboratory where they’re monitored for several days to see if anything grows. Blood testing can also measure other indicators of infection, such as elevated white blood cell counts or markers of inflammation that suggest the body is fighting an infection.^[25]

Urine testing is particularly important for diagnosing urinary tract infections, which are among the most common types of infections. A simple urinalysis can detect signs of infection, including bacteria, white blood cells, and blood in the urine. When resistance is suspected, a urine culture with susceptibility testing reveals which antibiotics will effectively treat the specific bacteria causing the infection.^[25]

Imaging tests sometimes help healthcare providers understand the extent and location of an infection. X-rays, CT scans (computed tomography), MRI scans (magnetic resonance imaging), and ultrasound can show areas of inflammation, fluid collections, or abscesses that might harbor resistant organisms. While these tests don’t directly identify resistance, they guide providers in collecting samples from the right locations and assessing how well treatment is working.^[25]

For certain types of infections, specialized molecular tests can identify resistance genes within bacteria. These advanced tests look for specific genetic sequences that allow organisms to resist antibiotics. Some can detect resistance markers much faster than traditional culture methods, providing results in hours rather than days. However, these rapid tests are not yet available for all types of resistant infections and may not completely replace culture-based testing, which can identify a broader range of resistance patterns.^[30]

When diagnosing fungal infections, healthcare providers may use blood tests that detect antifungal resistance. Just like bacteria, fungi can develop resistance to the medications used to treat them. Specialized laboratories can test fungal isolates against different antifungal drugs to determine which treatments are most likely to succeed.^[1]

Diagnostics for Clinical Trial Qualification

Clinical trials testing new treatments for antimicrobial-resistant infections require specific diagnostic procedures to determine which patients can participate. These qualification tests serve multiple purposes: they confirm that a patient has a resistant infection, identify the exact organism and its resistance pattern, and establish baseline measurements that researchers will use to evaluate whether the experimental treatment works.^[14]

The diagnostic requirements for clinical trials are typically more extensive and rigorous than those used in routine care. Researchers need very precise information about the resistant organism causing infection. Most trials require laboratory confirmation through culture and susceptibility testing that meets specific technical standards. The laboratory must identify not just the type of bacteria or fungus, but also document exactly which antibiotics or antifungals it resists and which ones it remains sensitive to.^[14]

Many clinical trials studying treatments for specific types of resistant infections require standardized methods for testing antimicrobial susceptibility. These methods ensure that results from different laboratories and different trial sites can be compared reliably. For example, trials studying infections caused by carbapenem-resistant Enterobacterales (CRE) or methicillin-resistant Staphylococcus aureus (MRSA) typically specify exactly how laboratories should perform susceptibility testing and how they should interpret the results.^[14]

Imaging studies often serve as qualification criteria for clinical trials, especially those studying serious infections like pneumonia or complicated abdominal infections. Researchers may require chest X-rays or CT scans to confirm the presence and extent of infection before enrolling patients. These images also provide baseline information that helps researchers measure whether the infection improves during treatment.^[28]

Some clinical trials require genetic testing of the resistant organisms. Researchers may want to understand exactly which genes allow the bacteria to resist treatment. This information can help scientists understand how the new treatment works and whether it might be effective against different types of resistance. Genetic sequencing of bacterial isolates provides this detailed information about resistance mechanisms.^[4]

Blood tests measuring markers of inflammation and infection severity are commonly required for trial enrollment. These might include tests for C-reactive protein, procalcitonin, white blood cell counts, and other indicators that help researchers gauge how sick a patient is at the start of treatment. Monitoring these same markers throughout the trial helps determine whether the experimental therapy is working.^[28]

Clinical trials may exclude patients whose diagnostic tests show certain characteristics. For instance, if preliminary testing suggests a patient has an infection that is still susceptible to standard antibiotics, they typically wouldn’t qualify for a trial testing treatments for resistant organisms. Similarly, if the resistant organism shows a pattern of resistance that the experimental drug isn’t designed to overcome, the patient might not be enrolled.^[14]

The timing of diagnostic testing matters in clinical trials. Most studies require that key diagnostic tests be performed within a specific timeframe before treatment starts—often within 24 to 48 hours of enrollment. This ensures that the test results accurately reflect the patient’s condition when they begin receiving the experimental treatment. Fresh samples are particularly important because organisms can change or because treatment with other medications might affect test results.^[28]