A number of pathogens are increasingly resistant to existing antibiotics and antifungals. NIAID is researching infections of growing concern to human health, including pathogens identified by the Centers for Disease Control and Prevention (CDC) as urgent, serious, and concerning threats.
The Gram stain test, developed in the 1800s by Hans Christian Gram, is a method for classifying different types of bacteria using a chemical stain and viewing through a microscope the results on the bacteria’s protective cell wall. Most bacteria are classified into two groups—gram-positive or gram-negative—depending on whether they retain a specific stain color. Gram-positive bacteria retain a purple-colored stain, while Gram-negative bacteria appear pinkish or red. Gram-negative bacteria have a double membrane that cannot be penetrated by many antibiotics. Types of Gram-negative bacteria include:
Carbapenem-resistant Enterobacteriaceae (CRE)
Enterobacteriaceae, such as Klebsiella pneumoniae and Escherichia coli (E. coli) can cause serious infections of the urinary tract, bloodstream and wounds, and can also cause pneumonia. These infections are becoming difficult to treat because some bacteria have become resistant to all or most available antibiotics. Some Enterobacteriaceae contain an enzyme called extended-spectrum β-lactamase (ESBL) which makes them resistant to nearly all penicillins and cephalosporins. Other Enterobacteriaceae can be resistant to carbapenems, which are considered drugs of last resort. Enterobacteriaceae-related disease usually occurs in patients at healthcare facilities who have weak immune systems, are on breathing machines or use urinary or intravenous catheters. The bacteria can enter the body through these devices or through wounds from surgery or injury. However, some people can have Enterobacteriaceae in their body without it causing any disease. Read more about NIAID research on E. coli.
N. gonorrhoeae bacteria causes gonorrhea, a sexually-transmitted infection that, if left untreated, can cause serious problems such as pelvic inflammatory disease, infertility and long-term pelvic or abdominal pain. Not all infections are drug-resistant, but N. gonorrhoeae has developed resistance to nearly all the antibiotics used for treatment, making it harder to cure. Read more about NIAID’s research on gonorrhea.
Infection with Acinetobacter (including Acinetobacter baumanii) bacteria can cause serious bloodstream and wound infections and pneumonia. Infections typically occur in patients in healthcare settings and intensive care units who have weakened immune systems, chronic lung disease, open wounds, or are on a breathing machine or catheter. Some people have Acinetobacter bacteria in their body but do not become infected or show symptoms. However, at least three different classes of antibiotics can no longer cure resistant Acinetobacter infections.
Multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa)
P. aeruginosa bacteria can cause mild illness in healthy people, such as ear infections and skin rashes after exposure to inadequately cleaned hot tubs or pools. However, serious P. aeruginosa-associated bloodstream infections and pneumonia can occur in hospitalized patients with weakened immune systems, including people who have wounds from surgery or are using breathing machines or catheters. Infections can spread among patients via the hands of healthcare workers or equipment that is not properly cleaned. Some strains of P. aeruginosa are resistant to most or all antibiotics, including aminoglycosides, cephalosporins, fluoroquinolones and carbapenems.
Salmonella bacteria can cause diarrhea, fever and abdominal cramps in people who consume contaminated food (raw or undercooked meat or eggs) or water. Some infections, such as those resistant to certain classes of drugs, can be more severe, spread to the blood and cause life-threatening complications. A serotype called Salmonella Typhi causes typhoid fever when people consume food or water contaminated with feces. Typhoid fever, uncommon in the U.S., can cause abdominal pain, headache, fever, bowel perforation, shock and death.
Shigella bacteria is found in the stool of infected humans. Shigella infection (shigellosis) can cause diarrhea, fever and abdominal pain. It is transmitted when people touch a surface that has been contaminated (including even tiny amounts of fecal matter that are too small to see) and then touch their mouths. It can also be transmitted by eating contaminated food, swallowing lake or river water or through exposure to feces through sexual contact. Resistance to the first-line antibiotics used to treat Shigella is widespread, so physicians must rely on alternatives (ciprofloxacin and azithromycin). However, resistance to the alternatives also is growing. Read more about NIAID research on Shigellosis.
Other pathogens of concern:
C. diff bacteria can cause mild to severe life-threatening diarrhea, most commonly in people who have recently taken antibiotics. C. diff is shed in feces and transmitted via spores that are present when someone touches a contaminated surface and then touches his or her mouth. Normally the microbes that live in the gut (called gut microbiota) can suppress C. diff-associated disease, but antibiotic treatment can deplete the microbiota in such a way that allows C. diff spores to germinate into vegetative cells which can produce up to three different toxins, causing extreme colonic inflammation. People at higher risk of infection include patients in healthcare settings who have recently taken antibiotics and older adults. C. diff is not yet significantly resistant to the drugs used to treat it, but these drugs are sometimes ineffective and can also leave the person vulnerable to disease recurrence. Moreover, the global burden of C. diff is driven by antibiotic use and the spread of microbes, the same factors that propel antibiotic resistance.
Candida is a yeast (type of fungus) that lives in the human mouth, throat, gut and vagina and usually does not cause problems. However, it can cause infections and varying symptoms if people have a weakened immune system or are taking antibiotics. Infection can occur in the mouth and throat (called thrush), esophagus or vagina. Candida can also cause serious invasive infections of the bloodstream (called candidemia), heart, brain, eyes and bones, most commonly in hospitalized patients. Some strains of Candida are becoming resistant to antifungal drugs, including fluconazole. The strain Candida auris is extremely rare but of increasing concern in the U.S. and can be resistant to all three types of antifungal medications.
People usually become infected with Campylobacter (including Campylobacter jejuni) bacteria by eating raw or undercooked poultry or drinking unpasteurized milk. Infection can cause diarrhea, cramping, abdominal pain, fever and can become life-threatening if spread to the bloodstream. The bacteria is becoming resistant to antibiotics (ciprofloxacin and azithromycin), which can cause longer, more severe infections as well as post-infectious problems such as gastrointestinal, neurological and joint disorders.
Enterococcus bacteria are commonly found in the human digestive and female genital tracts but do not pose a threat to healthy people. However, Enterococcus can cause urinary tract infections, bloodstream infections and wound infections in hospitalized patients. Infections typically occur in patients who have previously been treated with antibiotics for extended periods of time, have undergone surgery, have catheters, or have weakened immune systems. Infection can be deadly as about one-third of Enterococcus infections are resistant to the last-resort antibiotic vancomycin.
Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Staphylococcus aureus (VRSA)
S. aureus bacteria are a leading cause of healthcare-associated infections in the U.S. Some people carry the bacteria in their noses and it does not cause infection. However, it can cause skin infections and pneumonia in the general community and severe illness in hospitalized patients, including bloodstream, heart valve and surgical site infections, and pneumonia. Patients in healthcare settings who have weakened immune systems, have been treated with antibiotics, have wounds from surgery or have a breathing device or catheter are most at risk for severe infection. The bacteria can spread among patients from unclean hands of healthcare workers or visitors or when patients come in direct contact with contaminated bed linens and medical equipment. In addition to being resistant to methicillin and related antibiotics, a small number of S. aureus infections are also resistant to vancomycin, the drug most commonly used to treat serious S. aureus, leaving few to no treatment options.
TB is an airborne disease that typically infects the lungs but can attack any other organ of the body. TB is generally treated with a course of antibiotics that can last months to years. However, Mycobacterium tuberculosis, the bacteria that causes TB disease, is becoming resistant to the antibiotics commonly used to treat it. Multidrug-resistant TB (MDR-TB) refers to infections caused by bacteria resistant to isoniazid and rifampin, the two most potent TB drugs. Extensively drug-resistant TB (XDR-TB) refers to infections caused by bacteria that are resistant to isoniazid and rifampin, any fluoroquinolone and at least one of three injectable second-line drugs. People with drug-resistant TB face a higher risk of death and infections can be costly and time-consuming to treat. Learn more about NIAID’s TB research program.
Drug-resistant Streptococcus pneumoniae
S. pneumoniae can cause pneumococcal disease, which includes pneumonia, ear infections, sinus infections, meningitis and bloodstream infections. Some infections can become invasive, leading to hospitalization and potentially death. S. pneumoniae has developed resistance to commonly used antibiotics such as amoxicillin and azithromycin and is developing resistance to other drugs.
Erythromycin-resistant Group A Streptococcus
Group A Streptococcus bacteria can cause a range of disease such as strep throat, scarlet fever, impetigo, toxic shock syndrome, rheumatic fever and necrotizing fasciitis (“flesh-eating” disease). It is transmitted when an infected person coughs or sneezes and passes water droplets that touch another person’s nose or mouth. Group A Streptococcus can still be treated with the first-line drug penicillin, but the bacteria is developing resistance to clindamycin (the drug commonly used to treat severe, life-threatening infections) and macrolides, including erythromycin. Read more about NIAID research on Group A Streptococcal infections.
Clindamycin-resistant Group B Streptococcus
Group B Streptococcus bacteria can cause severe illness such as bloodstream infections, pneumonia, meningitis and skin infections. However, it is usually harmless in healthy adults and people can carry group B Streptococcus in their bodies without having symptoms. The bacterium is also a leading cause of severe infections in infants. If a pregnant woman tests positive for group B Streptococcus, physicians will prescribe her antibiotics during labor to prevent the spread of the bacteria to the baby. Group B Streptococcus can be treated with penicillin, but it is developing resistance to the recommended second-line drugs clindamycin and erythromycin.