18 deadliest drug-resistant infections



The U.S. Centers for Disease Control and Prevention in 2013 released a list of drug-resistant bacterial and fungal infections, labeling each as “urgent,” “serious” or “concerning,” reflecting how dangerous they are, how prevalent and how difficult to treat. Most bacteria are classified as either Gram positive or Gram negative, depending on how they react to a laboratory staining technique. While the Gram-positive bugs methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile are the most well-known drug-resistant bacteria, many Gram-negative species are particularly hard to treat because they have an extra outer membrane that shields them from drugs.
Clostridium difficile

 

Prolonged use of antibiotics can allow this common intestinal inhabitant to explode into a lethal infection as the drugs kill off its beneficial rivals in the human gut. Spread via hospital surfaces and human contact, C. difficile most often affects the elderly. It causes severe diarrhea and can damage the colon, and it has become very difficult to treat.

CDC threat category: Urgent
CDC death estimate: 15,000
Statistical uncertainty of CDC estimate: 7,600 to 20,000
Number of states requiring reporting of disease: 17
Number of states requiring reporting of deaths: 3
Gram positive
Carbapenem-resistant Enterobacteriaceae (CRE)

 

Drug-resistant members of this family of Gram-negative bacteria are spread largely in healthcare settings. Strains of some species in the group, including Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae and Klebsiella pneumoniae, are resistant to antibiotics called carbapenems, considered one of the last lines of defense against such infections. When carbapenems fail, doctors are often forced to turn to colistin, a decades-old drug that can have toxic side effects – and some CRE strains are already showing resistance to that drug, too.
CDC threat category: Urgent
CDC death estimate: 610
Statistical uncertainty of CDC estimate: 180 to 1,200
Number of states requiring reporting of disease: 22
Number of states requiring reporting of deaths: 6
Gram negative
Drug-resistant Neisseria gonorrhoeae

 

Some strains of this sexually transmitted infection, which can cause painful urination and inflammation in the pelvis, have developed resistance to the drugs commonly used to treat it.
CDC threat category: Urgent
CDC death estimate: Fewer than 5
Statistical uncertainty of CDC estimate: Not calculated
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram negative
Multidrug-resistant Acinetobacter

 

Acinetobacter baumannii and other members of this genus are typically found in soil and water, and can survive on human skin and on medical equipment. They can cause pneumonia, urinary tract infections and serious blood or wound infections.
CDC threat category: Serious
CDC death estimate: 500
Statistical uncertainty of CDC estimate: 140 to 920
Number of states requiring reporting of disease: 6
Number of states requiring reporting of deaths: 2
Gram negative
Drug-resistant Campylobacter

 

This bug infects humans through contaminated milk, water or food – especially poultry – causing diarrhea, cramps and fever.
CDC threat category: Serious
CDC death estimate: 28
Statistical uncertainty of CDC estimate: 0 to 120
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram negative
Fluconazole-resistant Candida

 

Candida is a fungus, not a bacterium. The CDC included it on its list because strains of the fungus are increasingly showing resistance to the drugs commonly used to treat it. Candida is present in many people without doing harm, but it can cause serious infections in patients with weakened immune systems or if introduced into the bloodstream.

CDC threat category: Serious
CDC death estimate: 220
Statistical uncertainty of CDC estimate: 65 to 430
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Extended spectrum β-lactamase producing Enterobacteriaceae (ESBLs)

 

These bacteria, including strains of Escherichia coli and Klebsiella pneumoniae, produce an enzyme that destroys many antibiotics. They most often manifest as urinary tract infections, but can also cause serious bloodstream and lung infections. They are spread through improperly washed hands, surfaces and medical equipment. Some of the ESBL E. coli strains are also foodborne.

CDC threat category: Serious
CDC death estimate: 1,700
Statistical uncertainty of CDC estimate: 500 to 3,300
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram negative

Vancomycin-resistant Enterococcus (VRE)

 

Enterococci normally live in human intestines and the female genital tract without issue, but they can lead to serious infection when they spread through urinary or intravenous catheters, or enter the bloodstream. Some strains have developed resistance to vancomycin, one of the most powerful antibiotics available.

CDC threat category: Serious
CDC death estimate: 1,300
Statistical uncertainty of CDC estimate: 390 to 2,600
Number of states requiring reporting of disease: 10
Number of states requiring reporting of deaths: 1
Gram positive
Multidrug-resistant Pseudomonas aeruginosa

 

This pathogen thrives in moist environments and mostly affects hospital patients, especially those using mechanical ventilation or catheters or with surgical or burn wounds. The Gram-negative bacteria are exceptionally difficult to treat as they have developed resistance to multiple classes of drugs, in addition to their broad natural resistance.
CDC threat category: Serious
CDC death estimate: 440
Statistical uncertainty of CDC estimate: 130 to 850
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram negative
Drug-resistant non-typhoidal Salmonella

 

Non-typhoidal Salmonella is a common foodborne pathogen that causes more dangerous infection when it is resistant to common antibiotics. It causes severe, sometimes bloody diarrhea, cramps and fever.
CDC threat category: Serious
CDC death estimate: 40
Statistical uncertainty of CDC estimate: 0 to 120
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram negative
Drug-resistant Salmonella typhi

 

A member of the Enterobacteriaceae family, these bacteria spread through contaminated food or water or through person-to-person contact. Typhoid fever, rare in developed countries, can lead to serious health complications and death if untreated.
CDC threat category: Serious
CDC death estimate: Fewer than 5
Statistical uncertainty of CDC estimate: Not calculated
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram negative
Drug-resistant Shigella

 

Shigella mostly affects young children and is spread through hand contact, food or water. In the U.S., a drug-resistant strain of the infection, which causes painful diarrhea, has been spread largely by travelers and spreads especially quickly in childcare settings and among homeless people and gay and bisexual men.
CDC threat category: Serious
CDC death estimate: Fewer than 5
Statistical uncertainty of CDC estimate: Not calculated
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram negative
Drug-resistant Shigella

 

Shigella mostly affects young children and is spread through hand contact, food or water. In the U.S., a drug-resistant strain of the infection, which causes painful diarrhea, has been spread largely by travelers and spreads especially quickly in childcare settings and among homeless people and gay and bisexual men.
CDC threat category: Serious
CDC death estimate: Fewer than 5
Statistical uncertainty of CDC estimate: Not calculated
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram negative
Drug-resistant Streptococcus pneumoniae

 

S. pneumoniae can cause pneumonia; ear, sinus and bloodstream infections; and meningitis. Some strains are resistant to multiple drugs, which can be especially dangerous to young children, the elderly and HIV patients. It is spread person-to-person, often in childcare and healthcare facilities.
CDC threat category: Serious
CDC death estimate: 7,000
Statistical uncertainty of CDC estimate: Not calculated
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram positive
Drug-resistant tuberculosis

 

Mycobacterium tuberculosis is spread through the air and usually infects the lungs, but can also infect organs such as the brain or kidneys. If caught early, the infection is largely treatable, but drug-resistant strains have emerged over the years. Some do not respond to many types of antibiotics and can be deadly in immunocompromised patients, such as those with HIV.
CDC threat category: Serious

The CDC conducts active tuberculosis surveillance in all 50 states and Washington, D.C. In 2011, 50 people died of drug-resistant tuberculosis.
Vancomycin-resistant Staphylococcus aureus (VRSA)

 

These S. aureus infections are resistant to vancomycin, one of the most powerful antibiotics available. They most often occur as skin infections. They can become deadly if they manifest as bloodstream or lung infections, especially in people with pneumonia or on ventilators.
CDC threat category: Concerning
CDC death estimate: Fewer than 5
Statistical uncertainty of CDC estimate: Not calculated
Number of states requiring reporting of disease: 40
Number of states requiring reporting of deaths: 14
Gram positive
Erythromycin-resistant Group A Streptococcus

 

Group A Streptococcus is the most common cause of strep throat in children and adults, and erythromycin is one of the most commonly used antibiotics to treat it. The infection is usually mild, but can sometimes be life-threatening. It is spread through contact with infected mucus or through skin wounds or sores.
CDC threat category: Concerning
CDC death estimate: 160
Statistical uncertainty of CDC estimate: Not calculated
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram positive
Clindamycin-resistant Group B Streptococcus



In newborns, Group B Streptococcus is a common cause of sepsis, a potentially fatal blood infection. Adults are susceptible, too. The widespread use of antibiotics to prevent the infection in newborns has caused some strains of bacteria to develop resistance to the drug clindamycin.
CDC threat category: Concerning
CDC death estimate: 440
Statistical uncertainty of CDC estimate: Not calculated
Number of states requiring reporting of disease: N/A
Number of states requiring reporting of deaths: N/A
Gram positive

Key facts

• Antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi.
• AMR is an increasingly serious threat to global public health that requires action across all government sectors and society.
• Without effective antibiotics, the success of major surgery and cancer chemotherapy would be compromised.
• The cost of health care for patients with resistant infections is higher than care for patients with non-resistant infections due to longer duration of illness, additional tests and use of more expensive drugs.
• Globally, 480 000 people develop multi-drug resistant TB each year, and drug resistance is starting to complicate the fight against HIV and malaria, as well.

What is antimicrobial resistance?

Antimicrobial resistance happens when microorganisms (such as bacteria, fungi, viruses, and parasites) change when they are exposed to antimicrobial drugs (such as antibiotics, antifungals, antivirals, antimalarials, and anthelmintics). Microorganisms that develop antimicrobial resistance are sometimes referred to as “superbugs”.
As a result, the medicines become ineffective and infections persist in the body, increasing the risk of spread to others.

Why is antimicrobial resistance a global concern?

New resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases, resulting in prolonged illness, disability, and death.
Without effective antimicrobials for prevention and treatment of infections, medical procedures such as organ transplantation, cancer chemotherapy, diabetes management and major surgery (for example, caesarean sections or hip replacements) become very high risk.
Antimicrobial resistance increases the cost of health care with lengthier stays in hospitals and more intensive care required.
Antimicrobial resistance is putting the gains of the Millennium Development Goals at risk and endangers achievement of the Sustainable Development Goals.

What accelerates the emergence and spread of antimicrobial resistance?

Antimicrobial resistance occurs naturally over time, usually through genetic changes. However, the misuse and overuse of antimicrobials is accelerating this process. In many places, antibiotics are overused and misused in people and animals, and often given without professional oversight. Examples of misuse include when they are taken by people with viral infections like colds and flu, and when they are given as growth promoters in animals and fish.
Antimicrobial resistant-microbes are found in people, animals, food, and the environment (in water, soil and air). They can spread between people and animals, and from person to person. Poor infection control, inadequate sanitary conditions and inappropriate food-handling encourage the spread of antimicrobial resistance.

Present situation

Resistance in bacteria

Antibiotic resistance is present in every country.
Patients with infections caused by drug-resistant bacteria are at increased risk of worse clinical outcomes and death, and consume more health-care resources than patients infected with non-resistant strains of the same bacteria.
Resistance in Klebsiella pneumoniae – common intestinal bacteria that can cause life-threatening infections – to a last resort treatment (carbapenem antibiotics) has spread to all regions of the world. K. pneumoniae is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections, and infections in newborns and intensive-care unit patients. In some countries, because of resistance, carbapenem antibiotics do not work in more than half of people treated for K. pneumoniae infections.
Resistance in E. coli to one of the most widely used medicines for the treatment of urinary tract infections (fluoroquinolone antibiotics) is very widespread. There are countries in many parts of the world where this treatment is now ineffective in more than half of patients.
Treatment failure to the last resort of medicine for gonorrhoea (third generation cephalosporin antibiotics) has been confirmed in at least 10 countries (Australia, Austria, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom of Great Britain and Northern Ireland).
WHO recently updated the treatment guidelines for gonorrhoea to address emerging resistance. The new WHO guidelines do not recommend quinolones (a class of antibiotic) for the treatment of gonorrhoea due to widespread high levels of resistance. In addition, treatment guidelines for chlamydial infections and syphilis were also updated.
Resistance to first-line drugs to treat infections caused by Staphlylococcus aureus—a common cause of severe infections in health facilities and the community—is widespread. People with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection.
Colistin is the last resort treatment for life-threatening infections caused by Enterobacteriaceae which are resistant to carbapenems. Resistance to colistin has recently been detected in several countries and regions, making infections caused by such bacteria untreatable.

Resistance in tuberculosis (TB)

WHO estimates that, in 2014, there were about 480 000 new cases of multidrug-resistant tuberculosis (MDR-TB), a form of tuberculosis that is resistant to the 2 most powerful anti-TB drugs. Only about a quarter of these (123 000 cases) were detected and reported. MDR-TB requires treatment courses that are much longer and less effective than those for non-resistant TB. Globally, only half of MDR-TB patients were successfully treated in 2014.
Among new TB cases in 2014, an estimated 3.3% were multidrug-resistant. The proportion is higher among people previously treated for TB, at 20%.
Extensively drug-resistant tuberculosis (XDR-TB), a form of tuberculosis that is resistant to at least 4 of the core anti-TB drugs, has been identified in 105 countries. An estimated 9.7% of people with MDR-TB have XDR-TB.

Resistance in malaria

As of July 2016, resistance to the first-line treatment for P. falciparum malaria (artemisinin-based combination therapies, also known as ACTs) has been confirmed in 5 countries of the Greater Mekong subregion (Cambodia, the Lao People’s Democratic Republic, Myanmar, Thailand and Viet Nam). In most places, patients with artemisinin-resistant infections recover fully after treatment, provided that they are treated with an ACT containing an effective partner drug. However, along the Cambodia-Thailand border, P. falciparum has become resistant to almost all available antimalarial medicines, making treatment more challenging and requiring close monitoring. There is a real risk that multidrug resistance will soon emerge in other parts of the subregion as well.The spread of resistant strains to other parts of the world could pose a major public health challenge and jeopardize important recent gains in malaria control.
A "WHO Strategy for Malaria Elimination in the Greater Mekong subregion (2015-2030)" was endorsed by all 5 countries, as well as China.

Resistance in HIV

In 2010, an estimated 7% of people starting antiretroviral therapy (ART) in developing countries had drug-resistant HIV. In developed countries, the same figure was 10–20%. Some countries have recently reported levels at or above 15% amongst those starting HIV treatment, and up to 40% among people re-starting treatment. This requires urgent attention.
Increasing levels of resistance have important economic implications as second and third-line regimens are 3 times and 18 times more expensive, respectively, than first-line drugs.
Since September 2015, WHO has recommended that everyone living with HIV start on antiretroviral treatment . Greater use of ART is expected to further increase ART resistance in all regions of the world. To maximize the long-term effectiveness of first-line ART regimens, and to ensure that people are taking the most effective regimen, it is essential to continue monitoring resistance and to minimize its further emergence and spread. In consultation with countries, partners and stakeholders, WHO is currently developing a new "Global Action Plan for HIV Drug Resistance (2017-2021)".

Resistance in influenza

Antiviral drugs are important for treatment of epidemic and pandemic influenza. So far, virtually all influenza A viruses circulating in humans were resistant to one category of antiviral drugs – M2 Inhibitors (amantadine and rimantadine). However, the frequency of resistance to the neuraminidase inhibitor oseltamivir remains low (1-2%). Antiviral susceptibility is constantly monitored through the WHO Global Influenza Surveillance and Response System.

Need for coordinated action

Antimicrobial resistance is a complex problem that affects all of society and is driven by many interconnected factors. Single, isolated interventions have limited impact. Coordinated action is required to minimize the emergence and spread of antimicrobial resistance.
All countries need national action plans on AMR.
Greater innovation and investment are required in research and development of new antimicrobial medicines, vaccines, and diagnostic tools.

WHO's response

WHO is providing technical assistance to help countries develop their national action plans, and strengthen their health and surveillance systems so that they can prevent and manage antimicrobial resistance. It is collaborating with partners to strengthen the evidence base and develop new responses to this global threat.
WHO is working closely with the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE) in a ‘One Health’ approach to promote best practices to avoid the emergence and spread of antibacterial resistance, including optimal use of antibiotics in both humans and animals.
A global action plan on antimicrobial resistance was adopted by Member States at the Sixty-eighth World Health Assembly and supported by the governing bodies of FAO and OIE in May and June 2015. The goal of the global action plan is to ensure, for as long as possible, continuity of successful treatment and prevention of infectious diseases with effective and safe medicines that are quality-assured, used in a responsible way, and accessible to all who need them.
A high-level meeting on antimicrobial resistance at the United Nations General Assembly will be held on 21 September 2016 to accelerate global commitments and enhance national multi-sectoral efforts to combat antimicrobial resistance.