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Antibiotic Resistance: The Top 10 List

Medically reviewed by L. Anderson, PharmD Last updated on Jul 29, 2019.

Intro | FAQs | Tables of Resistant Bacteria and Treatment Options | Recently Approved Antibiotics

What is Antibiotic Resistance?

Antibiotic resistance is an urgent threat to global health, and the US Centers for Disease Control and Prevention (CDC) considers it one of their top concerns. Antibiotic resistance is the ability of bacteria to withstand the antimicrobial power of antibiotics. In other words, an antibiotic that previously cured an infection does not work as well anymore, or may not work at all, to kill the bacteria.

The rates of resistance to antibiotics continue to rise due to overuse of antibiotics, and new antimicrobial agents are slow to be developed. Infections with drug-resistant bacteria may lead to longer and more costly hospital care, and increase the risk of dying from the infection. Dangerous, resistant bacteria known as "superbugs" are being reported.

Each year 2 million people get an antibiotic-resistance infection, and close to 23,000 people die. The annual costs of fighting resistant bacterial infections in the U.S. are estimated to be between $21 billion and $34 billion.

Frequently asked questions about antibiotic resistance include:

How do bacteria become resistant to antibiotics?

Bacteria become resistant to antibiotics by adapting their structure or function in some way as a defense mechanism. The antibiotic may have worked effectively before the resistance occurred; however, the change helps the bacteria to fend off the killing activity of the antibiotic. 

This adaptation can happen in several ways. Bacteria can:

  • neutralize the antibiotic before it has a "killing" effect
  • pump out the antibiotic from cells
  • change the site (or receptor) where the antibiotic normally works
  • share genetic material with other bacteria to also make them resistant.

The resistant bacteria that survive are able to multiply, spread and cause further infections in the individual, family, community, or health care setting. In turn, these infections are more resistant to another round of the same or similar antibiotic.

The Centers for Disease Control and Prevention (CDC) has posted a listing of the top 18 drug-resistant threats to the United States. The hazard levels are grouped as urgent, serious, and concerning. Urgents threats to human health include: Clostridium difficile, carbapenem-resistant Enterobacteriaceae, and drug resistant Neisseria gonorrhoeae.

Lists of Common Bacteria with High Antibiotic Resistance

To gain a better understanding of antibiotic resistance, the following tables list common bacteria that have become highly resistant, associated antibiotics with reduced activity, and antibiotics that may be appropriate for treatment of that resistant bacteria.

Final selection of an antibiotic treatment regimen for drug-resistant bacteria should always be tailored for a patient according to the antimicrobial susceptibility test result and the expertise of a medical professional. Treatment selection depends upon:

  • the type and severity of the infection
  • local drug susceptibility patterns
  • patient-specific factors like age, kidney and liver function
  • drug allergies
  • previous treatments
  • cost concerns.

1. Methicillin-resistant Staphylococcus aureus (MRSA)

Current/Emerging Resistant Bacteria Infection Types Resistance Notes Treatment Options
Methicillin-resistant Staphylococcus aureus “staph” (MRSA)

Infections can range from skin and soft tissue infections (cellulitis, abscess), to urinary tract infections, osteomyelitis (bone), endocarditis (heart), pneumonia (lung) infections, and meningitis (brain infection).

Incision/drainage or debridement may be required.

MRSA has become resistant to common antibiotics such as beta-lactams, including methicillin, amoxicillin, penicillin, nafcillin, oxacillin, and cephalosporins.

MRSA is spread by contact. MRSA usually affects the skin, such as surgical sites. MRSA can also cause lung or blood infections.

Infection outbreaks can be acquired in the community (CA-MRSA) or in healthcare settings such as nursing homes, dialysis centers, or hospitals (MRSA).

The CDC lists MRSA as a "serious" threat.

Antibiotics to treat MRSA at home (i.e., local soft tissue infection) may include a 7-10-day course of an oral antibiotic such as:

Patients with more complicated infections may require intravenous antibiotics for MRSA in the hospital such as vancomycin, linezolid, or daptomycin.

2. Vancomycin-resistant Staphylococcus aureus (VRSA)

Current/Emerging Resistant Bacteria Infection Types Resistance Notes Treatment Options

Vancomycin-intermediate and Vancomycin-resistant Staphylococcus aureus (VRSA and VISA)

MIC Breakpoints:

  • vancomycin susceptible: ≤2 mcg/mL
  • vancomycin intermediate: 4-8 mcg/mL
  • vancomycin resistant: ≥16 mcg/mL
Infections can range from skin and soft tissue infections, urinary tract infections, pneumonia (lung) infections, and meningitis (brain infection).

VRSA is resistant to the antibiotic vancomycin, an antibiotic used to treat serious infections including MRSA.

The CDC lists VRSA as a "concerning" threat.

Optimal regimens for VRSA treatment are uncertain. Options may  include:

3. Drug resistant Streptococcus pneumoniae

Current/Emerging Resistant Bacteria  Infection Types Resistance Notes Treatment Options
Drug-resistant Streptococcus pneumoniae

S. pneumoniae causes pneumococcal disease.

Infection types can include ear and sinus infections, community-acquired pneumonia (CAP) lung infections, meningitis, and bloodstream infections.

Drug-resistance to Streptococcus pneumoniae depends upon the area in which you live.

When these bacteria are resistant to penicillin, they are often resistant to many other antibiotic classes.

Resistance in the US is relatively high.

The CDC lists drug resistant S. pneumoniae as a "concerning" threat.

4. Vancomycin-resistant Enterococcus (VRE)

Current/Emerging Resistant Bacteria Infection Types Resistance Notes Treatment Options
Vancomycin-resistant Enterococcus (VRE)

Enteroccocci are bacteria that are normally present in the human body, such as the intestines and female genital tract.

VRE infections are resistant to the antibiotic vancomycin and often occur in hospitals.

VRE infection can easily be spread from person to person.

Infection types may include meningitis, urinary tract infections, bloodstream infections, surgical sites, and catheter-related infections.

The best regimen for treating VRE is not always known. 

Laboratory testing of the VRE can determine which antibiotics will work best.

The CDC lists drug-resistant VRE as a "serious" threat.

These agents have been used for VRE. Combinations are often needed.

Other agents that may be used for VRE include:

5. Multi-drug resistant Pseudomonas aeruginosa 

Current/Emerging Resistant Bacteria Infection Types Resistance Notes Treatment Options
Pseudomonas aeruginosa (multidrug resistant strains)

Severe Pseudomonas infections can occur in people with weakened immune systems or in the hospital.

Sites of infections may occur in the bloodstream, lungs (pneumonia), skin and soft-tissue (burns), complicated UTIs and abdominal infections, heart, brain, catheter-related, and at surgical sites.

Pseudomonas aeruginosa is resistant to many types of antibiotics.

Combination treatment may be needed in patients with more severe infections.

The CDC lists multidrug-resistant Pseudomonas aeruginosa as a "serious" threat.


Agents that may be used include:

6. Clostridioides difficile 

Current/Emerging Resistant Bacteria  Infection Types Resistance Notes Treatment Options
Clostridioides difficile (C. difficile or C. diff) (previously Clostridium difficile)

C. difficile causes life-threatening watery or bloody diarrhea and colitis (an inflammation of the colon), primarily in patients with both recent medical care and antibiotics.

C. diff occurs when someone with unwashed hands touches and contaminates surfaces, or from patient-to-patient spread in the hospital.

Patients need to be isolated in the hospital and hand sanitizer doesn’t kill C. diff.

Those on antibiotics are 7 to 10 times more likely to get C. diff while taking the drugs or during the month after. Antibiotics are often prescribed unnecessarily.

Studies have shown that 30% to 50% of all antibiotics prescribed in hospitals are either not needed or incorrect.

The CDC lists C. difficile infection as an "urgent" threat.

Stop causative antibiotic as soon as possible. Treatment options may include:

  • vancomycin
  • fidaxomicin (Dificid)
  • metronidazole
  • fecal microbiota transplant (FMT) may be needed for reccuring C. difficile infection*
  • other surgery may be needed.

*In June 2019, FDA issued a safety communication regarding the use of Fecal Microbiota for Transplantation (FMT) and the risk of serious or life-threatening infections due to transmission of multi-drug resistant organisms (MDROs).

7. Carbapenem-resistant Enterobacteriaceae (CRE)

Current/Emerging Resistant Bacteria Infection Types Resistance Notes Treatment Options

Carbapenem-resistant Enterobacteriaceae (CRE) include:

  • Klebsiella pneumoniae and other species
  • Escherichia coli (E. coli) species

Can lead to pneumonias (lung infections), bloodstream infections, urinary tract infections (UTI), upper respiratory tract infections, abdominal infections, febrile neutropenia, surgical wound infections, meningitis.


CRE infections tend to occur in hospitals, nursing homes, and in people with urinary or intravenous catheters, people on ventilators, contact with endoscopes, duodenoscopes.

The Enterobacteriaceae are a normal, usually harmless part of our digestive tract bacteria that can become resistant to a class of antibiotics known as carbapenems.

Carbapenems are a beta-lactam antibiotic class with a broad spectrum of activity that are structurally related to the penicillins. Examples include: meropenem, ertapenem, and imipenem-cilastatin (Primaxin). 

Carbapenems are noted for their ability to inhibit extended spectrum beta-lactamase enzymes and are usually reserved for the most serious infections or used as a last-line treatment when other antibiotics fail.

The CDC lists CRE as an "urgent" threat; its highest level of concern. 

Treatment selection for infections with carbapenem-resistant Enterobacteriaceae should be made on a case-by-case basis by an infectious disease specialist.

Agents FDA-approved for these types of infections include: 

8. Multi-drug resistant Mycobacterium tuberculosis (MDR-TB)

Current/Emerging Resistant Bacteria  Infection Types Resistance Notes Treatment Options
Multi-drug resistant Mycobacterium tuberculosis (MDR-TB) or extensively drug-resistant TB (XDR-TB)

Tuberculosis (TB) is a contagious disease caused by the bacteria Mycobacterium tuberculosis.

Multi-drug resistant TB (MDR-TB) leads to tuberculosis (a bacterial lung infection) that is resistant to different antibiotics including both isoniazid (INH) and rifampin, which are often used as first line agents.

Extensively drug-resistant TB (XDR-TB) is a rare type of MDR TB with resistance to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin), per the CDC.

Select treatment based on consult with an infectious disease specialist with MDR-TB experience. 

Treatment depends on the results of drug susceptibility testing, prior drug use, drug availability, cost and other patient-specific factors.

Based on susceptibility, use at least four active agents for MDR-TB; shorter or longer regimens are suggested based on risk factors.

Shortened, standard regimens or longer, patient-specific regimens may be selected for MDR-TB (refer to 2019 WHO Guidelines).

The CDC lists drug-resistant TB as a "serious" threat.

Selected medications are used in combination regimens for MDR-TB for varied durations.

For example, a combination of drugs (as recommended by the WHO) may be used for MDR-TB:

9. Multidrug-resistant Acinetobacter

Current/Emerging Resistant Bacteria Infection Types Resistance Notes Treatment Options
Multidrug-resistant Acinetobacter

People with weakened immune systems (immunocompromised), including hospitalized patients, are more at risk of getting an Acinetobacter infection, which can be resistant to many commonly prescribed antibiotics. Acinetobacter poses little risk to healthy people with a healthy immune system. 

Acinetobacter is often resistant to many commonly prescribed antibiotics.

Types of infections due to Acinetobacter can include: pneumonia (commonly ventilator-associated), UTI, septicemia, catheter-related infections, traumatic wound infections.

Acinetobacter can be spread by direct contact and may be found on skin or in food, water, or soil. It can spread from hospitals and intensive care units (ICU).

Acinetobacter baumannii is highly contagious and accounts for about 80% of Acinetobacter infections.

The CDC lists multidrug-resistant Acinetobacter as a "serious" threat.

Resistance to treatment is common with Acinetobacter; resistance can occur to initial therapies such as beta-lactams and carbapenems.

Dosing should be made on an individualized basis taking into account localized resistance pattern and antimicrobial susceptibility testing.

Treatment decisions should be made in conjunction with an infectious disease specialist that has experience treating drug-resistant Acinetobacter.

Options may include:

Addition of a second agent such as a carbapenem, minocycline, tigecycline (Tygacil), or rifampin, may be also preferred.

 

10. Drug-resistant Neisseria gonorrhoeae

Current/Emerging Resistant Bacteria Infection Types Resistance Notes Treatment Options
Drug-resistant Neisseria gonorrhoeae

N. gonorrhoeae causes the sexually transmitted disease gonorrhea.

Lack of effective treatments to cure at least 95% of the population with gonorrhea could lead to a significant public health concern.

Sexual partners should also be tested and treated for gonorrhea.

 

Gonorrhea has developed resistance to most antibiotics used for its treatment.

These bacteria are now resistant to the fluoroquinolone antibiotics like ciprofloxacin (Cipro).

The CDC lists drug-resistant Neisseria gonorrhoeae as an "urgent" threat.

  • Dual therapy: a single intramuscular injection of ceftriaxone (Rocephin) given with oral azithromycin (Zithromax, Zmax)
  •  

In patients with cephalosporin allergies, research suggests the use of gemifloxacin (Factive) or gentamicin, combined with oral azithromycin (Zithromax), is highly successful in treating gonorrhea.

* Note: These tables are not a comprehensive listing of all resistant bacteria and possible treatments. Antibiotic resistance patterns are constantly evolving and bacteria may not always exhibit resistance to select antibiotics in every patient. In all cases, antibiotic selection should be based on site of infection and clinical presentation as evaluated by a healthcare professional, culture/sensitivity and other needed laboratory results, local resistance/susceptibility patterns, and patient-specific characteristics. In many instances, the care of a team of healthcare providers, including an infectious disease specialist, may be required.

Other Types of Resistant Bacteria

Other types of bacteria that may be affected by antibiotic resistance include:

  • Staphylococcus epidermidis (coagulase-negative staphylococci, CoNS).
  • Drug-resistant Campylobacter
  • Fluconazole-resistant Candida
  • Extended-spectrum Beta-lactamase producing Enterobacteriaceae
  • Drug-resistant non-typhoidal Salmonella
  • Drug-resistant Salmonella Serotype Typhi
  • Drug-resistant Shigella
  • Erythromycin-resistant Group A Streptococcus
  • Clindamycin-resistant Group B Streptococcus

Why is antibiotic resistance so important?

Overuse and misuse of antibiotics worldwide is leading to the global health care issue of antibiotic resistance. Antibiotic resistant infections may occur, and in the worse-case scenario, there may be no antibiotics left that are effective for the infection. This situation can be life-threatening in a serious infection.

One reason bacteria are becoming resistant is because antibiotics are often inappropriately used for an illness caused by a virus. Antibiotics cannot kill viral illnesses. Examples of illnesses that are caused by viruses include:

  • most sore throats (pharyngitis)
  • coughs, colds and runny noses (rhinitis)
  • sinus infections, respiratory tract infections (sinusitis, bronchitis)
  • the flu (influenza virus)

Most viral illnesses do not need special medication and are “self-limiting”, meaning the patient’s own immune system can fight off the illness. A patient with a viral illness can also rest, drink plenty of fluids and use symptomatic treatment, such as acetaminophen or ibuprofen to relieve fever or body aches.

Sometimes, in complicated or prolonged viral infections, bacteria may invade as well, and cause what is known as a “secondary infection” In these cases, a health care practitioner can recommend an antibiotic, if one is needed.

What can patients and health care providers do to help stop the spread of antibiotic resistance?

In an illness where the infection is due to a virus, such as a cough, cold or the flu, patients should not ask or demand that their health care provider prescribe an antibiotic. The antibiotic will not cure the viral infection, and the patient may have side effects from the unnecessary medication. The health care provider can suggest other ways to help patients feel better if they have a viral illness.

Patients should not use antibiotics that were prescribed for someone else, and they should not share their antibiotics with others. Also, patients should discard any antibiotic that may be left-over from a previous illness, and should not save it to use for another infection. Why?

  • It may not be the right antibiotic for the infection.
  • It may be out of date and ineffective
  • There may not be enough medication for a full course.
  • If the new illness is a viral infection, an antibiotic is not be needed.
  • Antibiotic resistant bacteria can also be spread to others if the infection is not treated correctly.

All of these practices can further the problem of antibiotic resistance.

Staying up-to-date on vaccination is important. Some vaccines can prevent bacterial illnesses that might otherwise require an antibiotic. Antiviral vaccines, such as the flu shot, can help prevent a primary illness that may be associated with a secondary bacterial infection (like pneumonia), that eventually does require an antibiotic.

When a patient does receive an antibiotic prescription, there are further steps they can take to fight resistance and ensure safe drug use. Many antibiotics can be expensive. Health care providers can order and give a generic antibiotic if one is available that will treat the specific bacterial infection. A generic medicine may be more affordable and will treat the infection just as well as the higher cost brand-name drug. If a patient cannot afford their antibiotic, it is important to tell their physician or pharmacist so that an alternative, lower-cost medication can be ordered.

Finishing the full course of antibiotic is important to help prevent resistance to antibiotics and to keep the infection from recurring. Even if patients feel better or even cured in the first few days of treatment, they should still finish the entire course of their antibiotic.

What is being done about the future of antibiotic resistance?

The Food and Drug Administration (FDA) and the Centers for Disease Control (CDC) have launched initiatives to help address antibiotic resistance. The FDA has issued drug labeling regulations and recommends judicious prescribing of antibiotics by health care providers.

FDA is also encouraging new research into effective antibiotic regimens, vaccines and diagnostic tests. In fact, over the last decade, several new, innovative antibiotics have been approved to fight serious infections. Many of these new antibiotics are approved under the FDA's qualified infectious disease product (QIDP) program to encourage antibiotic development. The program offers incentive to manufacturers, such as expedited review and five extra years of marketing exclusivity.

Recently Approved Antibiotics for Resistant Infections

  • Recarbrio (imipenem, cilastatin, and relebactam) for intravenous injection approved in July 2019: a combination a penem antibacterial, renal dehydropeptidase inhibitor, and beta- lactamase inhibitor used for susceptible bacteria in adults 18 years and older with complicated urinary tract infections (cUTI), including pyelonephritis, and complicated intra-abdominal infections (cIAI) when there are limited or no alternative treatment options. Relebactam is a newly approved beta-lactamase inhibitor.
  • Nuzyra (omadacycline), an aminomethylcycline tetracycline antibiotic approved in October 2018 for adults with community-acquired bacterial pneumonia (CABP) and acute skin and skin structure infections (ABSSSI). Nuzyra is a once-daily intravenous (IV) and oral antibiotic that exhibits broad activity, including Gram-positive, Gram-negative, atypicals, and drug resistant bacteria.
  • Arikayce (amikacin liposome inhalation suspension), an aminoglycoside antibiotic, approved in September 2018 to treat resistant lung disease caused by Mycobacterium avium complex (MAC) in a limited population of patients who do not respond to conventional treatment (refractory disease). 
  • Xerava (eravacycline), a tetracycline antibiotic approved in August 2018 for the treatment of complicated intra-abdominal infections (cIAI) in patients 18 years and older. Xerava is a fluorocycline antibiotic in the tetracycline class with potent activity against multi-drug resistant pathogens. In studies, Xerava achieved high cure rates in patients with Gram-negative pathogens, including resistant isolates.
  • Xepi (ozenoxacin) Cream, 1%, a topical non-fluorinated quinolone, approved in December 2017 for impetigo due to Staphylococcus aureus or Streptococcus pyogenes in patients two months of age and older. In Phase III studies, Xepi showed excellent antibacterial activity against S. aureus and S. pyogenes (90.8% of patients using Xepi versus 69.8% for placebo), including methicillin-resistant S. aureus (MRSA).
  • Baxdela (delafloxacin), a fluoroquinolone antibiotic approved in June 2017 for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible bacteria. Baxdela targets both gram-positive and gram-negative bacteria, including the serious pathogen MRSA (methicillin-resistant Staphylococcus aureus).
  • Pretomanid, a oral nitroimidazo-oxazine antimycobacterial, was FDA-approved in August 2019 to be used in combination with bedaquiline (Sirturo) and linezolid (Zyvox) for the treatment of adults with pulmonary extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB). MDR-TB and XDR-TB are difficult to treat due to resistance to available drug options.

Antibiotic resistance is an epidemic that everyone can help to prevent: health care providers, patients and caregivers. Education, judicious use and prescribing of antibacterials, and 100% patient adherence to medication regimens are key in helping to stop the spread of antibiotic resistance.

For more information see: CDC: Be Antibiotics Aware

See Also

Sources

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