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Antibiotic Resistance: A Global Threat

Medically reviewed on Nov 28, 2016 by L. Anderson, PharmD

Antibiotic resistance is the ability of bacteria to withstand the antimicrobial power of antibiotics. Simply put, antibiotics that used to cure an infection may not work anymore. Antibiotic resistance is a global threat, and The US Center’s for Disease Control and Prevention (CDC) considers antibiotic resistance one of their top concerns. Infections with drug-resistant bacteria may lead to longer and more costly hospital care, and may increase the risk of dying from the infection.[1]

Questions to ask to help understand this topic include:

What are antibiotic resistant bacteria?

Antibiotic resistant bacteria are bacteria that cannot be fully inhibited or killed by an antibiotic. The antibiotic may have worked effectively before the resistance occurred. However, bacteria can become resistant to antibiotics by adapting their structure or function in some way that prevents them from being killed by the antibiotic. This mechanism might happen in several ways:[1]

  • bacteria can neutralize the antibiotic before it has an effect
  • bacteria may be able to pump the antibiotic out
  • bacteria may be able to change the site (receptor) where the antibiotic normally works
  • bacteria can mutate and transfer genetic material that codes for resistance to other bacteria

The resistant bacteria that survive the effect of the antibiotic are able to multiply, spread to others and cause further infections in the family, community, and/or health care setting. In turn, these infections are more resistant to another round of the same 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 include: Clostridium difficile, carbapenem-resistant Enterobacteriaceae, and Neisseria gonorrhoeae. Other threats may be viewed here.

List of Common Bacteria with High Antibiotic Resistance*

To gain a better understanding of antibiotic resistance, the following table lists 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 should always be tailored according to the antimicrobial susceptibility test result.

Current and Emerging Resistant Bacteria Type Representative Clinical Infections Antibiotics Associated with Resistance* Treatment Options (as determined based on infection type, susceptibility tests, local guidelines, clinical presentation, IV or PO route)
Methicillin-resistant Staphylococcus aureus (MRSA) [2,3] gram (+) cocci skin/soft tissue infections, UTI, bacteremia, toxic shock syndrome, pneumonia, osteomyelitis, endocarditis, meningitis; assoc. with IV catheters beta-lactam antibiotics (eg., oxacillin, penicillin, nafcillin, amoxicillin, and most cephalosporins) erythromycin IV: vancomycin or daptomycin (1st choice IV); ceftaroline; telavancin; dalbavancin; linezolid; tedizolid; oritavancin


Oral alternatives: clindamycin; minocycline; doxycycline; TMP-SMX; linezolid; tedizolid; dalbavancin; telavancin[27]

Vancomycin inter-
mediate and resistant Staphylococcus aureus (VISA/hVISA/VRSA) [4]
gram (+) cocci skin/soft tissue infections, UTI, bacteremia, toxic shock syndrome, pneumonia, osteomyelitis, endocarditis, meningitis vancomycin; beta-lactam antibiotics (eg., oxacillin, penicillin, nafcillin, amoxicillin, and most cepholosporins) erythromycin In-vitro testing should guide selection; daptomycin, linezolid, telavancin, ceftaroline, minocycline, or quinupristin-dalfopristin[28]
Community-acquired methicillin-resistant Staphylococcus aureus (cMRSA) [2] gram (+)
cocci
necrotizing pneumonia; skin infections, boils, abscess (seen in IV drug abusers, athletes who share equipment, day care centers, military personnel; prisons); drainage of abscess is primary treatment; treat with antibiotic only  if needed[2] beta-lactam antibiotics (eg., oxacillin, penicillin, amoxicillin, and most cephalosporins, erythromycin doxycycline or minocycline; clindamycin; linezolid; TMP-SMX; linezolid; tedizolid[27]
Streptococcus pneumoniae (multi-drug resistant) [5,6,7,8] gram (+)
diplo-
coccus
pneumonia, meningitis, otitis media, sinusitis, bronchitis, bacteremia, peritonitis, cellulitis, meningitis, arthritis [5]
 
multi-drug resistance; penicillin G, cephalosporins, TMP-SMX,
erythromycin, tetracycline, doxycycline [7]
for multi-drug resistance consider:
vancomycin +/- rifampin; fluoroquinolones (gemifloxacin, moxifloxacin), levofloxacin) - rates of resistance are on the rise.


alternatives: linezolid; clindamycin; imipenem/cilastatin[29]

Escherichia coli (E. Coli) - CTX-M extended spectrum beta-lactamases (ESBL) [9,10] gram (-)
rod
UTIs Penicillins,  cephalosporins, TMP/SMX, fluoroquinolones, aztreonam Carbapenems such as ertapenem, doripenem, meropenem, imipenem/cilastatin; fosfomycin (UTI); higher dose cefepime (2 g every eight hours)[30]
Enterococcus faecium (E. faecium)
vancomycin resistant enterococci (VRE) [11, 12]
gram (+)
cocci
meningitis, UTI, bacteremia (central venous catheter-related), endocarditis, surgical site infections vancomycin; streptomycin; gentamicin; penicillin; ampicillin; other beta lactams and aminoglycosides linezolid; daptomycin; tigecycline; alternative: quinupristine-dalfopristin[31, 32]
Pseudomonas aeruginosa (multidrug resistant strains) [13] gram (-)
rod
UTIs, bloodstream infections, pneumonias, skin and soft-tissue infections, endocarditis, meningitis, surgical site infections imipenem/cila-
statin, mero-
penem, non-antipseudo-monal penicillins, oral cephalosporins,
colistin, polymyxin B (for multidrug resistant strains); ceftazidime-avibactam or ceftolozane-tazobactam used for complicated intra-abdominal or UTIs resistant to other medications.[33]
Klebsiella pneumoniae
-extended spectrum beta-lactamases (ESBL) [14,15]
gram (-)
rod
pneumonias, UTIs, upper respiratory tract infections, surgical wound infections beta-lactam; 2nd, 3rd generation cephalosporins; aztreonam; carbapenems carbapenems: imipenem, meropenem, ertapenem, doripenem; possibly ceftolozane-tazobactam, ceftazidime-avibactam[30]
Multi-drug resistant Mycobacterium tuberculosis (MDR-TB) [16,17] acid-fast tuberculosis (lung infection) isoniazid; rifampin; possibly streptomycin

 
multiple agents required for treatment from WHO recommended groups (2016 update, at least five drugs): pyrazinamide, a fluoroquinolone, an injectable agent (i.e., amikacin), and two additional agents (ethionamide, cycloserine, linezolid, clofazimine); other agents may need to be substituted based on drug availability.[35]

Acinetobacter baumanii (carbapenem resistant)[18,19,20,21]

gram (-)
rod
immunocompromised patients: pneumonia (commonly ventilator-associated), UTI, septicemia, central venous catheter-related infections, traumatic wound infections imipenem; meropenem; antipseudomonal agents, fluoroquinolones, carbapenems; typically resistant to all beta-lactams and fluoroquinolones

polymyxins (ie, colistin and polymyxin B); addition of second agent, such as a carbapenem, minocycline, tigecycline, or rifampin, may be preferred.[36]

Staphylococcus epidermidis (methicillin resistant) [22, 23, 24, 25, 26] gram (+) bacteremia, catheter, implant, and prostheses-related infection (biofilm formations), endocarditis penicillin, amoxicillin vancomycin (agent of choice for empiric therapy)

if infected implant, surgical removal or replacement may be required; vancomycin +/- (rifampin + gentamicin)

alternative regimens if vancomycin resistant: daptomycin, linezolid, quinupristin-dalfopristin[37]

UTI = urinary tract infection, TMP-SMX = trimethoprim-sulfamethoxazole

* Note: This table is 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 health care 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.

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.[2]

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 few years, several new, innovative antibiotics have been approved to fight serious infections, such as the "superbug", next generation antibacterial Avycaz (ceftazidime-avibactam), which won FDA approval in February 2015.

Finally, antibiotic resistance is an epidemic that everyone can help to prevent: health care providers, patients and caregivers. Overall, education is key in helping to stop the spread of antibiotic resistance.

For more information, see the CDC - Get Smart: Know When Antibiotics Work

See Also:

Recommended for you

Sources

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2. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-55. Epub 2011 Jan 4. http://cid.oxfordjournals.org/content/52/3/e18 Accessed October 31, 2016.

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