Antibiotic Resistance: A Global Threat
What is Antibiotic Resistance?
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.
Questions to ask to help understand this topic include:
- What are antibiotic resistant bacteria?
- What types of bacteria are highly resistant?
- Why is antibiotic resistance so important?
- What can patients and health care providers do about antibiotic resistance?
- What can done about the future of antibiotic resistance?
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:
- 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.
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
mediate and resistant Staphylococcus aureus (VISA/hVISA/VRSA) 
|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|
|Community-acquired methicillin-resistant Staphylococcus aureus (cMRSA) ||
|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||beta-lactam antibiotics (eg., oxacillin, penicillin, amoxicillin, and most cephalosporins, erythromycin||doxycycline or minocycline; clindamycin; linezolid; TMP-SMX; linezolid; tedizolid|
|Streptococcus pneumoniae (multi-drug resistant) [5,6,7,8]||
pneumonia, meningitis, otitis media, sinusitis, bronchitis, bacteremia, peritonitis, cellulitis, meningitis, arthritis 
multi-drug resistance; penicillin G, cephalosporins, TMP-SMX,
erythromycin, tetracycline, doxycycline 
for multi-drug resistance consider:
vancomycin +/- rifampin; fluoroquinolones (gemifloxacin, moxifloxacin), levofloxacin) - rates of resistance are on the rise.
|Escherichia coli (E. Coli) - CTX-M extended spectrum beta-lactamases (ESBL) [9,10]||
|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)|
Enterococcus faecium (E. faecium)
vancomycin resistant enterococci (VRE) [11, 12]
|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) ||
|UTIs, bloodstream infections, pneumonias, skin and soft-tissue infections, endocarditis, meningitis, surgical site infections||
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.|
-extended spectrum beta-lactamases (ESBL) [14,15]
|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|
|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.|
Acinetobacter baumanii (carbapenem resistant)[18,19,20,21]
|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.
|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
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.
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.
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.
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.
In fact, it was in 2014-2015 when the FDA approved five new antibiotics, the first in many years. These new antibiotics were 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 5 extra years of marketing exclusivity.38
Recently Approved Antibiotics:
- Dalvance (dalbavancin) - A semisynthetic lipoglycopeptide antibiotic; approved May 2014 for treatment of adult patients with acute bacterial skin and skin structure infections caused by susceptible gram-positive organisms; given by IV injection.
- Sivextro (tedizolid) - An oxazolidinone antibiotic; approved June 2014 for treatment of adult patients with acute bacterial skin and skin structure infections caused by susceptible gram-positive organisms; given orally or by IV injection.
- Orbactiv (oritavancin) - A semisynthetic lipoglycopeptide antibiotic; approved August 2014 for treatment of adult patients with acute bacterial skin and skin structure infections caused by susceptible gram-positive organisms; given by IV injection.
- Zerbaxa (ceftolozane-tazobactam) - Approved December 2014; a combination cephalosporin-beta lactamase inhibitor injectable antibiotic used for treatment of complicated intra-abdominal infections (with metronidazole) and complicated urinary tract infections, including pyelonephritis; given by IV injection.
- Avycaz (ceftazidime-avibactam) - Approved February 2015; a combination cephalosporin-beta lactamase inhibitor injectable antibiotic used for treatment of complicated intra-abdominal infections (with metronidazole) and complicated urinary tract infections, including pyelonephritis; given by IV injection.
Antibiotic resistance is an epidemic that everyone can help to prevent: health care providers, patients and caregivers. Overall, education, judicious use of antibacterials, and 100% patient adherence to medication regimens are key in helping to stop the spread of antibiotic resistance.
For more information, see the CDC - Get Smart: Know When Antibiotics Work
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- Top 10 FAQs for Middle Ear Infections in Children
- Why Don’t Antibiotics Kill Viruses?
1. Centers for Disease Control and Prevention. Get Smart: Know When Antibiotics Work. Antibiotic Resistance: Questions and Answers. http://www.cdc.gov/getsmart/antibiotic-use/anitbiotic-resistance-faqs.html#e. Accessed October 31, 2016.
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.
3. Beibei L, Yun C, Mengli C, et al. Linezolid versus vancomycin for the treatment of gram-positive bacterial infections: meta-analysis of randomised controlled trials. Int J Antimicrob Agents: http://www.ncbi.nlm.nih.gov/pubmed/19900794 2010 Jan;35(1):3-12. Accessed Accessed October 31, 2016.
4. Fridkin SK. Vancomycin-Intermediate and -Resistant Staphylococcus aureus: What the Infectious Disease Specialist Needs to Know. Clin Infect Dis. 2001; 32:108-15. Epub 2000 Dec 13. http://cid.oxfordjournals.org/content/32/1/108.long Accessed Accessed October 31, 2016.
5. Centers for Disease Control and Prevention (CDC). Pneumococcal disease. Drug Resistance. http://www.cdc.gov/pneumococcal/drug-resistance.html. Accessed October 31, 2016.
6. Community Acquired Pneumonia in Adults. Guidelines Pocketcard. Adapted from: IDSA/ATS Consensus Guidelines. Mandell LA, Wunderlink RG, Anzueto A, et al. Clin Infect Dis. 2007:44 (Supplement 2): S27-S72 http://guidelinecentral.com/viewers/community_acquired_pneumonia.html Accessed October 31, 2016.
7. Thornsberry C et al: Antimicrobial activity among multidrug-resistant Streptococcus pneumoniae isolated in the United States, 2001-2005. Postgrad Med 2008; 120:32. Accessed October 31, 2016.
8. Jones RN, Cormican MG, Wanger A: Clindamycin resistance among erythromycin-resistant Streptococcus pneumoniae. Diagn Microbiol Infect Dis. 1996 Aug;25(4):201-4. Accessed October 31, 2016.
9. Prakash V, Lewis JS, Herrera ML, et al. Oral and parenteral therapeutic options for outpatient urinary infections caused by enterobacteriaceae producing CTX-M extended-spectrum beta-lactamases. Antimicrob Agents Chemother. 2009;53:1278-80. Accessed October 31, 2016.
10. Rodríguez-Baño J et al: Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Arch Intern Med 2008;168:1897. Accessed October 31, 2016.
11. Landman D, Quale JM. Management of infections due to resistant enterococci: a review of therapeutic options. J Antimicrob Chemother. 1997;40:161-70. Accessed October 31, 2016.
12. Arias CA. Contreras GA. Murray BE. Management of multidrug-resistant enterococcal infections. Clin Microbiol Infect. 2010;16(6):555-62. Accessed October 31, 2016.
13. Mesaros N, Nordmann P, Plésiat P, et al. Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin Microbiol Infect. 2007;13(6):560-78. Accessed October 31, 2016.
14. Paterson DL, Ko WC, Von Gottberg A, et al. Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases. Clin Infect Dis. 2004;39:31-7. Accessed October 31, 2016.
15. Woodford N, Tierno PM, Young K, et al. Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A beta-lactamase, KPC-3, in a New York Medical Center. Antimicrob Agents Chemother. 2004;48:4793-9. Accessed October 31, 2016.
16. Centers for Disease Control and Prevention (CDC). Tuberculosis: Treatment of Drug-Resistant Tuberculosis (TB). http://www.cdc.gov/tb/publications/factsheets/treatment/drugresistanttreatment.htm Accessed October 31, 2016.
17. Centers for Disease Control and Prevention (CDC). Treatment of tuberculosis. MMWR Recommendations and Reports. June 20, 2003 / 52(RR11);1-77 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5211a1.htm#tab16 Accessed September 8, 2011. Accessed October 31, 2016.
18. Fishbain J, Peleg AY. Treatment of Acinetobacter infections. Clin Infect Dis. 2010 Jul 1;51(1):79-84. Accessed October 31, 2016.
19. Wood GC, Hanes SD, Croce MA, Fabian TC, Boucher BA. Comparison of ampicillin-sulbactam and imipenem-cilastatin for the treatment of acinetobacter ventilator-associated pneumonia. Clin Infect Dis. 2002;34(11):1425-30. Accessed October 31, 2016.
20. Linden PK. Paterson DL. Parenteral and inhaled colistin for treatment of ventilator-associated pneumonia. Clin Infect Dis. 2006 Sep 1;43 Suppl 2:S89-94. Accessed October 31, 2016.
21. Fishbain J, Peleg AY: Treatment of Acinetobacter infections. Clin Infect Dis 2010; 51:79. Accessed October 31, 2016.
22. Murray BE. Vancomycin-resistant enterococcal infections. N Engl J Med. 2000; 342(10):710-21. Accessed October 31, 2016.
23. Archer GL, Climo MW. Antimicrobial Susceptibility of Coagulase-Negative Staphylococci. Antimicrob Agents Chemother. 1994; 38(10): 2231-37. Accessed October 31, 2016.
24. Uçkay I, Pittet D, Vaudaux P, et al. Foreign body infections due to Staphylococcus epidermidis. Ann Med. 2009;41(2):109-19. http://www.ncbi.nlm.nih.gov/pubmed/18720093 Accessed October 31, 2016.
25. Fey PD, Olson ME. Current concepts in biofilm formation of Staphylococcus epidermidis. Future Microbiol. 2010; 5(6): 917–33. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903046/?tool=pubmed Accessed October 31, 2016.
26. Ntziora F, Falagas ME. Linezolid for the treatment of patients with central nervous system infection. Ann Pharmacother. 2007;41(2):296-308. http://www.ncbi.nlm.nih.gov/pubmed/17284501 Accessed October 31, 2016.
27. Lowy F, et al. Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of skin and soft tissue infections. UpToDate. October 2016. Accessed November 29, 2016.
28. Lowy F, et al. Vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus infections. UpToDate. October 2016. Accessed November 29, 2016.
29. Musher D, et al. Resistance of Streptococcus pneumoniae to the fluoroquinolones, doxycycline, and trimethoprim-sulfamethoxazole. UpToDate. October 2016. Accessed November 29, 2016.
30. Munoz-Price, L Silvia, et al. Extended-spectrum beta-lactamases. UpToDate. October 2016. Accessed November 29, 2016.
31. Murray B, et al. Treatment of enterococcal infections. UpToDate. October 2016. Accessed November 29, 2016.
32. O'Driscoll T, et al. Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management. Infect Drug Resist. 2015; 8: 217–230. Accessed November 29, 2016 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521680/
33. Kanj S, Sexton D, et al. Principles of antimicrobial therapy of Pseudomonas aeruginosa infections. UpToDate. October 2016. Accessed November 29, 2016.
34. Yu, W, Chuang, Y, et al. Clinical features, diagnosis, and treatment of Klebsiella pneumoniae infection. UpToDate. October 2016. Accessed November 29, 2016.
35. World Health Organization (WHO). WHO treatment guidelines for drug-resistant tuberculosis (2016 update). Accessed November 29, 2016 at http://www.who.int/tb/areas-of-work/drug-resistant-tb/treatment/resources/en/
36. Kanafani, ZA, Kanj MS, et al. Acinetobacter infection: Treatment and prevention. UpToDate. November 2016. Accessed November 29, 2016.
37. Tufariello, JM, Lowy, FD, et al. Treatment of infections due to coagulase-negative staphylococci. UpToDate. October 2016. Accessed November 29, 2016.
38. Theuretzbacher U. Recent FDA Antibiotic Approvals: Good News and Bad News. Center for Disease Dynamics, Economics & Policy. March 12, 2015. Accessed March 8, 2017 at http://cddep.org/blog/posts/recent_fda_antibiotic_approvals_good_news_and_bad_news#sthash.Rvagi8A3.dpbs