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 do not always work anymore. Antibiotic resistance is a global issue, 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. Bacteria 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. To have a better understanding of antibiotic resistance, Table 1 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.

Table 1. Antibiotic Resistance: A Global Threat*

Current and Emerging Resistant Bacteria Type Representative Clinical Infections Antibiotics Associated with Resistance Treatment Options (as determined based on culture & sensitivity, local guidelines, clinical presentation)
Methicillin-resistant Staphylococcus aureus (MRSA) [2] 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 cepholosporins) erythromycin vancomycin

alternatives: linezolid; clindamycin (confirm with D-test); daptomycin; TMP-SMX; quinupristine-dalfopristin [2] [3]
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 linezolid; clindamycin; daptomycin; TMP-SMX; quinupristine-dalfopristin
[4]
Community-acquired methicillin-resistant Staphylococcus aureus (cMRSA) [2] gram (+)
cocci
necrotizing pneumonia; skin infections, boils, abcesses (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 cepholosporins, erythromycin doxycycline or minocycline; clindamycin (confirm with D-test); linezolid; TMP-SMX [2]
Streptococcus pneumoniae (multi-drug resistant) [5] [6] gram (+)
diplo-
coccus
pneumonia, otitis media, sinusitis, bronchitis, bacteremia, peritonitis, cellulitis, meningitis, arthritis [5]

multi-drug resistance; penicillin G, cephalosporins, TMP-SMX,
erythromycin, doxycycline [7]
for multi-drug resistance consider:
vancomycin +/- rifampin; fluoroquinolone (gemifloxacin, moxifloxacin), levofloxacin)

alternatives: linezolid; clindamycin [8]; imipenem/cilastatin
Escherichia coli (E. Coli) - CTX-M extended spectrum beta-lactamases (ESBL) [9] gram (-)
rod
UTIs Oral cephalosporins, TMP/SMX, fluoroquinolones Fosfomycin [10], nitrofurantoin, ertapenem, doripenem, imipenem/cilastatin
Enterococcus faecium (E. faecium)
vancomycin resistant enterococci (VRE) [11] [12]
gram (+)
cocci
meningitis, UTI, bacteremia (central venous catheter-related), endocarditis vancomycin; streptomycin; gentamicin; penicillin; ampicillin linezolid; quinupristine-dalfopristin; daptomycin,
fosfomycin (for UTI)
Pseudomonas aeruginosa (multidrug resistant strains) [13] gram (-)
rod
UTIs, pneumonias, skin and soft-tissue infections, endocarditis, meningitis imipenem/cila-
statin, mero-
penem, non-antipseudo-monal penicillins, oral cephalosporins,
colistin, polymyxin B (for multidrug resistant strains)
Klebsiella pneumoniae
-extended spectrum beta-lactamases (ESBL) [14] [15]
gram (-)
rod
pneumonias, UTIs, upper respiratory tract infections, surgical wound infections 2nd, 3rd generation cephalosporins; aztreonam; carbapenems imipenem; meropenem; colistin
multi-drug resistant Mycobacterium tuberculosis (MDR-TB) [16] [17] acid-fast tuberculosis (lung infection) isoniazid; rifampin; possibly streptomycin


multiple agents required for treatment:
aminoglycoside (amikacin or kanamycin) or polypeptide antibiotic (capreomycin) + antimycobacterials (pyrazinamide + ethambutol) + fluorquinolone (moxifloxacin) + rifabutin; other agents may need to be substituted based on drug availability
Acinetobacter baumanii [18]
gram (-)
rod
immunocompromised patients: pneumonia (commonly ventilator-associated), UTI, septicemia, central venous catheter-related infections, traumatic wound infections imipenem; meropenem; antipseudomonal agents, fluoroquinolones, carbapenems ampicillin-sulbactam [19]; colistin [20] [21]
Staphylococcus epidermidis (methicillin resistant) [22] [23] [24] [25] [26] gram (+) bacteremia, catheter, implant, and prostheses-related infection (biofilm formations), endocarditis penicillin, amoxicillin vancomycin

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

alternative regimens if vancomycin resistant: daptomycin, linezolid

UTI = urinary tract infection

* Note: Table 1 is not a comprehensive listing of all resistant bacteria and 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 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 may be 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
  • coughs, colds and runny noses
  • sinusitis, bronchitis
  • the flu

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 avoid asking or demanding 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 that is needed for the next illness, it may be out of date and ineffective, or there may not be enough medication to treat a current infection. If the new illness is a viral infection, an antibiotic would 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, that requires 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. Physicians and pharmacists 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. Receiving and 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. Research is lacking for novel antibiotics, and only 2 new classes of antibiotics, the oxazolidinones (linezolid) and the lipopeptides (daptomycin) have been developed since the late 1960’s.[27] Because of this, the FDA is also encouraging new research into effective antibiotic regimens, vaccines and diagnostic tests. 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: CDC Web Site: Get Smart: Know When Antibiotics Work - Centers for Disease Control and Prevention. http://www.cdc.gov/getsmart/

See Also:

References:

[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 August 20, 2011.

[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/early/2011/01/04/cid.ciq146.full Accessed Online 9/6/2011

[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. 2010 Jan;35(1):3-12. Accessed September 9, 2011

[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 onlne 9/6/2011

[5] Centers for Disease Control and Prevention (CDC). Active Bacterial Core Surveillance. Drug-Resistant Streptococcus pneumoniae (DRSP) Surveillance Toolkit. http://www.cdc.gov/abcs/reports-findings/surv-manual.html Accessed September 6, 2011

[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 Online September 6, 2011

[7] Thornsberry C et al: Antimicrobial activity among multidrug-resistant Streptococcus pneumoniae isolated in the United States, 2001-2005. Postgrad Med 2008; 120:32

[8] Jones RN, Cormican MG, Wanger A. Clindamycin resistance among erythromycin-resistant Streptococcus pneumoniae. Diagn Microbiol Infect Dis. 1996 Aug;25(4):201-4.

[9] Prakash V, Lewis JS 2nd, 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.

[10] Rodríguez-Baño J et al: Community infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Arch Intern Med  2008;168:1897

[11] Landman D, Quale JM. Management of infections due to resistant enterococci: a review of therapeutic options. J Antimicrob Chemother. 1997;40:161-70.

[12] Arias CA. Contreras GA. Murray BE. Management of multidrug-resistant enterococcal infections. Clin Microbiol Infect. 2010;16(6):555-62.

[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.

[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.

[15] Woodford N, Tierno PM Jr, 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.

[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 September 6, 2011

[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

[18] Fishbain J, Peleg AY. Treatment of Acinetobacter infections. Clin Infect Dis. 2010 Jul 1;51(1):79-84.

[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

[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.

[21] Fishbain J, Peleg AY: Treatment of Acinetobacter infections. Clin Infect Dis 2010; 51:79

[22] Murray BE. Vancomycin-resistant enterococcal infections. N Engl J Med. 2000; 342(10):710-21.

[23]  Archer GL, Climo MW. Antimicrobial Susceptibility of Coagulase-Negative Staphylococci. Antimicrob Agents Chemother. 1994; 38(10): 2231-37.

[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 September 9, 2011.

[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 September 9, 2011

[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 September 9, 2011

[27] 2] McCoy DM, Toussaint K, Gallagher JC. The Pharmacist’s Role in Preventing Antibiotic Resistance. US Pharm. 2011;36:42-9. http://www.uspharmacist.com/content/c/29137/. Accessed August 20, 2011.

Last updated: 2013-06-16 by Leigh Anderson, PharmD

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