Antibiotic resistance

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When the early antibiotics such as penicillin and streptomycin went into use, individual general and species of bacteria tended either to be susceptible to them. As antibiotics have been widely used, broadening the definition to include antiprotozoal, antifungal and antiviral drugs, organisms once exquisitely sensitive to specific drugs are no longer effective. In some cases, there may be partial resistance, so extremely high dosage levels, usually parenteral, may work, but in such cases, it is probably a matter of time until fully resistant forms emerge.

Given that resistant strains are developing faster than new antibiotics, resistance is a worldwide threat, according to U.S. intelligence analysis of patterns of infectious diseases and impacts. The first antibiotics became available a little more than a half-century ago, and antivirals are quite recent — yet a challenge of HIV therapy is the constant appearance of resistant viral strains. Multidrug resistant tuberculosis is a worldwide problem, given that any treatment of this disease is prolonged.

Development of resistance

At the microbial level, this may be due either to the antibiotic therapy allowing the survival of naturally resistant organisms of the species, or of the transfer of resistance genetic factors among bacteria. It is not, as once thought, a matter of natural selection, where a few organisms within a species randomly mutate, become resistant, and thus become better equipped for survival.

After a patient uses an antibiotic, the risk of resistant organisms is greatest after one month, but the risk may continue for one year.[1]

Other mechanisms, not yet fully understood in the ecology, include the transfer of resistance genes among totally different species.

Mechanisms of resistance

Human activities promoting antibiotic resistance

A number of organisms have developed resistance to antibiotics resistant to them. Assorted human actions cause much of the development of resistance, with reasons ranging to overprescribing antibiotics in situations where they are unlikely to help[2], to patients stopping therapy when they feel better but still have an active bacterial infection, to the use of antibiotics as agricultural growth stimulants.

Slowing the development of resistance

Interventions to reduce overprescribing have been systematically reviewed.[2] One study on respiratory tract infections found "physicians were more likely to prescribe antibiotics to patients who they believed expected them, although they (the physicians) correctly identified only about 1 in 4 of those patients".[3] The use of antibiotics varies among countries.[4] Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescribing of antibiotics. [5] Delaying antibiotics for 48 hours while waiting on improvement of respiratory tract infections[6][7] or cystitis[8] may reduce antibiotic usage; however, this strategy may reduce patient satisfaction.

Normal c-reactive protein levels have been used to help health care providers reduce antibiotic use.[9]

Normal procalcitonin levels have been used to help health care providers reduce antibiotic use.[10][11][12][13]

Treating resistant forms

When a form was found resistant, especially if the mechanism of resistance was known, a variant of the same class of antibiotics might be useful.

Bacterial resistance to the penicillins

For example, the earliest example of bacterial resistance to penicillins was bacterial production of an enzyme called penicillinase, or, more precisely, penicillin beta-lactamase, which breaks a chemical bond in the key lactam structure of penicillin molecules.

Among the first responses were the synthesis of penicillins, such as methicillin, which protected this bond. In time, however, methicillin did not work on some bacteria, beginning with Staphylococcus aureus. Since S. aureus is an important pathogen, common in wound infection but also appearing in systemic disease, methicillin-resistant staphylococcus aureus ('MRSA) became a matter of close surveillance by infectious disease specialists.

In serious infections with MRSA, the "last resort" tended to be vancomycin. Since vancomycin, for systemic infections, must be administered intravenously, it was relatively easy to restrict it to controlled hospital use, only for specific strains. Eventually, vancomycin resistance was seen among staphylococci; acquired resistance was first observed in Enterococci.

References

  1. ↑ Costelloe, Ceire; Chris Metcalfe, Andrew Lovering, David Mant, Alastair D Hay (2010-05-18). "Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis". BMJ 340 (may18_2): c2096. DOI:10.1136/bmj.c2096. Retrieved on 2010-05-19. Research Blogging.
  2. ↑ 2.0 2.1 Ranji SR, Steinman MA, Shojania KG, Gonzales R (August 2008). "Interventions to reduce unnecessary antibiotic prescribing: a systematic review and quantitative analysis". Med Care 46 (8): 847–62. DOI:10.1097/MLR.0b013e318178eabd. PMID 18665065. Research Blogging. Cite error: Invalid <ref> tag; name "pmid18665065" defined multiple times with different content
  3. ↑ Ong S, Nakase J, Moran GJ, Karras DJ, Kuehnert MJ, Talan DA (2007). "Antibiotic use for emergency department patients with upper respiratory infections: prescribing practices, patient expectations, and patient satisfaction". Annals of emergency medicine 50 (3): 213-20. DOI:10.1016/j.annemergmed.2007.03.026. PMID 17467120. Research Blogging.
  4. ↑ Butler CC, Hood K, Verheij T, et al. (2009). "Variation in antibiotic prescribing and its impact on recovery in patients with acute cough in primary care: prospective study in 13 countries". BMJ 338: b2242. PMID 19549995. [e]
  5. ↑ Metlay JP, Camargo CA, MacKenzie T, et al (2007). "Cluster-randomized trial to improve antibiotic use for adults with acute respiratory infections treated in emergency departments". Annals of emergency medicine 50 (3): 221-30. DOI:10.1016/j.annemergmed.2007.03.022. PMID 17509729. Research Blogging.
  6. ↑ Spurling G, Del Mar C, Dooley L, Foxlee R (2007). "Delayed antibiotics for respiratory infections". Cochrane database of systematic reviews (Online) (3): CD004417. DOI:10.1002/14651858.CD004417.pub3. PMID 17636757. Research Blogging.
  7. ↑ Moore M, Little P, Rumsby K, Kelly J, Watson L, Warner G et al. (2009). "Effect of antibiotic prescribing strategies and an information leaflet on longer-term reconsultation for acute lower respiratory tract infection.". Br J Gen Pract 59 (567): 728-34. DOI:10.3399/bjgp09X472601. PMID 19843421. PMC PMC2751917. Research Blogging.
  8. ↑ Little P, Turner S, Rumsby K, et al (March 2009). "Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study". Health Technol Assess 13 (19): iii–iv, ix–xi, 1–73. DOI:10.3310/hta13190. PMID 19364448. Research Blogging.
  9. ↑ Cals JW, Butler CC, Hopstaken RM, Hood K, Dinant GJ (2009). "Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial". BMJ 338: b1374. PMID 19416992. PMC 2677640. [e]
  10. ↑ Christ-Crain M, Stolz D, Bingisser R, et al. (July 2006). "Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial". Am. J. Respir. Crit. Care Med. 174 (1): 84–93. DOI:10.1164/rccm.200512-1922OC. PMID 16603606. Research Blogging.
  11. ↑ Stolz D, Christ-Crain M, Bingisser R, et al. (January 2007). "Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy". Chest 131 (1): 9–19. DOI:10.1378/chest.06-1500. PMID 17218551. Research Blogging.
  12. ↑ Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. (February 2004). "Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial". Lancet 363 (9409): 600–7. DOI:10.1016/S0140-6736(04)15591-8. PMID 14987884. Research Blogging.
  13. ↑ Briel M, Schuetz P, Mueller B, et al (October 2008). "Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care". Archives of internal medicine 168 (18): 2000–7; discussion 2007–8. DOI:10.1001/archinte.168.18.2000. PMID 18852401. Research Blogging.
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