Antibiotics and resistance: Information for professionals

-Automatic translation

Antibiotic-resistant bacteria are causing daily problems in hospitals across Europe (1).

Incorrect use of antibiotics can leave patients exposed to or infected with antibiotic-resistant bacteria.

The main types of antibiotic-resistant bacteria found in hospitals are MRSA (methicillin-resistant Staphylococcus Aureus), VOE (vancomycin-resistant Enterococci), and multi-resistant Gram-negative rods (2-3).

Incorrect or excessive use of antibiotics is also associated with increased rates of Clostridium difficile infections (4-5).

The presence and spread of resistant bacterial strains threaten patient safety in hospitals where:

• Infections caused by antibiotic-resistant bacteria are associated with severe morbidity and mortality and extended hospital stays (6-7).

• Antibiotic resistance often leads to a delay in appropriate antibiotic therapy (8).

• Inappropriate or delayed antibiotic treatment of patients with severe infections is associated with worse patient outcomes and even death (9-11).

• Few new antibiotics are in the development phase; therefore, sufficiently effective antibiotics will not be available if antibiotic resistance continues to increase (12).

-Automatic translation

Hospitalised patients are very likely to receive antibiotics (13), and up to 50% of all antibiotic use in hospitals is inappropriate (4.14).

Incorrect use of antibiotics in hospitals is one of the leading causes of the development of antibiotic resistance (15-17).

The wrong use of antibiotics can consist of any of the following points (18):

• When antibiotics are prescribed unnecessarily;

• When there is a delay in the prescription of antibiotics for critically ill patients;

• When the selected antibiotics are either too narrow-spectrum or too broad-spectrum;

• When the dose of an antibiotic is either too low or too high for the patient;

• When the duration of antibiotic treatment is too short or too long;

• When antibiotic therapy is not changed after culture and susceptibility test results are available.

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Prudent use of antibiotics can prevent antibiotic-resistant bacteria from emerging and multiplying at the expense of susceptible bacteria (4, 17, 19-21).

Less use of antibiotics can reduce the number of Clostridium difficile nosocomial infections (4, 17, 19-21).

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Comprehensive policies and actions that include continuing education, evidence-based clinical guidelines for antibiotic use, and advice from infectious disease specialists, bacteriologists, and pharmacists can contribute to improved antibiotic prescribing and reduce antibiotic resistance (4, 19, 23).

Active surveillance of antibiotic use and antibiotic resistance in hospitals can be helpful in the selection of appropriate antibiotics for critically ill patients (24).

Correct timing and duration of antibiotic prophylaxis before surgery is associated with a lower risk of postoperative infection (25) and a lower risk of emergence of antibiotic-resistant bacteria (26)

Research shows that in some instances, the duration of antibiotic treatment can be shortened without worsening the patient's prognosis. This is also associated with a lower incidence of antibiotic resistance (15, 27-28).

Pre-culture sampling, monitoring culture results, and changing antibiotic regimens based on culture/susceptibility testing reduce unnecessary antibiotic use (29).

1. European Antimicrobial Resistance Surveillance System . RIVM. 2009 [cited March 30, 2010].

2. Safdar N, Maki DG. The commonality of risk factors for nosocomial colonization and infection with antimicrobial-resistant Staphylococcus aureus, enterococcus, gram-negative bacilli, Clostridium difficile, and Candida. Ann Intern Med. 2002 Jun 4,136(11):834-44.

3. Tacconelli E, De Angelis G, Cataldo MA, Mantengoli E, Spanu T, Pan A, et al. Antibiotic use and risk of colonization and infection with antibiotic-resistant bacteria: a hospital population-based study. Antimicrob Agents Chemother. 2009 Oct;53 (10):4264-9.

4. Davey P, Brown E, Fenelon L, Finch R, Gould I, Hartman G, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2005(4):CD003543.

5. Bartlett JG, Onderdonk AB, Cisneros RL, Kasper DL. Clindamycin-associated colitis due to a toxin-producing species of Clostridium in hamsters. J Infect Dis. 1977 Nov;136(5):701-5.

6. Cosgrove SE, Carmeli Y. The impact of antimicrobial resistance on health and economic outcomes. Clin Infect Dis. 2003 Jun 1;36(11):1433-7.

7. Roberts RR, Hota B, Ahmad I, Scott RD, 2nd, Foster SD, Abbasi F, et al. Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin Infect Dis. 2009 Oct 15;49(8):1175-84.

8. Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999 Feb;115 (2):462-74.

9. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest. 2000 Jul;118(1):146-55.

10. Lodise TP, McKinnon PS, Swiderski L, Rybak MJ. Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia Clin Infect Dis. 2003 Jun 1;36(11):1418-23.

11. Alvarez-Lerma F. Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. ICU-Acquired Pneumonia Study Group. Intensive Care Med. 1996 May;22(5):387-94.

12. ECDC, EMEA. ECDC/EMEA Joint Technical Report: The bacterial challenge: time to react 2009.

13. Ansari F, Erntell M, Goossens H, Davey P. The European surveillance of antimicrobial consumption (ESAC) point-prevalence survey of antibacterial use in 20 European hospitals in 2006. Clin Infect Dis. 2009 Nov 15;49 (10):1496-504.

14. Willemsen I, Groenhuijzen A, Bogaers D, Stuurman A, van Keulen P, Kluytmans J. Appropriateness of antimicrobial therapy measured by repeated prevalence surveys. Antimicrob Agents Chemother. 2007 Mar;51(3):864-7.

15. Singh N, Yu VL. Rational empiric antibiotic prescription in the ICU. Chest. 2000 May;117(5):1496-9.

16. Lesch CA, Itokazu GS, Danziger LH, Weinstein RA. Multi-hospital analysis of antimicrobial use and resistance trends. Diagn Microbiol Infect Dis. 2001 Nov;41(3):149-54.

17. Lepper PM, Grusa E, Reichl H, Hogel J, Trautmann M. Consumption of imipenem correlates with beta-lactam resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2002 Sep;46(9):2920-5.

18. Gyssens IC, van den Broek PJ, Kullberg BJ, Hekster Y, van der Meer JW. Optimizing antimicrobial therapy. A method for antimicrobial drug use evaluation. J Antimicrob Chemother. 1992 Nov;30(5):724-7.

19. Carling P, Fung T, Killion A, Terrin N, Barza M. Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years. Infect Control Hosp Epidemiol. 2003 Sep;24(9):699-706.

20. Bradley SJ, Wilson AL, Allen MC, Sher HA, Goldstone AH, Scott GM. The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematology unit by changing antibiotic use. J Antimicrob Chemother. 1999 Feb;43 (2):261-6.

21. De Man P, Verhoeven BAN, Verbrugh HA, Vos MC, Van Den Anker JN. An antibiotic policy to prevent emergence of resistant bacilli. Lancet. 2000;355(9208):973-8.

22. Fowler S, Webber A, Cooper BS, Phimister A, Price K, Carter Y, et al. Successful use of feedback to improve antibiotic prescribing and reduce Clostridium difficile infection: a controlled interrupted time series. J Antimicrob Chemother. 2007 May;59(5):990-5.

23. Byl B, Clevenbergh P, Jacobs F, Struelens MJ, Zech F, Kentos A, et al. Impact of infectious disease specialists and microbiological data on the appropriateness of antimicrobial therapy for bacteremia. Clin Infect Dis. 1999 Jul;29(1):60-6; discussion 7-8.

24. Beardsley JR, Williamson JC, Johnson JW, Ohl CA, Karchmer TB, Bowton DL. Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia. Chest. 2006 Sep;130(3):787-93.

25. Steinberg JP, Braun BI, Hellinger WC, Kusek L, Bozikis MR, Bush AJ, et al. Timing of antimicrobial prophylaxis and the risk of surgical site infections: results from the Trial to Reduce Antimicrobial Prophylaxis Errors. Ann Surg. 2009 Jul;250(1):10-6.

26. Harbarth S, Samore MH, Lichtenberg D, Carmeli Y. Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on surgical site infections and antimicrobial resistance. Circulation. 2000 Jun 27;101(25):2916-21.

27. Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. Jama. 2003 Nov 19;290(19):2588-98.

28. Ibrahim EH, Ward S, Sherman G, Schaiff R, Fraser VJ, Kollef MH. Experience with a clinical guideline for the treatment of ventilator-associated pneumonia. Crit Care Med. 2001 Jun;29(6):1109-15.

29. Rello J, Gallego M, Mariscal D, Sonora R, Valles J. The value of routine microbial investigation in ventilator-associated pneumonia. Am J Respir Crit Care Med. 1997 Jul;156(1):196-200.

-Automatic translation

Antibiotic resistance is a growing problem and threat to public health in Europe [1, 2]. The number of infections caused by resistant bacteria is increasing, and the development of new types of antibiotics is slow. Therefore, there is uncertainty about the effectiveness of antibiotics in the future [3, 4]. The proliferation of antibiotic-resistant bacteria can be reduced by encouraging the targeted and appropriate use of antibiotics in healthcare. Antibiotic use is associated with the development of antibiotic resistance [5–8]. The total usage of antibiotics and how they have been used influence antibiotic resistance [9, 10]. The experience abroad shows that when antibiotic prescriptions for outpatients decrease, antibiotic resistance is also reduced [10–12]. Primary care accounts for about 80 to 90% of all antibiotic prescriptions, mainly for respiratory tract infections [9, 14, 15]. Studies show that antibiotics are often unnecessary for respiratory infections, as the patient's immune system takes care of most infections [16–18]. However, patients with certain risk factors, e.g. severely worsening symptoms of chronic lung disease, require antibiotics [19, 20].

Unnecessary or inappropriate prescribing of antibiotics in primary care is a complex phenomenon. Still, it may be related to factors such as misinterpretation of symptoms, uncertainty in diagnosis, and physician experience of patient expectations [14, 21]. The solution primarily lies in good communication. Research shows that the satisfaction of patients seeking health care is determined more by effective communication than by receiving a prescription for antibiotics [22–24]. It has also been shown that prescribing antibiotics for upper respiratory tract infections does not reduce the reinfection rate [25]. Professional medical advice impacts patients’ perceptions and attitudes towards their illness and perceived need for antibiotics. It is essential to inform patients about the likely course of the illness, the realistic recovery time, and self-management strategies. Primary care prescribers do not need to allocate more time for consultations that offer alternatives to antibiotic prescribing. Studies show that this can be done within the same average consultation time while maintaining high patient satisfaction [14, 27, 28].

[1] - European Antimicrobial Resistance Surveillance System. EARSS Annual Report 2007. Bilthoven, Netherlands: National Institute for Public Health and the Environment, 2008.

[2] - Cars O, Högberg LD, Murray M, Nordberg O, Sivaraman S, Lundborg CS, So AD, Tomson G. Meeting the challenge of antibiotic resistance. BMJ 2008;337:a1438. doi: 10.1136/bmj.a1438.

[3] Finch R. Innovation - drugs and diagnostics. J Antimicrob Chemother 2007;60(Suppl 1):i79-82.

[4] - Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009;48 (1):1-12.

[5] - Malhotra-Kumar S, Lammens C, Coenen S, Van Herck K, Goossens H. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet 2007;369(9560):482-90.

[6] Donnan PT, Wei L, Steinke DT, Phillips G, Clarke R, Noone A, Sullivan FM, MacDonald TM, Davey PG. Presence of bacteriuria caused by trimethoprim resistant bacteria in patients prescribed antibiotics: multilevel model with practice and individual patient data. BMJ 2004;328(7451):1297-301.

[7] - Hillier S, Roberts Z, Dunstan F, Butler C, Howard A, Palmer S. Prior antibiotics and risk of antibiotic-resistant community-acquired urinary tract infection: a case-control study. J Antimicrob Chemother 2007;60 (1):92-9.

[8] - London N, Nijsten R, Mertens P, v d Bogaard A, Stobberingh E. Effect of antibiotic therapy on the antibiotic resistance of faecal Escherichia coli in patients attending general practitioners. J Antimicrob Chemother 1994;34 (2):239-46.

[9] - Goossens H, Ferech M, Vander Stichele R, Elseviers M; ESAC Project Group. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 2005;365(9459):579-87.

[10] - Guillemot D, Carbon C, Balkau B, Geslin P, Lecoeur H, Vauzelle-Kervroëdan F, Bouvenot G, Eschwége E. Low dosage and long treatment duration of beta-lactam: risk factors for carriage of penicillin-resistant Streptococcus pneumoniae. JAMA 1998;279(5):365-70.

[11] - Butler CC, Dunstan F, Heginbothom M, Mason B, Roberts Z, Hillier S, Howe R, Palmer S, Howard A. Containing antibiotic resistance: reduced antibiotic-resistant coliform urinary tract infections with reduction in antibiotic prescribing by general practices. Br J Gen Pract 2007;57(543):785-92.

[12] - Goossens H, Coenenen S, Costers M, De Corte S, De Sutter A, Gordts B, Laurier L, Struelens MJ. Achievements of the Belgian Antibiotic Policy Coordination Committee (BAPCOC). Euro Surveill 2008;13(46):pii=19036.

[13] - Sabuncu E, David J, Bernède-Bauduin C, Pépin S, Leroy M, Boëlle PY, Watier L, Guillemot D. Significant reduction of antibiotic use in the community after a nationwide campaign in France, 2002-2007. PLoS Med 2009;6 (6):e1000084.

[14] - Cals JWL, Butler CC, Hopstaken RM, Hood K, Dinant GJ. 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 2009 May 5;338:b1374. doi: 10.1136/bmj.b1374.

[15] - Wise R, Hart T, Cars O, Streulens M, Helmuth R, Huovinen P, Sprenger M., Antimicrobial resistance. Is a major threat to public health. BMJ 1998;317(7159):609-10.

[16] - Butler CC, Hood K, Verheij T, Little P, Melbye H, Nuttall J, Kelly MJ, Mölstad S, Godycki-Cwirko M, Almirall J, Torres A, Gillespie D, Rautakorpi U, Coenenen S, Goossens H. Variation in antibiotic prescribing and its impact on recovery in patients with acute cough in primary care: prospective study in 13 countries. BMJ 2009;338:b2242.

[17] - Smucny J, Fahey T, Becker L, Glazier R. Antibiotics for acute bronchitis. Cochrane Database Syst Rev 2004;(4):CD000245.

[18] - Spurling GK, Del Mar CB, Dooley L, Foxlee R. Delayed antibiotics for respiratory infections. Cochrane Database Syst Rev 2007;(3):CD004417.

[19] - Puhan MA, Vollenweider D, Latshang T, Steurer J, Steurer-Stey C. Exacerbations of chronic obstructive pulmonary disease: when are antibiotics indicated? A systematic review. Respir Res 2007 Apr 4;8:30 a.m.

[20] - Puhan MA, Vollenweider D, Steurer J, Bossuyt PM, Ter Riet G. Where is the supporting evidence for treating mild to moderate chronic obstructive pulmonary disease exacerbations with antibiotics? A systematic review. BMC Med. 2008 Oct 10;6:28.

[21] - Akkerman AE, Kuyvenhoven MM, Wouden JC van der, Verheij TJM. Determinants of antibiotic overprescribing in respiratory tract infections in general practice. J Antimicrob Chemother 2005;56(5):930-6.

[22] - Butler CC, Rollnick S, Pill R, Maggs-Rapport F, Stott N. Understanding the culture of prescribing: qualitative study of general practitioners' and patients' perceptions of antibiotics for sore throats. BMJ 1998;317(7159):637-42.

[23] - Kallestrup P, Bro F. Parents' beliefs and expectations when presenting with a febrile child at an out-of-hours general practice clinic. Br J Gen Pract 2003;53(486):43-4.

[24] - Macfarlane J, Holmes W, Macfarlane R, Britten N. Influence of patients' expectations on antibiotic management of acute lower respiratory tract illness in general practice: questionnaire study. BMJ 1997;315(7117):1211-4.

[25] - Li J, De A, Ketchum K, Fagnan LJ, Haxby DG, Thomas A. Antimicrobial prescribing for upper respiratory infections and its effect on return visits. Fam Med 2009;41 (3):182-7.

[26] - Rutten G, Van Eijk J, Beek M, Van der Velden H. Patient education about cough: effect on the consulting behaviour of general practice patients. Br J Gen Pract 1991; 41(348):289-92.

[27] - Cals JWL, Scheppers NAM, Hopstaken RM, Hood K, Dinant GJ, Goettsch H, Butler CC. Evidence based management of acute bronchitis; sustained competence of enhanced communication skills acquisition in general practice. Patient Educ Couns 2007;68(3):270-8.

[28] - Welschen I, Kuyvenhoven MM, Hoes AW, Verheij TJM. Effectiveness of a multiple intervention to reduce antibiotic prescribing for respiratory tract symptoms in primary care: randomised controlled trial. BMJ 2004; 329(7463):431-3.