A decade ago the increase of bacterial resistance to antimicrobial agents was declared a crisis (1). Today we can look back and see how the medical community has acted to fight this crisis. During the last 6-7 years there have been a number of different conferences and committee meetings, and numerous statements have been published. The complete list is available at the end of the article.
Optimal use of antimicrobial agents
All the reports emphasise the importance of prudent use of antimicrobial agents, in other words, the decreased use of antimicrobial agents. It is evident that the more a particular antimicrobial agent is used, the higher the bacterial resistance to that drug. This fact concerns both hospitals and the community. Thus, a decrease in the use of antimicrobial agents is necessary to diminish the selection pressure on bacteria. Another way is to use antimicrobial agents that cause least resistance.
It has also been estimated that 20-50% of all antimicrobial use is clinically unnecessary or even harmful (2). A significant amount of scientific evidence has been presented to the medical community regarding the importance of optimal use of antimicrobial agents. What has happened?
It is unfortunate that the medical community in Europe and elsewhere in the world has been relatively incapable of reacting to the crisis of antimicrobial resistance (3). There have been many good plans but only a very limited amount of action. Financial investments to fight resistant bacteria have also been minimal.
It is interesting to note that nobody knows the extent of antimicrobial usage in different European countries. It is impossible to measure changes in antimicrobial use without knowing the consumption figures! Antimicrobial consumption data is available somewhere, at least in the files of the pharmaceutical industry, but authority has not been exercised to collect the information.
In addition, comparable data on antimicrobial resistance of key bacterial pathogens is not available in Europe. Exceptions are Staphylococcus aureus and Streptococcus pneumoniae, which are surveyed by the European EARSS network ( www.ears.nl ).This network needs, however, more resources to build operative nationwide networks within each participating country.
In northern Europe the situation is somewhat better than in the rest of Europe. Denmark, Finland, Iceland, Norway and Sweden have published an annual Nordic Medical Statistics for more than two decades, including data regarding the consumption of antimicrobial agents. In addition, resistance surveillance is organized. These countries also have their own strategy to combat bacterial resistance.
What more is needed?
The total consumption data is not enough to improve antibiotic use. The clinicians are led astray if they are solely accused of using antimicrobial agents indiscriminately. Thus, there is a need for improved knowledge concerning the appropriate use of antimicrobials in different infections. National or regional treatment recommendations for the most common infections are needed. As far as possible, the recommendations should be evidence-based, and be written and reviewed by a representative group of clinicians and specialist organisations. For the preparation and renewal of the treatment recommendations, information on how antimicrobials are used in particular infections such as otitis media are also needed. If the recommendations are different from current practise, either the recommendation should be re-evaluated or education provided to the clinician.
How to combat bacterial resistance?
How can these data be used in the fight against bacterial resistance? A decade ago, a recommendation was issued to decrease the use of macrolides in the treatment of tonsillitis and skin infections in Finland, because macrolide resistance was increased in Streptococcus pyogenes, which is a common cause of these infections (4). This recommendation was taken seriously by Finnish general practitioners, and macrolide resistance decreased in all geographical regions (5).
In 1990-1999, macrolide resistance of Streptococcus pneumoniae increased from 0.6% to 10%. Streptococcus pneumoniae is the major causative agent in otitis media, sinusitis and pneumonia. The increase of macrolide resistance is a threat because macrolides are important drugs in the treatment of pneumonia. Pneumonia caused by a macrolide-resistant pneumococcus treated with macrolides is potentially a life threatening combination.
Reports from the MIKSTRA program ( http://www.mikstra.fi/ ) indicate that macrolides were very often used as the first-line treatment of otitis media and sinusitis (6). More than half of all macrolide consumption was based on these indications, in contrast to the national evidence-based treatment recommendations. Doctors have been informed to avoid the use of macrolides in otitis media and sinusitis. We hope that this recommendation will lead to a decrease in the use of macrolides and thus decrease macrolide-resistant Streptococcus pneumoniae.
Hand hygiene in hospitals
In many European countries, hospital hygiene has been totally unsuccessful. A good measure of this is the increase in the proportion of methicillin-resistant Staphylococcus aureus (MRSA) among Staphylococcus aureus blood culture isolates. MRSA is susceptible to only one antimicrobial agent, vancomycin, which is used as a last reserve drug. Frequencies of MRSA strains among blood culture isolates in different European countries are shown in figure (7). The rapid increase of MRSA during the last decade in Great Britain is very illustrative; the proportion of MRSA among blood culture Staphylococcus aureus isolates increased from a few percent in 1990 to 37% in 1999.
A simple method to limit the spread of resistant bacteria in hospitals is to improve hand hygiene (8,9). In a recent Swiss study, increased use of an alcohol hand rub significantly reduced hospital infections over a three-year study period. When the compliance of hand hygiene improved from 48% to 66%, the amount of hospital infections decreased from 16.6% to 9.9% (p=0.04) and the frequency of MRSA decreased from 2.16 to 0.93 cases per 10,000 patient days.
Although we tend to believe that hospital hand hygiene is good in northern Europe, this may not be the case. Alcohol hand rub compliance needs improvement, especially among physicians. This issue must be addressed by each hospital in order to find a solution. However, Swiss hospitals have saved more than 3 million Swiss francs annually as a result of improved hand hygiene. This economical benefit combined with better medical care should be enough to convince everyone to adopt alcohol hand rub into routine practise.
The essentials are well known
The principle weapons against increasing bacterial resistance are very easy to adopt. We need to know the consumption of antimicrobial agents, including information on which infections the drugs are used to treat. In addition, bacterial resistance surveillance should be organized. Treatment recommendations for the most common infections are essential to guide antimicrobial consumption. Finally, the use of alcohol hand rub in hospitals including compliance control is an essential measure to control spread of resistant.
The methods presented are not very expensive and can be effectuated through good teamwork and a common spirit directed to the same goal: to keep antimicrobial agents effective as long as possible.
1. Neu HC. Crisis of antibiotic resistance. Science 1992;257:1064-73.
2. Wise R, Hart T, Cars O et al. Antimicrobial resistance is a major threat to public health. BMJ 1998;317:609-10.
3. Huovinen P, Cars O. Control of antimicrobial resistance: time for action. BMJ 1998;317:613-4.
4. Seppälä H, Nissinen A, Järvinen H et al. Emergence of erythromycin resistance in group A strep-tococci. N Engl J Med 1992;326:292-297.
5. Seppälä H, Klaukka T, Vuopio-Varkila J et al. The effects of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. New Engl J Med 1997;337:441-446.
6. MIKSTRA-working group. Increase of macrolide resistance in pneumococci. More consideration to the use of first-line macrolide treatment. Finn Med J 2000;55:4405-7. (in Finnish)
7. EARSS. Susceptibility test results of Staphylococcus aureus. EARSS Newsletter 2000;3:2.
8. Pittet D, Hugonnet S, Harbarth S et al. Effectiveness of a hospital-wide programme to improve compliance with had hygiene. Lancet 2000;356:1307-12.
9. Widmer AF. Replace hand washing with use of a waterless alcohol hand rub. Clin Infect Dis 2000;31:136-43.
Reports concerning the crisis of bacterial resistance
The Crisis of Antibiotic Resistance. Science 1992, August 21. A special issue on antibiotic resistance
WHO Scientific Working Group on Monitoring and Management of Bacterial Resistance 1994
Impacts of Antibiotic-Resistant Bacteria 1995. US Congress of Health Technology Assessment.
Antibiotic Resistance: Origins, Evolution, Selection and Spread 1997. Ciba Foundation Symposium
Antibioottiresistenssi – Säilyykö lääkkeiden teho? 1997. Suomen Akatemia ja Lääkäriseura Duodecim, konsensuskokous (Finnish antibiotic resistance concensus meeting)
Antimicrobial Resistance; Issues and Options 1998. Institute of Medicine, USA.
Resistance to Antibiotics and Other Antimicrobial Agents 1998. House of Lords, UK
Resistance to Antibiotics as a Threat to Public Health 1998. Economic and Social Committee of the European Communities
The Path of Least Resistance 1998. Department of Health, UK
British Medical Journal 1998 No.7159, September 5, a special issue on antibiotic resistance
The Copenhagen Recommendation 1998. EU Conference on The Microbial Threat
Principles of Judicious Use of Antimicrobial Agents 1998. American Academy of Pediatrics
Proposals for a national action plan to control antibiotics resistance in France 1999. Institute de Veille Sanitaire
Opinion on the Scientific Steering Committee on Antimicrobial Resistance 1999. European Commission
Plan for å motvirke antibiotikaresistens 1999. Sosial og helsedepartementet, Norway (Strategic plan to combat antibiotic resistance in Norway)
Public Health Action Plan to Combat Antimicrobial Resistance 2000. American Society for Microbiology
The Urgency of a Massive Effort Against Infectious Diseases 2000. Executive Director for Communicable Diseases, WHO
Bakteerien lääkeresistenssin torjuminen ja mikrobilääkepolitiikan kehittäminen 2000
STM työryhmäraportti 2000:4 A committee report for the Finnish Ministry of Social Affairs and Health (An official program to improve antimicrobial use and to continue fight against bacterial resistance)
Förslag till svensk handlingsplan mot antibiotikaresistens 2000. Socialstyrelsen. (Strategic plan to combat antibiotic resistance in Sweden)