Antimicrobial Research Laboratory
National Public Health Institute
Reduction of antimicrobial use combined with improved hygiene measures in hospitals has been shown to be effective in reducing levels of bacterial resistance.(1,2) However, only a few studies have examined the link between decreased antimicrobial consumption and bacterial resistance in the outpatient setting.
Establishing the link between resistance and antimicrobial use
In 1990, a rapid increase in macrolide resistance was observed in Streptococcus pyogenes isolates in Finland.(3) Resistance was geographically significantly more prevalent in areas where macrolides were commonly used.(4) This link led us to give a recommendation to decrease macrolide use in infections caused by S pyogenes (ie, tonsillitis and skin infections). Macrolide use was replaced mainly with first-generation cephalosporins, which are always effective against S pyogenes.
Consumption of macrolides declined significantly – to 42% of the level before the recommendation.(5) This decrease was very much indication- based; macrolide use decreased especially in tonsillitis and skin infections, and thereafter it has been minimal.(6) Following the decrease in macrolide use, macrolide resistance in S pyogenes started to decrease in all parts of Finland. From 1993, when the highest (19%) level of macrolide resistance was detected, resistance decreased to 8.6% in 1996. In some areas resistance decreased from 42% to a level of 5%.
Changing the diagnosis to justify antimicrobial prescription
In Iceland, a decrease in penicillin resistance levels in Streptococcus pneumoniae was detected when antibiotic use decreased due to a recommendation to avoid antimicrobial prescription in the treatment of respiratory tract infections in children. Interestingly, physicians made fewer otitis media diagnoses, replacing them with diagnoses of unspecified respiratory tract infection (ie, the common cold).(7) It can be assumed that physicians justified the reduction in antimicrobial prescribing by changing their clinical diagnoses; to avoid prescribing antibiotics they did not diagnose otitis media anymore but used a diagnosis of common cold instead.
In Finland, a clear correlation has been observed between overall antimicrobial prescribing and frequency of otitis media, sinusitis and acute bronchitis diagnoses at a healthcare centre level.(8) Tendency to make a specific diagnosis in unclear cases seems to be a common habit used to justify antimicrobial prescribing.
Success may be species dependent
Although decreasing resistance levels in both S pyogenes and S pneumoniae has been successful, this may not be the case with other bacteria. Seven years ago we predicted that, in view of the molecular genetics of trimethoprim and sulfonamide resistance in Gram-negative bacilli, there are no signs that removal of selection pressure will have an immediate impact on the level of resistance.(9)
This was recently shown to be the case in a UK study, where no correlation was found between a decrease in sulfonamide use and the existence of sulfonamide-resistant Escherichia coli.(10)
Decreasing antimicrobial consumption may become a less effective tool in the fight against resistant bacteria with the spread of multiresistant bacterial pathogens. In the case of Finnish macrolide-resistant S pyogenes isolates, the strains were susceptible to first-generation cephalosporins and the therapy was always successful. However, when the strains are multiresistant, as is the case with S pneumoniae isolates in many European countries, replacement of one particular antimicrobial agent with another may not be effective in decreasing the number of resistant strains.
New therapeutic approaches also needed
Prudent and careful use of antimicrobial agents is very important. However, new therapeutic approaches have to be found. New ways to tackle this problem may be bacteriotherapy or therapy with bacteriophages.(11,12) These methods and many others are, however, still in the development phase, and meanwhile we have to try to improve our diagnostic skills and methods as well as to avoid the inappropriate use of antimicrobial agents.
- Swartz MN. Use of antimicrobial agents and drug resistance. N Engl J Med 1997;337:491-2.
- Giamarellou H, Antoniadou A. The effect of monitoring of antibiotic use on decreasing antibiotic resistance in the hospital. Ciba Found Symp 1997;207:76-86.
- Seppälä H, Nissinen A, Järvinen H, et al. Resistance to erythromycin in group A streptococci. N Engl J Med 1992;326:292-7.
- Seppälä H, Klaukka T, Lehtonen R, et al. Outpatient erythromycin use – link to increased erythromycin resistance in group A streptococci. Clin Infect Dis 1995;21:1378-85.
- 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. N Engl J Med 1997;337:441-6.
- Rautakorpi U-M, Lumio J, Huovinen P, et al. Indication-based use of antimicrobials in Finnish primary health care. Description of a method for data collection and results of its application. Scand J Prim Health Care 1999;17:93-9.
- Kristinsson K. Effect of antimicrobial use and other risk factors on antimicrobial resistance in pneumococci. Microb Drug Res 1997;3:117-23.
- Huovinen P, Rautakorpi U-M, Klaukka T, et al. Indication-based analysis of antibiotic use in primary care. Abstract # ICAAC00-A-023862. 40th Interscience Congress of Antimicrobial Agents and Chemotherapy, 17–20 September, 2000. (See www.stakes.fi/mikstra/esitykset/poster_icaac2000.pdf)
- Huovinen P, Sundström L, Swedberg G, et al. Trimethoprim and sulfonamide resistance (Minireview). Antimicrob Agents Chemother 1995;39:279-89.
- Enne VI, Livermore DM, Stephens P, et al. Persistence of sulphonamide resistance in Escherichia coli in the UK despite national prescribing restriction. Lancet 2001;357:1325-8.
- Huovinen P. Bacteriotherapy: the time has come (Editorial). BMJ 2001;323:353-4.
- Sulakvelidze A, Alavidze Z, Morris JG. Bacteriophage therapy. Antimicrob Agents Chemother 2001;45:649-59.