Sir,
Jensen et al.1 recently described the relationship between decreasing prices and increasing demand for ciprofloxacin. This relationship was shown for the ambulatory setting in Denmark, a country where patients receive a relatively low reimbursement for outpatient medication (until 1999: fixed percentage of 50%; since 2000: 50%–85% after the patient has spent the deductible of about €67 for outpatient medication within the calendar year).
In Germany, outpatient medication is provided as benefits-in-kind to patients covered by statutory health insurance (SHI; nearly 90% of the German population). In the ambulatory sector, patients only have to make a small co-payment (between €5 and €10) for every prescription. However, following the introduction of generics into the German pharmaceuticals market (Figure 1), we noted a similar increase in demand for broad-spectrum antimicrobials.
Fluoroquinolone consumption and prices related to the German SHI (1991–2007) together with rates of ciprofloxacin resistance in E. coli. DDD, defined daily dose; CPI, consumer price index. *The ciprofloxacin resistance rate in E. coli in German ambulatory care (data of the Paul Ehrlich Society, http://www.p-e-g.org/ag_resistenz/).
Interestingly, in Germany, the increase in consumption of broad-spectrum antimicrobials is not due to the fact that respective antimicrobial agents have become affordable for a larger proportion of the population, as pointed out by Jensen et al.1 as a possible reason for the increase in consumption in Denmark. Rather, the increase may possibly be related to the fact that in Germany a physician's decision to prescribe an antibiotic is probably guided by financial incentives. In Germany, ambulatory care physicians are generally self-employed, and the SHI reimburses fixed budgets for pharmaceuticals, the size of which depends on the number of patients and their ages.2 According to this reimbursement system and the general assumption that physicians are influenced by pecuniary incentives, we may presume that a physician's decision to prescribe an antimicrobial is influenced by the incentive to prescribe an agent that is (i) cheap and (ii) assures effective treatment to avoid short-term re-examination of the patient.
In Germany, the rate at which antibiotics are used in ambulatory care settings falls within the lower third of European Union (EU) countries.3 However, around 85% of all antibiotics are prescribed in the outpatient setting. Consumption is the driving force behind the generation of antibiotic resistance, and German data on ciprofloxacin-resistant Escherichia coli show an almost linear increase in resistance, from 0.2% in 1990 to 26.4% in 2007 (Figure 1). In 2007, resistance in the outpatient setting was even higher than in high-consumption areas like intensive care units.4 The reasons for the increase in the burden of multidrug-resistant pathogens in German hospitals are not fully understood, although recent studies have highlighted the problem posed by the admission of patients colonized or infected with methicillin-resistant Staphylococcus aureus or pathogens producing extended-spectrum β-lactamases.5 Accordingly, we may conclude that the increased prescription of broad-spectrum antimicrobials in ambulatory care also affects the spread of resistance in the hospital setting, where the attributable morbidity, costs and mortality due to resistant pathogens are disproportionately higher than in ambulatory care.
Ideally, demand for necessities like antibiotics should not vary with the price, i.e. the quantity demanded should not change much with the price. However, this is not the case for broad-spectrum antimicrobials such as ciprofloxacin.1 Interestingly, overall outpatient antibiotic use in Germany was relatively stable between 1991 and 2007 (Figure S1, available as Supplementary data at JAC Online). The use of fluoroquinolones and second-generation cephalosporins, however, shows a strongly increasing trend during the study period.6 Accordingly, there is no general over-consumption, but a shift towards broad-spectrum agents that became relatively cheaper in recent years.
The main question now is how to counteract this process. Since antimicrobial resistance may be seen as an external effect of antibiotic use,7 some authors argue that we should counteract with policy options that are traditionally associated with environmental economics, such as regulation, permits and charges.8 Unfortunately, the exact interactions between antimicrobial use and the spread of resistance in ambulatory care are far from being well monitored. In other words, we are unable to make assumptions on what sort of impact the use of a specific antimicrobial agent has on the resistance rate of a specific pathogen in ambulatory care. Accordingly, there is no ‘hard’ argument for restriction (in whatever form) of a specific agent. We strongly believe that it is of primary interest for ambulatory care physicians to guarantee adequate and effective antibiotic treatment of their patients. Accordingly, the fact that pecuniary incentives play a role may also be interpreted as showing that physicians regard the falling price of broad-spectrum antimicrobials as a chance to deliver ‘broad-spectrum healing’, without taking into account the effects on the resistance situation. Therefore, prudent use of broad-spectrum antimicrobials should be supported by adequate training and feedback of antibiotic use data and the local resistance situation.
Transparency declarations
None to declare.
Funding
The work of K. K. is currently supported by an unrestricted grant from the Viamedica Foundation. In addition, research on health and economic impacts of antimicrobial resistance by K. K. and U. F. is supported by the European Commission (Project IMPLEMENT, grant agreement no. 20091107; http://www.eu-implement.info).
Acknowledgements
We would like to thank Christian Hagist, Maria Martin, Deborah Lawrie-Blum and Christine Wilson for their help in preparing the manuscript. Furthermore, we would like to thank Valentina Coca for her efforts in data collection.
