Section 2: 2008 Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) annual report – Antimicrobial use

Section Two – Antimicrobial Use

Humans

Canadian CompuScript Data

For the CIPARS analysis of antimicrobial use in humans, data were obtained from the Canadian CompuScript (CCS) dataset provided by Intercontinental Medical Statistics (IMS) Health for 2000 through 2008. This dataset provides information on prescriptions dispensed by Canadian retail pharmacies. Additional information on IMS Health data collection and CIPARS analytic methods is provided in Appendix A. Information on the total volume of active ingredients of oral antimicrobials and on population demographics is available in Tables C.7 and C.8 (Appendix C), respectively.

Canada Overall

In 2008, there was a decrease in the antimicrobial prescription dispensing rate (Table 24 and Figure 37) to the lowest level observed (671.16 prescriptions/1,000 inhabitants) during the 9-year surveillance period. The total expenditure ($20,555/1,000 inhabitants) was the second lowest observed during the same period (Figure 37). Compared with expenditures in 2007, expenditures in 2008 related to combinations of penicillins (including β-lactamase inhibitors), third-generation cephalosporins, fluoroquinolones, β-lactamase sensitive penicillins, β-lactamase resistant penicillins, and combinations of sulfonamides and trimethoprim (including derivatives) increased but remained lower than in 2000 (Table 25). On the other hand, expenditures related to glycopeptides, imidazole, linezolid, penicillins with extended spectrum, first-generation cephalosporins, lincosamides, and nitrofuran derivatives were higher in 2008 than in 2007 and 2000 (Table 25).

The 4 most commonly dispensed systemic antimicrobial classes in 2008 (in DDDs/1,000 inhabitant-days) were penicillins with extended spectrum (4.43), macrolides (3.73), tetracyclines (2.38), and fluoroquinolones (2.06; Table 26 and Figure 38). Although fluoroquinolones represented a lower number of DDD/1,000 inhabitant-days than tetracyclines, they were almost 3 times more frequently prescribed and cost 3 times more per 1,000 inhabitants (Tables 24, 25 and 26). Category I antimicrobials continued to represent a high proportion (17%, 3.08/17.91) of the total DDDs dispensed (Table 27).

The consumption^{Footnote 30} of drugs in most classes decreased or remained stable between 2000 and 2008 (Table 26). However, increases in DDDs/1,000 inhabitant-days were observed for combinations of penicillins, including β-lactamase inhibitors (amoxicillin-clavulanic acid, from 0.51 to 0.71), first-generation cephalosporins (driven primarily by cefadroxil, from 0.75 to 0.98), lincosamides (driven primarily by clindamycin, from 0.24 to 0.38), and nitrofuran derivatives (nitrofurantoin, from 0.42 to 0.61).

Consumption was slightly lower in 2008 than in 2007 for fluoroquinolones (2.06 and 2.09 DDDs per 1,000 inhabitant-days, respectively) and for macrolides (3.73 and 3.75 DDDs, respectively; Table 26). Among the fluoroquinolones, this decrease was explained mainly by small decreases in the consumption of norfloxacin and moxifloxacin (0.17 to 0.15 DDDs and 0.43 to 0.42 DDDs, respectively; Figure 39). Interestingly, the consumption of moxifloxacin markedly increased, from 0.01 DDDs in 2000 to 0.43 DDDs in 2007 (Figure 39).

Among the macrolides, most of the decrease observed between 2007 and 2008 was attributable to a decrease in consumption of erythromycin (0.27 DDDs per 1,000 inhabitant-days in 2007 to 0.25 DDDs in 2008; Figure 40). Overall, the consumption of erythromycin continuously decreased from 0.88 DDDs in 2000 to 0.25 DDDs in 2008. Consumption of clarithromycin continued to increase from 2.18 DDDs in 2004 to 2.68 DDDs in 2007 and 2.70 DDDs in 2008 (Figure 40).

Provincial Variations

In 2008, differences in the total consumption of oral antimicrobials (in DDDs/1,000 inhabitant-days) and total cost in dollars (per 1,000 inhabitant-days) were observed across Canada (Table 27 and Figure 41). Much of the inter-provincial variation in DDDs could be explained by differences in consumption of penicillins with extended spectrum, fluoroquinolones, tetracyclines, macrolides, first-generation cephalosporins, and combinations of sulfonamides and trimethoprim (including derivatives; Table 27 and Figure 41). Consumption and total cost per 1,000 inhabitant-days were still the highest in Newfoundland and Labrador (30.20 DDDs and $84.75, respectively), whereas Québec had the lowest overall antimicrobial consumption and total cost (13.54 DDDs and $48.85, respectively).

Compared with consumption in Québec, consumption in Newfoundland and Labrador was driven primarily by higher consumption of antimicrobials belonging to the classes penicillins with extended spectrum, fluoroquinolones, and macrolides (Table 27). The higher consumption of fluoroquinolones was attributable to ciprofloxacin consumption (3.53 DDDs in Newfoundland and Labrador vs. 1.13 DDDs in Québec). Ciprofloxacin consumption increased over the years (assuming the trend in the combined data from Prince Edward Island and Newfoundland and Labrador before 2005 was mostly influenced by consumption in Newfoundland and Labrador) but appeared to have reached a plateau in 2007 and 2008 (Figure 42). The high macrolide consumption was attributable to clarithromycin (4.55 DDDs in Newfoundland and Labrador vs. 2.52 DDDs in Québec).

Saskatchewan had the second highest total consumption of antimicrobials in 2008, driven by higher consumption of antimicrobials belonging to the classes penicillins with extended spectrum, tetracyclines, macrolides, and first-generation cephalosporins (Table 27). The higher consumption of tetracyclines was attributable to the consumption of doxycycline, which has always been higher and has increased in Saskatchewan, compared with consumption in other provinces (Figure 43). Total doxycycline consumption in Saskatchewan in 2008 was 3.29 DDDs, compared with 0.46 DDDs in Québec during the same year. In Saskatchewan, the high consumption of first-generation cephalosporins was influenced by levels of consumption of cephalexin (2.01 DDDs in Saskatchewan vs. 0.26 DDDs in Québec). Despite higher overall antimicrobial consumption in Saskatchewan than in Québec in 2008, consumption of antimicrobial classes such as fluoroquinolones and macrolides was lower in Saskatchewan than in Québec (fluoroquinolones, 1.41 DDDs vs. 1.96 DDDs, respectively; and macrolides, 2.94 DDDs vs. 3.19 DDDs, respectively).

As mentioned previously, consumption of moxifloxacin increased from 2000 to 2007 then slightly decreased from 2007 to 2008. The increase between 2000 and 2007 was observed in all provinces (Figure 44). Québec, New Brunswick, and Prince Edward Island had the highest increase in the level of consumption during this period. From 2007 to 2008, a decrease in moxifloxacin consumption was observed in Ontario and Québec, while consumption in all other provinces either increased or remained stable (Figure 44).

Also as mentioned, clindamycin consumption continued to increase since 2000. Until 2007, the province of Alberta had the highest levels of consumption (Figure 45). Toward the latter half of 2007 and throughout 2008, an increase in consumption was observed in Saskatchewan, making consumption of clindamycin in that province higher than consumption in Alberta during that same period (0.48 DDDs vs. 0.47 DDDs, respectively, in the latter half of 2007; and 0.53 DDDs vs. 0.49 DDDs, respectively, in 2008; Figure 45).

International Comparisons

The estimate of the total amount of oral antimicrobials dispensed in 2007 by Canadian retail pharmacies was compared with the total amount of outpatient antimicrobial use in 19 European countries^{Footnote 31} in the same year (Figure 46). This comparison showed that the level of consumption in Canada was similar to the level of consumption in Finland and Denmark. Canada's oral antimicrobial consumption represented almost twice the level of antimicrobial consumption reported by the Russian Federation (the country with the lowest level of consumption) and half the level estimated in Cyprus (the country with the highest level of consumption). Whereas Canada ranked 9th out of the 20 countries classified by increasing level of total antimicrobial consumption, it ranked 18th for its level of consumption of macrolides and lincosamides, and 13th for its level of consumption of quinolones (largely consisting of fluoroquinolones). Canada was among the top 5 countries with the lowest level of penicillins consumption.

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Animals^{Footnote 32}

Farm Surveillance

Pigs

Twenty-one veterinarians representing 96 sentinel swine herds were enrolled in CIPARS Farm Surveillance in 2008 (Appendix A). Of these, 20 veterinarians submitted completed questionnaires from 95 herds. Questionnaires provided data regarding herd characteristics (Figures C.1 and C.2, Appendix C), management, and antimicrobial use (AMU) and were administered 3 times per year. At least 3 completed AMU questionnaires were submitted by representatives for 60 participating herds, 2 questionnaires were submitted for 20 herds, and 1 questionnaire was submitted for 15 herds. Antimicrobial use may be underestimated in herds for which 3 completed questionnaires were not submitted in 2008.

The herds were distributed in the following provinces: Alberta, 24 (25%); Saskatchewan, 3 (3%); Manitoba, 7 (7%); Ontario, 24 (25%); and Québec, 27 (28%). For 10 (11%) corporate herds in western Canada, the province was not disclosed to CIPARS staff to maintain producer anonymity. Veterinarians of 47 (50%) herds reported continuous-flow management in the grower-finisher production phase, and veterinarians of 45 (47%) herds reported all-in-all-out management. Three (3%) herds were reported as having more than 1 pig-flow management system over the year. Half of the sentinel herds had a grower-finisher barn capacity that exceeded 1,700 pigs.

Canada Overall

Data regarding antimicrobial use practices were available for all herds. Ninety-five percent (90/95) of the herds reported using antimicrobials in the grower-finisher production phase and 5% (5/95) of the herds reported no antimicrobial use in the grower-finisher production phase. Among all participating herds, AMU was more common via feed (79%, 75/95) and injection (61%, 58/95) than by water (28%, 27/95).

Representatives of 61% (58/95) of the herds reported the use of antimicrobials from 3 or more classes (range, 0 to 6; Figure 47). The most commonly used antimicrobial class was the penicillins (68%, 65/95; Figure 48 and Table 28). Antimicrobials in the macrolide class were the most common antimicrobials administered through feed and were most commonly used to treat enteric disease or promote growth (Figure 49 and Figure 50). Use of macrolides and/or lincosamides via feed often persisted until pigs were close to market weight. Penicillins were the most common antimicrobials administered through water. These antimicrobials were administered to pigs of all weights and were predominantly used to prevent disease or treat respiratory disease (Figure 51 and Figure 52). Penicillins were also the most common drugs administered via injection (Figure 48). The 2 primary reasons for penicillin use via injection were to treat respiratory disease and lameness (Figure 53).

Injectable ceftiofur, an extended-spectrum cephalosporin, was used in 21% (20/95) of herds. Ceftiofur is the only antimicrobial used in these pig farms that is classified by Health Canada's Veterinary Drugs Directorate as a Category I antimicrobial (Table 29). Compared with the use of ceftiofur in 2007 (29%, 29/100), the reported use of ceftiofur in 2008 represents an 8% decrease. Ceftiofur was used in the treatment of respiratory disease, lameness, enteric disease, and other unspecified conditions (Figure 53).

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Canadian Animal Health Institute

The Canadian Animal Health Institute (CAHI) is the trade association representing the companies that manufacture and distribute drugs for administration to food, sporting, and companion animals in Canada. The association estimates that its members' sales represent over 95% of all sales of licensed animal pharmaceutical products in Canada. CAHI coordinates electronic collection of data from its members and 1 non-member on the total kilograms of antimicrobials distributed by Canadian companies. Data collection and analysis are performed by a third party, Impact Vet.^{Footnote 34}

Acquired data on active ingredients were aggregated and provided to the Public Health Agency of Canada by CAHI (Table 29). Data regarding all licensed antimicrobials for use in food, sporting, and companion animals and fish were included. These data do not represent actual antimicrobial use in a given year; rather, they reflect the volume of antimicrobials distributed by manufacturers. Distribution values should approximate amounts used, particularly when data from more than 1 year are included. However, when data from only 1 year are included, distribution values may vary from amounts actually used because of the time lag between distribution and actual use, as well as stockpiling of antimicrobials at various points in the distribution system. The data do not include antimicrobials imported for personal use (own use import) under the personal-use provision of the federal Food and Drugs Act & Regulations, nor do they include active pharmaceutical ingredients, which are drugs imported in non-dosage form and compounded by a licensed pharmacist or veterinarian and used in veterinary medicine and food-animal production. See the 2006 CIPARS report for more information.Footnote 33

The CAHI data on the distribution of antimicrobials for use in animals provide a context through which to interpret other data on antimicrobial use in animals generated through research and farm data collection. They also provide a means to monitor gross temporal changes in antimicrobial use in animals.

CAHI's data collection process resulted in several changes to the categorization of specific antimicrobials (in comparison to 2006 and 2007). The major changes are outlined below:

• The cephalosporin class was not reported separately. One 1st generation cephalosporin was included in "β-lactams." The remainder, a 1st generation and a 3rd generation cephalosporin, were included in "Other antimicrobials."
• "Amphenicols" were reported as a separate category (previously included in "Other antimicrobials").
• "Bacitracins" were grouped with "Macrolides and Pleuromutilins" (previously included in "Other antimicrobials").
• "Nitroimidazoles" were grouped with "Ionophores, chemical coccidiostats and arsenicals" (previously included in "Other antimicrobials").
• "Neomycin" (an aminoglycoside) was moved to "Other antimicrobials" (previously included in "Aminoglycosides").

These changes in aggregation are important to keep in mind when making year-to-year comparisons. Overall, the total kilograms of active ingredient distributed for sale by Canadian companies decreased by 8.52% relative to the 2006 total and by less than 1% relative to the 2007 total. In terms of Category I antimicrobials, the quantity of fluoroquinolones distributed for use in animals in 2008 decreased by 30.38% relative to the 2006 total and by 7.15% relative to the 2007 total. Reasons for these decreases are unknown but may be related to major livestock production changes in Canada (Appendix C, Tables C.9 and C.10).