Chapter 2: Human Antimicrobial Drug Use Report 2012/2013 – Pharmacy dispensation data

b. Defined daily doses per 1,000 inhabitant-days (DIDs) and cost per inhabitant

A reduction in the DIDs also occurred over this time frame. In 2013, 17.6 DIDs were dispensed, which was a 2.8% reduction from the 18.1 DIDs dispensed in 2012. Similarly, a 3.2% decline in DIDs was seen from 2011 to 2012 (18.7 to 18.1 DIDs). These reductions return the DID values to those seen in 2010 (Figure 2.2).

Finally, the cost of antimicrobial prescribing in Canada has also been declining. After accounting for the effects of inflation, approximately $19.20 was spent per inhabitant in Canada in 2013, $0.90 less than in 2012 ($20.10), and $2.40 less than in 2011 (Figure 2.2).

Figure 2.2: Number of defined daily doses and cost ¹ per inhabitant of antimicrobials dispensed by Canadian retail pharmacies, 2000 – 2013^*.

Use by age groups

Generally, antimicrobial use was highest among the youngest (0-5) and oldest (65+) age groups in the Canadian population from 2010 – 2013 (Figures 2.3 & 2.4). Use among the groups including 6-39 year olds was slightly below the national measures in 2013, while use in the remaining age groups was above national measures.

a. Children and young adults (≤ 17 years old)

The trend in prescribing was similar among the three age groups from 2010 – 2013, with an increase from 2010 to 2011, and a decline from 2011 to 2013 (Figure 2.3). Over the time frame, children 0-5 had the greatest prescription rate, followed by the 6-11 age group. Interestingly, the increase from 2010 to 2011 was most dramatic for the 6-11 age group (71 prescriptions / 1,000 inhabitant increase), while the greatest overall reduction 2010 – 2013 occurred for the 0-5 age group (131 prescriptions / 1,000 inhabitant reduction) (Figure 2.3). The least variation over time occurred in the 12-17 age group.

In 2013, children 0-5 received 230 prescriptions / 1,000 inhabitants more than the general population (872 compared to 642 prescriptions / 1,000 inhabitants) (Figure 2.3). In contrast, the prescription rate for children 6-11 was 107 prescriptions / 1,000 inhabitants lower than the overall rate in 2013 (535 compared to 642 prescriptions / 1,000 inhabitants). Even more dramatically, the prescription rate for the 12-17 age group was 220 prescriptions / 1,000 inhabitants lower than the overall rate.

Figure 2.3: Prescriptions per 1,000 inhabitant-days for oral and parenteral antimicrobials used in Canada 2010 – 2013, by age group.

b. Adults (≥ 18 years old)

In contrast with the decreasing antimicrobial use with increasing age in children and young adults, antimicrobial use increased in Canada from 2010 - 2013 as the age groups increased (Figure 2.4). Defined daily doses per 1,000 inhabitant-days were highest for the 60+ age group over the entire time frame, followed by the 60-64, 40-49, and finally, 18-39 age groups.

The pattern of use from 2010 – 2013 for the 18-39 and 40-59 age groups was similar to the prescribing rates seen in the children and young adult data, with an increase from 2010 – 2011 and subsequent decline. Interestingly, this pattern was not seen for the 60-64 or 65+ age groups.  In these groups, an increase from 2010 – 2011 was apparent, followed by a slight decline from 2011 – 2012, and a relative stabilization from 2012 – 2013.

In comparison to the national DID measure in 2013 (17.6 DIDs), the 65+ and 60-64 age groups were 4.8 and 3.4 DIDs greater, respectively (22.4 and 21.0, respectively). The DIDs for the 40-59 age group were slightly higher than the overall measure in 2013 (18.0 DIDs), while the DIDs for the 18-39 age group were slightly lower (16.5 DIDs).

Figure 2.4: Defined daily doses per 1,000 inhabitant-days for oral and parenteral antimicrobials used in Canada 2010 – 2013, by age group.

Use at the individual drug level

a. Prescriptions per 1,000 inhabitants

The most commonly prescribed antimicrobials in 2013 were amoxicillin (158.6 prescriptions / 1,000 inhabitants), ciprofloxacin (50.3 prescriptions / 1,000 inhabitants), and azithromycin (55.6 prescriptions / 1,000 inhabitants) (Table 2.1, Figure 2.5).

Figure 2.5: Prescriptions per 1,000 inhabitants for the eight most frequently dispensed antimicrobials in 2013 by retail pharmacies in Canada; oral antimicrobials (2000-2009), oral and parenteral antimicrobials (2010-2013).

The greatest reductions in prescribing over the 2000 to 2013 time frame occurred for erythromycin (26.2 prescriptions / 1,000 inhabitants), sulfamethoxazole and trimethoprim (25.4 prescriptions / 1,000 inhabitants) and penicillin V (22.5 prescriptions / 1,000 inhabitants) (Table 2.1, Figures 2.5 & 2.6). In contrast, the greatest increases in prescribing over this time frame occurred for nitrofurantoin (20.1 prescriptions / 1,000 inhabitants), moxifloxacin (13.9 prescriptions / 1,000 inhabitants), and azithromycin (13.5 prescriptions / 1,000 inhabitants) (Table 2.1, Figures 2.5 & 2.6).

It should be noted that the largest reductions far outweigh the increases seen during the 2000 to 2013 time frame. Furthermore, increases in the use of some products might be seen as favourable, if these increases reflect attention to prudent use guidelines (e.g., nitrofurantoin for acute uncomplicated cystitis). However, these data are not sufficient to assess the suitability of chosen courses of treatment.

Figure 2.6: Patterns in prescribing rates (prescriptions per 1,000 inhabitants) from 2000 – 2013 for antimicrobials with the greatest absolute difference in rates from 2000 to 2013*

b. Defined daily doses per 1,000 inhabitant-days (DIDs)

The antimicrobials with the greatest DIDs in 2013 were amoxicillin (4.77 DIDs), clarithromycin (2.25 DIDs), and doxycycline (1.38 DIDs) (Table 2.2, Figure 2.7).

Figure 2.7: Defined daily doses per 1,000 inhabitant-days for the eight antimicrobials with the highest DDD values in 2013; oral antimicrobials (2000-2009), oral and parenteral antimicrobials (2010-2013)

The greatest reductions in DIDs over the 2000 – 2013 time frame occurred for erythromycin (0.70 DIDs), tetracycline (0.69 DIDs), and sulfamethoxazole and trimethoprim (0.56 DIDs). In contrast, the greatest increases in DIDs over the same time frame were for doxycycline (0.63 DIDs), amoxicillin and enzyme inhibitor (0.50 DIDs), and nitrofurantoin (0.36 DIDs) (Table 2.2, Figures 2.7 & 2.8).

In comparison to the prescribing rate measure, where declines greatly outweighed increases, the declines in use seen from 2000 to 2013 by DIDs did not outweigh the increases seen over the same time period. This may reflect a move towards prescriptions of higher dose, and/or of longer duration.

Figure 2.8: Patterns in DID rates (defined daily doses per 1,000 inhabitant-days) from 2000 – 2013 for antimicrobials with the greatest absolute difference in rates from 2000 to 2013*

c. Defined daily doses per prescription

Changes in the average number of DDDs per prescription dispensed have occurred for a number of antimicrobials over the 2000 – 2013 time frame. Of the antimicrobials included in both of Figures 2.5 and 2.7, these patterns are displayed in Figure 2.9. Slight increases over time were seen for cephalexin, azithromycin, and amoxicillin, while more dramatic (> 25%) increases were seen for amoxicillin and enzyme inhibitor and for clarithromycin.

Figure 2.9: Defined daily doses per prescriptions for the six antimicrobials with the highest DDD and prescription rates; oral antimicrobials (2000-2009), oral and parenteral antimicrobials (2010-2013)

Use by route of administration

The use of oral antimicrobial products has not shown dramatic changes over the 2010 – 2013 time frame. For all measures, year over year changes were < 7% (Table 2.3). In contrast, the use of parenteral antimicrobial products has increased over this time frame, particularly from 2012 to 2013 (Table 2.3). Particularly striking increases in parenteral product use from 2012 to 2013 were seen for the total kilograms of active ingredient and kilograms of active ingredient / 1,000 inhabitants measures, which increased by 200% and 176%, respectively. Accordingly, as the volume of active ingredient dispensed increased, the cost of parenteral treatment also increased from 2012 to 2013, by 96%, equivalent to an increase of $382 / 1,000 inhabitants.

The majority of antimicrobials used in the Canadian outpatient population in 2013 were drugs for oral administration; more than 260 oral prescriptions are dispensed for each parenteral antimicrobial prescription at the national level. Interestingly, the parenteral products that were dispensed from outpatient pharmacies were not products that have an oral format. Figure 2.10 displays the proportion of oral DDDs by individual product, while Figure 2.11 displays the proportion of parenteral DDDs by individual product. No antimicrobial product appears on both of these figures.

a. Oral antimicrobials

Figure 2.10: Proportion of oral DDDs by individual antimicrobial dispensed by outpatient pharmacies in Canada, 2013

* Other drugs are products with < 2% share in 2013. These drugs (listed in order of greatest to least use) are: penicillin V, moxifloxacin, tetracycline, cefprozil, metronidazole, levofloxacin, cloxacillin, cefixime, erythromycin, norfloxacin, trimethoprim, cefadroxil, ofloxacin, ampicillin, vancomycin, linezolid, cefaclor, spiramycin, methenamine mandelate, fosfomycin, fidaxomicin, sulfadiazine, fusidic acid, flucloxacillin, sulfamethoxazole, and penicillin g.

b. Parenteral antimicrobials

Figure 2.11: Proportion of parenteral DDDs by individual antimicrobial dispensed by outpatient pharmacies in Canada, 2013

*Other drugs are products with < 2% share. These drugs (listed in order of greatest to least use) are: cloxacillin, clindamycin, ceftazidime, daptomycin, ampicillin, amikacin, metronidazole, ciprofloxacin, cefepime, tigecycline, imipenem and cilastatin, cefoxitin, levofloxacin, azithromycin, streptomycin, erythromycin, cefuroxime, cefotaxime, lincomycin, piperacillin, ticarcillin and clavulanic acid, linezolid, chloramphenicol, and sulfamethoxazole and trimethoprim.

Provincial Variation

Overall measures of use

Antimicrobial use continues to vary at the provincial level by all four measures assessed in this use report. In 2013, Newfoundland and Labrador displayed the highest values for all measures, while no single province held the lowest value for all measures.

a. Prescription rates and kilograms of active ingredients

In 2013, the prescription rate per 1,000 inhabitants ranged from 569 in Québec to 979 in Newfoundland and Labrador (Figure 2.12). A similar pattern was seen for the kilograms of active ingredient dispensed, with Newfoundland and Labrador dispensing a high of 10.0kg / 1,000 inhabitants, and Québec with a low of 4.7kg / 1,000 inhabitants (Figure 2.12).

Figure 2.12 also shows how the national prescription rate in 2013 (642 prescriptions / 1,000 inhabitants) was greatly driven by the lower- prescribing provinces (Québec, British Columbia, and Ontario). Similarly, at the national level, 5.7 kilograms of active ingredient were dispensed per 1,000 inhabitants; largely driven by the low volume dispensed in the same three provinces.

Figure 2.12: Number of prescriptions and kilograms of active ingredient per 1,000 inhabitants dispensed by retail pharmacies in 2013, by province

b. Defined daily doses and cost per inhabitant

In accordance with the prescription rates and kilograms of active ingredient, Newfoundland and Labrador had the highest DIDs and cost per inhabitant in 2013 (Figure 2.13 and Appendix C, Figure C.1). DIDs in Newfoundland and Labrador were approximately 30% higher than in the province with the second-highest use by this measure (Saskatchewan). Similarly, cost per inhabitant was $6.30 higher in Newfoundland and Labrador than in Saskatchewan, which is a >28% gap between these provinces.

Interestingly, although Québec displayed the lowest prescription rate, DIDs, and kilograms of active ingredient dispensed, the cost / inhabitant in Québec was within the median range of costs in 2013. This is also displayed by looking at the overall cost per DDD dispensed, which is highest in Québec (Appendix C, Figure C.2).The province with the lowest cost per inhabitant in 2013 was British Columbia.

In comparison with the national measures, the DIDs for Newfoundland and Labrador were again strikingly high in 2013 (29.2 DIDs compared to the national 17.6 DIDs). With increased use, associated costs were high in Newfoundland and Labrador in 2013 as well, where the cost per inhabitant was approximately $9.30 higher than the national measure.

In all provinces in 2013, the greatest DIDs dispensed were for the extended spectrum penicillin antimicrobial class, followed by either the macrolide or tetracycline class (Appendix C, Figure C.1).

Figure 2.13: Defined daily doses per 1,000 inhabitant-days and cost per inhabitant of antimicrobials dispensed by retail pharmacies in 2013, by province

Use at individual drug level

A considerable amount of variation in antimicrobial prescribing occurred among the provinces at the individual drug level. For example, although the prescription rate and DIDs were highest for amoxicillin among all provinces (Table 2.3), the prescription rate varied from a high of 279.9 prescriptions / 1,000 inhabitants in Newfoundland and Labrador to a low of 97.7 prescriptions / 1,000 inhabitants in Québec. Although the overall prescription rate in Québec was lower than the remaining provinces, there were a number of antimicrobials where the use was highest in Québec. Notably, cefadroxil, cefprozil, ertapenem, minocycline, moxifloxacin, penicillin V, and vancomycin (Table 2.3). Interestingly, although Newfoundland and Labrador displays the highest prescription rate overall, their rate of vancomycin prescriptions was the lowest in the country.

Other antimicrobials that displayed a large amount of variation in the prescription rate were cephalexin, with a high of 99.1 prescriptions / 1,000 inhabitants in Saskatchewan and low of 15.6 prescriptions / 1,000 inhabitants in Québec, ciprofloxacin (115.2 prescriptions / 1,000 inhabitants in Newfoundland and Labrador, 46.3 prescriptions / 1,000 inhabitants in Ontario), and azithromycin (91.2 prescriptions / 1,000 inhabitants in Newfoundland and Labrador, 29.5 prescriptions / 1,000 inhabitants in British Columbia) (Table 2.3). Provincial drug-level prescriptions per 1,000 inhabitants data from 2012 can be found in Appendix C, Table C.3)

Variation in the DIDs is also apparent among the provinces at the individual antimicrobial level. The greatest variation again occurred in the use of amoxicillin (high of 8.77 DIDs in Newfoundland and Labrador, low of 3.24 DIDs in Québec). High variation in use was also seen for doxycycline (3.95 DIDs in Saskatchewan, 0.82 DIDs in Québec), ciprofloxacin (3.03 DIDs in Newfoundland and Labrador, 0.95 DIDs in New Brunswick), and clarithromycin (3.42 DIDs in Newfoundland and Labrador, 1.45 DIDs in Manitoba). Provincial drug-level DID data from 2012 can be found in Appendix C, Table C.4).

Use by route of administration

The majority of antimicrobials used in the Canadian outpatient population are drugs for oral administration. In 2013, more than 240 oral prescriptions were dispensed for each parenteral antimicrobial prescription at the national level. However, when viewed at the provincial level, the variation in use of oral and parenteral antimicrobials was quite dramatic (Figure 2.14). The prescription rates for parenteral antimicrobials in Québec, New Brunswick, and Nova Scotia are more than twice the rate of any other province, and are more than fifteen-times the rate in others (British Columbia, Manitoba, and Ontario) (Figure 2.14).

In the community setting in all provinces with the exception of New Brunswick and Nova Scotia, the dispensing of oral vancomycin was roughly 50% greater than the dispensing of parenteral vancomycin. In New Brunswick and Nova Scotia, this was reversed (individual product data not shown due to the small volume of parenteral products dispensed in the community setting).

Figure 2.14: Provincial level antimicrobial prescriptions per 1,000 inhabitants in 2013, by route of administration.