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Review 4of18 Table 1. Cephalosporins most commonly used across Europe in the year ending August 2013 Country CDI incidence, cases/10000 patient bed-days Total cephalosporin use, SUs, 1000s cefuroxime axetil Cephalosporin use, SUs, % (1000s) of total cephalosporin use in that country cefpodoxime proxetil cefaclor cefixime cefalexin ceftriaxone cefuroxime cefazolin cefprozil cefadroxil ceftazidime other Austria 4.1 13059 17.4 (2271) 20.0 (2609) 18.3 (2386) 10.9 (1422) 17.4 (2279) 2.0 (265) 8.1 (1058) 3.4 (444) — — 0.7 (88) 1.8 (237) Belgium 4.0 10996 59.2 (6507) — ,0.05 (0.2) — 1.2 (129) 2.5 (275) 2.8 (306) 10.7 (1176) — 19.0 (2084) 2.7 (302) 2.0 (216) Bulgaria 0.7 16702 29.7 (4958) 8.8 (1465) — 9.5 (1582) 12.8 (2145) 12.7 (2116) 3.0 (502) — 5.6 (929) — 0.2 (32) 17.8 (2972) Czech Rep. 6.2 11048 62.7 (6928) — — — — 0.6 (64) 2.6 (287) 6.0 (668) 14.3 (1580) 8.4 (923) 1.2 (131) 4.2 (467) Finland 28.7 19486 1.1 (211) — 0.3 (59) — 84.9 (16540) 1.3 (255) 12.2 (2381) — — — 0.2 (40) ,0.05 (0.6) France 3.3 236373 10.0 (23708) 65.6 (155043) 3.3 (7878) 9.2 (21721) — 4.4 (10341) 0.4 (1043) 1.4 (3310) — — 0.6 (1432) 5.0 (11897) Germany 11.0 204103 48.2 (98358) 8.4 (17056) 23.0 (46928) 3.6 (7328) — 2.7 (5531) 6.8 (13796) 2.1 (4208) — — 0.7 (1399) 4.7 (9500) Greece 3.9 44798 48.4 (21680) — 23.0 (10300) 0.4 (199) — ,0.05 (20) 0.5 (221) — 27.1 (12162) — ,0.05 (12) 0.5 (204) Hungary 15.5 14361 42.3 (6072) — 8.7 (1250) 16.9 (2420) — 4.3 (615) 2.4 (345) 1.9 (269) 16.8 (2411) — 0.3 (37) 6.6 (941) Ireland 9.1 8492 15.4 (1306) 0.6 (51) 49.9 (4240) 4.9 (414) 22.6 (1917) 1.0 (83) 3.7 (314) 0.05 (4) — — 0.6 (51) 1.3 (113) Italy 7.2 127431 3.4 (4285) 11.9 (15123) 10.6 (13507) 30.7 (39125) — 17.7 (22527) 0.3 (418) 4.5 (5787) — — 4.6 (5822) 16.4 (20850) Netherlands 5.3 2913 5.9 (173) — 3.2 (94) — 2.3 (67) 10.2 (296) 30.6 (892) 32.2 (938) — — 8.8 (257) 6.8 (197) Poland 8.2 74377 58.8 (43701) — 12.3 (9132) — — 2.6 (1923) 9.7 (7250) 2.6 (1952) — 7.8 (5770) 1.1 (787) 5.2 (3901) Portugal 3.0 11544 33.2 (3837) — 10.8 (1246) 8.2 (952) — 7.9 (911) 1.8 (208) 6.8 (782) — — 1.6 (180) 29.7 (3427) Romania 7.4 69306 45.6 (31592) — 11.9 (8227) 6.0 (4181) 16.4 (11376) 9.9 (6847) 0.7 (456) — — 4.3 (2997) 2.3 (1616) 2.9 (2014) Slovakia 1.2 13901 61.7 (8575) — — 11.0 (1523) — 0.2 (24) 1.5 (202) 2.3 (315) 5.4 (746) 6.5 (904) 0.1 (14) 11.5 (1598) Spain 3.2 58333 43.8 (25568) — — 19.1 (11130) — 4.1 (2403) 1.2 (676) 5.7 (3299) — — 1.7 (966) 24.5 (14293) Sweden 13.3 3210 0 (0) — — — 0.4 (14) 1.2 (37) 4.5 (144) — — 51.6 (1657) 1.6 (52) 40.7 (1306) UK 3.7 52992 0.9 (458) — 3.1 (1664) 0.4 (232) 80.8 (42842) 1.5 (802) 4.1 (2191) — — 0.8 (415) 1.2 (618) 7.1 (3769) SU, standard unit. CDI incidence data for September 2012 to August 2013 from Davies et al. 17 Prescription data from IMS Health. Downloaded from http://jac.oxfordjournals.org/ by guest on September 28, 2016
Review JAC CDI incidence was among the lowest (0.7 cases/10000 patient bed-days). 17,18 The lack of correlation between cephalosporin use and CDI incidence is also apparent when the analysis is confined to second- and third-generation cephalosporins [r 2 ¼0.049 (P¼0.466); Figure 1b]. Under-testing/reporting and variations in the reporting systems used in the different European countries will clearly affect country-specific CDI rates, while the methods employed to capture antibiotic use may also vary between countries. Despite the limitations inherent in this type of analysis, however, it seems unlikely that ‘corrected’ incidence data would reveal a correlation with cephalosporin prescribing, given the existent data show a lack of correlation. Use of different cephalosporins and incidence of CDI in Europe Table 1 shows the usage of specific cephalosporin antibiotics in different European countries. These data also revealed no clear associations between the reported CDI incidence from EUCLID 17 and the use of any particular cephalosporin (Figure 2). There were considerable variations in the use of particular drugs (as a proportion of total cephalosporin use) across countries with similar CDI incidence. For example, the use of cefuroxime axetil differed markedly in France and Belgium (10.0% and 59.2%, respectively, of cephalosporin prescriptions), although reported rates for CDI were in the range of 1–4 cases/10000 patient bed-days in the two countries. Similarly, ceftriaxone use differed in Italy (17.7% of cephalosporin prescriptions) and Austria (2.0%), although CDI incidence was similar (4–8 cases/10000 patient bed-days). Proportion of total cephalosporin use (%) 90 80 70 60 50 40 30 20 10 Furthermore, similar levels of use for some cephalosporins were seen in countries with differing CDI incidence. For example, cefuroxime axetil accounted for 42%–46% of cephalosporin prescriptions in Spain, Romania and Hungary, but CDI incidence differed across these countries (1–4, 4–8 and 12–16 cases/10000 patient bed-days, respectively). Similarly, use of ceftriaxone was similar in Romania (9.9%) and Bulgaria (12.7%), although CDI incidence differed (4–8 and ,1 cases/10000 patient bed-days, respectively). In Slovakia and the Czech Republic, the overall profiles of cephalosporin use were similar, despite the differing incidence of CDI (1–4 and 4–8 cases/10000 patient bed-days, respectively). 17 Although confounding factors, such as the use of other antibiotics, could affect CDI incidence, the data do not suggest a close association between increased use of oral cephalosporins and CDI incidence. Oral agents comprised approximately 80%–90% of total cephalosporin use in more than half of the countries studied, and CDI incidence ranged from 1–4 to .20 cases per 10000 patient bed-days in these countries. In countries where oral cephalosporin use was less widespread (52%–66% overall), CDI incidence also varied markedly (from ,1 to 12–16 cases per 10000 patient bed-days). Thus, these data suggest that determining the association between CDI risk and antibiotic usage is more complicated than simply correlating the risk with the type of drug, highlighting the need for more detailed analysis. Principles underlying CDI risk Reported CDI incidence (cases/10 000 patient bed-days) The risk of CDI is not uniform across all patient populations, but is dependent on a number of issues, notably age, comorbidities and No data 4–8 >8–12 >12–16 >16–20 >20 Downloaded from http://jac.oxfordjournals.org/ by guest on September 28, 2016 0 Cefuroxime axetil Cefpodoxime proxetil Cefaclor Cefixime Cefalexin Ceftriaxone Cefuroxime Cefazolin Cefprozil Cefadroxil Ceftazidime Other Figure 2. Use of the most common cephalosporins across Europe, as a proportion of total cephalosporin use in each country, in the year ending August 2013. Countries (from left to right for each agent, arranged by CDI incidence): ,1: Bulgaria; 1–4: Belgium, France, Greece, Portugal, Slovakia, Spain, UK; .4–8: Austria, Czech Republic, Italy, Netherlands, Romania; .8–12: Germany, Ireland, Poland; .12–16: Hungary, Sweden; .20: Finland. CDI incidence data from September 2012 to August 2013 from Davies et al. 17 Prescription data from IMS Health. 5of18
Page 1 and 2: Journal of Antimicrobial Chemothera
Page 3: Review JAC antibiotics. 13 Addition
Page 7 and 8: Table 2. Summary of pharmacokinetic
Page 9 and 10: Review Second cefaclor (Ceclor w ;
Page 11 and 12: 11 of 18 Third cefixime (Fixx w ; Z
Page 13 and 14: Review JAC following a single 600 m
Page 15 and 16: Review JAC (P,0.001) in the inciden
Page 17 and 18: Review JAC 19 Eyre DW, Cule ML, Wil

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