Role of cephalosporins in the era of Clostridium difficile infection

Abstract

The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011-12 to 2012-13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes.

Figure 1.

Incidence of CDI and overall cephalosporin use in (a) the community and (b) hospital settings during 2012–13. The text overlay reports usage of first-, second-, third- and fourth-generation cephalosporins in EU/EEA countries in 2013, expressed as DDD per 1000 inhabitants and per day, if available. Community/hospital usage of second- and third-generation cephalosporins (as a percentage of first-, second-, third- and fourth-generation usage) is: Belgium, 92.8/53.6; Bulgaria, 82.1/87.0; Czech Republic, 94.5/NA; Finland, 2.6/77.9; France, 97.7/75.0; Germany, 97.8/NA; Greece, 100/94.1; Hungary, 99.4/90.1; Ireland, 85.3/95.8; Italy, 96.4/78.8; Netherlands, 100/71.3; Poland, 95.2/NA; Portugal, 77.6/67.4; Slovakia, 95.6/89.2; Spain, 99.4/NA; Sweden, 18.8/94.0; UK, 11.8/73.1. Data are from the ECDC. Regression analyses are based on least-squares means. CDI incidence data for 2012–13 are from Davies et al. ^aIncludes data for first-, second-, third- and fourth-generation cephalosporins.

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. Prescription data from IMS Health.