Role of cephalosporins in the era ofClostridium difficileinfection

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.

Antibiotic susceptibility and resistance profiles of Romanian Clostridioides difficile isolates

“…As most MLS B -resistant isolates were ermB-negative and no chloramphenicol-resistant isolates showed presence of catD, molecular resistance mechanisms against these antibiotics remain unclear and are to be analysed more thoroughly in future studies. The findings in the present study support the assertion that extensive administration of rifampin, carbapenems such as imipenem, fluoroquinolones, cephalosporins or MLS B [6,15,21,40,41], could involve high risk of CDI development and emergence of outbreaks, especially with epidemic PRs 027 or 017. In contrast, taking into consideration antibiotics demonstrated to be highly active against C. difficile, when selecting treatment for various types of infections, could contribute to minimising the risk of CDI spread.…”

“…Toxin A (TcdAenterotoxin) and toxin B (TcdB -cytotoxin) are the main virulence factors, although important epidemic strains also produce a third type -the binary toxin (C. difficile toxin -CDT) [5]. The main risk factors for colonization with toxigenic C. difficile and associated disease are considered to be hospitalisation in acute or long-term care units, advanced age (≥ 65 years) [1,6] and prolonged treatment with wide-spectrum antibiotics like clindamycin, cephalosporins or fluoroquinolones, to which many C. difficile strains are non-susceptible [2,[6][7][8][9][10]. C. difficile infection (CDI) may also be community-associated, targeting both paediatric (> 2 years) and adult patients [2,11], through contact with spore-contaminated surfaces, infected persons, or as zoonotic infections [3].…”

“…Chloramphencol-resistance may be induced by chloramphenicol acetyltransferase, encoded by the catD gene, specific to Tn4453a or Tn4453b transposons [10,17]. CDI has represented a considerable burden for public health in North America, Asia and Europe in the last decades [6,24].…”

National Surveillance forClostridioides difficileInfection, Sweden, 2009–2016

“…Countries in Europe have large variations in CDI incidence rates and distribution of prevalent PCR ribotypes, and the highest incidence rates occur in the northern countries, even though these countries have a low prevalence of RT027 ( 4 , 5 ). In addition, across Europe, a weak negative correlation has been observed between CDI incidence rates and cephalosporin use ( 5 ).…”

Clostridium Difficile Infection - An Optimistic View

“…Although nearly all antibiotics have been associated with CDI, clindamycin, third-generation cephalosporins, penicillins and fluoroquinolones have traditionally been considered to pose the greatest risk [8,16]. However newer studies show that there was no clear association between overall cephalosporin usage (or any cephalosporin) and CDI incidence [17]. The prophylactic dose given immediately before surgery is associated with dramatically reduced rates of wound infection and post-operative sepsis [18].…”