Clostridium difficileinfection: update on emerging antibiotic treatment options and antibiotic resistance

Abstract

Clostridium difficile infection (CDI) is the most common cause of identifiable diarrhea in hospitalized patients. The incidence and severity of CDIs are increasing. The increased incidence and severity of the disease has sparked interest in the optimal treatment of CDI as well as the use of new therapies and drug discovery. Current treatment strategies are inadequate with decreased response rates to metronidazole, and high recurrence rates with the use of metronidazole and oral vancomycin. Although incidence rates continue to be low, in vitro resistance to antibiotics used for the treatment of CDI has been noted. Recently, important data has emerged on new anti-C. difficile antibiotics such as rifaximin, rifalazil, fidaxomicin, nitazoxanide, tigecycline and ramoplanin. The purpose of this review is to provide an update on the in vitro susceptibility and new antibiotic treatment options for CDI. This review will focus primarily on scientific studies published in the last 36 months in order to provide an up-to-date review on the topic. KeywordsClostridium difficile; fidaxomicin; nitazoxanide; rifaximin; treatment update Clostridium difficile infection (CDI) is the most common cause of identifiable diarrhea in hospital ized patients. CDI is an evolving pathogen with high incidence and severity. Current treatment of CDI is evolving and a number of new antibiotic treatment options are available [1][2][3]. In vitro resistance to antibiotics used for the treatment of CDI continues to be low; however, resistance among certain strains has been identified. Recently, important data has emerged on new anti-C. difficile antibiotics such as rifaximin, rifalazil, fidaxomicin, nitazoxanide, tigecycline and ramoplanin. The purpose of this review is to provide an update on the in vitro susceptibility and new treatment options for CDI. The present article will focus on scientific studies published primarily in the last 36 months in order to provide an up-to-date review on the topic. With CDI and drugs that concentrate in the gut, the concept of using antimicrobial breakpoints for resistance or susceptibility based on systemic drug concentrations may be inadequate [22]. More studies are needed to determine a physiologic breakpoint for enteric infectious diseases considering drug pharmacokinetics and pharmacodynamics. Colonic concentrations of active antibiotics should be related to the MIC of the organism in order to generate appropriate breakpoints for nonsystemic infections. Update on treatment of CDI with metronidazole & oral vancomycinA summary of randomized controlled trials with metronidazole or oral vancomycin compared with new or emerging therapies is presented in 15,000 cells/mm 3 . The cure rate was similar for patients given metronidazole (90%; n = 41) and oral vancomycin (98%; n = 40) for mild CDI. There was a significantly higher cure rate for severe patients treated with oral vancomycin (97%; n = 31) than metronidazole (76%; n = 38; p = 0.02). These results were similar to a Phase III comparator trial of tolev...

Antimicrobial susceptibility of Clostridium difficile isolated from animals and humans in Brazil

“…This result is consistent with observations by BÅVERUD (2002), who reported that beta-lactams are commonly associated with CDI in foals and adult horses. In contrast to reports in other countries (HUANG et al, 2009, SHAH et al, 2010, none of the human isolates were resistant to penicillin in this study, and only one of the 13 strains tested (7.7%) was moderately susceptible to this compound.…”

“…In general, a large variation in the MIC values were observed for tetracycline, what has also been reported in studies with C. diffi cile strains isolated from pigs and humans (DELMÉE & AVESANI, 1988;POST & SONGER, 2004;SHAH et al, 2010). However, almost all isolates from the earlier studies were susceptible to this antimicrobial.…”

“…Currently, metronidazoleresistant strains have only been isolated from horses in the USA (JANG et al, 1997;MAGDESIAN et al, 2006). Similar to observations in animals, metronidazole-resistant C. diffi cile strains are rarely isolated from humans (SHAH et al, 2010;SPIGAGLIA et al, 2011). Vancomycin-resistant C. diffi cile isolates are also extremely rare for both animal and human strains.…”

“…Vancomycin-resistant C. diffi cile isolates are also extremely rare for both animal and human strains. In addition, vancomycin is considered clinically more effective and generates fewer relapse cases following CDI treatment in humans (SHAH et al, 2010); therefore, it is considered the best option by many clinicians. In addition to this study, only one other study in Brazil has evaluated antimicrobial susceptibility in six C. diffi cile strains isolated from humans with CDI; similar to this study, the isolates were also susceptible to metronidazole and vancomycin (BALASSIANO et al, 2009).…”

Clostridium difficile Carriage in Elderly Subjects and Associated Changes in the Intestinal Microbiota

“…In a study by Baines et al (3), 24% of C. difficile 001 ribotypes demonstrated reduced susceptibility to metronidazole, which may raise questions regarding the use of metronidazole to treat very refractory cases (3). The increased rate of disease recurrence has driven the search for alternative treatments, and antibiotics such as rifaximin, nitazoxanide, tigecycline, and fidaxomicin (OPT-80) are currently being proposed as different therapies with various degrees of success (31). In addition, bacteriocins have been suggested as substitute or adjunct therapies to conventional antibiotics (4,(25)(26)(27).…”