Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection

Abstract

Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and contain the spread of resistance and to ensure an efficacious therapy for CDI.

Epidemiology of antimicrobial resistance in bloodstream infections

“…60 This increase was associated with the emergence of hypervirulent C. difficile strains. 61 The most prominent hypervirulent strain is PCR-ribotype (RT) 027 which is responsible serious and frequently recurring infections and many of these strains carry an MDR phenotype. A European survey in 2005 indicated that 55% of 148 isolates with resistance to at least one antibiotic was multidrug resistant.…”

“…Among these RT078 cause Clostridium difficile disease both in community and hospital settings, and also in animals. 61 …”

“…These programmes are desparetely needed and may be lacking even in hospitals in the developed part of the world. 124,125 Conclusions Antimicrobial resistance, particularly MDR phenotype in clinically important community and nosocomial Table 1 Frequent resistance mechanisms for selected antibacterial antibiotics in clinically important gram-negative bacteria (47,48,50,55,58,59,61,63,70,76,84,91) Arm-A meythylase confers high-level resistance. rRNA methylases are also described.…”

Clostridium difficile Infection: Pathogenesis, Diagnosis and Treatment

“…C. difficile also generally displays resistance to second-generation cephalosporins but shows less resistance to third-generation cephalosporins. However, resistance to moxifloxacin and gatifloxacin has been detected in 34% of strains analysed [29]. Tenover and colleagues analysed the resistances of different ribotypes to clindamycin, metronidazole, moxifloxacin and rifampin.…”

“…Clostridium difficile has a number of putative β-lactamase genes that are probably involved in resistance to β-lactam antibiotics [29]. A ribosomal methylation mechanism related to macrolide resistance in C. difficile has been described (Ref).…”