Antimicrobial resistance in Clostridioides (Clostridium) difficile derived from humans: a systematic review and meta-analysis

Abstract

Background Clostridioides (Clostridium) difficile is an important pathogen of healthcare- associated diarrhea, however, an increase in the occurrence of C. difficile infection (CDI) outside hospital settings has been reported. The accumulation of antimicrobial resistance in C. difficile can increase the risk of CDI development and/or its spread. The limited number of antimicrobials for the treatment of CDI is matter of some concern. Objectives In order to summarize the data on antimicrobial resistance to C. difficile derived from humans, a systematic review and meta-analysis were performed. Methods We searched five bibliographic databases: (MEDLINE [PubMed], Scopus, Embase, Cochrane Library and Web of Science) for studies that focused on antimicrobial susceptibility testing in C. difficile and were published between 1992 and 2019. The weighted pooled resistance (WPR) for each antimicrobial agent was calculated using a random- effects model. Results A total of 111 studies were included. The WPR for metronidazole and vancomycin was 1.0% (95% CI 0–3%) and 1% (95% CI 0–2%) for the breakpoint > 2 mg/L and 0% (95% CI 0%) for breakpoint ≥32 μg/ml. Rifampin and tigecycline had a WPRs of 37.0% (95% CI 18–58%) and 1% (95% CI 0–3%), respectively. The WPRs for the other antimicrobials were as follows: ciprofloxacin 95% (95% CI 85–100%), moxifloxacin 32% (95% CI 25–40%), clindamycin 59% (95% CI 53–65%), amoxicillin/clavulanate 0% (0–0%), piperacillin/tazobactam 0% (0–0%) and ceftriaxone 47% (95% CI 29–65%). Tetracycline had a WPR 20% (95% CI 14–27%) and meropenem showed 0% (95% CI 0–1%); resistance to fidaxomicin was reported in one isolate (0.08%). Conclusion Resistance to metronidazole, vancomycin, fidaxomicin, meropenem and piperacillin/tazobactam is reported rarely. From the alternative CDI drug treatments, tigecycline had a lower resistance rate than rifampin. The high-risk antimicrobials for CDI development showed a high level of resistance, the highest was seen in the second generation of fluoroquinolones and clindamycin; amoxicillin/clavulanate showed almost no resistance. Tetracycline resistance was present in one fifth of human clinical C. difficile isolates.

Opportunities for Nanomedicine in Clostridioides difficile Infection

“…Fidaxomicin treatment also inhibits sporulation and decreases spore shedding into the environment [ 71 , 72 ]. Despite only one resistant isolate being reported to date [ 73 ], development of non-antibiotic therapy to prevent therapeutic resistance is urgently needed for CDI control.…”

Clostridioides difficile as a Dynamic Vehicle for the Dissemination of Antimicrobial-Resistance Determinants: Review and In Silico Analysis

“…Currently, C. difficile isolates with multiple-antibiotic resistance have emerged, such as the hyper-virulent ribotypes O27 and O78 strains, a phenomenon that is becoming a heavy burden in CDI treatment [ 7 , 8 ]. Further, the ability of C. difficile to form spores and their subsequent persistence in adverse environments may also have a role in the acquisition of novel antibiotic-resistance determinants.…”

“…A noteworthy point is that resistance rates depend on various factors, for examples, geographical locations and policies on the usage of antimicrobial agents [ 7 ]. Moreover, the breakpoints for defining resistance during laboratory testing differ between the Clinical & Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing for some antimicrobials (e.g., vancomycin), which can affect the interpretation of results.…”

Alimentary and Pharmaceutical Approach to Natural Antimicrobials against Clostridioides difficile Gastrointestinal Infection

“…In fact, it is expected that by 2050, more people will die due to multiresistant bacteria than cancer pathologies [ 1 ]. Among these highly antimicrobial-resistant bacteria, Clostridioides difficile is becoming a concerning threat worldwide [ 2 , 3 , 4 ]. These Gram-positive anaerobic and spore-forming bacteria has become the most frequent causal agent of hospital-acquired intestinal infection in Europe and all over the world, causing close to 30,000 death per year in the US (estimated mortality close to 16.7%) [ 3 , 5 ].…”