Updated Management Guidelines for Clostridioides difficile in Paediatrics

Abstract

Clostridioides difficile, formerly known as Clostridium difficile, causes infections (CDI) varying from self-limited diarrhoea to severe conditions, including toxic megacolon and bowel perforation. For this reason, a prompt diagnosis is fundamental to early treatment and the prevention of transmission. The aim of this article is to review diagnostic laboratory methods that are now available to detect C. difficile and to discuss the most recent recommendations on CDI treatment in children. Currently, there is no consensus on the best method for detecting C. difficile. Indeed, none of the available diagnostics possess at the same time high sensitivity and specificity, low cost and rapid turnaround times. Appropriate therapy is targeted according to age, severity and recurrence of the episode of infection, and the recent availability of new antibiotics opens new opportunities. De-escalation of antibiotics that are directly associated with CDI remains a priority and the cautious use of probiotics is recommended. Vancomycin represents the first-line therapy for CDI, although in children metronidazole can still be used as a first-line drug. Fidaxomicin is a new treatment option with equivalent initial response rates as vancomycin but lower relapse rates of CDI. Faecal microbiota transplantation should be considered for patients with multiple recurrences of CDI. Monoclonal antibodies and vaccines seem to represent a future perspective against CDI. However, only further studies will permit us to understand whether these new approaches could be effective in therapy and prevention of CDI in paediatric populations.

Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults

“…Depending on the degree of C. difficile risk induction, the antibiotics were divided into three groups: high (fluoroquinolones, 2nd and 3rd generation cephalosporins, clindamycin, ampicillin, broad-spectrum penicillins with inhibitors, except for ticarcillin with clavulanate, and piperacillin with tazobactam), moderate (macrolides, trimethoprim/sulfamethoxazole, other penicillins, and sulfonamides) and low risk (aminoglycosides, bacitracin, carbapenems, chloramphenicol, daptomycin, metronidazole, rifampicin, teicoplanin, tigecycline, tetracycline, and vancomycin) ( Kukla et al, 2020 ). Current standard treatment for CDI involves treatment with antibiotics such as metronidazole, vancomycin, or fidaxomicin ( Mills et al, 2018 ; Gnocchi et al, 2020 ). Vancomycin is the first-line antibiotic therapy for both first episode of infection and fulminant infections in adults ( Esposito et al, 2015 ; Wang et al, 2020 ).…”

“…Unfortunately, vancomycin is a strong disruptor of gut microbiota, while the rate of CDI recurrence after treatment cessation occurs in 20–30% of patients ( Lessa et al, 2015 ; Winston and Theriot, 2016 ). On the other hand, metronidazole is used especially in the first episodes of mild acute CDI and less for severe disease because the concentrations in the colon become readily undetectable due to the fact that it is absorbed very quickly ( Gnocchi et al, 2020 ). The rapid absorption from the gut is also reflected in a negligible effect on normal microbiota ( Lessa et al, 2015 ; Chilton et al, 2018 ).…”

“…The rapid absorption from the gut is also reflected in a negligible effect on normal microbiota ( Lessa et al, 2015 ; Chilton et al, 2018 ). Fidaxomicin can be used in C. difficile non-severe and also severe infections treatment due to the fact that it is poorly absorbed at the intestinal level, ensuring the persistence of killing concentration in the gut and has a narrow antimicrobial spectrum (e.g., Gram-positive and Gram-negative anaerobes and facultative aerobes) unaffecting the equilibrium of the normal intestinal microbiota ( Tannock et al, 2010 ; Louie et al, 2011 , 2012 ; Gnocchi et al, 2020 ). Moreover, in another study, vancomycin and metronidazole treatment, but not fidaxomicin were associated with the potentially pathogenic fungal operational taxonomic units’ emergence as well as with bacterial functions enriched for xenobiotic metabolism that could contribute to dysbiosis that could favor the occurrence, persistence and recurrence of CDI ( Lamendella et al, 2018 ).…”

“…Depending on the degree of C. difficile risk induction, the antibiotics were divided into three groups: high (fluoroquinolones, 2nd and 3rd generation cephalosporins, clindamycin, ampicillin, broad-spectrum (Kukla et al, 2020). Current standard treatment for CDI involves treatment with antibiotics such as metronidazole, vancomycin, or fidaxomicin (Mills et al, 2018;Gnocchi et al, 2020). Vancomycin is the first-line antibiotic therapy for both first episode of infection and fulminant infections in adults (Esposito et al, 2015;Wang et al, 2020).…”

Effects of antibiotics on the viability of and toxin production by Clostridium botulinum

“…Van, MNZ, and FDX are used to treat C. difficile infections. 14 We measured the minimal growth inhibitory concentrations (MICs) of these antibiotics against C. botulinum. The MIC assay was performed according to the serial dilution method using 96 well microplates.…”