Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium. The clinical features of C. difficile infections (CDIs) can vary, ranging from the asymptomatic carriage and mild self-limiting diarrhoea to severe and sometimes fatal pseudomembranous colitis. C. difficile infections (CDIs) are associated with disruption of the gut microbiota caused by antimicrobial agents. The infections are predominantly hospital-acquired, but in the last decades, the CDI patterns have changed. Their prevalence increased, and the proportion of community-acquired CDIs has also increased. This can be associated with the appearance of hypervirulent epidemic isolates of ribotype 027. The COVID-19 pandemic and the associated antibiotic overuse could additionally change the patterns of infections. Treatment of CDIs is a challenge, with only three appropriate antibiotics for use. The wide distribution of C. difficile spores in hospital environments, chronic persistence in some individuals, especially children, and the recent detection of C. difficile in domestic pets can furthermore worsen the situation. “Superbugs” are microorganisms that are both highly virulent and resistant to antibiotics. The aim of this review article is to characterise C. difficile as a new member of the “superbug” family. Due to its worldwide spread, the lack of many treatment options and the high rates of both recurrence and mortality, C. difficile has emerged as a major concern for the healthcare system.

Updating data on Clostridioides difficile antibiotic resistance is important for treatment improvement of C. difficile infections (CDIs). Results from 20 countries were included. The mean resistance to 2 mg/l vancomycin, 2 mg/l metronidazole, 4 mg/l moxifloxacin, and 4 mg/l clindamycin was 4.7% (0 to ≥ 26% in two studies), 2.6% (0 to ≥ 40% in 3 studies), 34.9% (6.6->80%), and 61.0% (30->90%), respectively. Resistance to erythromycin (>60-88%), rifampin (>23-55.0%), imipenem (0.6 to > 78% in a clone), tigecycline (0-<5.0%), and fidaxomicin (0-2%) was also found. Resistance to ≥ 5 antibiotics of different classes was reported in some countries. High resistance and multidrug resistance were observed in hypervirulent and epidemic strains. Although only 1% of COVID-19 patients had CDIs, the proportion might be underestimated. C. difficile antimicrobial susceptibility varied by country/region, study period, and circulating ribotypes. For CDI treatment, fidaxomicin (preferably) or vancomycin is recommended, while metronidazole is suitable for mild infections. New approaches, including biotherapeutics (Rebyota), strains, antibiotics (ridinilazole and ibezapolstat), and monoclonal antibodies/cocktails merit further evaluation. Because of the resistance rate variations, C. difficile antibiotic susceptibility should be regularly monitored. Post-COVID-19 resistance should be separately presented. Some discrepancies between vancomycin and metronidazole results need to be clarified.

Cutibacterium acnes subspecies/phylotypes can cause infections requiring antibiotic therapy. Phylotyping of 73 (55 acneic and 18 non-acneic) C. acnes strains was performed, and antibiotic susceptibility was tested by E tests, breakpoint susceptibility test, or disk diffusion method. The dominant phylotype in both acneic and non-acneic strains was IA1 (56.2%). Phylotype II was >3-fold more frequent in non-acneic than acneic isolates. Resistance in acneic strains was >41% for clindamycin, 36.4% for tetracycline and 15.9% for levofloxacin, and that in non-acneic strains was >38% for clindamycin, 22.2% for tetracycline and 5.6% for levofloxacin. No strain was piperacillin/tazobactam or vancomycin resistant. Amoxicillin resistance was found in both acneic (5.4%) and non-acneic strains (11.1%), and was rare (1.8%) in phylotype I but higher (23.5%) in other strains. Double resistance was found in 32.6% of acneic and 22.2% of the non-acneic strains, and 9.3% of acneic strains displayed multidrug resistance. In conclusion, IA1 phylotype was dominant in both acneic and non-acneic strains, and type II was more frequent in non-acneic isolates. The detection (at >6%) of amoxicillin resistance represents a rare yet important finding. The presence of double/multidrug resistance strongly implies the need of susceptibility-guided therapy of the associated infections.

The COVID-19 pandemic boosted antibiotic use in Bulgaria. The aim of the study was to evaluate for the first time in our country, the influence of the COVID-19 pandemic on both characteristic, prevalence and antibiotic susceptibility of Clostridioides difficile. We investigated 75 C. difficile strains isolated since the pandemic compared with 52 strains from 2013–2019. In 2020–2023, the toxigenic strains (TCDs) were 92.0% of all strains vs. 57.7% of those isolated beforehand. In 2020–2023, TCD resistance was metronidazole 5.8%, vancomycin 1.4%, and fidaxomicin 1.6%, without significant differences between the two periods. We observed a 5.5-fold increase in the prevalence of hypervirulent (HCD) strains. In HCD strains in 2020–2023, metronidazole resistance was 7.9%. Notably, resistance to levofloxacin 1 and 32 mg/l was 91.9% and 75.8%, respectively, in TCD strains from 2020–2023. Briefly, the increase in both TCD and HCD strains and the presence of resistance to all three antibiotics for treating C. difficile infections imply the need for susceptibility testing of all TCD isolates. The strikingly high levofloxacin resistance was linked to fluoroquinolone consumption in Bulgaria. The results stress the need for regular monitoring of antibiotic susceptibility of TCD strains, and strict adherence to the antibiotic policy.

It is crucial to consider newer antibiotics with activity against anaerobes and Helicobacter pylori, given their healthcare importance, and the constantly growing antibiotic resistance/multidrug resistance, which complicates the therapy. The aim of this review was to emphasize certain recently approved or still-under-investigation antibiotics with potential benefits for treating Clostridioides difficile infections (CDIs), other anaerobic infections, and those caused by H. pylori, covering recent data from articles published primarily in 2020–2026. Given the limited number of antibiotics for treating CDI and fidaxomicin nonavailability in many countries, it is necessary to conduct more extensive laboratory and clinical studies of promising antibiotics such as ibezapolstat, delafloxacin, lascufloxacin, omadacycline, eravacycline, ridinilazole, and CRS3123. Against Bacteroides fragilis group species, delafloxacin and eravacycline showed good activity. Research on rifasutenizol for bacterial vaginosis, sarecycline and nadifloxacin for acne vulgaris and amixicile for periodontal diseases needs to be expanded. For H. pylori infection, delafloxacin, sitafloxacin, nemonoxacin, zoliflodacin, and rifasutenizol may improve the suboptimal success of most eradication regimens. However, more efforts, in coordination between medical, scientific, manufacturing, and government representatives, should ensure wider access to and research on the newer antibacterials. Establishing more research groups, careful examination of market issues, and additional approaches, such as nanomaterials, efflux pump inhibitors, phage therapy, and CRISPR-Cas systems, should be beneficial. Notwithstanding the difficulties, there are many opportunities to promote research on and potential use of newer antibiotics which show advantages over the older antibacterials, and to make them available to numerous countries and patients worldwide.

The aim of the study was to investigate the MLST types and genes encoding Clostridioides difficile toxins from fecal clinical samples of patients from two large Bulgarian cities. Overall, 100 toxigenic isolates were obtained during a 10-year period from five hospitals in Sofia and Varna, Bulgaria. Toxin gene patterns of the isolates were determined with conventional polymerase chain reaction, and multilocus sequence typing (MLST) types were determined according to Griffith’s scheme. The evolutionary relatedness of ST types was analyzed through PHYLOViZ. Binary toxin-positive isolates accounted for 35% (35/100), and the most prevalent sequence type (ST) type was ST1 (clade2) with 34%. One binary toxin-positive isolate belonged to ST11 (clade5). The cdt-negative isolates were of two clades: clade 4 (ST37), with 1 tcdA-tcdB+ isolate, and clade 1, with 64 isolates. All the cdt-positive isolates showed 18 bp deletions of tcdC, except a ST11 isolate exhibiting a 39 bp deletion. Importantly, there was more than a 6-fold increase in ST1 isolates in the 2020–2023 period versus 2014–2019. The main cdt-negative isolates were ST3 (14%), ST2 (6%), ST42 (5%), and ST92 (5%). They were tcdA+tcdB+. Four main clonal complexes (with one allele difference) were found. The first one encompassed 19 isolates and included ST3 and ST42; the second included ST8, ST16, ST52, ST92 and ST36 (11 isolates); the third consisted of 13 isolates (ST2, ST49, ST13 and ST110 clones); and the fourth included ST10 and ST44 (5 isolates). The significance of our work is the detection of a high frequency of hypervirulent isolates during the COVID-19 pandemic period, which we attribute to the national consumption of systemic antibiotics, which increased during the second period, unlike the trend in other European countries. The results highlight the need for enhanced infection control measures and strict compliance with antibiotic stewardship programs.