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Mengoli, M.;  Barone, M.;  Fabbrini, M.;  D’amico, F.;  Brigidi, P.;  Turroni, S. Genetic Evolution and Global Spread of Clostridioides difficile. Encyclopedia. Available online: https://encyclopedia.pub/entry/38695 (accessed on 11 December 2025).
Mengoli M,  Barone M,  Fabbrini M,  D’amico F,  Brigidi P,  Turroni S. Genetic Evolution and Global Spread of Clostridioides difficile. Encyclopedia. Available at: https://encyclopedia.pub/entry/38695. Accessed December 11, 2025.
Mengoli, Mariachiara, Monica Barone, Marco Fabbrini, Federica D’amico, Patrizia Brigidi, Silvia Turroni. "Genetic Evolution and Global Spread of Clostridioides difficile" Encyclopedia, https://encyclopedia.pub/entry/38695 (accessed December 11, 2025).
Mengoli, M.,  Barone, M.,  Fabbrini, M.,  D’amico, F.,  Brigidi, P., & Turroni, S. (2022, December 13). Genetic Evolution and Global Spread of Clostridioides difficile. In Encyclopedia. https://encyclopedia.pub/entry/38695
Mengoli, Mariachiara, et al. "Genetic Evolution and Global Spread of Clostridioides difficile." Encyclopedia. Web. 13 December, 2022.
Genetic Evolution and Global Spread of Clostridioides difficile
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This entry is adapted from the peer-reviewed paper 10.3390/genes13122200

Clostridioides difficile is an obligate anaerobic pathogen among the most common causes of healthcare-associated infections. It poses a global threat due to the clinical outcomes of infection and resistance to antibiotics recommended by international guidelines for its eradication. In particular, C. difficile infection can lead to fulminant colitis associated with shock, hypotension, megacolon, and, in severe cases, death.

Clostridioides difficile PaLoc antibiotic resistance worldwide spread ribotypes genomic surveillance genetic engineering

1. Genetic Evolution of C. difficile Virulence

The C. difficile genome is characterized by a high level of plasticity. In particular, the evolution of its virulence concerns a specific genomic region, namely the Pathogenicity Locus (PaLoc). PaLoc consists of 19.6 kb of a chromosomally located element [1], which includes tcdA and tcdB, the genes encoding the two main toxins (TcdA and TcdB, respectively). PaLoc also comprises three accessory genes, namely tcdR, tcdC and tcdE. Specifically, tcdR encodes a positive regulator of toxin expression, while tcdC a negative regulator. tcdE encodes a putative holin-like protein, responsible for the secretion of microbial toxins [1][2]. Another toxin produced by C. difficile is the binary toxin (CDT), encoded by the Ctd Locus (CdtLoc), a distinct chromosomal region that carries cdtA and cdtB, the genes for catalytic and binding/translocation proteins, as well as cdtR, coding for a regulatory protein. The CdtLoc can be found in two versions, whole or truncated. In strains lacking CdtLoc, a unique 68-bp sequence is found inserted in the same genomic location [3][4]. In non-toxigenic strains, such as the recently discovered NTCD-035 by Maslanka et al. [5], PaLoc is replaced by a conserved non-coding sequence of 115 bp [1][6][7][8]. Ongoing works on the comparative genomics of C. difficile are highlighting some important features on the evolution of these two pathogenic regions. The entire PaLoc region appears to have a modular structure and its variability may be due to the substitution of single nucleotides and to recombination events that played a pivotal role in the evolution of PaLoc variants. This structure also affects the tcdA and tcdB genes. Interestingly, the CdtLoc region appears to be more conserved than the PaLoc region, but it is mainly observed that full-length CdtLoc is associated with C. difficile strains exhibiting significantly altered PaLoc [9]. Mansfield et al. [10] highlighted a difference between tcdA and tcdB: while the evolutionary history of tcdB may depend on extensive homologous recombination, tcdA shows a greater degree of sequence variation and a greater number of subtypes [10]. Therefore, the authors suggest that the extreme recombination events observed in tcdB, but not in tcdA, could lead to increased selective pressure for tcdB diversification, highlighting the potential role of tcdB in the pathogenesis of C. difficile. This observation seems to be confirmed also by studies focused on the use of monoclonal antibodies (e.g., bezlototumab and actoxumab) both in animal models (i.e., gnotobiotic piglets) [11] and in humans [10][12][13].
One of the few works so far focused on the evolutionary history of C. difficile is a study by Dingle et al. [8], which paves the way for understanding the genomic background of this bacillus. According to the authors, PaLoc acquisition occurred at separate times between the C. difficile clades. Based on multi-locus sequence typing (MLST), C. difficile strains can be stratified into at least eight phylogenetic clades: clade 1–5 and clades C-I, C-II and C-III [14]. Clade 1 includes over 200 toxigenic and non-toxigenic sequence type (STs). Clade 2 also contains several highly virulent strains (e.g., ST1). Little is known about clade 3, although it includes ST5, a toxigenic CDT-producing strain [14]. Clade 4 contains ST37, which is responsible for much of the endemic CDI burden in Asia [15] despite the absence of the tcdA gene. Clade 5 contains several CDT-producing strains (e.g., ST11), which are highly prevalent in production animals worldwide [16]. Clades C-I, C-II, and C-III, known as “cryptic clades”, were first described in 2012 [8][17] and contain more than 50 STs [8][17][18][19][20]; however, their evolution remains poorly understood [14][19]. In the study by Dingle et al. [8], the authors suggest that each lineage acquired its current PaLoc variant after the divergence and that the common ancestor of all modern C. difficile strains may have been non-toxigenic. In particular, clade 1, which includes the greatest diversity of toxigenic genotypes, may exemplify the most ancient acquisition; this fact would also explain the emergence of non-toxigenic strains within this clade, as sufficient time has elapsed for occasional PaLoc losses to occur. Moreover, the most recent PaLoc loss event occurred about 30 years ago within a genotype belonging to clade 1. In contrast, clades 4 and 5 exemplify the most recent PaLoc acquisition (about 500 years ago), because of their narrow genotypic diversity [8].

2. Molecular Typing Techniques for C. difficile Strains

Several molecular methods are available for typing C. difficile, and routine typing is not performed with the same techniques across countries. The most widely used C. difficile typing technique is PCR ribotyping. Specifically, this technique consists in the amplification of the intergenic spacer region (ISR) of the 16S-23S rRNA gene using primers targeting the 3′ end of the 16S rRNA gene and the 5′ end of the 23S rRNA gene [21]. Due to its high discrimination capacity, PCR ribotyping is currently recommended by the European Centre for Disease Prevention and Control (ECDC) for surveillance of the C. difficile spread [22]. However, this molecular technique has a delivery time of up to one week and often requires in-house protocol optimization, thus not being fully transferable between laboratories [23]. Another technique in use is pulsed-field gel electrophoresis (PFGE). This technique is based on DNA digestion, through enzymatic restriction, and separation of DNA fragments on gel. This method therefore provides for the clonal assignment of the bacterial strain based on PFGE banding patterns [24]. The criticality of this method can be identified in the tendency of C. difficile DNA to rapid degradation, resulting in non-typable isolates. To overcome this problem, a modified PGFE method has been designed, with different plate cultures compared to the standard protocol, but its application is rare in light of the other methods adopted for molecular typing [25]. Among these, restriction endonuclease analysis (REA) is a technique based on the use of restriction enzymes (e.g., HindIII) but, unlike PFGE, the digestion fragments obtained are separated by classical electrophoresis on agarose or polyacrylamide gels [21]. Other noteworthy typing methods are Multilocus VNTR Analysis (MLVA) and MLST. Specifically, the target of MLVA are variable number tandem repeats (VNTR), disseminated throughout the genome, while MLST uses PCR amplification of housekeeping genes to generate a complete allelic profile [26].
Since there are a multitude of different typing techniques, a web-accessible database [27] (always updated) was set up in 2011 by Griffiths et al. [28]: they typed a total of 49 isolates by MLST and classified them into 40 STs. Since MLST and PCR ribotyping are very similar in discriminatory abilities, they found a correspondence between RTs and STs: multiple RTs for the same ST and multiple STs for the same RT usually had very similar profiles. Some STs correspond to a single RT (e.g., ST54/RT012), while others to multiple (e.g., ST02/RT014, RT020, RT076 and RT220). However, it should be noted that RTs were not always predictive of STs [28].
In recent years, with the advancement of whole genome sequencing (WGS) techniques, the scientific community is moving towards these methods instead of standard PCR ribotyping and is trying to develop new methods for the characterization of C. difficile strains [23][29]. The two main approaches to discover genomic variations are single nucleotide variant (SNV) analysis and core genome or whole genome MLST (cgMLST, or wgMLST). The first technique is based on comparing the differences in single nucleotide polymorphisms (SNPs) while the second is based on the analysis of multiple genes across the whole genome. Cg- or wgMLST typing works according to the same principles as the classic MLST [29]. Three publicly available schemes for C. difficile are available for cg- and/or wgMLST typing, and analysis can be performed using commercial software (e.g., BioNumerics, Ridom) or freely accessible online resources (e.g., EnteroBase). Eyre et al. [30] were the first to use WGS of C. difficile genomes on benchtop sequencing platforms to investigate its transmission, demonstrating that the use of these technologies could improve infection control and patient outcomes in routine clinical practice. Since then, WGS typing has been widely adopted for CDI surveillance and has revealed some novel insights concerning the spread of C. difficile [29].

3. Worldwide Distribution of C. difficile Ribotypes

3.1. Europe

In Europe, several studies have highlighted a common genetic profile of C. difficile [31][32][33][34]. In particular, in 2021, a global study by Zhao et al. [32], based on data obtained from the MODIFY I (NCT01241552) and MODIFY II (NCT01513239) clinical studies using a WGS approach [35], found that in Europe there is a predominance of clade 1, with the exception of Poland where clade 2 predominates. Clade 2 was found to be one of the most virulent, along with clade 5. Interestingly, these two hypervirulent clades show the lowest recombination rates, while clade 3 and clade 4 show similar recombination rates [32]. Regarding the classification into RTs, clade 1 includes the non-toxigenic RT009, RT010, and RT039 [36], while the hypervirulent RT027 belongs to clade 2 [32]. The study conducted by Zhao et al. offers a broad view of the C. difficile genotype distribution at the global level but lacks comprehensive data. In fact, the study took into consideration only 1501 clinical isolates distributed globally. Another less recent but more accurate study analyzed 3499 isolates from 40 sites across Europe [31]. This describes the 2011–2016 epidemiological framework. In particular, there was a well-defined predominance of RT027 during the five years, followed by RT001 in 2011 and RT014 in 2012, 2013 and 2014 (both RTs are toxigenic). In 2015, a predominance of RT014 was observed, followed by RT106 and RT002 [31]. These results appear to be in contrast with the observation by Zhao et al. [32], but they are probably more accurate due to the greater number of isolates analyzed. It is also worth mentioning the two works by Abdrabou et al., who considered Germany in the periods 2014–2019 and 2019–2021 [33][34]. The authors noted that in the first period there was a prevalence of RT027, with a decrease in the following years [33][34]. As discussed by the European Medicines Agency (EMA), the Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA), such a decrease could be due to a potential reduction in fluoroquinolone administration [37][38][39]. Fluoroquinolones have in fact been associated with CDI outbreaks with RT027, which is highly resistant to them [40][41].
Similarly, comparing these results with other studies, a decrease in the prevalence of RT001 in Germany over time was observed [33][42][43]. It is also interesting to note that certain foods, such as potatoes, could be a vector for the introduction of C. difficile spores into the food chain or household environment. Indeed, potatoes have the highest rates of C. difficile contamination tested to date [44][45]. A recent study analyzed the positivity rate and distribution of RTs on potatoes in 12 European countries in the first half of 2018. Thirty-three of the 147 samples tested were positive for C. difficile, and the most common RTs were RT126, RT023, RT010, and RT014, in part overlapping what was discovered for human samples. The multiplicity of RTs was found to be substantial and the overlap between countries moderate.

3.2. America

In the USA, clinical specimens acquired from 2011 to 2015 showed a prevalence of RT027, belonging to the hypervirulent clade 2, as well as a prevalence of clade 1 [32]. Interestingly, the prevalence of clade 2 was higher on the East Coast and West Coast than inland. This observation was reversed for clade 1, which was more prevalent inland [32]. Another recent study [46] focusing on stool specimens recovered from 2011 to 2016 in the states of Illinois, Minnesota, New York, Massachusetts, California, and Virginia showed a marked decrease in the prevalence of RT027 over these six years in agreement with what was seen in Europe and Canada [43][46][47][48][49][50]. This decrease was also found in a 2020 study [51], covering the 2011–2018 period in Texas, where the most common RT was RT027, followed by RT014-020, RT106, and RT002. Curiously, the authors found a novel emerging RT, RT255 [51]. The complete RT255 genome has recently been made publicly available [52] and has occasionally been isolated [46]. However, its attributes and associated clinical outcomes are not yet well described [51].
Considering the transmission of C. difficile between humans and animals, an interesting study of samples collected from 13 Ohio swine farms (from farrowing rooms, nursery rooms and workers’ breakrooms) showed high contamination with toxigenic C. difficile [53]. The same C. difficile RTs recovered from most of the farm breakrooms were also recovered from at least one swine environment in those same farms. Furthermore, three RTs (i.e., RT078, RT005 and RT412) identified in the environment had previously been found in association with CDI in humans [54][55] and with animal-to-human transmission in Europe (i.e., Italy) [56]. Water and soil are also an important reservoir for this pathogen. At the Flagstaff site (Arizona), researchers found potential novel strains belongings to clades C-I, C-II and C-III and a hypothetical additional clade (C-V) [57].
In contrast to the literature describing the situation in North America, few recent articles are available on what concerns South America, mainly from Brazil. Regarding the latter, a study using MLST found that patient stool samples from different hospitals were positive for C. difficile distributed in 14 STs [58]. In particular, it was the first description of the STs 15 and 54 in the Brazilian country. ST15 has already been described in the UK [28], but as it is a non-toxigenic ST, there are not many data in the literature, while ST54 is already widespread in South America [58]. Unlike Europe and North America, the RT027 epidemic has never been reported in Brazil and the epidemiology of CDI is still underexplored. This is partly due to the lack of specialized technologies and facilities for the detection of obligate anaerobic bacteria, which is not a routine procedure in clinical laboratories [59]. However, numerous C. difficile RTs involved in CDI cases have been detected in Brazilian hospitals (e.g., RT014, RT043, RT046, RT106, RT132-135, RT142, and RT143) [59][60][61][62].

3.3. Asia and Middle East

While for Europe and North America there are numerous studies on the genetics and epidemiology of C. difficile strains, Asia appears to be split in half. For example, there is a lack of scientific reports on the prevalence of C. difficile in South Asian countries such as India, while these works appear to be abundant in East and Southeast Asian countries such as China and Japan. In India, a recent study using MLST on samples from a tertiary care center found that the most common STs were ST17, ST54, and ST63, with ST17 being the most prominent [63]. In Bangladesh, the first report on the prevalence of CDI in the hospital setting found that the most common RTs in stools (i.e., present in ≥10% of isolates) were RT017, RT053–163 (the same RTs found in environmental isolates), and a new RT (i.e., FP435) [64].
Furthermore, another study conducted in 2020 on the antimicrobial susceptibility of C. difficile in the 2014–2015 period in Asia-Pacific countries highlighted the prevalence of RT017 [65], confirming what was observed in a previous study [64]. Interestingly, the hypervirulent RT027 and RT078 have only rarely been isolated in the Asia-Pacific region [66][67][68][69]. In Japan, evidence suggests that the most common RT is RT018 [68][69][70][71]. In China, one of the dominant circulating RTs is RT017 [15][72][73]. However, another study published in 2021 on samples from different sources (e.g., soil, animals) found that the predominant RTs in China are RT001, RT046, and RT596 [74]. In 2021, the study by Zhao et al. found that the most common clade in the Asian country is clade 4 [32]. Furthermore, another report focusing on antibiotic resistance and molecular features of economic animals in China showed that RT126 is the most prevalent in Shandong province [75]. As for the Middle East region, RT001 is the most prevalent in Iran, followed by RT126, while RT258 is widespread in Qatar, RT139 in Kuwait and RT014 in Lebanon [76][77][78][79].

3.4. Oceania

Most of the data on the incidence of CDI come from Australia, the largest country in Oceania, particularly Western Australia. However, probably due to the variety of patient characteristics such as age, there is a discrepancy between the studies available to date.
For example, a study of C. difficile isolated from pediatric patients hospitalized in Perth, capital of Western Australia, in the period 2019–2020, reported a prevalence of RT002 (toxigenic) and RT009 (non-toxigenic) (on a total of 427 stool samples) [80]. On the other hand, a study conducted in the earlier period 2013–2018 in a geographically larger area covering 10 diagnostic laboratories from five states in Australia (Western Australia, New South Wales, Victoria, South Australia, and Queensland), reported 203 different RTs in predominantly elderly subjects, with RT014/020 being the most common, while RT027 and RT078 only rarely found [81]. Additionally, toxigenic RT014/020 was found to be more common among clinical cases in a tertiary hospital in Perth, while non-toxigenic RT010 was prevalent among floor samples and shoe soles of hospital staff, visitors and patients [82]. Outside of Australia, few research works are available. In particular, for New Zealand, a 2021 study reported that the two most common RTs were the same found in Australia (i.e., RT014, RT020) [83]. Interestingly, the dominance of RT014 has also been reported in Europe, particularly in 2015 [31]. The dominance of RT014 was also found in Auckland in 2014 [84]. In the study by Zhao et al., clade 1 was found to be the predominant one in Oceania [32].

3.5. Africa

In Africa, C. difficile is generally considered a minor pathogen, while the most common causative agents of diarrhea are Escherichia coli, Cryptosporidium, Shigella, and rotavirus [85]. No less important, there is a lack of recent literature on ribotyping and molecular characterization of C. difficile. For example, for Northern Africa, the latest PCR ribotyping report was released in 2018 in two Algerian hospitals, revealing the predominance of RT014, RT020 and non-toxigenic RT084, but only in 11 out of 159 stool samples collected between 2013 and 2015 [86]. In sub-Saharan Africa (i.e., Tanzania), a 2015 study identified RT038 among non-toxigenic strains, RT045 among toxigenic strains, and an unknown RT for two strains resulted positive for both tcdA and tcdB. Further analyses conducted on one of the two unknown strains highlighted a similarity with RT228 and RT043 [87]. Another study conducted in rural Ghana showed a high rate of non-toxigenic strains (e.g., RT084) isolated from patients with diarrhea and no hypervirulent strains [88]. A 2018 multi-centric cross-sectional study conducted between Germany, Ghana, Tanzania, and Indonesia showed that non-toxigenic strains were more abundant in Africa, with a prevalence of RT084 in the Ghanaian site and RT038 and RT045 in the Tanzanian site [89]. In light of this evidence, there appears to be a shortage of hypervirulent RTs in Africa (as opposed to Europe and the USA), while most of the CDIs found are attributable to non-toxigenic strains. Finally, it should be noted that in the Zimbabwe region, RT084 was the most common in human samples, while RT103, RT025, and RT070 were prevalent in chicken isolates, and RT025 and RT070 in soil samples [90]. Based on the study by Zhao et al., in South Africa, there is a prevalence of clade 1 [32].

References

  1. Braun, V.; Hundsberger, T.; Leukel, P.; Sauerborn, M.; von Eichel-Streiber, C. Definition of the Single Integration Site of the Pathogenicity Locus in Clostridium Difficile. Gene 1996, 181, 29–38.
  2. Martin-Verstraete, I.; Peltier, J.; Dupuy, B. The Regulatory Networks That Control Clostridium Difficile Toxin Synthesis. Toxins 2016, 8, 153.
  3. Stare, B.G.; Delmée, M.; Rupnik, M. Variant Forms of the Binary Toxin CDT Locus and TcdC Gene in Clostridium Difficile Strains. J. Med. Microbiol. 2007, 56, 329–335.
  4. Carter, G.P.; Lyras, D.; Allen, D.L.; Mackin, K.E.; Howarth, P.M.; O’Connor, J.R.; Rood, J.I. Binary Toxin Production in Clostridium Difficile Is Regulated by CdtR, a LytTR Family Response Regulator. J. Bacteriol. 2007, 189, 7290.
  5. Freeman, D.M. Invertible Carnot Groups. Anal. Geom. Metr. Spaces 2014, 2, 248–257.
  6. Maslanka, J.R.; Gu, C.H.; Zarin, I.; Denny, J.E.; Broadaway, S.; Fett, B.; Mattei, L.M.; Walk, S.T.; Abt, M.C. Detection and Elimination of a Novel Non-Toxigenic Clostridioides Difficile Strain from the Microbiota of a Mouse Colony. Gut Microbes 2020, 12, 1851999.
  7. Monot, M.; Eckert, C.; Lemire, A.; Hamiot, A.; Dubois, T.; Tessier, C.; Dumoulard, B.; Hamel, B.; Petit, A.; Lalande, V.; et al. Clostridium Difficile: New Insights into the Evolution of the Pathogenicity Locus. Sci. Rep. 2015, 5, 15023.
  8. Dingle, K.E.; Elliott, B.; Robinson, E.; Griffiths, D.; Eyre, D.W.; Stoesser, N.; Vaughan, A.; Golubchik, T.; Fawley, W.N.; Wilcox, M.H.; et al. Evolutionary History of the Clostridium Difficile Pathogenicity Locus. Genome Biol. Evol. 2014, 6, 36–52.
  9. Janezic, S.; Dingle, K.; Alvin, J.; Accetto, T.; Didelot, X.; Crook, D.W.; Borden Lacy, D.; Rupnik, M. Comparative Genomics of Clostridioides Difficile Toxinotypes Identifies Module-Based Toxin Gene Evolution. Microb. Genom. 2020, 6, 1–13.
  10. Mansfield, M.J.; Tremblay, B.J.M.; Zeng, J.; Wei, X.; Hodgins, H.; Worley, J.; Bry, L.; Dong, M.; Doxey, A.C. Phylogenomics of 8,839 Clostridioides Difficile Genomes Reveals Recombination-Driven Evolution and Diversification of Toxin A and B. PLoS Pathog. 2020, 16, e1009181.
  11. Steele, J.; Mukherjee, J.; Parry, N.; Tzipori, S. Antibody Against TcdB, but Not TcdA, Prevents Development of Gastrointestinal and Systemic Clostridium Difficile Disease. J. Infect. Dis. 2013, 207, 323–330.
  12. Gupta, S.B.; Mehta, V.; Dubberke, E.R.; Zhao, X.; Dorr, M.B.; Guris, D.; Molrine, D.; Leney, M.; Miller, M.; Dupin, M.; et al. Antibodies to Toxin B Are Protective Against Clostridium Difficile Infection Recurrence. Clin. Infect. Dis. 2016, 63, 730–734.
  13. Rounds, J.; Strain, J. Bezlotoxumab for Preventing Recurrent Clostridium Difficile Infections. J. South Dak. State Med. Assoc. 2017, 70, 422–423.
  14. Knight, D.R.; Imwattana, K.; Kullin, B.; Guerrero-Araya, E.; Paredes-Sabja, D.; Didelot, X.; Dingle, K.E.; Eyre, D.W.; Rodríguez, C.; Riley, T.V. Major Genetic Discontinuity and Novel Toxigenic Species in Clostridioides Difficile Taxonomy. Elife 2021, 10, e64325.
  15. Imwattana, K.; Knight, D.R.; Kullin, B.; Collins, D.A.; Putsathit, P.; Kiratisin, P.; Riley, T.V. Clostridium Difficile Ribotype 017—Characterization, Evolution and Epidemiology of the Dominant Strain in Asia. Emerg. Microbes Infect. 2019, 8, 796–807.
  16. Knight, D.R.; Kullin, B.; Androga, G.O.; Barbut, F.; Eckert, C.; Johnson, S.; Spigaglia, P.; Tateda, K.; Tsai, P.J.; Riley, T.V. Evolutionary and Genomic Insights into Clostridioides Difficile Sequence Type 11: A Diverse Zoonotic and Antimicrobial-Resistant Lineage of Global One Health Importance. mBio 2019, 10, e00446-19.
  17. Didelot, X.; Eyre, D.W.; Cule, M.; Ip, C.L.C.; Ansari, M.A.; Griffiths, D.; Vaughan, A.; O’Connor, L.; Golubchik, T.; Batty, E.M.; et al. Microevolutionary Analysis of Clostridium Difficile Genomes to Investigate Transmission. Genome Biol. 2012, 13, R118.
  18. Janezic, S.; Potocnik, M.; Zidaric, V.; Rupnik, M. Highly Divergent Clostridium Difficile Strains Isolated from the Environment. PLoS ONE 2016, 11, e0167101.
  19. Ramírez-Vargas, G.; López-Ureña, D.; Badilla, A.; Orozco-Aguilar, J.; Murillo, T.; Rojas, P.; Riedel, T.; Overmann, J.; González, G.; Chaves-Olarte, E.; et al. Novel Clade C-I Clostridium Difficile Strains Escape Diagnostic Tests, Differ in Pathogenicity Potential and Carry Toxins on Extrachromosomal Elements. Sci. Rep. 2018, 8, 13951.
  20. Ramirez-Vargas, G.; Rodriguez, C. Putative Conjugative Plasmids with TcdB and CdtAB Genes in Clostridioides Difficile. Emerg. Infect. Dis. 2020, 26, 2287.
  21. Collins, D.A.; Elliott, B.; Riley, T.V. Molecular Methods for Detecting and Typing of Clostridium Difficile. Pathology 2015, 47, 211–218.
  22. Krutova, M.; Kinross, P.; Barbut, F.; Hajdu, A.; Wilcox, M.H.; Kuijper, E.J.; Allerberger, F.; Delmée, M.; van Broeck, J.; Vatcheva-Dobrevska, R.; et al. How to: Surveillance of Clostridium Difficile Infections. Clin. Microbiol. Infect. 2018, 24, 469–475.
  23. Seth-Smith, H.M.B.; Biggel, M.; Roloff, T.; Hinic, V.; Bodmer, T.; Risch, M.; Casanova, C.; Widmer, A.; Sommerstein, R.; Marschall, J.; et al. Transition From PCR-Ribotyping to Whole Genome Sequencing Based Typing of Clostridioides Difficile. Front. Cell Infect. Microbiol. 2021, 11, 681518.
  24. Neoh, H.M.; Tan, X.E.; Sapri, H.F.; Tan, T.L. Pulsed-Field Gel Electrophoresis (PFGE): A Review of the “Gold Standard” for Bacteria Typing and Current Alternatives. Infect. Genet. Evol. 2019, 74, 103935.
  25. Alonso, R.; Martín, A.; Peláez, T.; Marín, M.; Rodríguez-Creixéms, M.; Bouza, E. An Improved Protocol for Pulsed-Field Gel Electrophoresis Typing of Clostridium Difficile. J. Med. Microbiol. 2005, 54, 155–157.
  26. Pérez-Losada, M.; Cabezas, P.; Castro-Nallar, E.; Crandall, K.A. Pathogen Typing in the Genomics Era: MLST and the Future of Molecular Epidemiology. Infect. Genet. Evol. 2013, 16, 38–53.
  27. PubMLST. Clostridioides Difficile. Available online: https://pubmlst.org/organisms/clostridioides-difficile (accessed on 23 September 2022).
  28. Griffiths, D.; Fawley, W.; Kachrimanidou, M.; Bowden, R.; Crook, D.W.; Fung, R.; Golubchik, T.; Harding, R.M.; Jeffery, K.J.M.; Jolley, K.A.; et al. Multilocus Sequence Typing of Clostridium Difficile. J. Clin. Microbiol. 2010, 48, 770–778.
  29. Janezic, S.; Rupnik, M. Development and Implementation of Whole Genome Sequencing-Based Typing Schemes for Clostridioides Difficile. Front. Public Health 2019, 7, 309.
  30. Eyre, D.W.; Golubchik, T.; Gordon, N.C.; Bowden, R.; Piazza, P.; Batty, E.M.; Ip, C.L.C.; Wilson, D.J.; Didelot, X.; O’Connor, L.; et al. A Pilot Study of Rapid Benchtop Sequencing of Staphylococcus Aureus and Clostridium Difficile for Outbreak Detection and Surveillance. BMJ Open 2012, 2, e001124.
  31. Freeman, J.; Vernon, J.; Pilling, S.; Morris, K.; Nicolson, S.; Shearman, S.; Clark, E.; Palacios-Fabrega, J.A.; Wilcox, M. Five-Year Pan-European, Longitudinal Surveillance of Clostridium Difficile Ribotype Prevalence and Antimicrobial Resistance: The Extended ClosER Study. Eur. J. Clin. Microbiol. Infect. Dis. 2020, 39, 169–177.
  32. Zhao, H.; Nickle, D.C.; Zeng, Z.; Law, P.Y.T.; Wilcox, M.H.; Chen, L.; Peng, Y.; Meng, J.; Deng, Z.; Albright, A.; et al. Global Landscape of Clostridioides Difficile Phylogeography, Antibiotic Susceptibility, and Toxin Polymorphisms by Post-Hoc Whole-Genome Sequencing from the MODIFY I/II Studies. Infect. Dis. Ther. 2021, 10, 853–870.
  33. Abdrabou, A.M.M.; Ul Habib Bajwa, Z.; Halfmann, A.; Mellmann, A.; Nimmesgern, A.; Margardt, L.; Bischoff, M.; von Müller, L.; Gärtner, B.; Berger, F.K. Molecular Epidemiology and Antimicrobial Resistance of Clostridioides Difficile in Germany, 2014–2019. Int. J. Med. Microbiol. 2021, 311, 151507.
  34. Abdrabou, A.M.M.; Bischoff, M.; Mellmann, A.; von Müller, L.; Margardt, L.; Gärtner, B.C.; Berger, F.K.; Haase, G.; Häfner, H.; Hoffmann, R.; et al. Implementation of a Clostridioides Difficile Sentinel Surveillance System in Germany: First Insights for 2019–2021. Anaerobe 2022, 77, 102548.
  35. Johnson, S.; Citron, D.M.; Gerding, D.N.; Wilcox, M.H.; Goldstein, E.J.C.; Sambol, S.P.; Best, E.L.; Eves, K.; Jensen, E.; Dorr, M.B. Efficacy of Bezlotoxumab in Trial Participants Infected With Clostridioides Difficile Strain BI Associated With Poor Outcomes. Clin. Infect. Dis. 2021, 73, e2616–e2624.
  36. Romano, V.; Pasquale, V.; Krovacek, K.; Mauri, F.; Demarta, A.; Dumontet, S. Toxigenic Clostridium Difficile PCR Ribotypes from Wastewater Treatment Plants in Southern Switzerland. Appl. Environ. Microbiol. 2012, 78, 6643.
  37. Skinner, A.M.; Petrella, L.; Siddiqui, F.; Sambol, S.P.; Gulvik, C.A.; Gerding, D.N.; Donskey, C.J.; Johnson, S. Unique Clindamycin-Resistant Clostridioides Difficile Strain Related to Fluoroquinolone-Resistant Epidemic BI/RT027 Strain. Emerg. Infect. Dis. 2020, 26, 247–254.
  38. FDA. FDA Updates Warnings for Fluoroquinolone Antibiotics. Available online: https://www.fda.gov/news-events/press-announcements/fda-updates-warnings-fluoroquinolone-antibiotics (accessed on 9 November 2022).
  39. European Medicines Agency. Fluoroquinolone and Quinolone Antibiotics: PRAC Recommends New Restrictions on Use Following Review of Disabling and Potentially Long-Lasting Side Effects. Available online: https://www.ema.europa.eu/en/news/fluoroquinolone-quinolone-antibiotics-prac-recommends-new-restrictions-use-following-review (accessed on 9 November 2022).
  40. Wieczorkiewicz, J.T.; Lopansri, B.K.; Cheknis, A.; Osmolski, J.R.; Hecht, D.W.; Gerding, D.N.; Johnson, S. Fluoroquinolone and Macrolide Exposure Predict Clostridium Difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. Difficile Strain BI/NAP1/027. Antimicrob. Agents Chemother. 2016, 60, 418–423.
  41. Tabak, Y.P.; Srinivasan, A.; Yu, K.C.; Kurtz, S.G.; Gupta, V.; Gelone, S.; Scoble, P.J.; Mcdonald, L.C. Hospital-Level High-Risk Antibiotic Use in Relation to Hospital-Associated Clostridioides Difficile Infections: Retrospective Analysis of 2016-2017 Data from US Hospitals HHS Public Access. Infect. Control Hosp. Epidemiol. 2019, 40, 1229–1235.
  42. Berger, F.K.; Rasheed, S.S.; Araj, G.F.; Mahfouz, R.; Rimmani, H.H.; Karaoui, W.R.; Sharara, A.I.; Dbaibo, G.; Becker, S.L.; von Müller, L.; et al. Molecular Characterization, Toxin Detection and Resistance Testing of Human Clinical Clostridium Difficile Isolates from Lebanon. Int. J. Med. Microbiol. 2018, 308, 358–363.
  43. Davies, K.A.; Ashwin, H.; Longshaw, C.M.; Burns, D.A.; Davis, G.L.; Wilcox, M.H. Diversity of Clostridium Difficile PCR Ribotypes in Europe: Results from the European, Multicentre, Prospective, Biannual, Point-Prevalence Study of Clostridium Difficile Infection in Hospitalised Patients with Diarrhoea (EUCLID), 2012 and 2013. Eurosurveillance 2016, 21, 30294.
  44. Tkalec, V.; Janezic, S.; Skok, B.; Simonic, T.; Mesaric, S.; Vrabic, T.; Rupnik, M. High Clostridium Difficile Contamination Rates of Domestic and Imported Potatoes Compared to Some Other Vegetables in Slovenia. Food Microbiol. 2019, 78, 194–200.
  45. Lim, S.C.; Foster, N.F.; Elliott, B.; Riley, T.V. High Prevalence of Clostridium Difficile on Retail Root Vegetables, Western Australia. J. Appl. Microbiol. 2018, 124, 585–590.
  46. Snydman, D.R.; McDermott, L.A.; Jenkins, S.G.; Goldstein, E.J.C.; Patel, R.; Forbes, B.A.; Johnson, S.; Gerding, D.N.; Thorpe, C.M.; Walk, S.T. Epidemiologic Trends in Clostridioides Difficile Isolate Ribotypes in United States from 2011 to 2016. Anaerobe 2020, 63, 102185.
  47. Freeman, J.; Vernon, J.; Pilling, S.; Morris, K.; Nicholson, S.; Shearman, S.; Longshaw, C.; Wilcox, M.H. The ClosER Study: Results from a Three-Year Pan-European Longitudinal Surveillance of Antibiotic Resistance among Prevalent Clostridium Difficile Ribotypes, 2011–2014. Clin. Microbiol. Infect. 2018, 24, 724–731.
  48. Cheknis, A.; Johnson, S.; Chesnel, L.; Petrella, L.; Sambol, S.; Dale, S.E.; Nary, J.; Sears, P.; Citron, D.M.; Goldstein, E.J.C.; et al. Molecular Epidemiology of Clostridioides (Clostridium) Difficile Strains Recovered from Clinical Trials in the US, Canada and Europe from 2006–2009 to 2012–2015. Anaerobe 2018, 53, 38–42.
  49. Eyre, D.W.; Davies, K.A.; Davis, G.; Fawley, W.N.; Dingle, K.E.; de Maio, N.; Karas, A.; Crook, D.W.; Peto, T.E.A.; Walker, A.S.; et al. Two Distinct Patterns of Clostridium Difficile Diversity Across Europe Indicating Contrasting Routes of Spread. Clin. Infect. Dis. 2018, 67, 1035–1044.
  50. Piepenbrock, E.; Stelzer, Y.; Berger, F.; Jazmati, N. Changes in Clostridium (Clostridioides) Difficile PCR-Ribotype Distribution and Antimicrobial Resistance in a German Tertiary Care Hospital Over the Last 10 Years. Curr. Microbiol. 2019, 76, 520–526.
  51. Gonzales-Luna, A.J.; Carlson, T.J.; Dotson, K.M.; Poblete, K.; Costa, G.; Miranda, J.; Lancaster, C.; Walk, S.T.; Tupy, S.; Begum, K.; et al. PCR Ribotypes of Clostridioides Difficile across Texas from 2011 to 2018 Including Emergence of Ribotype 255. Emerg. Microbes Infect. 2020, 9, 341–347.
  52. Spinler, J.K.; Gonzales-Luna, A.J.; Raza, S.; Runge, J.K.; Luna, R.A.; Savidge, T.C.; Garey, K.W. Complete Genome Sequence of Clostridioides Difficile Ribotype 255 Strain Mta-79, Assembled Using Oxford Nanopore and Illumina Sequencing. Microbiol. Resour. Announc. 2019, 8, e00935-19.
  53. O’shaughnessy, R.A.; Habing, G.G.; Gebreyes, W.A.; Bowman, A.S.; Weese, J.S.; Rousseau, J.; Stull, J.W. Clostridioides Difficile on Ohio Swine Farms (2015): A Comparison of Swine and Human Environments and Assessment of on-Farm Risk Factors. Zoonoses Public Health 2019, 66, 861–870.
  54. Fawley, W.N.; Davies, K.A.; Morris, T.; Parnell, P.; Howe, R.; Wilcox, M.H. Enhanced Surveillance of Clostridium Difficile Infection Occurring Outside Hospital, England, 2011 to 2013. Eurosurveillance 2016, 21, 30295.
  55. Cheng, A.C.; Collins, D.A.; Elliott, B.; Ferguson, J.K.; Paterson, D.L.; Thean, S.; Riley, T.V. Laboratory-Based Surveillance of Clostridium Difficile Circulating in Australia, September–November 2010. Pathology 2016, 48, 257–260.
  56. Tramuta, C.; Spigaglia, P.; Barbanti, F.; Bianchi, D.M.; Boteva, C.; di Blasio, A.; Zoppi, S.; Zaccaria, T.; Proroga, Y.T.R.; Chiavacci, L.; et al. Comparison of Clostridioides Difficile Strains from Animals and Humans: First Results after Introduction of C. Difficile Molecular Typing and Characterization at the Istituto Zooprofilattico Sperimentale of Piemonte, Liguria e Valle d’Aosta, Italy. Comp. Immunol. Microbiol. Infect. Dis. 2021, 75, 101623.
  57. Williamson, C.H.D.; Stone, N.E.; Nunnally, A.E.; Roe, C.C.; Vazquez, A.J.; Lucero, S.A.; Hornstra, H.; Wagner, D.M.; Keim, P.; Rupnik, M.; et al. Identification of Novel, Cryptic Clostridioides Species Isolates from Environmental Samples Collected from Diverse Geographical Locations. Microb. Genom. 2022, 8, 000742.
  58. Saldanha, G.Z.; Pires, R.N.; Rauber, A.P.; de Lima-Morales, D.; Falci, D.R.; Caierão, J.; Pasqualotto, A.C.; Martins, A.F. Genetic Relatedness, Virulence Factors and Antimicrobial Resistance of C. Difficile Strains from Hospitalized Patients in a Multicentric Study in Brazil. J. Glob. Antimicrob Resist. 2020, 22, 117–121.
  59. Balassiano, I.T.; Miranda, K.R.; Boente, R.F.; Pauer, H.; Oliveira, I.C.M.; Santos-Filho, J.; Amorim, E.L.T.; Caniné, G.A.; Souza, C.F.; Gomes, M.Z.R.; et al. Characterization of Clostridium Difficile Strains Isolated from Immunosuppressed Inpatients in a Hospital in Rio de Janeiro, Brazil. Anaerobe 2009, 15, 61–64.
  60. Secco, D.A.; Balassiano, I.T.; Boente, R.F.; Miranda, K.R.; Brazier, J.; Hall, V.; dos Santos-Filho, J.; Lobo, L.A.; Nouér, S.A.; Domingues, R.M.C.P. Clostridium Difficile Infection among Immunocompromised Patients in Rio de Janeiro, Brazil and Detection of Moxifloxacin Resistance in a Ribotype 014 Strain. Anaerobe 2014, 28, 85–89.
  61. Alcides, A.P.P.; Brazier, J.S.; Pinto, L.J.F.; Balassiano, I.T.; Boente, R.F.; Paula, G.R.; Ferreira, E.O.; Avelar, K.E.S.; Miranda, K.R.; Ferreira, M.C.S.; et al. New PCR Ribotypes of Clostridium Difficile Detected in Children in Brazil. Antonie Van Leeuwenhoek 2007, 92, 53–59.
  62. Carneiro, L.G.; Pinto, T.C.A.; Moura, H.; Barr, J.; Domingues, R.M.C.P.; Ferreira, E.d.O. MALDI-TOF MS: An Alternative Approach for Ribotyping Clostridioides Difficile Isolates in Brazil. Anaerobe 2021, 69, 102351.
  63. Chaudhry, R.; Sharma, N.; Bahadur, T.; Khullar, S.; Agarwal, S.K.; Gahlowt, A.; Gupta, N.; Kumar, L.; Kabra, S.K.; Dey, A.B. Molecular Characterization of Clostridioides Difficile by Multi-Locus Sequence Typing (MLST): A Study from Tertiary Care Center in India. Anaerobe 2022, 75, 102545.
  64. Collins, D.A.; Sohn, K.M.; Wu, Y.; Ouchi, K.; Ishii, Y.; Elliott, B.; Riley, T.V.; Tateda, K. Clostridioides Difficile Infection in the Asia-Pacific Region. Emerg. Microbes Infect. 2020, 9, 42–52.
  65. Lew, T.; Putsathit, P.; Sohn, K.M.; Wu, Y.; Ouchi, K.; Ishii, Y.; Tated, K.; Riley, T.V.; Collins, D.A. Antimicrobial Susceptibilities of Clostridium Difficile Isolates from 12 Asia-Pacific Countries in 2014 and 2015. Antimicrob. Agents Chemother. 2020, 64, e00296-20.
  66. Collins, D.A.; Hawkey, P.M.; Riley, T.V. Epidemiology of Clostridium Difficile Infection in Asia. Antimicrob. Resist. Infect. Control 2013, 2, 21.
  67. Collins, D.A.; Riley, T.V. Clostridium Difficile Guidelines. Clin. Infect. Dis. 2018, 67, 1639.
  68. Kato, H.; Kato, H.; Ito, Y.; Akahane, T.; Izumida, S.; Yokoyama, T.; Kaji, C.; Arakawa, Y. Typing of Clostridium Difficile Isolates Endemic in Japan by Sequencing of SlpA and Its Application to Direct Typing. J. Med. Microbiol. 2010, 59, 556–562.
  69. Senoh, M.; Kato, H.; Fukuda, T.; Niikawa, A.; Hori, Y.; Hagiya, H.; Ito, Y.; Miki, H.; Abe, Y.; Furuta, K.; et al. Predominance of PCR-Ribotypes, 018 (Smz) and 369 (Trf) of Clostridium Difficile in Japan: A Potential Relationship with Other Global Circulating Strains? J. Med. Microbiol. 2015, 64, 1226–1236.
  70. Kuwata, Y.; Tanimoto, S.; Sawabe, E.; Shima, M.; Takahashi, Y.; Ushizawa, H.; Fujie, T.; Koike, R.; Tojo, N.; Kubota, T.; et al. Molecular Epidemiology and Antimicrobial Susceptibility of Clostridium Difficile Isolated from a University Teaching Hospital in Japan. Eur. J. Clin. Microbiol. Infect. Dis. 2015, 34, 763–772.
  71. Aoki, K.; Takeda, S.; Miki, T.; Ishii, Y.; Tateda, K. Antimicrobial Susceptibility and Molecular Characterization Using Whole-Genome Sequencing of Clostridioides Difficile Collected in 82 Hospitals in Japan between 2014 and 2016. Antimicrob. Agents Chemother. 2019, 63, e01259-19.
  72. Jin, D.; Luo, Y.; Huang, C.; Cai, J.; Ye, J.; Zheng, Y.; Wang, L.; Zhao, P.; Liu, A.; Fang, W.; et al. Molecular Epidemiology of Clostridium Difficile Infection in Hospitalized Patients in Eastern China. J. Clin. Microbiol. 2017, 55, 801–810.
  73. Tang, C.; Cui, L.; Xu, Y.; Xie, L.; Sun, P.; Liu, C.; Xia, W.; Liu, G. The Incidence and Drug Resistance of Clostridium Difficile Infection in Mainland China: A Systematic Review and Meta-Analysis. Sci. Rep. 2016, 6, 37865.
  74. Zhou, Y.; Zhou, W.; Xiao, T.; Chen, Y.; Lv, T.; Wang, Y.; Zhang, S.; Cai, H.; Chi, X.; Kong, X.; et al. Comparative Genomic and Transmission Analysis of Clostridioides Difficile between Environmental, Animal, and Clinical Sources in China. Emerg. Microbes Infect. 2021, 10, 2244–2255.
  75. Zhang, W.Z.; Li, W.G.; Liu, Y.Q.; Gu, W.P.; Zhang, Q.; Li, H.; Liu, Z.J.; Zhang, X.; Wu, Y.; Lu, J.X. The Molecular Characters and Antibiotic Resistance of Clostridioides Difficile from Economic Animals in China. BMC Microbiol. 2020, 20, 70.
  76. Baghani, A.; Mesdaghinia, A.; Kuijper, E.J.; Aliramezani, A.; Talebi, M.; Douraghi, M. High Prevalence of Clostridiodes Diffiicle PCR Ribotypes 001 and 126 in Iran. Sci. Rep. 2020, 10, 4658.
  77. Sharara, A.; Karaoui, W.R.; Shayto, R.H.; Rimmani, H.; Chalhoub, J.M.; Zahreddine, N.; el Sabbagh, R.; Kanj, S.S.; Mahfouz, R.; Araj, G.; et al. Hypervirulent Clostridium Difficile Strains Are Rarely Associated With Nosocomial CDI in Adults in Lebanon: Results From a Prospective Study on the Incidence, Risk Factors for Relapse, and Outcome of Nosocomial CDI. Am. J. Gastroenterol. 2017, 112, S51.
  78. Jamal, W.; Pauline, E.; Rotimi, V. A Prospective Study of Community-Associated Clostridium Difficile Infection in Kuwait: Epidemiology and Ribotypes. Anaerobe 2015, 35, 28–32.
  79. Al-Thani, A.A.; Hamdi, W.S.; Al-Ansari, N.A.; Doiphode, S.H. Polymerase Chain Reaction Ribotyping of Clostridium Difficile Isolates in Qatar: A Hospital-Based Study. BMC Infect. Dis. 2014, 14, 502.
  80. Perumalsamy, S.; Lim, S.C.; Riley, T.V. Clostridioides (Clostridium) Difficile Isolated from Paediatric Patients in Western Australia 2019–2020. Pathology 2022, 54, 460–465.
  81. Hong, S.; Putsathit, P.; George, N.; Hemphill, C.; Huntington, P.G.; Korman, T.M.; Kotsanas, D.; Lahra, M.; McDougall, R.; Moore, C.V.; et al. Laboratory-Based Surveillance of Clostridium Difficile Infection in Australian Health Care and Community Settings, 2013 to 2018. J. Clin. Microbiol. 2020, 58, e01552-20.
  82. Lim, S.C.; Collins, D.A.; Imwattana, K.; Knight, D.R.; Perumalsamy, S.; Hain-Saunders, N.M.R.; Putsathit, P.; Speers, D.; Riley, T.V. Whole-Genome Sequencing Links Clostridium (Clostridioides) Difficile in a Single Hospital to Diverse Environmental Sources in the Community. J. Appl. Microbiol. 2021, 133, 1156–1168.
  83. Johnston, M.; Irwin, J.; Roberts, S.; Leung, A.; Andersson, H.S.; Orme, G.; Deroles-Main, J.; Bakker, S. Clostridioides Difficile Infection in a Rural New Zealand Secondary Care Centre: An Incidence Case–Control Study. Intern. Med. J. 2021, 52, 1009–1015.
  84. Sathyendran, V.; Mcauliffe, G.N.; Swager, T.; Freeman, J.T.; Taylor, S.L.; Roberts, S.A. Clostridium Difficile as a Cause of Healthcare-Associated Diarrhoea among Children in Auckland, New Zealand: Clinical and Molecular Epidemiology. Eur. J. Clin. Microbiol. Infect. Dis. 2014, 33, 1741–1747.
  85. Kotloff, K.L. The Burden and Etiology of Diarrheal Illness in Developing Countries. Pediatr. Clin. N. Am. 2017, 64, 799–814.
  86. Djebbar, A.; Sebaihia, M.; Kuijper, E.; Harmanus, C.; Sanders, I.; Benbraham, N.; Hacène, H. First Molecular Characterisation and PCR Ribotyping of Clostridium Difficile Strains Isolated in Two Algerian Hospitals. J. Infect. Dev. Ctries. 2018, 12, 15–21.
  87. Seugendo, M.; Mshana, S.E.; Hokororo, A.; Okamo, B.; Mirambo, M.M.; von Müller, L.; Gunka, K.; Zimmermann, O.; Groß, U. Clostridium Difficile Infections among Adults and Children in Mwanza/Tanzania: Is It an Underappreciated Pathogen among Immunocompromised Patients in Sub-Saharan Africa? New Microbes New Infect. 2015, 8, 99–102.
  88. Janssen, I.; Cooper, P.; Gunka, K.; Rupnik, M.; Wetzel, D.; Zimmermann, O.; Groß, U. High Prevalence of Nontoxigenic Clostridium Difficile Isolated from Hospitalized and Non-Hospitalized Individuals in Rural Ghana. Int. J. Med. Microbiol. 2016, 306, 652–656.
  89. Seugendo, M.; Janssen, I.; Lang, V.; Hasibuan, I.; Bohne, W.; Cooper, P.; Daniel, R.; Gunka, K.; Kusumawati, R.L.; Mshana, S.E.; et al. Prevalence and Strain Characterization of Clostridioides (Clostridium) Difficile in Representative Regions of Germany, Ghana, Tanzania and Indonesia—A Comparative Multi-Center Cross-Sectional Study. Front. Microbiol. 2018, 9, 1843.
  90. Berger, F.K.; Mellmann, A.; Bischoff, M.; von Müller, L.; Becker, S.L.; Simango, C.; Gärtner, B. Molecular Epidemiology and Antimicrobial Resistance of Clostridioides Difficile Detected in Chicken, Soil and Human Samples from Zimbabwe. Int. J. Infect. Dis. 2020, 96, 82–87.
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