Biogeographic distribution and molecular epidemiology of Clostridioides (Clostridium) difficile in Western Australian soils.

Clostridioides (Clostridium) difficile is a leading cause of infectious diarrhea in humans and production animals and can be found in a variety of environmental sources. The prevalence and diversity of multi-locus sequence type clade 5 strains of C. difficile in Australian production animals suggest Australia might be the ancestral home of this lineage of One Health importance. To better understand the role of the environment in the colonization of humans and animals in Australia, it is important to investigate these endemic sources. This study describes the prevalence, molecular epidemiology, and biogeographic distribution of C. difficile in soils of Western Australia. A total of 321 soil samples from remote geographical locations across the eight health regions of Western Australia were screened for C. difficile and isolates characterized by PCR ribotyping and toxin gene profiling. C. difficile was isolated from 31.15% of samples, with the highest prevalence in the Perth Metropolitan Health Region (49.25%, n = 33/67). Overall, 52 different strains [PCR ribotypes (RTs)] were identified, with 14 being novel, and 38% (38/100) of isolates being toxigenic, the most common of which was RT014/020. Five unique novel isolates showed characteristics similar to C. difficile clade 5. This is the first study of C. difficile isolated from soils in Australia. The high prevalence and heterogeneity of C. difficile strains recovered suggest that soils play a role in the survival and environmental dissemination of this organism, and potentially its transmission among native wildlife and production animals, and in community and hospital settings.IMPORTANCEClostridium difficile is a pathogen of One Health importance. To better understand the role of the environment in human and animal colonization/infection, it is critical that autochthonous reservoirs/sources of C. difficile be investigated. This is the first study of C. difficile isolated from soils of Western Australia (WA). Here, the ecology of C. difficile in WA is described by examining the geographic distribution, molecular epidemiology, and diversity of C. difficile isolated from soils across WA.

Genomic epidemiology and transmission dynamics of recurrent Clostridioides difficile infection in Western Australia.

Recurrent cases of Clostridioides difficile infection (rCDI) remain one of the most common and serious challenges faced in the management of CDI. The accurate distinction between a relapse (caused by infection with the same strain) and reinfection (caused by a new strain) has implications for infection control and prevention, and patient therapy. Here, we used whole-genome sequencing to investigate the epidemiology of 94 C. difficile isolates from 38 patients with rCDI in Western Australia. The C. difficile strain population comprised 13 sequence types (STs) led by ST2 (PCR ribotype (RT) 014, 36.2%), ST8 (RT002, 19.1%) and ST34 (RT056, 11.7%). Among 38 patients, core genome SNP (cgSNP) typing found 27 strains (71%) from initial and recurring cases differed by ≤ 2 cgSNPs, suggesting a likely relapse of infection with the initial strain, while eight strains differed by ≥ 3 cgSNPs, suggesting reinfection. Almost half of patients with CDI relapse confirmed by WGS suffered episodes that occurred outside the widely used 8-week cut-off for defining rCDI. Several putative strain transmission events between epidemiologically unrelated patients were identified. Isolates of STs 2 and 34 from rCDI cases and environmental sources shared a recent evolutionary history, suggesting a possible common community reservoir. For some rCDI episodes caused by STs 2 and 231, within-host strain diversity was observed, characterised by loss/gain of moxifloxacin resistance. Genomics improves discrimination of relapse from reinfection and identifies putative strain transmission events among patients with rCDI. Current definitions of relapse and reinfection based on the timing of recurrence need to be reconsidered.

Environmental contamination with Clostridioides (Clostridium) difficile in Vietnam.

AIMS: To investigate the prevalence, molecular type, and antimicrobial susceptibility of Clostridioides difficile in the environment in Vietnam, where little is known about C. difficile. METHODS AND RESULTS: Samples of pig faeces, soils from pig farms, potatoes, and the hospital environment were cultured for C. difficile. Isolates were identified and typed by polymerase chain reaction (PCR) ribotyping. The overall prevalence of C. difficile contamination was 24.5% (68/278). Clostridioides difficile was detected mainly in soils from pig farms and hospital soils, with 70%-100% prevalence. Clostridioides difficile was isolated from 3.4% of pig faecal samples and 5% of potato surfaces. The four most prevalent ribotypes (RTs) were RTs 001, 009, 038, and QX574. All isolates were susceptible to metronidazole, fidaxomicin, vancomycin, and amoxicillin/clavulanate, while resistance to erythromycin, tetracycline, and moxifloxacin was common in toxigenic strains. Clostridioides difficile RTs 001A+B+CDT- and 038A-B-CDT- were predominantly multidrug resistant. CONCLUSIONS: Environmental sources of C. difficile are important to consider in the epidemiology of C. difficile infection in Vietnam, however, contaminated soils are likely to be the most important source of C. difficile. This poses additional challenges to controlling infections in healthcare settings.

Clostridioides (Clostridium) difficile in adults with diarrhoea in Vietnam.

BACKGROUND: Clostridioides (Clostridium) difficile causes antimicrobial-associated diarrhoea, however, presentations may range from asymptomatic carriage to severe diarrhoea, life-threatening toxic megacolon and even death. Reports on C. difficile infection (CDI) in Vietnam remain limited. The objectives of this study were to evaluate the epidemiology, molecular characteristics, and antimicrobial susceptibility of C. difficile isolated from adults with diarrhoea in Vietnam. METHODS: Diarrhoeal stool samples from adult patients aged ≥17 years old were collected at Thai Binh General Hospital in northern Vietnam between March 1, 2021 and February 28, 2022. All samples were transported to The University of Western Australia, Perth, Western Australia for C. difficile culture, toxin gene profiling, PCR ribotyping and antimicrobial susceptibility testing. RESULTS: A total of 205 stool samples were collected from patients aged from 17 to 101 years old. The overall prevalence of C. difficile was 15.1% (31/205) with the recovery of toxigenic and non-toxigenic isolates 9.8% (20/205) and 6.3% (13/205), respectively. Thus 33 isolates were recovered comprising 18 known ribotypes (RTs) and one novel RT (two samples contained two different RTs in each sample). The most prevalent strains were RT 012 (five strains) and RTs 014/020, 017 and QX 070 three strains each. All C. difficile were susceptible to amoxicillin/clavulanate, fidaxomicin, metronidazole, moxifloxacin and vancomycin, while resistance to varying degrees was seen to clindamycin, erythromycin, tetracycline and rifaximin, 78.8% (26/33), 51.5% (17/33), 27.3% (9/33) and 6.1% (2/33), respectively. The prevalence of multidrug resistance was 27.3% (9/33) and multidrug resistance was most common in toxigenic RT 012 and non-toxigenic RT 038 strains. CONCLUSION: The prevalence of C. difficile in adults with diarrhoea and multidrug resistance in C. difficile isolates was relatively high. A clinical assessment to differentiate between CDI/disease and colonisation is required.

Clostridioides difficile infection and One Health: an equine perspective.

Clostridioides (Clostridium) difficile presents a significant health risk to humans and animals. The complexity of the bacterial-host interaction affecting pathogenesis and disease development creates an ongoing challenge for epidemiological studies, control strategies and prevention planning. The recent emergence of human disease caused by strains of C. difficile found in animals adds to mounting evidence that C. difficile infection (CDI) may be a zoonosis. In equine populations, C. difficile is a known cause of diarrhoea and gastrointestinal inflammation, with considerable mortality and morbidity. This has a significant impact on both the well-being of the animal and, in the case of performance and production animals, it may have an adverse economic impact on relevant industries. While C. difficile is regularly isolated from horses, many questions remain regarding the impact of asymptomatic carriage as well as optimization of diagnosis, testing and treatment. This review provides an overview of our understanding of equine CDI while also identifying knowledge gaps and the need for a holistic One Health approach to a complicated issue.

Genetically related Clostridium difficile from water sources and human CDI cases revealed by whole-genome sequencing.

Clostridium difficile isolates from the environment are closely related to those from humans, indicating a possible environmental transmission route for C. difficile infection (CDI). In this study, C. difficile was isolated from 47.3% (53/112) of lake/pond, 23.0% (14/61) of river, 20.0% (3/15) of estuary and 0.0% (0/89) of seawater samples. The most common toxigenic strain isolated was C. difficile PCR ribotype (RT) 014/020 (10.5%, 8/76). All water isolates were susceptible to fidaxomicin, metronidazole, rifaximin, amoxicillin/clavulanic acid, moxifloxacin and tetracycline. Resistance to vancomycin, clindamycin, erythromycin and meropenem was detected in 5.3% (4/76), 26.3% (20/76), 1.3% (1/76) and 6.6% (5/76) of isolates, respectively. High-resolution core-genome analysis was performed on RT 014/020 isolates of water origin and 26 clinical RT 014/020 isolates from the same year and geographical location. Notably, both human and water strains were intermixed across three sequence types (STs), 2, 13 and 49. Six closely related groups with ≤10 core-genome single nucleotide polymorphisms were identified, five of which comprised human and water strains. Overall, 19.2% (5/26) of human strains shared a recent genomic relationship with one or more water strains. This study supports the growing hypothesis that environmental contamination by C. difficile plays a role in CDI transmission.

Esculin hydrolysis negative and TcdA-only producing strains of Clostridium (Clostridioides) difficile from the environment in Western Australia.

BACKGROUND AND AIMS: Clostridium (Clostridiodes) difficile clade 3 ribotype (RT) 023 strains that fail to produce black colonies on bioMérieux ChromID agar have been reported, as well as variant strains of C. difficile that produce only toxin A. We have recently isolated strains of C. difficile from the environment in Western Australia (WA) with similar characteristics. The objective of this study was to characterize these strains. It was hypothesized that a putative ß-glucosidase gene was lacking in these strains of C. difficile, including RT 023, leading to white colonies. METHODS AND RESULTS: A total of 17 environmental isolates of C. difficile from garden soil and compost, and gardening shoe soles in Perth, WA, failed to produce black colonies on ChromID agar. MALDI-TOF MS analysis confirmed these strains as C. difficile. Four strains contained only a tcdA gene (A+ B- CDT- ) by PCR and were a novel RT (QX 597). All isolates were susceptible to all antimicrobials tested except one with low-level resistance to clindamycin (MIC = 8 mg/L). The four tcdA-positive strains were motile. All isolates contained neither bgl locus but only bgl K or a putative ß-glucosidase gene by PCR. Whole-genome sequencing showed the 17 strains belonged to novel multi-locus sequence types 632, 848, 849, 850, 851, 852 and 853, part of the evolutionarily divergent clade C-III. Four isolates carried a full-length tcdA but not tcdB nor binary toxin genes. CONCLUSIONS: ChromID C. difficile agar is used for the specific detection of C. difficile in the samples. To date, all strains except RT 023 strains from clinical samples hydrolyse esculin. This is the first report to provide insights into the identification of esculin hydrolysis negative and TcdA-only producing (A+ B- CDT- ) strains of C. difficile from environmental samples. SIGNIFICANCE AND IMPACT OF THE STUDY: White colonies of C. difficile from environmental samples could be overlooked when using ChromID C. difficile agar, leading to false-negative results, however, whether these strains are truly pathogenic remains to be proven.

Whole-genome sequencing links Clostridium (Clostridioides) difficile in a single hospital to diverse environmental sources in the community.

AIMS: To investigate if Clostridium (Clostridioides) difficile infection (CDI), traditionally thought of as hospital-acquired, can be genomically linked to hospital or community environmental sources, and to define possible importation routes from the community to the hospital. METHODS AND RESULTS: In 2019, C. difficile was isolated from 89/300 (29.7%) floor and 96/300 (32.0%) shoe sole samples at a tertiary hospital in Western Australia. Non-toxigenic C. difficile ribotype (RT) 010 predominated among floor (96.6%) and shoe sole (73.2%) isolates, while toxigenic RT 014/020 was most prevalent among contemporaneous clinical cases (33.0%) at the hospital. Whole-genome sequencing and high-resolution core genome single nucleotide polymorphism (cgSNP) analysis on C. difficile strains from hospital and community sources showed no clinical C. difficile RT 014/020 strains were genetically related, and evidence of frequent long-distance, multi-directional spread between humans, animals and the environment. In addition, cgSNP analysis of environmental RT 010 strains suggested transportation of C. difficile via shoe soles. CONCLUSIONS: While C. difficile RT 014/020 appears to spread via routes outside the healthcare system, RT 010 displayed a pattern of possible importation from the community into the hospital. SIGNIFICANCE AND IMPACT OF STUDY: These findings suggest developing community-based infection prevention and control strategies could significantly lower rates of CDI in the hospital setting.

Ridinilazole: a novel, narrow-spectrum antimicrobial agent targeting Clostridium (Clostridioides) difficile.

Clostridium (Clostridioides) difficile infection (CDI) remains an urgent threat to patients in health systems worldwide. Recurrent CDI occurs in up to 30% of cases due to sustained dysbiosis of the gut microbiota which normally protects against CDI. Associated costs of initial and recurrent episodes of CDI impose heavy financial burdens on health systems. Vancomycin and metronidazole have been the mainstay of therapy for CDI for many years; however, these agents continue to cause significant disruption to the gut microbiota and thus carry a high risk of recurrence for CDI patients. Treatment regimens are now turning towards novel narrow spectrum antimicrobial agents which target C. difficile while conserving the commensal gut microbiota, thus significantly reducing risk of recurrence. One such agent, fidaxomicin, has been in therapeutic use for several years and is now recommended as a first-line treatment for CDI, as it is superior to vancomycin in reducing risk of recurrence. Another narrow spectrum agent, ridnilazole, was recently developed and is undergoing evaluation of its potential clinical utility. This review aimed to summarize experimental reports of ridinilazole and assess its potential as a first-line agent for treatment of CDI. Reported results from in vitro assessments, and from hamster models of CDI, show potent activity against C. difficile, non-inferiority to vancomycin for clinical cure and non-susceptibility among most gut commensal bacteria. Phase I and II clinical trials have been completed with ridinilazole showing high tolerability and efficacy in treatment of CDI, and superiority over vancomycin in reducing recurrence of CDI within 30 days of treatment completion. Phase III trials are currently underway, the results of which may prove its potential to reduce recurrent CDI and lessen the heavy health and financial burden C. difficile imposes on patients and healthcare systems.

Antimicrobial-resistant Bacteroides fragilis in Thailand and their inhibitory effect in vitro on the growth of Clostridioides difficile.

OBJECTIVES: The aim of this study was to investigate antimicrobial-resistant Bacteroides fragilis in Thailand and possible effects of such strains on human health and disease. METHODS: Phenotypic antimicrobial susceptibility testing was performed on 17 clinical B. fragilis isolates. The genome of one isolate was sequenced and analysed to explore its resistance genotype. An in vitro growth assay was conducted to evaluate the inhibitory effect of B. fragilis on Clostridioides difficile. RESULTS: There was a high prevalence of clindamycin (71%), meropenem (47%) and moxifloxacin (29%) resistance. Most strains remained susceptible to metronidazole, but one had high-level metronidazole resistance conferred by a nimD-containing plasmid. B. fragilis displayed an in vitro inhibitory effect on the growth of C. difficile and a drug-resistant strain retained this inhibition in the presence of clindamycin. CONCLUSIONS: Antimicrobial resistance was seen in Thai B. fragils isolates, which may help protect the host against C. difficile infection.

Linkage study of surveillance and hospital admission data to investigate Clostridium difficile infection in hospital patients in Perth, Western Australia.

OBJECTIVES: Increasing incidence rates of Clostridium difficile infection (CDI) and outbreaks of emerging strains have highlighted the need for continuous monitoring and surveillance of CDI in Australia. Active surveillance captures all hospital-identified CDI cases in Western Australia (WA), where all C. difficile isolates recovered are routinely PCR ribotyped. The aim of this study was to determine incidence rates and descriptive and molecular epidemiology of CDI among patients in Perth, WA using linkage of surveillance and hospital administrative records. METHODS: All CDI cases (confirmed by tcdB PCR) from July 2012 to June 2014 captured in the Hospital Infection Surveillance WA dataset for three hospitals were linked with hospital admission records from the Patient Administration System and ribotyping data to calculate incidence rates of CDI and the distribution of various ribotypes (RTs). RESULTS: There were 381 individual cases of CDI identified among 354 hospital patients (including outpatients and ED) who experienced ≥1 CDI episode during the study period. CDI was hospital-associated in 62.7% of cases and community-associated (CA)-CDI in 31.2%. The overall incidence rate was 4.40/10,000 patient days (PD, 95% CI 3.98-4.86), females across all age groups experienced higher incidence (risk ratio 1.29, p < 0.05). The risk ratio for CA-CDI was highest (7.76, p < 0.01) for females vs males aged 15-29 years. Overall, 10.8% of cases were admitted to ICU, 15.2% had a recurrent infection and the mortality rate was 7.2%. C. difficile RT 014/020 predominated (34.9%) among 339 isolates of 71 different RTs. CONCLUSIONS: The incidence of CDI in WA is high and RT 014/020 continues to be the dominant molecular type in an otherwise diverse array of strains. High strain diversity suggests CDI cases arise from exposure to many different reservoirs.

Clostridioides difficile infection in Africa: A narrative review.

Clostridioides (Clostridium) difficile infection (CDI) places a burden on healthcare facilities worldwide. Most research studies have been concentrated in high-income countries in North America, Europe, Asia and Australia, where C. difficile is the leading cause of diarrhoea associated with antimicrobial use. This narrative review summarises African CDI studies, focussing on reports published in the last 20 years. Although relatively sparse, the data suggest that CDI is an important cause of diarrhoea on the continent. African CDI patient populations are often younger than in European and North American settings, probably due to the high prevalence of co-morbid conditions such as tuberculosis, particularly in sub-Saharan Africa. Strain typing data are rare and where reported generally limited to single sites and institutions. Despite challenges, including a lack of facilities and awareness, there is a need for further investigation to more accurately determine the true burden of disease caused by C. difficile in Africa.

Clostridioides (Clostridium) difficile in children with diarrhoea in Vietnam.

BACKGROUND: Clostridioides (Clostridium) difficile commonly causes hospital-acquired infection which can range from mild diarrhoea to life-threatening toxic megacolon and even death. Reports on C. difficile infection (CDI) in Vietnam are limited, so this study was designed to evaluate the prevalence, molecular epidemiology and antimicrobial susceptibility of C. difficile isolated from children with diarrhoea in Vietnam. Infants are often colonised with C. difficile and it was hypothesised that those colonising strains would represent strains of C. difficile circulating in the hospital/region at the time, however, this was not an attempt to determine if C. difficile was the cause of the diarrhoea. METHODS: Diarrhoeal stool samples collected at two children's hospitals in northern Vietnam from October 1, 2020 to February 28, 2021 were transported to Perth, Western Australia, for culture of C. difficile and further investigations on isolates; PCR ribotyping, toxin gene profiling and antimicrobial susceptibility testing. RESULTS: From these hospitals, 370 diarrhoeal stool samples were collected, most from children aged 1-15 months (71.9%; 266/370). The overall prevalence of C. difficile in stool samples from children aged ≤16 years was 37.8% (140/370) and the highest prevalence was in the 2-12 months age group (52.9%; 74/140). In total, 151 isolates of C. difficile were recovered; the proportion of toxigenic isolates was 16.6% (25/151). Of the 25 toxigenic C. difficile isolates, the toxin gene profiles A+B+CDT- and A-B+CDT- comprised 72% and 28%, respectively. The four most prevalent C. difficile ribotypes (RTs) were QX 011 (25/151), RT 010 (25/151), QX 107 (12/151) and RT 012 (11/151). All isolates were susceptible to vancomycin, metronidazole and fidaxomicin, while there was significant resistance to clindamycin (90.1%), and some to moxifloxacin (6.6%) and rifaximin (3.3%). CONCLUSION: The prevalence of C. difficile in children with diarrhoea was high (37.8%) although the proportion of toxigenic strains was comparatively low. The clinical significance of any isolate needs to be determined.

Antibiotics and healthcare facility-associated Clostridioides difficile infection: systematic review and meta-analysis 2020 update.

BACKGROUND: Antibiotic use is the most important modifiable risk factor for healthcare facility-associated Clostridioides difficile infection (HCFA-CDI). Previous systematic reviews cover studies published until 31 December 2012. OBJECTIVES: To update the evidence for associations between antibiotic classes and HCFA-CDI to 31 December 2020. METHODS: PubMed, Scopus, Web of Science Core Collection, WorldCat and Proquest Dissertations & Theses were searched for studies published since 1 January 2013. Eligible studies were those conducted among adult hospital inpatients, measured exposure to individual antibiotics or antibiotic classes, included a comparison group and measured the occurrence of HCFA-CDI as an outcome. The Newcastle-Ottawa Scale was used to appraise study quality. To assess the association between each antibiotic class and HCFA-CDI, a pooled random-effects meta-analysis was undertaken. Meta-regression and subgroup analysis was used to investigate study characteristics identified a priori as potential sources of heterogeneity. RESULTS: Carbapenems and third- and fourth-generation cephalosporin antibiotics remain the most strongly associated with HCFA-CDI, with cases more than twice as likely to have recent exposure to these antibiotics prior to developing HCFA-CDI. Modest associations were observed for fluoroquinolones, clindamycin and ß-lactamase inhibitor combination penicillin antibiotics. Individual study effect sizes were variable and heterogeneity was observed for most antibiotic classes. CONCLUSIONS: This review provides the most up-to-date synthesis of evidence in relation to the risk of HCFA-CDI associated with exposure to specific antibiotic classes. Studies were predominantly conducted in North America or Europe and more studies outside of these settings are needed.

Evaluation of the antimicrobial activity of ridinilazole and six comparators against Chinese, Japanese and South Korean strains of Clostridioides difficile.

BACKGROUND: Clostridioides difficile is the most common cause of antimicrobial-associated diarrhoea in high-income countries. Fluoroquinolone resistance enabled the emergence and intercontinental spread of the epidemic ribotype (RT) 027 strain of C. difficile in the early 2000s. Despite frequent inappropriate antimicrobial use in Asia, RT 027 is rarely isolated in the region, but the often fluoroquinolone- and clindamycin-resistant RT 017 strain predominates. OBJECTIVES: This study evaluated the antimicrobial activity of ridinilazole, a novel antimicrobial agent with highly specific activity for C. difficile, against clinical strains of C. difficile from Asia. METHODS: C. difficile strains from Japan (n = 64), South Korea (n = 32) and China (n = 44) were tested by the agar dilution method for susceptibility to ridinilazole, metronidazole, vancomycin, clindamycin, moxifloxacin, rifaximin and fidaxomicin. RESULTS: All strains were susceptible to ridinilazole, with low MICs (0.03-0.25 mg/L). Several strains showed multiresistance profiles, particularly RT 017 (100% clindamycin resistant, 91.3% moxifloxacin resistant, 82.6% rifaximin resistant) and RT 369 (94.4% clindamycin resistant, 100% moxifloxacin resistant). Rifaximin resistance was absent in all strains from Japan. Multiresistance to clindamycin, moxifloxacin and rifaximin was found in 19 RT 017 strains (from China and South Korea), 2 RT 001 strains (South Korea) and 1 RT 046 strain (South Korea). CONCLUSIONS: Ridinilazole showed potent activity against a range of Asian C. difficile strains, which otherwise frequently displayed resistance to several comparator antimicrobial agents. Ongoing surveillance of antimicrobial resistance profiles is required to monitor and control the spread of resistant strains.

Antimicrobial resistance surveillance of Clostridioides difficile in Australia, 2015-18.

BACKGROUND: Clostridioides difficile was listed as an urgent antimicrobial resistance (AMR) threat in a report by the CDC in 2019. AMR drives the evolution of C. difficile and facilitates its emergence and spread. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is nationwide longitudinal surveillance of C. difficile infection (CDI) in Australia. OBJECTIVES: To determine the antimicrobial susceptibility of C. difficile isolated in Australia between 2015 and 2018. METHODS: A total of 1091 strains of C. difficile were collected over a 3 year period by a network of 10 diagnostic microbiology laboratories in five Australian states. These strains were tested for their susceptibility to nine antimicrobials using the CLSI agar incorporation method. RESULTS: All strains were susceptible to metronidazole, fidaxomicin, rifaximin and amoxicillin/clavulanate and low numbers of resistant strains were observed for meropenem (0.1%; 1/1091), moxifloxacin (3.5%; 38/1091) and vancomycin (5.7%; 62/1091). Resistance to clindamycin was common (85.2%; 929/1091), followed by resistance to ceftriaxone (18.8%; 205/1091). The in vitro activity of fidaxomicin [geometric mean MIC (GM) = 0.101 mg/L] was superior to that of vancomycin (1.700 mg/L) and metronidazole (0.229 mg/L). The prevalence of MDR C. difficile, as defined by resistance to ≥3 antimicrobial classes, was low (1.7%; 19/1091). CONCLUSIONS: The majority of C. difficile isolated in Australia did not show reduced susceptibility to antimicrobials recommended for treatment of CDI (vancomycin, metronidazole and fidaxomicin). Resistance to carbapenems and fluoroquinolones was low and MDR was uncommon; however, clindamycin resistance was frequent. One fluoroquinolone-resistant ribotype 027 strain was detected.

Antimicrobial resistance in Clostridioides difficile.

Antimicrobial resistance (AMR) in Clostridioides difficile remains a significant threat to global healthcare systems, not just for the treatment of C. difficile infection (CDI), but as a reservoir of AMR genes that could be potentially transferred to other pathogens. The mechanisms of resistance for several antimicrobials such as metronidazole and MLSB-class agents are only beginning to be elucidated, and increasingly, there is evidence that previously unconsidered mechanisms such as plasmid-mediated resistance may play an important role in AMR in this bacterium. In this review, the genetics of AMR in C. difficile will be described, along with a discussion of the factors contributing to the difficulty in clearly determining the true burden of AMR in C. difficile and how it affects the treatment of CDI.

Cost-effectiveness of an Environmental Cleaning Bundle for Reducing Healthcare-associated Infections.

BACKGROUND: Healthcare-associated infections (HAIs) remain a significant patient safety issue, with point prevalence estimates being ~5% in high-income countries. In 2016-2017, the Researching Effective Approaches to Cleaning in Hospitals (REACH) study implemented an environmental cleaning bundle targeting communication, staff training, improved cleaning technique, product use, and audit of frequent touch-point cleaning. This study evaluates the cost-effectiveness of the environmental cleaning bundle for reducing the incidence of HAIs. METHODS: A stepped-wedge, cluster-randomized trial was conducted in 11 hospitals recruited from 6 Australian states and territories. Bundle effectiveness was measured by the numbers of Staphylococcus aureus bacteremia, Clostridium difficile infection, and vancomycin-resistant enterococci infections prevented in the intervention phase based on estimated reductions in the relative risk of infection. Changes to costs were defined as the cost of implementing the bundle minus cost savings from fewer infections. Health benefits gained from fewer infections were measured in quality-adjusted life-years (QALYs). Cost-effectiveness was evaluated using the incremental cost-effectiveness ratio and net monetary benefit of adopting the cleaning bundle over existing hospital cleaning practices. RESULTS: Implementing the cleaning bundle cost $349 000 Australian dollars (AUD) and generated AUD$147 500 in cost savings. Infections prevented under the cleaning bundle returned a net monetary benefit of AUD$1.02 million and an incremental cost-effectiveness ratio of $4684 per QALY gained. There was an 86% chance that the bundle was cost-effective compared with existing hospital cleaning practices. CONCLUSIONS: A bundled, evidence-based approach to improving hospital cleaning is a cost-effective intervention for reducing the incidence of HAIs.

Antimicrobial Susceptibilities of Clostridium difficile Isolates from 12 Asia-Pacific Countries in 2014 and 2015.

Clostridium (Clostridioides) difficile causes toxin-mediated diarrhea and pseudomembranous colitis, primarily among hospital inpatients. Outbreaks of C. difficile infection (CDI) have been caused by strains with acquired antimicrobial resistance, particularly fluoroquinolone resistance, including C. difficile ribotype (RT) 027 in North America and Europe and RT 017, the most common strain in Asia. Despite being the most common cause of hospital-acquired infection in high-income countries, and frequent misuse of antimicrobials in Asia, little is known about CDI in the Asia-Pacific region. We aimed to determine the antimicrobial susceptibility profiles of a collection of C. difficile isolates from the region. C. difficile isolates (n = 414) from a 2014 study of 13 Asia-Pacific countries were tested for susceptibility to moxifloxacin, amoxicillin-clavulanate, erythromycin, clindamycin, rifaximin, metronidazole, vancomycin, and fidaxomicin according to the Clinical and Laboratory Standards Institute's agar dilution method. All isolates were susceptible to metronidazole, vancomycin, amoxicillin-clavulanate, and fidaxomicin. Moxifloxacin resistance was detected in all countries except Australia, all RT 369 and QX 239 strains, and 92.7% of RT 018 and 70.6% of RT 017 strains. All C. difficile RT 012, 369, and QX 239 strains were also resistant to erythromycin and clindamycin. Rifaximin resistance was common in RT 017 strains only (63.2%) and was not detected in Australian, Japanese, or Singaporean isolates. In conclusion, antimicrobial susceptibility of C. difficile varied by strain type and by country. Multiresistance was common in emerging RTs 369 and QX 239 and the most common strain in Asia, RT 017. Ongoing surveillance is clearly warranted.

Mild or Malign: Clinical Characteristics and Outcomes of Clostridium difficile Infection in Thailand.

Little is known about the clinical characteristics of Clostridium difficile infection (CDI) in Asia in general, and Thailand specifically, with a few studies suggesting that the disease may be milder than elsewhere. This study aimed to describe CDI in Thailand, evaluate treatment options and their outcomes, and explore possible protective factors responsible for any unique disease characteristics. From 2015 to 2018, 469 patients were included in the study. All patients had their stools tested for the tcdB gene by direct PCR and detection of toxigenic C. difficile by culture. C. difficile isolates were subjected to toxin gene profiling and ribotyping, and patient medical records were reviewed retrospectively. There were 248 and 221 patients included in CDI and control groups, respectively. The CDI group had a higher overall 30-day mortality rate than the control group (21% versus 14%, P = 0.046), but only 2 deaths (1%) were directly attributable to CDI. Metronidazole treatment was not inferior to vancomycin in this population, and vancomycin was associated with a higher 30-day mortality rate (P = 0.047). The prevalence of severe CDI and disease outcomes were not different between patients infected with A-B+ C. difficile and A+B+ C. difficile strains or between patients with and without colonization by nontoxigenic C. difficile Besides C. difficile-specific tests, neither a single laboratory result nor a combination of results was predictive of CDI. In conclusion, CDI in Thailand was relatively mild, and metronidazole remained an effective treatment option for these mild infections.