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1.
Eur J Clin Microbiol Infect Dis ; 42(5): 607-619, 2023 May.
Article in English | MEDLINE | ID: mdl-36940050

ABSTRACT

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.


Subject(s)
Clostridioides difficile , Clostridium Infections , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Western Australia/epidemiology , Reinfection , Clostridioides difficile/genetics , Recurrence , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Genomics
2.
J Appl Microbiol ; 134(6)2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37296244

ABSTRACT

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.


Subject(s)
Clostridioides difficile , Clostridium Infections , Animals , Swine , Clostridioides difficile/genetics , Clostridioides , Vietnam/epidemiology , Clostridium Infections/epidemiology , Clostridium Infections/veterinary , Clostridium Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Clostridium , Ribotyping , Microbial Sensitivity Tests
3.
Anaerobe ; 81: 102741, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37244476

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Clostridioides difficile , Clostridium Infections , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , Aged, 80 and over , Clostridioides difficile/genetics , Clostridioides/genetics , Vietnam/epidemiology , Clostridium Infections/epidemiology , Clostridium Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Diarrhea/epidemiology , Diarrhea/drug therapy , Clostridium/genetics , Microbial Sensitivity Tests , Ribotyping
4.
Environ Microbiol ; 24(3): 1221-1230, 2022 03.
Article in English | MEDLINE | ID: mdl-34693624

ABSTRACT

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.


Subject(s)
Clostridioides difficile , Clostridium Infections , Anti-Bacterial Agents/pharmacology , Clostridioides difficile/genetics , Humans , Microbial Sensitivity Tests , Ribotyping , Water , Whole Genome Sequencing
5.
J Appl Microbiol ; 133(3): 1156-1168, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34894035

ABSTRACT

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.


Subject(s)
Clostridioides difficile , Clostridium Infections , Animals , Clostridioides , Clostridioides difficile/genetics , Clostridium , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Hospitals , Humans , Ribotyping
6.
Lett Appl Microbiol ; 75(3): 526-536, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35119124

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Clostridioides difficile , Clostridium Infections , Anti-Bacterial Agents/therapeutic use , Benzimidazoles , Clostridioides , Clostridium , Clostridium Infections/drug therapy , Clostridium Infections/microbiology , Clostridium Infections/prevention & control , Fidaxomicin/therapeutic use , Humans , Metronidazole/therapeutic use , Pyridines , Vancomycin/pharmacology , Vancomycin/therapeutic use
7.
Anaerobe ; 74: 102528, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35104667

ABSTRACT

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.


Subject(s)
Bacterial Toxins , Clostridioides difficile , Clostridium Infections , Cross Infection , Enterocolitis, Pseudomembranous , Clostridioides difficile/genetics , Clostridium Infections/epidemiology , Cross Infection/epidemiology , Female , Hospitals , Humans , Male , Ribotyping , Western Australia/epidemiology
8.
Anaerobe ; 74: 102550, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35331913

ABSTRACT

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.


Subject(s)
Clostridioides difficile , Clostridium Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Child , Clostridioides , Clostridioides difficile/genetics , Clostridium/genetics , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Diarrhea/drug therapy , Diarrhea/epidemiology , Humans , Infant , Microbial Sensitivity Tests , Ribotyping , Vietnam/epidemiology
9.
J Antimicrob Chemother ; 76(4): 967-972, 2021 03 12.
Article in English | MEDLINE | ID: mdl-33351917

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Clostridioides difficile , Clostridium Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Asia , Benzimidazoles , China , Clostridioides , Clostridium Infections/drug therapy , Humans , Japan , Microbial Sensitivity Tests , Pyridines , Republic of Korea , Ribotyping
10.
Article in English | MEDLINE | ID: mdl-32393487

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Clostridioides difficile , Clostridium Infections , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Asia/epidemiology , Australia , Clostridioides difficile/genetics , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Europe , Humans , Microbial Sensitivity Tests , North America , Ribotyping
11.
J Clin Microbiol ; 56(6)2018 06.
Article in English | MEDLINE | ID: mdl-29563206

ABSTRACT

Accumulating evidence shows a high prevalence of Clostridium difficile in Southeast Asia associated with a range of clinical presentations. However, severe infections are rarely reported. We investigated C. difficile infection (CDI) across four hospitals in Kuala Lumpur and Kota Bharu, Malaysia. Enzyme immunoassays for glutamate dehydrogenase (GDH) and toxin A or B were performed on diarrheal stool specimens collected from patients in 2015 and 2016. Specimens were also cultured and isolates of C. difficile characterized by PCR ribotyping and detection of toxin genes. In total, 437 specimens were collected and fecal toxin was detected in 3.0%. A further 16.2% of specimens were GDH positive and toxin negative. After culture, toxigenic strains were isolated from 10.3% and nontoxigenic strains from 12.4% of specimens. The most prevalent PCR ribotypes (RTs) were RT 017 (20.0%) and RT 043 (10.0%). The high prevalence of RT 017 and nontoxigenic strains in Malaysia and in neighboring Thailand and Indonesia suggests that they localize to the region of Southeast Asia, with an implication that they may mediate the burden of CDI in the region.


Subject(s)
Bacterial Proteins/genetics , Bacterial Toxins/genetics , Clostridioides difficile/genetics , Clostridioides difficile/isolation & purification , Clostridium Infections/epidemiology , Enterotoxins/genetics , Adolescent , Adult , Aged , Aged, 80 and over , DNA, Bacterial/genetics , Diarrhea/epidemiology , Diarrhea/microbiology , Feces/chemistry , Feces/microbiology , Female , Glutamate Dehydrogenase/analysis , Humans , Immunoenzyme Techniques , Indonesia/epidemiology , Malaysia/epidemiology , Male , Middle Aged , Polymerase Chain Reaction , Prevalence , Ribotyping , Thailand/epidemiology , Young Adult
12.
Anaerobe ; 51: 12-16, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29534914

ABSTRACT

Strains of Clostridium difficile producing only binary toxin (CDT) are found commonly in animals but not humans. However, human diagnostic tests rarely look for CDT. The Cepheid Xpert C. difficile BT assay detects CDT with equal sensitivity (≥92%) in human and animal faecal samples.


Subject(s)
ADP Ribose Transferases/genetics , Bacterial Proteins/genetics , Clostridioides difficile/genetics , Clostridium Infections/diagnosis , Clostridium Infections/veterinary , Molecular Diagnostic Techniques/methods , Animals , Humans , Sensitivity and Specificity
13.
Anaerobe ; 48: 121-125, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28807622

ABSTRACT

Clostridium difficile infection (CDI) is primarily associated with hospitalised patients, however, community-associated CDI (CA-CDI) has increased in Australia. We aimed to investigate the epidemiology and outcomes of CA-CDI cases presenting to hospital emergency departments in Western Australia (WA). A retrospective case-control study of CA-CDI cases presenting at six emergency departments in WA from July 2013 to June 2014 was performed. Clinical signs, recent medication, hospitalisations and potential risk factors for CA-CDI were investigated for cases (n = 34) and unmatched controls (n = 62) who were infected with another gastrointestinal pathogen, including Campylobacter spp., Salmonella spp., Aeromonas spp., Shigella sonnei and Escherichia coli O157. Elevated white cell count (31.3% vs 8.2%, p < 0.01), female gender (67.6% vs 41.9%, p < 0.05), age ≥65 years (41.2% vs 21.0%, p < 0.05) and antimicrobial use in the previous month (41.2% vs 11.3%, p < 0.01) were significantly more frequent among cases compared to controls. After multivariable analysis, antibiotic use (odds ratio 8.49, 95% confidence interval 2.75-26.21) and age ≥65 years (3.03, 1.05-8.75) were significantly associated with CA-CDI. Ribotype (RT) 014/020 was most common (40.7%) among 27 C. difficile isolates followed by RTs 002 (14.8%), 001, 056 and 244 (all 7.4%). CA-CDI was associated with advanced age and recent antibiotic use compared to those infected with other gastrointestinal pathogens. RT 014 has also recently been found at high prevalence in public lawn spaces, and previously RT 014 strains from humans and pigs in Australia were closely genetically related, suggesting CA-CDI may be linked with these community reservoirs.


Subject(s)
Clostridioides difficile , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Emergency Service, Hospital , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Clostridium Infections/drug therapy , Community-Acquired Infections/drug therapy , Comorbidity , Female , Humans , Male , Middle Aged , Odds Ratio , Western Australia/epidemiology , Young Adult
14.
Anaerobe ; 37: 34-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26592987

ABSTRACT

Despite increasing infection rates, Clostridium difficile is not currently routinely tested for in all diarrhoeal faecal specimens in Australia. In July 2014, all diarrhoeal specimens submitted to a diagnostic laboratory in Western Australia were surveyed to determine the true prevalence of C. difficile. In total, 1010 diarrhoeal non-duplicate faecal specimens were received during the month. Testing for C. difficile was requested, or the criteria for a C. difficile investigation were met, for 678 specimens which were investigated by PCR for the tcdB gene using the BD MAX platform, followed by toxigenic culture on PCR-positive samples. The remaining 332 specimens, with either no C. difficile test request or the criteria for a C. difficile investigation were not met, were examined by toxigenic culture. All isolates were PCR ribotyped. C. difficile was the most commonly detected diarrhoeal pathogen among all specimens. The overall prevalence of C. difficile in all 1010 specimens was 6.4%; 7.2% in the routinely tested group, and 4.8% in the non-requested group. The proportion of non-requested positive detections among all cases was 24.6%. Community-onset infection was present in 50.8% of all cases. The median age of all CDI cases was 60.0 years and the age range in CDI patients in the routine group was 0.6-96.6 years (median 72.7 years), compared to 0.2-2.3 years (median 0.8 years) in the non-requested group. The most common ribotype (RT) found was RT 014/020 (34.1% in the routine group, 43.8% in the non-requested group), followed by RTs 002, 056, 005 and 018. While the routine testing group and the non-requested group differed markedly in age and patient classification, C. difficile was the most common cause of diarrhoea in hospitals and the community in Western Australia. The significance of finding C. difficile in the community paediatric population requires further study.


Subject(s)
Clostridioides difficile/isolation & purification , Clostridium Infections/diagnosis , Diagnostic Tests, Routine , Adolescent , Adult , Aged , Child , Child, Preschool , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Diarrhea/microbiology , Female , Health Care Surveys , Humans , Infant , Male , Middle Aged , Prevalence , Western Australia/epidemiology , Young Adult
15.
J Infect Chemother ; 21(10): 718-22, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26238001

ABSTRACT

Physicians often fail to suspect Clostridium difficile infection (CDI) and many microbiology laboratories use suboptimal diagnostic techniques. To estimate the extent of and reasons for incorrect diagnosis of CDI in Japan, we investigated toxigenic C. difficile isolated from all stool culture samples and clinical course. Over a 12-month period in 2010, all stool culture samples (n = 975) submitted from inpatients in a university hospital in Japan were cultured for C. difficile and routine microbiological testing was conducted. In total, 177 C. difficile isolates were recovered, and 127 isolates were toxigenic. Among the toxin-A-positive/toxin-B-positive isolates, 12 were also positive for the binary toxin gene. However, clinically important ribotypes, such as 027 and 078, were not identified. A total of 58 (45.7%) cases with toxigenic C. difficile had unformed stool, and the incidence CDI was 1.6 cases per 10,000 patient-days. Of these 58 cases, 40 were not diagnosed in routine testing due to a lack of clinical suspicion (24.1%, 14/58) or a negative C. difficile toxin assay result (44.8%, 26/58). A stool toxin assay was performed in 54 patients (78.2%, 54/69) who did not have unformed stool. The present study demonstrated that a significant number of CDI cases in Japan might be overlooked or misdiagnosed in clinical practice due to a lack of clinical suspicion and limitations of microbiological testing for CDI in Japan. Providing education to promote awareness of CDI among physicians is important to improve the accuracy of diagnosis in Japan.


Subject(s)
Clostridioides difficile , Clostridium Infections/diagnosis , Diagnostic Errors , ADP Ribose Transferases , Aged , Bacterial Proteins/genetics , Bacterial Toxins/genetics , Clostridioides difficile/genetics , Clostridioides difficile/isolation & purification , Clostridioides difficile/pathogenicity , Clostridium Infections/epidemiology , Enterotoxins/genetics , Feces/microbiology , Female , Hospitals, University , Humans , Japan , Male , Middle Aged , Retrospective Studies
17.
Emerg Microbes Infect ; 9(1): 42-52, 2020.
Article in English | MEDLINE | ID: mdl-31873046

ABSTRACT

Clostridioides difficile causes healthcare-related diarrhoea in high-income countries. Highly resistant spores persist in healthcare facilities, primarily infecting patients who have recently received antimicrobials. C. difficile infection (CDI) has been studied in detail in North America and Europe; however, the epidemiology of CDI elsewhere, including the Asia-Pacific region, is largely unknown. A survey of CDI was performed in 13 Asia-Pacific countries. Epidemiological data on 600 cases were collected and molecular typing undertaken on 414 C. difficile isolates. Healthcare facility-associated CDI comprised 53.6% of cases, while community-associated CDI was 16.5%. The median age of cases was 63.0 years and 45.3% were female, 77.5% had used antibiotics in the previous 8 weeks, most frequently third-generation cephalosporins (31.7%), and 47.3% had used proton pump inhibitors. Recurrence (9.1%) and mortality (5.2%) rates were low, while complications including colitis or pseudomembranous colitis (13.8%), colectomy (0.4%), and toxic megacolon (0.2%) were uncommon. Common C. difficile strains were ribotypes 017 (16.7%), 014/020 (11.1%) and 018 (9.9%), with wide variation between countries. Binary toxin-positive strains of C. difficile were detected rarely. Overall, disease severity appeared mild, and mortality and recurrence were low. Continued education about, and surveillance of, CDI in Asia are required to reduce the burden of disease.


Subject(s)
Clostridioides difficile/isolation & purification , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Asia/epidemiology , Australia/epidemiology , Clostridioides difficile/classification , Clostridioides difficile/genetics , Clostridioides difficile/physiology , Clostridium Infections/drug therapy , Clostridium Infections/etiology , Diarrhea/microbiology , Female , Humans , Male , Middle Aged , Risk Factors , Young Adult
18.
Expert Rev Anti Infect Ther ; 18(1): 17-25, 2020 01.
Article in English | MEDLINE | ID: mdl-31800331

ABSTRACT

Introduction: Antimicrobial resistance (AMR) played an important role in the initial outbreaks of Clostridium difficile infection (CDI) in the 1970s. C. difficile ribotype (RT) 017 has emerged as the major strain of C. difficile in Asia, where antimicrobial use is poorly regulated. This strain has also caused CDI outbreaks around the world for almost 30 years. Many of these outbreaks were associated with clindamycin and fluoroquinolone resistance. AMR and selective pressure is likely to be responsible for the success of this RT and may drive future outbreaks.Areas covered: This narrative review summarizes the prevalence and mechanisms of AMR in C. difficile RT 017 and transmission of these AMR mechanisms. To address these topics, reports of outbreaks due to C. difficile RT 017, epidemiologic studies with antimicrobial susceptibility results, studies on resistance mechanisms found in C. difficile and related publications available through Pubmed until September 2019 were collated and the findings discussed.Expert opinion: Primary prevention is the key to control CDI. This should be achieved by developing antimicrobial stewardship in medical, veterinary and agricultural practices. AMR is the key factor that drives CDI outbreaks, and methods for the early detection of AMR can facilitate the control of outbreaks.


Subject(s)
Anti-Bacterial Agents/pharmacology , Clostridioides difficile/drug effects , Clostridium Infections/drug therapy , Animals , Antimicrobial Stewardship , Clostridioides difficile/genetics , Clostridioides difficile/isolation & purification , Clostridium Infections/epidemiology , Clostridium Infections/microbiology , Disease Outbreaks , Drug Resistance, Bacterial , Humans , Microbial Sensitivity Tests , Ribotyping
19.
Infect Dis Health ; 24(4): 208-211, 2019 11.
Article in English | MEDLINE | ID: mdl-31387799

ABSTRACT

BACKGROUND: Clostridium difficile is a major nosocomial pathogen causing mild diarrhoea to life-threatening pseudomembranous colitis, and its spores frequently contaminate hospital environments and equipment. Washer/Disinfectors (WDs) are commonly used to clean and decontaminate soiled equipment in health care facilities. This study aimed to evaluate the effectiveness of the DEKO-190 WD in removing C. difficile spores from bedpans. METHODS: Plastic carriers were inoculated with suspensions of C. difficile spores in autoclaved (sterile) human faeces. The carriers were then taped to a sterile plastic bedpan which was subjected to short, long or intensive wash cycles in the WD using one of two test detergents: Formula A (generic) and Formula B (highly alkaline). Mean log10 reductions in spores were calculated for each wash cycle. RESULTS: Mean log10 reductions were 3.21(SEM ± 0.20) and 2.82 (±0.13) for Formula A and B, respectively, for the short cycle. The mean log10 reductions using the long wash cycle were 3.65 (±0.44) using Formula A and 5.30 (±0.43) using Formula B, while log10 reductions were 3.37 (±0.58) (Formula A) and 4.64 (±0.47) (Formula B) for the intensive cycle. Washing with the DEKO-190 significantly reduced spore concentrations on carrier surfaces on a bedpan. Spore counts were most effectively reduced when carriers were washed on a long or intensive wash cycle using an alkaline detergent.


Subject(s)
Clostridioides difficile/growth & development , Disinfectants/pharmacology , Disinfection/methods , Equipment and Supplies, Hospital/microbiology , Spores, Bacterial/drug effects , Clostridioides difficile/drug effects , Clothing , Colony Count, Microbial , Cross Infection/microbiology , Cross Infection/prevention & control , Disinfection/instrumentation , Hospitals , Humans , Spores, Bacterial/growth & development
20.
Emerg Microbes Infect ; 8(1): 796-807, 2019.
Article in English | MEDLINE | ID: mdl-31138041

ABSTRACT

Clostridium difficile ribotype (RT) 017 is an important toxigenic C. difficile RT which, due to a deletion in the repetitive region of the tcdA gene, only produces functional toxin B. Strains belonging to this RT were initially dismissed as nonpathogenic and circulated largely undetected for almost two decades until they rose to prominence following a series of outbreaks in the early 2000s. Despite lacking a functional toxin A, C. difficile RT 017 strains have been shown subsequently to be capable of causing disease as severe as that caused by strains producing both toxins A and B. While C. difficile RT 017 strains can be found in almost every continent today, epidemiological studies suggest that the RT is endemic in Asia and that the global spread of this MLST clade 4 lineage member is a relatively recent event. C. difficile RT 017 transmission appears to be mostly from human to human with only a handful of reports of isolations from animals. An important feature of C. difficile RT 017 strains is their resistance to several antimicrobials and this has been documented as a possible factor driving multiple outbreaks in different parts of the world. This review summarizes what is currently known regarding the emergence and evolution of strains belonging to C. difficile RT 017 as well as features that have allowed it to become an RT of global importance.


Subject(s)
Clostridioides difficile/genetics , Clostridium Infections/microbiology , Evolution, Molecular , Animals , Asia/epidemiology , Clostridioides difficile/classification , Clostridioides difficile/isolation & purification , Clostridioides difficile/physiology , Clostridium Infections/epidemiology , Humans , Phylogeny , Ribotyping
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