Growing consumption of antibiotics and epidemiology of Clostridioides difficile infections in Poland: A need to develop new solutions.

Clostridioides (formerly Clostridium) difficile infections (CDIs) are becoming more common and more serious. C. difficile is the etiologic agent of antibiotic-associated diarrhea, pseudomembranous enterocolitis, and toxic megacolon while CDIs recur in 7.9% of patients. About 42.9 CDI cases/10,000 patient-days are diagnosed each day in Europe, whereas in Poland 5.6 CDI cases/10,000 patient-days are reported; however, the median for European countries is 2.9 CDI cases/10,000 patient-days. Epidemiology of CDIs has changed in recent years and risk of developing the disease has doubled in the past decade that is largely determined by use of antibiotics. Studies show that rate of antibiotic consumption in the non-hospital sector in Poland is much higher than the European average (27 vs. 21.8 DDD/1,000 patient-days), and this value has increased in recent years. Antibiotic consumption has also increased in the hospital sector, especially in the intensive care units - 1,520 DDD/1,000 patient-days (ranging from 620 to 3,960 DDD/1,000 patient-days) - and was significantly higher than in Germany 1,305 (ranging from 463 to 2,216 DDD/1,000 patient-days) or in Sweden 1,147 (ranging from 605 to 2,134 DDD/1,000 patient-days). The recent rise in CDI incidence has prompted a search for alternative treatments. Great hope is placed in probiotics, bacteriocins, monoclonal antibodies, bacteriophages, and developing new vaccines.

Early Colectomy Saves Lives in Toxic Megacolon Due to Clostridium difficile Infection.

OBJECTIVE: The purpose of the study was to evaluate whether early colectomy in patients who have toxic megacolon due to Clostridium difficile colitis reduces mortality. METHODS: The study was performed using the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2016. All patients 18 to 89 years of age who underwent colectomy for toxic megacolon resulting from C. difficile colitis were included in the study. Other variables included in the study were patient demography, comorbidities, and outcomes. Patients who underwent colectomy before the presentation of septic shock (early group) were compared with patients who underwent colectomy after the onset of septic shock (late group). The main outcome of the study is 30-day all-cause mortality. Because there were some significant differences found in patient baseline characteristics in the univariate analysis, the propensity score of each patient was calculated and pair-matched analysis was performed. All P values are reported as 2-sided, and P < 0.05 was considered statistically significant. RESULTS: One hundred sixty-three patients met the inclusion criteria of the study. Approximately 85% of the patients underwent total abdominal colectomy. The average age of the patients was 65 years old, 51% of the patients were female, and 66% of the patients were white. The overall 30-day mortality was approximately 39%. The mortality rate of patients who underwent colectomy early compared to late was 13 (21%) vs 28 (45%), P = 0.009. The absolute risk difference was 0.24 with 95% CI: 0.07-0.42. CONCLUSIONS: There was a reduction of 24% in 30-day mortality when colectomies were performed before the development of septic shock.

Clostridioides difficile-related toxic megacolon after Cryptococcus neoformans cellulitis: A complex of two rare infections in an immunocompromised host.

A 76-year-old Japanese woman was admitted due to uncontrolled cellulitis of the right lower leg. She had deep vein thrombosis on the right limb. Moreover, she had a long history of rheumatoid arthritis treated with corticosteroids. Skin biopsy and lumbar puncture were performed to diagnose disseminated cryptococcosis. She was administered antifungal agents (liposomal amphotericin B and 5-fluorocytosine). On treatment day 14, debridement was performed, and cryptococcosis was controlled. However, she developed toxic megacolon due to Clostridioides difficile infection (CDI). On day 32, she was transferred to the intensive care unit due to severe acidosis and acute kidney injury secondary to CDI-related toxic megacolon. Vancomycin, metronidazole, and tigecycline were administered for treatment of CDI. After several weeks of intensive care, toxic megacolon was improved, but renal replacement therapy was discontinued according to the patient's will. On day 73, she died of renal failure. We experienced a complex of rare diseases, Cryptococcus neoformans cellulitis and Clostridioides difficile-related toxic megacolon. Both diseases were presumed to be the result of corticosteroid and methotrexate use. Hence, careful monitoring is required when treating immunocompromised hosts to reduce the risk of developing complications.

New-onset ulcerative colitis in pregnancy associated to toxic megacolon and sudden fetal decompensation: Case report and literature review.

Ulcerative colitis (UC) is a chronic inflammatory disease rarely arising during gestation. Because the available information is based on case reports or small retrospective studies, diagnosis may be difficult and treatment is still controversial. A case of toxic megacolon developing in late pregnancy associated to a sudden fetal decompensation is described. Diagnostic and clinical topics of acute UC onset in pregnancy are debated.A primipara, 34 years old, 33/0 weeks of gestation, was admitted with a diagnosis of preterm labor, associated to acute bloody diarrhea (up to 10 daily motions) and cramping abdominal pain. A diagnosis of new-onset early-stage UC was made by sigmoidoscopy. An intensive care regimen including hydrocortisone, antibiotics and parenteral nutrition was immediately started. Magnetic resonance imaging of maternal abdomen, fostered by the worsening patient conditions, evidenced dilatation of the entire colon and a severely hampered of fetal muscular tone.Toxic megacolon complicated by superimposed Clostridium difficile infection was associated to a sudden fetal decompensation diagnosed by chance during maternal abdominal magnetic resonance imaging. An emergency cesarean section was mandatory. According to a senior surgeon's decision, total colectomy was not immediately performed following cesarean section with reference to the absence of colonic perforation. We obtained a good short-term maternal outcome and an uncomplicated neonatal course. Counseling of those patients must be focused on timely and multidisciplinary intervention in order to improve the course of maternal disease and to prevent fetal distress.

[Clostridium difficile infection : What is currently available for treatment?] / Clostridium-difficile-Infektion : Was ist gesichert in der Therapie?

Clostridium difficile (C. difficile) is an anaerobic, Gram-positive, spore-forming, toxin-secreting bacillus. It is transmitted via a fecal-oral route and can be found in 1-3 % of the healthy population. Symptoms caused by C. difficile range from uncomplicated diarrhea to a toxic megacolon. The incidence, frequency of recurrence, and mortality rate of C. difficile infections (CDIs) have increased significantly over the past few decades. The most important risk factor is antibiotic treatment in elderly patients and patients with severe comorbidities. There is a screening test available to detect C. difficile-specific glutamate dehydrogenase (GDH), which is produced by both toxigenic and non-toxigenic strains. To confirm CDIs, it is necessary to test for toxins in a fresh, liquid stool sample via polymerase chain reaction or an enzyme-coupled immune adsorption test. If CDIs are diagnosed, then ongoing antibiotic treatment should be ended. Metronidazole is used to treat mild cases, and vancomycin is recommended for severe cases. Vancomycin or fidaxomicin should be used to treat recurrences (10-25 % of patients). In cases with several recurrences, a treatment option is fecal microbiome transfer (FMT). The cure rate following FMT is approximately 80 %. The treatment of severe and complicated CDI with a threatening toxic megacolon remains problematic. The degree of evidence of medicated treatment in this situation is low; the significance of metronidazole i. v. as an additional therapeutic measure is controversial. Tigecycline i. v. is an alternative option. Surgical treatment must be considered in patients with a toxic megacolon or an acute abdomen.

NAP1 strain type predicts outcomes from Clostridium difficile infection.

BACKGROUND: Studies are conflicting regarding the importance of the fluoroquinolone-resistant North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) outcome. We describe strain types causing CDI and evaluate their association with patient outcomes. METHODS: CDI cases were identified from population-based surveillance. Multivariate regression models were used to evaluate the associations of strain type with severe disease (ileus, toxic megacolon, or pseudomembranous colitis within 5 days; or white blood cell count ≥15 000 cells/µL within 1 day of positive test), severe outcome (intensive care unit admission after positive test, colectomy for C. difficile infection, or death within 30 days of positive test), and death within 14 days of positive test. RESULTS: Strain typing results were available for 2057 cases. Severe disease occurred in 363 (17.7%) cases, severe outcome in 100 (4.9%), and death within 14 days in 56 (2.7%). The most common strain types were NAP1 (28.4%), NAP4 (10.2%), and NAP11 (9.1%). In unadjusted analysis, NAP1 was associated with greater odds of severe disease than other strains. After controlling for patient risk factors, healthcare exposure, and antibiotic use, NAP1 was associated with severe disease (adjusted odds ratio [AOR], 1.74; 95% confidence interval [CI], 1.36-2.22), severe outcome (AOR, 1.66; 95% CI, 1.09-2.54), and death within 14 days (AOR, 2.12; 95% CI, 1.22-3.68). CONCLUSIONS: NAP1 was the most prevalent strain and a predictor of severe disease, severe outcome, and death. Strategies to reduce NAP1 prevalence, such as antibiotic stewardship to reduce fluoroquinolone use, might reduce CDI morbidity.

A unique strain of community-acquired Clostridium difficile in severe complicated infection and death of a young adult.

BACKGROUND: Clostridium difficile is the major cause of nosocomial antibiotic-associated diarrhoea with the potential risk of progressing to severe clinical outcomes including death. It is not unusual for Clostridium difficile infection to progress to complications of toxic megacolon, bowel perforation and even Gram-negative sepsis following pathological changes in the intestinal mucosa. These complications are however less commonly seen in community-acquired Clostridium difficile infection than in hospital-acquired Clostridium difficile infection. To the best of our knowledge, this was the first case of community-acquired Clostridium difficile infection of its type seen in Jamaica. CASE PRESENTATION: We report a case of a 22-year-old female university student who was admitted to the University Hospital of the West Indies, Jamaica with a presumptive diagnosis of pseudomembranous colitis PMC. She presented with a 5-day history of diarrhoea following clindamycin treatment for coverage of a tooth extraction due to a dental abscess. Her clinical condition deteriorated and progressed from diarrhoea to toxic megacolon, bowel perforation and Gram-negative sepsis. Clostridium difficile NAP12/ribotype 087 was isolated from her stool while blood cultures grew Klebsiella pneumoniae. Despite initial treatment intervention with empiric therapy of metronidazole and antibiotic clearance of Klebsiella pneumoniae from the blood, the patient died within 10 days of hospital admission. CONCLUSIONS: We believe that clindamycin used for coverage of a dental abscess was an independent risk factor that initiated the disruption of the bowel micro-flora, resulting in overgrowth of Clostridium difficile NAP12/ribotype 087. This uncommon strain, which is the same ribotype (087) as ATCC 43255, was apparently responsible for the increased severity of the infection and death following toxic megacolon, bowel perforation and pseudomembranous colitis involving the entire large bowel. K. pneumoniae sepsis, resolved by antibiotic therapy was secondary to Clostridium difficile infection. The case registers community-acquired Clostridium difficile infection as producing serious complications similar to hospital-acquired Clostridium difficile infection and should be treated with the requisite importance.

Conservative surgical treatment for toxic megacolon due to Clostridium difficile infection in a transplanted pediatric patient.

Severe disease caused by Clostridium difficile is frequently encountered in transplant recipients and carries a high mortality. Numerous studies have been published on this subject in the adult population, but few in the pediatric setting. A 4-year-old boy who had undergone heart transplant 20 months earlier was admitted to the pediatric intensive care unit after humoral rejection. Seven days after admission, he developed septic shock, abdominal distension, and paralytic ileus without diarrhea. Pseudomembranous colitis due to C. difficile was confirmed by microbiological and radiological studies. Despite treatment with rectal vancomycin and intravenous metronidazole, the patient did not improve and required decompressive laparotomy; because of the poor subsequent clinical course, terminal ileostomy and cecostomy were performed in a second operation. Recovery was satisfactory, and surgical reconstruction of intestinal tract was performed 3 months later without complications. Although early surgery with total colectomy is indicated, when there is a poor response to medical treatment in cases of C. difficile toxic megacolon, the case we present responded favorably to a conservative surgical approach that enabled intestinal integrity to be restored 3 months later. In the pediatric population, less aggressive therapeutic options should be considered, as they have benefits on the subsequent quality of life of the patient.

Fatal Clostridium difficile infection associated with vinorelbine chemotherapy: case report and literature review.

Differentiating between chemotherapy-related diarrhoea and Clostridium difficile-associated diarrhoea (CDAD) can be extremely difficult. There is increasing evidence that CDAD can be seen in patients on chemotherapy without prior antibiotic usage. We report the first case of CDAD secondary to vinorelbine chemotherapy and review the literature.

Campylobacter colitis leads to toxic megacolon and multiple organ failure.

A 58-year-old woman presented to the emergency department in a district general hospital with severe abdominal pain and diarrhoea, after collapsing at home. She was admitted to the intensive care unit (ICU) in septic shock, and with acute kidney injury. An initial CT scan was suggestive of colitis. She was treated for suspected gastroenteritis and her microbiology results showed Campylobacter coli as the causative organism. She failed to respond to antibiotics, and underwent serial contrast CTs which showed no progression of colitis. Colonoscopy performed on day 10 of her admission, however, revealed fulminant colitis. After a multidisciplinary meeting among gastroenterologists, general surgeons and intensivists, the patient underwent total colectomy with ileostomy. She made a slow but steady recovery in ICU, and subsequently in the ward, and was discharged to a local community hospital for further rehabilitation.

Clostridium difficile ribotypes 001, 017, and 027 are associated with lethal C. difficile infection in Hesse, Germany.

From January 2008 to April 2009, 72 cases of severe Clostridium difficile infection were reported from 18 different districts in the state of Hesse, Germany. A total of 41 C. difficile isolates from 41 patients were subjected to PCR ribotyping. PCR ribotype (RT) 027 was the most prevalent strain accounting for 24 of 41 (59%) of typed isolates, followed by RT 001 (eight isolates, 20%), RT 017 and 042 (two isolates each), and RT 003, 066, 078, 081, and RKI-034 (one isolate each). Eighteen patients had died within 30 days after admission. C. difficile was reported as underlying cause of or contributing to death in 14 patients, indicating a case fatality rate of 19%. The patients with lethal outcome attributable to C. difficile were 59-89 years-old (median 78 years). Ribotyping results were available for seven isolates associated with lethal outcome, which were identified as RT 027 in three and as RT 001 and 017 in two cases each. Our data suggest that C. difficile RT 027 is prevalent in some hospitals in Hesse and that, in addition to the possibly more virulent RT 027, other toxigenic C. difficile strains like RT 001 and 017 are associated with lethal C. difficile infections in this region.

An unusual case of caecal perforation following ileostomy reversal.

A 63-year-old man with a history of gastro-oesophageal reflux disease underwent defunctioning loop ileostomy for obstructing metastatic rectal cancer prior to receiving long-course neoadjuvant chemoradiotherapy. Four months post completion of neoadjuvant therapy, he underwent an uncomplicated elective ultra-low anterior resection with formation of colonic J pouch and first stage liver metastasectomy for bilobar liver disease. At 1 year, he proceeded to an elective closure of loop ileostomy. Unfortunately, his postoperative course was complicated by profuse diarrhoea with subsequent colonic perforation, necessitating an emergency laparotomy and ileocolic resection with end ileostomy formation. Histopathology and stool studies were consistent with Salmonella Typhi infection. At the present time, Salmonella Typhi causing toxic megacolon and subsequent colonic perforation is an uncommon phenomenon in Australia. Here, we present an unusual case and explain why bowel perforation in this instance likely had a multifactorial aetiology.

Community-acquired fulminant colitis caused by binary toxin-producing Clostridium difficile in Japan.

We report a case of community-acquired fulminant colitis caused by Clostridium difficile in Japan. A 46-year-old woman was diagnosed with severe infectious enterocolitis and was admitted at another hospital. The stool culture was positive for toxigenic C. difficile. Since the patient presented with fulminant C. difficile infection (CDI) with toxic megacolon, respiratory insufficiency, and circulatory failure, she was transferred to Kyorin University Hospital for intensive care. Intubation and antibiotic therapy were performed. The general condition improved with conservative treatment, and she was discharged without sequelae. While the recovered isolate was toxin A and B-positive and binary toxin-positive, it was identified as polymerase chain reaction (PCR) ribotype ts0592 and slpA sequence type ts0592. The isolate was different from PCR ribotype 027 epidemic in Europe and North America. In Japan, binary toxin-producing strains are rare and have not caused an epidemic to date. Furthermore, there are few data on community-acquired CDI in Japan. In this case, a non-elderly woman with no major risk factors such as antibiotic use, administration of proton pump inhibitor and history of gastrointestinal surgery developed community-acquired fulminant CDI caused by the binary toxin-positive strain, and ICU treatment was required. Further studies focusing on the role of binary toxin-positive C. difficile in the severity of community-acquired CDI are necessary.

Acute primary abdominal compartment syndrome due to Clostridium difficile induced toxic megacolon: a case report and review of the literature.

BACKGROUND: Without timely diagnosis, acute primary abdominal compartment syndrome (ACS) is a potentially fatal syndrome and often goes unrecognized until severe symptoms appear. Early diagnosis may significantly improve the prognosis of these patients. CASE PRESENTATION: We present the case of a 54-year-old man, successfully treated for acute myeloid leukemia with cytosine arabinoside, admitted to the intensive care unit with severe shock, refractory to standard therapy with antibiotics, fluid resuscitation, and vasopressors. Early diagnosis of acute primary abdominal syndrome was made based on an intra-abdominal pressure of 20 mm Hg (3 kPa) with new onset organ failure, after which decompressive laparotomy was performed. Stool cultures grew Clostridium difficile. Despite abdominal decompression, the abdominal compartment syndrome persisted with the development of toxic megacolon and a total colectomy was performed with favorable evolution. METHODS: A systematic review of published case reports was performed describing a primary ACS due to C. difficile toxic megacolon. A PubMed database search was performed with the following search terms, single or in combination: 'clostridium difficile', 'toxic megacolon', 'abdominal compartment syndrome', and 'CDI'. The latest search was performed for March 2019; only case reports after 1998 were included. RESULTS: We found a total of 19 case reports with C. difficile toxic megacolon (including the present case). The male/female ratio was 12/7, and there were 3 children. The mean age was 48.7 ± 23.5 years. The reason for admission was sepsis in 6, trauma in 2, postoperative in 4, enterocolitis in 5, pregnancy in 1 and abdominal complaints after topical antibiotics in 1. Three patients did not develop diarrhea. Five patients presented with diarrhea on average 5.8 ± 5.1 (median 4, 1-14) days prior to hospital admission while 7 patients developed diarrhea on average after 10 ± 19.6 (median 3, 0-54) days during admission. The intra-abdominal pressure (measured in 6 patients, including ours) was 29.2 ± 11 (20-50) mm Hg (3-7 kPa). Treatment consisted of (a combination of) vancomycin (orally or via rectal enemas), metronidazole (orally or intravenously), and surgical intervention (with decompressive laparotomy). Three patients died (15.8%). CONCLUSIONS: Monitoring of intra-abdominal pressure allows early detection of abdominal compartment syndrome and is warranted in patients with C. difficile infection and/or toxic megacolon. Early decompression can lead to improved outcomes in patients with severe shock and organ failure.

The changing spectrum of clostridium difficile associated disease: implications for dentistry.

BACKGROUND: Clostridium difficile is an anaerobic, spore-forming bacterium that causes a wide range of diseases of the gastrointestinal tract. It is best known for its association with uncomplicated antimicrobial-agent-associated diarrhea. CASE DESCRIPTION: The authors describe two previously published cases of Clostridium difficile-associated disease (CDAD) to highlight its varied clinical manifestations. A 48-year-old woman had mild CDAD after receiving antibiotics after undergoing endodontic surgery. She took metronidazole, and her C. difficile infection resolved. A 31-year-old pregnant woman developed severe CDAD after receiving antibiotics for a urinary tract infection. She underwent surgery to remove part of her colon, but her condition worsened, and she died. CLINICAL IMPLICATIONS: Dentists often prescribe antimicrobial agents to treat infections. Until recently, these agents also were recommended as prophylaxis for infective endocarditis during invasive oral procedures. An important risk factor for CDAD and recurrent CDAD is antimicrobial agent exposure. Dentists should be aware of CDAD to help prevent its spread and facilitate early recognition and treatment to minimize severe outcomes.

A case of toxic megacolon caused by clostridium difficile infection and treated with fecal microbiota transplantation.

Clostridium difficile infection. The mortality rate of fulminant C. difficile infection is reported to be as high as 50%. Fecal microbiota transplantation is a highly effective treatment in patients with recurrent or refractory C. difficile infection. However, there are few published articles on the use of such transplantation for fulminant C. difficile infection. Here, we report on a patient with toxic megacolon complicated by C. difficile infection who was treated successfully with fecal mi-crobiota transplantation. (Gut Liver, 2015;9:247-250).

Self-Administered Home Series Fecal "Minitransplants" for Recurrent Clostridium difficile Infection on a Rectal Remnant.

A fecal microbiota transplant has proved to be an extremely effective method for patients with recurrent infections with Clostridium difficile. We present the case of a 65-year-old female patient with multiple Clostridium difficile infection (CDI) relapses on the rectal remnant, post-colectomy for a CDI-related toxic megacolon. The patient also evidenced associated symptomatic Clostridium difficile vaginal infection. She was successfully treated with serial fecal "minitransplants" (self-administered at home) and metronidazole ovules.