Veli-Jukka Anttila

Fecal Transplantation, Through Colonoscopy, Is Effective Therapy for Recurrent Clostridium difficile Infection

BACKGROUND & AIMS Treatment of recurrent Clostridium difficile infection (CDI) with antibiotics leads to recurrences in up to 50% of patients. We investigated the efficacy of fecal transplantation in treatment of recurrent CDI. METHODS We reviewed records from 70 patients with recurrent CDI who had undergone fecal transplantation. Fecal transplantation was performed at colonoscopy by infusing fresh donor feces into cecum. Before transplantation, the patients had whole-bowel lavage with polyethylene glycol solution. Clinical failure was defined as persistent or recurrent symptoms and signs, and a need for new therapy. RESULTS During the first 12 weeks after fecal transplantation, symptoms resolved in all patients who did not have strain 027 C difficile infections. Of 36 patients with 027 C difficile infection, 32 (89%) had a favorable response; all 4 nonresponders had a pre-existing serious condition, caused by a long-lasting diarrheal disease or comorbidity and subsequently died of colitis. During the first year after transplantation, 4 patients with an initial favorable response had a relapse after receiving antibiotics for unrelated causes; 2 were treated successfully with another fecal transplantation and 2 with antibiotics for CDI. Ten patients died of unrelated illnesses within 1 year after transplantation. No immediate complications of fecal transplantation were observed. CONCLUSIONS Fecal transplantation through colonoscopy seems to be an effective treatment for recurrent CDI and also for recurrent CDI caused by the virulent C difficile 027 strain.

An outbreak of Listeria monocytogenes serotype 3a infections from butter in Finland.

In February 1999, an outbreak of listeriosis caused by Listeria monocytogenes serotype 3a occurred in Finland. All isolates were identical. The outbreak strain was first isolated in 1997 in dairy butter. This dairy began delivery to a tertiary care hospital (TCH) in June 1998. From June 1998 to April 1999, 25 case patients were identified (20 with sepsis, 4 with meningitis, and 1 with abscess; 6 patients died). Patients with the outbreak strain were more likely to have been admitted to the TCH than were patients with other strains of L. monocytogenes (60% vs. 8%; odds ratio, 17.3; 95% confidence interval, 2.8-136.8). Case patients admitted to the TCH had been hospitalized longer before cultures tested positive than had matched controls (median, 31 vs. 10 days; P=.008). An investigation found the outbreak strain in packaged butter served at the TCH and at the source dairy. Recall of the product ended the outbreak.

Candidemia in Finland, 1995-1999

We analyzed laboratory-based surveillance candidemia data from the National Infectious Disease Register in Finland and reviewed cases of candidemia from one tertiary-care hospital from 1995 to 1999. A total of 479 candidemia cases were reported to the Register. The annual incidence rose from 1.7 per 100,000 population in 1995 to 2.2 in 1999. Species other than Candida albicans accounted for 30% of cases without change in the proportion. A total of 79 cases of candidemia were identified at the hospital; the rate varied from 0.03 to 0.05 per 1,000 patient-days by year. Predisposing factors included indwelling catheters (81%), gastrointestinal surgery (27%), hematologic malignancy (25%), other types of surgery (21%), and solid malignancies (20%). Crude 7-day and 30-day case-fatality ratios were 15% and 35%, respectively. The rate of candidemia increased in Finland but is still substantially lower than in the United States. No shift to non–C. albicans species could be detected.

Secular trend in candidemia and the use of fluconazole in Finland, 2004-2007

BackgroundIn a previous study we observed an increasing trend in candidemia in Finland in the 1990s. Our aim was now to investigate further population-based secular trends, as well as outcome, and evaluate the association of fluconazole consumption and prophylaxis policy with the observed findings.MethodsWe analyzed laboratory-based surveillance data on candidemia from the National Infectious Diseases Register during 2004-2007 in Finland. Data on fluconazole consumption, expressed as defined daily doses, DDDs, was obtained from the National Agency for Medicines, and regional prophylaxis policies were assessed by a telephone survey.ResultsA total of 603 candidemia cases were identified. The average annual incidence rate was 2.86 cases per 100,000 population (range by year, 2.59-3.09; range by region, 2.37-3.85). The highest incidence was detected in males aged >65 years (12.23 per 100,000 population). Candida albicans accounted for 67% of cases, and C. glabrata ranked the second (19%), both without any significant change in proportions. C. parapsilosis accounted for 5% of cases and C. krusei 3% of cases. The one-month case-fatality varied between 28-32% during the study period. Fluconazole consumption increased from 19.57 DDDs per 100,000 population in 2000 to 25.09 in 2007. Systematic fluconazole prophylaxis was implemented for premature neonates, patients with acute leukemias and liver transplant patients.ConclusionThe dominant proportion of C. albicans remained stable, but C. glabrata was the most frequent non-albicans species. The proportion of C. glabrata had increased from our previous study period in the presence of increasing use of fluconazole. The rate of candidemia in Finland is still low but mortality high like in other countries.

A randomized, double-blind study comparing Clostridium difficile immune whey and metronidazole for recurrent Clostridium difficile-associated diarrhoea: Efficacy and safety data of a prematurely interrupted trial

A prospective, randomized, double-blind study was designed to compare Clostridium difficile immune whey (CDIW) with metronidazole for treatment of laboratory-confirmed, recurrent, mild to moderate episodes of Clostridium difficile-associated diarrhoea (CDAD). CDIW was manufactured by immunization of cows in their gestation period with inactivated C. difficile vaccine. The resulting colostrum was processed, immunoglubulins were concentrated and the end-product containing high titres of C. difficile immunoglobulin was used as CDIW. 20 patients received metronidazole at a dosage of 400 mg t.i.d. and 18 patients CDIW 200 ml t.i.d. The study was interrupted early because of the bankruptcy of the sponsor. After 14 d of treatment, all 20 (100%) of 20 patients had responded to metronidazole therapy, compared with 16 (89%) of 18 who had received CDIW. 70 d after the beginning of treatment, sustained responses were observed in 11 (55%) of 20 patients receiving metronidazole and 10 (56%) of 18 patients treated with CDIW. In this preliminary study CDIW was as effective as metronidazole in the prevention of CDAD recurrences and it was well tolerated.

Invasive fungal infections in autologous stem cell transplant recipients: a nation-wide study of 1188 transplanted patients

Abstract:  Based on small single‐centre series, the risk of invasive fungal infections (IFI) has been considered small in autologous stem cell transplant (ASCT) recipients. Purpose: To analyse epidemiological and clinical features of (IFI) among ASCT recipients in Finland 1990–2001. Patients: During the study period, 1188 adult patients received high‐dose therapy supported by ASCT in six centres. Altogether, 1112 patients (94%) received blood progenitor cells. The graft was CD34+ selected in 261 patients (22%). The major diagnostic groups were non‐Hodgkins lymphoma (n = 417), multiple myeloma (n = 395), breast cancer (n = 132) and Hodgkins lymphoma (n = 53). Results: Eighteen patients (1.5%) with IFI were identified. The incidence of proven or probable invasive aspergillosis was 0.8%, followed by candidaemia with an incidence of 0.3%. The median time to the diagnosis of IFI was 35 d (6–162) from the progenitor cell infusion. In fourteen patients (78%) IFI was diagnosed during lifetime and they were treated with antifungal therapy for a median of 50 d. Nine patients (64%) were cured. Conclusions: IFI appears to be a rare event after ASCT and Aspergillus infections seem to be predominant. These epidemiological features have an impact in planning prophylactic and empirical antifungal strategies in ASCT recipients.

Carbamazepine‐Induced Eosinophilic Colitis

Summary: Severe watery diarrhea and eosinophilic colitis induced by carbamazepine (CBZ) has not been described previously. We report the first known case of CBZ‐induced watery diarrhea and eosinophilic colitis in a 57‐year‐old man receiving CBZ for secondarily generalized tonic‐clonic seizures that developed after a cerebral infarction.

Magnetic resonance imaging is superior to computed tomography and ultrasonography in imaging infectious liver foci in acute leukaemia.

Abstract: We conducted a prospective study in order to compare ultrasonography, computed tomography and magnetic resonance imaging in the detection of liver foci in patients with acute leukaemia and clinical suspicion of hepatic candidiasis. 28 adult patients fulfilling set entry criteria after recovery from neutropenia were studied. Lesions in the liver were detected by at least one imaging modality in 21 patients: by ultrasonography in 7 (33% of detected cases), computed tomography in 12 (57%) and by magnetic resonance imaging in 20 patients (95%). Magnetic resonance imaging was significantly more sensitive than ultrasonography (p<0.001) and computed tomography (p<0.02). The difference between computed tomography and ultrasonography was not statistically significant (p = 0.1). Invasive procedures performed in 10 patients provided definite proof of candidiasis in 5 patients, and nodes on the liver surface, compatible with yeast infection, were seen during laparoscopy in 3 other patients without proof of fungal infection. We confirm that magnetic resonance imaging is superior to ultrasonography and computed tomography in imaging liver foci in leukaemic patients recovering from neutropenia with persistent non‐specific signs of infection or hepatic involvement.

Rifaximin in the treatment of recurrent Clostridium difficile infection

Clostridium difficile can cause severe antibiotic‐associated colitis. Conventional treatments with metronidazole and vancomycin improve symptoms, but after discontinuation of treatment, C. difficile infection (CDI) recurs in a number of patients. Rifaximin is a rifamycin‐based non‐systemic antibiotic that has effect against C. difficile.

Association between Chronic Disseminated Candidiasis in Adult Acute Leukemia and Common IL4 Promoter Haplotypes

Chronic disseminated candidiasis (CDC) is a form of Candida species infection observed primarily in patients with acute leukemia. To investigate possible genetic factors associated with CDC, we conducted a pilot study of 40 patients with both leukemia and CDC and 50 control patients with leukemia only. A common haplotype of the IL4 promoter (-1098T/-589C/-33C) was overrepresented in patients with CDC (P= .01; odds ratio [OR], 2.16), whereas another common haplotype (-1098T/-589T/-33T) appeared to be protective against CDC (P= .018; OR, 0.47). Genetic variants of IL4 could contribute to the development of CDC in patients with acute leukemia.