CLOSTRIDIUM DIFFICILE INFECTIONS IN PATIENTS WITH HEMATOLOGICAL MALIGNANCY IN CZECH AND SLOVAK REPUBLIC – A RETROSPECTIVE ANALYSIS

ABSSUB-4683

Background: Clostridium difficile infections (CDI) with associated diarrhea represent an important cause of morbidity and mortality. Despite its importance, there is still lack of data about this infection in the group of hematological patients.

Aims: To analyze the risk factors, clinical manifestation, treatment and its outcome in this high risk patients group.

Methods: We performed a retrospective analysis of CDI episodes in 4 hematological centers in Czech and Slovak Republic occurred between 1/2007 and 12/2012. CDI was defined as a diarrhea and/or ileus and/or toxic megacolon and microbiological evidence of toxin-producing Clostridium difficile in stool without evidence of another cause of these symptoms. Pts. with targeted antibiotic therapy shorter than 3 days were excluded from analysis of treatment outcome. Recurrence was defined as reappearance of diarrhea and other symptoms within 1 month after therapy.

Results: 208 episodes that occurred in 193 pts. were analyzed (male 38.5%, female 61.5%, mean age 57.3 years [18 - 88] years,). 76 pts. (36.5%) received induction/consolidation therapy for acute leukemia, 26 pts. (12.5%) underwent allogeneic stem cell transplantation (SCT) and 21 pts. (10%) autologous transplantation before CDI onset. Neutropenia was present in 102 pts. (49%) and 82 pts. (39.5%) had neutropenia grade 3 and 4 CTCAE 4.0. Before CDI onset, 132 pts. (63.5%) had antibiotic therapy (prophylactic or curative for another infection) - 23% quinolones, 11% penicillins, 19% cephalosporins, 46% combination, 1% others. 24 pts. (11.5%) were on parenteral nutrition. 49% of all episodes fulfilled criteria for severe CDI and 51% were mild/moderate CDI episodes. In pts. without neutropenia were 42.8% severe CDI, with neutropenia gr. 3 and 4 were 58.5% severe CDI and in pts. after SCT were 34.5% severe CDI.

Initial therapy for CDI was: oral metronidazole 77%; intravenous metronidazole 4.8%; oral and intravenous metronidazole 1.4%; oral vancomycin 0.5%; intravenous vancomycin 2.4%; oral metronidazole and oral vancomycin 4.3%; oral metronidazole and intravenous vancomycin 4.3%; intravenous metronidazole and oral vancomycin 3.3%; intravenous metronidazole and intravenous vancomycin 2%. Colectomy was necessary in one case. Time to initial response was 6 days (mean). Overall cure rate was 92% and recurrence rate 8.3%. For oral metronidazole cure rate was 95% and recurrence rate 7.9% and for intravenous metronidazole 80% and 0%, respectively. Overall cure rate in pts. with neutropenia was 87.8% and recurrence rate 8.3%. In non-neutropenic pts. cure rate was 95.2% and recurrence rate 8.3%. In the group of pts. after allogeneic SCT was cure rate 96.1% and recurrence rate 4%.

Summary/Conclusion: Our study proved severe morbidity of CDI in pts. with hematological malignancy, where half of episodes were severe infections. Surprisingly, the overall cure rate using standard therapy (metronidazole +/- vancomycin) and frequency of recurrence was similar to non-hematological populations.

Supported by Masaryk University MUNI/A/0830/2013, supported by CELL, supported by unrestricted grant of Astellas ltd.

Keywords: Hematological malignancy