The Magnitude of Carbapenemase and ESBL Producing Enterobacteriaceae Isolates from Patients with Urinary Tract Infections at Tikur Anbessa Specialized Teaching Hospital, Addis Ababa, Ethiopia.

BACKGROUND: The emergence of multidrug-resistant organisms, such as extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), and carbapenemase-producing Enterobacteriaceae (CPE) is a public health concern. Therefore, this study aimed to determine the magnitude of carbapenemase and ESBL producing bacteria isolated from patients affected by Urinary Tract Infection (UTI). METHODS: A cross-sectional study was conducted from December 2018 to March 2019 at Tikur Anbessa Specialized Hospital. A total of 120 Enterobacteriaceae isolates from UTI patients were collected and identified on species level using standard microbiological methods. Antimicrobial susceptibility test was determined according to the guidelines of the Clinical and Laboratory Standards Institute. Detection of ESBL production was carried out by using ESBL ChromoSelect Agar medium and the combined disk diffusion. Production of carbapenemase was determined by using Hodge-test and modified carbapenem inactivation method as described in CLSI guidelines. RESULTS: Out of the total 120 Enterobacteriaceae isolates, 74 (61.7%) were ESBL-producers, and 8 (6.7%) were carbapenemase producers. The most common ESBL producing isolate was E.coli 38 (51.4%) and the most common carbapenemase-producing isolate was K.pneumoniae five (62.5%). Most of the ESBL and carbapenemase-producing isolates were recovered from hospitalized patients 46 (62.2%) and 7 (87.5%) respectively. The rate of ESBL and CPE production was observed high among patients taking antibiotics 64.8% (59/91) and 7.7% (7/91) respectively, but no significant association was observed p > 0.05. Furthermore, about 1.7% (2/120) isolates were found both ESBL and carbapenemase producers. Significant resistances rates were observed in ESBL and CPE isolates. CONCLUSION: Enterobacteriaceae isolates showed a significantly higher rate of ESBL production. A significant figure of carbapenemase production was observed among Enterobacteriaceae isolates causing UTI. The production of ESBL and CPE enhanced for an increased rate of MDR patterns. Efforts need to be made to introduce a system for tracking and detecting ESBL-PE and CPE-producing bacteria in hospitals, and monitoring dissemination of ESBL and CPE-producing Enterobacteriaceae is strongly recommended.

Systemic FasL and TRAIL neutralisation reduce leishmaniasis induced skin ulceration.

Cutaneous leishmaniasis (CL) is caused by Leishmania infection of dermal macrophages and is associated with chronic inflammation of the skin. L. aethiopica infection displays two clinical manifestations, firstly ulcerative disease, correlated to a relatively low parasite load in the skin, and secondly non-ulcerative disease in which massive parasite infiltration of the dermis occurs in the absence of ulceration of epidermis. Skin ulceration is linked to a vigorous local inflammatory response within the skin towards infected macrophages. Fas ligand (FasL) and Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expressing cells are present in dermis in ulcerative CL and both death ligands cause apoptosis of keratinocytes in the context of Leishmania infection. In the present report we show a differential expression of FasL and TRAIL in ulcerative and non-ulcerative disease caused by L. aethiopica. In vitro experiments confirmed direct FasL- and TRAIL-induced killing of human keratinocytes in the context of Leishmania-induced inflammatory microenvironment. Systemic neutralisation of FasL and TRAIL reduced ulceration in a model of murine Leishmania infection with no effect on parasitic loads or dissemination. Interestingly, FasL neutralisation reduced neutrophil infiltration into the skin during established infection, suggesting an additional proinflammatory role of FasL in addition to direct keratinocyte killing in the context of parasite-induced skin inflammation. FasL signalling resulting in recruitment of activated neutrophils into dermis may lead to destruction of the basal membrane and thus allow direct FasL mediated killing of exposed keratinocytes in vivo. Based on our results we suggest that therapeutic inhibition of FasL and TRAIL could limit skin pathology during CL.