IP-10 Levels in Patients Infected with HBV Predicts The Response to Treatment with Entecavir.

Interferon--inducible protein-10 (IP-10), is an inflammatory cytokine produced by different subsets of the immune cells and induces chemotaxis, apoptosis, growth of cells and angiostasis after binding to its receptor CXCR3. Inflammatory disorders, involving infectious diseases, immune dysfunction, and tumour growth have been linked to changes in CXCL10 levels. We aimed to investigate serum levels of IP-10 in chronic HBV infected patients undergoing treatment with entecavir and possible correlation with response to therapy. A total of 53 chronic HBV infected patients and 25 healthy controls were enrolled in this study. Patients included 20 with cirrhosis and 33 non-cirrhotic individuals. All patients received 0.5 mg/day entecavir and serum IP-10 level was determined by ELISA at baseline and at week 24 of treatment. mRNA expression of CXCR3 of PBMC was assessed by real-time polymerase chain reaction (RT-PCR). Response to therapy was achieved in 27/33 (81.8%) non-cirrhotic and 14/20 (70%) cirrhotic patients. Mean serum IP-10 levels was higher in patients than healthy controls, and cirrhotic patients had higher IP-10 than non-cirrhotic patients (520 vs 293.5 pg/ml; P<0.005). Response to treatment was associated with decreased IP-10 levels. Before treatment, the mean level in non-cirrhotic patients was 235±54 pg/ml, which decreased to 95±34 pg/ml (P<0.005) at week 24 of treatment. Similarly, in the cirrhotic group, IP-10 decreased from 458±42 pg/ml to 354±25 pg/ml (P <0.05) after 24 weeks of treatment. On the other hand, no change in IP-10 levels was observed for patients who did not respond to treatment. Interestingly, IP-10 levels correlated with PBMC's expression of CXCR3 mRNA (r= 0.448, P = 0.004), ALT level (r=0.273, P =0.048), liver fibrosis score 4 (FIB-4) (r=0.664, P = 0.01) and HBV DNA level (r=0.762, P =0.0001). In conclusion; IP10 may be used to predict response to therapy in HBV-infected patients.

Nosocomial blood stream infection in intensive care units at Assiut University Hospitals (Upper Egypt) with special reference to extended spectrum beta-lactamase producing organisms.

AIM: This study investigated the nosocomial blood stream infection (BSI) in the adult ICUs in Assiut university hospitals to evaluate the rate of infection in different ICUs, causative microorganisms, antimicrobial resistance, outcome of infection, risk factors, prevalence of extended spectrum B-lactamase producing organisms and molecular typing of Klebsiella pneumoniae strains to highlight the role of environment as a potential source of nosocomial BSI. METHODS: This study was conducted over a period of 12 months from January 2006 to December 2006. All Patients admitted to the different adult ICUs were monitored daily by attending physicians for subsequent development of nosocomial BSI. Blood cultures were collected from suspected patients to detect the causative organisms. After antimicrobial susceptibility testing, detection of ESBLs was conducted among gram negative isolates. Klebsiella pneumoniae isolates were tested by PCR to determine the most common group of B-lactamase genes responsible for resistance. Klebsiella pneumoniae isolates from infected patients and those isolated from the environment were typed by RAPD technique to investigate the role of environment in transmission of infection. RESULTS: The study included 2095 patients who were admitted to different ICUs at Assiut University Hospitals from January 2006 to December 2006. Blood samples were collected from infected patients for blood cultures. The colonies were identified and antibiotic sensitivities were performed. This study showed that the rate of nosocomial BSI was 75 per 1000 ICU admissions with the highest percentages in Trauma ICU (17%). Out of 159 patients with primary bloodstream infection, 61 patients died representing a crude mortality rate of 38%. Analysis of the organisms causing BSI showed that Gram positive organisms were reported in 69.1% (n = 121); MRSA was the most prevalent (18.9%), followed by methicillin resistant coagulase negative Staphylococci (16%). Gram negative bacilli were reported in 29.1% (n = 51). In this case, Klebsiella pneumoniae was the most common (10.3%) followed E coli (8.6%). Candida spp. was reported only in (1.7%) of isolates. Antibiotics sensitivities of Gram positive organisms showed that these organisms were mostly sensitive to vancomycin (90.1%), while Gram negative organisms were mostly sensitive to imipenem (90.2%). In this study we tested Gram negative isolates for the production of the ESBL enzyme and concluded that 64.7% (33/51) of patients' isolates and 20/135 (14.8%) environmental isolates were confirmed to be ESBL producers. The type of beta-lactamase gene was determined by polymerase chain reaction which showed that SHV was the main type. Molecular typing was done for 18 Klebsiella pneumoniae strains that caused nosocomial BSI and for the 36 Klebsiella pneumoniae strains which were isolated from the environmental samples by the RAPD method. The two environmental strains were identical, with one isolated from a patient, which confirms the serious role of the hospital environment in the spread of infections. CONCLUSION: Nosocomial BSI represents a current problem in Assiut University Hospitals, Egypt. Problems associated with BSI include infection with multidrug resistant pathogens (especially ESBLs) which are difficult to treat and are associated with increased mortality. Of all available anti-microbial agents, carbapenems are the most active and reliable treatment options for infections caused by ESBL isolates. However, overuse of carbapenems may lead to resistance of other Gram-negative organisms.