BACKGROUND European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. METHODS A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. RESULTS Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P < .001). CONCLUSIONS These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.

Introduction: Acinetobacter baumannii is a frequent cause of infections in hospitals around the world, which is very difficult to control and treat. It is particularly prevalent in intensive care wards. Aim: The main objective of the research was to establish the application of epidemiological monitoring of nosocomial infections (NIs) caused by A. baumannii in order to determine: the type and distribution of NIs, and to investigate antimicrobial drug resistance of A. baumannii. Material and Methods: 855 patients treated at the Clinic of Anesthesiology and Reanimation, University Clinical Center Tuzla during 2013 were followed prospectively for the development of NIs. Infections caused by A. baumannii were characterized by the anatomical site and antibiotics resistance profile. Results: NIs were registered in 105 patients (12.3%; 855/105). The predominant cause of infection was A. baumannii with an incidence of 51.4% (54/105), followed by ESBL-producing Klebsiella pneumoniae with 15.2% (16/105) of cases, methicillin-resistant Staphylococcus aureus with 8.6% (9/105), and ESBL-producing Proteus mirabilis with 7.6% (8/105). According to the anatomical site, and type of NIs caused by A. baumannii, the most frequent were respiratory infections (74.1%; 40/54). Infections of surgical sites were registered in 11.1% (6/54) of cases, while bloodstream infections in 9.2% (5/54). A. baumannii isolates tested resistant against most antibiotics examined, but showed a high degree of susceptibility to tobramycin (87%; 47/54) and colistin (100%; 54/54). Conclusion: The increasing incidence of multi- and extensively drug-resistant Acinetobacter spp. emphasizes the importance of administration of an adequate antibiotic strategy and the implementation of strict monitoring of the measures for controlling nosocomial infections.

Introduction: The finding of reduced value of immunoglobulin A (IgA) in children is frequent in daily medical practice. It is important to correctly interpret the findings as adequate further diagnostic evaluation of the patient in order to make the determination on the significance of such findings. In children younger than 4 years always consider the transient impairment of immunoglobulins, maturation of child and his immune system can lead to an improvement in the clinical picture. In older children decreased IgA may lead to serious illnesses that need to be recognize and acknowledge through the appropriate diagnostic methods. Material and methods: Research was realized at the University Clinical Center Tuzla. Children with suspected deficient immune response due to reduced values of IgA observed and, goes through further diagnostic evaluation at the Polyclinic for Laboratory Medicine, Department of Immunology and Department of Microbiology, as well as the Clinic of Radiology. In the period of year 2013, there were a total of 91 patients with reduced values of IgA, age up to 13 years, of which 55 boys and 36 girls. Results: Our study followed 91 patients, for the year 2013, through their medical charts and made evaluation of diagnostic and screening tests. The significance of this paper is to draw attention to the importance of diagnostic approach to IgA deficient pediatric patient and relevance of knowledge of individual diagnostic methods as well as to the proper interpretation of the results thereof.

Introduction: The finding of reduced value of immunoglobulin A (IgA) in children is frequent in daily medical practice. It is important to correctly interpret the findings as adequate further diagnostic evaluation of the patient in order to make the determination on the significance of such findings. In children younger than 4 years always consider the transient impairment of immunoglobulins, maturation of child and his immune system can lead to an improvement in the clinical picture. In older children decreased IgA may lead to serious illnesses that need to be recognize and acknowledge through the appropriate diagnostic methods. At the University Clinical Center Tuzla, children with suspected deficient immune response due to reduced values of IgA, goes through further diagnostic evaluation at the Polyclinic for Laboratory Medicine, Department of Immunology and Department of Microbiology, as well as the Clinic of Radiology. Material and methods: Our study followed 91 patients, for the year 2013, through their medical charts and made evaluation of diagnostic and screening tests. Conclusion: The significance of this paper is to draw attention to the importance of diagnostic approach to IgA deficient pediatric patient and relevance of knowledge of individual diagnostic methods as well as to the proper interpretation of the results thereof.

Introduction: Intensive care units (ICUs) are associated with a greater risk of developing nosocomial infections (NIs) than other departments. Aim: The aim of this study was to determine the rate, the site and causative organisms of NIs in the surgical ICU at University Clinical Center Tuzla. Methods: All patients admitted to the surgical ICU were followed prospectively, for the development of NIs (January-December 2010). Determination of NIs was performed using standardized the Centers for Disease Control and Prevention (CDC) criteria. Results: 94 out of 834 patients (11.27%) developed NIs. Respiratory tract infections were seen in 56 (60%), urinary tract infections in 15 (16%) and gastrointestinal tract infections in 8 (9%) patients. Other infections identified were surgical site, bloodstream and skin infections. Gram-negative organisms were reported in approximately 75% of cases (78.7% extended-spectrum beta-lactamase (ESBL)-producers). Klebsiella pneumoniae was the commonest (51.0%), followed by Proteus mirabilis (21.3%) and Pseudomonas aeruginosa (10.6%). Methicillin-resistant Staphylococcus aureus (MRSA) (16%), and Clostridium difficile (9.6%) were the commonest among gram-positive bacteria. Conclusion: Respiratory and urinary tract infections made up the great majority of NIs. ICU patients are more susceptible to NIs, emphasizing the importance of continuous surveillance and enforcement of specific infection control measures.

AIM To determine the prevalence and antimicrobial resistance of dominant causes of urinary tract infections (UTI) in patients treated at the Clinic for Infectious Diseases, University Clinical Center Tuzla during the period January 2010 to June 2011. METHODS This prospective study included 438 patients divided into three groups: hospital-treated patients group (H-T), outpatient- treated group (O-T) and patients with hospital-acquired (H-A) UTI. Identification of UTI causes completed using standard microbiological methods; antimicrobial susceptibility was done by disc-diffusion method according to the CLSI. RESULTS E. coli was significantly more commonly isolated in females H-T, 111 (68-1%) (p=0.012) and O-T, 148 (82.7%) (p=0.006) groups, as well as in females less than 65 years from the H-T, 87 (84.5%) (p=0.000) and H-A, four (40%) (p=0.044) groups. Klebsiella pneumoniae and Pseudomonas aeruginosa were significantly more commonly isolated in male H-T, 11 (29.7%) (p=0.000) and five (13.5%) (p=0.009), and O-T UTI, two (9.5%) (p=0.009) and three (14.3%) (p=0.000) groups. E. coli showed significantly higher prevalence of resistance to amoxycillin, coamoxiclav, cefuroxime, ceftriaxone, gentamicin and co-trimoxazole in the H-A group comparing to other two groups (p less than 0.05), as well as to ampicillin, amoxycillin and cefixime in the O-T comparing to H-T group (p less than 0.05). CONCLUSION Empirical antimicrobial therapy should include coamoxiclav, nitrofurantoin, cefepime, and ceftazidime for females less than 65 years old in both H-T and H-A, cefalosporines, co-amoxiclav and nitrofurantoin in O-T UTIs; for females more than 65 years old, cefalosporines, aminoglicosides, and ciprofloxacin, in H-T and O-T UTIs. For H-A UTI in females more than 65 years as well as for all male patients antimicrobial susceptibility testing should be performed.

Objective – Outbreaks of sepsis caused by multidrug-resistant Acinetobacter baumannii in neonatal intensive care units have been reported, but rarely from our country. We describe such an outbreak in the Department of Paediatrics of the University Clinical Centre Tuzla in 2012 to investigate risk factors, the mode of transmission and to assess control measures. Setting – An 18 bed, level 3 neonatal intensive care unit in a university affiliated teaching hospital. Patients and methods – Seventeen neonates who developed multidrug-resistant Acinetobacter baumannii nosocomial infection were matched to 17 neonates who were admitted to the same unit without infections, during the outbreak period. Cases and controls were compared for possible risk factors (birth weight, gender, intubation, antibiotic use, etc.). Surveillance cultures were collected from health care personnel and the environment. Results – Six out of the 17 neonates (35.3%) died. Surveillance cultures were negative. Seventeen isolates from newborns had the same patterns of resistance. Multidrug-resistant Acinetobacter baumannii was brought into the unit by an infected infant who was transferred from the neurosurgery hospital. Risk factors significantly associated with the infection were: incubator care (OR 6.66; p =0.034), exposure to a central venous catheter (OR 13.75; p=0.004), mechanical ventilation (OR 5.25;p =0.031) and exposure to a patient with Acinetobacter baumannii infection (OR 38.40; p =0.02). Conclusion – Surveillance cultures for all newborns transferred from other hospitals and isolation measures are important to prevent nosocomial infections and outbreak. Negative environmental and health care worker cultures have to be meticulously analyzed. Cohorting of affected newborns and nursing staff, contact isolation, and environmental cleaning are crucial to control the outbreak.

OBJECTIVE This study is to define the statistical significance for detection of ESBL producers by the double disk synergy test and molecular test (Check-MDR CT102), microdilution test (VITEK 2 with AES) and double disk synergy test (DDST), as well as the microdilution test and molecular test. MATERIALS AND METHODS Phenotypic testing of 55 isolates Enterobacteriaceae (Escherichia coli (14/55), Klebsiella pneumoniae (34/55), Klebsiella oxytoca (3/55) and Proteus mirabilis (4/55) was performed by VITEK 2 Compact/AES. When this test showed positive results for the ESBL phenotype, then DDST with amoxicillin/clavulanate, ceftazidime, cefpodoxime, aztreonam, ceftriaxone and cefoxitin disks was performed along with Check-MDR CT102 which identified CTX-M, TEM and SHV β-lactamases. RESULTS Applying the McNemar test, we determined that there was a statistically significant difference in the results of detection of ESBLs bacteria using DDST compared to molecular methods (95% CI=41.92 to 54.55; p<0.0001), as well as a DDST and VITEK 2/AES (95% CI=40.13 to 52.73; p<0.0001). We did not find any statistically significant difference in the results of detection of ESBL producers using molecular techniques and VITEK 2/AES (CI=-4,43 to 5,36; p=1). Also we did not find any statistical.. difference between the resistance to cefpodoxime and ceftriaxone (50/50) compared to the results of molecular tests. CONCLUSION In routine daily testing, good detection of ESBLs bacteria, especially CTX-M can be obtained with phenotypic methods with VITEK 2/AES and by DDST with cefpodoxime, and ceftriaksone disks.

Introduction: Clostridium difficile (C. difficile) is currently the leading cause of healthcare-associated diarrhea, but almost nothing is known about the extent of C. difficile infection (CDI) in Bosnia and Herzegovina. Goal: We aimed to retrospectively analyze CDI in hospitalized patients at University Clinical Center (UCC) Tuzla, Bosnia and Herzegovina from January 2009 through June 2012. Methods: We analyzed all patients (except children ages 0-2), diagnosed with CDI based on anamnestic and epidemiological, clinical picture and microbiological tests (proof of toxins in the stool by enzyme-linked immunosorbent assay). Results: From a total of 989 patients tested for C. difficile toxin (60.2 per 10,000 inpatient days) 347 (35.08%) were positives. The mean incidence rate of CDI was 2.23 per 10,000 inpatient days (range 1.32-2.87). Annual rates of hospitalization were 15.68 per 10,000 admissions (range 8.99-20.35). Most patients had a previously identified risk profile of old age, comorbidity and recent use of antibiotics. 41/276 (14.86%) patients had died, and 11/41 (26.82%) were CDI-associated deaths. Complicated CDI were registered in 53/276 (19.21%) patients, and recurrent infections in 65/276 (23.55%). Conclusion: Our data suggest that CDI is largely present in our setting which represents a serious problem and points to the importance of international surveillance, detection and control of CDI.

Candidiasis is defined as an infection or disease caused by a fungus of the genus Candida. Rate of disseminated candidiasis increases with the growth of the number of immunocompromised patients. In the the last few decades the incidence of disseminated candidiasis is in growth as well as the mortality rate. The aim of this survey is to show the importance of serological tests implementation in disseminated candidiasis diagnose. This is a prospective study involving 60 patients with malign diseases with and without clinical signs of disseminated candidiasis and 30 healthy people who represent the control group. Apart from hemoculture, detection of circulating mannan antigen and adequate antibodies of Candida species applying comercial ELISA test was determined in each patient. This survey deals with relevant factors causing disseminated candidiasis. This survey showed that the group of patients with clinical signs of disseminated candidiasis had more patients with positive hemoculture to Candida species, then the group of patients without clinical signs of disseminated candidiasis. The number of patients being examined and positive to antigens and antibodies was higher (p < 0.01) in the group of patients with clinical signs of disseminated candidiasis (7/30; 23.3%), then in the group of patients without clinical signs of disseminated candidiasis (0/30; 0%): Average value of titra antigen was statistically higher (p < 0.001) in patients with Candida spp. positive hemocultures rather then in patients with Candida spp. negative hemocultures. In the group of patients with clinical signs of disseminated candidiasis 6/30 (20%) of patients had Candida spp.positive hemocultures while in the group of patients without clinical signs of disseminated candidiasis 1/30 (3.3%) of patients had Candida spp. positive hemocultures, which was considerably higher (p < 0.05). Correlation of results of hemoculture and mannan antigens and antibodies in patients with disseminated candidiasis were statistically significant, while correlation of results of hemoculture and antibodies was insignificant. Because of low sensitivity of hemoculture and time needed for isolation of Candida spp., introducing serological tests in regular procedures would speed disseminated candidiasis diagnose.

INTRODUCTION The prevalence of human brucellosis in Bosnia and Herzegovina and the Tuzla Canton reached its peak in 2008, with a reported total of 994 cases within country, and with 104 cases within the Tuzla Canton. AIM to analyze the clinical and epidemiological features of human brucellosis in patients hospitalized at the University Clinical Center Tuzla during the period from 01/01/2000 till the 31/12/2010. METHODS We retrospectively analyzed the clinical symptoms, the laboratory and X-ray findings, the treatments, and the course and outcome of the disease. The diagnosis of brucellosis was based on anamnesis, clinical presentation, in correlation with a positive blood-culture, and/or serological tests. RESULTS The majority of patients (93.18%) were from rural regions. There were more males (79.54%) than females. Most of the patients were aged between 30 to 39 years (21% cases). Contact with infected animals was registered for 83.40% of the patients. The main symptoms and signs were fever, joint-pains, night sweating, anorexia, headaches, and hepatosplenomegaly. The important laboratory findings were increased erythrocyte sedimentation rates, increased values of C-reactive protein, and anemia. Adult patients were treated with a combination of gentamicin or streptomycin with doxycycline, and the children with a combination of gentamicin, and trimethoprim-sulfametaxasol, over at least 6 weeks. Complications were documented in 20.45% of the patients. Relapses were observed in 14.20%, and a chronic form of brucellosis in 5.11% of patients. There were no cases with lethal outcomes. CONCLUSION Brucellosis is a growing public health problem, not only within the Tuzla Canton, but throughout Bosnia and Herzegovina.

UNLABELLED The use of central venous catheters (CVC) carries a risk from local and systemic infectious complications, with prevalence of 6% in patients in Intensive care unit. Microorganisms colonizing the CVC usually originate from patient's or staff member's skin, but the source can also be a contaminated infusion solution or hematogenous dissemination from a distant focus. The infective agents often show increased resistance to antibiotics, which is an additional therapeutic problem. There is no knowledge of the frequency of the colonization of CVC by microorganisms in hospitals in Bosnia and Herzegovina, neither of the types of microorganisms which usually colonize CVC, nor their sensitivity to antimicrobial agents. METHODS During the period 2004-2008, the analysis of 188 CVC samples was performed in patients in ICU at which the doubt for CVC connected infection was present. The microorganism identification was performed by standard microbiological antibiotics sensitivity methods. RESULTS Out of 188 checked samples, 101 (54%) had positive cultures and 87 (46%) were sterile. Out of 101 positive microbiological cultures, in 33 (32.67%) the gram-positive bacteria had been found, gram-negative in 62 (61.37%) and Candida albicans in 6 (5.94%) cultures. Gram-ne-gative bacteria were 93.55% sensitive to imipenem, and Gram-positive bacteria were sensitive to vancomycin. CONCLUSION Gram-negative bacilli and Coagulase-negative staphylococci are the most frequent micro-organisms which colonize the CVC. The increase of bacteria antibiotics resistance represents a big problem. All those facts leads to the need for bigger control and supervision over the CVC implantation, its proper maintenance and rational use.

Prevalence of hepatitis C virus (HCV) genotypes in Bosnia and Herzegovina (B&H) is an issue that is not sufficiently researched and there is a need for studies that would explore this in detail.The aim of this study was to determine the distribution of HCV genotypes in the group of patients with chronic hepatitis C and also in the group of first time blood donors that tested positive for anti HCV antibodies during the blood screening process. Our secondary goal was to compare the proportions of HCV genotypes between these two groups.We analyzed 75 blood samples of patients with confirmed chronic hepatitis C. We also analyzed 13/16082 blood samples of first time blood donors found to be HCV positive during the blood screening process. We also determined HCV genotype in HCV RNA positive samples.We have found that genotype 1b was more prevalent in chronic hepatitis C patients (52/75; 69,3%) than in first time blood donors (6/13; 46,1%), however this difference was not statistically significant (c2=1,721; df=1; p=0,19). Genotype 1a was more prevalent in the group of first time blood donors (3/13; 23,1%) than in the group of chronic hepatitis C patients (3/75; 4%), but this was also with limited statistical significance (c2=3,71; df=1; p=0,054). We have not found any significant difference in prevalence of genotypes 1a (p=0,2) and genotypes 3 (p=0,70) when compared between chronic patients (3/75 and 16/75; respectively) and first time blood donors (3/13 and 4/13; respectively). Our study confirmed domination of genotype 1b in the region of northeastern B&H which is in accordance with HCV genotype prevalence in other countries in our part of Europe.