Antibiotic utility and susceptibility changes of multidrug-resistant Escherichia coli and Klebsiella spp: 5-year experience in a tertiary healthcare centre.

OBJECTIVES: Multiple studies have identified cross-sectional relationships between antibiotic use and bacterial resistance. The aim of this study was to analyse the susceptibility of multidrug-resistant (MDR) and non-MDR (nMDR) isolates of Escherichia coli and Klebsiella spp to cephalosporins: ceftazidime (CTZ), ceftriaxone (CTX), cefepime (CEF) and fluoroquinolones: ciprofloxacin (CIP) and levofloxacin (LEV) in a tertiary healthcare centre from 2014 to 2018. In addition, we aimed to evaluate a correlation between the antibiotic utility and susceptibility of the selected enterobacteria. METHODS: Antibiotics consumption and antimicrobial resistance were monitored in a tertiary care university hospital from 2014 to 2018. Utilisation of antibiotics in the observed period was expressed as defined daily dose (DDD) per 100 bed/days (DBD). Bacterial susceptibility was reported as the percentage of susceptible results among all tested isolates from all patient samples. In further analysis, bacterial strains were considered as MDR or nMDR species. An MDR bacterial strain was defined as one with acquired non-susceptibility to at least one agent in three or more antimicrobial categories. RESULTS: Our results suggest that cephalosporins were the most used antibiotics, followed by fluoroquinolones, during the entire observed period 2014-2018. Our findings show that MDR isolates of E. coli had an increasing trend in susceptibility in relation to CTX (p=0.005), whereas a decreasing trend was observed for MDR isolates of E. coli susceptibility towards CIP and LEV (p<0.001). Klebsiella spp susceptibility for MDR isolates showed a decreasing trend in relation to CEF (p<0.001) and both fluoroquinolones (p<0.001). A significant negative association between CEF consumption and Klebsiella spp MDR isolates susceptibility was observed (p=0.045). CONCLUSION: Implementation of antimicrobial stewardship programmes with early detection and close monitoring of MDR bacterial strains of E. coli and Klebsiella spp may be a crucial step in reducing the menace of antimicrobial resistance, which is now a global problem.

The Impact of Hepatitis C Virus Genotypes on Oxidative Stress Markers and Catalase Activity.

Hepatitis C virus (HCV) is a major cause of liver disease worldwide. Chronic HCV infections are usually associated with increased oxidative stress in the liver tissue. The intensity of oxidative stress may be a detrimental factor in liver injury and may determine the severity of the disease. The aim of the present case-control study was to determine the level of lipid peroxidation (TBARS), protein oxidative modification (AOPP), and catalase activity in sera of patients infected with HCV, in relation to different HCV genotypes and viral load. Considering the HCV patients with chronic hepatitis C (52) and control subject (50) recruitment, the study was designed as a case-control-type. The HCV RNA isolation, viral load, and HCV genotyping were performed according to the standard protocols. A significant difference compared to control healthy subjects was reported for TBAR (p < 0.001), AOPP (p = 0.001), and catalase activity (p = 0.007). In a gender-based comparison, a significantly higher level of AOPP for females was reported (p < 0.001). As stratified by HCV genotype, the most common was HCV-1 (HCV-1a and HCV 1b), with the overall participation of more than 60%, followed by genotype 3, while the least represented was genotype 2. No significant difference was documented among genotypes in regard to oxidative stress markers, although somewhat higher TBARS level, but not significant, was registered in patients infected with genotype 1b. A statistically significant positive correlation was found between the concentration of HCV genome copies and AOPP (r = 0.344; p = 0.012). A high level of HCV viral load was more likely to have a higher TBARS, but still without statistical significance (p = 0.072). In conclusion, the results obtained confirmed an imbalance between the ROS production and antioxidative defense system in HCV-infected patients. Since oxidative stress may have a profound influence on disease progression, fibrosis, and carcinogenesis, our results may meet the aspirations of mandatory introduction of antioxidants as early HCV therapy to counteract ROS consequences.

SUSCEPTIBILITY OF RESPIRATORY ISOLATES OF STREPTOCOCCUS PNEUMONIAE ISOLATED FROM CHILDREN HOSPITALIZED IN THE CLINICAL CENTER NIS.

INTRODUCTION: Streptococcus pneumoniae is one of the most common causes of respiratory infections. The aim was to study the susceptibility to antimicrobial agents of respiratory isolates ofStreptococcus pneumoniae obtained from hospitalized children. MATERIAL AND METHODS: A total of 190 respiratory pneumococcal isolates obtained from children aged from 0 to 14 years were isolated and identified by using standard microbiological methods. Susceptibility to oxacillin, erythromycin, clindamycin, tetracycline, cotrimoxazole, ofloxacin and rifampicin was tested by disc diffusion method. Minimal inhibitory concentrations for amoxicillin and ceftriaxone were determined by means of E test. The macrolide-resistant phenotype was detected by double disc diffusion test. RESULTS: All tested isolates were susceptible to amoxicillin and ceftriaxone. The minimal amoxicillin concentration inhibiting the growth of 50% of isolates and of 90% of isolates was 0.50 microg/ml and 1.0 microg/ml, respectively and the minimal ceftriaxone concentration inhibiting the growth of 50% of isolates and of 90% of isolates was 0.25 microg/ml and 0.50 microg/ml, respectively. Susceptibility to erythromycin and clindamycin was observed in 21.6% and 29.47% of isolates, respectively. The resistence to macrolides-M phenotype was detected in 10.07% of isolates and constitutive macrolide-lincosamide-streptogramin phenotype (constitutive MLS phenotype) was found in 89.93% of isolates. All tested isolates were susceptible to ofloxacin and rifampicin. CONCLUSION: Amoxicillin could be the therapy of choice in pediatric practice. The macrolides should not be recommended for the empirical therapy of pneumococcal respiratory tract infection in our local area.

Listeria monocytogenes meningitis in an immunocompetent 18-year-old patient as a possible diagnostic and therapeutical problem.

INTRODUCTION: Listeria monoytogenes is the third most frequent cause of bacterial meningitis in adults. It commonly affects persons with defective cell-mediated immunity or advanced age, and only a few patiens with no underlying predisposition have been reported. CASE REPORT: We presented an previously healthy, 18-year-old man with typical clinical features of meningitis. On the account of earlier treatment with ceftriaxone and cerebrospinal fluid finding, an assumption of partially treated bacterial meningitis was made. The initial treatment with vancomycin and ceftriaxone, substituted on day 4 with meropenem, did not produce any clinical effect. On day 6 Listeria monocytogenes was isolated and, even as late as that, the administration of ampicillin was followed by complete recovery of the patient. CONCLUSION: In younger, immunocompetent individuals, in spite of the existent diagnostic and therapeutic problems, the subacute course of Listeria monocytogenes meningitis provides enough time for appropriate treatment and favorable disease outcome.

Serum anti-Helicobacter pylori IgA and IgG antibodies in asymptomatic children in Serbia.

The aim of this study was to determine the seroprevalence of Helicobacter pylori and the distribution of anti-H.pylori IgA and IgG antibodies in asymptomatic children aged between 7 and 18 y. We studied the serum samples of 283 children using the commercial ELISA test for the detection of anti-H. pylori IgA and IgG antibodies. The overall prevalence of anti-H. pylori antibodies was 36.4%. The seroprevalence was 35%, 28.3%, 37.5%, and 42.2% for the ages of 7, 10, 14 and 18 y, respectively. Serum IgG antibodies alone were detected in 88.3%, IgA alone in 4.9%, and both IgA and IgG antibodies were detected in 6.8% of samples. The mean levels of IgG antibodies to H. pylori increased with age. We concluded that the prevalence of H. pylori antibodies in Serbian children was high (36.4%), ranging from 35% to 42.2%. The detection of IgG antibodies is useful for the determination of seroprevalence in asymptomatic children.

Hepatitis C virus genotypes and the development of hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to investigate the prevalence of hepatitis C virus (HCV) infection in patients with hepatocellular carcinoma (HCC) in our geographic area, and to determine if there is a correlation between HCV genotypes and the development of HCC. METHODS: Thirty-six patients with HCV-related HCC and 35 controls with HCV-associated cirrhosis without HCC were studied. The diagnosis of HCV infection was performed by the enzyme-linked immunosorbent assay test for the detection of anti-HCV antibodies and by reverse transcription-polymerase chain reaction for the detection of HCV-RNA. HCV genotyping was performed by line probe assay-Inno-LIPA HCV II. The diagnosis of underlying disease in the patients with HCC was performed on the basis of clinical, biochemical or histological evidence. RESULTS: Genotype 1b was found in 28 (77.77%) patients with HCC, and in 16 (45.71%) controls. There was significant difference in the prevalence of genotype 1b between the patients with HCC and those with cirrhosis without HCC (P<0.05). Having analyzed the diagnosis of underlying diseases, underlying cirrhosis in 29 (80.55%) and chronic active hepatitis in 7 (19.44%) patients with HCC was found. CONCLUSION: Results of the present study suggest that there is a correlation between HCV genotype 1b and the development of HCC. Our findings also add support to the hypothesis that cirrhosis is a major step in liver carcinogenesis associated with HCV, which suggests an indirect role of HCV in the pathogenesis of HCC.

Helicobacter pylori: an underestimated factor in acute anterior uveitis and spondyloarthropathies?

Acute anterior uveitis (AAU) is the most common form of intraocular inflammation, but its aetiology is still unclear. Fifty percent of AAU patients are HLA-B27-positive, and half of these also have spondyloarthropathies (SpA). Numerous serological studies have shown elevated levels of serum antibodies to various Gram-negative bacteria in HLA-B27-positive AAU and SpA patients. Antigenic similarities between these bacteria and host components (HLA-B27) have already been shown. Still, the mechanism underlying these diseases has not been clarified. Among the Gram-negative bacteria, Helicobacter pylori has not been screened in AAU patients. The purpose of our study was to see if this common human pathogen somehow interferes with AAU. In addition Chlamydia trachomatis, Yersinia enterocolitica 03 and 09, Salmonella sp. and Proteus OX19 were also examined. A total of 60 patients consisting of 4 groups (15 patients with AAU, 15 with SpA, 15 with AAU+SpA and 15 healthy control persons) were examined. A high percentage of the serological results of all investigated bacteria was positive: 80% in the AAU, 93.3% in the SpA and 100% in the AAU+SpA group, while it amounted to 66.7% in the control group (p < 0.05). H. pylori showed the highest percentage of positivity in all 3 patient groups (66.7% in the AAU, 73.3% in the SpA and 80% in the AAU+SpA group). In contrast, 26.7% of the controls were anti-H.-pylori-positive, thus showing a statistically significant difference between the patients and the control group (p < 0.05). HLA-B27/B7-CREG positivity was detected in 53.3% of the AAU, 66.7% of the SpA and 93.3% of the AAU+SpA patients and in none of the controls. Our results suggest that H. pylori might be a candidate participating in the development of AAU and SpA. They also support the theory of genetic (HLA-B27) and exogenous factors (Gram-negative bacteria) as probable background of these diseases.