AimAcute respiratory infections caused by viral pathogens are the most common reason for hospitalization of children. Annually, 150 million infants worldwide are diagnosed with bronchiolitis, and 2-3% of them are hospitalized. This study aimed to compare bronchiolitis severity before and after the COVID-19 pandemic. MethodsThis retrospective study was conducted at the Department of Pulmonology, Paediatric Clinic, Clinical Centre University of Tuzla, covering the period from November 1st, 2018, to April th 30, 2019 (pre-COVID period) and November 1st, 2023, to April 30th, 2024 (post-COVID period). A total 129 children under the age of 2 years were involved. Results No significant differences in the age, body mass, comorbidities, duration of hospitalization, use of oxygen therapy, and mechanical ventilation was found. There was a significant reduction in antibiotic in the post-COVID group (p=0.0173), and a significant increase in the use of aminophylline and inhalation therapy drugs in the post-COVID group. There was a significantly higher number of isolated respiratory syncytial virus (RSV) cases in the post-COVID group, 32 (42.7%). prevalence of fully vaccinated children was significantly higher in the pre-COVID period compared to the post-COVID period,  34 (74.4%?) and  29 (45.3%), respectively. Conclusion This study reveals a significant increase in the severity of bronchiolitis and an increase in RSV cases after the COVID-19 pandemic. Keywords: anti-bacterial agents,coinfection, oxygen inhalation therapy,respiratory syncytial virus infections, vaccination.

Pseudomonas aeruginosa is an opportunistic pathogen that frequently causes infections in immunocompromised patients and is involved in outbreaks of hospital-acquired infections with a high mortality rate. Aminoglycosides are a large category of antibiotics that bind specifically to 16S rRNA in 30S ribosomal subunits and disturb protein translation. This antibiotic class plays a significant bactericidal role against a wide range of Gram-negative bacteria such as P. aeruginosa. Among different aminoglycoside resistance mechanisms, inactivation of drugs by plasmid-encoded aminoglycoside-modifying enzymes (AMEs) is a common determinant of aminoglycoside resistance in  P. aeruginosa. These plasmids are spread worldwide, and they are transferred to a wide range of different species. This study aims to detect resistance mechanisms and  identify the most prevalent aminoglycoside resistance genes in P. aeruginosa clinical isolates, collected from the University Clinical Centre Tuzla. This study included a total of 230 clinical P. aeruginosa isolates. Antimicrobial susceptibility tests were performed using the disk diffusion method and the Vitek2 system. Isolates displaying increased MIC values for aminoglycoside antibiotics were included in the multiplex PCR reaction, for the detection of aminoglycoside-modifying enzyme genes. The most prevalent genotype among isolates was aac (6')-I. All aac (6')-I genotyped isolates also displayed a high rate of resistance to other classes of antibiotics, and they were characterized as multidrug-resistant (MDR) or extensively drug-resistant (XDR). Results indicate that the aminoglycoside-resistance genes are highly prevalent and could easily spread among P. aeruginosa strains.

We report on an ongoing measles outbreak in the Federation of Bosnia and Herzegovina with 141 cases notified between week 52 2023 and week 6 2024. Among those with known vaccination status, 97% were unvaccinated and the most affected group is children under the age of 5 years (n = 87) who were not vaccinated during the pandemic years. Sixty-eight cases were hospitalised, the most common complications were measles-related pneumonia and diarrhoea. The sequenced measles viruses from four cases belonged to genotype D8.

Aim To evaluate Helicobacter pylori (H. pylori) resistance to clarithromycin and quinolones in patients with dyspepsia in Tuzla Canton, Bosnia and Herzegovina, a region with no data on clarithromycin or quinolones resistance. Methods A prospective cross-sectional study was conducted at the Department of Gastroenterology and Hepatology at University Clinical Centre Tuzla between January 2021 and June 2022. The study included 99 patients who underwent esophagogastroduodenoscopy (EGDS) due to dyspepsia. In all patients biopsies were taken for rapid urease test (RUT) and histology findings, concomitantly with blood samples for IgG serology. All RUT positive patient samples were tested for clarithromycin and quinolones susceptibility with GenoType HelicoDr, a PCR method which detects point mutations in 23S rRNA and mutations in the gyrA gene. Results Out of 99 dyspeptic patients, 67 (67.7%) were serologically positive to H. pylori, 46 (46.4.%) were RUT positive, and 19 (19.2 %) had a positive histology finding. Antibiotic (AB) resistance was tested in the total of 46/99 (46.4%) patients. Resistance to clarithromycin was detected in 28.26% (13/46), quinolones resistance in 36.96% (17/46) , and resistance to both AB was detected in 8.69% (4/46) tested biopsies. Conclusions Due to high clarithromycin and quinolones resistance rates, we recommend the use of bismuth quadruple or non-bismuth concomitant quadruple therapy for H. pylori eradication in Tuzla Canton, Bosnia and Herzegovina.

Aim To evaluate clinical and epidemiological characteristics and outcome of patients with COVID-19, and impact of vaccine against COVID-19 on them. Methods This retrospective study included 225 patients treated from COVID-19 in the period from 1 to 30 September 2021 at the Clinic for Infectious Diseases, University Clinical Centre Tuzla (UCC Tuzla). For the diagnosis confirmation of Covid-19, RTPCR was used. Patients were divided in two groups: fully vaccinated with two doses of vaccine, and non-vaccinated or partially vaccinated. Results Of 225 patients, 120 (53.3%) were females, and 105 (46.7%) males. Mean age was 65.6 years. There were 26 (11.6%) fully vaccinated patients. Most common symptoms in unvaccinated patients were fatigue (70.9%), cough (70.4%) and fever (69.8%), and in vaccinated fever (76.9%), fatigue (69.2%) and cough (46.2%). Cough was more common in unvaccinated patients (p=0.013). Fatal outcome happened in 84 (37.3%) patients. Transfer to the Intensive Care Unit (ICU) and older age had a higher risk of death (p<0.001). Older age patients were more likely to have comorbidities like atrial fibrillation (p=0.017), hypertension (p<001) and diabetes mellitus (p=0.002). Atrial fibrillation (p<0.001), hypertension (p<0.001), diabetes mellitus (p=0.009) and history of stroke (p=0.026), were related to fatal outcome in unvaccinated patients, also did a shorter duration of illness prior to hospitalization (p<0.001) and shorter length of hospitalization (p=0.002). Conclusion Older patients with comorbidities, as well as those who were not vaccinated against COVID-19, were at higher risk for severe form of the disease and poor outcome.

Aims: The aims of this study was to investigate the susceptibility of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae clinical isolates to antibiotics and essential oils - Origanum compactum, Origanum majorana and Thymus serpyllum. Study Design: Study included 30 isolates of Klebsiella pneumoniae obtained from clinical material provided from the University Clinical Center Tuzla. Place and Duration of Study: Department of Biology, Faculty of Science, University of Tuzla, BiH, between September 2019 to September 2020. Methodology: Antibiotic susceptibility testing was performed by the Kirby-Bauer disk diffusion method. The following commercially available antibiotic discs were used: amoxicillin (30µg), cefalexin (30 µg), gentamicin (10 µg), amikacin (30 µg), imipenem (10 µg), piperacillin (75µg), ampicilin (10 µg), meropenem (10 µg), ciprofloksacin (10 µg), ceftazidim (30 µg), cefotaksim (30 µg), ceftriaxone (30 µg), cefepime (30 µg) and aztreonam (30 µg). The antibacterial effect of the essential oils was tested for ESBL K. pneumoniae isolates using the diffusion method according to Clinical laboratory standards institute (CLSI) guidelines. Results: O. compactum and O. majorana essential oils showed the same antimicrobial activity with 80.0% effect on ESBL K. pneumoniae isolates, Thymus serpyllum EO showed antimicrobial activity of 60.0%. The lowest MIC value had the O. compactum essential oil (MIC 6 mg/ml-10.5 mg/ml), followed by the T. serpyllum (MIC 17.2 mg/ml-43 mg/ml), while the O. majorana essential oil showed MIC values in range from 11 mg/ml to 39 mg/ml. Conclusion: The results of the study showed the exceptional sensitivity of ESBL K. pneumoniae clinical isolates to the essential oils from Origanum and Thymus genera, which highly suggests their potential application in the struggle against these pathogens in the future.

Aim To characterize methicillin-resistant S. aureus (MRSA) strains phenotypically and genotypically and to determine their clonal affiliation, representation and antibiotic resistance profile. Methods A total of 62 randomly selected MRSA isolates of different clinical samples collected from 2009 to 2017 were phenotypically and genotypically analysed. Phenotypic analyses were performed by standard microbiological procedures, and using VITEK 2/AES instrument as well as MALDI-TOF (matrix-assisted laser desorption/ionization) technology. Genotypic characterization included spa, MLST (multilocus sequence typing) and SCCmec typing, and detection of the Panton-Valentine leukocidin (PVL) and other enterotoxin encoding genes. Results The largest number of isolates, 21 (33.87%) belonged to ST228-MRSA-I, spa type t041, t1003 and t001. Other major clones were: ST239-MRSA-III, spa type t037 and t030 (27.41%); ST8-MRSA-IV, spa type t008 and t121 (12.9%); ST247-MRSA-I, spa type t051 (4.83%). PVL was detected in 10 isolates (SCCmec IV/V). During 2009 and 2010 the most frequent MRSA strain was South German clone, ST228-MRSA-I (80% and 90%, respectively), while in later years it was replaced with Brazilian-Hungarian clone ST239-MRSA-III (75% in 2015 and 2016). The South German clone, spa type t041 in 90.48% of cases was resistant to clindamycin, ciprofloxacin, erythromycin, cefoxitin, gentamicin, kanamycin, tobramycin and penicillin, while 70.58% samples of the Brazilian-Hungarian clone spa type t037 were additionally resistant to tetracycline and rifampicin. Conclusion This research can supplement the existing knowledge about the clonal distribution of MRSA in Bosnia and Herzegovina and their sensitivity to antibiotics in order to improve the national control of these infections.

Whole Genome Sequence of four samples from COVID-19 outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, England). The constructed phylogenetic tree indicates probable multiple independent introduction events. The success of future containment measures concernig new introductions will be highly challenging for country due to the significant proportion of BH population living abroad.

Aim To present combined measles cases data and phylogenetic analysis of the virus circulated in 2018 in the Federation of Bosnia and Herzegovina (FB&H, the entity of Bosnia and Herzegovina), in order to analyse endemic transmission patterns of circulating strains and its implications for elimination efforts. Methods The data were derived from epidemiological case investigations and laboratory diagnoses based on serology, molecular detection and genotyping of the measles virus. Results During 2018 16 measles cases were reported in FB&H, of which five were classified as laboratory confirmed cases, one was an epidemiologically linked case and 10 were clinically compatible cases. Among them 12 (75.00%) cases were unvaccinated or had unknown vaccination status. The most affected population was up to 14 years of age (13/16; 81.25%). None of the cases was fully vaccinated. Viruses of other genetic lineages had been introduced in FB&H in the recent period. Two virus lineages of genotype B3 were identified. Phylogenetic analysis indicated the presence of a unique sequence of measles B3 virus in FB&H (Sarajevo). Conclusion Further strengthening of measles surveillance system and renewed efforts to increase vaccination levels are necessary to prevent disease and for elimination setting.

Objectives: To assess the prognostic value of pentraxin 3 (PTX3) in patients with ST-elevation myocardial infarction (STEMI) after bare-metal stent (BMS) implantation. Methods: In this prospective study, PTX3, interleukin (IL-6), IL-10, high-sensitivity c-reactive protein (hsCRP), and cardiac troponin I (cTnI) plasma values were determined before and 24hours after BMS implantation in 97 consecutively enrolled patients with STEMI who were admitted to University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina between February 2016 and February 2017. Patients were followed for 24 months to assess major adverse cardiovascular events (MACEs). Results: At 24 hours after percutaneous coronary intervention (PCI), plasma values of PTX3, IL-6, hsCRP, and cTnI were significantly increased; and IL-10 levels were significantly decreased compared with the values determined before PCI. Patients with MACEs had significantly higher plasma PTX3 levels at 24 hours after BMS-PCI than in patients without MACEs. Patients with PTX3 plasma values ≥5042 ng/ml had a significantly higher risk of MACEs than patients with PTX3 levels <5.042 ng/mL. Pentraxin 3 levels exhibited strong and significant correlations with IL-6 and IL-10 levels. Pentraxin 3, cTnI, and IL-6, but not hsCRP levels have showed independent association with MACEs, according to the multivariate Cox regression analysis. Conclusion: Pentraxin 3 might be better serum prognostic marker than IL-6, IL-10 or high sensitivity CRP for MACEs after BMS-PCI. It might help to make better risk stratification of those patients who are undergoing BMS-PCI.

BackgroundHBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe.MethodsThis study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence.The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence.ResultsAt least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32–3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA.At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32–3.10],P = 0.001).Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties.ConclusionsImmune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.