Evaluation of PD-L1 Expression in Colorectal Carcinomas by Comparing Scoring Methods and Their Significance in Relation to Clinicopathologic Parameters.

BACKGROUND: This study aims to evaluate PD-L1 expression in colorectal carcinomas (CRCs) by using the tumor proportion score (TPS) and the combined positive score (CPS), and to investigate whether there is a correlation with clinicopathologic features. METHODS: A cross-sectional study was conducted that included samples from patients with colorectal adenocarcinoma treated with colon resection and rectal resection after neoadjuvant radio- and chemotherapy at the Department of Abdominal Surgery at Pozega Hospital in the period from 2017 to 2022. The study included 102 tumor tissue samples from patients after resection and the pathohistological diagnosis of adenocarcinoma. RESULTS: In our study, the PD-L1 positivity rate after the TPS was 42 (41%) samples, and after the CPS, 97 (95%) of them (p < 0.001). The positive expression of PD-L1 in tumor cells using the TPS method showed a statistically significant association with adenocarcinoma (TPS ≥ 10-50% and ≥50%). There were significantly more that were moderately differentiated, with TPS ≥ 50%, and those poorly differentiated had values ≥ 10-50%. There were significantly more patients with a status of more than one positive lymph node with TPS values ≥ 10-50%. Patients without metastases in the lymph nodes are significantly more likely to have CPS values > 50%, compared with other lymph node statuses. CONCLUSIONS: These results suggest that the total number of PD-L1-expressing cells, including tumor and immune cells, is a more sensitive biomarker than the number of PD-L1-expressing tumor cells alone in CRC.

Clinical Efficacy, Pharmacokinetics, and Safety of the Available Medical Options in the Treatment of Endometriosis-Related Pelvic Pain: A Scoping Review.

BACKGROUND: In this scoping review, we sought to identify published studies evaluating the drugs currently used in the treatment of endometriosis-related pelvic pain, with reflection on their chemical properties, pharmacokinetics, safety profile, and clinical efficacy. METHODS: A literature search was conducted with the use of the PubMed and EMBASE electronic databases, focusing on identifying articles published in English between January 1990 and 2023. RESULTS: Based on the included studies, current therapy options for the treatment of endometriosis-related pain identified and reviewed in this article were: (1) non-steroidal anti-inflammatory drugs; (2) combined oral contraceptive (COCs); (3) progestins; (4) gonadotropin-releasing hormone agonists and antagonists; (5) aromatase inhibitors (AIs); (6) selective estrogen and progesterone receptor modulators; and (7) levonorgestrel-intrauterine device. CONCLUSIONS: Based on the published evidence, clinicians should consider NSAIDs, COCs, and progestins as the first-line medical therapies. Compared with second-line options, such as GnRH agonists/antagonists or AIs, the abovementioned first-line options are well tolerated, efficacious, and exhibit lower overall price. Future research priorities should be to identify novel target therapies and to evaluate the effects of available drugs through different routes of administration.

Comparison end-to-end anastomosis with ostomy after secondary surgical cytoreduction for recurrent high-grade serous ovarian cancer: observational single-center study.

We conducted an observational single-center cohort study on patients with recurrent high-grade serous ovarian carcinoma that underwent secondary surgical cytoreduction with extent of partial ileectomy and/or colectomy, followed by adjuvant chemotherapy (Paclitaxel-Carboplatin). All patients performed previously primary debulking surgery without residual disease, followed by three cycles of adjuvant chemotherapy. The aim of this study was to compare survival in patients with ostomy or end-to-end anastomosis that underwent secondary cytoreduction. Furthermore, we investigated the morbidity, the rate, timing and complications of the ostomy or end-to-end anastomosis after secondary cyto-reduction.

The short form endometriosis health profile questionnaire (EHP-5): psychometric validity assessment of a Croatian version.

PURPOSE: To translate, adapt and validate the Endometriosis Health Profile-5 (EHP-5) in Croatian population. METHODS: This validation study is a part of a prospective, observational study (EHP-5 CRO) with aim of implementation of EHP-5 and to provide better insight in quality of life consideration of women with endometriosis in Croatian clinical practice. A 150 consecutive patients with surgically proven endometriosis were enrolled. The translation to Croatian followed standardized procedure. Cronbach's Alpha was calculated to calculate internal consistency reliability of EHP-5. The test-retest reliability was calculated using intraclass correlation coefficient (ICC). The t test for independent samples was used to assess known-groups validity. RESULTS: Both EHP-5 core and EHP-5 modular parts of the questionnaire had good internal consistency, assessed by the Cronbach's Alpha coefficient (α = 0.793 and α = 0.842, respectively). Obtained results indicate very good reliability for core as well as for modular part of EHP-5 questionnaire (ICC = 0.896 and 0.936, respectively). The independent t test showed that women who reported their pain with VAS scale 7 or more had significantly higher results (p < 0.001) on EHP-5 (M = 50.63) compared with women who reported their pain 6 or less (M = 26.91). Furthermore, we found statistically significant difference between women who are infertile with women who are fertile (p < 0.001), whereby infertile women had higher average result on EHP-5 (M = 49.55) compared with fertile women (M = 34.36). CONCLUSIONS: The Croatian version of the EHP-5 have very good psychometric characteristics and can be used as a reliable tool for assessing patients with endometriosis in everyday clinical practice.

Increasing trend in enterococcal bacteraemia and vancomycin resistance in a tertiary care hospital in Croatia, 2017-2021.

BACKGROUND: The epidemiology of enterococcal bacteraemia has changed worldwide and vancomycin-resistant enterococci increasingly cause healthcare-associated infections) with limited treatment options. Studies show heterogeneity among countries, regions and individual hospitals. METHODS: We retrospectively analysed enterococcal bacteraemia with Enterococcus faecalis and E. faecium at the largest hospital in Croatia, University Hospital Centre Zagreb from January 2017 to December 2021. RESULTS: A total of 432 cases of enterococcal bacteraemia were identified with 256 (59.3%) due to E. faecalis and 176 (40.7%) to E. faecium. Enterococcal bacteraemia occurred more frequently in men (n = 270; 62.5%) and the median age of all patients was 62 years (IQR: 0-92). We found statistically significant increase in the incidence trend of bacteraemic episodes with an annual percent change of 20.9% (95% confidence interval 14.3 to 27.8; p = .002) predominantly due to an increase of E. faecalis bacteraemia. The majority of patients (362/432; 83.8%) had healthcare-associated infections and 38.0% (165/432) of patients were in the intensive care unit. The proportion of vancomycin-resistant enterococcal bacteraemia increased from 12.7% (n = 8/63) in 2017 to 25.7% (n = 29/113) in 2021, statistically significant increasing trend (p = .0455), mainly due to an increased proportion of vancomycin-resistant E. faecium (p = .0169). CONCLUSIONS: This is the first study describing the trends in enterococcal bacteraemia and vancomycin-resistance in enterococci in Croatia. We found a rising trend in enterococcal bacteraemia and in the proportion of vancomycin resistance and identified the most vulnerable patient groups, notably intensive care unit patients.

Efficacy Comparison between Kegel Exercises and Extracorporeal Magnetic Innervation in Treatment of Female Stress Urinary Incontinence: A Randomized Clinical Trial.

Background and Objectives: To estimate the effectiveness of Kegel exercises versus extracorporeal magnetic innervation (EMI) in the treatment of stress urinary incontinence (SUI). Materials and Methods: A parallel group, randomized clinical trial was conducted in the Department of Obstetrics and Gynecology, Clinical Hospital Centre Zagreb, Croatia. After assessing the inclusion/exclusion criteria, each eligible participant was randomized to one of the two observed groups by flipping a coin: the first group underwent treatment with Kegel exercises for 8 weeks, while the second group underwent EMI during the same time interval. The primary outcome was the effectiveness of treatment as measured by the ICIQ-UI-SF overall score, eight weeks after the commencement of treatment. Results: During the study period, 117 consecutive patients with SUI symptoms were assessed for eligibility. A total of 94 women constituted the study population, randomized into two groups: Group Kegel (N = 48) and Group EMI (N = 46). After 8 weeks of follow-up, intravaginal pressure values in the EMI group were 30.45 cmH2O vs. the Kegel group, whose values were 23.50 cmH2O (p = 0.001). After 3 months of follow-up, the difference was still observed between the groups (p = 0.001). After the end of treatment and 3 months of follow-up, the values of the ICIQ-UI SF and ICIQ-LUTSqol questionnaires in the EMI group were lower than in the Kegel group (p < 0.001). Treatment satisfaction was overall better in the EMI group than in the Kegel group (p < 0.001). Conclusions: Patients treated with EMI had a lower number of incontinence episodes, a better quality of life, and higher overall satisfaction with treatment than patients who performed Kegel exercises.

State of the art, new treatment strategies, and emerging drugs for non-hormonal treatment of endometriosis: a systematic review of randomized control trials.

Objective: The aim of this systematic review is to recap the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on non-hormonal therapeutic options alleviating endometriosis-associated pelvic pain.Methods: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 179 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, seven primary articles met the inclusion criteria. A systematic review of the data was conducted.Results: This review included several, non-hormonal emerging drug therapies for endometriosis-associated pelvic pain. Based on our results, we divided well-founded studies into three subgroups: antiangiogenic agents, immunomodulators, and natural components. Randomized control trials showed promising results with dopamine agonists (cabergoline, quinagolide, and bromocriptine), and the immunomodulatory JNK inhibitor bentamapimod. Agents that have not been represented in randomized control trials or have failed to demonstrate efficacy include statins and TNF-α inhibitors.Conclusion: Although there are substantial improvements in non-hormonal therapy options, majority of the currently available treatment options are supressive rather than curative and do not present a final solution for patients. Future research priorities should be to identify novel target therapies and to evalute the effects of available drugs through different routes of administration.

CTLA4-Linked Autoimmunity in the Pathogenesis of Endometriosis and Related Infertility: A Systematic Review.

Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid in patients with endometriosis-related infertility. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through a search of the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database and Web of Science, and Clinical Trials research register. We included observational or prospective human and animal studies with any features related to endometriosis and/or infertility studies involving CTLA4-related pathogenesis published in English. The results of studies in which the size and characteristics of the observed groups were not stated were excluded. From the initial pool of 73 publications identified and screened, we finally included 5 articles to summarize the most recent knowledge about CTLA4-linked autoimmunity in the pathogenesis of endometriosis and related infertility. Evidence from clinical studies shows that CTLA4-based autoimmunity is involved in the maintenance of chronic inflammation in the peritoneal environment, with pre-clinical evidence of anti-CTLA antibodies as a potential novel target therapy for endometriosis. However, CTLA4 gene analyses do not support findings of CTLA4-linked autoimmunity as a primary determinant of the pathogenesis of endometriosis. These findings underlie the role of complex interactions within the family of immune checkpoint molecules involved. Further studies are needed to investigate the clinical relevance of anti-CTLA target therapy, taking into account the potential adverse events and repercussions of novel immunologic therapy modalities. However, with the general scarcity of studies investigating this topic, the clinical importance of CTLA4 autoimmunity still remains unclear.

Current status and challenges of drug development for hormonal treatment of endometriosis: a systematic review of randomized control trials.

OBJECTIVE: The aim of this systematic review is to summarize the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on hormonal therapeutic options for endometriosis-associated pelvic pain (EAPP), excluding studies focusing on fertility. METHODS: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 219 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, 11 primary articles met the inclusion criteria. A systematic review of the data was conducted. RESULTS: This review included several emerging drug therapies for EAPP. Randomized control trials showed promising results with several oral gonadotropin-releasing hormone antagonists (elagolix, relugolix, ASP1707, linzagolix). However, studies of other hormonal agents such as aromatase inhibitors and selective progesterone receptor modulators have not yielded significant or new advantages. Selective estrogen receptor modulators have not been represented in randomized control trials and have failed to demonstrate clinical efficacy. CONCLUSION: Although numerous novel agents are being investigated for the treatment of endometriosis, there is still no significant progress in the development of curative rather than suppressive drugs. Therefore, further efforts are needed to develop an effective and hopefully curative treatment for this chronic, costly, and overwhelming disease.

In vitro susceptibility of carbapenem-resistant Enterobacterales to eravacycline - the first report from Croatia.

The main obstacle in treatment of infections caused by carbapenem-resistant Enterobacterales (CRE) are limited treatment options. The novel antimicrobial agents other than ß-lactams with activity not being dependent on ß-lactamase class are especially important. Eravacycline (ERV) is the first fully synthetic fluorocycline indicated for the treatment of complicated intra-abdominal infections in adults. Eighty CRE isolates at the University Hospital Centre Zagreb, Croatia were examined for susceptibility to ERV by disc diffusion method and minimal inhibitory concentration (MIC). Total of 54 (54/80; 67.5%) isolates were susceptible to ERV with MIC50 of ≤0.5 µg/mL and MIC90 of 4 µg/mL. Susceptibility of OXA-48 positive isolates was not significantly higher in comparison with NDM positive (P = 0.539) and VIM positive (P = 0.7805) isolates. ERV is possible alternative to novel ß-lactamase inhibitor combinations for treatment of CRE infections with antimicrobial susceptibility testing of CRE isolate to ERV in particular patient as condicio sine qua non before administration.

Endometriosis, Pain and Mental Health.

BACKGROUND: Endometriosis is a chronic and progressive disease which can significantly affect a woman's personal, as well as intimate and professional aspects of life. The aim of this study was to asses health-related quality of life and mental health status in patients with endometriosis, investigating also their relationship with endometriosis-related comorbid symptoms and conditions, such as pain and infertility. SUBJECTS AND METHODS: An observational cross-sectional study involved 79 women with endometriosis. All patients filled the Endometriosis Health Profile (EHP-5), the Depression Anxiety Stress Scales (DASS-21) and the Visual Analogue Scale (VAS). Their medical data were retrieved from medical records. Data was analyzed using the SPSS 23.0 (IBM Corp., Armonk, NY). RESULTS: Of all the patients evaluated in our study, 44.3% presented depressive symptoms and 25.3% presented anxiety, while 31.7% reported stress symptoms. Moderate correlations were found between results on EHP-5 and depression (r=0.515), stress (r=0.558) and VAS score (r=0.565). Furthermore, weak positive relationship was observed between EHP-5 and anxiety (r=0.295) and infertility (r=0.267). Additionally, moderate correlation was found between depression and infertility (r=0.519), while there was weak association between VAS score and stress (r=0.236). CONCLUSIONS: This study showed complex relationships between symptoms and conditions manifesting in patients with endometriosis. Due to diversity of symptoms, potentially including mental health issues, it is important to emphasize the need for combined personalized treatment for these patients, taking into account both physical and psychological aspect of the disease.

Validation of the Croatian Version of the 8-Item Overactive Bladder Questionnaire (OAB-V8).

OBJECTIVES: The present study was conducted with the aim to translate, adapt, and validate the 8-item Overactive Bladder Questionnaire (OAB-V8) in Croatia. METHODS: This study included a total of 58 female patients with OAB and 66 healthy women. The translation to Croatian followed standardized procedure. All eligible participants completed OAB-V8 at inclusion and 2 weeks after to assess test-retest reliability. Cronbach α coefficient was calculated to assess internal consistency. RESULTS: Our study demonstrated high internal consistency for all items at both visits (Cronbach α between 0.799 and 0.847), with stable internal consistency reliability across items during the 2-week period. However, the exception is the item "waking up at night to urinate," which significantly changed during the 2-week period. Intraclass correlation for OAB-V8 items ranged from 0.810 to 1.0, with Spearman correlations greater than 0.9 for all items (P < 0.01). There were strong significant correlations between frequency of urination during daytime and uncomfortable and sudden urge to urinate, and between nocturia and waking up at night. Discriminative validity showed statistically significant score differences between patients and the control group. CONCLUSIONS: The Croatian version of the OAB-V8 was successfully translated, adapted, and validated so the questionnaire is now ready for use as a reliable tool for initial screening and assessing patients with OAB in everyday Croatian clinical practice.

Distribution of human papillomavirus genotypes in women with high-grade cervical intraepithelial lesions and cervical carcinoma and analysis of human papillomavirus-16 genomic variants.

AIM: To analyze the distribution of high-risk human papillomavirus (HR-HPV) genotypes and the diversity of HPV-16 genomic variants in Croatian women with high-grade squamous intraepithelial lesions (HSIL) and cervical carcinoma. METHODS: Tissue biopsy specimens were obtained from 324 women with histopathologically confirmed HSIL or cervical carcinoma, 5 women with low-grade SIL, and 49 women with negative histopathology. HR-HPV DNA was detected with Ampliquality HPV-type nucleic-acid hybridization assay, which identifies 29 different HPV genotypes. HPV-16 genomic variants were analyzed by an in-house sequencing. RESULTS: The most common HPV type in women with HSIL was HPV-16, detected in 127/219 (57.9%) specimens. HPV-16 was also the dominant type in squamous cell cervical carcinoma (46/69 or 66.7%) and in adenocarcinoma (18/36 or 50.0%). Out of 378 patients, 360 had HR-HPV (282 single infections and 79 multiple infections), 3 (0.8%) patients had low-risk HPV, and 15 (4%) tested negative. HPV-16 variants were determined in 130 HPV-16 positive specimens, including 74 HSIL and 46 carcinoma specimens. In HSIL specimens, 41 distinct variants were found, 98.6% belonging to the European branch and 1.4% belonging to the African branch. In cervical carcinoma specimens, 95% isolates grouped in 41 variants belonging to the European branch, one isolate (2.5%) belonged to the North American, and one (2.5%) to the Asian-American branch. CONCLUSION: HPV-16, mainly belonging to the European branch, was the most frequent HPV genotype in women from Croatia with histologically confirmed HSIL and cervical cancer.

The pharmacoeconomic impact of follitropin alpha biosimilars in IVF therapy in Europe: a report of the literature.

Introduction: To study the impact of biosimilars in assisted reproductive treatments, we performed a review of the literature. Biosimilars are a bioequivalent chemical drug referred to the original. Their production is strongly requested in order to reduce drug cost and reduce health economic impact on national health system. In assisted reproductive treatments different gonadotropin biosimilars are being produced.Areas covered: For this reason, we performed a review of the literature on follitropin alfa Gonal-F biosimilar, Ovaleap and Bemfola, to assess their cost efficacy in national health system. Cost effective (CE) analysis and incremental cost-effectiveness ratio (ICER) were used as parameters for biosimilar impact evaluation in the national health system economy. In particular, they had only slight impact on cost reduction of recombinant follitropin alfa products in Europe.Expert opinion: considering cost-effective analysis, Gonal-F remains the first choice for national health systems. However, well-designed powered methods are strongly needed to assess biosimilars cost-effectiveness.

Comparison of efficacy of extracorporeal magnetic innervation and Kegel exercises for stress urinary incontinence in adult women: study protocol for a randomized controlled trial.

Stress urinary incontinence (SUI) is defined as a complaint of inadvertent loss of urine occurring as a result of an increase in intraabdominal pressure. Strong evidence supports the use of pelvic floor muscle training (PFMT) as the first-line conservative treatment for SUI. Extracorporeal magnetic stimulation (EMS) is a non-invasive, effective, acceptable, and safe therapeutic modality for SUI. Although PFMT and EMS share most of their influences on the pathophysiology of SUI, it is unclear whether one of these routinely used treatment modalities is superior to another in terms of improvement of clinical outcomes or cost-effectiveness. To the best of our knowledge, no randomized controlled trials have so far directly compared PFMT with EMS. Our aim here is to describe a protocol for such a study. This will be a parallel-group, single-blind, randomised controlled trial compliant with the SPIRIT, CONSORT, and TIDieR reporting guidelines. Participants will be women aged 18 to 65 years who have previously given at least one vaginal delivery (at least 12 months before joining the study) who present with symptoms of SUI lasting at least 6 months yet have not previously received treatment for it. In the first study arm, patients will receive an eight-week, high-intensity, home-based Kegel exercises regimen. In the second study arm, the treatment scheme will consist of 2 sessions of EMS per week for a total of eight weeks. The primary outcome will be effectiveness of treatment as measured by the International Consultation on Incontinence Questionnaire Urinary Incontinence-Short Form overall score, eight weeks, three months, and six months after commencement of treatment.

Validation of the UDI-6 and the ICIQ-UI SF - Croatian version.

INTRODUCTION AND HYPOTHESIS: Despite the widespread use of UDI-6 and ICIQ-UI SF in Croatia, it remains unknown whether a realiable and valid measure for the population of interest is used. Thus, the aim of this study was to translate, adapt and validate the UDI-6 and the ICIQ-UI SF in Croatia. METHODS: The study included a total of 232 consecutive patients with urinary incontinence symptoms. The translation to Croatian followed standardized procedure. All participants underwent urodynamic assesment and completed UDI-6 and ICIQ-UI SF questionnaires at inclusion and 2 weeks after to assess test-retest reliability. Cronbach α coefficient was calculated in order to assess internal consistency. RESULTS: Both questionnaires had high internal consistency (Cronbach α for UDI-6 and ICIQ-UI SF was .83 and .85, respectively) and high test-retest reliability (intraclass correlation coefficient .99 for instruments). Strong correlation was found between urodynamic findings and total scores in UDI-6 and ICIQ-UI SF (ρ = 0.88 and 0.89, respectively). Women with stress urinary incontinence (SUI) and detrusor overactivity (DOA) group had significantly higher scores on UDI-6 (Mdn = 33.33 and Mdn = 50, respectively) compared to women with no urodynamic abnormality (Mdn = 0; p < 0.001). Women with no urodynamic abnormality scored significantly lower on ICIQ-UI SF (Mdn = 0; p < 0.001) compared to women with SUI (Mdn = 14) and DOA (Mdn = 16). Women with DOA scored worse on Irritative and Obstructive symptoms when comparing with two other groups (p < 0.001), while women with SUI had significantly worse score on Stress symptoms subscale (p < 0.001). CONCLUSIONS: The UDI-6 and ICIQ-UI SF have very good psychometric characteristics and can be used in Croatian urogynecology practice.

Fertility-sparing surgery for patients with malignant ovarian germ cell tumors: 10 years of clinical experience from a tertiary referral center.

PURPOSE: To describe a case series of patients with malignant ovarian germ cell tumors (MOGCT) treated exclusively with fertility-sparing surgery (FSS) with or without adjuvant chemotherapy. METHODS: We retrospectively reviewed the records of 27 patients with MOGCT treated in the Department of Obstetrics and Gynecology, University Hospital Center Zagreb, Croatia, between January 2009 and July 2019. RESULTS: The median age at diagnosis was 22 years, and the main symptom was abdominal distension (57.0%). The most prevalent histological subtype was immature teratoma (n = 13, 48.1%). Twenty-three patients (85.2%) had laparotomy and 4 (14.8%) had laparoscopy, without conversions. Lymphadenectomy was performed in 16 (59.3%) patients, with 184 removed lymph nodes, and omentectomy was performed in 19 (70.4%) patients. The rate of chemotherapy administration was 81.5%. The follow-up length ranged between 6.30 and 115.1 months (median: 49.60 months). No patient experienced tumor recurrence. The rate of complete gross resection was 100%. At the time of analysis, all patients were alive and disease free. Fifty percent of patients who actively tried to conceive after FSS became pregnant, with 12 deliveries. CONCLUSION: This study suggests that FSS is a safe treatment option for MOGCT, regardless of tumor stage and histological type.

Susceptibility of Escherichia coli to nitroxoline, an option for uncomplicated urinary tract infections - the first report from Croatia.

Nitroxoline (NTX), 5-nitro-8-hydroxyquinoline is an oral antibiotic with mechanism of bacteriostatic activity that is based on chelation of divalent cations required for bacterial RNA polymerase. Susceptibility to NTX of 100 Escherichia coli urine isolates was determined at the Department of Clinical and Molecular Microbiology, University Hospital Centre Zagreb during September and October 2017. Antimicrobial susceptibility was tested by disc diffusion and the results were interpreted according to the European Committee for Antimicrobial Susceptibility Testing (EUCAST) standards. All E. coli isolates, including ESBL-positive ones, were fully susceptible to imipenem, meropenem, amikacin, fosfomycin and NTX. This is the first report from Croatia about sensitivity of E. coli isolates to NTX. Besides fosfomycin, NTX was the only antimicrobial drug available for peroral administration demonstrating the sensitivity for all tested isolates. The results of the study demonstrated the potential of NTX as an additional therapeutically applicable option for the treatment of uncomplicated UTI.