INTRODUCTION Stenotrophomonas maltophilia (S. Maltophilia) is a multidrug-resistant pathogen causing severe infections in intensive care units (ICUs). This study aimed to identify the risk factors influencing 30-day mortality and evaluate antimicrobial susceptibility patterns in ICU patients with S. maltophilia infections. METHODOLOGY A prospective, multicenter, international observational study was conducted between 15 October 2023 and 15 April 2024, in 36 ICUs across 12 countries. Adult patients (≥ 18 years) with S. maltophilia isolated from blood, urine, or respiratory cultures were included if isolates were considered clinically consistent with infection. Colonized or coinfected patients were excluded. Clinical, laboratory data were collected prospectively. Thirty-day outcome was defined as survival or death after the first positive culture. RESULTS A total of 207 patients were included; 109 (52.7%) died within 30 days. The primary infection sites were pneumonia (28.5%) and bloodstream infections (38.0%). Resistance rates were 7.2% for trimethoprim-sulfamethoxazole (TMP-SMX), 10.4% for levofloxacin, and 27% for ceftazidime. None of the patients received effective empiric therapy. Older age (p = 0.030), acute renal failure (p = 0.016), chronic obstructive pulmonary disease (COPD; p = 0.008), malignancy (p = 0.001), and sequential organ failure assessment (qSOFA) ≥ 2 (p = 0.001) were independently associated with higher mortality. Repeat culturing and antimicrobial modification according to susceptibility testing reduced mortality (p = 0.017). CONCLUSIONS S. maltophilia remains a lethal ICU pathogen. Early risk assessment, cultures, susceptibility testing, and therapy changes are vital. TMP-SMX and levofloxacin stay effective; but surveillance, infection control, and prudent antibiotic use remain essential.

Increasing travel, climate change, spread of antimicrobial resistance and pandemics increased the need for well-trained infectious diseases (ID) specialists and qualified ID specialist training for protecting public health all over the world. In this study, we aimed to provide a comprehensive overview of ID specialty training programs for standardization and quality improvement in a large geographical area. We conducted a cross-sectional study among national respondents of 29 countries [Central Asia (Azerbaijan, Uzbekistan, the Kyrgyz Republic, Kazakhstan), the Middle East (Iran, Saudi Arabia, Jordan, Iraq, Oman, the United Arab Emirates, Qatar, Lebanon), Southeast Europe (Albania, Greece, Kosovo, Slovenia, Bosnia and Herzegovina, Serbia, the Republic of North Macedonia, Croatia), Eastern Europe (Russia, Moldova, Romania, Bulgaria), South Asia (India, Pakistan, Afghanistan), Southeast Asia (Malaysia), Türkiye] to evaluate the structure and components of ID training programs. In this study, structural variability in ID training programs was notable. 65.5% of the countries offered independent specialty program, 59% of the countries reported a required exam for entry into the ID specialization. Nearly all of the countries had a formal training curriculum; written exams were the most common used assessment method. This study provides a comprehensive overview of ID specialty training across diverse regions, highlighting major structural differences in curricula, training duration, and national standards. Its broad geographic scope and contributions from actively engaged ID educators offer a unique global perspective. The findings underscore the urgent need for harmonized training frameworks, the strengthening of national curricula, and the promotion of international collaboration and inclusive strategies, all essential for developing a skilled, competent and resilient global ID workforce.

INTRODUCTION Acute bacterial meningitis (ABM) is a serious infectious disease and medical emergency. Given the fact of its high mortality and morbidity, detecting prognostic factors is potentially useful in improving treatment strategies. This paper aims to determine prognostic factors of short-term outcomes of patients with ABM in a developing country - Bosnia and Herzegovina, measured by the Modified Rankin Scale (MRS) at discharge. METHODOLOGY In this retrospective cohort study, 56 patients treated at the Clinic of Infectious Diseases, Clinical Center University of Sarajevo, for 11 years (2012-2022) were included. Statistical analysis was performed using IBM SPSS Statistics version 29.0.1.0. RESULTS The subjects' average age was 31.6 ± 27.7 years, with the youngest patient being 4 months and the oldest 75 years old. Among those, 31 were male and 25 were female. Unfavorable outcomes had 16 (28.6%) patients, including fatal outcomes in four patients and severe disabilities in 12 patients (MRS: 2-6), while 40 (71.4%) patients had favorable outcomes (MRS: 0-1). In the multivariate analysis, predictors of unfavorable outcomes included age older than 60 years, duration of symptoms longer than 24 hours, presence of neurological defects at admission, impaired consciousness, respiratory distress, and no corticosteroid use during treatment. CONCLUSIONS There is certainly a window of opportunity for patients with ABM: The shorter the time between disease onset and treatment initiation, the better the disease outcome.

BACKGROUND Arboviruses have expanded into new regions in Europe, yet data indicate gaps in disease notifications and a risk of further spread. We aimed to report on prevalence, clinical management, and outcomes of endemic arbovirus infections in southeast Europe. METHODS In this prospective observational study (MERMAIDS-ARBO), we enrolled adults (age ≥18 years) hospitalised with an arbovirus-compatible disease syndrome within 21 days of symptom onset across 21 hospitals in seven countries in southeast Europe over four arbovirus seasons (May 1-Oct 31, during 2016-19). We obtained data from case report forms completed by site investigators on admission and discharge. Participants were excluded if they had non-infectious CNS disorders, symptoms of another confirmed cause, an identified focal source of infection, or symptoms caused by recurrence of a pre-existing condition. The primary outcome was the proportion of participants with confirmed or probable acute infections with West Nile virus (WNV), tick-borne encephalitis virus (TBEV), Crimean-Congo haemorrhagic fever virus (CCHFV), or Toscana virus (TOSV), per reference laboratory criteria. Secondary outcomes were the proportions of patients treated with antivirals, antibiotics, or corticosteroids; the proportion of patients requiring intensive care; hospital length of stay; and mortality. FINDINGS Of 2896 adults screened for eligibility, 929 were recruited and 913 met protocol-defined eligibility criteria (median age 43·1 years [IQR 29·5-59·7]; 550 [60%] men, 361 [40%] women, and two [<1%] with missing data). 530 (58%) participants presented with suspected meningitis, encephalitis, or both, and 318 (35%) with fever plus myalgia, fever plus arthralgia, or both. 820 (90%) reported no international travel within 21 days before symptom onset. 727 (80%) were administered antibiotics, 379 (42%) corticosteroids, and 222 (24%) antivirals. The median length of hospital stay was 9 days (IQR 6-14), and 113 (12%) required intensive care. Of 847 participants with a reference laboratory sample who met full eligibility criteria for analysis, 110 (13%) were diagnosed with 114 confirmed or probable acute arbovirus infections (four had coinfections or cross-reactivity): one (<1%) with CCHFV, 16 (2%) with TBEV, 44 (5%) with TOSV, and 53 (6%) with WNV. There was one death (<1%) of an individual with WNV. Of the 110 participants, 49 (45%) had a local clinician-attributed arbovirus discharge diagnosis. INTERPRETATION Our data highlight the need to strengthen arbovirus surveillance systems for the early detection of emerging and re-emerging outbreaks, including investments to increase awareness of arbovirus infections among clinicians, to improve access to specialist diagnostics, and to develop effective and accessible vaccines and treatments to protect populations and health systems in southeast Europe. FUNDING European Commission and Versatile Emerging infectious disease Observatory. TRANSLATIONS For the Greek, Albanian, Romanian, Bosnian, Serbian, and Croatian translation of the summary see Supplementary Materials section.

BACKGROUND Arboviruses are increasingly affecting Europe, partly due to the effects of climate change. This increase in range and impact emphasises the need to improve preparedness for emerging arboviral infections that often co-circulate and might have overlapping clinical syndromes. We aimed to strengthen surveillance networks for four clinically relevant arboviruses in southeast Europe. METHODS This study reports an in-depth analysis of the MERMAIDS-ARBO prospective observational study in adults (ie, aged ≥18 years) hospitalised with an arbovirus-compatible disease syndrome in 21 hospitals in seven countries in southeast Europe over four arbovirus seasons (May 1-Oct 31, 2016-19) to obtain arbovirus prevalence outcomes. The main objectives of the MERMAIDS-ARBO study, describing the clinical management and outcomes of four arboviruses endemic to southeast Europe, including Crimean-Congo haemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), Toscana virus, and West Nile virus (WNV), are reported elsewhere. In this analysis, given the challenges associated with arbovirus diagnostics, we developed a diagnostic algorithm accounting for serology outcomes and sample timing to study arbovirus prevalence in southeast Europe. Serum samples were collected on days 0, 7, 28, and 60 after hospital admission and tested for anti-CCHFV IgG and IgM antibodies with ELISAs (confirmed with an indirect immunofluorescence test) and for IgG and IgM antibodies specific to TBEV, Toscana virus, and WNV with custom-printed protein microarrays (confirmed with virus neutralisation tests). All acute-phase samples were tested by PCR for all four viruses. Descriptive analyses were performed for virus-reactive cases by geography and year, and possible factors (eg, age, sex, and insect bites) associated with virus reactivity were assessed. FINDINGS Of 2896 individuals screened, 913 were eligible for inclusion, of whom 863 (514 men, 332 women, and 17 unknown) had samples sent to the study reference laboratories and were included in molecular and serological analyses. Some individuals had insufficient clinical data to be included in the clinical analysis, but met the eligibility criteria for and were included here. Serum sampling was incomplete (eg, samples missing from one or more timepoints or no data on time since symptom onset) for 602 (70%) patients, and the timing of collection was often heterogeneous after symptom onset up to 40 days (average median delay of 5-6 days across all timepoints), affecting the ability to diagnose arbovirus infection by serology. By use of an interpretation table incorporating timing and completeness of sampling, one (<1%) participant had a confirmed recent infection with CCHFV, ten (1%) with TBEV, 40 (5%) with Toscana virus, and 52 (6%) with WNV. Most acute confirmed infections of Toscana virus were found in Albania (25 [63%] of 40), whereas WNV was primarily identified in Romania (36 [69%] of 52). Albania also had the highest overall Toscana virus seropositivity (168 [60%] of 282), mainly explained by patients confirmed to be exposed or previously exposed (104 [62%] of 168). Patients without antibodies to WNV or Toscana virus were significantly younger than patients with antibodies (mean difference -8·48 years [95% CI -12·31 to -4·64] for WNV, and -6·97 years [-9·59 to -4·35] for Toscana virus). We found higher odds of Toscana virus reactivity in men (odds ratio 1·56 [95% CI 1·15 to 2·11]; p=0·0055), WNV reactivity with mosquito bites versus no mosquito bites (2·47 [1·54 to 3·97]; p=0·0002), and TBEV reactivity with tick bites versus no tick bites (2·21 [1·19 to 4·11]; p=0·018). INTERPRETATION This study shows that despite incomplete and heterogeneous data, differential diagnosis of suspected arbovirus infections is possible, and the diagnostic interpretation algorithm we propose could potentially be used to strengthen routine diagnostics in clinical settings in areas at risk for arboviral diseases. Our data highlight potential hotspots for arbovirus surveillance and risk factors associated with these particular arbovirus infections. FUNDING European Commission and Versatile Emerging infectious disease Observatory. TRANSLATIONS For the Greek, Albanian, Romanian, Bosnian, Serbian, and Croatian translation of the summary see Supplementary Materials section.

Background: COVID-19 is a respiratory disease caused by a novel coronavirus, with a high mortality, especially in patients with underlying diseases. Patients with COVID-19 pneumonia may express an immune response such as cytokine storm or macrophage activation syndrome, which can lead to organ failure and death.Some studies suggest that corticosteroid and tocilizumab can improve the respiratory status and clinical outcome of patients with COVID-19 pneumonia. Aim: The aim of the study was to determine the potential effect of the use of tocilizumab and corticosteroids in patients with concomitant cardiovascular diseases on the clinical course and outcome during COVID-19 infection. Methods: We performed an observational retrospective study of adult patients admitted to “Travnik” and “Jajce” Hospital, Bosnia and Herzegovina, between 01.03.2020 and 01.12.2022 with confirmed COVID-19 and underlying cardiovascular disease (CVD). Results: The majority of patients (110 or 60.4%) had previously reported cardiomyopathy, and other cardiovascular disease included earlier myocardial infarction, stroke, cardiac arrhythmias, cardiac surgery, compensated cardial disease, and acute myocardial infarction. Total of 159 (87.4%) patients received corticosteroids during treatment. Tocilizumab has been used in 16 patients; nine survived and seven died. Conclusion: Even some studies proved that it might improve clinical presentation and prevent lethal outcomes; in our study there were no significant results to confirm this thesis.             Peer Review History: Received 28 September 2024;   Reviewed 15 November; Accepted 21 December; Available online 15 January 2025 Academic Editor: Dr. DANIYAN Oluwatoyin Michael, Obafemi Awolowo University, ILE-IFE, Nigeria, toyinpharm@gmail.com Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.5/10

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has underscored the significant role of cardiovascular risk factors in determining the severity and outcomes of the disease. Pre-existing conditions such as hypertension, diabetes, obesity, and cardiovascular diseases have emerged as key contributors to increased susceptibility to severe forms of COVID-19, influencing both short-term and long-term health outcomes. This review examines the complex interplay between these risk factors and the virus’s direct impact on the cardiovascular system. Key findings suggest that conditions like hypertension, diabetes, and obesity not only predispose individuals to more severe disease but also exacerbate complications such as myocardial injury, arrhythmias, and heart failure. Furthermore, the long-term cardiovascular effects of COVID-19, including myocarditis and pericarditis, are of growing concern, particularly in patients with pre-existing cardiovascular conditions. The virus’s ability to induce myocardial damage through mechanisms involving ACE2 receptor binding and inflammatory cytokine storms has been well-documented. The pandemic has also highlighted significant cardiovascular complications, including left and right ventricular dysfunction, myocardial injury, and elevated pulmonary arterial pressure, with the right ventricle being particularly affected due to pulmonary damage. Imaging modalities such as echocardiography and cardiac magnetic resonance have proven valuable for diagnosing myocardial injury and complications, although accessibility may be limited in routine clinical practice. Survivors of severe COVID-19, especially those with pre-existing cardiovascular conditions, face an elevated risk of major adverse cardiovascular events for up to two years post-infection. Evaluation of post-COVID patients includes ECGs, laboratory tests, echocardiography, and cardiac MRI, which provide critical insights into myocardial injury and complications. Preventive measures, including vaccination, regular monitoring of cardiovascular health, and lifestyle modifications, play a crucial role in reducing the long-term risk of cardiovascular complications. The role of vaccination in mitigating the risk of severe disease and cardiovascular complications is well-established, despite rare cases of vaccine-related myocarditis. Understanding these interactions is essential for developing targeted management strategies, improving patient outcomes in both acute and long-term COVID-19 effects, and addressing the broader challenges posed by COVID-19’s impact on cardiovascular health.

Background: Acute nasopharyngitis is often treated with hypertonic saline that can be combined with additional compounds, such as lysozyme. The aim of this study was to compare efficacy and safety of hypertonic saline solution with or without lysozyme in the treatment of acute nasopharyngitis. Methods: Non-interventional, prospective, multicentre, observational, parallel study was conducted on adult subjects with symptoms of acute nasopharyngitis. Subjects were divided into hypertonic saline or lysozyme group (receiving slightly hypertonic nasal spray with addition of lysozyme). Time until the patency of both nasal passages was measured after the first application of therapy. The congestion severity was assessed by using a visual analogue scale before the therapy application, after 30 minutes, and after seven days. Adverse reactions were monitored and evaluated.   Results: The total number of included subjects was 252 (60 in the hypertonic saline group and 192 in the lysozyme group). In both groups, a significantly better assessment of the severity of the nasal passages’ obstruction was recorded after 30 minutes and seven days from therapy start (for all compared time intervals p<0.001). The lysozyme group had a significantly lower nasal congestion score compared to hypertonic saline 30 minutes after therapy (p<0.001) and seven days from the therapy start (p=0.001). In the hypertonic saline group, a significantly shorter time was observed to establish the patency of the nasal passages after the first therapy application (p<0.001). All adverse events were mild. Conclusions: Addition of lysozyme to slightly hypertonic nasal spray brings added value in the pharmacotherapy of acute nasopharyngitis.