Browsing by Author "Milosevic, Branko (57204639427)"

Neurologic manifestations are prominent characteristic of West Nile virus (WNV) infection. The aim of this article was to describe neurological manifestations in patients with WNV neuroinvasive disease and their functional outcome at discharge in the first human outbreak of WNV infection in Serbia. The study enrolled patients treated in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia in Belgrade, with serological evidence of acute WNV infection who presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP). Functional outcome at discharge was assessed using modified Rankin Scale (mRS) and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among patients with AFP, 12 resembled poliomyelitis and one had clinical and electrodiagnostic findings consistent with polyradiculoneuritis. Among patients with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight (15.4 %) presented with cerebellitis. Respiratory failure with subsequent mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %) patients died, five (9.6 %) were functionally dependent (mRS 3-5), and 38 (73.1 %) were functionally independent at discharge (mRS 0-2). In univariate analysis, the presence of AFP, respiratory failure and consciousness impairment were found to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p < 0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection in Serbia caused a notable case fatality ratio, especially in patients with AFP, respiratory failure and consciousness impairment. Rhombencephalitis and cerebellitis could be underestimated presentations of WNV neuroinvasive disease. © 2014 Springer-Verlag Berlin Heidelberg.

Neurologic manifestations are prominent characteristic of West Nile virus (WNV) infection. The aim of this article was to describe neurological manifestations in patients with WNV neuroinvasive disease and their functional outcome at discharge in the first human outbreak of WNV infection in Serbia. The study enrolled patients treated in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia in Belgrade, with serological evidence of acute WNV infection who presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP). Functional outcome at discharge was assessed using modified Rankin Scale (mRS) and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among patients with AFP, 12 resembled poliomyelitis and one had clinical and electrodiagnostic findings consistent with polyradiculoneuritis. Among patients with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight (15.4 %) presented with cerebellitis. Respiratory failure with subsequent mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %) patients died, five (9.6 %) were functionally dependent (mRS 3-5), and 38 (73.1 %) were functionally independent at discharge (mRS 0-2). In univariate analysis, the presence of AFP, respiratory failure and consciousness impairment were found to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p < 0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection in Serbia caused a notable case fatality ratio, especially in patients with AFP, respiratory failure and consciousness impairment. Rhombencephalitis and cerebellitis could be underestimated presentations of WNV neuroinvasive disease. © 2014 Springer-Verlag Berlin Heidelberg.

Background: Acute meningitis has a high case-fatality rate and survivors can have severe lifelong disability. We aimed to provide a comprehensive assessment of the levels and trends of global meningitis burden that could help to guide introduction, continuation, and ongoing development of vaccines and treatment programmes. Methods: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study estimated meningitis burden due to one of four types of cause: pneumococcal, meningococcal, Haemophilus influenzae type b, and a residual category of other causes. Cause-specific mortality estimates were generated via cause of death ensemble modelling of vital registration and verbal autopsy data that were subject to standardised data processing algorithms. Deaths were multiplied by the GBD standard life expectancy at age of death to estimate years of life lost, the mortality component of disability-adjusted life-years (DALYs). A systematic analysis of relevant publications and hospital and claims data was used to estimate meningitis incidence via a Bayesian meta-regression tool. Meningitis deaths and cases were split between causes with meta-regressions of aetiological proportions of mortality and incidence, respectively. Probabilities of long-term impairment by cause of meningitis were applied to survivors and used to estimate years of life lived with disability (YLDs). We assessed the relationship between burden metrics and Socio-demographic Index (SDI), a composite measure of development based on fertility, income, and education. Findings: Global meningitis deaths decreased by 21·0% from 1990 to 2016, from 403 012 (95% uncertainty interval [UI] 319 426–458 514) to 318 400 (265 218–408 705). Incident cases globally increased from 2·50 million (95% UI 2·19–2·91) in 1990 to 2·82 million (2·46–3·31) in 2016. Meningitis mortality and incidence were closely related to SDI. The highest mortality rates and incidence rates were found in the peri-Sahelian countries that comprise the African meningitis belt, with six of the ten countries with the largest number of cases and deaths being located within this region. Haemophilus influenzae type b was the most common cause of incident meningitis in 1990, at 780 070 cases (95% UI 613 585–978 219) globally, but decreased the most (–49·1%) to become the least common cause in 2016, with 397 297 cases (291 076–533 662). Meningococcus was the leading cause of meningitis mortality in 1990 (192 833 deaths [95% UI 153 358–221 503] globally), whereas other meningitis was the leading cause for both deaths (136 423 [112 682–178 022]) and incident cases (1·25 million [1·06–1·49]) in 2016. Pneumococcus caused the largest number of YLDs (634 458 [444 787–839 749]) in 2016, owing to its more severe long-term effects on survivors. Globally in 2016, 1·48 million (1·04—1·96) YLDs were due to meningitis compared with 21·87 million (18·20—28·28) DALYs, indicating that the contribution of mortality to meningitis burden is far greater than the contribution of disabling outcomes. Interpretation: Meningitis burden remains high and progress lags substantially behind that of other vaccine-preventable diseases. Particular attention should be given to developing vaccines with broader coverage against the causes of meningitis, making these vaccines affordable in the most affected countries, improving vaccine uptake, improving access to low-cost diagnostics and therapeutics, and improving support for disabled survivors. Substantial uncertainty remains around pathogenic causes and risk factors for meningitis. Ongoing, active cause-specific surveillance of meningitis is crucial to continue and to improve monitoring of meningitis burdens and trends throughout the world. Funding: Bill & Melinda Gates Foundation. © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Background: Acquisition of Hospital-acquired infections (HAIs) in intensive care units (ICUs) predispose patients to higher mortality rates and additional adverse events. Serbian adult ICUs are rarely investigated for HAIs. The aim of this study was to look into HAIs in an adult ICU and identify risk factors for acquisition of HAIs and mortality. Methods: This retrospective study included 355 patients hospitalized over a 2-year period. Patient characteristics, antimicrobial resistance patterns, and risk factors of acquisition and predictors of mortality in patients who had a HAI were examined. Results: HAIs were diagnosed in 32.7% of patients. Resistance rates > 50% were observed in all antimicrobials except for tigecycline (14%), colistin (9%), and linezolid (0%). Predictors of HAI acquisition were underlying viral CNS infections and invasive devices—urinary and central venous catheters, and nasogastric tubes. Diabetes mellitus and intubation (odds ratio 2.5 and 6.7, P = .042 and <.001) were identified as predictors for increased mortality in patients who had a HAI. Conclusions: Prevalence of HAIs and resistance rates are high compared to ICUs in other European countries. Risk factors for both acquisition of HAI and mortality were identified. Large-scale studies are necessary to look at HAIs in adult ICUs in Serbia. © 2020 Association for Professionals in Infection Control and Epidemiology, Inc. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Introduction: Pregnant women are at higher risk of developing severe influenza. Our aim was to analyze clinical course and risk factors for fatal outcome in pregnant women with influenza (H1N1) infection. Methodology: This retrospective study enrolled eleven pregnant women with confirmed Influenza A (H1N1) infection treated in the Clinic for Infectious and Tropical Diseases, Belgrade, Serbia in a 6-years period. Results: The mean age of pregnant women was 28.9 ± 5.2 years, and mean gestational age was 23.1 ± 7.0 weeks. Nine (81.8%) pregnant women had pneumonia (six had interstitial and three had bacterial pneumonia). Pregnant women developed pneumonia more often than other women in the reproductive period, but without statistical significance (81.8% vs. 65.7%, p = 0.330, OR (95% CI) 2.35 (0.47-11.80)). Nine (81.8%) pregnant women recovered. None of them experienced preterm delivery or abortion. Two women (18.2%) died due to acute respiratory distress syndrome. In one of them fetal death occurred one day before she died. The other one was performed caesarean section three days before death. Her newborn and children of all recovered women were healthy at birth. Prolonged time to initiation of oseltamivir and higher body mass index were statistically significantly associated with fatal outcome (p = 0.002, and p = 0.007, respectively). Gestational week of pregnancy, the etiology of pneumonia and comorbidity were not found to be risk factors for death (p = 0.128, p = 0.499 and p = 1.000, respectively). Conclusion: Pregnant women with H1N1 infection are at higher risk of pneumonia and death than other women in the reproductive period. Early antiviral therapy reduces the risk of unfavorable outcome. © 2018 Milosevic et al.

Introduction: Pregnant women are at higher risk of developing severe influenza. Our aim was to analyze clinical course and risk factors for fatal outcome in pregnant women with influenza (H1N1) infection. Methodology: This retrospective study enrolled eleven pregnant women with confirmed Influenza A (H1N1) infection treated in the Clinic for Infectious and Tropical Diseases, Belgrade, Serbia in a 6-years period. Results: The mean age of pregnant women was 28.9 ± 5.2 years, and mean gestational age was 23.1 ± 7.0 weeks. Nine (81.8%) pregnant women had pneumonia (six had interstitial and three had bacterial pneumonia). Pregnant women developed pneumonia more often than other women in the reproductive period, but without statistical significance (81.8% vs. 65.7%, p = 0.330, OR (95% CI) 2.35 (0.47-11.80)). Nine (81.8%) pregnant women recovered. None of them experienced preterm delivery or abortion. Two women (18.2%) died due to acute respiratory distress syndrome. In one of them fetal death occurred one day before she died. The other one was performed caesarean section three days before death. Her newborn and children of all recovered women were healthy at birth. Prolonged time to initiation of oseltamivir and higher body mass index were statistically significantly associated with fatal outcome (p = 0.002, and p = 0.007, respectively). Gestational week of pregnancy, the etiology of pneumonia and comorbidity were not found to be risk factors for death (p = 0.128, p = 0.499 and p = 1.000, respectively). Conclusion: Pregnant women with H1N1 infection are at higher risk of pneumonia and death than other women in the reproductive period. Early antiviral therapy reduces the risk of unfavorable outcome. © 2018 Milosevic et al.

Introduction: Clostridium difficile is the leading cause of hospital-acquired diarrhoea. There is no defined protocol for treating severe Clostridium difficile infection (CDI) refractory to vancomycin or vancomycin and metronidazole combination therapy. The aim of this study was to evaluate the rate of clinical cure, time to resolution of diarrhoea and recurrence rate in patients with severe refractory CDI treated with oral teicoplanin. Methodology: A one-year prospective study was carried out in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia. Patients with severe and complicated CDI who failed to respond to oral vancomycin and intravenous metronidazole combination therapy were enrolled. They were given oral teicoplanin 100 mg bi-daily. Patients were followed for recurrence for eight weeks. Results: Nine patients with a mean age of 70.8±9.4 years were analyzed. All patients had pseudomembranous colitis, and five had complicated disease. In four patients intracolonic delivery of vancomycin was also performed in addition to oral vancomycin and intravenous metronidazole prior to initiating teicoplanin, but without improvement. After teicoplanin initiation all patients achieved clinical cure. The mean time to resolution of diarrhoea after teicoplanin introduction was 6.3±4.5 days. There was no statistically significant difference in time to resolution of diarrhoea according to initial leucocyte count, age over 65 years, the presence of ileus, complicated disease and the use of concomitant antibiotic therapy (p = 0.652, 0,652, 0.374, 0.374, and 0,548, respectively). None of the patients experienced recurrence. Conclusions: Oral teicoplanin might be a potential treatment for severe and complicated refractory CDI, but further studies are required. © 2015 Popovic et al.

Introduction: Clostridium difficile is the leading cause of hospital-acquired diarrhoea. There is no defined protocol for treating severe Clostridium difficile infection (CDI) refractory to vancomycin or vancomycin and metronidazole combination therapy. The aim of this study was to evaluate the rate of clinical cure, time to resolution of diarrhoea and recurrence rate in patients with severe refractory CDI treated with oral teicoplanin. Methodology: A one-year prospective study was carried out in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia. Patients with severe and complicated CDI who failed to respond to oral vancomycin and intravenous metronidazole combination therapy were enrolled. They were given oral teicoplanin 100 mg bi-daily. Patients were followed for recurrence for eight weeks. Results: Nine patients with a mean age of 70.8±9.4 years were analyzed. All patients had pseudomembranous colitis, and five had complicated disease. In four patients intracolonic delivery of vancomycin was also performed in addition to oral vancomycin and intravenous metronidazole prior to initiating teicoplanin, but without improvement. After teicoplanin initiation all patients achieved clinical cure. The mean time to resolution of diarrhoea after teicoplanin introduction was 6.3±4.5 days. There was no statistically significant difference in time to resolution of diarrhoea according to initial leucocyte count, age over 65 years, the presence of ileus, complicated disease and the use of concomitant antibiotic therapy (p = 0.652, 0,652, 0.374, 0.374, and 0,548, respectively). None of the patients experienced recurrence. Conclusions: Oral teicoplanin might be a potential treatment for severe and complicated refractory CDI, but further studies are required. © 2015 Popovic et al.

The aim of this study was to compare clinical cure rate, recurrence rate and time to resolution of diarrhea in patients with severe and severe-complicated Clostridium difficile infection (CDI) treated with teicoplanin or vancomycin. This two-year prospective observational study included patients with first episode or first recurrence of CDI who had severe or severe-complicated CDI and were treated with teicoplanin or vancomycin. Primary outcomes of interest were clinical cure rate at discharge and recurrence rate after eight weeks follow up, and secondary outcomes were all-cause mortality and time to resolution of diarrhea. Among 287 study patients, 107 were treated with teicoplanin and 180 with vancomycin. The mean age of patients was 73.5 ± 10.6 years. One hundred eighty six patients (64.8%) had prior CDI episode. Severe complicated disease was detected in 23/107 (21.5%) and 42/180 (23.3%) patients treated with teicoplanin and vancomycin, respectively. There was no statistically significant difference in time to resolution of diarrhea between two treatment arms (6.0 ± 3.4 vs 6.2 ± 3.1 days, p = 0.672). Treatment with teicoplanin resulted in significantly higher clinical cure rate compared to vancomycin [90.7% vs 79.4%, p = 0.013, odds ratio (OR) (95% confidence interval (CI)) 2.51 (1.19–5.28)]. Recurrence rates were significantly lower in patients treated with teicoplanin [9/97 (9.3%) vs 49/143 (34.3%), p < 0.001, OR (95%CI) 0.20 (0.09–0.42)]. There was no statistically significant difference in overall mortality rate. Teicoplanin might be a good treatment option for patients with severe CDI. Patients treated with teicoplanin experienced remarkably lower recurrence rates compared to vancomycin-treated patients. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Introduction: Management of pyogenic spinal infections (PSI) after the development of neurological deficit has not been specifically addressed in the literature. We aimed to describe real-life clinical outcomes of PSI in patients admitted to an intensive care unit with neurological deficit and identify factors associated with good prognosis. Methodology: Consecutive patients admitted to ICU with a possible diagnosis of spinal infection over five years’ period were included. Descriptive statistics were performed to examine the demographics and clinical parameters. Results: The majority (71%) of patients were male. The mean age was 57.4 years (27-79), and 71% were > 50 years old. At least one underlying risk factor was identified in 68% of the patients; the most common comorbidity was diabetes mellitus (DM). All patients have presented with fever accompanied by a neurological deficit (86%) and back pain (79%). A complete recovery was achieved in 25% of patients. However, the majority of patients had adverse outcomes with 21.4% mortality, and 43% remaining neurological sequelae. Increased age with a cut-off of 65 years and pre-existing DM were identified as being associated with poor outcome. Conclusion: Mortality among patients admitted to ICU with PSI was significantly higher than reported in the literature. The residual neurological deficit was common, one-third of patients had remaining neurological sequelae, and only one-fourth had complete recovery. Increased age and background DM were the most important determinants of poor clinical outcome. The impact of DM appears to be much more important than currently recognised in this population. Copyright © 2020 Milosevic et al.

Introduction: Management of pyogenic spinal infections (PSI) after the development of neurological deficit has not been specifically addressed in the literature. We aimed to describe real-life clinical outcomes of PSI in patients admitted to an intensive care unit with neurological deficit and identify factors associated with good prognosis. Methodology: Consecutive patients admitted to ICU with a possible diagnosis of spinal infection over five years’ period were included. Descriptive statistics were performed to examine the demographics and clinical parameters. Results: The majority (71%) of patients were male. The mean age was 57.4 years (27-79), and 71% were > 50 years old. At least one underlying risk factor was identified in 68% of the patients; the most common comorbidity was diabetes mellitus (DM). All patients have presented with fever accompanied by a neurological deficit (86%) and back pain (79%). A complete recovery was achieved in 25% of patients. However, the majority of patients had adverse outcomes with 21.4% mortality, and 43% remaining neurological sequelae. Increased age with a cut-off of 65 years and pre-existing DM were identified as being associated with poor outcome. Conclusion: Mortality among patients admitted to ICU with PSI was significantly higher than reported in the literature. The residual neurological deficit was common, one-third of patients had remaining neurological sequelae, and only one-fourth had complete recovery. Increased age and background DM were the most important determinants of poor clinical outcome. The impact of DM appears to be much more important than currently recognised in this population. Copyright © 2020 Milosevic et al.

Hospital-acquired infections (HAIs) are a global public health concern. As the COVID-19 pandemic continues, its contribution to mortality and antimicrobial resistance (AMR) grows, particularly in intensive care units (ICUs). A two-year retrospective study from April 2019–April 2021 was conducted in an adult ICU at the Hospital for Infectious and Tropical Diseases, Belgrade, Serbia to assess causative agents of HAIs and AMR rates, with the COVID-19 pandemic ensuing halfway through the study. Resistance rates >80% were observed for the majority of tested antimicrobials. In COVID-19 patients, Acinetobacter spp. was the dominant cause of HAIs and more frequently isolated than in non-COVID-19 patients. (67 vs. 18, p = 0.001). Also, resistance was higher for imipenem (56.8% vs. 24.5%, p < 0.001), meropenem (61.1% vs. 24.3%, p < 0.001) and ciprofloxacin (59.5% vs. 36.9%, p = 0.04). AMR rates were aggregated with findings from our previous study to identify resistance trends and establish empiric treatment recommendations. The increased presence of Acinetobacter spp. and a positive trend in Klebsiella spp. resistance to fluoroquinolones (R2 = 0.980, p = 0.01) and carbapenems (R2 = 0.963, p = 0.02) could have contributed to alarming resistance rates across bloodstream infections (BSIs), pneumonia (PN), and urinary tract infections (UTIs). Exceptions were vancomycin (16.0%) and linezolid (2.6%) in BSIs; tigecycline (14.3%) and colistin (0%) in PNs; and colistin (12.0%) and linezolid (0%) in UTIs. COVID-19 has changed the landscape of HAIs in our ICUs. Approval of new drugs and rigorous surveillance is urgently needed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Hospital-acquired infections (HAIs) are a global public health concern. As the COVID-19 pandemic continues, its contribution to mortality and antimicrobial resistance (AMR) grows, particularly in intensive care units (ICUs). A two-year retrospective study from April 2019–April 2021 was conducted in an adult ICU at the Hospital for Infectious and Tropical Diseases, Belgrade, Serbia to assess causative agents of HAIs and AMR rates, with the COVID-19 pandemic ensuing halfway through the study. Resistance rates >80% were observed for the majority of tested antimicrobials. In COVID-19 patients, Acinetobacter spp. was the dominant cause of HAIs and more frequently isolated than in non-COVID-19 patients. (67 vs. 18, p = 0.001). Also, resistance was higher for imipenem (56.8% vs. 24.5%, p < 0.001), meropenem (61.1% vs. 24.3%, p < 0.001) and ciprofloxacin (59.5% vs. 36.9%, p = 0.04). AMR rates were aggregated with findings from our previous study to identify resistance trends and establish empiric treatment recommendations. The increased presence of Acinetobacter spp. and a positive trend in Klebsiella spp. resistance to fluoroquinolones (R2 = 0.980, p = 0.01) and carbapenems (R2 = 0.963, p = 0.02) could have contributed to alarming resistance rates across bloodstream infections (BSIs), pneumonia (PN), and urinary tract infections (UTIs). Exceptions were vancomycin (16.0%) and linezolid (2.6%) in BSIs; tigecycline (14.3%) and colistin (0%) in PNs; and colistin (12.0%) and linezolid (0%) in UTIs. COVID-19 has changed the landscape of HAIs in our ICUs. Approval of new drugs and rigorous surveillance is urgently needed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Introduction: In the Europe, the number of tick-borne encephalitis (TBE) has been increased in the last decade, and the number of endemic areas has been also increased and is still growing. In the present case series, we present clinical and socio-epidemiological data of patients with TBE hospitalized in the period of TBE virus epidemic in Serbia. Methodology: A case series was conducted in Serbia in 2017. Patients with confirmed TBE were included in the study. Biochemical and serological analysis of blood and CSF, as well as radiological imaging (CT and MRI) were done. Results: In total, 10 patients with TBE were included in the study. M:F ratio was 1.5:1, while average age was 45.1 years. Half of the patients had severe clinical picture. Endocranial CT scan and MRI did not reveal any abnormality, except in the patient with the most severe CNS infection (meningoencephalomyelitis). Mean value of sedimentation and CRP was slightly elevated (29.6 mm/1hours and 20.1 mg/L, respectively) in 80% of the patients, although elevation was almost negligible. The average number of leucocytes in the cerebrospinal fluid (CSF) was 171×106/L, the mean value of the CSF protein was 1.1g/L. There were no fatal outcomes. Conclusion: Since other CNS infections have similar clinical picture and CSF finding as TBE, serological analysis for TBE should be included in routine diagnostic practice. © 2019 Poluga et al.

Introduction: In the Europe, the number of tick-borne encephalitis (TBE) has been increased in the last decade, and the number of endemic areas has been also increased and is still growing. In the present case series, we present clinical and socio-epidemiological data of patients with TBE hospitalized in the period of TBE virus epidemic in Serbia. Methodology: A case series was conducted in Serbia in 2017. Patients with confirmed TBE were included in the study. Biochemical and serological analysis of blood and CSF, as well as radiological imaging (CT and MRI) were done. Results: In total, 10 patients with TBE were included in the study. M:F ratio was 1.5:1, while average age was 45.1 years. Half of the patients had severe clinical picture. Endocranial CT scan and MRI did not reveal any abnormality, except in the patient with the most severe CNS infection (meningoencephalomyelitis). Mean value of sedimentation and CRP was slightly elevated (29.6 mm/1hours and 20.1 mg/L, respectively) in 80% of the patients, although elevation was almost negligible. The average number of leucocytes in the cerebrospinal fluid (CSF) was 171×106/L, the mean value of the CSF protein was 1.1g/L. There were no fatal outcomes. Conclusion: Since other CNS infections have similar clinical picture and CSF finding as TBE, serological analysis for TBE should be included in routine diagnostic practice. © 2019 Poluga et al.