Publications by authors named "Nenad Pandak"

37 Publications

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey.

J Infect Public Health 2022 Jul 25;15(9):950-954. Epub 2022 Jul 25.

Environmental Health Research Centre, Public Health School, Université Libre de Bruxelles (ULB), Brussels, Belgium.

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.
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http://dx.doi.org/10.1016/j.jiph.2022.07.009DOI Listing
July 2022

Amoebic Liver Abscess: A disease native to Oman?

Sultan Qaboos Univ Med J 2022 May 26;22(2):253-256. Epub 2022 May 26.

Department of Infectious Disease, Royal Hospital, Muscat, Oman.

Objectives: Amoebic liver abscess (ALA) is endemic to many areas of the world. This study sought to investigate the epidemiology, presentation, laboratory tests and imaging characteristics of ALA in Oman and ultimately determine whether it is native to Oman or originated abroad.

Methods: This case series study was conducted at the Royal Hospital, Muscat, Oman, from January 2013 to December 2017 with patients older than 13 years and having a discharge diagnosis of ALA. Patient data were extracted from the Royal Hospital patient database.

Results: 22 patients were included in the study-18 Omani patients and four expatriates. Only two Omanis had a history of traveling abroad. There were 15 male patients and seven were female with an average age of 45.2 years. The most common presentation was abdominal pain, which was seen in 17 patients. Fever was seen in 13 patients. Alanine transferase was found to be elevated in 13 patients. The majority of patients (90%) had no symptomatic infections prior to developing ALA.

Conclusion: The data suggests that ALA is endemic to Oman, considering the high number of local patients and lack of travel abroad in this population. As the number of patients treated for ALA is rather small, it can be concluded that the occurrence of ALA is much lower in Oman than in other endemic areas. The majority of patients had no prior symptomatic infections; thus, a method of control involves screening to prevent amoebic spread.
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http://dx.doi.org/10.18295/squmj.6.2021.083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9155025PMC
May 2022

Characteristics of Pyogenic Liver Abscess: Experience of a single centre in Oman.

Sultan Qaboos Univ Med J 2022 May 26;22(2):257-261. Epub 2022 May 26.

Department of Medicine, Royal Hospital, Muscat, Oman.

Objectives: This study aimed to analyse the epidemiological, aetiological and clinical characteristics of pyogenic liver abscess (PLA) occurring in Oman. The intention was to obtain the information needed for the adequate liver abscess (LA) empirical treatment. LA can develop as a complication of hepatobiliary disease or other intraabdominal infections, but more recently, it is associated with primary and secondary liver malignancies and their treatment.

Methods: This retrospective study took place in the Royal Hospital, Muscat, Oman. Consecutive patients treated for LA from January 2013 to December 2017 were enrolled. Their demographic and clinical data were used to study the characteristics of PLA occurring in Oman.

Results: A total of 53 patients with PLA were enrolled in the study. They were predominantly male and younger than 60 years. was found to be the most common bacteria causing LA. Clinical presentation was non-specific, and abdominal pain and high fever were the most common symptoms.

Conclusion: The majority of PLAs are caused by , so the empirical treatment should begin with antibiotic directed against it. Further studies are needed to establish the local role of anaerobic bacteria in PLA and monitor the presence of hypervirulent in Oman.
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http://dx.doi.org/10.18295/squmj.5.2021.105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9155044PMC
May 2022

West nile virus infection: One-Year postkidney transplant.

Saudi J Kidney Dis Transpl 2021 Mar-Apr;32(2):532-542

Directorate General for Disease Surveillance and Control, Ministry of Health, Muscat, Oman.

West Nile virus (WNV) infections are a mosquito-borne virus of the Flaviviridae family. The clinical feature of the virus varies between individuals from being asymptomatic in most of the cases to severe central nervous system disease manifested as meningitis, encephalitis, and paralysis. Diabetic nephropathy patient with microvascular and macrovascular complications, who received a kidney transplant a year ago on immunosuppressive therapy, presented with a three-day history of upper respiratory tract infection and fever. He lived in an endemic area of brucella infection. He underwent a thorough and full evaluation with various laboratory and radiological evaluations. The patient was started empirically on ceftriaxone and acyclovir for a presumptive diagnosis of herpes encephalitis and covering also Listeria with ampicillin. The patient did not improve with the initial management, so a T2-weighted magnetic resonance imaging of the brain executed that showed nonspecific hyper-intensity in the left frontal area suggestive of microangiopathic changes. WNV-neutralizing antibodies were positive with a high titer >1:640, whereas WNV RNA was not detected in the plasma sample. In the serum sample, WNV IgM and IgG were both positive. WNV IgM antibodies were detected with 6.55 and 5.97 antibody index and were done by a semiquantitative ELISA. Furthermore, WNV-neutralizing antibodies were positive as well as with a titer of 1:80. As there is no specific antiviral treatment available, the patient management was supportive; reduction in immunosuppressive agents and the use of IV IgG. This is the first reported case of one-year post renal transplant who developed WNV encephalitis and neuropathy with significant response to immunoglobulin after 18 days of infections.
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http://dx.doi.org/10.4103/1319-2442.335467DOI Listing
February 2022

Vector-borne and zoonotic infections and their relationships with regional and socioeconomic statuses: An ID-IRI survey in 24 countries of Europe, Africa and Asia.

Travel Med Infect Dis 2021 Nov-Dec;44:102174. Epub 2021 Oct 23.

Department of Infectious and Tropical Diseases, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.

Background: In this cross-sectional, international study, we aimed to analyze vector-borne and zoonotic infections (VBZI), which are significant global threats.

Method: VBZIs' data between May 20-28, 2018 was collected. The 24 Participatingcountries were classified as lower-middle, upper-middle, and high-income.

Results: 382 patients were included. 175(45.8%) were hospitalized, most commonly in Croatia, Egypt, and Romania(P = 0.001). There was a significant difference between distributions of VBZIs according to geographical regions(P < 0.001). Amebiasis, Ancylostomiasis, Blastocystosis, Cryptosporidiosis, Giardiasis, Toxoplasmosis were significantly more common in the Middle-East while Bartonellosis, Borreliosis, Cat Scratch Disease, Hantavirus syndrome, Rickettsiosis, Campylobacteriosis, Salmonellosis in Central/East/South-East Europe; Brucellosis and Echinococcosis in Central/West Asia; Campylobacteriosis, Chikungunya, Tick-borne encephalitis, Visceral Leishmaniasis, Salmonellosis, Toxoplasmosis in the North-Mediterranean; CCHF, Cutaneous Leishmaniasis, Dengue, Malaria, Taeniasis, Salmonellosis in Indian Subcontinent; Lassa Fever in West Africa. There were significant regional differences for viral hemorrhagic fevers(P < 0.001) and tick-borne infections(P < 0.001), and according to economic status for VBZIs(P < 0.001). The prevalences of VBZIs were significantly higher in lower-middle income countries(P = 0.001). The most similar regions were the Indian Subcontinent and the Middle-East, the Indian Subcontinent and the North-Mediterranean, and the Middle-East and North-Mediterranean regions.

Conclusions: Regional and socioeconomic heterogeneity still exists for VBZIs. Control and eradication of VBZIs require evidence-based surveillance data, and multidisciplinary efforts.
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http://dx.doi.org/10.1016/j.tmaid.2021.102174DOI Listing
December 2021

International Multicentre Study of Infections.

J Fungi (Basel) 2021 Oct 19;7(10). Epub 2021 Oct 19.

Department of Infectious Diseases, Bahrain Oncology Center, King Hamad University Hospital, Busaiteen 24343, Bahrain.

has emerged globally as a multi-drug resistant yeast and is commonly associated with nosocomial outbreaks in ICUs. We conducted a retrospective observational multicentre study to determine the epidemiology of infections, its management strategies, patient outcomes, and infection prevention and control practices across 10 centres from five countries. Significant risk factors for infection include the age group of 61-70 years (39%), recent history of ICU admission (63%), diabetes (63%), renal failure (52%), presence of CVC (91%) and previous history of antibiotic treatment (96%). was commonly isolated from blood (76%). Echinocandins were the most sensitive drugs. Most common antifungals used for treatment were caspofungin (40%), anidulafungin (28%) and micafungin (15%). The median duration of treatment was 20 days. Source removal was conductedin 74% patients. All-cause crude mortality rate after 30 days was 37%. Antifungal therapy was associated with a reduction in mortality (OR:0.27) and so was source removal (OR:0.74). Contact isolation precautions were followed in 87% patients. infection carries a high risk for associated mortality. The organism is mainly resistant to most azoles and even amphotericin-B. Targeted antifungal therapy, mainly an echinocandin, and source control are the prominent therapeutic approaches.
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http://dx.doi.org/10.3390/jof7100878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539607PMC
October 2021

Convalescent Plasma Therapy in Critically Ill COVID-19 Patients: An Open Label Trial.

Oman Med J 2021 Sep 30;36(5):e296. Epub 2021 Sep 30.

Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.

Objectives: The novel severe acute respiratory syndrome coronavirus 2 pandemic continues to spread globally without an effective treatment. In search of the cure, convalescent plasma (CP) containing protective antibodies from survivors of coronavirus disease 2019 (COVID-19) infection has shown potential benefit in a non-intensive care unit setting. We sought to evaluate the effectiveness of CP therapy for patients with COVID-19 on mechanical ventilation (MV) and/or acute respiratory distress syndrome (ARDS).

Methods: We conducted an open-label trial in a single center, Royal Hospital, in Oman. The study was conducted from 17 April to 20 June 2020. The trial included 94 participants with laboratory-confirmed COVID-19. The primary outcomes included extubation rates, discharges from the hospital and overall mortality, while secondary outcomes were the length of stay and improvement in respiratory and laboratory parameters. Analyses were performed using univariate statistics.

Results: The overall mean age of the cohort was 50.0±15.0 years, and 90.4% (n = 85) were males. A total of 77.7% (n = 73) of patients received CP. Those on CP were associated with a higher extubation rate (35.6% vs. 76.2%; < 0.001), higher extubation/home discharges rate (64.4% vs. 23.8%; 0.001), and tendency towards lower overall mortality (19.2% vs. 28.6%; 0.354; study power = 11.0%) when compared to COVID-19 patients that did not receive CP.

Conclusions: CP was associated with higher extubation/home discharges and a tendency towards lower overall mortality when compared to those that did not receive CP in COVID-19 patients on MV or in those with ARDS. Further studies are warranted to corroborate our findings.
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http://dx.doi.org/10.5001/omj.2021.105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491110PMC
September 2021

Immunological predictors of disease severity in patients with COVID-19.

Int J Infect Dis 2021 Sep 1;110:83-92. Epub 2021 Jul 1.

Internal Medicine Department, Royal Hospital, Muscat, Oman. Electronic address:

Background: Identifying the immune cells involved in coronavirus disease 2019 (COVID-19) disease progression and the predictors of poor outcomes is important to manage patients adequately.

Methods: This prospective observational cohort study enrolled 48 patients with COVID-19 hospitalized in a tertiary hospital in Oman and 53 non-hospitalized patients with confirmed mild COVID-19.

Results: Hospitalized patients were older (58 years vs 36 years, P < 0.001) and had more comorbid conditions such as diabetes (65% vs 21% P < 0.001). Hospitalized patients had significantly higher inflammatory markers (P < 0.001): C-reactive protein (114 vs 4 mg/l), interleukin 6 (IL-6) (33 vs 3.71 pg/ml), lactate dehydrogenase (417 vs 214 U/l), ferritin (760 vs 196 ng/ml), fibrinogen (6 vs 3 g/l), D-dimer (1.0 vs 0.3 μg/ml), disseminated intravascular coagulopathy score (2 vs 0), and neutrophil/lymphocyte ratio (4 vs 1.1) (P < 0.001). On multivariate regression analysis, statistically significant independent early predictors of intensive care unit admission or death were higher levels of IL-6 (odds ratio 1.03, P = 0.03), frequency of large inflammatory monocytes (CD14+CD16+) (odds ratio 1.117, P = 0.010), and frequency of circulating naïve CD4+ T cells (CD27+CD28+CD45RA+CCR7+) (odds ratio 0.476, P = 0.03).

Conclusion: IL-6, the frequency of large inflammatory monocytes, and the frequency of circulating naïve CD4 T cells can be used as independent immunological predictors of poor outcomes in COVID-19 patients to prioritize critical care and resources.
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http://dx.doi.org/10.1016/j.ijid.2021.06.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245310PMC
September 2021

Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Eur J Clin Microbiol Infect Dis 2021 Nov 21;40(11):2323-2334. Epub 2021 Jun 21.

Infectious and Tropical Disease Unit, AOU Policlinico "P. Giaccone" - Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties - University of Palermo, 90127 , Palermo, Italy.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.
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http://dx.doi.org/10.1007/s10096-021-04288-1DOI Listing
November 2021

Prevalence and predictors of in-hospital mortality of patients hospitalized with COVID-19 infection.

J Infect Public Health 2021 Jun 18;14(6):759-765. Epub 2021 Apr 18.

Department of Pharmacology & Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman.

Background: The severity and mortality from COVID-19 infection vary among populations. The aim of this study was to determine the prevalence and predictors of mortality among patients hospitalized with COVID-19 infection in a tertiary care hospital in Oman.

Methods: We conducted a retrospective study using database that included: demographic, clinical characteristics, laboratory parameters, medications and clinical outcomes of all patients hospitalized in Royal Hospital, Muscat, Oman, between March 12, 2020 and December 1st 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 infected patients.

Results: In total,1002 patients with COVID-19 infection with mean age of the cohort was 54±16 years (65% (n=650) male) were included, with an overall and intensive care unit (ICU) mortalities of 26% (n=257) and 42% (n=199/473), respectively. The prevalence of ICU admission was 47% (n=473) and the need for mechanical ventilation was 41% (n=413). The overall length of stay in the ICU was 13 (9-21) days. Adjusting for other factors in the model, the multivariable logistic regression demonstrated that in-hospital mortality in admitted COVID-19 patients was associated with old age (p<0.001), heart diseases (adjusted odds ratio (aOR), 1.84; 95% confidence interval (CI): 1.11-3.03; p=0.018), liver diseases (aOR, 4.48; 95% CI: 1.04-19.3; p=0.044), those with higher ferritin levels (aOR, 1.00; 95% CI: 1.00-1.00; p=0.006), acute respiratory distress syndrome (ARDS) (aOR, 3.20; 95% CI: 1.65-6.18; p=0.001), sepsis (aOR, 1.77; 95% CI: 1.12-2.80; p=0.022), and those that had ICU admission (aOR, 2.22; 95% CI: 1.12-4.38; p=0.022).

Conclusion: In this cohort, mortality in hospitalized COVID-19 patients was high and was associated with advanced age, heart diseases, liver disease, high ferritin, ARDS, sepsis and ICU admission. These high-risk groups should be prioritized for COVID-19 vaccinations.
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http://dx.doi.org/10.1016/j.jiph.2021.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053361PMC
June 2021

Corrigendum to "A fatal case of COVID-19 due to metabolic acidosis following dysregulate inflammatory response (cytokine storm)" [ID Cases 21 (2020) e00829].

IDCases 2020 Jun 11:e00865. Epub 2020 Jun 11.

Directorate General of Disease Surveillance and Control, Ministry of Health, Muscat, Oman.

[This corrects the article DOI: 10.1016/j.idcr.2020.e00829.].
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http://dx.doi.org/10.1016/j.idcr.2020.e00865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836823PMC
June 2020

Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia.

Int J Infect Dis 2021 Jan 9;102:538-543. Epub 2020 Nov 9.

Department of Pharmacology & Clinical Pharmacy, College of Medicine & Clinical Pharmacy, Sultan Qaboos University, Muscat, Oman. Electronic address:

Objective: To evaluate the therapeutic effectiveness of favipiravir combined with inhaled interferon beta-1b in adult patients hospitalized with moderate to severe COVID-19 pneumonia.

Methods: A randomized, open-label controlled trial of oral favipiravir in adults hospitalized with moderate to severe COVID-19 pneumonia from June 22nd 2020 to August 13th 2020 was conducted. Patients were randomly assigned to receive either a combination of favipiravir with interferon beta-1b by inhalation aerosol or hydroxychloroquine (HCQ). The outcome endpoints included improvement in inflammatory markers, lower length of hospital stay (LOS), discharges and lower overall 14-day mortality.

Results: A total of 89 patients underwent randomization with 49% (n = 44) assigned to favipiravir and 51% (n = 45) assigned HCQ. The overall mean age was 55 ± 14 years and 58% (n = 52) were males. There were no significant differences in the inflammatory biomarkers at hospital discharge between the two groups; C-reactive protein (p = 0.413), ferritin (p = 0.968), lactate dehydrogenase (p = 0.259) and interleukin 6 (p = 0.410). There were also no significant differences between the two groups with regards to the overall LOS (7 vs 7 days; p = 0.948), transfers to the ICU (18.2% vs 17.8%; p = 0.960), discharges (65.9% vs 68.9%; p = 0.764) and overall mortality (11.4% vs 13.3%; p = 0.778).

Conclusions: No differences in clinical outcomes were found between favipiravir plus inhaled interferon beta-1b and hydroxychloroquine in adults hospitalized with moderate to severe COVID-19 pneumonia.
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http://dx.doi.org/10.1016/j.ijid.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833906PMC
January 2021

Therapeutic plasma exchange in adults with severe COVID-19 infection.

Int J Infect Dis 2020 Oct 23;99:214-218. Epub 2020 Jun 23.

Research and Innovative Centre, King Saud Medical City, Ministry of Health, Riyadh, Saudi Arabia.

Objective: To evaluate the therapeutic use of plasma exchange in COVID-19 patients compared to controls.

Methods: A case series of critically ill adult men and non-pregnant women, ≥18 years of age, with laboratory-confirmed COVID-19, was studied at the Royal Hospital, Oman, from April 17 to May 11, 2020. Therapeutic plasma exchange (TPE) was performed on patients admitted to the intensive care unit (ICU) with confirmed or imminent acute respiratory distress syndrome (ARDS) or severe pneumonia. The analysis was performed using univariate statistics.

Results: A total of 31 COVID-19 patients were included with an overall mean age of 51±15 years (range: 27-76 years); 90% (n=28) were males, and 35% (n=11) of the patients had TPE as a mode of treatment. The TPE group was associated with higher extubation rates than the non-TPE cohort (73% versus 20%; p=0.018). Additionally, patients on TPE had a lower 14 days (0 versus 35%; p=0.033) and 28 days (0 versus 35%; p=0.033) post plasma exchange mortality compared to patients not on TPE. However, all-cause mortality was only marginally lower in the TPE group compared to the non-TPE group (9.1% versus 45%; p=0.055; power=66%). Laboratory and ventilatory parameters also improved post TPE (n = 11).

Conclusions: The use of TPE in severe COVID-19 patients has been associated with improved outcomes, however, randomized controlled clinical trials are warranted to draw final, conclusive findings.
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http://dx.doi.org/10.1016/j.ijid.2020.06.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308750PMC
October 2020

Clinical characteristics and outcomes of the first 63 adult patients hospitalized with COVID-19: An experience from Oman.

J Infect Public Health 2020 Jul 8;13(7):906-913. Epub 2020 Jun 8.

Department of Anaesthesia and Critical Care e, Royal Hospital, Ministry of Health, Muscat Oman. Electronic address:

Introduction: To identify the clinical characteristics and outcomes of hospitalized patients with COVID-19 in Oman.

Methods: A case series of hospitalized COVID-19 laboratory-confirmed patients between February 24th through April 24th, 2020, from two hospitals in Oman. Analyses were performed using univariate statistics.

Results: The cohort included 63 patients with an overall mean age of 48±16 years and 84% (n=53) were males. A total of 38% (n=24) of the hospitalized patients were admitted to intensive care unit (ICU). Fifty one percent (n=32) of patients had at least one co-morbidity with diabetes mellitus (DM) (32%; n=20) and hypertension (32%; n=20) as the most common co-morbidities followed by chronic heart and renal diseases (12.8%; n=8). The most common presenting symptoms at onset of illness were fever (84%; n=53), cough (75%; n=47) and shortness of breaths (59%; n=37). All except two patients (97%; n=61) were treated with either chloroquine or hydroxychloroquine, while the three most prescribed antibiotics were ceftriaxone (79%; n=50), azithromycin (71%; n=45), and the piperacillin/tazobactam combination (49%; n=31). A total of 59% (n=37), 49% (n=31) and 24% (n=15) of the patients were on lopinavir/ritonavir, interferons, or steroids, respectively. Mortality was documented in (8%; n=5) of the patients while 68% (n=43) of the study cohort recovered. Mortality was associated with those that were admitted to ICU (19% vs 0; p=0.009), mechanically ventilated (31% vs 0; p=0.001), had DM (20% vs 2.3%; p=0.032), older (62 vs 47 years; p=0.045), had high total bilirubin (43% vs 2.3%; p=0.007) and those with high C-reactive protein (186 vs 90mg/dL; p=0.009) and low corrected calcium (15% vs 0%; p=0.047).

Conclusions: ICU admission, those on mechanical ventilation, the elderly, those with high total bilirubin and low corrected calcium were associated with high mortality in hospitalized COVID-19 patients.
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http://dx.doi.org/10.1016/j.jiph.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832725PMC
July 2020

A fatal case of COVID-19 due to metabolic acidosis following dysregulate inflammatory response (cytokine storm).

IDCases 2020 19;21:e00829. Epub 2020 May 19.

Directorate General of Disease Surveillance and Control, Ministry of Health, Muscat, Oman.

The ongoing outbreak of COVID-19 has been expanding worldwide. As of 17 April 2020, the death toll stands at a sobering 147,027 and over two million cases, this has been straining the health care systems all over. Respiratory failure has been cited as the major cause of death but here we present a case about a patient who instead succumbed to severe metabolic acidosis with multiple organ failure.
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http://dx.doi.org/10.1016/j.idcr.2020.e00829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236721PMC
May 2020

Emerging and neglected zoonoses in transplant population.

World J Transplant 2020 Mar;10(3):47-63

Department of Virology, Croatian Institute of Public Health; School of Medicine, University of Zagreb, Zagreb 10000, Croatia.

Zoonoses represent a problem of rising importance in the transplant population. A close relationship and changes between human, animal and environmental health ("One Health" concept) significantly influence the transmission and distribution of zoonotic diseases. The aim of this manuscript is to perform a narrative review of the published literature on emerging and neglected zoonoses in the transplant population. Many reports on donor-derived or naturally acquired (re-)emerging arboviral infections such as dengue, chikungunya, West Nile, tick-borne encephalitis and Zika virus infection have demonstrated atypical or more complicated clinical course in immunocompromised hosts. Hepatitis E virus has emerged as a serious problem after solid organ transplantation (SOT), leading to diverse extrahepatic manifestations and chronic hepatitis with unfavorable outcomes. Some neglected pathogens such as lymphocytic choriomeningitis virus can cause severe infection with multi-organ failure and high mortality. In addition, ehrlichiosis may be more severe with higher case-fatality rates in SOT recipients. Some unusual or severe presentations of borreliosis, anaplasmosis and rickettsioses were also reported among transplant patients. Moreover, toxoplasmosis as infectious complication is a well-recognized zoonosis in this population. Although rabies transmission through SOT transplantation has rarely been reported, it has become a notable problem in some countries. Since the spreading trends of zoonoses are likely to continue, the awareness, recognition and treatment of zoonotic infections among transplant professionals should be imperative.
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http://dx.doi.org/10.5500/wjt.v10.i3.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109593PMC
March 2020

Prediction of unfavorable outcomes in West Nile virus neuroinvasive infection - Result of a multinational ID-IRI study.

J Clin Virol 2020 01 11;122:104213. Epub 2019 Nov 11.

ESCMID Study Group for Infectious Diseases of the Brain - ESGIB, Switzerland; ID-IRI, Ankara, Turkey.

Background: WNV causes 1.4% of all central nervous system infections and is the most common cause of epidemic neuro-invasive disease in humans.

Objectives: Our main objective was to investigate retrospectively West Nile virus neuroinvasive disease (WNND) cases hospitalized during 2010-2017 and identified factors that can influence prognosis.

Study Design: We documented the demographic, epidemiologic, clinical and laboratory data of WNND and identified factors that can influence prognosis. The data were recruited through Infectious Diseases International Research Initiative (ID-IRI), which serves as a network for clinical researches.

Results: We investigated 165 patients with WNND in 10 countries from three continents. 27 patients died and the mortality rate was 16.4%. In an univariate analysis age, congestive heart failure, neoplasm and ischemic heart disease (p < 0.001), neuropsychiatric disorders (p = 0.011), chronic hepatitis (p = 0.024) and hypertension (p = 0.043) were risk factors for death. Fatal evolution was also correlated with ICU addmission, disorientation, speech disorders, change in consciousnes, coma, a low Glasgow coma score, obtundation, confusion (p < 0.001), history of syncope (p = 0.002) and history of unconsciousness (p = 0.037). In a binomial logistic regresssion analysis only age and coma remained independent prediction factors for death. We created an equation that was calculated according to age, co-morbidities and clinical manifestations that may be used to establish the prognosis of WNND patients.

Conclusions: WNND remain an important factor for morbidity and mortality worldwide, evolution to death or survival with sequelae are not rare. Our study creates an equation that may be used in the future to establish the prognosis of WNND patients.
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http://dx.doi.org/10.1016/j.jcv.2019.104213DOI Listing
January 2020

Scrub Typhus Complicated by ARDS, Myocarditis, and Encephalitis Imported to Oman from Nepal.

Oman Med J 2019 May;34(3):254-256

Infectious Diseases Unit, Department of Medicine, Royal Hospital, Muscat, Oman.

Scrub typhus is a potentially fatal rickettsial infection caused by . It is an obligate intracellular Gram-negative bacterium transmitted by the bite of infected chigger larva. The disease is distributed from Asia to the Pacific islands, and this region is known as the Tsutsugamushi Triangle. A 28-year-old man was admitted to the Royal Hospital with a four-day history of fever, headache, rigors, anorexia, and a nonspecific macular rash. Clinical presentation, laboratory results as well as epidemiological data indicated that this might be a case of scrub typhus. Additional serology tests confirmed the presumed diagnosis, and the patient was successfully treated with empirical therapy. Untreated scrub typhus has high mortality and early diagnosis and adequate treatment can prevent the potentially fatal outcome of the disease.
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http://dx.doi.org/10.5001/omj.2019.48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505338PMC
May 2019

Genetic diversity of hepatitis E virus (HEV) strains derived from humans, swine and wild boars in Croatia from 2010 to 2017.

BMC Infect Dis 2019 Mar 19;19(1):269. Epub 2019 Mar 19.

University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Mirogojska 8, 10 000, Zagreb, Croatia.

Background: To fulfill epidemiological data and investigate possible interspecies transmission, this study shall attempt to sequence representative HEV strains of human, swine and wild boar origin collected from 2010 to 2017 in Croatia.

Methods: In total, 174 anti-HEV antibody positive human sera samples; 1419 blood or faeces samples of swine, as well as 720 tissue and/or blood samples of wild boar originating from different counties (18 in total) in Croatia were tested for the presence of HEV RNA.

Results: HEV RNA was detected in 26 human sera samples (14.9%; 95% CI 10.4-21.0%). HEV RNA was detected in 216 tested swine (15.2%; 95% CI 13.5-17.1%), regardless of age, farm breeding system or geographical origin. Viral RNA was also detectable in faeces samples which prove that swine actively participate in shedding HEV into the environment. Of the total of 720 tested wild boar samples, 83 were HEV RNA positive (11.5, 95% CI 9.4-14.1%) originating from six counties. According to the sequence analysis all strains have shown to be members of Orthohepevirus A genotype HEV-3, regardless of host. The genotyping results confirm grouping of sequences into four subtypes of HEV strains of which subtypes 3a and 3c belong to the general cluster 3abchij, and were predominately detected during the study, while subtypes 3e and 3f fall within cluster 3efg. Strains within subtypes 3a and 3e were found in humans, swine and wild boars; subtype 3c strains were derived from humans and swine, whereas subtype 3f strains were found only in humans. Strains belonging to subtypes 3a and 3c were derived during the entire investigated period and may be considered endemic in Croatia, whereas strains within subtypes 3e and 3f were detected sporadically indicating the possibility of newly imported infections.

Conclusions: All detected strains show to be genetically highly related to strains found in humans and/or animals from other European Countries, indicating that trade of live animals or wild boar movement increases the risk of HEV infection spread. Furthermore, homologous strains found in different investigated species within this study indicate interspecies transmission of HEV and/or an existence of an accessible mutual source of infection.
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http://dx.doi.org/10.1186/s12879-019-3906-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425696PMC
March 2019

First case of imported chikungunya infection in Croatia, 2016.

Int Med Case Rep J 2017 3;10:117-121. Epub 2017 Apr 3.

Croatian National Institute of Public Health, Zagreb, Croatia.

In recent years, several European countries reported cases of imported chikungunya infection. We present the first imported clinically manifested chikungunya fever in Croatia. A 27-year-old woman returned to Croatia on 21 March 2016, after she stayed in Costa Rica for two months where she had noticed a mosquito bite on her left forearm. Five days after the mosquito bite she developed severe arthralgias, fever and erythematous papular rash. In next few days symptoms gradually subsided. After ten days she felt better, but arthralgias re-appeared accompanied with morning stiffness. Two weeks after the onset of the disease she visited the infectious diseases outpatient department. The physical examination revealed rash on the trunk, extremities, palms and soles. Laboratory findings showed slightly elevated liver transaminases. Serological tests performed on day 20 after disease onset showed a high titer of chikungunya virus (CHIKV) IgM and IgG antibodies which indicated CHIKV infection. CHIKV-RNA was not detected. Serology to dengue and Zika virus was negative. The patient was treated with nonsteroid anti-inflammatory drugs and paracetamol. Her symptoms ameliorated, however, three months later she still complaint of arthralgias. The presented case highlights the need for inclusion of CHIKV in the differential diagnosis of arthralgia in all travelers returning from countries with documented CHIKV transmission.
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http://dx.doi.org/10.2147/IMCRJ.S130210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388347PMC
April 2017

Epidemiology of hepatitis C in Croatia in the European context.

World J Gastroenterol 2015 Aug;21(32):9476-93

Tatjana Vilibic-Cavlek, Department of Virology, Croatian National Institute of Public Health and School of Medicine University of Zagreb, Zagreb 10000, Croatia.

We analyzed prevalence, risk factors and hepatitis C virus (HCV) genotype distribution in different population groups in Croatia in the context of HCV epidemiology in Europe, with the aim to gather all existing information on HCV infection in Croatia which will be used to advise upon preventive measures. It is estimated that 35000-45000 of the Croatian population is chronically infected with HCV. Like in other European countries, there have been changes in the HCV epidemiology in Croatia over the past few decades. In some risk groups (polytransfused and hemodialysis patients), a significant decrease in the HCV prevalence was observed after the introduction of routine HCV screening of blood/blood products in 1992. Injecting drug users (IDUs) still represent a group with the highest risk for HCV infection with prevalence ranging from 29% to 65%. Compared to the prevalence in the Croatian general population (0.9%), higher prevalence rates were found in prison populations (8.3%-44%), human immunodeficiency virus-infected patients (15%), persons with high-risk sexual behavior (4.6%) and alcohol abusers (2.4%). Low/very low prevalence was reported in children and adolescents (0.3%) as well as in blood donors (0%-0.009%). In addition, distribution of HCV genotypes has changed due to different routes of transmission. In the general population, genotypes 1 and 3 are most widely distributed (60.4%-79.8% and 12.9%-47.9%, respectively). The similar genotype distribution is found in groups with high-risk sexual behavior. Genotype 3 is predominant in Croatian IDUs (60.5%-83.9%) while in the prison population genotypes 3 and 1 are equally distributed (52.4% and 47.6%). Data on HCV prevalence and risk factors for transmission are useful for implementation of preventive measures and HCV screening.
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http://dx.doi.org/10.3748/wjg.v21.i32.9476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548109PMC
August 2015

[TICK-BORNE ENCEPHALITIS VIRUS: EPIDEMIOLOGICAL AND CLINICAL PICTURE, DIAGNOSIS AND PREVENTION].

Acta Med Croatica 2014 Dec;68(4-5):393-404

Tick-borne encephalitis virus (TBEV) is a small, enveloped virus that belongs to the family Flaviviridae, genus Flavivirus, tick-borne encephalitis serocomplex. There are three subtypes of TBEV: European, Far-Eastern and Siberian subtypes, which differ in geographical distribution, tick vector and clinical manifestation of disease in humans. TBEV is endemic in a wide geographic area ranging from Central Europe and the Scandinavian Peninsula to Japan. The virus is maintained in nature in so-called natural foci in cycles involving ticks and wild vertebrate hosts (mainly small rodents). The principal vector for the European subtype is Ixodes (I.) ricinus tick, whereas for Far-Eastern and Siberian subtypes it is I. persulcatus. In the Baltic States and Finland, co-circulation of two or all three subtypes was documented. Several animals, principally small rodents, serve as virus reservoirs. In the tick population, TBEV is transmitted by feeding/co-feed ing on the same host, transovarially (from infected females to their eggs) and trans-stadially (from one development stage to the next). An infected tick remains infected for life. While most TBE infections in humans occur following a tick bite, alimentary routes of TBEV transmission (consumption of unpasteurized milk/milk products from infected livestock) have also been described. All three tick stages can transmit the infection to humans. In the last decade, an increase of TBE incidence has been observed in some endemic areas. This could be due to a number of interacting factors such as changes in the climatic conditions affecting tick habitats, improvements in the quality of epidemiological surveillance systems and diagnostics, in landscape resources and their utilization and more outdoor recreation activity. In addition, the endemic area of TBEV has expanded to higher altitudes (up to 1500 m), apparently influenced by climatic changes. The typical clinical picture of infection with European subtype TBEV is characterized by a biphasic course (50%-77%). The first phase is characterized by nonspecific, flu-like symptoms followed by an asymptomatic interval of about one week. In 20%-30% of persons who develop symptoms, the second phase occurs with symptoms of central nervous system involvement (meningitis, encephalitis, myelitis, radiculitis). The mortality rate for European subtype is 1%-2%. Diagnosis is usually based on detection of specific antibodies (enzyme immunoassay, indirect immunofluorescent assay, plaque reduction neutralization test). From 1993 to 2013, a total of 777 cases of TBE were reported in Croatia. Endemicity is highest in north-western counties (mean incidence 3.61-6.78/100,000 inhabitants). The majority of patients were older than 20 years (88%). Most cases (73%) were reported from May to July.
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December 2014

Co-infection of Borrelia burgdorferi sensu lato and Rickettsia species in ticks and in an erythema migrans patient.

Parasit Vectors 2013 Dec 10;6:347. Epub 2013 Dec 10.

Centre for Infectious Disease Control Netherlands, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands.

Background: Lyme borreliosis is the most prevalent tick-borne disease in Europe. Ixodes ricinus also carries other pathogenic bacteria, but corresponding human diseases are rarely reported. Here, we compared the exposure to Rickettsia helvetica and Rickettsia monacensis with that to Lyme borreliosis spirochetes. We assumed that their exposure corresponds to their infection rate in questing I. ricinus.

Findings: Three Rickettsia species were detected in ticks with a total prevalence of 7.9%, of which the majority was R. helvetica (78%) and R. monacensis (21%). From the same geographic area, skin biopsies of erythema migrans patients were investigated for possible co-infections with Rickettsia spp.. Forty-seven out of 67 skin biopsies were PCR positive for Borrelia burgdorferi s.l. and one sample was positive for R. monacensis. The Borrelia genospecies from the R. monacensis positive patient was identified as Borrelia afzelii. The patient did not show any symptoms associated with rickettsiosis.

Conclusions: Co-infections of I. ricinus with Rickettsia spp. and B. burgdorferi s.l. were as high as expected from the individual prevalence of both pathogens. Co-infection rate in erythema migrans patients corresponded well with tick infection rates. To our knowledge, this is the first reported co-infection of B. afzelii and R. monacensis.
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http://dx.doi.org/10.1186/1756-3305-6-347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878868PMC
December 2013

West Nile virus outbreak in humans in Croatia, 2012.

Coll Antropol 2013 Sep;37(3):943-7

"Josip Juraj Strossmayer" University, Department of Biology, Osijek, Croatia.

During August and September 2012, seven cases of West Nile neuroinvasive disease were identified in three north-eastern counties of Croatia. Four cases were reported in Osijek-Baranja County, two in Brod-Posavina County and one in Vukovar-Srijem County. The median age of the patients was 62.7 years. All patients were hospitalized for 2-5 weeks. The patients from Slavonski Brod had more severe clinical presentation of disease with prolonged hospitalization. Medical entomological research was carried out in 64 localities, where 1785 mosquitoes were captured. Among the analyzed mosquitoes, 114 were determined to be Culex pipiens and subjected to molecular characterization for the presence of virus. No viral RNA was detected in mosquitoes. Subsequent public health measures taken include mosquito control in all settlements where disease was detected.
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September 2013

First outbreak of West Nile virus neuroinvasive disease in humans, Croatia, 2012.

Vector Borne Zoonotic Dis 2014 Jan 27;14(1):82-4. Epub 2013 Nov 27.

1 Communicable Diseases Epidemiology Service, Croatian National Institute of Public Health , Zagreb, Croatia .

Between September 6 and 21, 2012, seven human cases of West Nile virus (WNV) neuroinvasive infection were laboratory confirmed in Croatia. The median patient age was 62 years (range 48-77). Five patients presented with meningoencephalitis and two patients with meningoencephalitis followed by acute flaccid paralysis. Four of them had an underlying disease (hypertension). Using enzyme-linked immunosorbent assay (ELISA), WNV-specific immunoglobulin M (IgM) and IgG antibodies of low avidity were detected in six patients, whereas one showed only IgM antibodies. All samples were confirmed using plaque-reduction neutralization and microneutralization tests. Five patients recovered fully. Before human cases were reported, acute asymptomatic WNV infection was demonstrated by detection of IgM antibodies in sentinel horses. Moreover, an increased WNV IgG seropositivity in horses was detected in counties where human cases occurred. Adulticidal and larvicidal treatments were administered immediately in the respective places of residence. The end of the warm season contributed to the fact that there were no new cases of WNV disease recorded.
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http://dx.doi.org/10.1089/vbz.2012.1295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880908PMC
January 2014

Chlamydophila pneumoniae and Mycoplasma pneumoniae were not identified in sinus mucosa of patients with chronic rhinosinusitis.

Eur Arch Otorhinolaryngol 2014 Jun 6;271(6):1553-5. Epub 2013 Oct 6.

General Hospital Slavonski Brod, Slavonski Brod, Croatia,

Chronic rhinosinusitis is a symptomatic inflammation of the mucosa of the nose and paranasal sinuses lasting for at least 12 weeks. Atypical bacteria Chlamydophila pneumoniae and Mycoplasma pneumoniae are important causes of human respiratory tract infection. Also, they were identified in bronchial respiratory epithelium of patients with chronic obstructive pulmonary disease or asthma. Having in mind the unified airway concept, it is also possible that these bacteria can cause persistent infection of sinus mucosa in patients with chronic rhinosinusitis. Sixty consecutive patients with chronic rhinosinusitis who underwent the functional endoscopic sinus surgery due to medical therapy failure were included in the study. During the operation, sinuses were irrigated with sterile 0.9% NaCl solution and this lavage was immediately aspirated. Aspirates were used for the detection of C. pneumoniae and M. pneumoniae DNA using real-time PCR. C. pneumoniae and M. pneumoniae DNA were not detected in samples analysed. Atypical bacteria C. pneumoniae and M. pneumoniae did not cause persistent infection of sinus mucosa in patients with chronic rhinosinusitis.
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http://dx.doi.org/10.1007/s00405-013-2745-0DOI Listing
June 2014

Ability to cause erythema migrans differs between Borrelia burgdorferi sensu lato isolates.

Parasit Vectors 2013 Jan 22;6:23. Epub 2013 Jan 22.

Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P,O, Box 1, 3720BA, Bilthoven, Netherlands.

Background: Lyme borreliosis is a tick-borne disease caused by Borrelia burgdorferi sensu lato. The variety of characteristic and non-specific clinical manifestations is partially explained by its genetic diversity. We investigated the ability of B. burgdorferi sl isolates to cause erythema migrans.

Methods: The genetic constellation of isolates from ticks was compared to isolates found in erythema migrans. PCR and sequence analysis was performed on the plasmid-encoded ospC and the chromosomal 5S-23S rDNA spacer region (IGS).

Results: Seven different B. burgdorferi sl genospecies were identified in 152 borrelia isolates from ticks and erythema migrans biopsies. B afzelii (51%) and B. garinii (27%) were the most common in ticks. From the 44 sequences obtained from erythema migrans samples 42 were B. afzelii, one B. garinii and one B. bavariensis. Significant associations with erythema migrans formation were found for four IGS and two ospC types. Five from 45 ospC types were associated with more than one genospecies.

Conclusions: B. burgdorferi sl isolates differ in their propensity to cause erythema migrans. These differences were also found within genospecies. In other words, although B. afzelii was mostly associated with erythema migrans, some B. afzelii isolates had a low ability to cause erythema migrans. Our data further support the occurrence of plasmid exchange between borrelia genospecies under natural conditions.
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http://dx.doi.org/10.1186/1756-3305-6-23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599126PMC
January 2013

Bacterial colonization or infection in chronic sinusitis.

Wien Klin Wochenschr 2011 Dec 30;123(23-24):710-3. Epub 2011 Nov 30.

Department of Infectious Diseases, General Hospital "Dr. Josip Benčević", Slavonski Brod, Croatia.

The aim of this study was the determination of bacteria present in maxillary and ethmoid cavities in patients with chronic sinusitis and to correlate these findings with bacteria simultaneously present in their nasopharynx. The purpose of this correlation was to establish the role of bacteria found in chronically inflamed sinuses and to evaluate if the bacteria present colonized or infected sinus mucosa. Nasopharyngeal and sinus swabs of 65 patients that underwent functional endoscopic sinus surgery were cultivated and at the same time the presence of leukocytes were determined in each swab. The most frequently found bacteria in nasopharynx were Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp., Streptococcus viridans and Streptococcus pneumoniae. Maxillary or ethmoidal sinus swabs yielded bacterial growth in 47 (72.31%) patients. The most frequently found bacteria in sinuses were Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella spp. and Streptococci (pneumoniae, viridans and spp.). The insignificant number of leukocytes was present in each sinus and nasopharyngeal swab. Every published microbiology study of chronic sinusitis proved that sinus mucosa were colonized with bacteria and not infected, yet antibiotic therapy was discussed making no difference between infection and colonization. Chronic sinusitis should be considered a chronic inflammatory condition rather than bacterial infection, so routine antibiotic therapy should be avoided. Empiric antibiotic therapy should be prescribed only in cases when the acute exacerbation of chronic sinusitis occurs and the antibiotics prescribed should aim the usual bacteria causing acute sinusitis. In case of therapy failure, antibiotics should be changed having in mind that under certain circumstances any bacteria colonizing sinus mucosa can cause acute exacerbation of chronic sinusitis.
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http://dx.doi.org/10.1007/s00508-011-0093-xDOI Listing
December 2011

Simultaneous chickenpox and measles infection among migrant children who stayed in Italy during the second half of June 2011.

Clin Pract 2011 Sep 10;1(4):e113. Epub 2011 Nov 10.

Brodsko-posavska County Institute of Public Health, Slavonski Brod;

We are reporting on a household outbreak of measles, in which cases of simultaneous measles and chickenpox infection occured in children of a family who resided in Italy during the incubation period (June 2011). In three children, fever and generalized confluent macular rash were the dominant symptoms. Serology testing revealed simultaneous measles and chickenpox infection in four children.
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http://dx.doi.org/10.4081/cp.2011.e113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981447PMC
September 2011
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