Mijomir Pelemiš

The Frequency of Poststroke Infections and Their Impact on Early Stroke Outcome

INTRODUCTION Poststroke infections are the most common medical complications of stroke and can occur in up to 65% of patients. The aim of this study was to assess the rate of infectious complications during hospitalization of stroke patients and to evaluate the impact of infection in general, including each of the urinary tract infection (UTI), pneumonia, and sepsis, on fatal and poor functional outcome at discharge. METHODS This retrospective study enrolled patients who have been diagnosed with acute ischemic stroke treated in a 1-year period. Poor functional outcome at discharge was defined as severe invalidity and included patients with modified Rankin Scale score of 3-5. Univariate and multivariate analyses were performed. RESULTS We analyzed 133 patients with acute ischemic stroke. Poststroke infection occurred in 63 (47.4%) patients. The most common infection was UTI that was present in 27 (20.3%) patients. Multivariate logistic regression analysis after adjustment for confounders demonstrated that poststroke infection was an independent predictor of poor functional outcome (odds ratio [OR] 12.82, 95% confidence interval [CI] 4.09-40.0, P < .001) and death at discharge (OR 14.92, 95% CI 2.97-76.92, P = .001). When analyzing the impact of each infectious complication, multivariate logistic regression showed that UTIs were an independent predictor of poor functional outcome (OR 14.08, 95% CI 3.06-64.84, P = .001) and death (OR 9.81, 95% CI 1.46-65.68, P = .019) at discharge. CONCLUSION Infection is a frequent poststroke complication and represents an independent predictor of poor functional and fatal early stroke outcome.

Oral teicoplanin for successful treatment of severe refractory Clostridium difficile infection.

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.

Imported malaria in Belgrade, Serbia, between 2001 and 2009

ZusammenfassungSeit 2000 steigt die Zahl serbischer Bürger, die Reisen in die Tropen machen, langsam aber ständig. Um die epidemiologischen und klinischen Charakteristika der nach Serbien verschleppten Malaria zu erfassen, analysierten wir die klinische Anamnese aller Reisenden, die sich nach der Rückkehr aus tropischen oder subtropischen Gebieten zwischen 2001 und 2009 am Institut für Infektionen und Tropenkrankheiten in Belgrad vorstellten. Insgesamt wurden 2981 Reisende erfasst, von denen 847 gesundheitliche Probleme hatten. Eine Malaria wurde bei 102 (3,4 % aller Reisenden; 12 % aller Reisenden mit Fieberschüben) diagnostiziert. Mit einer Inzidenzrate von 6-16 Fälle pro Jahr wurde die Malaria hauptsächlich aus Afrika (92,2 %), vor allem Äquatorial Guinea (38,2 %) und Nigeria (15,7 %) eingeschleppt. Der häufigste Grund für die Reisen war geschäftlich, beziehungsweise beruflich. Die Patienten waren zumeist Männer (87,3 %) in einem Alter großteils zwischen 40 und 59 Jahren (66,7 %). Insgesamt nahmen 15 der erkrankten Personen (14,7 %) irgendeine Form einer Malariaprophylaxe ein. Plasmodium (P) falciparum (78), alleine (70) oder gemischt mit P. vivax (5) war die häufigste ursächliche Spezies. P. vivax, P. ovale und P. malariae konnten in 11, 1 und 1 der Fälle als alleiniger Erreger nachgewiesen werden. Von den 11 Fällen, in denen der Parasit nicht gefunden wurde, schienen sechs echte submikroskopische Fälle zu sein. Der klinische Verlauf war bei 13 Patienten (alle mit P. falciparum infiziert) schwer. Drei dieser Patienten (2,9 %) verstarben. Screening auf Malaria sollte in Serbien für in endemische Regionen Reisende, die sich mit Fieber präsentieren, (unabhängig davon, ob sie eine Chemoprophylaxe einnehmen oder nicht), verpflichtend sein. Nicht ausreichende Sensitivität der konventionellen Methoden (wie wir sie bei den submikroskopischen Fällen beobachtet haben) erfordert die Einführung molekularer Diagnostik in die Routinepraxis.SummarySince 2000, travel of Serbian citizens to tropical areas has been slowly but steadily increasing. To determine the epidemiological and clinical characteristics of imported malaria in Serbia, we analyzed clinical history data of all travelers who presented at the Clinic for Infectious and Tropical Diseases in Belgrade after their return from tropical and subtropical areas between 2001 and 2009. The study series involved a total of 2981 travelers, and included both those with (847) and without (2134) health problems. Malaria was diagnosed in 102 cases (3.4% of all travelers; 12.0% of travelers with febrile episodes). Occurring at a rate of 6 to 16 cases per year, it was predominantly imported from Africa (92.2%), particularly from Equatorial Guinea (38.2%) and Nigeria (15.7%). The most frequent reason for travel was work/business. Patients were predominantly (87.3%) male, and the majority (66.7%) was between 40 and 59 years of age. A total of 15 (14.7%) patients took some form of anti-malarial chemoprophylaxis. The dominant causative species was Plasmodium falciparum (78), alone (70) or in mixed infection with P. vivax (5) and P. malariae (3). P. vivax, P. ovale and P. malariae as single agents were each identified in 11, 1 and 1 cases, respectively. Of the 11 cases in which the parasite was not detected, six appeared to be true submicroscopic cases. The clinical course of the disease was severe in 13 patients, all with falciparum malaria, of which three (2.9%) died. Rather than for all travelers, in Serbia screening for malaria should be mandatory in all travelers to endemic regions who present with fever irrespective of chemoprophylaxis history. Inadequate sensitivity of conventional diagnostic methods, illustrated by the cases of submicroscopic malaria, requires introduction of molecular diagnosis in routine practice.

Imported parasitic infections in Serbia

BACKGROUND Travel to the tropics is associated with a risk of parasitic infection, which is increasing in parallel with the rise in travel to these areas. We thus examined the prevalence and trend in the occurrence of parasitic infections in Serbian travelers. METHODS A retrospective analysis of the medical records of all travelers returning from tropical and subtropical areas, who presented at the Institute for Infectious and Tropical Diseases in Belgrade between January 2001 and January 2008, was performed. RESULTS Of a total of 2440 travelers, 169 (6.9%) were diagnosed with a parasitic infection, including malaria in 79, intestinal parasites in 84 (pathogenic species in 30 and non-pathogenic in 54), filariasis in four, and visceral leishmaniasis and fascioliasis in one patient each. Importantly, of the whole series only 583 (23.9%) were symptomatic, of which 19.4% were found to be infected with a parasite. The single pathogenic parasite occurring in asymptomatic patients was Giardia intestinalis. CONCLUSIONS Parasitic infection causing symptomatic disease among travelers returning from tropical areas to Serbia is not infrequent. In view of the expected increase in travel to the tropics, diagnostic protocols for tropical parasitic diseases should take these data into account.

Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a phase I randomized clinical trial in healthy Serbian adults

ABSTRACT This study was a phase I double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a Serbian-produced seasonal trivalent split, inactivated influenza vaccine in healthy adults. The vaccine was manufactured in eggs by the Torlak Institute of Virology, Vaccines and Sera, Belgrade, Serbia and contained A/H1N1, A/H3N2 and B viruses. The clinical trial took place at the Clinical Center of Serbia in Belgrade. Sixty healthy volunteers, aged 18–45 years, were enrolled in the trial. On the day of immunization, volunteers were randomly assigned to receive either a single dose of the trivalent seasonal influenza vaccine (15 μg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Subjects were monitored for adverse events through a clinical history and physical examination, and blood was taken for testing at screening and on day 8 to assess vaccine safety. Serum samples obtained before and 21 days after immunization were tested for influenza antibody titers using hemagglutination-inhibition (HAI) and microneutralization (MN) tests. No serious adverse events were reported. Pain and tenderness at the injection site were the most commonly reported symptoms in both vaccine and placebo groups. Overall, serum HAI responses of fourfold or greater magnitude were observed to H1, H3, and B antigen in 80%, 75%, and 70% of subjects, respectively. Seroprotection rates as measured by HAI were also high (100%, 100% and 86.67%, respectively, for H1, H3 and B). Thus, Torlaks seasonal trivalent influenza vaccine was not associated with adverse events, was well-tolerated and immunogenic. It should be further evaluated in clinical trials to provide sufficient safety and immunogenicity data for licensing in Serbia.

Predictors of Hospitalization and Admission to Intensive Care Units of Influenza Patients in Serbia through Four Influenza Seasons from 2010/2011 to 2013/2014

A retrospective analysis of the surveillance data on laboratory confirmed cases of influenza in 4 post pandemic seasons in Serbia was performed to evaluate predictors of hospitalization and admission to intensive care units (ICU). The specimens, including nasal and throat swabs were tested for influenza. Univariate and multivariate logistic regression analyses were performed. Data of a total of 777 confirmed influenza cases were analyzed. Age > 65 years, the presence of any co-morbidity or the presence of ≥ 2 comorbidities, infection with influenza virus subtype A (H1) pdm09, and an interval greater than 3 days between symptom onset and the first physician visit, were independently associated with hospital admission. These variables, as well as infection with non-subtype influenza virus A, were predictors for ICU admission. Obesity and chronic neurological disease were independent predictors for ICU admission but not hospitalization. Overall, 41.7% of patients with influenza had at least one co-morbidity, but only 3% of all patients were vaccinated against influenza. Identification of high risk groups and education of these groups regarding their increased susceptibility to severe forms of influenza, and in particular regarding the importance of influenza vaccination, is essential.

Molecular characterization of vancomycin-resistant enterococci in Serbia: intensive care unit as the source.

The purpose of this study was to evaluate the molecular relatedness of clinical isolates of vancomycin-resistant enterococci (VRE) collected from patients of the Clinic for Infectious and Tropical Diseases in Belgrade. Among 40 isolates available for the investigation, 36 were identified as Enterococcus faecium, whereas 2 were Enterococcus faecalis and Enterococcus raffinosus, respectively. Pulsed-field gel electrophoresis (PFGE) typing revealed 21 strain types, comprising 7 clusters which contained at least two isolates and 14 unique PFGE patterns. Although we searched for pathogenicity factor genes (gelE, cylB, asa1, efaAfs, esp, cpd, cob) in representatives of all macro-restriction patterns, they have been confirmed in only one clone of E. faecalis. Genes esp and hyl, commonly found in E. faecium, were yilded in 10 macro-restriction patterns of this species, and their presence could not be ascribed to clonally related strains (p = 0.05). All VRE isolates were multiresistant and positive for vanA gene. Twenty strains of VRE and 6 clusters obtained from Intensive care unit (ICU) are proof of intensive transmission of these microorganisms at this department. The results of this study suggest wide genotypic variability among the clinical VRE isolates, but also intrahospital dissemination of some of them.

Antimicrobial resistance in patients with urinary tract infections and the impact on empiric therapy in Serbia.

INTRODUCTION Surveillance of antimicrobial resistance is essential in establishing treatment guidelines for urinary tract infections. The aim of this pilot study was to analyse resistance rates of pathogens, across different demographics and determine whether adjustments in empiric therapy should be considered for different age and gender groups. METHODOLOGY A 5-year retrospective study included 256 patients hospitalised, under the initial diagnosis of Fever of Unknown Origin who were then subsequently diagnosed with a urinary tract infection at the Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia. Patients were evaluated using demographic, clinical, and antimicrobial resistance data with appropriate statistical analysis including ANOVA significance testing, univariate, and multivariate analysis. RESULTS Resistance rates were above the threshold of 20% for the majority of the antimicrobials tested, the only exception being carbapenems. Amikacin, cefepime, and norfloxacin were agents that could be effectively used as empiric therapy in younger adults with resistance rates of 4.2, 8.0, and 10.0%, respectively. Moderate resistance rates of 17.4% for amikacin and 19.1% for cefepime were observed in the age group 35-64 years. High resistance rates were observed for all antimicrobials among patients 65 years and over. Among male patients, resistance rates to most antimicrobials were high. In female patients, amikacin and cefepime had resistance rates less than 20%. Younger age presented as a negative risk factor for infection by a multi-drug resistant pathogen. CONCLUSION Age and gender demonstrated to be significant factors for determining proper empiric therapy; large-scale studies from Serbia are needed to solidify these findings.

Retrospective PCR-based species identification of Leishmania in two patients with visceral leishmaniasis in Serbia

Introduction: Retrospective molecular identification of Leishmania parasites in two patients with visceral leishmaniasis (VL) previously treated in Serbia was carried out. DNA was isolated from unstained bone marrow smears (BMSs) kept for 11 and 8 years. Genus-specific real-time PCR was combined with conventional PCR and sequencing for detection and species identification. Case presentation: In 2003, a 40-year-old Serbian male was admitted to the Clinical Centre of Serbia (CCS) with fever, sweating, fatigue and splenomegaly, which developed over a period of 7 weeks. He had frequently travelled around Europe. VL was confirmed by microscopy of Giemsa-stained BMS. Treatment by pentavalent antimonials was successfully completed. Two years later, the patient developed post-kala-azar dermal leishmaniasis. Treatment resulted in symptom resolution. Later on, Leishmania infantum was identified as the causative agent of the VL by sequencing of the ITS (internal transcribed spacer) region; mixed Leishmania spp. infection could not be excluded. In 2006, a 33-year-old female from Vojvodina, Serbia, with pre-existing diabetes mellitus and chronic meningoencephalitis and a history of frequent visits to the Montenegrin seacoast, was admitted to the CCS with fever, pancytopenia and moderate hepatosplenomegaly. A stained BMS revealed abundant Leishmania amastigotes. Indirect haemagglutination analysis was positive with a titre of 1 : 2048, and a rapid dipstick rK39 test was also positive. Treatment by liposomal amphotericin B was successful; however, shortly after, the patient developed neural infection and pneumonia and died. The causative agent was identified as L. infantum. Conclusion: Molecular diagnosis of VL and species delineation using DNA from unstained BMSs stored for several years is possible.