Branko Milosevic

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.

Human case of fasciolosis in Serbia treated with triclabendazole

INTRODUCTION The number of humans infected by Fasciola hepatica is increasing worldwide. Humans can become accidental hosts by ingesting drinking water or plants contaminated with metacercariae. CASE REPORT We reported a case of a 68-year-old Serbian woman, in which the diagnosis of acute fasciolosis had been established after serious diagnostic concerns. Based on clinical picture (episodic right upper quadrant abdominal pain, febrility and generalized body pain) and biochemical analyses (high eosinophilia and high activity of alkaline phosphatase), she was appointed as suspected to the acute fasciolosis. Stool and duodenal aspirate exams were negative for Fasciola ova. In the absence of adequate serologic diagnostic for fasciolosis in Serbia, the diagnosis was confirmed using enzyme immunoassays and immunoblot at the Institute for Tropical Diseases in Hamburg, Germany. Soon after triclabendazole was administered, the symptoms disappeared and biochemical values returned to normal. CONCLUSION The diagnosis of human fasciolosis may be problematic and delayed, especially in non endemic areas, because physicians rarely encounter this disease and a long list of other diseases must be considered in the differential diagnosis. The syndrome of eosinophilia, fever, and right upper quadrant abdominal pain suggest acute fasciolosis. Unclear source does not rule out fasciolosis.

Non-specific inflammatory parameters in patients with pandemic H1N1 influenza.

The measurement of non-specific inflammation parameters, such as erythrocyte sedimentation rate (ESR), fibrinogen, C-reactive protein (CRP) and procalctinon (PCT) are very important tools for diagnosis of infections, as well as for monitoring of treatment response. The aim of this study was to determine the significance of non-specific inflammatory parameters in patients with influenza H1N1 infection. ESR, fibrinogen, CRP and PCT were analyzed in patients with influenza H1N1 infection. The diagnosis of influenza H1N1 was established from the nasopharyngeal swabs using Real Time Polymerase Chain Reaction - (RT PCR) method. Chest X-ray was performed to diagnose pneumonia Sixty-three out of 340 hospitalized patients with influenza had pandemic influenza. Their mean age was 34.60±13.82 years. They were referred to hospital 1 to 7 (4.06±2.0) days after onset of symptoms. Of these, 46 had pneumonia, while the majority (41 patients) had interstitial pneumonia, and only five had lobar or segmental pneumonia. Patients with pneumonia had significantly higher levels of CRP and PCT in comparison with those without pneumonia. Patients with lobar pneumonia had significantly higher CRP than those with interstitial pneumonia. However, mean values of PCT between interstitial and lobar pneumonia cases did not differ significantly. Interstitial pneumonia was the most common complication of H1N1 infection among our patients. Non-specific parameters of inflammation, especially CRP and PCT were increased in all pneumonia cases, regardless of the etiology. Monitoring of non-specific inflammatory parameters in patients with H1N1 infection allows recognition of patients with complications, their prompt hospitalization and early initiation of antimicrobial therapy.

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.

Molecular typing, pathogenicity factor genes and antimicrobial susceptibility of vancomycin resistant enterococci in Belgrade, Serbia

In this study the distribution of species and antimicrobial resistance among vancomycin resistant enterococci (VRE) recovered from clinical specimens obtained from five hospitals in Belgrade was analyzed. Strains were further characterized by pulsed-field gel electrophoresis (PFGE). Polymerase chain reaction (PCR) was used to investigate the presence of vanA and vanB genes and pathogenicity factor genes. Identification of 194 VRE isolates revealed 154 Enterococcus faecium, 21 Enterococcus faecalis, 10 Enterococcus raffinosus and 9 Enterococcus gallinarum. This study revealed existence of 8 major clones of VRE. PCR determined vanA gene to be present in all of the VRE studied. Esp and hyl genes were present in 29.22% and 27.92% of E. faecium, respectively, and in 76.19% and 0 of E. faecalis, respectively. Esp and hyl genes were not found more frequently in members of predominant clones of E. faecium than in single isolates; nor was their presence connected to invasiveness.

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.

The Importance of Haematological and Biochemical Findings in Patients with West Nile Virus Neuroinvasive Disease

Summary Background: West Nile virus neuroinvasive disease (WNND) occurs in less than 1% of infected people. Leukocytosis with lymphocytopenia, mild anaemia, thrombocytopenia, elevated liver and muscle enzymes and hyponatremia are occasionally present in patients with WNND. Cerebrospinal fluid (CSF) findings resemble other viral neuroinfections. The purpose of this study is to present some of the most important laboratory findings of our patients with WNND and to evaluate their correlation with fatal outcome. Methods: The study included 161 patients with WNND. Their blood and CSF samples were cytobiochemically analysed and the obtained variables were then tested for predictive significance of the disease outcome, or used for differentiation between two clinical syndromes (encephalitis vs meningitis). Results: West Nile encephalitis was present in 127 (78.9%) patients and West Nile meningitis was diagnosed in 34 (21.1%) cases. Leukocytosis was found in 45.9% patients. CRP level higher than 100 mg/L was registered only in those with encephalitis (p=0.020). CSF leukocyte count was 146±171 per microlitre, with slight lymphocytic predominance (mean 52%). Hypoglycorrhachia was registered in 9.3% of our patients with WNND. Twenty-eight (17.4%) patients died and all of them had encephalitis. Independent predictors of fatal outcome in WNND were serum CRP > 100 mg/L (p=0.011) and CSF proteins > 1 g/L (p=0.002). Conclusions: WNND usually affects older males. Prolonged neutrophilic predominance in CSF can occasionally be present, as well as hypoglycorrhachia. Patients with encephalitis, high serum CRP and high CSF protein level have a higher risk of fatal outcome.

Clinical characteristics of imported malaria: An 11-year experience in a Serbian referral center

INTRODUCTION Due to intercontinental traffic, population migration trends, natural disasters, and climate change, imported malaria remains important to consider in a febrile returning traveler. This study aims to raise awareness about malaria and help European clinicians maintain a working knowledge of this disease by reviewing the most important clinical characteristics in a non-endemic setting. METHODOLOGY Using medical records, a retrospective study was performed on clinical and laboratory data in order to analyze 103 malaria cases managed at the Clinic for Infectious and Tropical Diseases in Belgrade, from 2000 to 2010. Descriptive statistics, Chi-squared test, Spearmans rank correlation, and analysis of variance were used. RESULTS Patients were predominantly male (89.3%) with a mean age of 46.66 ± 12.45 years, and most (98.06%) returned from Africa without having taken chemoprophylaxis (72.88%). Fever, arthralgia, myalgia, headache, vomiting, dark urine, and cough were common at presentation. Hepatosplenomegaly, jaundice, neurological and pulmonary findings, and thrombocytopenia were dominant findings on physical and laboratory examinations. Most (73.48%) were infected with P. falciparum. Few patients (17.55%) who were hyperparasitemic had significantly higher values of bilirubin and more frequent neurological complications. All patients were treated with artemisinin-based drug combinations regardless of Plasmodium species. Three (2.9%) patients succumbed to P. falciparum malaria. CONCLUSION We suggest a high index of suspicion of malaria be maintained when evaluating febrile patients returning from endemic regions, especially if thrombocytopenia and hemolysis are present. Hyperparasitemia, high bilirubin levels, and neurological symptoms are associated with severe malaria. The importance of adequate malaria chemoprophylaxis cannot be overstated.