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To quantify retinal microvascular findings in the acute phase of COVID-19 using multimodal imaging and compare them with healthy, age-matched controls.Hospitalized patients in the acute phase of COVID-19 without known systemic comorbidities (n = 75) and healthy controls (n = 101) aged 18-65 were enrolled in this prospective cross-sectional study. The retinal microcirculation and microvasculature impairments were assessed using fundus photography, swept-source optical coherence tomography, and swept-source optical coherence tomography angiography in the COVID-19 unit and compared with healthy, age-matched controls.Retinal findings were predominately observed in patients with severe disease (P = 0.006). Patients with severe disease were shown to have increased both mean vein diameter (Coef. = 19.28, 95% CI: 7.34-31.23, P = 0.002) and mean artery diameter (Coef. = 11.07, 95% CI: 0.84-21.67, P = 0.044). Neither blood vessel diameters were correlated with any confounding variables (age, sex, treatment with oxygen, LDH, or ferritin). Patients with severe COVID-19 were shown to have significantly increased retinal nerve fiber layer thickness in the superior and inferior quadrants both in the inner (S: P = 0.046; I: P = 0.016) and outer (S: P = 0.026; I: P = 0.014) ring and significantly increased GCL thickness in the outer temporal quadrant (P = 0.038). There were no statistically significant differences in vessel density or the foveal avascular zone area between the groups.The severity of COVID-19 was significantly correlated with the presence of retinal microangiopathy, which could become a biomarker of angiopathy in patients with COVID-19.

Preschool children are particularly susceptible to recurrent upper and lower respiratory tract infections due to their immune immaturity and other contributing factors. Preventing and/or treating children suffering from recurrent respiratory tract infections (RRTIs) is challenging, and it is important to provide more clinical evidence about the safety and efficacy of natural immunomodulating preparations, including β-glucans. The aim of the present study was to assess the incidence of respiratory tract infections (RTIs) in children with a history of RRTIs for a period of 6 months (3 months of pleuran supplementation and 3 months of follow-up) compared with the same period from October to March of the previous year prior to enrolment in the study. A total of 1,030 children with a mean age of 3.49 ± 1.91 years from seven countries were included in this study. The total number of RTIs observed during the study period was significantly lower compared to the same period of the previous year (7.07 ± 2.89 vs. 3.87 ± 3.19

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

This study aimed to quantify possible long-term impairment of the retinal microcirculation and microvasculature by reassessing a cohort of patients with acute COVID-19 without other known comorbidities one year after their discharge from the hospital. Thirty patients in the acute phase of COVID-19 without known systemic comorbidities were enrolled in this prospective longitudinal cohort study. Fundus photography, SS-OCT, and SS-OCTA using swept-source OCT (SS-OCT, Topcon DRI OCT Triton; Topcon Corp., Tokyo, Japan) were performed in the COVID-19 unit and 1-year after hospital discharge. The cohort’s median age was 60 years (range 28–65) and 18 (60%) were male. Mean vein diameter (MVD) significantly decreased over time, from 134.8 μm in the acute phase to 112.4 μm at a 1-year follow-up (p < 0.001). A significantly reduced retinal nerve fiber layer (RNFL) thickness was observed at follow-up in the inferior quadrant of the inner ring (mean diff. 0.80 95% CI 0.01–1.60, p = 0.047) and inferior (mean diff. 1.56 95% CI 0.50–2.61, p < 0.001), nasal (mean diff. 2.21 95% CI 1.16–3.27, p < 0.001), and superior (mean diff. 1.69 95% CI 0.63–2.74, p < 0.001) quadrants of the outer ring. There were no statistically significant differences between the groups regarding vessel density of the superior and deep capillary plexuses. The transient dilatation of the retinal vessels in the acute phase of COVID-19, as well as RNFL thickness changes, could become a biomarker of angiopathy in patients with severe COVID-19.

We aimed to explore factors for optimizing antimicrobial treatment in emergency departments. A single-day point prevalence survey was conducted on January 18, 2020, in 53 referral/tertiary hospitals in 22 countries. 1957 (17%) of 11557 patients presenting to EDs had infections. The mean qSOFA score was 0.37 +/- 0.74. Sepsis (qSOFA >= 2) was recorded in 218 (11.1%) patients. The mean qSOFA score was significantly higher in low-middle (1.48 +/- 0.963) compared to upper-middle (0.17 +/- 0.482) and high-income (0.36 +/- 0.714) countries ( P < 0.001). Eight (3.7%) patients with sepsis were treated as outpatients. The most common diagnoses were upper-respiratory (n = 877, 43.3%), lower-respiratory (n = 316, 16.1%), and lower-urinary (n = 201, 10.3%) infections. 1085 (55.4%) patients received antibiotics. The most-commonly used antibiotics were beta-lactam (BL) and BL inhibitors (n = 307, 15.7%), third-generation cephalosporins (n = 251, 12.8%), and quinolones (n = 204, 10.5%). Irrational antibiotic use and inappropriate hospitalization decisions seemed possible. Patients were more septic in countries with limited resources. Hence, a better organizational scheme is required.

Vascular graft infections (VGI) are associated with considerable morbidity and mortality, and antimicrobial treatment is an important adjunct to surgical treatment. While microbial aetiology of VGI is often difficult to determine, other techniques such as sonication of implanted material may be used to enhance the recovery of biofilm-associated organisms.We performed a retrospective analysis of 22 consecutive patients treated for VGI at University Medical Centre Ljubljana from May 2011 through January 2015. Explanted vascular grafts were flooded with sterile Ringer solution, sonicated for 1 min at a frequency of 40 kHz and inoculated on solid and liquid culture media. Aerobic and anaerobic cultures were performed, incubated for 14 days and any significant bacterial growth was quantitatively evaluated. Additionally, broad-range PCR from sonicate fluid was performed. Microbiological results were compared with the results of preoperatively taken blood cultures and the results of intraoperative tissue cultures (material from peri-graft collection).Identification of the causative organism (irrespective of the method) was achieved in 95.8%. Preoperative blood cultures were positive in 35.3%, intraoperative tissue cultures in 31.8%, sonicate fluid culture in 79.2%, while broad-range PCR from sonicate fluid was positive in 66.7%. In 37.5% the pathogen detected in sonicate fluid culture or broad-range PCR was the only positive microbiological result.Sonicate fluid culture and broad-range PCR from explanted vascular grafts may contribute to optimization of antimicrobial treatment. Optimal timing of antibiotic therapy before explantation should be further assessed to improve diagnostic yield.

Background Different diagnostic methods have been used for the laboratory confirmation of leptospirosis. Molecular diagnostic techniques are not only faster and more sensitive than culture analysis, but can also detect a Leptospira infection before the appearance of antibodies. The aim of the present study was to analyze and compare two different PCR approaches applied to blood and urine specimens obtained from patients with clinical manifestations that were suggestive of leptospirosis. Furthermore, the results of these different PCR approaches were compared with the results of culture and serology analyses. Results A total of 400 samples (234 blood or 58.5% and 166 urine of 41.5%) from 310 Slovenian patients with clinical manifestations suggestive of leptospirosis were tested using conventional PCR assays targeting the rrs gene and RT-PCR targeting the lipL32 gene. Additionally, culture, serology and sequence analysis were performed for the majority of these samples. The PCR and RT-PCR results were concordant in 376 out of 400 of these samples (94.0%). Conventional PCR was positive for 27 out of 400 samples (6.8%) and RT-PCR was positive for 47 out of 400 samples (11.8%). Culture and microscopic agglutination tests supported these diagnoses. Conclusions A comparison of the two PCR methods indicated that the RT-PCR targeting of the lipL32 gene was faster, more sensitive and more specific for the determination of Leptospira DNA in these clinical samples.

Summary Background Carbapenemase-producing Enterobacteriaceae (CPE) occur only sporadically in Slovenia. Aim To describe the first Slovenian carbapenemase-producing (CP) Klebsiella pneumoniae and Escherichia coli outbreak which occurred at the tertiary teaching hospital University Medical Centre Ljubljana from October 2014 to April 2015. Methods A CPE-positive case was defined as any patient infected or colonized with CPE. A strict definition of a contact patient was adopted. Measures to prevent cross-transmission included cohorting of all CPE carriers with strict contact precautions and assignment of dedicated healthcare workers, cohorting of all contact patients until obtaining the result of screening cultures, systematic rectal screening of contact patients, and tagging of all CPE-positive cases and their contacts. Educational campaigns on CPEs were implemented. Clinical specimens were processed using standard procedures. Pulsed-field gel electrophoresis (PFGE) was used to determine relatedness. Multi-locus sequence typing was performed on CP K. pneumoniae isolates that belonged to different pulsotypes. Findings Before the outbreak was brought under control, 40 patients were colonized or infected with OXA-48 and/or New Delhi metallo-β-lactamase (NDM)-producing CPE; in 38 patients OXA-48 and/or NDM-producing K. pneumoniae was detected, in seven OXA-48 and/or NDM-producing E. coli was found together with K. pneumoniae, and in two patients only CP E. coli was isolated. The outbreak was oligoclonal with two major CP K. pneumoniae clusters belonging to ST437 and ST147 in epidemiologically linked patients. Conclusion Initial standard control measures failed to prevent the outbreak. Once the problem had been recognized, strict infection control measures and the education of healthcare workers contributed to the successful control of the outbreak.

A 21-year-old man with Wolff-Parkinson-White syndrome presented to the authors' hospital with ventricular fibrillation. Coronary angiography failed to demonstrate coronary stenosis, but temporary mechanical circulatory support resolved the ventricular fibrillation and the patient was extubated eight days later. On the next day, however, he had to be re-intubated with symptoms of congestive heart failure. Echocardiography revealed new severe mitral regurgitation and a mobile mass, while emergency surgery revealed a posteromedial papillary muscle rupture (PMR). The mitral regurgitation was repaired with ruptured papillary muscle relocation, artificial chordae implantation, and ring annuloplasty. Postoperative examinations suggested that an arrhythmia-induced coronary circulation hypoperfusion and septic embolization had caused the PMR.

Candida spp. are a rare but important cause of infective endocarditis. The study aim was to describe pertinent clinical data on consecutive patients with Candida endocarditis treated at a tertiary referral center between 1984 and 2013.A retrospective search of the authors' endocarditis database was performed and the medical records of patients with confirmed Candida endocarditis were reviewed. Important data relating to demographics, medical history and clinical data, as well as information on outcome and treatment, were extracted.Between 1984 and 2013, a total of 12 episodes of Candida endocarditis in 11 patients (age range: 18 to 85 years) were treated at the authors' department (1.6% of all endocarditis episodes). Prosthetic valve endocarditis (PVE) was present in six patients. In 72% of cases the infection was healthcare-acquired. Endocarditis was shown to occur from 30 days to more than 600 days after cardiovascular surgery. Six patients were surgically treated. All removed valves were microbiologically positive, despite previous antifungal treatment. One patient with two episodes of Candida parapsilosis PVE was successfully treated conservatively, as was one patient with polymicrobial liver abscess, fungal spondylodiscitis and vegetation on the aortic valve. The total mortality rate was 45%.Candida endocarditis has a high mortality, and because of its rare occurrence it is difficult to define the most appropriate treatment. There may be a considerable time lag between cardiovascular surgery and the advent of endocarditis.

Catheter-related bloodstream infection (CRBSI) accounts for 10% to 20% of hospital-acquired infections and is associated with both increased ICU stay and mortality. CRBSI represent a considerable toll on patients and hospital resources. A lot of effort is put into the prevention of CRBSI.[1].

Leptospirosis is a febrile worldwide zoonosis. Routine diagnosis of leptospiral infection is based on demonstration of specific antibodies with serological tests. Performance of the reference serological test, the microscopic agglutination test (MAT), requires significant expertise. The aim of our study was to find out if leptospiral infection can be proven with simple, rapid, commercially available immunochromatographic Leptocheck test in order to introduce it for the first level diagnosis in emergency cases with less specialized laboratory staff. In all, 590 serum samples of patients with clinical manifestations suggestive of leptospirosis were collected and tested with MAT and Leptocheck test. For confirmation of the results some other diagnostic methods such as polymerase chain reaction (PCR) and Leptospira isolation were performed. Results of both serological tests were consistent in 576/590 (97.63 %) cases but Leptocheck gave more positive results in comparison to MAT (36 and 12, respectively) at first patient’s testing. Following up the patient, MAT became positive in majority of Leptocheck positive patients at first visit. Leptospiral DNA was detected in nine blood and six urine samples belonging to thirteen different patients while only two samples were culture positive. In comparison with serological tests, PCR and culture have low sensitivity. According to our findings we conclude that Leptocheck test can prove leptospiral infection and could be used for rapid diagnosis of leptospirosis, later the sample should be confirmed with MAT.

OBJECTIVE: To present epidemiological data and clinical characteristics of tick-borne encephalitis (TBE) in adult patients, and to compare findings in the subgroup over the age of 60 years with those aged 60 or under. METHODS: The information for this retrospective study was obtained by review of medical documentation. All patients over 15 years of age hospitalized at the Department of Infectious Diseases, University Medical Center Ljubljana, Slovenia, between 2000 and 2004 with pleocytosis (cerebrospinal fluid leukocyte count >5 × 106 cells/l) and the presence of serum IgM antibodies against TBE virus qualified for inclusion in this report. Patients were divided into two groups according to their age (patients over the age of 60 were classified as seniors and those aged 60 or under as adults); the findings in the two groups were compared. RESULTS: Of 448 patients with TBE, 318 were in the adult group and 130 in the senior group. Males predominated in both groups. A biphasic course of the illness was reported by 56% of patients. There were no significant differences in the majority of clinical parameters in the initial phase of TBE but several distinctions between adults and seniors were found in the second phase of the illness. Adults more often presented with fever, headache, stiff neck and photophobia, whereas seniors more frequently reported fatigue, altered consciousness and decreased muscle strength, these differences indicating a more classic course of TBE in the younger group and a somehow different and more severe acute disease in the older group. More severe acute disease and less favorable outcome in seniors was further corroborated by the occurrence of urine retention (18/318, 5.7% versus 27/130, 20.8%; P < 0.001), frequency of pareses (10/318, 3.1% versus 7/130, 5.4%; P = 0.002) and the need for antiedematous treatment (103/318, 32.4% versus 61/130, 46.9%; P = 0.005), as well as by the duration of treatment, duration of hospital stay and the death rate (0/318 versus 3/130, 2.3%; P = 0.024). Several distinctions were present also in laboratory findings, including higher cerebrospinal fluid leukocyte count in the adults than in the seniors (107 × 106 cells/l versus 47 × 106 cells/l; P < 0.001). CONCLUSION: Direct comparison of the course and outcome of TBE revealed several distinctions between patients over 60 years of age and those aged 60 or under and corroborates previous assumptions that TBE is a more serious illness in the elderly population.

Different media have been utilized for borrelial cultivation. The aim of the present study was to evaluate the isolation rate of Borrelia burgdorferi sensu lato from two commonly used media, i.e. modified Kelly–Pettenkofer (MKP) and Barbour–Stoenner–Kelly II (BSK-II) medium, and to compare the isolated strains with regard to their phenotypic and genotypic characteristics. Skin biopsy specimens of 2×2×4 mm were taken from the peripheral site of human solitary erythema lesions and were divided in two pieces, one of which was inoculated into MKP and the other one into BSK-II medium. Species analysis of the obtained strains was performed and their plasmid and protein profiles were determined. Borrelia strains were isolated from 48/96 patients (50%) with erythema migrans. We obtained in 26/48 patients (54%) from MKP as well as from BSK-II, in 11 patients (23%) only from MKP, and in another 11 (23%) only from BSK-II medium a positive result. B. afzelii was isolated from 43 patients (23 were positive in both media, nine in MKP only and 11 in BSK-II medium only), while B. garinii was isolated from five patients (in three from both media, in two from MKP only). All strains of the obtained strain pairs were identical according to species and the type within the species. Plasmid profiles were identical in 17/21 B. afzelii strain pairs (81%) and in 1/3 B. garinii strain pairs; in 6/24 strain pairs, distinctions in the number of plasmids or in their molecular mass were present. Differences in the protein profile were found in 7/24 strain pairs (29%). The distinctions were uniform and were limited to the expression of OspC. In conclusion, our study showed comparable Borrelia isolation rates from MKP and BSK-II medium. The results of the present study indicate that human patients with Lyme borreliosis may simultaneously harbor heterogeneous B. burgdorferi s.l. strains.

The aim of the present study was to analyze and compare Borrelia strains isolated from two different specimens obtained simultaneously from individual patients with Lyme borreliosis. Fifty such patients and 50 corresponding pairs of Borrelia isolates (100 low-propagated strains) were subjected to genotypic and phenotypic analysis, including pulsed-field gel electrophoresis for species identification and plasmid profile determination and protein profile electrophoresis for the assessment of the presence and molecular masses of separated proteins. The strains were isolated from two distinct skin lesions (12 patients), skin and blood (28 patients), skin and cerebrospinal fluid (8 patients), and blood and cerebrospinal fluid (2 patients). Out of 100 isolates, 63 were typed as B. afzelii and 37 as B. garinii . From each individual specimen only a single Borrelia species was cultured. Comparison of 50 Borrelia strain pairs isolated from two different specimens of an individual patient revealed that 12/50 (24%) patients were simultaneously infected with two different Borrelia strains; in 3/50 (6%) patients strains differed at the species level, in 4 out of the remaining 47 (9%) patients a strain difference in plasmid profile was established, while 5 out of the remaining 43 (11%) patient strain pairs differed in regard to the protein profiles of the two concurrently isolated strains. The results of the present study indicate that human patients with Lyme borreliosis may simultaneously harbor different B. burgdorferi sensu lato strains.

We compared epidemiological and clinical characteristics of patients with erythema migrans (EM) caused by Borrelia afzelii and Borrelia garinii. 200 consecutive adult patients with B. afzelii isolated from the skin lesion and 53 consecutive adult patients with EM caused by B. garinii qualified for the present study. Comparison of the two groups revealed several distinctions. Patients with EM caused by B. garinii were older, had their skin lesions more often located on the trunk but less often on extremities, had shorter incubation and faster evolution of EM, more often reported associated local and certain systemic symptoms, had abnormal liver function test results more often and were more frequently seropositive. Early localized Lyme borreliosis caused by B. afzelii and B. garinii has distinct epidemiological and clinical characteristics. Clinical features of EM depend upon the genospecies of Borrelia burgdorferi sensu lato causing the illness.

The aim of the present study was to quantify the severity of acute illness in patients with tick-borne encephalitis and to ascertain this approach by comparing it to standard clinical assessment. We designed scoring system for quantification of the severity of acute illness in patients with tick-borne encephalitis. Certain number of points was allotted to the presence, intensity, and duration of individual symptoms/signs. According to the obtained score the disease was classified as mild, moderate, and severe. Tick-borne encephalitis was assessed clinically as mild when only signs/symptoms of meningeal involvement were found, moderate in case of monofocal neurological signs and/or mild to moderate signs/symptoms of central nervous system dysfunction, and severe in patients with multifocal neurological signs and/or symptoms of severe dysfunction of central nervous system. By designed scoring system 282 adult patients, 146 males and 136 females, average aged 52.2 ± 15.5 years (range 15–82 years), with confirmed tick-borne encephalitis, were prospectively assessed. In 279/282 (98.9%) patients the severity according to clinical assessment matched with the score ranges for mild, moderate, and severe disease. The proposed approach enables precise and straightforward appraisal of the severity of acute illness and could be useful for comparison of findings within/between study groups.

Cellulomonas spp. are often believed to be of low virulence. There are only a few reports of human infections. We report the first case of endocarditis caused by Cellulomonas in an intravenous drug abuser. The diagnosis of infective endocarditis (IE) in this case was definite using the Duke criteria. The course of the disease was complicated with a heart failure and possible mycotic aneurysm in the left leg. After the end of antimicrobial therapy aortic valve replacement was done because of severe heart failure.

Heart failure (HF) is the most common complication of infective endocarditis. However, clinical characteristics of HF in patients with infective endocarditis, use of surgical therapy, and their associations with patient outcome are not well described.To determine the clinical, echocardiographic, and microbiological variables associated with HF in patients with definite infective endocarditis and to examine variables independently associated with in-hospital and 1-year mortality for patients with infective endocarditis and HF, including the use and association of surgery with outcome.The International Collaboration on Endocarditis-Prospective Cohort Study, a prospective, multicenter study enrolling 4166 patients with definite native- or prosthetic-valve infective endocarditis from 61 centers in 28 countries between June 2000 and December 2006.In-hospital and 1-year mortality.Of 4075 patients with infective endocarditis and known HF status enrolled, 1359 (33.4% [95% CI, 31.9%-34.8%]) had HF, and 906 (66.7% [95% CI, 64.2%-69.2%]) were classified as having New York Heart Association class III or IV symptom status. Within the subset with HF, 839 (61.7% [95% CI, 59.2%-64.3%]) underwent valvular surgery during the index hospitalization. In-hospital mortality was 29.7% (95% CI, 27.2%-32.1%) for the entire HF cohort, with lower mortality observed in patients undergoing valvular surgery compared with medical therapy alone (20.6% [95% CI, 17.9%-23.4%] vs 44.8% [95% CI, 40.4%-49.0%], respectively; P.001). One-year mortality was 29.1% (95% CI, 26.0%-32.2%) in patients undergoing valvular surgery vs 58.4% (95% CI, 54.1%-62.6%) in those not undergoing surgery (P.001). Cox proportional hazards modeling with propensity score adjustment for surgery showed that advanced age, diabetes mellitus, health care-associated infection, causative microorganism (Staphylococcus aureus or fungi), severe HF (New York Heart Association class III or IV), stroke, and paravalvular complications were independently associated with 1-year mortality, whereas valvular surgery during the initial hospitalization was associated with lower mortality.In this cohort of patients with infective endocarditis complicated by HF, severity of HF was strongly associated with surgical therapy and subsequent mortality, whereas valvular surgery was associated with lower in-hospital and 1-year mortality.

A comparison of patients with erythema migrans due to Borrelia garinii versus Borrelia burgdorferi has not been reported.One hundred nineteen patients from New York State with erythema migrans caused by B. burgdorferi were compared with 116 patients from Slovenia with erythema migrans due to B. garinii infection.Patients with B. garinii infection were older, more often reported a tick bite, and developed larger lesions (median largest diameter: 18 and 14 cm, respectively; p = 0.01) that more often had central clearing (61.2% compared with 35.3%; p0.0001). Patients infected with B. burgdorferi, however, more often had systemic symptoms (68.9% vs. 37.1%; p0.0001), including fatigue (p0.0001), arthralgia (p = 0.0003), myalgia (p0.0001), headache (p = 0.0008), fever and/or chills (p0.0001), and stiff neck (p0.0001), and more often had abnormal physical findings (57.1% compared with 11.2%; p0.0001), such as fever (p = 0.0002) or regional lymphadenopathy (p0.0001). There was a trend for more patients with B. burgdorferi infection to have multiple erythema migrans skin lesions (13.4% compared with 5.2%; p = 0.051), and among patients with multiple erythema migrans the number of lesions was greater in B. burgdorferi-infected patients (median: 5.5 compared with 2.0; p = 0.006).The results of the present study indicate that in patients with erythema migrans the clinical features vary according to whether infection is caused by B. garinii or B. burgdorferi.

Six adult solid-organ transplant recipients who had chronic drug-induced immunosuppression and who presented with solitary erythema migrans were treated with antibiotics administered at the same dosage and for the same duration used for the treatment of early, localized Lyme borreliosis in immunocompetent patients. The patients had a smooth course of illness and a favorable outcome but did not develop a measurable borrelial serum antibody response.

BACKGROUND: Therapeutic guidelines for treatment of late manifestations of Lyme borreliosis have not yet become well established. Patients with symptoms suggesting central nervous system involvement are often treated with courses of intravenous ceftriaxone. This is an expensive treatment approach with potentially severe side effects. We compared the efficacy, side effects and costs of doxycycline and ceftriaxone in the treatment of such patients. PATIENTS AND METHODS: Adult patients qualified for the study if they had nonspecific symptoms suggesting central nervous system involvement for more than six months (but without overt clinical signs of the involvement), had positive serum borrelial antibody titers and/or erythema migrans prior to the onset of symptoms, had not been previously treated with antibiotics and did not have pleocytosis in the cerebrospinal fluid. Patients were given either 100 mg of oral doxycycline twice daily for 4 weeks (23 patients) or 2 g of intravenous ceftriaxone daily for 2 weeks followed by 100 mg of doxycycline twice daily for another 2 weeks (23 patients). Clinical outcome was assessed during a 12-month follow-up period. RESULTS: Improvement in the frequency and/or the intensity of symptoms was reported by more than two-thirds of the 46 patients enroled in the study. The two treatment regimens were found to be correspondingly effective. Photosensitivity reactions and gastrointestinal symptoms were noted more often among patients receiving doxycycline than in those receiving ceftriaxone. Treatment with doxycycline proved to be much cheaper than with ceftriaxone. CONCLUSIONS: In patients with previously untreated chronic Lyme borreliosis with symptoms suggesting central nervous system involvement but without overt clinical signs of it, and without pleocytosis in the cerebrospinal fluid, treatment with doxycycline is as effective as with ceftriaxone. Treatment with doxycycline is cheap and relatively safe, but gastrointestinal symptoms and photosensitivity reactions can be expected more often than with ceftriaxone.

The aim of the present study was to establish which combination of serological method and Borrelia strain used as an antigen would provide the most appropriate demonstration of borrelial infection in patients with eythema migrans residing in Slovenia. Four different strains were chosen as antigens: two strains of B. afzelii and two strains of B. garinii which differed in their expression of the outer proteins OspA, OspB and OspC. Each individual strain was used as antigen in immunofluorescence test (IFT), enzyme-linked immunosorbent assay (EIA) with whole borrelial cells, and EIA with ultrasonicated borrelial cells. With these 12 different tests, 100 samples were examined for the presence of specific IgM and IgG antibodies: 50 sera of blood donors and 50 sera of patients with erythema migrans. The latter were further subdivided into skin culture-positive and -negative subgroups. A commercial Western blot (WB) test was performed for 26 sera of the control group and 25 sera of patients with erythema migrans. The four different methods had distinct specificity and sensitivity. The most specific approaches were IFT (100% for IgM and 90-92% for IgG) and the WB test (100% for IgM and 73% for IgG), followed by EIA with whole borrelial cells (80-98% for IgM and 76-84% for IgG) and EIA with ultrasonicated borrelial cells (76-94% for IgM and 72-80% for IgG). The sensitivity levels of all these tests were low. The most sensitive were EIA tests with whole borrelial cells (28-36% for IgM and 32-42% for IgG) followed by EIA with ultrasonicated borrelial cells (22-32% for IgM and 24-36% for IgG), the WB test (16% for IgM and 32% for IgG) and IFT (0-2% for IgM and 14-20% for IgG). The following methods gave significant differences between patients and negative controls in detecting IgM antibodies: EIA with whole borrelial cells with both B. afzelii antigens and with antigen B. garinii that expressed OspA and OspC, EIA with ultrasonicated borrelial cells with antigen B. afzelii that expressed OspA, OspB and OspC. In detecting IgG antibodies, significant differences were observed between EIA with whole borrelial cells and with antigen B. afzelii that expressed OspA and OspB. Borreliae were isolated from the skin of 34/50 (68%) patients with erythema migrans: two strains failed to grow, while 26/32 (81%) strains were identified as B. afzelii, 5/32 (16%) as B. garinii and 1/32 (3%) as B. burgdorferi sensu stricto. No statistically significant differences in serologic test results between culture-positive and -negative patients with erythema migrans were found.

The aim of the study was to assess genotypic and phenotypic diversity among a large number of clinical isolates of Borrelia burgdorferi sensu lato obtained from patients in Slovenia. Plasmid profiles and species identification were determined by PFGE, protein profiles by SDS-PAGE. Of 706 B. burgdorferi sensu lato human isolates 599 (85%) were found to be B. afzelii, 101 (14%) B. garinii and six (1%) B. burgdorferi sensu stricto. The vast majority of strains (605; 86%) were isolated from skin, 58 (8%) from blood, and 43 (6%) from CSF. When analysed by RFLP, B. afzelii strains were unique, while heterogeneity was found within B. garinii and B. burgdorferi sensu stricto species. An unusual plasmid content was found in 52/706 (7%) isolated strains, more often in B. garinii than in B. afzelii strains. A plasmid dimer was found in B. afzelii and B. garinii strains, whereas multiple copies of the large plasmid were associated nearly exclusively with B. garinii strains. Analysis of protein profiles revealed that OspA and OspB are expressed more often by B. afzelii strains, and OspC by B. garinii strains. Heterogeneity of Borrelia strains may play a significant role in the virulence and pathogenesis of the infection. Differences in antigenic components have an important impact on serological testing and vaccine development.

To establish epidemiological, clinical and laboratory differences between adult patients with proven acute human granulocytic ehrlichiosis (HGE) and patients with the initial phase of tick-borne encephalitis (TBE).Epidemiological, clinical and laboratory findings were compared in nine patients with acute HGE (established by the presence of specific DNA sequences of Ehrlichia phagocytophila in whole blood by polymerase chain reaction and/or by seroconversion or at least a four-fold change of serum antibody titres to E. phagocytophila by indirect immunofluorescence assay) and 29 patients with the initial phase of TBE (demonstrated in ELISA tests by the presence of serum IgM antibodies to TBE virus).Findings were similar for the majority of the general parameters examined, which included sex, age, incubation period, duration of fever, and frequency of additional tick bites. However, a statistically significant difference was found for the duration of fever before the first visit (median 7 days in patients with acute HGE and 4 days in patients with the initial phase of TBE; p = 0.0169), and for the frequency of hospitalisation, which was higher for patients with the initial phase of TBE (29/29) than for those with acute HGE (5/9; p = 0.0017). Comparison of clinical signs and symptoms and laboratory findings in the two groups revealed significant differences: in patients with acute HGE there was a higher frequency of chills (4/9 versus 3/29, respectively; p = 0.0407), myalgia (8/9 versus 13/29, respectively; p = 0.0263), and arthralgia (7/9 versus 3/29, respectively; p = 0.0003), and elevated values of lactate dehydrogenase (7/9 versus 3/29, respectively; p = 0.0003) and concentration of C-reactive protein (9/9 versus 6/29, respectively; p = 0.0000).In a patient with febrile illness occurring after a tick bite, a clinical report of chills, myalgia and arthralgia, and laboratory findings of elevated values for lactate dehydrogenase and concentration of C-reactive protein direct towards a diagnosis of acute HGE rather than the initial phase of TBE.

Skin biopsy samples from 150 patients with typical cutaneous manifestation of Lyme borreliosis, erythema migrans, were cultivated for the presence of Borrelia burgdorferi sensu lato in modified Kelly Pettenkofer (MKP) medium and analysed with two different polymerase chain reactions using either flagellin or nested OspA primers. Cultivation was successful in 75 of 150 (50%) skin samples. Out of 70 strains that were typed using PFGE, B. afzelii was identified in 60 (86%), B. garinii in 10 (14%) specimens, while no B. burgdorferi sensu stricto strains were found. B. burgdorferi sensu lato DNA was detected with polymerase chain reaction in 28% and 61% of skin samples, using flagellin and nested OspA primers, respectively. Concordant results in all three procedures employed in the present study were found in 62 (41%) specimens: 25/150 (17%) were positive with all three methods and 37/150 (25%) samples were completely negative.

Experimental studies have shown that the efficacy of transmission of B. burgdorferi sensu lato from an infected tick to an experimental animal is significantly associated with the duration of tick attachment. Scutal index is the ratio between body length and scutum width and was found to be an objective indicator of the duration of Ixodes scapularis tick attachment, but no data for I. ricinus have been published. In this preliminary report on 30 volunteers with an attached I. ricinus tick (21 had an adult female tick and 9 a nymph), none developed any sign of Lyme borreliosis but we were able to demonstrate two asymptomatic seroconversions in a six-week follow-up period. Twenty-six (87%) volunteers claimed that they were able to determine the approximate duration of tick attachment; participants with attached adult female ticks estimated the duration of attachment to be 30 (2-90) hours, while those with attached nymphs reported 48 (18-90) hours (p = 0.681). Scutal indices were 3.2 (2-5) for nymphs and 3.2 (1-5) for adult ticks, indicating 60- and 48-hour attachment, respectively. According to the volunteers' assessment and scutal index findings, approximately 80% and 45% of adult female ticks were removed within 48 hours after the tick bite (p = 0.032), respectively, while the corresponding values for nymphs were 85% and 17% (p = 0.053). Our findings were limited by low numbers of volunteers and by the lack of experimental data on the value of the scutal index for estimation of the duration of I. ricinus tick attachment.

To identify asymptomatic heart involvement early in the course of Lyme borreliosis by analysis of electrocardiograms (ECGs) of patients with solitary erythema migrans (EM).We enrolled in this prospective study 220 consecutive previously healthy patients, receiving no medication, who were diagnosed with typical solitary EM at our Lyme borreliosis Outpatient Clinic in 1998. Their ECG findings were compared with the ECG results in 165 age and sex-matched healthy persons.Three patients with EM but none in the control group had first degree AV block (p = 0.319). Second and third degree AV blocks, electrocardiographic signs of pericarditis, myocarditis or rhythm disturbances were not found in any of the ECGs. Comparison of findings in patients with EM and the control group revealed statistically significant differences in frequency (66.2 +/- 1.47 beats/min in patients with EM versus 68.4 +/- 1.52 beats/min in controls; p = 0.043), duration of Q (0.013 +/- 0.001 s in patients with EM versus 0.015 +/- 0.001 s in controls; p0.001), and in depth of S (0.135 +/- 0.016 mV in patients with EM versus 0.104 +/- 0.012 mV in controls; p0.05), but not for several other ECG parameters. These differences were found in females as well as in males. Comparison of ECG findings in subgroups of patients with EM (grouped according to EM characteristics such as length of incubation, duration of skin lesion and the presence of associated systemic symptoms) did not reveal any significant difference.AV blocks, the most typical heart manifestation of early disseminated Lyme borreliosis, are a rare finding in patients with solitary EM, and in our study their frequency did not differ from that in the control group. We do not have a reliable explanation for the shorter duration of Q and deeper S wave in patients with EM compared with age and sex-matched controls.

ContextProsthetic valve endocarditis (PVE) is associated with significant mortality and morbidity. The contemporary clinical profile and outcome of PVE are not well defined.ObjectivesTo describe the prevalence, clinical characteristics, and outcome of PVE, with attention to health care–associated infection, and to determine prognostic factors associated with in-hospital mortality.Design, Setting, and ParticipantsProspective, observational cohort study conducted at 61 medical centers in 28 countries, including 556 patients with definite PVE as defined by Duke University diagnostic criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to August 2005.Main Outcome MeasureIn-hospital mortality.ResultsDefinite PVE was present in 556 (20.1%) of 2670 patients with infective endocarditis. Staphylococcus aureus was the most common causative organism (128 patients [23.0%]), followed by coagulase-negative staphylococci (94 patients [16.9%]). Health care–associated PVE was present in 203 (36.5%) of the overall cohort. Seventy-one percent of health care–associated PVE occurred within the first year of valve implantation, and the majority of cases were diagnosed after the early (60-day) period. Surgery was performed in 272 (48.9%) patients during the index hospitalization. In-hospital death occurred in 127 (22.8%) patients and was predicted by older age, health care–associated infection (62/203 [30.5%]; adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.08-2.44; P = .02), S aureus infection (44/128 [34.4%]; adjusted OR, 1.73; 95% CI, 1.01-2.95; P = .05), and complications of PVE, including heart failure (60/183 [32.8%]; adjusted OR, 2.33; 95% CI, 1.62-3.34; P