Prospective observational cohort study of cerebrovascular CO2 reactivity in patients with inflammatory CNS diseases.

The purpose of this study was to evaluate the significance of cerebrovascular CO(2) reactivity (CO(2) R) in the course and outcome of inflammatory central nervous system (CNS) diseases. Sixty-eight patients with inflammatory CNS diseases and 30 healthy volunteers were included in this prospective observational cohort study. The observational period was between January 2005 and May 2009. The CO(2) R was measured by transcranial Doppler (TCD) ultrasound using the breath-holding method. We compared patients with normal CO(2) R (breath-holding index [BHI(m)] ≥ 1.18 = BHI(N) group) with patients who showed impaired CO(2) R (BHI(m) < 1.18 = BHI(R) group). We also analyzed the association of impaired CO(2) R with the etiology, severity, and outcome of disease. When compared to the BHI(N) group, the patients from the BHI(R) group were older, had a heavier consciousness disturbance, experienced more frequent respiratory failure, and, subsequently, had worse outcomes. There were no fatalities among the 28 patients in the BHI(N) group. The comparison of subjects with bacterial and non-bacterial meningitis revealed no significant differences. The unfavorable outcome of disease (Glasgow Outcome Scale [GOS] score 1-3) was significantly more common in subjects with impaired CO(2) R (62.5% vs. 10.7%). Logistic regression analysis was performed in order to establish the prognostic value of BHI(m). The outcome variable was unfavorable outcome (GOS 1-3), while the independent variables were age, Glasgow Coma Scale (GCS) score, and BHI(m). The age and BHI(m) showed the strongest influence on disease outcome. A decrease of BHI(m) for each 0.1 unit increased the risk of unfavorable outcome by 17%. Our study emphasizes the importance of CO(2) R assessment in patients with inflammatory CNS diseases.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients.

OBJECTIVES: To describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance. METHODS: Cirrhotic patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model. RESULTS: We enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure-SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29-18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93-5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28-1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73-4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48-4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12-0.73; p 0.008). CONCLUSIONS: MDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.

Central nervous system involvement of previously undiagnosed chronic lymphocytic leukemia in a patient with neuroborreliosis.

Leukemic involvement of the central nervous system (CNS) in previously undiagnosed chronic lymphocytic leukemia (CLL) is very rare. We report the case of a 62-year-old man with neuroborreliosis in which cytologic, immunocytochemical, and flow cytometry analyses revealed the presence of clonal B-lymphocytes in the cerebrospinal fluid (CSF). After the patient received antimicrobial therapy, his meningeal symptoms cleared up, and the number of cells in the CSF decreased. Monoclonal lymphocytes were still detectable at the same percentage, however, despite systemic chlorambucil therapy. The application of intrathecal dexamethasone therapy led to the disappearance of B-cell CLL (B-CLL) cells in the CSF. We presumed that the neuroborreliosis enabled the transmigration of leukocytes, including B-CLL cells, across the blood-brain barrier via activation of matrix metalloproteinase 9, an enzyme known to open the blood-brain barrier.

Managing atypical and typical herpetic central nervous system infections: results of a multinational study.

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

One-year outcome following biological or mechanical valve replacement for infective endocarditis.

BACKGROUND: Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality. METHODS AND RESULTS: Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p=0.0009) and 25.3% vs 16.6% (p<.0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). CONCLUSIONS: Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.

Antibiotic resistance among gram-negative nosocomial pathogens in the intensive care unit: results of 6-year body-site monitoring.

Results of 6-year body-site monitoring in an intensive care unit (ICU) are presented and antimicrobial resistance of gram-negative isolates analyzed. The study included 622 patients. Six hundred thirty-five bacterial isolates-causes of nosocomial sepsis, pneumonia, and urinary tract infections (UTIs)-were tested during the study. Gram-negative bacteria were the predominant isolates, causing 65% of cases of sepsis, 78.7% of pneumonias, and 70.2% of UTIs. Gram-negative isolates (454) were highly resistant to antimicrobials commonly used in the ICU, with the exception of imipenem. Resistance was 1.1% among pathogens responsible for UTIs, 6.7% among those causing sepsis, and 13.6% among those responsible for pneumonia. Klebsiella pneumoniae associated with pneumonia and sepsis was significantly less resistant to ciprofloxacin than were isolates from urine (22.8% and 13.9%, respectively, vs 44.4%). Pseudomonas aeruginosa strains responsible for pneumonia were less resistant to ceftazidime than were isolates causing sepsis and UTI (35.7% vs 51.3% and 51.5%, respectively). Acinetobacter calcoaceticus strains associated with UTI were significantly more resistant to netilmicin than were strains responsible for sepsis and pneumonia (83.3% vs 40.3% and 42.6%, respectively). The study confirmed that in addition to focused microbiologic surveillance, multiple-body-site monitoring can provide unique information about the sensitivity of the pathogens involved. The results suggest that antimicrobial resistance among nosocomial pathogens depends on the site of infection or the type of microbiologic specimen.

Antibiotic resistance among nosocomial isolates in a Croatian intensive care unit--results of a twelve-year focal surveillance of nosocomial infections.

Continuous 12-year (1990--2001) focal surveillance of the antibiotic resistance among the most common nosocomial pathogens (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter sp., and Staphylococcus aureus) in 1325 Intensive Care Unit patients was performed. The surveillance period was divided in three 4-year time intervals (1990--1993, 1994--1997 and 1998--2001) and the prevalence of resistance was compared between intervals. Specimens included blood, urine and respiratory tract specimens. The incidence and trends of resistance to six antibiotics showed inconsistent results. Aminoglycoside resistance decreased among K. pneumoniae_isolates (gentamicin 83%, 72.7% and 49.6%; amikacin 50.9%, 51.5% and 18.2%) and Acinetobacter sp. strains (amikacin 77%, 63.4% and 58.2%) but increased in P. aeruginosa (amikacin 27.5%, 63.3% and 44.1%). Overall, resistance to ceftazidime, ciprofloxacin, and imipenem increased but imipenem resistance is still low, particularly among Acinetobacter sp. isolates (0, 2.1% and 1.5%). However, imipenem resistance increased among P. aeruginosa (10.2%, 31.6%, 22.1%). The prevalence of methicillin resistance was high but did not change during the surveillance period (82.3%, 78.3% and 82.2%). The present study suggests a complex picture of the development of antibiotic resistance in a single ICU. Significant changes occur over time but they are unpredictable and do not show identical tendencies for different species and antibiotics.

Comparative analysis of azithromycin and clarithromycin efficacy and tolerability in the treatment of chronic prostatitis caused by Chlamydia trachomatis.

A total of 123 patients, older than 18 years of age, with symptoms of chronic prostatitis and inflammatory findings as well as the presence of Chlamydia trachomatis confirmed by DNA/RNA DIGENE hybridization method in expressed prostatic secretion or in voided bladder urine collected immediately after prostatic massage, were examined. The patients were randomized to receive a total of 4.5 g of azithromycin for 3 weeks, given as a 3-day therapy of 1 x 500 mg weekly or clarithromycin 500 mg b.i.d. for 15 days. Patients' sexual partners were treated at the same time. Clinical and bacteriological efficacy were evaluated 4-6 weeks after the end of therapy. In the group of patients with chronic chlamydial prostatitis the eradication rates (azithromycin 37/46, clarithromycin 36/45) and the clinical cure rates (azithromycin 32/46, clarithromycin 32/45) were not significantly different with regards to the administered drug (p > 0.05). In the group of patients with asymptomatic chlamydial prostatitis the eradication rates (azithromycin 11/16, clarithromycin 10/15) were not significantly different with regards to the administered drug (p = 1.00, OR = 1.1).

National and local antibiotic policies in Central and Eastern Europe.

To assess the antibiotic policies of Central European countries, we performed an overview of antibiotic stewardship, prescription habits and antibiotic prescription regulatory procedures. Since most Central European countries have had centralized health care and drug policies, the situation 10 years after decentralization is surprising. Only 3 of 10 Central European countries have some regulation of prescription of antibiotics, only 4 restrict some antibiotics, only 5 have hospital and only 3 national antibiotic policies. In all but 3 countries physicians can prescribe quinolones and/or 3rd generation oral cephalosporins as first-line antibiotics. Information on local and national antibiotic policies in Central and Eastern European countries is given including prescription guidelines for antibiotic use in community and hospital.

Creutzfeldt-Jakob disease in a patient with a lyophilized dura mater graft.

A 37-year-old patient with Creutzfeldt-Jakob disease (CJD) is presented, who had received a cadaveric dura matter graft 12 year before the onset of neurologic symptoms. Initial clinical presentation included cerebellar symptoms, with dementia and myoclonus developing in later stages of the disease. EEG showed diffuse slowing with sporadic triphasic periodic activity. CT was normal in the early stage but pronounced cerebral and cerebellar atrophy with widened sulci were seen on MRI in the late stage of the disease. The prion protein (PrP) gene was homozygous for valin at the polymorphic codon 129. Cerebrospinal fluid analysis for 14-3-3 protein was positive. We believe that this patient is the first Croatian to acquire CJD by dural implant. Based on this case and a review of 66 cases from the literature, it is manifest that the awareness of iatrogenic transmission of CJD and adoption of preventive measures are the only effective way to stop the spread of CJD among surgically treated patients.

[Treatment of erythema migrans]. / Lijecenje erythema migrans.

The article reviews existing clinical trials of the treatment of erythema migrans, localized early manifestation of Lyme disease. Although the treatment of this phase of Lyme disease is the best studied of all clinical manifestations, some questions remained to be answered. Author critically reviews definitions of the treatment success. Methodological diversities of the trials are emphasized. Often, treatment recommendations are not supported by existing clinical trials. Unnecessary use of antibiotics in the treatment and prophylaxis of erythema migrans is emphasized, too.

[Hospital infections and resistance to new antibiotics in intensive care units: relation to diagnostic and therapeutic procedures]. / Bolnicke infekcije i rezistencija na neke novije antibiotike u jedinici intenzivne skrbi: ovisnost o dijagnosticko-terapijskim zahvatima.

The results of hospital infection surveillance over an eight-month period in the Intensive Care Unit (ICU) of the University Hospital of Infectious Diseases "Dr Fran Mihaljevic", Zagreb, are presented together with the results of the antibiotic resistance of isolated gram-negative bacteria in relation to the clinical material taken for culture. Of 110 strains of gram-negative bacteria isolated, 103 (93.6%) were resistant to ampicillin, 80 (72%) to gentamicin, 74 (67%) to cefotaxime, 50 (45.5%) to pefloxacin. Imipenem, ciprofloxacin, ceftazidime and amikacin were the most active representatives of their respective groups with 5, 25, 49 and 50% of resistant strains. Strains isolated in urinary tract infections were significantly less resistant to amikacin and ceftazidime (p < 0.05) than strains isolated from other sources. Our findings stress the need for close surveillance of antibiotic resistance in these selected groups of patients, and are particularly relevant for planning empirical anmtibiotic therapy of hospital infection in the ICU.

Entry of ciprofloxacin into cerebrospinal fluid during bacterial, viral and tuberculous meningitis.

We studied the entry of ciprofloxacin into the cerebrospinal fluid (CSF) in 37 patients with various types of meningitis (bacterial meningitis 10 patients, viral 12 patients, tuberculous 7 patients). Eight patients were in the control group with normal CSF finding. Mean ciprofloxacin concentrations in the CSF 50-60 minutes after 200 mg of ciprofloxacin was given in infusion were 0.20 +/- 0.12 mg/L in patients with bacterial meningitis, which was significantly higher than in other tested groups (p = 0.0325). Ciprofloxacin achieved concentrations in the CSF 6.5-39% of serum (mean value 15% +/- 9%) in the bacterial meningitis group, while in the groups with viral and tuberculous meningitis the levels were significantly lower (approximately 9% of serum) but still higher than in the control group (approximately 5% of serum). Our data suggest that ciprofloxacin should be very cautiously used in selected patients with bacterial meningitis caused by multiple resistant strains of gram negative bacteria.

Pneumococcal meningitis in the elderly.

The authors reviewed 70 cases of Streptococcus pneumoniae meningitis occurring over a 5-years period (1985-1989). Clinical features, outcome and laboratory findings in elderly patients (> 60 years of age, 21 patients) were compared with those in younger patients (< 59 years of age, 49 patients). Mortality rate was 57% in elderly group vs. 20% in younger. Admission to the hospital was delayed in the elderly. Only 67.6% of them were admitted on the first two days of the illness vs. 81.6% of younger patients. Nearly 62% of them were deeply soporous or comatose on admission (Mathew-Lawson grade 3 and 4), while in the control group only 31% of patients had such severely altered mental status. Although glucose cerebrospinal fluid (CSF)/blood ratio tended to be lower in the elderly (0.09 vs 0.17) the difference did not reach statistical significance. Thrombocytes in the peripheral blood were lower in the elderly (113 x 10(9)/L vs. 148 x 10(9)/L, p < 0.05). When we compared laboratory findings in survivors and nonsurvivors from both groups, nonsurvivors had significantly lower glucose CSF/blood ratio (0.054 vs. 0.174, p = 0.008), and higher bilirubin levels in serum (27.9 vs 14.7, p = 0.003), but differences were more obvious in younger group of patients. Our results suggest that there is increased risk of death among elderly patients. It can be at least partially attributed to their later admittance to the hospital and because of that delayed start of the appropriate therapy and more severe conscious disturbances. All these factors contribute to the greater case-fatality ratio observed in elderly patients with pneumococcal meningitis.

The clinical picture of rabies in a child.

An eight-year-old boy developed rabies 31 days after having been scratched by a dog and died 9 day later. Intensive supportive medical treatment was complicated by apnea, cardiac arrest, hypotension, increased secretion of antidiuretic hormone and severe hypoproteinemia. The treatment with intramuscular human antirabies immunoglobulin (HRIG) 2400 I.U. and intrathecal 1200 I.U. in combination with intramuscular interferon alpha 4 million I.U. was given every second day. The diagnosis of rabies was confirmed before death, on the third day of the disease, by direct fluorescent antibody staining of the saliva and cerebrospinal fluid for viral antigen. At the autopsy, the brain tissue specimens were tested for the presence of the virus by inoculation into the suckling mice brain and for the viral antigen by direct fluorescent antibody method. The brain tissue specimens collected at autopsy were also tested for virus by direct fluorescent antibody method.