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.

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.

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.

MRI and clinical syndrome in dura mater-related Creutzfeldt-Jakob disease.

OBJECTIVE: Iatrogenic Creutzfeldt-Jakob disease (iCJD) is mainly associated with dura mater (DM) grafts and administration of human growth hormones (hGH). Data on disease course in DM-CJD are limited. We describe the clinical and diagnostic findings in this patient group with special emphasis on MRI signal alterations. METHODS: Ten DM-CJD patients were studied for their clinical symptoms and diagnostic findings. The MRIs were evaluated for signal increase of the cortical and subcortical structures. RESULTS: DM-CJD patients had a median incubation time of 18 years and median disease duration of 7 months. The majority of patients were MM homozygous at codon 129 of the prion protein gene (PRNP) and presented with gait ataxia and psychiatric symptoms. No correlation between the graft site and the initial disease course was found. The MRI showed cortical and basal ganglia signal increase each in eight out of ten patients and thalamic hyperintensity in five out of ten cases. Of interest, patients with thalamic signal increase were homozygous for methionine. CONCLUSION: The MRI findings in DM-CJD largely resemble those seen in sporadic CJD, as the cortex and basal ganglia are mainly affected.

Candida infective endocarditis.

Candida infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore the epidemiology, treatment patterns, and outcomes of patients with Candida IE. We compared 33 Candida IE cases to 2,716 patients with non-fungal IE in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS). Patients were enrolled and the data collected from June 2000 until August 2005. We noted that patients with Candida IE were more likely to have prosthetic valves (p < 0.001), short-term indwelling catheters (p < 0.0001), and have healthcare-associated infections (p < 0.001). The reasons for surgery differed between the two groups: myocardial abscess (46.7% vs. 22.2%, p = 0.026) and persistent positive blood cultures (33.3% vs. 9.9%, p = 0.003) were more common among those with Candida IE. Mortality at discharge was higher in patients with Candida IE (30.3%) when compared to non-fungal cases (17%, p = 0.046). Among Candida patients, mortality was similar in patients who received combination surgical and antifungal therapy versus antifungal therapy alone (33.3% vs. 27.8%, p = 0.26). New antifungal drugs, particularly echinocandins, were used frequently. These multi-center data suggest distinct epidemiologic features of Candida IE when compared to non-fungal cases. Indications for surgical intervention are different and mortality is increased. Newer antifungal treatment options are increasingly used. Large, multi-center studies are needed to help better define Candida IE.

Community-acquired bacterial meningitis in adults: antibiotic timing in disease course and outcome.

OBJECTIVES: Despite improvements in diagnostic and therapeutic approach to adult patients with bacterial meningitis, the overall mortality rate is still high. The aim of this study was to evaluate antibiotic timing in the course and outcome of bacterial meningitis. METHODS: Two hundred and eighty six patients with community-acquired bacterial meningitis aged 14 years and more were included in this retrospective cohort study. Observational period was between 1 January 1990 and 31 December 2004. To assess the association of antibiotic timing and disease outcome we analyzed three timing periods (according to the onset of disease, onset of consciousness disturbance and the time of admission to hospital). Analysis was also performed in a subgroup of culture positive meningitis in 176 patients with altered mental status. RESULTS: Unfavorable outcome was found in 125 (43,7%) patients. In this group, the start of appropriate antibiotic treatment in relation to the onset of first symptoms and particularly to the onset of consciousness disturbance was significantly delayed (p = 0.018 and p < 0.001, respectively) compared to the favorable group. Logistic regression analysis in a subgroup of culture positive meningitis in patients with altered mental status revealed that early adequate antibiotic treatment related to the onset of overt signs of meningitis was independently associated with favorable outcome (OR = 11.19; 95% CI 4.37-32.57; p < 0.001). Advanced age, lower GCS and seizures (OR = 1.05, OR = 1.45 and OR = 3.65, respectively) were other risk factors of poor outcome. The presence of chronic diseases, pneumococcal etiology and clinical and laboratory variables which are indicators of disease severity (renal and/or liver dysfunction, hypotension and low cerebrospinal fluid glucose) were not confirmed as independent risk factors of poor outcome. CONCLUSIONS: Our study emphasizes the importance of early and adequate antibiotic treatment in the management of bacterial meningitis which significantly enhances the chances for favorable outcome.

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.

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.

Establishment of an active laboratory-based surveillance for bacterial meningitis in Croatia and molecular characterization of Neisseria meningitidis isolates causing meningococcal disease that were collected in the year 2000, the first year of activity.

In 2000, 23 Neisseria meningitidis (meningococcal [Men]) isolates were collected in Croatia through an active laboratory-based surveillance for bacterial meningitis (17 Men serogroup B [MenB], 4 MenC, 1 MenW135, and 1 nongroupable isolate). Molecular characterization revealed a substantial level of diversity with only six isolates belonging to electrophoretic type 5 (ET-5) and ET-37 hypervirulent complexes.

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).

Comparison of azithromycin and doxycycline in the treatment of erythema migrans.

BACKGROUND: A randomized, multicenter, open clinical trial was undertaken in order to compare the efficacies of azithromycin and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. PATIENTS AND METHODS: A total of 48 patients was treated orally with azithromycin, 500 mg bid on the 1st day, followed by 500 mg once daily for the next 4 days or doxycycline (40 patients) 100 mg bid for 14 days. RESULTS: Intention-to-treat analysis of clinical efficacy showed no difference between the two treatment regimens. Clinical success was observed in 46 (95.8%) azithromycin- and 33 (82.5%) doxycycline-treated patients, (p = 0.0731). Minor symptoms persisted or appeared in the posttreatment period in two of 47 azithromycin- and three of 35 doxycycline-treated patients (p = 0.646). Major manifestations appeared only in two patients in the doxycycline group (p = 0.179). There was no difference in the tolerability of both drugs. CONCLUSION: Azithromycin (a total dose of 3 g) is equally effective as standard doxycycline treatment for erythema migrans in adult patients.

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.

[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.

Nosocomial infections in critically ill infectious disease patients: results of a 7-year focal surveillance.

An incidence study on nosocomial infections in critically ill infectious disease patients was carried out in the intensive care unit (ICU) of a university hospital for infectious diseases over a 7-year period (1 January 1990 to 31 December 1996). A total of 660 patients who stayed in the ICU for over 48 h were prospectively observed. The patients were divided into two groups: one with central nervous system infections (442 patients) and the other with other severe infections (218 patients). The risk of nosocomial sepsis and pneumonia was significantly higher in patients suffering from severe central nervous system infections. The incidence of sepsis was 24.2% vs 11.4% (relative risk 1.95; 95% confidence interval 1.32-2.89); the incidence of pneumonia was 30.5% vs 14.7% (relative risk 2.09; 95% confidence interval 1.47-2.96). The incidence of urinary tract infection was 14.3% vs 13.3% (relative risk 1.07; 95% confidence interval 0.71-1.61). Density rates of nosocomial septic episodes were 21.1 +/- 37.1 vs 11.7 +/- 32.4 episodes/100 central venous-line days (P < 0.006). Nosocomial pneumonia occurred only in mechanically ventilated patients (36.9 +/- 61.2 vs 28.5 +/- 65.8 episodes per 1000 ventilatory days, P = 0.012). Nosocomial urinary tract infection occurred only in patients with urinary catheters (11.6 +/- 60.7 episodes/1000 urinary catheter days vs 18.7 +/- 90.1, P = 0.886). Multivariate regression analysis identified age, diagnosis of CNS infection, duration of urinary tract catheterization, the use of central venous lines and mechanical ventilation as independent risk factors of nosocomial sepsis. Duration of mechanical ventilation, use of steroids and diagnosis of CNS infection were independent risk factors of nosocomial pneumonia. A subanalysis identified tetanus patients to be at particular risk of nosocomial infections.

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.