Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients, particularly human immunodeficiency virus (HIV)-positive patients, but CM may also occur in apparently immunocompetent individuals. Outcome analyses have been performed in such patients but, due to the high prevalence of HIV infection worldwide, CM patients today may be admitted to hospitals with unknown HIV status, particularly in underdeveloped countries. The objective of this multicenter study was to analyze all types of CM cases in an aggregate cohort to disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics, clinical, microbiological, radiological, therapeutic data, and outcomes were included. Death, neurological sequelae, or relapse were unfavorable outcomes. Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104 (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale (GCS) scores (p = 0.021), cerebrospinal fluid (CSF) leukocyte counts > 20 (p = 0.038), and higher CSF glucose levels (p = 0.048) were associated with favorable outcomes. On the other hand, malignancy (p = 0.026) was associated with poor outcomes. Although all CM patients require prompt and rational fungal management, those with significant risks for poor outcomes need to be closely monitored.

Correction to: Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

In the original version of this article, Mustafa Sunbul was not included in the list of authors for this article. The name has been added accordingly.

The burden and epidemiology of community-acquired central nervous system infections: a multinational study.

Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.

Epidemiology of meningitis with a negative CSF Gram stain: under-utilization of available diagnostic tests.

Meningitis with a negative cerebrospinal fluid Gram stain (CSF-GS) poses a diagnostic challenge as more than 50% of patients remain without an aetiology. The introduction of polymerase chain reaction (PCR) and arboviral serologies have increased diagnostic capabilities, yet large scale epidemiological studies evaluating their use in clinical practice are lacking. We conducted a prospective observational study in New Orleans between November 1999 and September 2008 (early era) when PCR was not widely available, and in Houston between November 2008 and June 2013 (modern era), when PCR was commonly used. Patients presenting with meningitis and negative CSF-GS were followed for 4 weeks. All investigations, PCR used, and results were recorded as they became available. In 323 patients enrolled, PCR provided the highest diagnostic yield (24·2%) but was ordered for 128 (39·6%) patients; followed by serology for arboviruses (15%) that was ordered for 100 (31%) of all patients. The yield of blood cultures was (10·3%) and that of CSF cultures was 4%; the yield for all other tests was <10%. Overall, 65% of the patients remained without a diagnosis at 4 weeks: 72·1% in early era vs. 53·4% (P < 0·01) in modern era; this change was attributed to diagnosing more viral pathogens, 8·3% and 26·3% (P < 0·01), respectively. The introduction of PCR and arboviral serologies has improved the yield of diagnosing patients with meningitis and a negative CSF-GS, but both tests are being under-utilized.

Outpatient parenteral antimicrobial therapy for the treatment of methicillin-susceptible Staphylococcus aureus: a comparison of cefazolin and ceftriaxone.

PURPOSE: Although the antistaphylococcal penicillins remain the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections, cefazolin and ceftriaxone are often prescribed due to their less frequent dosing and reduced cost. The purpose of this study was to compare clinical outcomes and adverse events in patients receiving outpatient parenteral antimicrobial therapy (OPAT) with ceftriaxone or cefazolin for the treatment of MSSA infections. METHODS: A retrospective study was carried out of 122 patients evaluated at Ben Taub and Lyndon B. Johnson General Hospitals in Houston, Texas, between January 1, 2006, and March 31, 2012, with a documented MSSA infection who received cefazolin or ceftriaxone as OPAT. A favorable clinical outcome was determined by their primary care physician's assessment at follow-up in the clinic. RESULTS: Out of 122 patients, 78 (64 %) were treated with cefazolin and 44 (36 %) with ceftriaxone. Patients were predominantly young (median age 46 years), male (54.2 %), and Hispanic (51.2 %). Patients were similar in terms of baseline demographics, types of infections, and management of infections. Favorable clinical outcomes were similar between cefazolin and ceftriaxone (67.9 versus 79.8 %, p = 0.17), along with a similar incidence of adverse events and complications (5.1 versus 2.3 %, p = 0.65, and 26.9 versus 18.2 %, p = 0.38, respectively). CONCLUSIONS: OPAT with either cefazolin or ceftriaxone is similar in terms of favorable outcomes, adverse events, and complications when treating MSSA infections. A randomized clinical trial is needed in order to confirm these results.

DNA methylation during sexual embryogenesis and implications on the induction of somatic embryogenesis in Castanea sativa Miller.

From anthesis to mature seed formation, burrs from cross-pollinated adult Castanea sativa Miller trees were characterized and seven developmental stages defined based on macro and micromorphological traits. In order to get an insight into the involvement of epigenetic mechanisms in sexual embryogenesis and to define somatic embryogenesis induction capability, global DNA methylation and the somatic embryogenic competence were quantified. On cross-pollinated trees once fertilization takes place, at least one ovule per ovary becomes dominant, and transient DNA demethylation occurs coinciding with the start of the sexual embryogenic programme. Unfertilized ovules from the same cluster, which maintain their prior size, increase their methylation level and undergo degeneration. These results were validated using non-cross-pollinated trees and the asynchrony of flower receptivity. When testing in vitro somatic embryogenesis response of isolated dominant ovules and axes from zygotic embryos under cross-pollinated conditions, the highest competence was found for reaching seed maturity. Thus, a "developmental window" of somatic embryogenesis in chestnut has been characterized. It includes from fertilization to embryo maturity, and a transient decrease in methylation is necessary after fertilization for the development of the somatic embryogenesis response.

The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study.

We aimed to describe clinical, laboratory, diagnostic and therapeutic features of spinal tuberculosis (ST), also known as Pott disease. A total of 314 patients with ST from 35 centres in Turkey, Egypt, Albania and Greece were included. Median duration from initial symptoms to the time of diagnosis was 78 days. The most common complications presented before diagnosis were abscesses (69%), neurologic deficits (40%), spinal instability (21%) and spinal deformity (16%). Lumbar (56%), thoracic (49%) and thoracolumbar (13%) vertebrae were the most commonly involved sites of infection. Although 51% of the patients had multiple levels of vertebral involvement, 8% had noncontiguous involvement of multiple vertebral bodies. The causative agent was identified in 41% of cases. Histopathologic examination was performed in 200 patients (64%), and 74% were consistent with tuberculosis. Medical treatment alone was implemented in 103 patients (33%), while 211 patients (67%) underwent diagnostic and/or therapeutic surgical intervention. Ten percent of the patients required more than one surgical intervention. Mortality occurred in 7 patients (2%), and 77 (25%) developed sequelae. The distribution of the posttreatment sequelae were as follows: 11% kyphosis, 6% Gibbus deformity, 5% scoliosis, 5% paraparesis, 5% paraplegia and 4% loss of sensation. Older age, presence of neurologic deficit and spinal deformity were predictors of unfavourable outcome. ST results in significant morbidity as a result of its insidious course and delayed diagnosis because of diagnostic and therapeutic challenges. ST should be considered in the differential diagnosis of patients with vertebral osteomyelitis, especially in tuberculosis-endemic regions. Early establishment of definitive aetiologic diagnosis and appropriate treatment are of paramount importance to prevent development of sequelae.

Treatment of bacterial meningitis.

Major epidemiological changes have altered the empiric therapy of patients with bacterial meningitis, a disease with significant morbidity and mortality. We offer recommendations for empiric management decisions and specific antibiotic choices for patients with bacterial meningitis.

The Acute Aseptic Meningitis Syndrome.

The aseptic meningitis syndrome (AMS) is as a diagnostic and management challenge. Since the initial description of AMS in 1925, the differential diagnosis of infectious and noninfectious agents associated with this syndrome has progressed. Although most cases of aseptic meningitis have a benign outcome, several etiologies require urgent therapy if the patient is to survive and be cured. This review will address the differential diagnosis of AMS and focus on recent empiric data that may aid the clinician treating these patients.

Computed tomography of the head before lumbar puncture in adults with suspected meningitis.

BACKGROUND: In adults with suspected meningitis clinicians routinely order computed tomography (CT) of the head before performing a lumbar puncture. METHODS: We prospectively studied 301 adults with suspected meningitis to determine whether clinical characteristics that were present before CT of the head was performed could be used to identify patients who were unlikely to have abnormalities on CT. The Modified National Institutes of Health Stroke Scale was used to identify neurologic abnormalities. RESULTS: Of the 301 patients with suspected meningitis, 235 (78 percent) underwent CT of the head before undergoing lumbar puncture. In 56 of the 235 patients (24 percent), the results of CT were abnormal; 11 patients (5 percent) had evidence of a mass effect. The clinical features at base line that were associated with an abnormal finding on CT of the head were an age of at least 60 years, immunocompromise, a history of central nervous system disease, and a history of seizure within one week before presentation, as well as the following neurologic abnormalities: an abnormal level of consciousness, an inability to answer two consecutive questions correctly or to follow two consecutive commands, gaze palsy, abnormal visual fields, facial palsy, arm drift, leg drift, and abnormal language (e.g., aphasia). None of these features were present at base line in 96 of the 235 patients who underwent CT scanning of the head (41 percent). The CT scan was normal in 93 of these 96 patients, yielding a negative predictive value of 97 percent. Of the three misclassified patients, only one had a mild mass effect on CT, and all three subsequently underwent lumbar puncture, with no evidence of brain herniation one week later. CONCLUSIONS: In adults with suspected meningitis, clinical features can be used to identify those who are unlikely to have abnormal findings on CT of the head.

[An assessment of myocardial ischemia in women with the exercise test validated by coronary angiography]. / Evaluación de la isquemia miocárdica en mujeres con la prueba de esfuerzo validada mediante coronariografía.

Ischemic heart disease has been studied in men and women only as a group. We studied the sensitivity and specificity of the exercise stress testing in women. The exercise stress testing (EST) was validated with the coronary arteriography. We studied 72 women and 129 men, the mean age was 55 years for women and 51 years for men. We found in women 83.2% of estimated maximal heart rate; the rate pressure product was 2.4, no different from the values recorded in men (p greater than 0.06). The blood pressure response to exercise was higher in women, and the maximal work capacity was more elevated in men (p less than 0.006). We found normal coronary arteries in 41 women, 70.7% with a positive (EST) compared with a 87.07% in men. The sensitivity and specificity of the exercise stress testing for the diagnosis of ischemic heart disease is smaller in women.

Non- epidermidis coagulase-negative staphylococcal bacteremia: clinical predictors of true bacteremia.

In order to explore the clinical significance and risk factors for true bacteremia caused by coagulase-negative staphylococci (CNS) other than Staphylococcus epidermidis, a retrospective cohort study of 160 patients with at least one blood culture positive for non- epidermidis CNS was performed. True bacteremia was diagnosed in 32 (20%) of the patients. On multivariate analysis the following factors were associated with true bacteremia: (i) more than one positive blood culture, (ii) presence of a central venous catheter, and (iii) methicillin resistance. The results of this study indicate that non- epidermidis CNS can cause significant bloodstream infections.