Therapeutic drug monitoring of polymyxin B cerebrospinal fluid concentrations in patients with carbapenem-resistant Gram-negative bacteria-induced central nervous system infection.

OBJECTIVES: Central nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections. METHODS: Forty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality. RESULTS: All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin. CONCLUSIONS: After intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.

Maternal celiac disease and the risk for long-term infectious morbidity of the offspring.

PROBLEM: Celiac disease is an autoimmune disease, patients with celiac have increased risk for infections, and offspring of celiac mothers have increased morbidity. The aim of the study was to assess long-term infectious morbidity among offspring of pregnant women with celiac disease. METHOD OF STUDY: A population-based cohort study was conducted, including all singleton deliveries between the years 1991-2014 at a tertiary medical center. The offsprings were subdivided into two groups: offsprings of mothers with and without celiac disease. Data on demographics, maternal, perinatal, and long-term hospitalizations for infectious morbidity were compared between the two groups. RESULTS: During the study period there were 210 (0.09%) deliveries of mothers with celiac, and they were compared to 242170 (99.91%) deliveries of non-celiac mothers. Cumulative infectious morbidity was significantly higher in offspring of mothers with celiac compared to offspring of mothers without celiac (Kaplan-Meier, log-rank p = .004). Specifically, among the offspring of mothers with celiac significantly higher rates of bacteremia was noted (1.0% vs. 0.1%; p = .001), and infections of the central nervous system (1% vs. 0.2%; p = .028). In the Cox multivariable model which accounted for confounding variables, being born to mothers with celiac disease was associated with significantly increased risk for long-term infectious morbidity of the offspring (adjusted HR = 1.6, 95% CI 1.165-2.357, p = .005). CONCLUSIONS: Maternal celiac disease is an independent risk factor for long-term infectious morbidity for the offspring.

The epidemiology and clinical spectrum of infections of the central nervous system in adults in north India.

Infections of the central nervous system (CNS) are a leading cause of mortality in low- and middle-income countries. We studied the spectrum, aetiology and outcome of CNS infections in 401 consecutive patients aged ≥12 years admitted at the medical emergency centre of PGIMER, Chandigarh, India. An aetiological diagnosis was made in 365 (91.0%) patients, with 149 (40.8%) microbiologically confirmed cases. CNS tuberculosis was the most prevalent cause (51.5%), followed by viral meningoencephalitis (13.9%), community-acquired bacterial meningitis (9.7%), cryptococcal meningitis (6.2%), scrub typhus meningoencephalitis (1.7%), neurocysticercosis (1.7%) and fungal brain abscess (1.7%). Human immunodeficiency virus (11.0%) and diabetes mellitus (6.2%) remained the usual predisposing conditions. We found a mortality rate of 27.9%, highest in cases without an aetiology (64.5%). Tuberculosis remained the most common cause; however, an increasing number of scrub typhus, dengue, fungal infections and non-classical bacterial pathogens may indicate a change in the epidemiology of community-acquired CNS infections in India.

Multidrug resistant and extensively drug resistant Acinetobacter baumannii hospital infection associated with high mortality: a retrospective study in the pediatric intensive care unit.

BACKGROUND: Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors and overall mortality for MDR/XDR Acinetobacter baumannii infected pediatric patients. METHODS: This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children's Hospital in China from December 2014 to May 2018. Acinetobacter baumannii clinical isolates were recovered from different specimens including blood, sputum, bronchoalveolar lavage fluid, cerebrospinal fluid, ascites, hydrothorax, and urine. Antibiotic susceptibility test was determined according to the Clinical and Laboratory Standards Institute interpretive criteria. Clinical and biological data were obtained from the patients' medical records. RESULTS: 102 patients with Acinetobacter baumannii infection were enrolled. The median age was 36 (9.6, 98.8) months, and there were 63 male in the case group. The overall mortality rate was 29.4%, while the Acinetobacter baumannii-associated mortality rate was 16.7% (17/102, 12 bloodstream infections, 4 meningitis and 1 intra-abdominal infection). Bloodstream infections occurred in 28 patients (27.5%), and 10 patients (9.8%) among them had central line-associated bloodstream infections (6 central venous catheters, 2 PICCs, 1 venous infusion port and 1 arterial catheter). Cerebrospinal fluid (CSF) cultures were positive in 4(3.9%) patients. 14(13.7%) patients got positive cultures in ascites and hydrothorax. Lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity (6.2% ± 3.61% vs. 9.15% ± 6.21%, P = 0.029), higher CD4+ T cell ratio (39.67% ± 12.18% vs. 32.66% ± 11.44%, P = 0.039),and a higher serum level of interlukin-8 (IL-8, 15.25 (1.62, 47.22)pg/mL vs. 0.1 (0.1, 22.99)pg/mL, P = 0.01) when Acinetobacter baumannii infection developed. Multivariate logistic analysis indicated that high serum level of Cr (RR, 0.934, 95%CI, 0.890-0.981; P = 0.007) and high BUN/ALB level (RR, 107.893, 95%CI, 1.425-870.574; p = 0.005) were associated with high risk of mortality in MDR/XDR Acinetobacter baumannii infected patients. CONCLUSION: MDR/XDR Acinetobacter baumannii infection is a serious concern in pediatric patients with high mortality. Bloodstream and central nervous system infection accounted for high risk of death. Acute kidney injury is associated with high risk of mortality.

Early surgery may lower mortality in patients suffering from severe spinal infection.

PURPOSE: Spinal infection (SI) is a life-threatening condition and treatment remains challenging. Numerous factors influence the outcome of SI and both conservative and operative care can be applied. As SI is associated with mortality rates between 2 and 20% even in developed countries, the purpose of the present study was to investigate the occurrence and causes of death in patients suffering from SI. METHODS: A retrospective analysis was performed on 197 patients, categorized into two groups according to their outcome: D (death) and S (survival). The diagnosis was based on clinical and imaging (MRI) findings. Data collected included demographics, clinical characteristics, comorbidities, infection parameters, treatment details, outcomes, and causes of death. RESULTS: The number of deaths was significantly higher in the conservative group (n = 9/51, 18%) compared with the operative counterpart (n = 8/146, 6%; p = 0.017). Death caused by septic multiorgan failure was the major cause of fatalities (n = 10/17, 59%) followed by death due to cardiopulmonary reasons (n = 4/17, 24%). The most frequent indication for conservative treatment in patients of group D included "highest perioperative risk" (n = 5/17, 29%). CONCLUSION: We could demonstrate a significantly higher mortality rate in patients solely receiving conservative treatment. Mortality is associated with number and type of comorbidities, but also tends to be correlated with primarily acquired infection. As causes of death are predominantly associated with a septic patient state or progression of disease, our data may call for an earlier and more aggressive treatment. Nevertheless, prospective clinical trials will be mandatory to better understand the pathogenesis and course of spinal infection, and to develop high quality, evidence-based treatment recommendations.

Cerebrospinal fluid biomarkers in patients with central nervous system infections: a retrospective study.

BACKGROUND: Central nervous system (CNS) may be infected by several agents, resulting in different presentations and outcomes. Analysis of cerebrospinal fluid (CSF) markers could be helpful to differentiate specific conditions and setting an appropriate therapy. METHODS: Patients presenting with signs and symptoms were enrolled if, before receiving a diagnostic lumbar puncture, signed a written informed consent. We analyzed CSF indexes of blood-brain barrier permeability (CSF to serum albumin ratio or CSAR), inflammation (CSF to serum IgG ratio, neopterin), amyloid deposition (1-42 ß-amyloid), neuronal damage (Total tau (T-tau), Phosphorylated tau (P-tau), and 14.3.3 protein) and astrocyte damage (S-100ß). RESULTS: Two hundred and eighty-one patients were included: they were mainly affected by herpesvirus encephalitis, enterovirus meningoencephalitis, bacterial meningitis (Neisseria meningitidis and Streptococcus pneumoniae), and infection by other etiological agents or unknown pathogen. Their CSF features were compared with HIV-negative patients and native HIV-positive individuals without CNS involvement. 14.3.3 protein was found in bacterial and HSV infections while T-tau and neopterin were abnormally high in the herpesvirus group. P-tau, instead, was elevated in enterovirus meningitis. S-100ß was found to be high in patients with HSV-1 and HSV-2 infections but not in those with Varicella Zoster Virus (VZV). Thirty-day mortality was unexpectedly low (2.7%): patients who died had higher levels of T-tau and, significantly, lower levels of Aß1-42. CONCLUSION: This work demonstrates that CSF biomarkers of neuronal damage or inflammation may vary during CNS infections according to different causative agents. The prognostic value of these biomarkers needs to be assessed in prospective studies.

Clinical Presentations and Outcomes of Post-Operative Central Nervous System Infection Caused by Multi-Drug-Resistant/Extensively Drug-Resistant Acinetobacter baumannii: A Retrospective Study.

Background: Post-operative central nervous system infection (PCNSI) caused by multi-drug-resistant/extensively drug-resistant (MDR/XDR) Acinetobacter baumannii is a severe complication. This study aimed to analyze the clinical presentation and treatment of this disorder. Patients and Methods: A retrospective study that recruited patients having PCNSI caused by MDR/XDR Acinetobacter baumannii was performed at our institute. The patients' demographic information and clinical data were recorded and analyzed. To analyze treatment, we assigned patients to different groups according to whether they had intraventricular/intrathecal injection of antibiotic agents or cerebrospinal fluid (CSF) drainage therapy. Results: Twenty-four patients were included. The risk factors were classified into two categories: environmental factors (intensive care unit stay, tracheal intubation or tracheotomy, positive culture of MDR/XDR Acinetobacter baumannii from other samples) or infectious approaches (CSF drainage, incision CSF leakage). Cerebrospinal fluid sterilization was achieved in 13 patients (54.2%) and the 30-day mortality was 50%. In the seven patients having intraventricular/intrathecal injection of antibiotic agents, the CSF sterilization rate was 71.4% (5/7) and 30-day mortality was 28.6% (2/7), compared with 47.1% (8/17; p = 0.27) and 58.8% (10/17; p = 0.18) in patients having only intravenous antibiotic agents. In 19 patients having CSF drainage therapy for PCNSI, the CSF sterilization rate was 63.2% (12/19) and 30-day mortality was 42.1% (8/19) compared with 20% (1/5; p = 0.08) and 80% (4/5; p = 0.13) in the remaining patients. Conclusions: The risk factors for PCNSI caused by Acinetobacter baumannii can be classified in two categories: environmental factors or infectious approaches. Both intraventricular/intrathecal injection of antibiotic agents and CSF drainage are helpful for CSF sterilization.

Comparison of medical and/or surgical management of 23 cats with intracranial empyema or abscessation.

OBJECTIVES: Feline intracranial abscessation or empyema is infrequently reported in the veterinary literature. To date, the largest study is based on a population of 19 cats with otogenic infection. The aim of this study was to review a larger population of cats with intracranial empyema from multiple aetiologies and document their signalment, imaging findings, treatment protocols (including medical and/or surgical management) and to compare outcomes. METHODS: Cases presenting to a single referral centre over a 10 year period with compatible history, neurological signs and imaging findings consistent with intracranial abscessation and empyema were reviewed retrospectively. RESULTS: Twenty-three cats met the inclusion criteria. Advanced imaging (CT and/or MRI) was performed in 22/23 cats; one case was diagnosed via ultrasound. Ten cases underwent medical and surgical management combined, 10 underwent solely medical management and three were euthanased at the time of diagnosis. Short-term outcome showed that 90% of surgically managed and 80% of medically managed cats were alive at 48 h post-diagnosis. Long-term survival showed that surgically managed cases and medically managed cases had a median survival time of 730 days (range 1-3802 days) and 183 days (range 1-1216 days), respectively. No statistical significance in short- or long-term survival ( P >0.05) was found between medically and surgically managed groups. CONCLUSIONS AND RELEVANCE: Feline intracranial abscessation and empyema are uncommon conditions that have historically been treated with combined surgical and medical management. This study documents that, in some cases, intracranial abscessation and empyema can also be successfully treated with medical management alone.

Intra-cerebrospinal fluid antibiotics to treat central nervous system infections: A review and update.

Central nervous system infections can be complications of neurosurgical procedures or can occur spontaneously, and occasionally lead to devastating neurological complications, increased rate of mortality, and lengthier stays in the hospital, subsequently increasing costs. The use of intrathecal antibiotics to bypass the blood brain barrier and provide effective concentrations to the central nervous system has been described as an adjunct treatment option. However, the regimens of antibiotics utilized intrathecally have not been standardized. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from inception to 2017 and after removing duplicates and checking for relevancy, the final number of articles yielded was 200. This review summarizes the use of antibiotics intrathecally to treat CNS infections, the dosages, therapeutic efficacies, and highlights significant side effects. The current rates of mortality in patients suffering from CNS infections is high, thus intrathecal antibiotic therapy should be considered as a potential therapeutic strategy in this patient population. Multiple antibiotics have demonstrated safety and efficacy when used intrathecally, and further studies, including clinical trials, need to be performed to elucidate their full therapeutic potential and outline proper dosing regimens.

Factors associated with fatal outcome of children with enterovirus A71 infection: a case series.

Enterovirus A-71 (EV-A71) may be fatal, but the natural history, symptoms, and signs are poorly understood. This study aimed to examine the natural history of fatal EV-A71 infection and to identify the symptoms and signs of early warning of deterioration. This was a clinical observational study of fatal cases of EV-A71 infection treated at five Chinese hospitals between 1 January 2010 and 31 December 2012. We recorded and analysed 91 manifestations of EV-A71 infection in order to identify early prognosis indicators. There were 54 fatal cases. Median age was 21.5 months (Q1-Q3: 12-36). The median duration from onset to death was 78.5 h (range, 6 to 432). The multilayer perceptron analysis showed that ataxia respiratory, ultrahyperpyrexia, excessive tachycardia, refractory shock, absent pharyngeal reflex, irregular respiratory rhythm, hyperventilation, deep coma, pulmonary oedema and/or haemorrhage, excessive hypertension, tachycardia, somnolence, CRT extension, fatigue or sleepiness and age were associated with death. Autopsy findings (n = 2) showed neuronal necrosis, softening, perivascular cuffing, colloid and neuronophagia phenomenon in the brainstem. The fatal cases of enterovirus A71 had neurologic involvement, even at the early stage. Direct virus invasion through the neural pathway and subsequent brainstem damage might explain the rapid progression to death.

Incidence and mortality of acquired brain injury in young Danish adults between 1994 and 2013: a nationwide study.

BACKGROUND: We estimated the annually incidence and mortality of acquired brain injury (ABI) in people aged 15-30 years during 1994-2013. METHODS: All Danes with a first-ever hospital diagnosis of ABI, including traumatic brain injury (TBI), encephalopathy, CNS-infection or brain tumour, were identified in the Danish National Patient Register. Incidence rates (IRs) and estimated annual percentage changes (EAPC) were estimated by Poisson regression. Mortality was estimated by the Kaplan-Meier estimator and adjusted hazard ratios (aHR) were computed using Cox regression with 1994-1998. RESULTS: A total of 10,542 individuals were hospitalized with a first-time diagnosis of ABI. The IR for ABI decreased from 63.36 to 33.91/100,000 person-years from 1994 to 2013 [EAPC: -2.78% (95% CI: -3.26 to -2.28)] mainly driven by a decreasing IR of TBI [EAPC: -6.53% (95% CI: -9.57 to -3.39)] during 2007-2013. IRs of brain tumour and CNS infections also decreased significantly. The mortality after ABI tended to be higher during 1999-2013 compared to 1994-1998. For brain tumour, the 1-year mortality decreased significantly [2009-2013 aHR: 0.41 (95% CI: 0.23-0.72)]. CONCLUSION: Incidence of hospitalisations for ABI and in particular TBI has decreased significantly. Overall, the mortality after ABI has not improved, but the mortality after brain tumour has decreased significantly.

Molecular diagnosis of central nervous system opportunistic infections and mortality in HIV-infected adults in Central China.

BACKGROUND: CSF PCR is the standard diagnostic technique used in resource-rich settings to detect pathogens of the CNS infection. However, it is not currently used for routine CSF testing in China. Knowledge of CNS opportunistic infections among people living with HIV in China is limited. METHODS: Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral and fungal etiologies. Pathogen-specific primers were used to detect DNA from cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and John Cunningham virus (JCV) via real-time polymerase chain reaction (PCR). RESULTS: Cryptococcal meningitis accounted for 63.0% (34 of 54) of all causes of meningitis, 13.0% (7/54) for TB, 9.3% (5/54) for Toxoplasma gondii. Of 54 samples sent for viral PCR, 31.5% (17/54) were positive, 12 (22.2%) for CMV, 2 (3.7%) for VZV, 1 (1.9%) for EBV, 1 (1.9%) for HHV-6 and 1 (1.9%) for JCV. No patient was positive for HSV. Pathogen-based treatment and high GCS score tended to have a lower mortality rate, whereas patients with multiple pathogens infection, seizures or intracranial hypertension showed higher odds of death. CONCLUSION: CNS OIs are frequent and multiple pathogens often coexist in CSF. Cryptococcal meningitis is the most prevalent CNS disorders among AIDS. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve the diagnosis of AIDS related OIs in resource-limited developing countries, but the cost-efficacy remains to be further evaluated.

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.

CNS infections in Greenland: A nationwide register-based cohort study.

BACKGROUND: Indigenous Arctic people suffer from high rates of infectious diseases. However, the burden of central nervous system (CNS) infections is poorly documented. This study aimed to estimate incidence rates and mortality of CNS infections among Inuits and non-Inuits in Greenland and in Denmark. METHODS: We conducted a nationwide cohort study using the populations of Greenland and Denmark 1990-2012. Information on CNS infection hospitalizations and pathogens was retrieved from national registries and laboratories. Incidence rates were estimated as cases per 100,000 person-years. Incidence rate ratios were calculated using log-linear Poisson-regression. Mortality was estimated using Kaplan-Meier curves and Log Rank test. RESULTS: The incidence rate of CNS infections was twice as high in Greenland (35.6 per 100,000 person years) as in Denmark (17.7 per 100,000 person years), but equally high among Inuits in Greenland and Denmark (38.2 and 35.4, respectively). Mortality from CNS infections was 2 fold higher among Inuits (10.5%) than among non-Inuits (4.8%) with a fivefold higher case fatality rate in Inuit toddlers. CONCLUSION: Overall, Inuits living in Greenland and Denmark suffer from twice the rate of CNS infections compared with non-Inuits, and Inuit toddlers carried the highest risk of mortality. Further studies regarding risk factors such as genetic susceptibility, life style and socioeconomic factors are warranted.

Central nervous system infection following allogeneic hematopoietic stem cell transplantation.

OBJECTIVE/BACKGROUND: Here, we described the clinical characteristics and outcomes of central nervous system (CNS) infections occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution over the previous 6 years. METHODS: Charts of 353 consecutive allogeneic transplant recipients were retrospectively reviewed for CNS infection. RESULTS: A total of 17 cases of CNS infection were identified at a median of 38 days (range, 10-1028 days) after allo-HSCT. Causative pathogens were human herpesvirus-6 (n=6), enterococcus (n=2), staphylococcus (n=2), streptococcus (n=2), varicella zoster virus (n=1), cytomegalovirus (n=1), John Cunningham virus (n=1), adenovirus (n=1), and Toxoplasma gondii (n=1). The cumulative incidence of CNS infection was 4.1% at 1 year and 5.5% at 5 years. CONCLUSION: Multivariate analysis revealed that high-risk disease status was a risk factor for developing CNS infection (p=.02), and that overall survival at 3 years after allo-HSCT was 33% in patients with CNS infection and 53% in those without CNS infection (p=.04).

Infections of the Central Nervous System after Unrelated Donor Umbilical Cord Blood Transplantation or Human Leukocyte Antigen-Matched Sibling Transplantation.

We analyzed the incidence, clinical characteristics, prognostic factors, and outcome of central nervous system (CNS) infections in consecutive patients with receiving umbilical cord blood transplantation (UCBT) (n = 343) or HLA-matched sibling donor stem cell transplantation (MST) (n = 366). Thirty-four CNS infections were documented at a median time of 116 days after transplantation (range, 7 to 1161). The cumulative incidence (CI) risk of developing a CNS infection was .6% at day +30, 2.3% at day +90, and 4.9% at 5 years. The 5-year CI of CNS infection was 8.2% after UCBT and 1.7% after MST (P < .001). The causative micro-organisms of CNS infections were fungi (35%), virus (32%), Toxoplasma spp. (12%), and bacteria (12%). Fungal infections occurred in 11 patients after UCBT and 1 after MST and were due to Aspergillus spp. (n = 8), Cryptococcus neoformans (n = 2), Scedosporium prolificans (n = 1), and Mucor (n = 1). Except for 1 patient, all died from CNS fungal infection. Viral infections occurred in 9 patients after UCBT and 1 after MST and were due to human herpes virus 6 (n = 7), cytomegalovirus (n = 2), and varicella zoster virus (n = 1). CNS toxoplasmosis was diagnosed in 3 patients after UCBT and 1 after MST. Other pathogens were Staphylococcus spp, Nocardia spp, Streptococcus pneumoniae, and Mycobacterium tuberculosis. Twenty of the 34 patients (59%) died from the CNS infection. In multivariable analysis, UCBT and disease stage beyond first complete remission were independently associated with the risk of developing CNS infections. The 5-year overall survival was 19% in patients who developed a CNS and 39% for those who did not (P = .006). In conclusion, our study showed that CNS infections are a significant clinical problem after stem cell transplantation associated with poor survival. They were more frequent after UCBT compared to MST.

Predictive performance of quick Sepsis-related Organ Failure Assessment for mortality and ICU admission in patients with infection at the ED.

OBJECTIVE: The objectives of this study are to investigate the performance of the quick Sepsis-related Organ Failure Assessment (qSOFA) in predicting mortality and intensive care unit (ICU) admission in patients with clinically diagnosed infection and to compare its performance with that of Mortality in Emergency Department Sepsis (MEDS), Acute Physiology and Chronic Health Evaluation (APACHE) II, and Sepsis-related Organ Failure Assessment (SOFA). METHODS: From July to December 2015, we retrospectively analyzed 477 patients clinically diagnosed with infection in the emergency department. We compared the performance of SOFA, MEDS, APACHE II, and qSOFA in predicting ICU admission and 28-day mortality. RESULTS: All scores were higher in nonsurvivors and ICU patients than in survivors and non-ICU patients (P< .001). The area under the receiver operating characteristic curve of qSOFA was lower than that of MEDS (0.666 vs 0.751; P< .05) and similar to that of SOFA (0.729) and APACHE II (0.732) in predicting 28-day mortality. The areas under the receiver operating characteristic curve of qSOFA, SOFA, MEDS, and APACHE II in predicting ICU admission were 0.636, 0.682, 0.661, and 0.640, respectively. There were no significant differences among the score systems. In patients with qSOFA scores less than 2 and greater than or equal to 2, 28-day mortality rates were 17.4% and 42.9% (P< .001), and ICU admission rates were 16.0% and 33.3% (P< .001). CONCLUSIONS: Quick SOFA predicted ICU admission with similar performance to that of SOFA, MEDS, and APACHE II. Its prognostic ability was similar to that of SOFA and APACHE II but slightly inferior to that of MEDS.

Tuberculous meningitis is a major cause of mortality and morbidity in adults with central nervous system infections in Kota Kinabalu, Sabah, Malaysia: an observational study.

BACKGROUND: Central nervous system (CNS) infections are a significant contributor to morbidity and mortality globally. However, most published studies have been conducted in developed countries where the epidemiology and aetiology differ significantly from less developed areas. Additionally, there may be regional differences due to variation in the socio-economic levels, public health services and vaccination policies. Currently, no prospective studies have been conducted in Sabah, East Malaysia to define the epidemiology and aetiology of CNS infections. A better understanding of these is essential for the development of local guidelines for diagnosis and management. METHODS: We conducted a prospective observational cohort study in patients aged 12 years and older with suspected central nervous system infections at Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia between February 2012 and March 2013. Cerebrospinal fluid was sent for microscopy, biochemistry, bacterial and mycobacterial cultures, Mycobacterium tuberculosis polymerase chain reaction (PCR), and multiplex and MassCode PCR for various viral and bacterial pathogens. RESULTS: A total of 84 patients with clinically suspected meningitis and encephalitis were enrolled. An aetiological agent was confirmed in 37/84 (44 %) of the patients. The most common diagnoses were tuberculous meningitis (TBM) (41/84, 48.8 %) and cryptococcal meningoencephalitis (14/84, 16.6 %). Mycobacterium tuberculosis was confirmed in 13/41 (31.7 %) clinically diagnosed TBM patients by cerebrospinal fluid PCR or culture. The acute case fatality rate during hospital admission was 16/84 (19 %) in all patients, 4/43 (9 %) in non-TBM, and 12/41 (29 %) in TBM patients respectively (p = 0.02). CONCLUSION: TBM is the most common cause of CNS infection in patients aged 12 years or older in Kota Kinabalu, Sabah, Malaysia and is associated with high mortality and morbidity. Further studies are required to improve the management and outcome of TBM.

Comorbidities and factors associated with central nervous system infections and death in non-perinatal listeriosis: a clinical case series.

BACKGROUND: Listeriosis is a rare disease caused by the bacterium Listeria monocytogenes and mainly affects at risk people. Listeriosis can lead to sepsis, central nervous system (CNS) infections and death. The objectives of this study were to describe and quantify comorbidities and neurological sequelae underlying non-perinatal listeriosis cases and to describe the factors associated with death and CNS infections in non-perinatal listeriosis. METHODS: We retrospectively collected clinical data through computerized, paper or microfilmed medical records in two Belgian university hospitals. Logistic regression models and likelihood ratio tests allowed identifying factors associated with death and CNS infections. RESULTS: Sixty-four cases of non-perinatal listeriosis were included in the clinical case series and 84 % were affected by at least one comorbid condition. The main comorbidities were cancer, renal and severe cardio-vascular diseases. Twenty-nine patients (45 %) suffered from a CNS infection and 14 patients (22 %) died during hospitalization, among whom six (43 %) had a CNS involvement. Among surviving patients, eleven suffered from neurological sequelae (22 %) at hospital discharge; all had CNS infection. Five of these patients (45 %) still suffered of their neurological sequelae after a median follow-up of one year (range: 0.08-19). The factor associated with death during the hospitalization was the presence of a severe cardiovascular disease (OR = 4.72, p = 0.015). Two factors inversely related with CNS infections were antibiotic monotherapy (OR = 0.28, p = 0.04) and the presence of renal disease (OR = 0.18, p = 0.02). CONCLUSIONS: In a public health context these results could be a starting point for future burden of listeriosis studies taking into account comorbidity.

Thirty-Day Mortality After Infection Among Persons With Severe Mental Illness: A Population-Based Cohort Study in Denmark.

OBJECTIVE: Persons with severe mental illness die 15-20 years earlier on average than persons without severe mental illness. Although infection is one of the leading overall causes of death, no studies have evaluated whether persons with severe mental illness have a higher mortality after infection than those without. METHOD: The authors studied mortality rate ratios and cumulative mortality proportions after an admission for infection for persons with severe mental illness compared with persons without severe mental illness by linking data from Danish national registries. RESULTS: The cohort consisted of all persons hospitalized for infection during the period 1995-2011 in Denmark (N=806,835), of whom 11,343 persons had severe mental illness. Within 30 days after an infection, 1,052 (9.3%) persons with a history of severe mental illness and 58,683 (7.4%) persons without a history of severe mental illness died. Thirty-day mortality after any infection was 52% higher in persons with severe mental illness than in persons without (mortality rate ratio=1.52, 95% CI=1.43-1.61). Mortality was increased for all infections, and the mortality rate ratios ranged from 1.27 (95% CI=1.15-1.39) for persons hospitalized for sepsis to 2.61 (95% CI=1.69-4.02) for persons hospitalized for CNS infections. Depending on age, 1.7 (95% CI=1.2-2.2) to 2.9 (95% CI=2.0-3.7) more deaths were observed within 30 days after an infection per 100 persons with a history of severe mental illness compared with 100 persons without such a history. CONCLUSIONS: Persons with severe mental illness have a markedly elevated 30-day mortality after infection. Some of these excess deaths may be prevented by offering individualized and targeted interventions.