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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Medical management of invasive fungal infections of the central nervous system in pediatric cancer patients.

Fungal infections of the central nervous system (CNS) are associated with high mortality rates in immunocompromised patients. Surgical intervention is a mainstay of therapy, but not always possible. We describe the use of medical therapy for the treatment of CNS fungal infections in four pediatric cancer patients. Definitive resection was not performed in any patient. All patients initially received combination antifungal therapy with good clinical response; long-term survival was documented in two patients able to transition to long-term azole therapy. Prolonged antifungal therapy is an important option for treating invasive CNS fungal infections when surgery is not feasible.

Adjunctive intraventricular antibiotic therapy for bacterial central nervous system infections in critically ill patients with traumatic brain injury.

BACKGROUND: Limited data exist on the role of adjunctive intraventricular (IVT) antibiotics for the treatment of central nervous system (CNS) infections in traumatic brain injury (TBI) patients. OBJECTIVE: To evaluate differences in CNS infection cure rates for TBI patients who received adjunctive IVT antibiotics compared with intravenous (IV) antibiotics alone. METHODS: We retrospectively identified patients with TBI and bacterial CNS infections admitted to the trauma intensive care unit (ICU) from 1997 to 2013. Study patients received IV and IVT antibiotics, and control patients received IV antibiotics alone. Clinical and microbiological cure rates were determined from patient records, in addition to ICU and hospital lengths of stay (LOSs), ventilator days, and hospital mortality. RESULTS: A total of 83 patients were enrolled (32 study and 51 control). The duration of IV antibiotics was similar in both groups (10 vs 12 days, P = 0.14), and the study group received IVT antibiotics for a median of 9 days. Microbiological cure rates were 84% and 82% in study and control groups, respectively (P = 0.95). Clinical cure rates were similar at all time points. No significant differences were seen in days of mechanical ventilation, ICU or hospital LOS, or hospital mortality. When only patients with external ventricular drains were compared, cure rates remained similar between groups. CONCLUSIONS: TBI patients with CNS infections had similar microbiological and clinical cure rates whether they were treated with adjunctive IVT antibiotics or IV antibiotics alone. Shorter than recommended durations of antibiotic therapy still resulted in acceptable cure rates and similar clinically relevant outcomes.

Molecular diagnosis of central nervous system opportunistic infections in HIV-infected Zambian adults.

BACKGROUND: Knowledge of central nervous system (CNS) opportunistic infections (OIs) among people living with human immunodeficiency virus (HIV) in sub-Saharan Africa is limited. METHODS: We analyzed 1 cerebrospinal fluid (CSF) sample from each of 331 HIV-infected adults with symptoms suggestive of CNS OI at a tertiary care center in Zambia. We used pathogen-specific primers to detect DNA from JC virus (JCV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) types 1 and 2, Mycobacterium tuberculosis, and Toxoplasma gondii via real-time polymerase chain reaction (PCR). RESULTS: The patients' median CD4(+) T-cell count was 89 cells/µL (interquartile range, 38-191 cells/µL). Of 331 CSF samples, 189 (57.1%) had at least 1 pathogen. PCR detected DNA from EBV in 91 (27.5%) patients, M. tuberculosis in 48 (14.5%), JCV in 20 (6.0%), CMV in 20 (6.0%), VZV in 13 (3.9%), HSV-1 in 5 (1.5%), and HSV-2 and T. gondii in none. Fungal and bacteriological studies showed Cryptococcus in 64 (19.5%) patients, pneumococcus in 8 (2.4%), and meningococcus in 2 (0.6%). Multiple pathogens were found in 68 of 189 (36.0%) samples. One hundred seventeen of 331 (35.3%) inpatients died during their hospitalization. Men were older than women (median, 37 vs 34 years; P = .01), more recently diagnosed with HIV (median, 30 vs 63 days; P = .03), and tended to have a higher mortality rate (40.2% vs 30.2%; P = .07). CONCLUSIONS: CNS OIs are frequent, potentially treatable complications of AIDS in Zambia. Multiple pathogens often coexist in CSF. EBV is the most prevalent CNS organism in isolation and in coinfection. Whether it is associated with CNS disease or a marker of inflammation requires further investigation. More comprehensive testing for CNS pathogens could improve treatment and patient outcomes in Zambia.

Neuroinfectious diseases at a European neurological tertiary care center: one-third of patients require treatment in the neurological intensive care unit.

BACKGROUND AND PURPOSE: Studies on the impact of infectious diseases affecting the nervous system are sparse. METHODS: All patients with neuroinfectious diseases (NIDs) who were treated at our Department of Neurology from 2005 until 2009 were retrospectively analyzed. RESULTS: Patients with NIDs required treatment at the intensive care unit in 34.8%. The mortality rate of patients with NIDs was significantly higher than that of other inpatients with neurological diseases (5.1% vs. 3.0%, respectively, P = 0.018). CONCLUSION: In summary, this study shows that patients with NIDs are severely ill and mortality is high.

Three years of paediatric morbidity and mortality at the National Hospital in Dili, East Timor.

AIM: The aim of this study was to undertake a retrospective review of admissions and discharges to the paediatric wards at the National Hospital Guido Valadares, Dili, as the epidemiology of hospitalised children in East Timor cannot be easily understood from the hospital health management information system. METHOD: Data were sourced from unit registers for 3 years, 2008-2010 inclusive. Demographic characteristics and principal diagnoses were related to the risk of dying using stepwise multivariate logistic regression. RESULTS: There were 5909 children admitted to the wards over the study period and 60% were <2 years of age. The commonest reasons for admission were lower respiratory tract infections (LRIs) and gastroenteritis (43% and 16%, respectively). Severe malnutrition (MN) was recorded in only 5% of admissions. Overall, 6% of children died, mainly attributed to LRI (28%), central nervous system infections (16%) and MN (11%). Younger age, residence outside of Dili and admission during a busier period were independently associated with an increased risk of death. Nine per cent of hospitalised infants aged 1-6 months of age died and half of all deaths occurred within 2 days of admission. CONCLUSIONS: The study provides, for the first time, an understanding of the admissions and outcomes of the busiest paediatric inpatient unit in East Timor. It emphasises important health system issues which impact on both data quality and hospital outcomes.

Clinical profile and difficulties in diagnosis of central nervous system infections in adult patients in a tertiary care hospital.

OBJECTIVES: We aimed to describe the pattern of central nervous system (CNS) infections and accuracy of diagnosis in a Sri Lankan tertiary care hospital. METHODS: We prospectively studied all adult patients with suspected CNS infection admitted over a two-year period. Data were collected on demographic and clinical features, laboratory findings, treatment and immediate outcome. Diagnosis of CNS infection was categorized as definite, probable, possible and uncertain. RESULTS: We studied 215 patients [59.1% males; mean age (SD) 44 (20) years]. Blood cultures were done in 65 (30.2%) and only one was positive. Lumbar puncture was done in 146 (67.9%), and cerebrospinal fluid Gram stains, culture and acid-fast bacilli stains were all negative. Diagnosis of CNS infection was considered 'definite' in only one patient, 'probable' in 57.2%, 'possible' in 5.6%, and 'uncertain' in 26%. An alternative diagnosis was found in 23 patients (10.7%). Intravenous antibiotics and aciclovir were given on emperical grounds, largely without microbiological confirmation. CONCLUSIONS: Diagnosis of CNS infections is highly unsatisfactory with available facilities, even in a tertiary care setting.

CNS infections caused by Mycobacterium abscessus complex: clinical features and antimicrobial susceptibilities of isolates.

OBJECTIVES: CNS infections caused by non-tuberculous mycobacteria (NTM) are rare and only three cases of CNS infections due to Mycobacterium abscessus complex have been reported. METHODS: We searched the Mycobacteriology Database of the National Taiwan University Hospital and identified patients with CNS infections due to NTM. RESULTS: A total of 15 patients, namely 4 HIV-seropositive patients and 11 HIV-seronegative patients, with CNS infections caused by NTM were identified during 2000-10. All of the HIV-seropositive patients had disseminated Mycobacterium avium complex infections. Among the 11 HIV-seronegative patients, NTM CNS infections were due to M. abscessus complex in 8 patients, M. avium complex in 2 patients and Mycobacterium kansasii in 1 patient. All the six preserved M. abscessus complex isolates were confirmed to be Mycobacterium massiliense by erm(41) PCR and 23S rRNA gene sequence analysis. Among the eight patients with infections due to M. abscessus complex, three had otolaryngological diseases, four had received neurosurgery and one had disseminated disease. Five patients received surgical debridement or intracranial device removal and three patients died of M. abscessus complex CNS infection. Among the five patients who survived, all received clarithromycin-based combination therapy with a median duration of 12 months and four received surgical intervention. All six isolates available for drug susceptibility testing showed uniform susceptibility to clarithromycin and five were susceptible to amikacin. CONCLUSIONS: Our study revealed that M. abscessus complex isolates, particularly M. massiliense, should be considered potential pathogens causing CNS infections. Long-duration clarithromycin-based combination therapy plus surgical intervention may provide the best chance of cure.

Optimal glycemic control in neurocritical care patients: a systematic review and meta-analysis.

INTRODUCTION: Hyper- and hypoglycemia are strongly associated with adverse outcomes in critical care. Neurologically injured patients are a unique subgroup, where optimal glycemic targets may differ, such that the findings of clinical trials involving heterogeneous critically ill patients may not apply. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing intensive insulin therapy with conventional glycemic control among patients with traumatic brain injury, ischemic or hemorrhagic stroke, anoxic encephalopathy, central nervous system infections or spinal cord injury. RESULTS: Sixteen RCTs, involving 1248 neurocritical care patients, were included. Glycemic targets with intensive insulin ranged from 70-140 mg/dl (3.9-7.8 mmol/L), while conventional protocols aimed to keep glucose levels below 144-300 mg/dl (8.0-16.7 mmol/L). Tight glycemic control had no impact on mortality (RR 0.99; 95% CI 0.83-1.17; p = 0.88), but did result in fewer unfavorable neurological outcomes (RR 0.91; 95% CI 0.84-1.00; p = 0.04). However, improved outcomes were only observed when glucose levels in the conventional glycemic control group were permitted to be relatively high [threshold for insulin administration > 200 mg/dl (> 11.1 mmol/L)], but not with more intermediate glycemic targets [threshold for insulin administration 140-180 mg/dl (7.8-10.0 mmol/L)]. Hypoglycemia was far more common with intensive therapy (RR 3.10; 95% CI 1.54-6.23; p = 0.002), but there was a large degree of heterogeneity in the results of individual trials (Q = 47.9; p<0.0001; I2 = 75%). Mortality was non-significantly higher with intensive insulin in studies where the proportion of patients developing hypoglycemia was large (> 33%) (RR 1.17; 95% CI 0.79-1.75; p = 0.44). CONCLUSIONS: Intensive insulin therapy significantly increases the risk of hypoglycemia and does not influence mortality among neurocritical care patients. Very loose glucose control is associated with worse neurological recovery and should be avoided. These results suggest that intermediate glycemic goals may be most appropriate.