Not Just Endocarditis: Hospitalizations for Selected Invasive Infections Among Persons With Opioid and Stimulant Use Diagnoses-North Carolina, 2010-2018.

BACKGROUND: While increases in overdoses, viral hepatitis, and endocarditis associated with drug use have been well-documented in North Carolina, the full scope of invasive drug-related infections (IDRIs) has not. We characterized trends in IDRIs among hospitalized patients in North Carolina. METHODS: We compared invasive infections that were related or not related to drug use among hospitalized patients aged 18-55 years based on retrospective review of administrative records from 2010-2018. Hospitalizations for endocarditis, central nervous system/spine infections, osteomyelitis, and septic arthritis were labeled as IDRIs if discharge codes included opioid and/or amphetamine misuse. Trends, rates, and distributions were calculated. RESULTS: Among 44 851 hospitalizations for the specified infections, 2830 (6.3%) were IDRIs. The proportion of infections attributable to drug use increased from 1.5% (2010) to 13.1% (2018), and the rate grew from 1.2 to 15.1 per 100 000. Compared with those who had non-drug-related infections, patients with IDRIs were younger (median age, 35 vs 46 years), more likely to be non-Hispanic white (81% vs 56%), and had longer hospitalizations (median, 8 vs 6 days). 43% of hospitalizations for IDRIs involved infective endocarditis. CONCLUSIONS: The rate of IDRIs in North Carolina increased substantially during 2010-2018, indicating an urgent need for enhanced infection prevention, harm reduction, and addiction services aimed at community and inpatient settings.

CNS infections in HIV.

PURPOSE OF REVIEW: Central nervous system (CNS) infections associated with HIV remain significant contributors to morbidity and mortality, particularly among people living with HIV (PLWH) in resource-limited settings worldwide. In this review, we discuss several recent important scientific discoveries in the prevention, diagnosis, and management around two of the major causes of CNS opportunistic infections-tuberculous meningitis (TBM) and cryptococcal meningitis including immune reconstitution syndrome (IRIS) associated with cryptococcal meningitis. We also discuss the CNS as a possible viral reservoir, highlighting Cerebrospinal fluid viral escape. RECENT FINDINGS: CNS infections in HIV-positive people in sub-Saharan Africa contribute to 15-25% of AIDS-related deaths. Morbidity and mortality in those is associated with delays in HIV diagnosis, lack of availability for antimicrobial treatment, and risk of CNS IRIS. The CNS may serve as a reservoir for replication, though it is unclear whether this can impact peripheral immunosuppression. SUMMARY: Significant diagnostic and treatment advances for TBM and cryptococcal meningitis have yet to impact overall morbidity and mortality according to recent data. Lack of early diagnosis and treatment initiation, and also maintenance on combined antiretroviral treatment are the main drivers of the ongoing burden of CNS opportunistic infections. The CNS as a viral reservoir has major potential implications for HIV eradication strategies, and also control of CNS opportunistic infections.

The primary prevention of epilepsy: A report of the Prevention Task Force of the International League Against Epilepsy.

Among the causes of epilepsy are several that are currently preventable. In this review, we summarize the public health burden of epilepsy arising from such causes and suggest priorities for primary epilepsy prevention. We conducted a systematic review of published epidemiologic studies of epilepsy of 4 preventable etiologic categories-perinatal insults, traumatic brain injury (TBI), central nervous system (CNS) infection, and stroke. Applying consistent criteria, we assessed the quality of each study and extracted data on measures of risk from those with adequate quality ratings, summarizing findings across studies as medians and interquartile ranges. Among higher-quality population-based studies, the median prevalence of active epilepsy across all ages was 11.1 per 1000 population in lower- and middle-income countries (LMIC) and 7.0 per 1000 in high-income countries (HIC). Perinatal brain insults were the largest attributable fraction of preventable etiologies in children, with median estimated fractions of 17% in LMIC and 15% in HIC. Stroke was the most common preventable etiology among older adults with epilepsy, both in LMIC and in HIC, accounting for half or more of all new onset cases. TBI was the attributed cause in nearly 5% of epilepsy cases in HIC and LMIC. CNS infections were a more common attributed cause in LMIC, accounting for about 5% of all epilepsy cases. Among some rural LMIC communities, the median proportion of epilepsy cases attributable to endemic neurocysticercosis was 34%. A large proportion of the overall public health burden of epilepsy is attributable to preventable causes. The attributable fraction for perinatal causes, infections, TBI, and stroke in sum reaches nearly 25% in both LMIC and HIC. Public health interventions addressing maternal and child health care, immunizations, public sanitation, brain injury prevention, and stroke prevention have the potential to significantly reduce the burden of epilepsy.

Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

Opportunistic Neurologic Infections in Patients with Acquired Immunodeficiency Syndrome (AIDS).

Infections of the central nervous system (CNS) in individuals with human immunodeficiency virus (HIV) remain a substantial cause of morbidity and mortality despite the introduction of highly active antiretroviral therapy (HAART) especially in the resource-limited regions of the world. Diagnosis of these infections may be challenging because findings on cerebrospinal fluid (CSF) analysis and brain imaging are nonspecific. While brain biopsy provides a definitive diagnosis, it is an invasive procedure associated with a relatively low mortality rate, thus less invasive modalities have been studied in recent years. Diagnosis, therefore, can be established based on a combination of a compatible clinical syndrome, radiologic and CSF findings, and understanding of the role of HIV in these infections. The most common CNS opportunistic infections are AIDS-defining conditions; thus, treatment of these infections in combination with HAART has greatly improved survival.

A reappraisal of contributing factors leading to shunt infection.

BACKGROUND: Central nervous shunt infection (CNSI) is a cause of significant morbidity, causing shunt malfunction and chronic ill health. It can also lead to prolong hospital stay. The aim of this study was to look into the factors responsible for neurosurgical shunt infection and measures to prevent them. METHOD: This retrospective case study was done with nonrandomized convenience sampling. We studied 121 patients who underwent neurosurgical shunt operations during year 1994 to 1999. These patients received pre, per and post operative antibiotics to combat shunt infection. Study design was retrospective case study with non randomized convenience sampling. RESULT: Out of 121 patients, 65 patients were females and 56 males. The total number of shunts procedures performed in these patients was 151. Ninety-seven patients operated once for shunt procedure. Eighty-three (83) patients underwent ventriculo-peritoneal shunt, 10 patients underwent lumbo-peritoneal shunt, 3 had ventriculo-pleural shunt and 1 had ventriculo-atrial shunting done. Three patients developed shunt infection, only one had true primary infection. All were adults with male to female ratio of 2 to 1 and in all of them shunt was inserted first time. CONCLUSION: Strict aseptic technique and prophylactic use of antibiotics have critical role in the prevention of shunt infections.

Contemporary Approaches to Preventing and Treating Infections of Novel Intrathecal Neurostimulation Devices.

INTRODUCTION: Contemporary approaches to surgical site infections have evolved significantly over the last several decades in response to the economic pressures of soaring health care costs and increasing patient expectations of safety. Neurosurgeons face multiple unique challenges when striving to avoid as well as manage surgical implant infections. The tissue compartment, organ system, or joint is characterized by biological factors and physical forces that may not be universally relevant. Such implants, once rare, are now routine. Although the prevention, diagnosis, and treatment of surgical site infections involving neural implants has advanced, guidelines are ever changing, and the incidence still exceeds acceptable levels. We assess the impact of these factors on a new class of implantable neuromodulation devices. METHODS: The available evidence along with practice patterns were examined and organized to establish relevant groupings for continuing evaluation and to propose justifiable recommendations for the treatment of infections that might arise in the case of intradural spinal cord stimulators. RESULTS: Few studies in the modern era have systematically evaluated preventive behaviors that were applied to intradural neural implants alone. We anticipate that future efforts will focus even more on the investigation of modifiable factors along a continuum from bacterially repellant implants to weight management. Early diagnosis could offer the best hope for device salvage but to date has been largely understudied. CONCLUSIONS: Historically, prevention is the cornerstone to infection mitigation. However, immediate diagnosis and hardware salvage have not received the attention deserved, and that approach may be especially important for intradural devices.

Impact of Operating Room Environment on Postoperative Central Nervous System Infection in a Resource-Limited Neurosurgical Center in South Asia.

BACKGROUND: Postoperative central nervous system infections (PCNSIs) are serious complications following neurosurgical intervention. We previously investigated the incidence and causative pathogens of PCNSIs at a resource-limited, neurosurgical center in south Asia. This follow-up study was conducted to analyze differences in PCNSIs at the same institution following only one apparent change: the operating room air filtration system. METHODS: This was a retrospective study of all neurosurgical cases performed between December 1, 2013, and March 31, 2016 at our center. Providers, patient demographic data, case types, perioperative care, rate of PCNSI, and rates of other complications were reviewed. These results were then compared with the findings of our previous study of neurosurgical cases between June 1, 2012, and June 30, 2013. RESULTS: All 623 neurosurgical operative cases over the study period were reviewed. Four patients (0.6%) had a PCNSI, and no patients had a positive cerebrospinal fluid (CSF) culture. In the previous study, among 363 cases, 71 patients (19.6%) had a PCNSI and 7 (1.9%) had a positive CSF culture (all Gram-negative organisms). The differences in both parameters are statistically significant (P < 0.001). Between the 2 studies, there was no change in treatment providers, case types, case durations, antibiotic administration practices, and patient demographics. CONCLUSIONS: The rates of PCNSI and positive CSF culture were significantly lower in our present cohort compared with the cohort in our previous study. The sole apparent change involves the air filtration system inside the neurosurgical operating rooms; this environmental change occurred during the 5 months between the 2 studies. This study demonstrates the impact of environmental factors in reducing infections.

AIDS-associated central nervous system cryptococcosis: a Brazilian case study.

In recent years the effect of HAART in patients with AIDS has been great at decreasing the incidence of opportunistic infections. Nonetheless, patients with AIDS living in developing countries still present with severe central nervous system cryptococcosis, with high mortality rates. The study of the clinical-epidemiological-laboratory aspects of the patients treated before the HAART era might be useful in an assessment of the impact of these drugs in the prognosis of cases.

Antimicrobial prophylaxis for external ventricular drains in pediatric neurosurgical patients.

BACKGROUND: Our goal was to describe the use of antibiotics for surgical prophylaxis of external ventricular drains (EVDs) in a pediatric neurosurgical population and determine the incidence of EVD-related infections among different antimicrobial prophylaxis strategies. MAIN OUTCOME MEASURES: This retrospective chart review included patients up to 18 years old who underwent EVD insertion at either of two tertiary care academic hospitals in the same health system between August 1, 2008, and July 31, 2012. Patients were included if they received at least one dose of antibiotics before EVD insertion. Patients who received only perioperative antibiotics were compared with those who also received antibiotics after this period. The primary endpoint was incidence of EVD-related infection. Descriptive statistics were used to summarize baseline characteristics and compare antibiotic regimens between groups. Pearson's chi square and Mann Whitney U tests compared nonparametric data. RESULTS: A total of 182 EVD insertions were documented, and 88 included in the study. Of these 88, 27 were associated only with perioperative doses of antibiotics, and 61 with prolonged antibiotic use. Baseline characteristics and antibiotic choices were similar between the groups. At least 55 (63%) catheters were antibiotic-impregnated, but types of catheters couldn't be compared between groups due to insufficient data. No central nervous system infections were identified in either group, so the primary objective could not be evaluated statistically. CONCLUSION: No infections were identified in any study subjects during EVD treatment. An adequately powered, multi-center prospective study should be performed to determine if prolonged use of antibiotics beyond the perioperative period is of benefit.

Potential neuroprotective strategies for perinatal infection and inflammation.

Preterm born infants have high rates of brain injury, leading to motor and neurocognitive problems in later life. Infection and resulting inflammation of the fetus and newborn are highly associated with these disabilities. However, there are no established neuroprotective therapies. Microglial activation and expression of many cytokines play a key role in normal brain function and development, as well as being deleterious. Thus, treatment must achieve a delicate balance between possible beneficial and harmful effects. In this review, we discuss potential neuroprotective strategies targeting systemic infection or the resulting systemic and central inflammatory responses. We highlight the central importance of timing of treatment and the critical lack of studies of delayed treatment of infection/inflammation.

Nosocomial bacterial meningitis, including central nervous system shunt infections.

Nosocomial bacterial meningitis and CSF shunt infections result in considerable morbidity and mortality, necessitating an organized and thoughtful approach to prevention, diagnosis, and management. Prophylactic antibiotics appear to reduce the rate of postcraniotomy meningitis often caused by S. aureus. On the other hand, prophylactic antibiotics do not appear to reduce the risk of developing a CSF shunt infection. CSF shunt infections usually require shunt removal and antimicrobial chemotherapy to effect a successful outcome.

The efficacy and cost of prophylactic and perioprocedural antibiotics in patients with external ventricular drains.

OBJECTIVE: Prophylactic antibiotics are routinely administered to patients with external ventricular drains (EVDs); however, no conclusive evidence supports this practice. This study compared the efficacy and cost of prophylactic and periprocedural antibiotics in patients with EVDs. METHODS: We reviewed the charts of 308 patients who had an EVD in place for 3 or more days between January 1996 and June 1997. Patients with EVDs placed for shunt infections or meningitis were excluded. A standard protocol was used to insert and monitor EVDs. Catheters were left in place as long as clinically indicated and changed only if they malfunctioned. Cerebrospinal fluid cultures were obtained twice weekly. Prophylactic antibiotics were used at the discretion of the attending neurosurgeon. Patients were divided into two groups: Group A comprised 209 patients who received prophylactic antibiotics for the duration of the EVD (intravenously administered cefuroxime, 1.5 g every 8 h); Group B comprised 99 patients who received only periprocedural antibiotics (intravenously administered cefuroxime, 1.5 g every 8 h, three or less doses). RESULTS: Although there were significantly more males in Group A than in Group B, the two groups were otherwise well matched, with no significant differences in age, indications, or duration of EVD placement. The overall rate of ventriculitis was 3.9%. The infection rates for Group A (3.8%) and Group B (4.0%) were almost identical. CONCLUSION: Prophylactic antibiotics did not significantly reduce the rate of ventriculitis in patients with EVDs, and they may select for resistant organisms. Discontinuing the use of prophylactic antibiotics for EVDs at the authors' institution would save approximately $80,000 per year in direct drug costs.

Infections of the central nervous system in the newborn.

Safe, effective vaccines and potent antimicrobial agents have diminished substantially the morbidity and mortality associated with neonatal infections of the central nervous system (CNS), and new molecular methods, such as the polymerase chain reaction, enable clinicians to detect micro-organisms rapidly. Despite these advances, CNS infections remain an important cause of death and neurodevelopmental sequelae. This article summarizes current concepts regarding infections of the developing CNS.

Central nervous system infections in the rainforest zone of Nigeria.

OBJECTIVES: To ascertain incidence rates of central nervous system infections and provide information for health care planners. DESIGN: A two-stage screening through supervised case referrals and diagnostic evaluation at referral centre to establish a register of CNS infections. SETTING: A rural community in the rainforest zone of Nigeria with land area of 186500 m2, average daily temperature of 28 degrees C, annual rainfall of 2080 mm, adult population of 109851 and served by 26 primary, three secondary and twelve comprehensive care facilities. More than two per cent of the populations live in waterlogged areas. SUBJECTS: Adults aged sixteen years and above, constituting incident cases of CNS infections. MAIN OUTCOME MEASURES: Incident CNS infections per 100,000 populations averaged over a two year observational period. RESULTS: Incidence rates were 3.6, 4.1, 2.3, 09, 1.8, 0.9 for acute bacterial meningitis, aseptic meningitis, rabies encephalitis, non-rabies encephalitis, tuberculous meningitis and chronic non-tuberculous meningoencephalitis, respectively. Syphilitic neuroarthropathy had 0.46. CONCLUSIONS: Mortality from acute pyogenic meningitis and tuberculous meningitis remained distressingly high. Aseptic meningitis had the highest incidence rate, yet remained inadequately emphasised. Rabies encephalitis was the third commonest cause of CNS infection in the area.

Reduction of drain-associated cerebrospinal fluid infections in neurosurgical inpatients: a prospective study.

BACKGROUND: External cerebrospinal fluid (CSF) diversion via a drain is associated with a variable risk of associated infections which cause significant morbidity. AIM: To establish whether simple interventions can reduce the incidence of such infections at a single centre. METHODS: A retrospective review of all patients undergoing an external CSF diversion procedure was carried out to determine the historical rate of infection. Following an institutional protocol which included standards on drain insertion, care, sampling and antibiotic prescribing a prospective study was carried out to observe whether infection rates had changed and which factors continued to predict drain-related infections. FINDINGS: Retrospective analysis identified 234 procedures in 159 patients over a two-year period. There were 54 drain-related infections, a rate of 21.5 per 1000 drainage days. Duration of CSF drainage [odds ratio (OR) = 1.15, P < 0.05] and the number of CSF samples taken per drain (OR = 5.98, P < 0.05) were independently associated with infection. In the prospectively gathered phase, 132 procedures were recorded in 107 patients over a one-year period. There were 18 infections, a rate of 13.7 per 1000 drainage days. The only independent prognostic factor was duration of CSF drainage (OR = 1.20, P < 0.05). Coagulase-negative staphylococci were the most commonly isolated type of organism in both series. CONCLUSION: Ensuring drains are removed promptly as soon as CSF diversion is no longer required may reduce the rate of nosocomial infections in this population despite multiple confounding factors. Institutional guidelines may promote best practice in this regard.

Comparison of two antibiotic-impregnated ventricular catheters: a prospective sequential series trial.

BACKGROUND: External ventricular drains (EVDs) are valuable adjuncts in the management of neurosurgical patients but are associated with a significant risk of cerebrospinal fluid (CSF) infection (range, 0% to 27%); a review of 23 studies reported a mean of 8.8%. OBJECTIVE: To compare the efficacy of 2 different antibiotic-impregnated EVD catheters in preventing CSF infections. METHODS: Patients were prospectively enrolled in an Institutional Review Board-approved study. During alternating 3-month periods, all patients received either a minocycline/rifampin-impregnated (M/R) ventricular catheter or a clindamycin/rifampin-impregnated (C/R) EVD catheter. CSF cultures were collected at the time of insertion and twice weekly. Positive cultures were defined a priori as growth of the same bacteria on 2 media (eg, blood agar and broth) or 2 cultures of the same bacteria on 1 medium (eg, broth). RESULTS: Altogether, 129 patients (mean age, 58.4 years; 55 male) received 65 C/R catheters and 64 M/R catheters. The most common indications for EVD placement were aneurysmal subarachnoid hemorrhage (48.1%), spontaneous intraparenchymal hemorrhage (13.2%), and tumor (11.6%). The mean duration of ventriculostomy drainage was 11.8 and 12.7 days in the C/R and M/R groups, respectively. No positive CSF cultures were identified in either cohort. CONCLUSIONS: The use of antibiotic-impregnated catheters was associated with an extremely low risk of CSF infection compared with the reported mean of nearly 9% for standard EVD catheters. Infection rates for both C/R and M/R EVD catheters were zero. These results support the use of antibiotic-impregnated EVD catheters in routine clinical practice.