Cerebrospinal Fluid Culture Research Articles

Rare Cause of Arrhythmia and Seizures in a Late-Preterm Newborn

Rare Cause of Arrhythmia and Seizures in a Late-Preterm Newborn

Importance of Lumbar Puncture in Late Onset Sepsis

Neonatal sepsis is the significant reason of neonatal mortality and morbidity and mostly results in extended hospitalization of infants in the neonatal intensive care unit. The sepsis was confirmed by a positive blood culture and a condition is considered clinical sepsis when the blood culture is negative. It is practically not possible to clinically differentiate sepsis from neonatal meningitis. However, a positive CSF for pathogenic bacteria indicates meningitis. Aim: The purpose of this study was to evaluate the frequency of late-onset sepsis in neonates with meningitis and to determine whether CSF analysis and lumbar puncture is mandatory in all cases of late-onset sepsis. Methods: This study was conducted in the Paediatrics department of CMH Abbottabad, and Sharif Medical City Hospital Lahore, and Pathology department of Women Medical and Dental College, Abbottabad for the duration from January 2022 to June 2022 among neonates with late neonatal sepsis. All neonates underwent clinical examination, history, routine tests (blood culture, C-reactive protein, complete blood count) and analysis and culture of cerebrospinal fluid for clinical evaluation of sepsis. Results: All 80 neonates tested positive for clinical sepsis: hematological sepsis was seen in 59 patients and 21 were CSF culture positive for sepsis; 8 (38.9%) of the 21 have positive CSF culture and 13 cases have negative blood culture. The most common clinical symptom was poor suction 70(87.5%), followed by weak moor 61(76.3%), and lethargy 46(57.5%). The Klebsiella spp was common organism seen in 15 children in the blood culture and the most communal organism in the cerebrospinal fluid culture was Staphylococcus aureus in 6 cases. Conclusions: The incidence of neonatal meningitis is high in new-borns with late-onset sepsis. Meningitis in neonates often transpires in the absence of bacteraemia. Therefore, the CSF examination and lumbar puncture are compulsory in all children with late onset sepsis. Keywords: Lumbar puncture, Meningitis, Neonatal sepsis

Clinical and microbiological characteristics of Candida meningitis/ventriculitis in children

Background: Candida meningitis/ventriculitis is rather rare during childhood. In this study, we investigated the clinical characteristics, risk factors, treatment, and prognosis of patients with Candida meningitis/ventriculitis.Methods: Patients under the age of 18 years who were diagnosed with Candida meningitis/ventriculitis were evaluated retrospectively.Results: A total of 10 cases with Candida meningitis/ventriculitis were analyzed. Three patients (30%) were below the age of one, and two (20%) were neonates. The two most common underlying conditions were hydrocephalus shunt and prematurity. Predisposing factors were a history of broad-spectrum antibiotic use, external ventricular drainage, total parenteral nutrition, central venous catheter, and staying in intensive care. The cerebrospinal fluid culture was positive in all patients, and 10% (1/1) had bacteremia. Of the isolates, 50% were C. albicans, 30% were C. tropicalis, 10% were C. lusitaniae, and 10% were C. dubliniensis. Fluconazole treatment was initiated in four (40%) and voriconazole in three (30%) patients. Two patients received combined treatment (amphotericin B + fluconazole/voriconazole). The median treatment duration was 38.6 days (range: 16–70 days). Three patients received intraventricular Amphotericin B.Central nervous system devices which were assumed to be infected were removed. A complication of endophthalmitis developed in one patient. The mortality rate was 10%.Conclusions: Among agents causing meningitis/ventriculitis, Candida should also be kept in mind in premature neonates and patients with ventricular-peritoneal shunts. The history of antibiotic use and external ventricular drainage are important predisposing factors. It can be successfully treated with fluconazole, voriconazole, amphotericin B, and removal of the central nervous system device.

The Antibiotic Resistance Patterns of Pseudomonas Aeruginosa Strains Isolated from Microbiological Specimens

To determine the antibiotic resistance rates of Pseudomonas aeruginosa strains isolated from samples collected by the microbiology laboratory of a single center for four years. The samples of wound, blood, tracheal aspirate, abscess, vagina, cerebrospinal fluid, sputum, and urine culture isolated from 789 patients who were hospitalized in the service, intensive care and outpatient services between 2017-2020 were evaluated retrospectively for Pseudomonas species. Most of culture were urine (42.7%) and sputum cultures (20.4%). Most patients applied to the service were from department of chest diseases (38.6%) or from department of urology (14.3%) or palliative care unit (12.5%). The highest resistances were against cefuroxime, levofloxacin and netilmicin; lowest resistance was against amikacin. The aztreonam, cefepime and gentamicin resistances were significantly reduced by years (P=0.0321, 0.0038 and 0.0004, respectively) while colistin and levofloxacin resistance considerably increased (P<0.0001 and P=0.0407, respectively). Significant decreases were observed in resistance against cefepime, ceftazidime and ciprofloxacin over years (P=0.0321, 0.0038 and 0.0004, respectively). A significant decrease in resistance of strains isolated from urine culture was only observed for cefepime over years (P=0.0003). The resistance of strains isolated from cultures of sputum, urine and respiratory secretions against levofloxacin significantly increased in 2019 while those of wound culture increased in 2020 (P=0.0145). Alterations in the antibiotic resistance profile were detected in patients over years due to frequently varied use of antimicrobials.

Acute Bacterial Meningitis in Children with Fever and Fits Aged 6-59 Months Old

Objective: To find out the frequency of acute bacterial meningitis (ABM) in children presented with fever and fits aged 6-59 months old. Methodology: This cross-sectional study was done at The Department of Pediatric Medicine, Bolan Medical College/Hospital Quetta from September 2017 to February 2019. A total of 168 children, of either gender, aged between 6-59 months who presented with 1st episode of febrile seizure, and who arrived at emergency department within 12 hours of episode were included. Samples of cerebrospinal fluid (CSF) were obtained. Later, results were analyzed. Results: Of total 168 patients, 111 (66.1%) were male. The mean age was 27.19±13.80 months while the mean weight and frontooccipital circumference (FOC) was found 12.01 ± 2.05 kg and 48.68 ± 2.77 cm correspondingly. Twenty-four (14.3%) patients were diagnosed with ABM. The most common organism found among 11 positive CSF cultures was Streptococcus pneumonia in 6 (54.6%). Conclusion: Every clinician needs to thoroughly evaluate infants or young children after a simple febrile seizure. Lumber puncture can be done in every child if there is any suspicion of meningitis. Keywords: Acute bacterial meningitis, febrile seizures, fever, fits.

Population pharmacokinetic model of vancomycin in postoperative neurosurgical patients.

Objective: Vancomycin is commonly used in postoperative neurosurgical patients for empirical anti-infective treatment due to the low success rate of bacterial culture in cerebrospinal fluid (about 20%) and the high mortality of intracranial infection. At conventional doses, the rate of target achievement for vancomycin trough concentration is low and the pharmacokinetics of vancomycin varies greatly in these patients, which often leads to treatment failure. The objective of this study was to establish a population pharmacokinetic (PPK) model of vancomycin in postoperative neurosurgical patients for precision medicine. Method: A total of 895 vancomycin plasma concentrations from 560 patients (497 postoperative neurosurgical patients) were retrospectively collected. The model was analyzed by nonlinear mixed effects modeling method. One-compartment model and mixed residual model was employed. The influence of covariates on model parameters was tested by forward addition and backward elimination. Goodness-of-fit, bootstrap and visual predictive check were used for model evaluation. Monte Carlo simulations were employed for dosing strategies with AUC24 targets 400–600. Result: Estimated glomerular filtration rate (eGFR), body weight (BW) and mannitol had significant influence on vancomycin clearance (CL). , for female, a = 0.7, Scr 0.7 mg/dl, b = −0.329, Scr 0.7 mg/dl, b = −1.209; for male, a = 0.9, Scr 0.9 mg/dl, b = −0.411, Scr 0.9 mg/dl, b = −1.210. Vancomycin clearance was accelerated when co-medicated with mannitol and increased with eGFR and BW. In the final model, the population typical value is 7.98 L/h for CL and 60.2 L for apparent distribution volume, , where A = 0.13 when co-medicated with mannitol, otherwise A = 0. The model is stable and effective, with good predictability. Conclusion: In postoperative neurosurgical patients, a higher dose of vancomycin may be required due to the augmented renal function and the commonly used mannitol, especially in those with high body weight. Our vancomycin PPK model could be used for individualized treatment in postoperative neurosurgical patients.

Induction therapy with high-dose fluconazole plus flucytosine for human immunodeficiency virus-uninfected cryptococcal meningitis patients: Feasible or not?

Cryptococcal meningitis (CM) is increasingly recognised in human immunodeficiency virus (HIV)-uninfected patients with high mortality. The efficacy and safety profiles of induction therapy with high-dose fluconazole plus flucytosine remain unclear. HIV-uninfected CM patients who received high-dose fluconazole (800 mg/d) for initial therapy in Huashan Hospital were included in this retrospective study from January 2013 to December 2018. Efficacy and safety of initial therapy, clinical outcomes and risk factors were evaluated. Twenty-seven (71.1%) patients who received high-dose fluconazole with flucytosine combination therapy and 11 (28.9%) having fluconazole alone for induction therapy were included. With a median duration of 42 days (IQR, 28-86), the successful response rate of initial therapy was 76.3% (29/38), while adverse drug reactions occurred in 14 patients (36.8%). The rate of persistently positive cerebrospinal fluid (CSF) culture results was 30.6% at 2 weeks, which was significantly associated with CSF CrAg titre >1:1280 (OR 9.56; 95% CI 1.40-103.65; p=.010) and CSF culture of Cryptococcus >3.9 log10 CFU/ml (OR 19.20; 95% CI 1.60-920.54; p=.011), and decreased to 8.6% at 4 weeks. One-year mortality was 15.8% (6/38), and low serum albumin (35 g/L) was found as an independent risk factor for 1-year mortality (HR 6.31; 95% CI 1.150-34.632; p=.034). Induction therapy with high-dose fluconazole (800 mg/d), combined with flucytosine, effectively treated HIV-uninfected CM and was well tolerated. Long-term fluconazole treatment with continued monitoring is beneficial for patients with persistent infection.

Risk Factors for 30-Day Mortality in Neonates With Carbapenem-resistant A. baumannii Sepsis.

Carbapenem-resistant Acinetobacter baumannii (CRAB) sepsis is becoming an extreme threat caused by high-case fatality rates and poor prevention and control in ICUs worldwide. However, the risk of mortality among neonatal CRAB sepsis is still unclear. A retrospective medical records review study, which aimed to identify the risk factors of mortality in neonates with CRAB sepsis (including both bacteremia and/or meningitis) in Thailand from 1996 to 2019. All cases featuring positive blood and cerebrospinal fluid cultures for CRAB were reviewed. A multivariable logistic regression model was analyzed for nonsurvivors and survivors of neonatal CRAB sepsis. In a 24-year period, 47 of these were identified with CRAB sepsis. The median (interquartile range) gestational age and birth weight were 30 (28-35) weeks and 1500 (933-2482) g, respectively. The 30-day case fatality rate was 55% (26/47). In multivariable analysis, nonsurvivors of neonatal CRAB sepsis were associated with congenital heart disease (adjusted odds ratio [OR] = 1.33; 95% CI 1.06-1.66, P = 0.02), CRIB II score ≥9 (adjusted OR = 1.65; 95% CI: 1.20-2.27, P = 0.004), severe thrombocytopenia (adjusted OR = 1.45; 95% CI: 1.09-1.94, P = 0.02), and septic shock (adjusted OR = 1.62; 95% CI: 1.33-1.99, P <0.001). The risk factors of mortality in neonates with CRAB sepsis are associated with congenital heart disease, CRIB II score ≥9, shock, and severe thrombocytopenia.

Comparison of Suspected and Confirmed Internal External Ventricular Drain-Related Infections: A Prospective Multicenter United Kingdom Observational Study.

BackgroundDiagnosis of internal external ventricular drain (EVD)-related infections (iERI) is an area of diagnostic difficulty. Empiric treatment is often initiated on clinical suspicion. There is limited guidance around antimicrobial management of confirmed versus suspected iERI.MethodsData on patients requiring EVD insertion were collected from 21 neurosurgical units in the United Kingdom from 2014 to 2015. Confirmed iERI was defined as clinical suspicion of infection with positive cerebrospinal fluid (CSF) culture and/or Gram stain. Cerebrospinal fluid, blood, and clinical parameters and antimicrobial management were compared between the 2 groups. Mortality and Modified Rankin Scores were compared at 30 days post-EVD insertion.ResultsInternal EVD-related infection was suspected after 46 of 495 EVD insertions (9.3%), more common after an emergency insertion. Twenty-six of 46 were confirmed iERIs, mostly due to Staphylococci (16 of 26). When confirmed and suspected infections were compared, there were no differences in CSF white cell counts or glucose concentrations, nor peripheral blood white cell counts or C-reactive protein concentrations. The incidence of fever, meningism, and seizures was also similar, although altered consciousness was more common in people with confirmed iERI. Broad-spectrum antimicrobial usage was prevalent in both groups with no difference in median duration of therapy (10 days [interquartile range {IQR}, 7–24.5] for confirmed cases and 9.5 days [IQR, 5.75–14] for suspected, P = 0.3). Despite comparable baseline characteristics, suspected iERI was associated with lower mortality and better neurological outcomes.ConclusionsSuspected iERI could represent sterile inflammation or lower bacterial load leading to false-negative cultures. There is a need for improved microbiology diagnostics and biomarkers of bacterial infection to permit accurate discrimination and improve antimicrobial stewardship.

Cryptococcal Meningitis Disguised As A Stroke: A Case Report

We present a case of cryptococcal meningitis initially misdiagnosed as stroke. Our patient is a young man on long-term corticosteroid due to gouty arthritis, who presented with acute onset of left-sided body weakness. Computed tomography of the brain revealed multifocal chronic lacunar infarcts with acute communicating hydrocephalus and cerebrospinal fluid culture isolated Cryptococcus neoformans. He was subsequently treated with amphotericin B and fluconazole but passed away due to multiorgan failure. This case report highlights the importance of considering chronic meningitis as a differential diagnosis when encountering stroke in young and immunocompromised patients.

Diagnosis of pathogens causing bacterial meningitis using Nanopore sequencing in a resource-limited setting

AimThe aim of the present study is to compare the performance of 16S rRNA Nanopore sequencing and conventional culture in detecting infectious pathogens in patients with suspected meningitis in a resource-limited setting without extensive bioinformatics expertise.MethodsDNA was isolated from the cerebrospinal fluid (CSF) of 30 patients with suspected bacterial meningitis. The isolated DNA was subjected to 16S sequencing using MinION™. The data were analysed in real time via the EPI2ME cloud platform. The Nanopore sequencing was done in parallel to routine microbiological diagnostics.ResultsNanopore sequencing detected bacterial pathogens to species level in 13 of 30 (43%) samples. CSF culture showed 40% (12/30) positivity. In 21 of 30 patients (70%) with suspected bacterial meningitis, both methods yielded concordant results. About nine of 30 samples showed discordant results, of these five were false positive and four were false negative. In five of the culture negative results, nanopore sequencing was able to detect pathogen genome, due to the higher sensitivity of the molecular diagnostics. In two other samples, the CSF culture revealed Cryptococcus neoformans and Streptococcus pneumoniae, which were not detected by Nanopore sequencing. Overall, using both the cultures and 16S Nanopore sequencing, positivity rate increased from 40% (12/30) to 57% (17/30).ConclusionNext-generation sequencing could detect pathogens within six hours and could become an important tool for both pathogen screening and surveillance in low- and middle-income countries (LMICs) that do not have direct access to extensive bioinformatics expertise.

Epidemiological evolution of early-onset neonatal sepsis over 12 years: A single center, population-based study in central Taiwan.

We aimed to explore the epidemiology and evolution of pathogens, antibiotic susceptibility, and mortality rate in cases of neonatal early-onset sepsis (EOS) reported over a period of 12 years in a level III neonatal center in Central Taiwan. Patients' medical records in a neonatal center from 2007 to 2018 were reviewed to obtain information on infants with culture-proven EOS, which included pathogens found in the blood or cerebrospinal fluid cultures. The incidence of neonatal EOS during this period was 2.11 cases/1,000 admissions. Group B streptococcal (GBS) and Escherichia coli were the most common pathogens. The overall rates of GBS and E. coli infections were 0.68/1,000 and 0.77/1,000 live births, respectively. The incidence of EOS in infants with a birth weight ≥1,500 g decreased significantly with decreasing incidence of GBS-related sepsis. The incidence of EOS remained high in very-low-birth-weight (VLBW) infants and increased over time. There was an increasing trend in of E. coli infection and emergence of drug-resistant strains. In addition, E. coli sepsis had high mortality in VLBW infants. Novel screening and prevention strategies against E. coli and reserving broad-spectrum antibiotics for the most critically ill or VLBW patients with maternal chorioamnionitis might help in early diagnosis and further improve the outcomes of EOS.

Memory Impairment, Pro-Inflammatory Host Response and Brain Histopathologic Severity in Rats Infected with K. pneumoniae or P. aeruginosa Meningitis.

Meningitis caused by Klebsiella pneumoniae and Pseudomonas aeruginosa has lately become a prevalent cause of the central nervous system (CNS) infection. Bacterial invasion into the subarachnoid space prompts the releasing mechanism of chemokines and pro-inflammatory cytokines. The present study aimed to compare K. pneumoniae and P. aeruginosa meningitis concerning the memory, pro-inflammatory mediators and brain histopathological changes at different time intervals in adult Albino rats. The animals were sacrificed at three time intervals comprising 5, 10 and 15 days after meningitis induction. Cerebrospinal fluid (CSF) culture, relative brain weights, complete blood analysis, biochemical markers, levels of cytokine, chemokine and brain-derived neurotrophic factor (BDNF), neurotransmitter acetylcholine esterase (AChE) activity, and the brain histopathology of the infected rats in comparison to those in the control group were assessed. There was a significant increase in the levels of pro-inflammatory cytokines and chemokines including TNF-α, IL-1β, IL-6 and AChE after 5 days of bacterial meningitis infection with both K. pneumoniae and P. aeruginosa. The histopathological analysis of the cerebral cortex in the P. aeruginosa meningitis model at different time intervals revealed abundant numbers of dilated and congested blood vessels with severe hemorrhage, cerebral infarct, intracellular and extracellular vacuoles, and gliosis. Fifteen days post infection, a significant reduction in the brain tissue weight was observed. The meningitis model employing P. aeruginosa exhibited more evident time-dependent severity compared to K. pneumoniae, which may advocate its validity as a simple and effective research model to study meningitis of the CNS. This model may be utilized for further investigation to ascertain the molecular and biological association between bacterial meningitis and the development of the pathophysiological hallmarks underlying Alzheimer’s disease in preclinical and clinical setups. Clinical extrapolation based on studies employing animal disease models should be carefully interpreted.

Case Report of Nocardial Brain Abscess in a Patient on Steroids

Nocardial brain abscesses are a rare cause of cerebral abscesses that usually arise in immunocompromised patients and are associated with high morbidity and mortality. We present the case of a 57-year old male who presented with fever, progressive vision loss and disorientation in the emergency room while on treatment for community acquired pneumonia. He has been using steroids for 20 years and has uncontrolled diabetes mellitus, and secondary adrenal insufficiency as a result. Chest computed tomography (CT) showed consolidation in left posterior-inferior lobe. Blood and cerebrospinal fluid (CSF) cultures were negative. Magnetic resonance imaging (MRI) of the head revealed multiple small dispersed lesions with peripheral ring enhancement after contrast administration, concerning for abscesses. Pus was sampled from a superficial occipital abscess and content grew Nocardia sensitive to trimethoprim/sulfamethoxazole (TMP/SMX) and imipenem so the patient was switched to targeted therapy. The following days he developed new motor deficits and became unresponsive to verbal stimulus. Another MRI revealed enlargement of the existing lesions and new lesions with signal restriction on diffusion (DWI) in the levels of the midbrain and pons. The patient developed respiratory insufficiency and passed away regarding of ongoing supportive treatment.

Following Birth Hospitalization: Invasive Bacterial Infections in Preterm Infants Aged 7-90 Days

To assess the incidence rate of invasive bacterial infections in preterm infants and compare invasive bacterial infection rates and pathogens between preterm and full-term infants at age 7-90days. This is a retrospective cohort study of the incidence rate of invasive bacterial infections among all infants born at Kaiser Permanente Northern California (KPNC), with blood and cerebrospinal fluid cultures collected between 7 and 90days of chronological age from outpatient clinics, from emergency departments, and in the first 24hours of hospitalization presenting for care between January 1, 2005, and December 31, 2017. Incidence rates of invasive bacterial infection by chronological age and postmenstrual age (PMA) and pathogens were compared between preterm and full-term infants. Between January 1, 2005, and December 31, 2017, a total of 479 729 infants were born at KPNC, including 440 070 full-term infants and 39 659 preterm infants. There were 283 cases of bacteremia in 282 infants. The incidence rate of invasive bacterial infection was significantly higher for preterm infants compared with full-term infants. The highest incidence rates of invasive bacterial infection were in preterm infants at chronological age 7-28days and/or 37-39weeks PMA. There was a trend toward lower rates of invasive bacterial infection with increasing PMA in preterm infants aged 61-90days. Preterm infants aged 29-60days or at ≥40weeks PMA and those aged 61-90days or at ≥43weeks PMA had a rate of invasive bacterial infection equivalent to the overall rate seen in full-term infants of the same chronological age group. The distribution of pathogens causing bacteremia and meningitis did not differ between preterm and full-term infants. PMA and chronological age together were more useful than either alone in informing the incidence rate of invasive bacterial infection in preterm infants during the first 90days of life.

COVID-19 and Serious Bacterial Infection in Febrile Infants Less Than 60 Days Old.

IntroductionThe pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the coronavirus disease 2019 (COVID-19) pandemic that drastically impacted the United States. The evidence was not clear on how SARS-CoV-2 infection impacted children, given the high prevalence of SAR-CoV-2 infection. Febrile infants less than 60 days old are an ongoing challenge to risk-stratify for serious bacterial infection (SBI), including urinary tract infection (UTI), bacteremia, and meningitis. We hypothesized there would be a lower rate of SBI in SARS-CoV-2 positive febrile infants compared to those SARS-CoV-2 negative.MethodsThis was a retrospective chart review with a nested, age-matched, case-control study performed from March 2020–June 2021. Infants less than 60 days old presenting with fever were assigned groups based on SARS-CoV-2 infection. Blood, urine, and cerebrospinal fluid cultures were used as the gold standard to diagnose SBI. We compared overall rate of SBI as well as individual rates of SBI between each group. We performed a subgroup analysis evaluating the age group 29–60 days old.ResultsA total of 164 subjects met criteria for analysis: 30 COVID-19 positive and 134 COVID-19 negative subjects. Rate of SBI was 17.9% (95% confidence interval [CI]: 11.8–25.5%) in the COVID-19 negative group compared to 0% (95% CI: 0.0%-11.1%) in the COVID-19 group, which demonstrated statistical significance (p = 0.008). In the age-matched data, we found statistical significance for any SBI (p = <0.001). For individual rates of SBI, we found statistical significance for UTI (p = <0.001) and bacteremia (p = <0.001). The 29–60 days-old subgroup analysis did not achieve statistical significance (p = 0.11).ConclusionThis study demonstrated the utility of including SARS-CoV-2 infection as part of the risk stratification of febrile infants less than 60 days old. While overall there is a low incidence of bacteremia and meningitis in this age group, these results can contribute to existing literature and potentially help decrease invasive testing and exposure to broad-spectrum antibiotics.

Heparin Binding Protein in Early Differential Diagnosis of Bacterial Meningitis.

Heparin-binding protein is a serine protease that is mobilized rapidly from emigrating polymorphonuclear leukocytes that acts as a chemoattractant activator of monocyte and macrophages. We investigated the potential role and efficacy of serum and cerebrospinal fluid heparin binding protein in differentiating bacterial meningitis from tuberculosis and viral meningitis. A case diagnosed with acute bacterial meningitis (n:37), viral meningitis (n:30) and tuberculous meningitis (n:30) was included in this study. The diagnosis was based on history, clinical criteria, cerebrospinal fluid examination, latex agglutination and culture, and response to therapy. Heparin-binding protein was measured using enzyme-linked immunosorbent technique in both cerebrospinal fluid and serum. Cerebrospinal fluid heparin-binding protein levels were 7.81 ± 0.23ng/mL in bacterial meningitis, 6.11 ± 0.3ng/mL in tuberculosis meningitis and 5.75 ± 0.1ng/mL in viral meningitis. The mean serum level was 14.98 ± 1.1ng/mL in bacterial meningitis, 6.89 ± 0.4ng/mL in tuberculosis meningitis, and 6.02 ± 0.4ng/mL in viral meningitis. Both heparin-binding protein levels were significantly higher in patients with bacterial meningitis. We found that serum and cerebrospinal fluid heparin binding protein is a useful marker for differentiating bacterial meningitis from non-bacterial meningitis.

Comparison of amphotericin B deoxycholate in combination with either flucytosine or fluconazole, and voriconazole plus flucytosine for the treatment of HIV-associated cryptococcal meningitis: a prospective multicenter study in China

BackgroundThe most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective.MethodsA prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups.ResultsFewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use.ConclusionOur results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective.Clinical Trials: Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362.

Prevalence and Management of Invasive Bacterial Infections in Febrile Infants Ages 2 to 6 Months

Validated prediction rules identify febrile neonates at low risk for invasive bacterial infection. The optimal approach for older febrile infants, however, remains uncertain. We performed a retrospective cohort and nested case-control study of infants 2 to 6 months of age presenting with fever (≥38.0 °C) to 1 of 5 emergency departments. The study period was from 2011 to 2019. The primary outcome was invasive bacterial infection, defined by the growth of pathogenic bacteria from either blood or cerebrospinal fluid culture. Secondary outcomes included obtaining bacterial cultures (blood, cerebrospinal fluid, or urine), administering antibiotics, and hospitalization. For the nested case-control study, we age-matched infants with invasive bacterial infection to 3 infants without invasive bacterial infection, sampled from the overall cohort. There were 21,150 eligible patient encounters over 9-years, and 101 infants had a documented invasive bacterial infection (0.48%; 95% confidence interval [CI], 0.39% to 0.58%). Invasive bacterial infection prevalence ranged from 0.2% to 0.6% among the 5 sites. The frequency of bacterial cultures ranged from 14.5% to 53.5% for blood, 1.6% to 12.9% for cerebrospinal fluid, and 31.8% to 63.2% for urine. Antibiotic administration varied from 19.2% to 46.7% and hospitalization from 16.6% to 28.3%. From the case-control study, the estimated invasive bacterial infection prevalence for previously healthy, not pretreated, and well-appearing febrile infants was 0.32% (95% CI, 0.24% to 0.41%). Although invasive bacterial infections were uncommon among febrile infants 2 to 6 months in the emergency department, the approach to diagnosis and management varied widely between sites. Therefore, evidence-based guidelines are needed to reduce low-value testing and treatment while avoiding missing infants with invasive bacterial infections.

Uncommon cause of trigeminal neuritis and central nervous system involvement by herpes labialis: a case report

BackgroundTrigeminal neuropathy is characterized by numbness in the region innervated by the trigeminal nerves, with or without neuropathic weakness in the muscles of mastication. Trigeminal neuritis is a form of trigeminal neuropathy in which the lesion is caused by an inflammation. Herein, we report a patient with trigeminal neuritis due to central nervous system (CNS) involvement of herpes labialis (HL) infection, which was successfully treated with anti-viral and anti-inflammatory agents.Case presentationA young healthy female presented with numbness in the left hemiface for two weeks. She had a preceding typical HL infection on left facial lip one week before the sensory symptom onset. Brain magnetic resonance imaging revealed high signal intensities and asymmetrical thickening with enhancement along the cisternal segment of the left trigeminal nerve. Additionally, brain MR angiography showed multifocal stenoses in the M1 segment of the middle cerebral artery and the cavernous portion of the internal carotid artery. Cerebrospinal fluid (CSF) examination showed mild pleocytosis with normal protein level, glucose ratio, but CSF polymerase chain reaction assay for specific anti-viral antibodies including herpes simplex virus was negative, and CSF culture also did not identify a specific pathogen. The results of serologic testing including tumor markers and autoimmune markers were all unremarkable. A tentative diagnosis of trigeminal neuritis as a complication of HL involving the CNS was made considering the clinical, neuroradiological, and laboratory findings of the patient. Therefore, the patient was treated with intravenous methylprednisolone and acyclovir for 10 days. After the treatments, her sensory disturbance was markedly improved. Brain MRI at the 3-month follow-up also demonstrated improvement of previously identified high signal intensity lesions and multifocal intracerebral artery stenoses.ConclusionHL is usually a self-limiting, benign disease without complications, but rarely presents as trigeminal neuritis due to CNS involvement. Therefore, meticulous evaluation may be necessary if trigeminal neuritis or CNS involving symptoms occur after HL.