Evaluation of the host immune response assay SeptiCyte RAPID for potential triage of COVID-19 patients.

Tools for the evaluation of COVID-19 severity would help clinicians with triage decisions, especially the decision whether to admit to ICU. The aim of this study was to evaluate SeptiCyte RAPID, a host immune response assay (Immunexpress, Seattle USA) as a triaging tool for COVID-19 patients requiring hospitalization and potentially ICU care. SeptiCyte RAPID employs a host gene expression signature consisting of the ratio of expression levels of two immune related mRNAs, PLA2G7 and PLAC8, measured from whole blood samples. Blood samples from 146 adult SARS-CoV-2 (+) patients were collected within 48 h of hospital admission in PAXgene blood RNA tubes at Hospital del Mar, Barcelona, Spain, between July 28th and December 1st, 2020. Data on demographics, vital signs, clinical chemistry parameters, radiology, interventions, and SeptiCyte RAPID were collected and analyzed with bioinformatics methods. The performance of SeptiCyte RAPID for COVID-19 severity assessment and ICU admission was evaluated, relative to the comparator of retrospective clinical assessment by the Hospital del Mar clinical care team. In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity: critical vs. mild (AUC = 0.93, p < 0.0001), critical vs. moderate (AUC = 0.77, p = 0.002), severe vs. mild (AUC = 0.85, p = 0.0003), severe vs. moderate (AUC = 0.63, p = 0.05). This discrimination was significantly better (by AUC or p-value) than could be achieved by CRP, lactate, creatine, IL-6, or D-dimer. Some of the critical or severe cases had "early" blood draws (before ICU admission; n = 33). For these cases, when compared to moderate and mild cases not in ICU (n = 37), SeptiCyte RAPID had AUC = 0.78 (p = 0.00012). In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity as defined by the WHO COVID-19 Clinical Management Living Guidance of January 25th, 2021. Measurements taken early (before a patient is considered for ICU admission) suggest that high SeptiScores could aid in predicting the need for later ICU admission.

Penicillin- and Cephalosporin-Resistant Pneumococcal Meningitis: Treatment in the Real World and in Guidelines.

To report on the therapy used for penicillin- and cephalosporin-resistant pneumococcal meningitis, we conducted an observational cohort study of patients admitted to our hospital with pneumococcal meningitis between 1977 and 2018. According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations, we defined pneumococci as susceptible and resistant to penicillin with MIC values of ≤0.06 mg/L and > 0.06 mg/L, respectively; the corresponding values for cefotaxime (CTX) were ≤0.5 mg/L and >0.5 mg/L. We treated 363 episodes of pneumococcal meningitis during the study period. Of these, 24 had no viable strain, leaving 339 episodes with a known MIC for inclusion. Penicillin-susceptible strains accounted for 246 episodes (73%), penicillin-resistant strains for 93 (27%), CTX susceptible for 58, and CTX resistant for 35. Nine patients failed or relapsed and 69 died (20%), of whom 22% were among susceptible cases and 17% were among resistant cases. During the dexamethasone period, mortality was equal (12%) in both susceptible and resistant cases. High-dose CTX (300 mg/Kg/day) helped to treat failed or relapsed cases and protected against failure when used as empirical therapy (P = 0.02), even in CTX-resistant cases. High-dose CTX is a good empirical therapy option for pneumococcal meningitis in the presence of a high prevalence of penicillin and cephalosporin resistance, effectively treating pneumococcal strains with MICs up to 2 mg/L for either penicillin or CTX.

Comparison of Hospitalized Coronavirus Disease 2019 and Influenza Patients Requiring Supplemental Oxygen in a Cohort Study: Clinical Impact and Resource Consumption.

BACKGROUND: To compare clinical characteristics, outcomes, and resource consumption of patients with coronavirus disease 2019 (COVID-19) and seasonal influenza requiring supplemental oxygen. METHODS: Retrospective cohort study conducted at a tertiary-care hospital. Patients admitted because of seasonal influenza between 2017 and 2019, or with COVID-19 between March and May 2020 requiring supplemental oxygen were compared. Primary outcome: 30-day mortality. Secondary outcomes: 90-day mortality and hospitalization costs. Attempted sample size to detect an 11% difference in mortality was 187 patients per group. RESULTS: COVID-19 cases were younger (median years of age, 67; interquartile range [IQR] 54-78 vs 76 [IQR 64-83]; P < .001) and more frequently overweight, whereas influenza cases had more hypertension, immunosuppression, and chronic heart, respiratory, and renal disease. Compared with influenza, COVID-19 cases had more pneumonia (98% vs 60%, <.001), higher Modified Early Warning Score (MEWS) and CURB-65 (confusion, blood urea nitrogen, respiratory rate, systolic blood pressure, and age >65 years) scores and were more likely to show worse progression on the World Health Organization ordinal scale (33% vs 4%; P < .001). The 30-day mortality rate was higher for COVID-19 than for influenza: 15% vs 5% (P = .001). The median age of nonsurviving cases was 81 (IQR 74-88) and 77.5 (IQR 65-84) (P = .385), respectively. COVID-19 was independently associated with 30-day (hazard ratio [HR], 4.6; 95% confidence interval [CI], 2-10.4) and 90-day (HR, 5.2; 95% CI, 2.4-11.4) mortality. Sensitivity and subgroup analyses, including a subgroup considering only patients with pneumonia, did not show different trends. Regarding resource consumption, COVID-19 patients had longer hospital stays and higher critical care, pharmacy, and complementary test costs. CONCLUSIONS: Although influenza patients were older and had more comorbidities, COVID-19 cases requiring supplemental oxygen on admission had worse clinical and economic outcomes.

Economic impact of a care bundle to prevent surgical site infection after craniotomy: a cost-analysis study.

BACKGROUND: Surgical site infections after craniotomy (SSI-CRAN) significantly impact patient outcomes and healthcare costs by increasing length of stay and readmission and reoperation rates. However, to our knowledge, no study has yet analysed the economic impact of a surgical care bundle for preventing SSI-CRAN. The aim is to analyse the hospital cost saving after implementation of a care bundle for the prevention of SSI-CRAN. METHODS: A retrospective cost-analysis was performed, considering two periods: pre-care bundle (2013-2015) and care bundle (2016-2017). A bottom-up approach was used to calculate the costs associated with infection in patients who developed a SSI-CRAN in comparison to those who did not, in both periods and on a patient-by-patient basis. The derived cost of SSI-CRAN was calculated considering: (1) cost of the antibiotic treatment, (2) cost of length of stay in the neurosurgery ward within the 1-year follow up period, (3) cost of the re-intervention, and (4) cost of the implant for cranial reconstruction, when necessary. RESULTS: A total of 595 patients were included in the pre-care bundle period and 422 in the care bundle period. Mean cost of a craniotomy procedure was approximately €8000, rising to €24,000 in the case of SSI-CRAN. Mean yearly hospital costs fell by €502,857 in the care bundle period (€714,886 vs. €212,029). Extra costs between periods were mainly due to increased length of hospital stay (€573,555.3 vs. €183,958.9; difference: €389,596.4), followed by the cost of implant for cranial reconstruction (€69,803.4 vs. €9,936; difference: €59,867.4). Overall, implementation of the care bundle saved the hospital €500,844.3/year. CONCLUSION: The implementation of a care bundle for SSI-CRAN had a significant economic impact. Hospitals should consider the deployment of this multimodal preventive strategy to reduce their SSI-CRAN rates, and also their costs.

A Care Bundle Intervention to Prevent Surgical Site Infections After a Craniotomy.

BACKGROUND: Although surgical site infections after a craniotomy (SSI-CRANs) are a serious problem that involves significant morbidity and costs, information on their prevention is scarce. We aimed to determine whether the implementation of a care bundle was effective in preventing SSI-CRANs. METHODS: A historical control study was used to evaluate the care bundle, which included a preoperative shower with 4% chlorhexidine soap, appropriate hair removal, adequate preoperative systemic antibiotic prophylaxis, the administration of 1 g of vancomycin powder into the subgaleal space before closing, and a postoperative dressing of the incisional surgical wound with a sterile absorbent cover. Patients were divided into 2 groups: preintervention (January 2013 to December 2015) and intervention (January 2016 to December 2017). The primary study end point was the incidence of SSI-CRANs within 1 year postsurgery. Propensity score matching was performed, and differences between the 2 study periods were assessed using Cox regression models. RESULTS: A total of 595 and 422 patients were included in the preintervention and intervention periods, respectively. The incidence of SSI-CRANs was lower in the intervention period (15.3% vs 3.5%; P < .001). Using a propensity score model, 421 pairs of patients were matched. The care bundle intervention was independently associated with a reduced incidence of SSI-CRANs (adjusted odds ratio, 0.23; 95% confidence interval, .13-.40; P < .001). CONCLUSIONS: The care bundle intervention was effective in reducing SSI-CRAN rates. The implementation of this multimodal preventive strategy should be considered in centers with high SSI-CRAN incidences.

Linezolid for therapy of Staphylococcus aureus meningitis: a cohort study of 26 patients.

BACKGROUND: Linezolid has good penetration to the meninges and could be an alternative for treatment of Staphylococcus aureus meningitis. We assessed the efficacy and safety of linezolid therapy for this infection. METHODS: Retrospective multicenter cohort study of 26 adults treated with linezolid, derived from a cohort of 350 cases of S. aureus meningitis diagnosed at 11 university hospitals in Spain (1981-2015). RESULTS: There were 15 males (58%) and mean age was 47.3 years. Meningitis was postoperative in 21 (81%) patients. The infection was nosocomial in 23 (88%) cases, and caused by methicillin-resistant S. aureus in 15 cases and methicillin-susceptible S. aureus in 11. Linezolid was given as empirical therapy in 10 cases, as directed therapy in 10, and due to failure of vancomycin in 6. Monotherapy was given to 16 (62%) patients. Median duration of linezolid therapy was 17 days (IQR 12-22 days) with a daily dose of 1,200 mg in all cases. The clinical response rate to linezolid was 69% (18/26) and microbiological response was observed in 14 of 15 cases evaluated (93%). Overall 30-day mortality was 23% and was directly associated with infection in most cases. When compared with the patients of the cohort, no significant difference in mortality was observed between patients receiving linezolid or vancomycin for therapy of methicillin-resistant S. aureus meningitis (9% vs. 20%; p = .16) nor between patients receiving linezolid or cloxacillin for therapy of methicillin-susceptible S. aureus meningitis (20% vs 14%; p = .68). Adverse events appeared in 14% (3/22) of patients, but linezolid was discontinued in only one patient. CONCLUSIONS: Linezolid appears to be effective and safe for therapy of S. aureus meningitis. Our findings showed that linezolid may be considered an adequate alternative to other antimicrobials in meningitis caused by S. aureus.

Delayed Cerebral Vasculopathy in Pneumococcal Meningitis: Epidemiology and Clinical Outcome. A Cohort Study.

BACKGROUND: To describe the prevalence, clinical characteristics, impact of systemic steroids exposure and outcomes of delayed cerebral vasculopathy (DCV) in a cohort of adult patients with pneumococcal meningitis (PM). METHODS: Observational retrospective multicenter study including all episodes of PM from January 2002 to December 2015. DCV was defined as proven/probable/possible based upon clinical criteria and pathological-radiological findings. DCV-patients and non-DCV-patients were compared by univariate analysis. RESULTS: 162 PM episodes were included. Seventeen (10.5%) DCV-patients were identified (15 possible, 2 probable). At admission, DCV-patients had a longer duration of symptoms (>2 days in 58% vs. 25.5% (p 0.04)), more coma (52.9% vs. 21.4% (p 0.03)), lower median CSF WBC-count (243 cells/uL vs. 2673 cells/uL (p 0.001)) and a higher proportion of positive CSF Gram stain (94.1% vs. 71% (p 0.07)). Median length of stay was 49 vs. 15 days (p 0.001), ICU admission was 85.7% vs. 49.5% (p 0.01) and unfavorable outcome was found in 70.6% vs. 23.8% (p 0.001). DCV appeared 1-8 days after having completed adjunctive dexamethasone treatment (median 2,5, IQR=1.5-5). CONCLUSIONS: One tenth of the PM developed DCV. DCV-patients had a longer duration of illness, were more severely ill, had a higher bacterial load at admission and had a more complicated course. Less than one third of cases recovered without disabilities. The role of corticosteroids in DCV remains to be established.

An external ventricular drainage catheter impregnated with rifampicin, trimethoprim and triclosan, with extended activity against MDR Gram-negative bacteria: an in vitro and in vivo study.

BACKGROUND: External ventricular drainage (EVD) carries a high risk of ventriculitis, increasingly caused by MDR Gram-negative bacteria such as Escherichia coli and Acinetobacter baumannii. Existing antimicrobial EVD catheters are not effective against these, and we have developed a catheter with activity against MDR bacteria and demonstrated the safety of the new formulation for use in the brain. OBJECTIVES: Our aim was to determine the ability of a newly formulated impregnated EVD catheters to withstand challenge with MDR Gram-negative bacteria and to obtain information about its safety for use in the CNS. METHODS: Catheters impregnated with three antimicrobials (rifampicin, trimethoprim and triclosan) were challenged in flow conditions at four weekly timepoints with high doses of MDR bacteria, including MRSA and Acinetobacter, and monitored for bacterial colonization. Catheter segments were also inserted intracerebrally into Wistar rats, which were monitored for clinical and behavioural change, and weight loss. Brains were removed after either 1 week or 4 weeks, and examined for evidence of inflammation and toxicity. RESULTS: Control catheters colonized quickly after the first challenge, while no colonization occurred in the impregnated catheters even after the 4 week challenge. Animals receiving the antimicrobial segments behaved normally and gained weight as expected. Neurohistochemistry revealed only surgical trauma and no evidence of neurotoxicity. CONCLUSIONS: The antimicrobial catheter appears to withstand bacterial challenge for at least 4 weeks, suggesting that it might offer protection against infection with MDR Gram-negative bacteria in patients undergoing EVD. It also appears to be safe for use in the CNS.

Impact of pre-hospital antibiotic therapy on mortality in invasive meningococcal disease: a propensity score study.

The role of pre-hospital antibiotic therapy in invasive meningococcal diseases remains unclear with contradictory data. The aim was to determine this role in the outcome of invasive meningococcal disease. Observational cohort study of patients with/without pre-hospital antibiotic therapy in invasive meningococcal disease attended at the Hospital Universitari de Bellvitge (Barcelona) during the period 1977-2013. Univariate and multivariate analyses of mortality, corrected by propensity score used as a covariate to adjust for potential confounding, were performed. Patients with pre-hospital antibiotic therapy were also analyzed according to whether they had received oral (group A) or parenteral antibiotics (early therapy) (group B). Five hundred twenty-seven cases of invasive meningococcal disease were recorded and 125 (24%) of them received pre-hospital antibiotic therapy. Shock and age were the risk factors independently related to mortality. Mortality differed between patients with/without pre-hospital antibiotic therapy (0.8% vs. 8%, p = 0.003). Pre-hospital antibiotic therapy seemed to be a protective factor in the multivariate analysis of mortality (p = 0.038; OR, 0.188; 95% CI, 0.013-0.882). However, it was no longer protective when the propensity score was included in the analysis (p = 0.103; OR, 0.173; 95% CI, 0.021-1.423). Analysis of the oral and parenteral pre-hospital antibiotic groups revealed that there were no deaths in early therapy group. Patients able to receive oral antibiotics had less severe symptoms than those who did not receive pre-hospital antibiotics. Age and shock were the factors independently related to mortality. Early parenteral therapy was not associated with death. Oral antibiotic therapy in patients able to take it was associated with a beneficial effect in the prognosis of invasive meningococcal disease.

Risk factors for surgical site infection after craniotomy: a prospective cohort study.

Background: Although surgical site infection after craniotomy (SSI-CRAN) is a serious complication, risk factors for its development have not been well defined. We aim to identify the risk factors for developing SSI-CRAN in a large prospective cohort of adult patients undergoing craniotomy. Methods: A series of consecutive patients who underwent craniotomy at a university hospital from January 2013 to December 2015 were prospectively assessed. Demographic, epidemiological, surgical, clinical and microbiological data were collected. Patients were followed up in an active post-discharge surveillance programm e for up to one year after surgery. Multivariate analysis was carried out to identify independent risk factors for SSI-CRAN. Results: Among the 595 patients who underwent craniotomy, 91 (15.3%) episodes of SSI-CRAN were recorded, 67 (73.6%) of which were organ/space. Baseline demographic characteristics were similar among patients who developed SSI-CRAN and those who did not. The most frequent causative Gram-positive organisms were Cutibacterium acnes (23.1%) and Staphylococcus epidermidis (23.1%), whereas Enterobacter cloacae (12.1%) was the most commonly isolated Gram-negative agent. In the univariate analysis the factors associated with SSI-CRAN were ASA score > 2 (48.4% vs. 35.5% in SSI-CRAN and no SSI-CRAN respectively, p = 0.025), extrinsic tumour (28.6% vs. 19.2%, p = 0.05), and re-intervention (4.4% vs. 1.4%, p = < 0.001). In the multivariate analysis, ASA score > 2 (AOR: 2.26, 95% CI: 1.32-3.87; p = .003) and re-intervention (OR: 8.93, 95% CI: 5.33-14.96; p < 0.001) were the only factors independently associated with SSI-CRAN. Conclusion: The risk factors and causative agents of SSI-CRAN identified in this study should be considered in the design of preventive strategies aimed to reduce the incidence of this serious complication.

Invasive Meningococcal Disease: What We Should Know, Before It Comes Back.

BACKGROUND: Invasive meningococcal disease (IMD), sepsis and/or meningitis continues to be a public health problem, with mortality rates ranging from 5% to 16%. The aim of our study was to further knowledge about IMD with a large series of cases occurring over a long period of time, in a cohort with a high percentage of adult patients. METHODS: Observational cohort study of patients with IMD between 1977 hand 2013 at our hospital, comparing patients with only sepsis and those with meningitis and several degrees of sepsis. The impact of dexamethasone and prophylactic phenytoin was determined, and an analysis of cutaneous and neurological sequelae was performed. RESULTS: A total of 527 episodes of IMD were recorded, comprising 57 cases of sepsis (11%) and 470 of meningitis with or without sepsis (89%). The number of episodes of IMD decreased from 352 of 527 (67%) in the first to 20 of 527 (4%) in the last quarter (P < .001). Thirty-three patients died (6%): 8 with sepsis (14%) and 25 with meningitis (5%) (P = .02). Cutaneous and neurological sequelae were present in 3% and 5% of survivors of sepsis and meningitis, respectively. The use of dexamethasone was safe and resulted in less arthritis, and patients given prophylactic phenytoin avoided seizures. CONCLUSIONS: The frequency of IMD has decreased sharply since 1977. Patients with sepsis only have the highest mortality and complication rates, dexamethasone use is safe and can prevent some arthritis episodes, and prophylactic phenytoin might be useful in a selected population. A rapid response and antibiotic therapy may help improve the prognosis.

Delayed surgical site infection 2 years after cervical disk arthroplasty. Case report and literature review / Infección diferida del sitio quirúrgico 2 años después de la artroplastia de disco cervical. Caso clínico y revisión de la literatura

Anterior cervical discectomy has a low non-mechanical complication rate. In our literature review, we found 7 cases of delayed surgical site infection. We report a case of cervical prevertebral abscess due to Propionibacterium acnes 2 years after discectomy and arthroplasty, with a beta-2-transferrin false positive test as a complementary highlighted finding. We discuss the diagnosis and etiology of this rare delayed infectious complication

La discectomía cervical anterior tiene una baja tasa de complicaciones no mecánicas. En la revisión de la literatura, encontramos 7 casos de infección diferida del sitio quirúrgico. Presentamos un caso de absceso cervical prevertebral secundario a Propionibacterium acnes 2 años después de la cirugía, asociado a un falso positivo del test de beta-2-transferrina como hallazgo complementario a destacar, y discutimos el diagnóstico y la etiología de esta rara complicación infecciosa diferida

Delayed surgical site infection 2 years after cervical disk arthroplasty. Case report and literature review.

Anterior cervical discectomy has a low non-mechanical complication rate. In our literature review, we found 7 cases of delayed surgical site infection. We report a case of cervical prevertebral abscess due to Propionibacterium acnes 2 years after discectomy and arthroplasty, with a beta-2-transferrin false positive test as a complementary highlighted finding. We discuss the diagnosis and etiology of this rare delayed infectious complication.

Invasive meningococcal disease: Impact of short course therapy. A DOOR/RADAR study.

BACKGROUND: Invasive meningococcal disease is a severe infection. The appropriate duration of antibiotic therapy is not well established. METHODS: Two hundred and sixty-three consecutive patients with invasive meningococcal disease treated with 4 days' antibiotic therapy were compared with 264 consecutive patients treated previously at the same center with 7 days' antibiotic therapy. A Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) study was also performed. RESULTS: No relapses were recorded in any patient. Patients on the 4-day course were 63% female, with a median age of 23 years old (IQR 16-54) and patients on the 7-day course were 61% female, with a median age of 17 years old (IQR 12-43). Case fatality rate was 7% in the 4-d patients and 6% in the 7-d patients (p = 0.582). Neurological sequelae were recorded in 6% of the 4-d group and in 7% of the 7-d group ((p = 0.509) and cutaneous sequelae in 3% in both groups. There were no statistical significant differences between the groups in terms of clinical characteristics, laboratory findings or complications. The probability that a patient had a randomly chosen DOOR better with the 4-day regimen than with the 7-day regimen was 80.4% [95% CI 80.1-80.7%]. CONCLUSION: Invasive meningococcal disease may be successfully treated with a four-day course of antibiotic therapy without relapses.

Management of Ventriculoperitoneal Shunt Infections in Adults: Analysis of Risk Factors Associated With Treatment Failure.

Background: Little is known regarding the optimal treatment of ventriculoperitoneal (VP) shunt infections in adults. Our aim was to assess the efficacy of treatment strategies and to identify factors that predict failure. Methods: Retrospective, observational study of patients aged ≥12 years with VP shunt infections (1980 -2014). Therapeutic approaches were classified under 4 headings: only antibiotics (OA), one-stage shunt replacement (OSSR), two-stage shunt replacement (TSSR), and shunt removal without replacement (SR). The primary endpoint was failure of the treatment strategy, defined as the absence of definite cerebrospinal fluid (CSF) sterilization or related mortality. The parameters that predicted failure were analyzed using logistic regression. Results: Of 108 episodes (51% male, median age 50 years), 86 were analyzed. Intravenous antibiotics were administered for a median of 19 days. Eighty episodes were treated using strategies that combined antibiotic and surgical treatment (37 TSSR, 24 SR, 19 OSSR) and 6 with OA. Failure occurred in 30% of episodes, mostly due to lack of CSF sterilization in OSSR and OA groups. Twelve percent died of related causes and 10% presented superinfection of the CSF temporary drainage/externalized peritoneal catheter. TSSR was the most effective strategy when VP shunt replacement was attempted. The only independent risk factor that predicted failure was retention of the VP shunt, regardless of the strategy. Conclusions: This is the largest series of VP shunt infections in adults reported to date. VP shunt removal, particularly TSSR when the patient is shunt dependent, remains the optimal choice of treatment and does not increase morbidity.

Primary lumbar epidural abscess without spondylodiscitis caused by Fusobacterium necrophorum diagnosed by 16S rRNA PCR.

We report the case of a 71-year-old woman who presented a primary spinal epidural abscess caused by Fusobacterium necrophorum. This is the second report in the medical literature to associate this organism with a primary spinal epidural abscess without spondylodiscitis. After treatment with emergency laminectomy followed by 8 weeks of antibiotic treatment the patient was cured. Oral metronidazole (500 mg every 8 h) was the definitive choice of treatment. F. necrophorum spinal epidural abscess is rare, although samples for anaerobic culture should be collected in order to improve detection of anaerobic spinal infections. PCR amplification and sequencing of the 16S rRNA permits early diagnosis in anaerobic infections.