Time is of the Essence: Achieving Prompt and Effective Antimicrobial therapy of Bloodstream infection With Advanced Hospital Information Systems.

The early administration of appropriate antibiotic therapy is crucial for the survival of patients with bacteremia. Current research focuses on improving analytical times through technology while there have been very few efforts to improve post-analytical times even though they represent 40% of the time between blood taking and appropriate treatment administration. One of the clues is the efficiency and appropriateness of the result communication system. Here, we review all delays in the whole process with the aim of improving time to appropriate treatment administration. We discuss causes for long times to adjust treatment once microbiological results are released. We argue that that the pervasive health information system in this organization serves as both a bottleneck and a rigid framework to focus on. Finally, we explore how should be conceived the next generation hospital information systems to effectively assist the doctors in treating patients with bacteremia.

COVID-19: The forgotten cases of hidden exiles.

PURPOSE OF THE RESEARCH: We describe two interventions to screen for SARS-CoV-2 in two squats of exiled persons in France following the diagnosis of symptomatic COVID-19 cases. PRINCIPAL RESULTS: In squat A, 50 (25%) persons were screened; 19 were found positive, and three accepted a transfer. In squat B, 65 (54%) persons were screened at three different times, and only two were found positive. MAJOR CONCLUSIONS: Discrepant outcomes may reflect different levels of sanitation, prevention, and acceptance of interventions. Refusal to be transferred to specific COVID-19 homes if tested positive underscores the importance of local sanitary solutions for all. Cross-curricular strategies addressed to exiled persons are essential means of providing medical and public health solutions designed to deter COVID-19 outbreaks in these populations.

Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients.

OBJECTIVES: SARS-CoV-2 antibody assays are needed for serological surveys and as a complement to molecular tests to confirm COVID-19. However, the kinetics of the humoral response against SARS-CoV-2 remains poorly described and relies on the performance of the different serological tests. METHODS: In this study, we evaluated the performance of six CE-marked point-of-care tests (POC) and three ELISA assays for the diagnosis of COVID-19 by exploring seroconversions in hospitalized patients who tested positive for SARS-CoV-2 RNA. RESULTS: Both the ELISA and POC tests were able to detect SARS-CoV-2 antibodies in at least half of the samples collected seven days or more after the onset of symptoms. After 15 days, the rate of detection rose to over 80% but without reaching 100%, irrespective of the test used. More than 90% of the samples collected after 15 days tested positive using the iSIA and Accu-Tell® POC tests and the ID.Vet IgG ELISA assay. Seroconversion was observed 5 to 12 days after the onset of symptoms. Three assays suffer from a specificity below 90% (EUROIMMUN IgG and IgA, UNscience, Zhuhai Livzon). CONCLUSIONS: The second week of COVID-19 seems to be the best period for assessing the sensitivity of commercial serological assays. To achieve an early diagnosis of COVID-19 based on antibody detection, a dual challenge must be met: the immunodiagnostic window period must be shortened and an optimal specificity must be conserved.

Implant retention and high rate of treatment failure in hematogenous acute knee and hip prosthetic joint infections.

OBJECTIVES: Only few studies evaluated hematogenous prosthetic joint infections. We aimed to describe the characteristics of these infections and factors associated with management failure. METHODS: We selected hematogenously-acquired infections, defined by the occurrence of infectious symptoms more than a year after implantation among records of patients treated for hip and knee prosthetic joint infections at Montpellier University Hospital between January 2004 and May 2015. Failure was defined by death due to prosthesis-related infection, need for prosthesis removal in case of conservative treatment, or recurrence of infectious signs on a new prosthesis. RESULTS: Forty-seven patients with hematogenous prosthetic joint infection were included (33 knee infections and 14 hip infections). Infectious agents were streptococci (43%), Staphylococcus aureus (43%), Gram-negative bacilli (13%), and Listeria monocytogenes (2%). Thirty-one patients were initially treated with debridement and implant retention and 15 with prosthesis removal (three with one-stage surgery, 10 with two-stage surgery). The median duration of antibiotic therapy was 66.5 days. The overall failure rate was 52% (24/48), 71% (22/31) with implant retention strategy, 13% (2/15) with prosthesis removal, and 63% (12/19) in case of Staphylococcus aureus infection. Conservative treatment was appropriate (arthrotomy on a well-implanted prosthesis without sinus tract and symptom onset <21 days) in 13/31 patients (42%) with a failure rate still high at 69% (9/13). The only factor associated with failure was conservative surgical treatment. CONCLUSION: The high risk of failure of conservative treatment for hematogenous prosthetic joint infections should lead to considering prosthesis replacement as the optimal strategy, particularly with Staphylococcus aureus.

Potential lung cancer screening outcomes using different age and smoking thresholds in the ANRS-CO4 French Hospital Database on HIV cohort.

OBJECTIVES: In most lung screening programmes, only subjects ≥ 55 years old and smoking ≥ 30 pack-years are eligible to undergo chest low-dose computed tomography. Whether the same criteria should apply to people living with HIV (PLHIV) is uncertain, given the increased lung cancer risks associated with immunodeficiency and high rates of smoking. We assessed different outcomes obtained from simulating one round of lung cancer screening in PLHIV using different age and smoking thresholds for eligibility. METHODS: Data from the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS)-CO4 French Hospital Database on HIV (FHDH) cohort of PLHIV and a national representative survey of PLHIV in care in 2011 (the ANRS-VESPA2 [enquête sur les personnes atteintes] study) were used to estimate the maximum proportion of incident lung cancers occurring between 2012 and 2016 that would have potentially been detected by screening in 2011. Secondary outcomes were numbers of eligible subjects in the cohort and numbers of subjects needed to screen (NNS) to detect one lung cancer. RESULTS: Among 77819 PLHIV in 2011 (median age 46 years; 66% men), 285 subjects subsequently developed lung cancer. Adoption of the US Preventive Services Task Force (USPSTF) recommendations (55-80 years; ≥ 30 pack-years) would have detected 31% of lung cancers at most. Lowering the minimum age to 50 and 45 years would have detected 49% and 60% of cancers, respectively, but would have greatly increased the number of eligible subjects and the NNS to detect one case of lung cancer. CONCLUSIONS: Use of the USPSTF criteria would have detected only a minority of lung cancers in a large French cohort of PLHIV in 2011. Screening PLHIV at younger ages (45 or 50 years) and/or the use of lower smoking thresholds (20 pack-years) may be beneficial, despite the consequently higher numbers of eligible subjects and NNS to detect one case of lung cancer, and should be evaluated in future studies.

Time to blood culture positivity: An independent predictor of infective endocarditis and mortality in patients with Staphylococcus aureus bacteraemia.

OBJECTIVES: Time to blood culture positivity (TTP), a routinely available parameter in automated blood culture systems, may be a proxy for infectious burden in patients with bloodstream infections. We aimed to study the association between TTP and infective endocarditis (IE), or death, in patients with Staphylococcus aureus bacteraemia. METHODS: VIRSTA is a multicentre prospective cohort study that included all adult patients with S. aureus bacteraemia in eight university hospitals in France (2009-2011). We analysed data from four centres which collected data on TTP. Regression models were used to study the association between TTP and definite IE (Duke-Li criteria), and 30 day-mortality. RESULTS: We included 587 patients with S. aureus bacteraemia: mean age was 65.3 ± 16.3 years, 420 out of 587 patients (71.6%) were male, 121 out of 587 (20.6%) died, and 42 out of 587 (7.2%) had definite IE. Median TTP of first positive blood culture was 13.7 h (interquartile range 9.9-18). On multivariate analysis, 30-day mortality was associated with TTP ≤13.7 h (74/295 (25.1%) vs. 47/292 (16.1%), p 0.02), as well as old age, McCabe score, methicillin resistance, stroke, pneumonia, and C-reactive protein. TTP was also independently associated with IE, but with a U-shape curve: IE was more common in the first (TTP <10 h, 17/148, 11.5%), and the last (TTP ≥18 h, 8/146, 5.5%) quartiles of TTP, p 0.002. CONCLUSIONS: TTP provides reliable information in patients with S. aureus bacteraemia, on the risk of IE, and prognosis, with short TTP being an independent predictor of death. These data, readily available at no cost, may be used to identify patients who require specific attention.

Investigation of pre-XDR Beijing Mycobacterium tuberculosis transmission to a healthcare worker in France, 2016.

A case of occupational contamination of a healthcare worker by a pre-extensively drug-resistant (pre-XDR) Beijing strain of Mycobacterium tuberculosis at the University Hospital of Montpellier, France is reported. The index case was identified using genetic fingerprinting of isolates. This report underscores the risk of healthcare-associated contamination by pre-XDR tuberculosis (TB) in low-incidence countries and the importance of molecular tools for TB care. It also calls for increased vigilance in the management of multi-drug-resistant/XDR TB patients.

Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/µL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/µL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. CONCLUSIONS: Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control.

Impact of T cell activation, HIV replication and hepatitis C virus infection on neutrophil CD64 expression.

BACKGROUND: Overexpression of the Fc receptor CD64 on neutrophils is associated with innate immune response and bacterial infections. During HIV infection a large set of immune disorders including T-lymphocyte over-activation, microbial translocation, impairment of neutrophil functions, and immunodeficiency may interplay with neutrophil CD64 expression. METHODS: Associations of neutrophil CD64 expression with CD8+ T cell activation, CD4+ T cells number, HIV, and HCV replications were investigated in HIV infected patients using a standardized method. RESULTS: Higher neutrophil CD64 expression was observed in HIV infected subjects compared to healthy controls (0.91 vs. 0.75, P < 0.001). Among 115 HIV infected patients, nine (8.8%) had a CD64 expression over the clinical threshold as calculated against bead standard (i.e., 1.5). HIV viremic patients were more likely to have an index above 1.5 (OR: 6.68, P values: 0.01). A trend for correlation between CD64 expression and CD8 T cell activation was observed (P values: 0.08). Blood CD4+ T lymphocyte depletion and HCV replication did not affect neutrophil CD64 expression. CONCLUSIONS: HIV infection and HIV replication are associated with up-regulation of neutrophil CD64. CD64 overexpression above the clinical threshold was observed in a minor proportion of HIV infected individuals treated by antiretroviral therapy and may be a marker of neutrophil activation related to non-AIDS-linked comorbidities. © 2016 International Clinical Cytometry Society.

Factors associated with 12 week case-fatality in Staphylococcus aureus bacteraemia: a prospective cohort study.

Staphylococcus aureus bacteraemia (SAB) is a frequent and deadly disease. Given the lack of a randomized trial, optimal first-line antibiotic treatment is still debated. Our aim was to identify prognostic factors in SAB patients and to analyse the impact of first-line antibiotics. The VIRSTA prospective cohort study was conducted in eight tertiary care centres in France. Consecutive incident adults in whom a blood culture drawn in participating centres grew S. aureus between April 2009 and October 2011 were prospectively followed for 12 weeks. Factors associated with 12-week case-fatality were identified by multivariate logistic regression. We enrolled 2091 patients and analysed survival in 1972 (median age 67.8 years, interquartile range 55.5-78.9; females 692/1972, 35.1%). SAB was nosocomial or healthcare-related in 1372/1972 (69.6%) of cases and the primary focus was unknown in 414/1972 (21.0%) of cases. Week 12 case-fatality rate was 671/1972 (34.0%). The main independent prognostic factors on multivariate analysis were age (adjusted OR by 10-year increment 1.56; 95% CI 1.44-1.69), septic shock (OR 5.11; 95% CI 3.84-6.80), metastatic cancer (OR 4.28; 95% CI 2.88-6.38), and unknown primary focus (OR 2.62; 95% CI 2.02-3.41). In the 1538 patients with methicillin-sensitive S. aureus (MSSA) bacteraemia, first-line empiric antistaphylococcal penicillins (OR 0.40; 95% CI 0.17-0.95) and vancomycin (OR 0.37; 95% CI 0.17-0.83), alone or combined with an aminoglycoside, were associated with better outcome compared with other antibiotics. There are few modifiable prognostic factors for SAB. Initiating empiric antibiotics with antistaphylococcal penicillins or vancomycin may be associated with better outcome in MSSA bacteraemia.

Diagnosing pelvic osteomyelitis beneath pressure ulcers in spinal cord injured patients: a prospective study.

There is no consensus on a diagnostic strategy for osteomyelitis underlying pressure ulcers. We conducted a prospective study to assess the accuracy of multiple bone biopsies and imaging to diagnose pelvic osteomyelitis. Patients with clinically suspected osteomyelitis beneath pelvic pressure ulcers were enrolled. Bone magnetic resonance imaging (MRI) and surgical bone biopsies (three or more for microbiology and one for histology per ulcer) were performed. Bacterial osteomyelitis diagnosis relied upon the association of positive histology and microbiology (at least one positive culture for non-commensal microorganisms or three or more for commensal microorganisms of the skin). From 2011 to 2014, 34 patients with 44 pressure ulcers were included. Bacterial osteomyelitis was diagnosed for 28 (82.3%) patients and 35 (79.5%) ulcers according to the composite criterion. Discrepancy was observed between histology and microbiology for 5 (11.4%) ulcers. Most common isolates were Staphylococcus aureus (77.1%), Peptostreptococcus (48.6%) and Bacteroides (40%), cultured in three or more samples in 42.9% of ulcers for S. aureus and ≥20% for anaerobes. Only 2.8% of ulcers had three or more positive specimens with coagulase-negative staphylococci, group B Streptococcus, and nil with enterococci and Pseudomonas aeruginosa. Staphylococcus aureus, Proteus and group milleri Streptococcus were recovered from one sample in 22.8%, 11.4% and 11.4% of ulcers, respectively. Agreement was poor between biopsies and MRI (κ 0.2). Sensitivity of MRI was 94.3% and specificity was 22.2%. The diagnosis of pelvic osteomyelitis relies on multiple surgical bone biopsies with microbiological and histological analyses. At least three bone samples allows the detection of pathogens and exclusion of contaminants. MRI is not routinely useful for diagnosis.

Efficacy of ceftriaxone and doxycycline in the treatment of early syphilis.

INTRODUCTION: An increase of syphilis cases has been recorded in the past few decades, especially among HIV-infected patients. These patients often present with concomitant primary and secondary lesions or extensive presentations of syphilis. OBJECTIVE: Our goal was to compare alternative regimens to the recommended penicillin treatment. METHOD: We retrospectively studied 116 patient files (80% HIV1-infected) treated for a first episode of early syphilis. RESULTS: Patients mainly presented with symptoms of secondary syphilis. In 15.5% of the cases patients were asymptomatic and 17.2% of patients with secondary syphilis presented with neurologic or ophthalmic symptoms. Some less usual clinical presentations included diffuse polyadenopathy or isolated fever. The time to serological response was similar among those treated with benzathine-penicillin (n=52), ceftriaxone (n=49), or doxycycline (n=15). CONCLUSION: Ceftriaxone and doxycycline could be suitable alternatives to penicillin in the treatment of early syphilis in HIV-infected patients. These two treatments have a concomitant effectiveness even for asymptomatic forms of neurosyphilis.

[Meningomyeloradiculitis in an immunocompetent patient]. / Méningomyéloradiculite àCandida albicans chez un sujet immunocompétent.

INTRODUCTION: Candida infection limited to the central nervous system is extremely rare, and may be confused with tuberculosis on the grounds of the clinical and cerebrospinal fluid findings. CASE REPORT: A 23-year-old immunocompetent drug addict presented with alternating sciatica over a period of several months, followed by multiple cranial nerve involvement in the setting of marked weight loss. The histopathologic examination of a leptomeningeal neurosurgical biopsy was required to establish the diagnosis of neuromeningeal infection with Candida albicans. CONCLUSION: This case report underlines diagnostic difficulties of candidal meningitis and reviews current therapeutic recommendations.

[Adherence to antibiotherapy guidelines for acute community-acquired pneumonia in adults, in a teaching hospital]. / Audit des prescriptions d'antibiotiques dans les pneumonies aiguës communautaires de l'adulte dans un centre hospitalier universitaire.

OBJECTIVE: The authors had for aim to assess the conformity of antibiotic prescription with guidelines, for the management of community-acquired pneumonia, in a French University Hospital. DESIGN: This prospective study included adults patients hospitalized for pneumonia over a period of six months. The attending physician estimated the severity of pneumonia. The adequacy to guidelines focused on: first antibiotic choice and prescription modality, antibiotic choice in case of treatment modification at 48 to 72 hours, and duration of antibiotherapy. RESULTS: A hundred and nine cases of pneumonia were included in 106 patients. The mean age was 66 years, the mortality rate was 17 %. Bacterial documentation was recorded in 40.4 % of cases. The first antibiotics used were in accordance with guidelines in 52.3 % of cases. The non conformity rate was minor in 55.8 % of cases. Antibiotherapies putting the patient at risk were used in less than 10 % of the cases. The rate of antibiotic modification at 48 to 72 hours was 46.8 %, primarily for bacteriological purposes (35.3 %) or initial treatment failure (27.4 %). The treatment duration was inappropriate in 52.7 % of cases and generally too long in case of non conformity. CONCLUSION: It seems important to support guideline information, training of prescribers, and to consult an antibiotic expert.

Pregnancy may be followed by an inflexion of the immune reconstitution in HIV-infected women who receive antiretroviral drugs before conception.

BACKGROUND: Whether pregnancy has an impact on the evolution of CD4 cell counts in women treated with highly potent antiretrovirals before conception remains largely unknown. METHODS: Among patients enrolled in the ANRS CO8 (APROCO/COPILOTE) cohort, we selected all women aged between 18 and 50 years at initiation of combination antiretroviral therapy (cART). Slopes of CD4 cell counts during follow-up were estimated using mixed longitudinal models with time-dependent indicators for pregnancy and delivery. RESULTS: Of the 260 selected HIV-infected women, a pregnancy occurred in 39 women in a median follow-up time of 66 months. Women who became pregnant had higher CD4 cell count at baseline but this difference progressively lessened during follow-up because they had a slower increase than women who did not become pregnant. The estimated slope of CD4 cell count decreased significantly from +2.3 cells/muL/month before pregnancy and in women who did not become pregnant to -0.04 cells/microL/month after delivery (P=0.0003). CONCLUSION: A significant increase in CD4 cell count may be preferable before pregnancy in women treated with cART, in order to overcome the evolution observed after pregnancy.