Impact of Subarachnoid Hemorrhage in Ventriculostomy-Related Infections Prospective Comparison of Two Neurosurgical Injury Contexts.

BACKGROUND: Long thought to be immune privileged, the central nervous system is far from being devoid of local immunity. Subarachnoid hemorrhage (SAH) and traumatic brain injury represent 2 distinct central nervous system injury situations which, while both exposed to external ventricular drains, present different incidences of ventriculostomy-related infection (VRI). We sought to compare VRI incidence and initial cerebrospinal fluid (CSF) inflammatory profiles in these 2 clinical situations. METHODS: From 2015 to 2020, 227 patients treated for SAH (193) or traumatic brain injury (34) with an external ventricular drain were prospectively included. CSF samples were sent daily for microbiological examination, cell count, and biochemical analysis. VRI was defined as a positive CSF culture associated with CSF profile modifications and clinical signs. Ventriculostomy-related colonization was defined as positive catheter culture at removal. Positive events were defined as VRI and/or ventriculostomy-related colonization. RESULTS: Eleven patients suffered from VRI, with an incidence of 3.6 VRI per 1000 catheter-days. All VRIs occurred among SAH patients without a significant difference. Median duration of drainage was 12 (7-18) days, there were no significant differences for known VRI risk factors. Positive events were significantly higher in SAH patients (20.7% vs. 2.9%, P = 0.013). Inflammatory CSF markers and serum white blood cells were higher in SAH patients. CONCLUSIONS: Local inflammatory markers were markedly higher in SAH than in traumatic brain injury. However, positive events were more frequent in SAH. Furthermore, SAH may be a risk factor for VRI. Hypothesis that a primary injury to the subarachnoid space could impair central nervous system immune functions should be explored.

Biofilm Assessment and Metagenomic Analysis of Venoarterial Extracorporeal Membrane Oxygenation Cannulas and Membrane Oxygenators.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) exposes the patient to infectious complications related to the cannulas or the site of insertion. The aim of the current study was to investigate and compare the prevalence of cannula and membrane oxygenators colonization using three different methods: microbiological culture, scanning electron microscopy, and metagenomic (rRNA 16S analysis). A monocentric prospective study was conducted between December 2017 and June 2018. Consecutive patients undergoing VA-ECMO support for refractory cardiac arrest or cardiogenic shock were included. Ten patients were included with a median age of 64 (52-62) years. Venoarterial extracorporeal membrane oxygenation was inserted for refractory cardiac arrest in five (50%), cardiogenic shock in four (40%), and self-poisoning in one (10%) cases. Microbiological culture of all (8/8, 100%) membrane oxygenators was negative, whereas all (10/10, 100%) were colonized by biofilm, and eight (8/9, 89%) presented bacterial DNA. Three (3/9, 33%) arterial and venous cannulas were positive in culture and seven (7/9, 78%) were colonized by biofilm, respectively. Seven (7/9, 78%) arterial and four (4/9, 44%) venous cannulas presented bacterial DNA. Colonization of cannulas and membranes is more frequent when assessed by electron microscopy or metagenomic analysis than with culture. Membrane oxygenators are more often colonized than cannulas.

Real-life use of ceftobiprole for severe infections in a French intensive care unit.

Ceftobiprole (CBP) is an anti-methicillin-resistant Staphylococcus aureus (MRSA) cephalosporin with a wide spectrum of activity. We aimed to describe our experience of real-life use of CBP for the treatment of severe infections of critically ill patients with multiple infected sites and related trough CBP concentrations. We performed a retrospective, observational, monocentric study in our intensive care unit (ICU) that included all patients treated with CBP for documented infections between January 2016 and December 2021. We collected demographic, clinical, and microbiological data. When available, we report the CBP trough concentrations. The primary endpoint was clinical cure at the end of treatment. The secondary endpoints were in-hospital mortality and documentation of the carriage of multidrug-resistant (MDR) bacteria not present before CBP treatment. Between January 2016 and December 2021, 47 patients were treated in the ICU with CBP. The main indication for treatment was pneumonia (51%) and most patients presented with associated bacteremia (72%). All infections were polymicrobial. A clinical cure was achieved for nearly 80% of the patients. Only five patients presented new carriage of MDR bacteria. In-hospital mortality was 32%. Out of 21 strains of Enterobacterales for which the MIC was available, 33% were considered to be resistant to CBP according to the EUCAST 2023 clinical breakpoint. Trough CBP concentrations were reported for 16 patients. In our real-life experience, treatment of ICU patients with CBP for polymicrobial severe infections resulted in most cases in a clinical cure. Monitoring of trough concentrations is critical, especially in cases of high MIC.

The effects of prolonged stress exposure on the brain of rats and insights to understand the impact of work-related stress on caregivers.

Introduction: Stress exposure is a significant concern in the healthcare sector. This animal model study aims to reproduce caregivers' working conditions and determine their impact on the brain. Method: Twenty-four healthy male rats of the Wistar strain were divided into four groups. Three groups were submitted each to one stressor for 21 days, while the fourth group was used as a control. Stressors were food and water deprivation (FW), permanent illumination (PI), and forced swimming (FS). At the end of the experiment, rats were euthanized, and stress biomarkers, biological parameters, and DNA damage were measured. Results: Prooxidant biomarker rates increased in the different groups (+50 to +75%) compared to the control (p < 0.0001). Urinary corticosterone rates increased in all stressed animals, mainly in the PI group, with changes of up to +50% compared to the control group. Acetylcholinesterase levels decreased to -50% (p < 0.0001 for the three exposed groups). Total ATPase, (Na+/K+)-ATPase, and Mg2+-ATPase activities decreased in all stressed groups. The percentage of brain cell congestion and apoptosis was 3% for the FW group (p < 0.0001), 2% for the PI group (p < 0.0001), and 4% for the FS group (p < 0.0001) compared to the control (0.8%). DNA damage was observed in all exposed groups. Finally, we noticed behavioral changes and a depression-like syndrome in all stressed rats. Conclusion: Stressful conditions such as the working environment of caregivers can trigger several pathophysiological processes leading to oxidative, neurochemical, and hypothalamic-pituitary-adrenal disorders. These changes can progress to cell damage and apoptosis in the brain and trigger psychological and physical disorders.

Prospective Comparative Study of External Ventricular Drain Catheter Colonization: Antibiotic-Impregnated versus Conventional Drains.

OBJECTIVE: Our aim was to compare the prevalence of biofilm formation on antibiotic-impregnated (AIC) versus standard (SC) external ventricular drain (EVD) catheters. METHODS: From March 2018 to November 2020, all consecutive EVD catheters inserted in adult patients were included. After removal, EVD catheters were analyzed under scanning electronic microscopy, on both extraluminal and intraluminal faces. Standard culture of catheter tips was also performed. RESULTS: Overall, 114 catheters were included in 101 patients. There were 48 AICs and 66 SCs. Standard culture showed that ventriculostomy-related colonization was more frequent in SC than in AIC (26 vs. 10%; P = 0.06). Gram-negative rods accounted for 25% of ventriculostomy-related colonization in AICs, and none was documented in SCs. Scanning electronic microscopy observation showed mature biofilm on more than 80% of catheters, without significant difference between catheter type. Also, there was no difference between extraluminal and intraluminal colonization rate. There were 2 ventriculostomy-related infections in each group (5% and 3% among AICs and SCs respectively; P = 1). CONCLUSIONS: Mature biofilm presence on the intraluminal and the extraluminal faces is similar on AICs and SCs. Accordingly, AICs do not seem to efficiently prevent biofilm formation on EVD catheters. The impact of AICs on the microbiological epidemiology of colonizing biofilm should be further evaluated.

Prevention of Ventriculostomy Related Infection: Effectiveness of Impregnated Biomaterial.

External ventricular drain(EVD) exposes the patient to infectious complications which are associated with significant morbidity and economic burden. Biomaterials impregnated with various antimicrobial agents have been developed to decrease the rate of bacterial colonization and subsequent infection. While promising, antibiotics and silver-impregnated EVD showed conflicting clinical results. The aim of the present review is to discuss the challenges associated with the development of antimicrobial EVD catheters and their effectiveness from the bench to the bedside.

Clinical outcome of wild-type AmpC-producing Enterobacterales infection in critically ill patients treated with ß-lactams: a prospective multicenter study.

BACKGROUND: ß-lactams are the main antibiotics used against wild-type AmpC-producing Enterobacterales (wtAE). However, they may fail or select AmpC-overproducing mutants. Our aim was to assess factors associated with clinical failure of ß-lactams in the treatment of wtAE infection. METHODS: From September 2017 to December 2020, we prospectively included all consecutive patients treated by definitive ß-lactams therapy for wtAE infection in four university ICUs. Clinical failure was defined as inadequate response to antimicrobial therapy leading to death or to the switch for a broader-spectrum antibiotic. RESULTS: 177 patients were included and 29.4% progressed to clinical failure. E. cloacae was the most prevalent species (42.4%) and ventilator-associated pneumonia (VAP) was the most frequent wtAE infection (69.5%). Cefepime and cefotaxime were used as definitive antibiotic treatment in 42.9% and 27.7% of patients, respectively. Occurrence of AmpC-overproduction was documented in 5.6% of patients and was associated with clinical failure (p = 0.004). In multivariate analysis, VAP (p < 0.001, OR 11.58 [95% CI 3.11-43.02] and K. aerogenes (p = 0.030, OR 3.76 [95% CI 1.13-12.46]) were independently associated with clinical failure. Conversely, cefotaxime as definitive treatment was found inversely associated with the risk of clinical failure (p = 0.022, OR 0.25 [95% CI 0.08-0.82]). After inverse probability weighting, cefotaxime showed a 20% risk reduction of clinical failure (95% CI 5-35%, p = 0.007) whatever the location of infection, the SOFA score on the day of wtAE infection, or the bacterial species. CONCLUSIONS: Clinical failure in the treatment of wtAE infections is associated with the infection site and the causal microorganism. Additionally, cefotaxime use is probably protective against clinical failure in wtAE infection.

In vitro study of factors influencing the duration of antimicrobial protection of antimicrobial-impregnated external ventricular drains.

BACKGROUND: In vitro and clinical studies assessing the duration of the protective activity of antimicrobial-impregnated external ventricular drains (AI-EVDs) gave conflicting results. OBJECTIVES: To identify factors associated with decreased antimicrobial activity of AI-EVDs that were not taken into account in previous in vitro models. METHODS: We performed in vitro experiments with Bactiseal™ AI-EVDs, under different conditions. Tested parameters were chosen to mimic conditions in which AI-EVDs are used: perfusion by saline (at different flow rates) or not perfused, dwelling medium (air, saline, saline+protein, lipid) and temperature. Antimicrobial activity was assessed by measurement of inhibitory diameters of a 0.5 cm portion of an AI-EVD (cut every 2 days) placed onto agar plates covered by a standardized Staphylococcus spp. inoculum (three different isolates). MS was used to measure concentrations of rifampicin and clindamycin after 48 h of dwelling. RESULTS: In univariate analysis, most of the tested factors were associated with reduced antimicrobial activity: liquid media (as compared with ambient air), perfusion whatever the rate flow (as compared with no perfusion) and presence of protein in the media. In multivariate analysis, dwelling in media (lipid or saline) was the most constantly associated with a reduction of inhibition diameters (P < 0.01), as compared with ambient air. After 48 h of dwelling, the clindamycin concentration was higher than 100 and 450 mg/L in saline and saline+BSA, respectively. CONCLUSIONS: The medium in which an AI-EVD is dwelling plays a significant role in the duration of AI-EVD activity. These results may explain conflicting results between clinical and in vitro studies.

Analysis of Paradoxical Efficacy of Carbapenems against Carbapenemase-Producing Escherichia coli in a Murine Model of Lethal Peritonitis.

The clinical benefit of carbapenems against carbapenemase-producing Enterobacteriaceae (CPE) remains in question. MICs of imipenem (IMP) and ertapenem (ERT) against isogenic derivatives of the wild-type strain Escherichia coli CFT073 producing KPC-3, OXA-48, or NDM-1 were 0.25, 2, 16, and 64 mg/liter for IMP and 0.008, 0.5, 8, and 64 mg/liter for ERT, respectively. Swiss ICR-strain mice with peritonitis were treated for 24 h with IMP or ERT. Despite a limited duration of time during which free antibiotic concentrations were above the MIC (down to 0% for the NDM-1-producing strain), IMP and ERT significantly reduced bacterial counts in spleen and peritoneal fluid at 24 h (P < 0.005) and prevented mortality. Several possible explanations were investigated. Addition of 4% albumin or 50% normal human serum did not modify IMP activity. Bacterial fitness of resistant strains was not altered and virulence did not decrease with resistance. In the presence of subinhibitory concentrations of ERT, growth rates of OXA-48, KPC-3, and NDM-1 strains were significantly decreased and filamentation of the NDM-1 strain was observed. The expression of blaNDM-1 was not decreased in vivo compared to in vitro No zinc depletion was observed in infected mice compared with Mueller-Hinton broth. In conclusion, a paradoxical in vivo efficacy of IMP and ERT against highly resistant carbapenemase-producing E. coli was confirmed. Alternative mechanisms of antibacterial effects of subinhibitory concentrations of carbapenems may be involved to explain in vivo activity. These results are in agreement with a potential clinical benefit of carbapenems to treat CPE infections, despite high carbapenem MICs.

Multidrug-Resistant Staphylococcus epidermidis Ventriculostomy-Related Infection Successfully Treated by Intravenous Ceftaroline after Failure of Daptomycin Treatment.

BACKGROUND: Ventriculostomy-related infection with multidrug-negative strains are challenging to treat. We report the use of new antibiotics in such a case. CASE DESCRIPTION: We report the case of a neurosurgical intensive care unit patient who developed ventriculostomy-related infection with a multidrug-resistant Staphylococcus epidermidis. Vancomycin, recommended in such cases, was not used due to high minimal inhibitory concentrations and concerns for lack of pharmacokinetic/pharmacodynamic target attainment. Daptomycin and ceftaroline remained the only treatment options. Daptomycin was shown microbiologically ineffective after 10 treatment days, with undetectable cerebrospinal fluid (CSF) concentration. Ceftaroline, a novel beta-lactam agent to which the strain showed susceptibility, was thus used. Serum and CSF samples were assessed for antibiotic concentrations. Our results show that CSF bacterial clearance was obtained after 6 days of such treatment. Serum and CSF samplings showed low penetration ratios (2.6%-4.8%), probably due to mild inflammatory CSF profile, with CSF concentration at minimal inhibitory concentration level. CONCLUSIONS: We observed than even in the case of mild meningeal inflammation, ceftaroline penetration in CSF, although moderate, enabled efficient bacterial clearance and clinical efficacy, in adjunction to correct ventriculoperitoneal shunt management.

Influence of Fraction of Inspired Oxygen on Noninvasive Hemoglobin Measurement: Parallel Assessment of 2 Monitors.

BACKGROUND: Previous reports have brought specific attention to the relationship between oxygenation of the patient and the accuracy of noninvasive measurement of hemoglobin (Hb) using an optical sensor. This study aimed to assess prospectively the relationship between fraction of inspired oxygen (FIO2) and the bias of the measurement of Hb by the use of 2 different noninvasive monitors compared with the classic invasive technique. METHODS: Forty-four patients were included prospectively. In each individual, Hb level was determined noninvasively by monitor Pronto-7™ (Masimo Corporation, Irvine, CA) and by monitor NBM-200MP™ (OrSense Ltd, Petah-Tikva, Israel), with the probe placed on 2 fingers on the same hand of the patient. Three measures were performed, first under breathing air and 2 others when fraction of expired oxygen rose to 50% ± 5% and to 90 ± 5%. Simultaneously, a nurse collected a venous blood sample, which was sent immediately to the hematology laboratory for Hb measurement. The main outcome measurement was the mean bias between noninvasive and invasive measurements. RESULTS: Results show no change in median bias [interquartile range] with FIO2 for Pronto-7 (from 1.1 g/dL [0.0-2.0] in FIO2 21% to 1.0 g/dL [0.2-1.5] in FIO2 100%), but increasingly negative median bias with increasing FIO2 for NBM-200MP (from -0.3 g/dL [-1.3 to 0.3] in FIO2 21% to -0.8 g/dL [-1.5 to -0.1] in FIO2 100%, P = .04). DISCUSSION: This study showed that noninvasive measurement of Hb could be influenced by inspired fraction of oxygen when the monitor NBM-200MP is used.

Antibiotics against Pseudomonas aeruginosa for COPD exacerbation in ICU: a 10-year retrospective study.

SUMMARY: Chronic obstructive pulmonary disease (COPD) is a frequent source of hospitalization. Antibiotics are largely prescribed during COPD exacerbation. Our hypothesis is that large broad-spectrum antibiotics are more and more frequently prescribed. Our results confirm this trend and highlight that the increase in large broad-spectrum use in COPD exacerbation is largely unexplained. BACKGROUND: Acute COPD exacerbation (AECOPD) is frequently due to respiratory tract infection, and the benefit of antipseudomonal antibiotics (APA) is still debated. Health care-associated pneumonia (HCAP) was defined in 2005 and requires broad-spectrum antibiotherapy. The main objectives are to describe the antibiotic use for AECOPD in intensive care unit and to identify factors associated with APA use and AECOPD prognosis. METHODS: We conducted a monocentric, retrospective study on all AECOPDs in the intensive care unit treated by antibiotics for respiratory tract infection. Treatment failure (TF) was defined by death, secondary need for mechanical ventilation, or secondary systemic steroid treatment. A multivariate analysis was used to assess factors associated with APA prescription and TF. RESULTS: From January 2000 to December 2011, 111 patients were included. Mean age was 69 years (±12), mean forced expiratory volume 38% of theoretic value (±13). Thirty-five (31%) patients were intubated, and 52 (47%) were treated with noninvasive ventilation. From 107 patients, 8 (7%) cases of Pseudomonas aeruginosa were documented. APAs were prescribed in 21% of patients before 2006 versus 57% after (P=0.001). TF prevalence was 31%. Risk factors for P. aeruginosa in COPD and HCAP diagnosis did not influence APA, whereas the post-2006 period was independently associated with APA prescription (odds ratio 6.2; 95% confidence interval 1.9-20.3; P=0.0013). APA did not improve TF (odds ratio 1.09; 95% confidence interval 0.37-3.2). CONCLUSION: HCAP guidelines were followed by an increase in APA use in AECOPD, without an improvement in prognosis. HCAP prevalence cannot account for the increasing APA trend. Time effect reveals a drift in practices. The microbiological effect of such a drift must be evaluated.