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.

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.

Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study.

OBJECTIVES: Cerebral infections related to the presence of an intraparenchymal intracranial pressure transducer (ICPT) are rare. We assessed the incidence of ICPT-related infections and colonization using culture, molecular biology, and electron microscopy. METHODS: All consecutive patients in a neurosurgical intensive care unit who had an ICPT inserted between March 2017 and February 2018 were prospectively included. Presence of colonization on the ICPTs was assessed after removal using culture, scanning electron microscopy (SEM), and next-generation sequencing (NGS). RESULTS: Fifty-three ICPTs (53 patients), indwelling for a median of 4 (range 3-7) days, were studied. Median patient follow-up was 3 months. SEM, microbial culture, and NGS were performed for 91%, 79%, and 72% of ICPTs, respectively; 28 ICPTs (53%) were assessed using all three techniques. No patient developed ICPT-related infection. Microbial cultures were positive for two of the ICPTs (5%); colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was observed on 35/48 (73%) of ICPTs. A median of 10 (8-12) operational taxonomic units were identified for each ICPT, most being of environmental origin. There was no association between biofilm maturity and antimicrobial treatment or duration of ICPT insertion. Antimicrobial treatment was associated with decreased alpha and beta-diversity (p = 0.01). CONCLUSIONS: We observed no ICPT-related cerebral infections although colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was the main bacterial lifestyle on the ICPTs.

Durability of antimicrobial activity of antibiotic-impregnated external ventricular drains: a prospective study.

BACKGROUND: Antibiotic-impregnated external ventricular drains (AI-EVDs) have a debated efficacy in clinical studies. OBJECTIVES: Our aim was to assess the durability of antimicrobial activity of AI-EVDs used in clinical settings. METHODS: From April 2017 to January 2018, all consecutive AI-EVDs (Bactiseal™) inserted in adult patients were prospectively included. After removal, each AI-EVD was cultured and assessed for antimicrobial activity on both internal and external sides of AI-EVDs. Catheters were each challenged with a single Staphylococcus strain [MSSA, MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE)]. MS was used to measure residual concentrations of rifampicin and clindamycin. RESULTS: Sixty-five AI-EVDs were included (56 patients). Among these, 21 were challenged with MSSA, 23 with MRSA and 21 with MRSE. Five ventriculostomy-related colonizations (9%) and two ventriculostomy-related infections (4%) occurred. Staphylococcus was the main bacterium responsible for colonization (4/5). AI-EVD inhibition decreased significantly against MRSA and MRSE according to duration of catheterization (for external and internal sides, P < 0.02) and overall volume of CSF drained (P < 0.005 for both sides against MRSE, P < 0.005 for external side against MRSA), but not against MSSA. Clindamycin concentration was not correlated with duration of catheterization or CSF volume drained, but <20% of initial concentration was recovered even after 5 days of AI-EVD dwelling. Conversely, rifampicin concentration showed a rapid and significant decline correlated to duration and CSF volume (P < 0.001 and P = 0.03, respectively). CONCLUSIONS: Antimicrobial activity of AI-EVDs dropped quickly in vivo. Antimicrobial impregnation did not prevent AI-EVD colonization by susceptible strains in 9% of the cases.

Secondary Insults and Adverse Events During Intrahospital Transport of Severe Traumatic Brain-Injured Patients.

BACKGROUND: Our aim was to assess the occurrence of secondary insults (SIs) or adverse events (AEs) during intrahospital transport (IHT) of severe traumatic brain injury (TBI) patients for head computed tomography (CT) scanning. METHODS: A prospective study based on severe TBI patients admitted from June 2011 through June 2013 in a level I trauma center. Patients received an IHT to perform a control CT scan in the first 3 days following trauma. The occurrence of SIs and AEs was assessed during the IHT for a control CT scan. The frequency of SIs was compared to the periods "before," "during," and "after" IHT. SI was defined by an intracranial pressure (ICP) >30 mmHg, a cerebral perfusion pressure (CPP) <50 mmHg, systolic blood pressure (SBP) <90 mmHg, or saturation pulse O2 (SpO2) <90 % for more than five consecutive minutes. An AE was defined as failures of hardware or ventilator asynchrony requiring therapeutic intervention during transport. In addition, we assessed the therapeutic benefit of a CT scan control. RESULTS: The final analysis included 31 patients and 31 IHTs. The median duration of IHT was 29 min [25;37]. SIs occurred in 16 patients (52 %) during transport, whereas it was observed in 4 patients (13 %) before (p = 0.002) and 4 patients (13 %) after IHT (p = 0.001). Twenty-four AEs occurred during transport of 19 patients (61 %). One patient benefited from hematoma evacuation after implementation of control CT. CONCLUSION: IHT carries significant SIs and AEs in severe TBI patients. To improve a risk/benefit ratio favorable for patients, a program focusing on IHT complications regarding therapeutic impact of control CT scan is needed.

Biofilm-associated infection: the hidden face of cerebrospinal fluid shunt malfunction.

Diagnosis of cerebrospinal fluid (CSF) shunt infection is difficult. Growing evidence links this pattern to biofilm-associated infections (BAI). Biofilm may explain the indolent development of the infection, and the poor efficiency of traditional microbiologic methods. We report the case of a patient admitted for hydrocephalus associated to CSF shunt malfunction. None of the clinical, serum, or CSF laboratory findings were in favor of an infectious process. Only scanning electron microscopy (SEM) revealed the presence of biofilm. Hence, despite a broad CSF shunt infection definition, some infections could remain undiagnosed by the traditional approach. This study is the first to provide some direct evidence for bacterial biofilm-associated CSF shunt infection.

Clinical, biological, and microbiological pattern associated with ventriculostomy-related infection: a retrospective longitudinal study.

BACKGROUND: Our aim was to describe the pattern of ventriculostomy-related infection (VRI) development using a dynamic approach. STUDY DESIGN: Retrospective longitudinal study. METHODS: We analyzed the files of 449 neurosurgical patients who underwent placement of external ventricular drain (EVD). During the study period, CSF sampling was performed on a daily base setting. VRI was defined as a positive CSF culture resulting in antibiotic treatment. For VRI patients, we arbitrary defined day 0 (D0) as the day antibiotic treatment was started. In these patients, we compared dynamic changes in clinical and biological parameters at four pre-determined time points: (D-4, D-3, D-2, D-1) with those of D0. For all CSF-positive cultures, we compared CSF biochemical markers' evolution pattern between VRI patients and the others, considered as a control cohort. RESULTS: Thirty-two suffered from VRI. Peripheral white blood cell count did not differ between D-4-D0. Median body temperature, CSF cell count, median Glasgow Coma Scale, CSF protein, and glucose concentrations were significantly different between D-4, D-3, D-2, and D0. At D0, 100 % of CSF samples yielded organisms in culture. The physician caring for the patient decided to treat VRI based upon positive CSF culture in only 28 % (9/32) of cases. In the control cohort, CSF markers' profile trends to normalize, while it worsens in the VRI patients. CONCLUSIONS: We showed that clinical symptoms and biological abnormalities of VRI evolved over time. Our data suggest that VRI decision to treat relies upon a bundle of evidence, including dynamic changes in CSF laboratory exams combined with microbiological analysis.

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.

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.

Antimicrobial Susceptibility of Community-Acquired Urine Bacterial Isolates in French Amazonia.

Bacterial resistance in community-acquired urinary tract infections (UTIs) is increasing worldwide. Our study aimed to assess the microbiological epidemiology and antimicrobial susceptibility patterns of community-acquired urine bacterial isolates in French Amazonia. Our study is retrospective. It was conducted from January 2015 to December 2019 in the microbiology laboratory of the Cayenne General Hospital (French Guiana). It includes all positive urine samples from adult (> 18 years) outpatients (N = 2,533). Isolated microorganisms were Gram-negative rods in 83.9%, mainly Enterobacterales (98.4%). The main isolated bacteria were Escherichia coli (58.7%) and Klebsiella pneumoniae (13.3%). Among the isolated E. coli, 37.2% were susceptible to amoxicillin, 77.9% to amoxicillin/clavulanic acid, 94.9% to cefotaxime, 78.9% to ofloxacin, and 98.9% to nitrofurantoin. In 106 cases (5.1%), isolated Enterobacterales were extended-spectrum ß-lactamase producers (5% of E. coli and 8.9% of K. pneumoniae). Overall, high levels of cross- and co-resistance were registered. The main isolated Gram-positive bacteria was Staphylococcus saprophyticus (28.9%). It was resistant to oxacillin in 52.5% of cases and susceptible to nitrofurantoin in 99.1% of cases. Patients with S. saprophyticus were young women in almost all cases. In conclusion, the most isolated microorganisms from outpatient urinalyses were E. coli and K. pneumoniae. They showed a high resistance rate to amoxicillin, but they were susceptible to the most remaining antibiotics. S. saprophyticus was isolated mainly in young women and was resistant to oxacillin in half of the cases. Interestingly, nitrofurantoin was active against most isolated organisms and can be considered as empirical treatment in uncomplicated UTIs.

In-Flight Medical Emergencies Management by Anesthetist-Intensivists and Emergency Physicians.

BACKGROUND: In-flight medical emergencies (IME) are challenging situations: aircraft cabins are noisy and narrow, medical supplies are scarce, and high-altitude related physiological changes may worsen chronic respiratory or cardiac conditions. The aim of this study was to assess the extent to which anesthetist-intensivists and emergency physicians are aware of IME specificities.METHODS: A questionnaire containing 21 items was distributed to French anesthetist-intensivists and emergency physicians between January and May 2020 using the mailing list of the French Society of Anesthesia and Intensive Care Medicine and the French Society of Emergency Medicine. The following topics were evaluated: high-altitude related physiological changes, medical and human resources available inside commercial aircraft, common medical incidents likely to happen on board, and previous personal experiences.RESULTS: The questionnaire was completed by 1064 physicians. The items corresponding to alterations in the arterial oxygen saturation, respiratory rate, and heart rate at cruising altitude were answered correctly by less than half of the participants (respectively, 3%, 42%, and 44% of the participants). Most responders (83%) were interested in a complementary training on IME management.DISCUSSION: The present study illustrates the poor knowledge in the medical community of the physiological changes induced by altitude and their consequences. In addition to offering specific theoretical courses to the medical community, placing sheets in commercial aircraft summarizing the optimal management of the main emergencies likely to happen on board might be an interesting tool.Diop S, Birnbaum R, Cook F, Mounier R. In-flight medical emergencies management by anesthetist-intensivists and emergency physicians. Aerosp Med Hum Perform. 2022; 93(8):633-636.

Impact of Antibiotic Consumption on the Acquisition of Extended-Spectrum ß-Lactamase Producing Enterobacterales Carriage during the COVID-19 Crisis in French Guiana.

(1) Background: During the COVID-19 outbreak, several studies showed an increased prevalence of extended-spectrum ß-lactamase producing Enterobacterales (ESBL-PE) carriage in intensive care units (ICUs). Our objective was to assess the impact of antibiotic prescriptions on the acquisition of ESBL-PE in ICUs during the COVID-19 crisis. (2) Methods: We conducted an observational study between 1 April 2020, and 31 December 2021, in the medical-surgical ICU of the Cayenne General Hospital. We defined two periods: Period 1 with routine, empirical antibiotic use, and Period 2 with no systematic empiric antibiotic prescription. (3) Results: ICU-acquired ESBL-PE carriage was 22.8% during Period 1 and 9.4% during Period 2 (p = 0.005). The main isolated ESBL-PE was Klebsiella pneumoniae (84.6% in Period 1 and 58.3% in Period 2). When using a generalized linear model with a Poisson family, exposure to cefotaxime was the only factor independently associated with ESBL-PE acquisition in ICU (p = 0.002, IRR 2.59 (95% IC 1.42-4.75)). The propensity scores matching estimated the increased risk for cefotaxime use to acquire ESBL-PE carriage at 0.096 (95% CI = 0.02-0.17), p = 0.01. (4) Conclusions: Exposure to cefotaxime in patients with severe COVID-19 is strongly associated with the emergence of ESBL-PE in the context of maximal infection control measures.

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.