Best practice in the use of peripheral venous catheters: A consensus from French experts.

BACKGROUND: Peripheral intravenous catheters (PIVCs) are the most commonly used invasive medical devices in healthcare. While they are often perceived as innocuous because they are common, this perception does not match their risk factors. In France, 16% of intravenous device-associated bacteremia are due to PIVCs. This consensus document reports the French experience in PIVC management, issues arising from their complications, and a proposed path toward improved PIVC care. METHODS: A panel of five French experts discussed this topic based on evidence and personal experience. A consensus process was applied to highlight the issues in need of increased awareness and to suggest possible improvements. PIVC topics were organized as General Statements, Indication, Preparation, Insertion, Maintenance, and Removal. An electronic survey was used to record agreement or disagreement; to expand the dataset, five additional French experts also answered the questions. RESULTS: Out of 67 statements, 62 reached a consensus (the 80% agreement threshold was exceeded). Experts are increasingly aware that PIVCs are a significant source of complications, including local and bloodstream infections. Practices need to progress to improve patient outcomes, which will require better education for all personnel involved with the insertion and maintenance of PIVCs. CONCLUSIONS: Current practice around PIVCs does not always comply with the recommendations issued. A new surveillance network targeting catheter-related healthcare-associated infections is now in place in France. Simplified, standardized, bundled solutions are needed to reduce avoidable harm from PIVCs. Healthcare practice has changed over time and new educational tools are needed to adapt to increased workload and time constraints.

Telemedicine in Nursing Home Residents Requiring a Call to an Emergency Medical Communication Center.

OBJECTIVES: To compare the proportion of nursing home residents dispatched to an emergency department (ED) after a call to the emergency medical communication center (EMCC) according to the availability or nonavailability of telemedicine. DESIGN: This prospective, observational trial was conducted in the EMCC and 74 nursing homes in a French county. SETTING AND PARTICIPANTS: All nursing home residents who needed to contact the EMCC between June 2019 and April 2020 were included in the study. We excluded calls notifying the death of a resident, for completing data from a previous call, and for nursing home staff. METHODS: The primary outcome was the proportion of residents dispatched to an ED after their first call to the EMCC. The secondary outcomes were the proportion of second calls, proportion of residents dispatched to an ED after a second call, and proportion of death within 30 days. RESULTS: We included 3103 calls in the final analysis (355 from equipped nursing homes and 2748 from unequipped nursing homes). The proportion of patients dispatched to an ED after the first call was lower among telemedicine-equipped than among telemedicine-unequipped nursing homes (41% vs 50%; odds ratio, 0.71; 95% CI, 0.56-0.90). The proportion of a second call for the same purpose within 72 hours, proportion of dispatching to an ED at the second call, and proportion of deaths within 30 days were similar between the groups. CONCLUSION AND IMPLICATIONS: The use of telemedicine by nursing home residents requiring a call to the EMCC is associated with a reduction in the number of dispatches to an ED without any increase in the number of 72-hour callbacks or 30-day mortality rates.

High-flow nasal cannula oxygen versus noninvasive ventilation for the management of acute cardiogenic pulmonary edema: a randomized controlled pilot study.

BACKGROUND: Whether high-flow nasal oxygen can improve clinical signs of acute respiratory failure in acute heart failure (AHF) is uncertain. OBJECTIVE: To compare the effect of high-flow oxygen with noninvasive ventilation (NIV) on respiratory rate in patients admitted to an emergency department (ED) for AHF-related acute respiratory failure. DESIGN, SETTINGS AND PARTICIPANTS: Multicenter, randomized pilot study in three French EDs. Adult patients with acute respiratory failure due to suspected AHF were included. Key exclusion criteria were urgent need for intubation, Glasgow Coma Scale <13 points or hemodynamic instability. INTERVENTION: Patients were randomly assigned to receive high-flow oxygen (minimum 50 l/min) or noninvasive bilevel positive pressure ventilation. OUTCOMES MEASURE: The primary outcome was change in respiratory rate within the first hour of treatment and was analyzed with a linear mixed model. Secondary outcomes included changes in pulse oximetry, heart rate, blood pressure, blood gas samples, comfort, treatment failure and mortality. MAIN RESULTS: Among the 145 eligible patients in the three participating centers, 60 patients were included in the analysis [median age 86 (interquartile range (IQR), 90; 92) years]. There was a median respiratory rate of 30.5 (IQR, 28; 33) and 29.5 (IQR, 27; 35) breaths/min in the high-flow oxygen and NIV groups respectively, with a median change of -10 (IQR, -12; -8) with high-flow nasal oxygen and -7 (IQR, -11; -5) breaths/min with NIV [estimated difference -2.6 breaths/min (95% confidence interval (CI), -0.5-5.7), P = 0.052] at 60 min. There was a median SpO2 of 95 (IQR, 92; 97) and 96 (IQR, 93; 97) in the high-flow oxygen and NIV groups respectively, with a median change at 60 min of 2 (IQR, 0; 5) with high-flow nasal oxygen and 2 (IQR, -1; 5) % with NIV [estimated difference 0.8% (95% CI, -1.1-2.8), P = 0.60]. PaO2, PaCO2 and pH did not differ at 1 h between groups, nor did treatment failure, intubation and mortality rates. CONCLUSION: In this pilot study, we did not observe a statistically significant difference in changes in respiratory rate among patients with acute respiratory failure due to AHF and managed with high-flow oxygen or NIV. However, the point estimate and its large confidence interval may suggest a benefit of high-flow oxygen. TRIAL REGISTRATION: NCT04971213 (https://clinicaltrials.gov).

Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial.

BACKGROUND: Patients with acute brain injury are at high risk of ventilator-associated pneumonia (VAP). The benefit of short-term antibiotic prophylaxis remains debated. We aimed to establish the effect of an early, single dose of the antibiotic ceftriaxone on the incidence of early VAP in patients with severe brain injury who required mechanical ventilation. METHODS: PROPHY-VAP was a multicentre, randomised, double-blind, placebo-controlled, assessor-masked, superiority trial conducted in nine intensive care units in eight French university hospitals. We randomly assigned comatose (Glasgow Coma Scale score [GCS] ≤12) adult patients (age ≥18 years) who required mechanical ventilation for at least 48 h after acute brain injury to receive intravenous ceftriaxone 2 g or placebo once within the 12 h following tracheal intubation. Participants did not receive selective oropharyngeal and digestive tract decontamination. The primary outcome was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, confirmed by masked assessors. The analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew or did not give consent to continue and those who did not receive the allocated treatment because they met a criterion for non-eligibility. The trial is registered with ClinicalTrials.gov, NCT02265406. FINDINGS: From Oct 14, 2015, to May 27, 2020, 345 patients were randomly assigned (1:1) to receive ceftriaxone (n=171) or placebo (n=174); 330 received the allocated intervention and 319 were included in the analysis (162 in the ceftriaxone group and 157 in the placebo group). 166 (52%) participants in the analysis were men and 153 (48%) were women. 15 patients did not receive the allocated intervention after randomisation and 11 withdrew their consent. Adjudication confirmed 93 cases of VAP, including 74 early infections. The incidence of early VAP was lower in the ceftriaxone group than in the placebo group (23 [14%] vs 51 [32%]; hazard ratio 0·60 [95% CI 0·38-0·95], p=0·030), with no microbiological impact and no adverse effects attributable to ceftriaxone. INTERPRETATION: In patients with acute brain injury, a single ceftriaxone dose decreased the risk of early VAP. On the basis of our findings, we recommend that an early, single dose of ceftriaxone be included in all bundles for the prevention of VAP in patients with brain injury who require mechanical ventilation. FUNDING: French Ministry of Social Affairs and Health.

Risk of infections in intravascular catheters in situ for more than 10 days: a post hoc analysis of randomized controlled trials.

OBJECTIVES: We aimed to describe the infectious risk during the dwell time for different catheter types. Furthermore, we wanted to identify risk factors for infections from catheters in place for >10 days. METHODS: We performed a post hoc analysis using prospectively collected data from four randomized controlled trials. First, we evaluated the infectious risk after 10 days of analysing the significance of the interaction between dwell time and catheter type in a Cox model. Second, we investigated risk factors for infection in catheters in place for >10 days using multivariable marginal Cox models. RESULTS: We included 15 036 intravascular catheters from 24 intensive care units. Infections occurred in 46 (0.7%) of 6298 arterial catheters (ACs), 62 (1.0%) of 6036 central venous catheters (CVCs) and 47 (1.7%) of 2702 short-term dialysis catheters (DCs). The interaction between dwell time beyond 10 days and catheter type was significant for CVCs (p 0.008) and DCs (p < 0.001), thus indicating an increased risk of infection after 10 days. The interaction was not significant for ACs (p 0.98). Therefore, we selected 1405 CVCs and 454 DCs in place for >10 days for further analyses. In the multivariable marginal Cox model, we observed an increased hazard ratio (HR) for infection for femoral CVC (HR, 6.33; 95% CI, 1.99-20.09), jugular CVC (HR, 2.82; 95% CI, 1.13-7.07), femoral DC (HR, 4.53; 95% CI, 1.54-13.33) and jugular DC (HR, 4.50; 95% CI, 1.42-14.21) compared with subclavian insertions. DISCUSSION: We showed that the risk of catheter infection for CVCs and DCs increased 10 days after insertion, thus suggesting routine replacement for nonsubclavian catheters in situ for >10 days.

Impact of Radial Arterial Location on Catheter Lifetime in ICU Surgical Intensive Care.

The use of arterial catheters is frequent in intensive care for hemodynamic monitoring of patients and for blood sampling, but they are often removed because of dysfunction. The primary objective is to compare the prevalence of radial arterial catheter dysfunction according to location in relation to the radiocarpal joint in intensive care patients. DESIGN: Prospective randomized, controlled, single-center study. SETTING: The surgical ICU of the university hospital of Poitiers in France. PATIENTS: From January 2016 to April 2017, all patients over 18 years old admitted to the surgical ICU and requiring an arterial catheter were included. INTERVENTIONS: Randomization into two groups: catheter placed near the wrist (within 4 cm of the radiocarpal joint) and catheter placed away the wrist. The primary endpoint was the prevalence of dysfunction. We also compared the prevalence of infection and colonization. MEASUREMENTS AND MAIN RESULTS: One hundred seven catheters were analyzed (14 failed placements with no difference between the two groups, and 16 catheters excluded for missing data), with 58 catheters in near the wrist group and 49 in away the wrist group. We did not find any significant difference in the number of catheter dysfunctions between the two groups (p = 0.56). The prevalence density of catheter dysfunction was 30.5 of 1,000 catheter days for near the wrist group versus 26.7 of 1,000 catheter days for away the wrist group. However, we observed a significant difference in terms of catheter-related infection in favor of away the wrist group (p = 0.04). In addition, distal positioning of the catheter was judged easier by the physicians. CONCLUSIONS: The distal or proximal position of the arterial catheter in the radial position has no influence on the occurrence of dysfunction. However, there may be an association with the prevalence of infections.

Development and validation of a multivariable model predicting the required catheter dwell time among mechanically ventilated critically ill patients in three randomized trials.

BACKGROUND: The anatomic site for central venous catheter insertion influences the risk of central venous catheter-related intravascular complications. We developed and validated a predictive score of required catheter dwell time to identify critically ill patients at higher risk of intravascular complications. METHODS: We retrospectively conducted a cohort study from three multicenter randomized controlled trials enrolling consecutive patients requiring central venous catheterization. The primary outcome was the required catheter dwell time, defined as the period between the first catheter insertion and removal of the last catheter for absence of utility. Predictors were identified in the training cohort (3SITES trial; 2336 patients) through multivariable analyses based on the subdistribution hazard function accounting for death as a competing event. Internal validation was performed in the training cohort by 500 bootstraps to derive the CVC-IN score from robust risk factors. External validation of the CVC-IN score were performed in the testing cohort (CLEAN, and DRESSING2; 2371 patients). RESULTS: The analysis was restricted to patients requiring mechanical ventilation to comply with model assumptions. Immunosuppression (2 points), high creatinine > 100 micromol/L (2 points), use of vasopressor (1 point), obesity (1 point) and older age (40-59, 1 point; ≥ 60, 2 points) were independently associated with the required catheter dwell time. At day 28, area under the ROC curve for the CVC-IN score was 0.69, 95% confidence interval (CI) [0.66-0.72] in the training cohort and 0.64, 95% CI [0.61-0.66] in the testing cohort. Patients with a CVC-IN score ≥ 4 in the overall cohort had a median required catheter dwell time of 24 days (versus 11 days for CVC-IN score < 4 points). The positive predictive value of a CVC-IN score ≥ 4 was 76.9% for > 7 days required catheter dwell time in the testing cohort. CONCLUSION: The CVC-IN score, which can be used for the first catheter, had a modest ability to discriminate required catheter dwell time. Nevertheless, preference of the subclavian site may contribute to limit the risk of intravascular complications, in particular among ventilated patients with high CVC-IN score. Trials Registration NCT01479153, NCT01629550, NCT01189682.

Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance.

OBJECTIVES: Ceftaroline could be suitable to treat early-onset ventilator-associated pneumonia (VAP) because of its antibacterial spectrum. However, augmented renal clearance (ARC) is frequent in ICU patients and may affect ceftaroline pharmacokinetics and efficacy. The objective of the study was to explore the impact of ARC on ceftaroline pharmacokinetics and evaluate whether the currently recommended dosing regimen (600 mg every 12 h) is appropriate to treat VAP in ICU patients. METHODS: A population pharmacokinetic model was developed using pharmacokinetic data from 18 patients with measured creatinine clearance (CLCR) ranging between 83 and 309 mL/min. Monte Carlo simulations were conducted to determine the PTA and the cumulative fraction of response (CFR) against Streptococcus pneumoniae and MRSA for five dosing regimens. Study registered at ClinicalTrials.gov (NCT03025841). RESULTS: Ceftaroline clearance increased non-linearly with CLCR, with lower concentrations and lower probability of reaching pharmacokinetic/pharmacodynamic targets when CLCR increases. For the currently recommended dosing regimen, the probability of having unbound ceftaroline concentrations above the MIC over the entire dose range is greater than 90% for MICs below 0.125 mg/L. Considering the distribution of MICs, this regimen would not be effective against MRSA infections (CFR between 21% and 67% depending on CLCR), but would be effective against S. pneumoniae infections (CFR >86%). CONCLUSIONS: The recommended dosing regimen of ceftaroline seems sufficient for covering S. pneumoniae in ICU patients with ARC, but not for MRSA. Among the dosing regimens tested it appears that a constant infusion (50 mg/h) after a loading dose of 600 mg could be more appropriate for MRSA infections.

Impact of Skin Disinfection on Cutaneous Microbiota, before and after Peripheral Venous Catheter Insertion.

Introduction. Patients with invasive medical devices are at high risk for infection. Skin colonization is the initial stage of these infections, leading to the recommendation of practices requiring disinfection using antiseptics. Microbial communities playing a major role in skin health could be impacted by antiseptic procedures. Aim. To characterize and compare the bacterial communities of skin samples from patients before an antisepsis procedure, and after removal of the medical device itself, according to the nature of the antiseptic molecule (povidone iodine or chlorhexidine). Methods. The study focused on alterations in bacterial communities depending on the nature of the antiseptic procedure and type of intravascular device. After amplification of 16S rDNA, libraries (n = 498 samples) were sequenced using MiSeq platform. Results. Using an in-house pipeline (QIIME2 modules), while no alteration in skin microbiota diversity was associated with antiseptic procedure or PVC type, according to culture results (p < 0.05), alterations were at times associated with restricted diversity and higher dissimilarity (p < 0.05). Antiseptic procedures and PVC types were associated with the modification of specific bacterial representations with modulation of the Bacillota/Bacteroidota (Firmicutes/Bacteroidetes) ratio (modulation of C. acnes, Prevotella, Lagierella, and Actinomyces spp.) (p < 0.05). At baseline, the microbiota shows certain bacteria that are significantly associated with future PVC colonization and/or bacteremia (p < 0.05). All of these modulations were associated with altered expression of metabolic pathways (p < 0.05). Discussion. Finally, this work highlights the need to optimize the management of patients requiring intravascular devices, possibly by modulating the skin microbiota.

Development and validation of a multivariable prediction model of central venous catheter-tip colonization in a cohort of five randomized trials.

BACKGROUND: The majority of central venous catheters (CVC) removed in the ICU are not colonized, including when a catheter-related infection (CRI) is suspected. We developed and validated a predictive score to reduce unnecessary CVC removal. METHODS: We conducted a retrospective cohort study from five multicenter randomized controlled trials with systematic catheter-tip culture of consecutive CVCs. Colonization was defined as growth of ≥103 colony-forming units per mL. Risk factors for colonization were identified in the training cohort (CATHEDIA and 3SITES trials; 3899 CVCs of which 575 (15%) were colonized) through multivariable analyses. After internal validation in 500 bootstrapped samples, the CVC-OUT score was computed by attaching points to the robust (> 50% of the bootstraps) risk factors. External validation was performed in the testing cohort (CLEAN, DRESSING2 and ELVIS trials; 6848 CVCs, of which 588 (9%) were colonized). RESULTS: In the training cohort, obesity (1 point), diabetes (1 point), type of CVC (dialysis catheter, 1 point), anatomical insertion site (jugular, 4 points; femoral 5 points), rank of the catheter (second or subsequent, 1 point) and catheterization duration (≥ 5 days, 2 points) were significantly and independently associated with colonization . Area under the ROC curve (AUC) for the CVC-OUT score was 0.69, 95% confidence interval (CI) [0.67-0.72]. In the testing cohort, AUC for the CVC-OUT score was 0.60, 95% CI [0.58-0.62]. Among 1,469 CVCs removed for suspected CRI in the overall population, 1200 (82%) were not colonized. The negative predictive value (NPV) of a CVC-OUT score < 6 points was 94%, 95% CI [93%-95%]. CONCLUSION: The CVC-OUT score had a moderate ability to discriminate catheter-tip colonization, but the high NPV may contribute to reduce unnecessary CVCs removal. Preference of the subclavian site is the strongest and only modifiable risk factor that reduces the likelihood of catheter-tip colonization and consequently the risk of CRI. CLINICAL TRIALS REGISTRATION: NCT00277888, NCT01479153, NCT01629550, NCT01189682, NCT00875069.

Cost-effectiveness analysis of bundled innovative devices versus standard approach in the prevention of unscheduled peripheral venous catheters removal due to complications in France.

The objective of the study was to perform a cost-effectiveness analysis of bundled devices (BDs) versus standard devices (SDs) for the prevention of unscheduled peripheral venous catheter (PVC) removal due to complication from a French investigator-initiated, open-label, single center, randomized-controlled, two-by-two factorial trial (CLEAN-3 study). A 14-day time non homogeneous semi-markovian model was performed to be fitted to longitudinal individual patient data from CLEAN-3 database. This model includes five health states and eight transitional events; a base case scenario, two scenario analyses and bootstrap sensitivity analyses were performed. The cost-effectiveness criterion was the cost per patient with unscheduled PVC removal avoided. 989 adult (age≥18 years) patients were analyzed to compare the BDs group (494 patients), and the SDs group (495 patients). The assessed intervention was a combination of closed integrated catheters, positive displacement needleless-connectors, disinfecting caps, and single-use prefilled flush syringes compared with the use of open catheters and three-way stopcocks for treatment administration. For the base case scenario, an unscheduled 1st PVC removal before discharge was significantly more frequent in the SDs group (235 patients (47.5%) in the SDs group and 172 patients (34.8%) in the BDs group, p = 0.00006). After adjustment for 1st catheter time, the number of patients with unscheduled PVC removal per day was of 16 (95%CI: 15; 18) patients (out of 100) in the BDs group and of 26 (95%CI: 24; 28) patients (out of 100) in the SDs group. The mean cost per patient (adjusted on catheter-time) was of €144 (95%CI: €135-€154) for patients in the SDs group versus €102 (95%CI: €95-€109) for patients in the BDs group; the mean saving per patient was of €42 (95%CI: €32-€54). As a consequence, the assessed BDs strategy was less costly and more effective than the SDs strategy. Trail registration: CLEAN-3 study is registered with ClinicalTrials.gov, NCT03757143.

Guidelines for the choice of intravenous fluids for vascular filling in critically ill patients, 2021.

PURPOSE: To provide recommendations for the appropriate choice of fluid therapy for resuscitation of critically ill patients. DESIGN: A consensus committee of 24 experts from the French Society of Anaesthesia and Intensive Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Society of Emergency Medicine (Société française de médecine d'urgence, SFMU) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guideline elaboration process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Some recommendations were left ungraded. METHODS: Four fields were defined: patients with sepsis or septic shock, patients with haemorrhagic shock, patients with acute brain failure, and patients during the peripartum period. For each field, the panel focused on two questions: (1) Does the use of colloids, as compared to crystalloids, reduce morbidity and mortality, and (2) Does the use of some specific crystalloids effectively reduce morbidity and mortality. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. The analysis of the literature and the recommendations were then conducted according to the GRADE methodology. RESULTS: The SFAR/SFMU guideline panel provided nine statements on the appropriate choice of fluid therapy for resuscitation of critically ill patients. After two rounds of rating and various amendments, strong agreement was reached for 100% of the recommendations. Out of these recommendations, two have a high level of evidence (Grade 1 +/-), six have a moderate level of evidence (Grade 2 +/-), and one is based on expert opinion. Finally, no recommendation was formulated for two questions. CONCLUSIONS: Substantial agreement among experts has been obtained to provide a sizable number of recommendations aimed at optimising the choice of fluid therapy for resuscitation of critically ill patients.

Nebulized Antibiotics for Healthcare- and Ventilator-Associated Pneumonia.

Global emergence of multidrug-resistant and extensive drug-resistant gram-negative bacteria has increased the risk of treatment failure, especially for healthcare- or ventilator-associated pneumonia (HAP/VAP). Nebulization of antibiotics, by providing high intrapulmonary antibiotic concentrations, represents a promising approach to optimize the treatment of HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria, while limiting systemic antibiotic exposure. Aminoglycosides and colistin methanesulfonate are the most common nebulized antibiotics. Although optimal nebulized drug dosing regimen is not clearly established, high antibiotic doses should be administered using vibrating-mesh nebulizer with optimized ventilator settings to ensure safe and effective intrapulmonary concentrations. When used preventively, nebulized antibiotics reduced the incidence of VAP without any effect on mortality. This approach is not yet recommended and large randomized controlled trials should be conducted to confirm its benefit and explore the impact on antibiotic selection pressure. Compared with high-dose intravenous administration, high-dose nebulized colistin methanesulfonate seems to be more effective and safer in the treatment of ventilator-associated tracheobronchitis and VAP caused by multidrug resistant and extensive-drug resistant gram-negative bacteria. Adjunctive nebulized aminoglycosides could increase the clinical cure rate and bacteriological eradication in patients suffering from HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria. As nebulized aminoglycosides broadly diffuse in the systemic circulation of patients with extensive bronchopneumonia, monitoring of plasma trough concentrations is recommended during the period of nebulization. Large randomized controlled trials comparing high dose of nebulized colistin methanesulfonate to high dose of intravenous colistin methanesulfonate or to intravenous new ß-lactams in HAP/VAP due to multidrug-resistant and extensive drug-resistant gram-negative bacteria are urgently needed.

Practices and intravascular catheter infection during on- and off-hours in critically ill patients.

BACKGROUND: The potential relationship between intravascular catheter infections with their insertion during weekend or night-time (i.e., off-hours or not regular business hours) remains an open issue. Our primary aim was to describe differences between patients and catheters inserted during on- versus off-hours. Our secondary aim was to investigate whether insertions during off-hours influenced the intravascular catheter infectious risks. METHODS: We performed a post hoc analysis using the databases from four large randomized-controlled trials. Adult patients were recruited in French ICUs as soon as they required central venous catheters or peripheral arterial (AC) catheter insertion. Off-hours started at 6 P.M. until 8:30 A.M. during the week; at weekend, we defined off-hours from 1 P.M. on Saturday to 8.30 A.M. on Monday. We performed multivariable marginal Cox models to estimate the effect of off-hours (versus on-hours) on major catheter-related infections (MCRI) and catheter-related bloodstream infections (CRBSIs). RESULTS: We included 7241 patients in 25 different ICUs, and 15,208 catheters, including 7226 and 7982 catheters inserted during off- and on-hours, respectively. Catheters inserted during off-hours were removed after 4 days (IQR 2, 9) in median, whereas catheters inserted during on-hours remained in place for 6 days (IQR 3,10; p < 0.01) in median. Femoral insertion was more frequent during off-hours. Among central venous catheters and after adjusting for well-known risk factors for intravascular catheter infection, we found a similar risk between off- and on-hours for MCRI (HR 0.91, 95% CI 0.61-1.37, p = 0.65) and CRBSI (HR 1.05, 95% CI 0.65-1.68, p = 0.85). Among central venous catheters with a dwell-time > 4 or > 6 days, we found a similar risk for MCRI and CRBSI between off- and on-hours. Similar results were observed for ACs. CONCLUSIONS: Off-hours did not increase the risk of intravascular catheter infections compared to on-hours. Off-hours insertion is not a sufficient reason for early catheter removal, even if femoral route has been selected.

Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives.

Clinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20-25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.