Abstract Background Inspiratory muscle training (IMT) is well-established as a safe option for combating inspiratory muscles weakness in the intensive care setting. It could improve inspiratory muscle strength and decrease weaning duration but a lack of knowledge on the optimal training regimen raise to inconsistent results. We made the hypothesis that an innovative mixed intensity program for both endurance and strength improvement could be more effective. We conducted a multicentre randomised controlled parallel trial comparing the impacts of three IMT protocols (low, high, and mixed intensity) on inspiratory muscle strength and endurance among difficult-to-wean patients. Methods Ninety-two patients were randomly assigned to three groups with different training programs, where each performed an IMT program twice daily, 7 days per week, from inclusion until successful extubation or 30 days. The primary outcome was maximal inspiratory pressure (MIP) increase. Secondary outcomes included peak pressure (Ppk) increase as an endurance marker, mechanical ventilation (MV) duration, ICU length of stay, weaning success defined by a 2-day ventilator-free after extubation, reintubation rate and safety. Results MIP increases were 10.8 ± 11.9 cmH2O, 4.5 ± 14.8 cmH2O, and 6.7 ± 14.5 cmH2O for the mixed intensity (MI), low intensity (LI), and high intensity (HI) groups, respectively. There was a non-statistically difference between the MI and LI groups (mean adjusted difference: 6.59, 97.5% CI [− 14.36; 1.18], p = 0.056); there was no difference between the MI and HI groups (mean adjusted difference: − 3.52, 97.5% CI [− 11.57; 4.53], p = 0.321). No significant differences in Ppk increase were observed among the three groups. Weaning success rate observed in MI, HI and LI group were 83.7% [95% CI 69.3; 93.2], 82.6% [95% CI 61.2; 95.0] and 73.9% [95% CI 51.6; 89.8], respectively. MV duration, ICU length of stay and reintubation rate had similar values. Over 629 IMT sessions, six adverse events including four spontaneously reversible bradycardia in LI group were possibly related to the study. Conclusions Among difficult-to-wean patients receiving invasive MV, no statistically difference was observed in strength and endurance progression across three different IMT programs. IMT appears to be feasible in usual cares, but some serious adverse events such as bradycardia could motivate further research on the specific impact on cardiac system. Trial registration Clinicaltrials.gov identifier: NCT02855619. Registered 28 September 2014

OBJECTIVE:We hypothesized that the use of mechanical insufflation-exsufflation can reduce the incidence of acute respiratory failure within the 48-hour post-extubation period in intensive care unit-acquired weakness patients.METHODS:This was a prospective randomized controlled open-label trial. Patients diagnosed with intensive care unit-acquired weakness were consecutively enrolled based on a Medical Research Council score ≤ 48/60. The patients randomly received two daily sessions; in the control group, conventional chest physiotherapy was performed, while in the intervention group, chest physiotherapy was associated with mechanical insufflation-exsufflation. The incidence of acute respiratory failure within 48 hours of extubation was evaluated. Similarly, the reintubation rate, intensive care unit length of stay, mortality at 28 days, and survival probability at 90 days were assessed. The study was stopped after futility results in the interim analysis.RESULTS:We included 122 consecutive patients (n = 61 per group). There was no significant difference in the incidence of acute respiratory failure between treatments (11.5% control group versus 16.4%, intervention group; p = 0.60), the need for reintubation (3.6% versus 10.7%; p = 0.27), mean length of stay (3 versus 4 days; p = 0.33), mortality at Day 28 (9.8% versus 15.0%; p = 0.42), or survival probability at Day 90 (21.3% versus 28.3%; p = 0.41).CONCLUSION:Mechanical insufflation-exsufflation combined with chest physiotherapy seems to have no impact in preventing postextubation acute respiratory failure in intensive care unit-acquired weakness patients. Similarly, mortality and survival probability were similar in both groups. Nevertheless, given the early termination of the trial, further clinical investigation is strongly recommended.CLINICAL TRIALS REGISTER:NCT01931228.

OBJECTIVE: We hypothesized that the use of mechanical insufflation-exsufflation can reduce the incidence of acute respiratory failure within the 48-hour post-extubation period in intensive care unit-acquired weakness patients. METHODS: This was a prospective randomized controlled open-label trial. Patients diagnosed with intensive care unit-acquired weakness were consecutively enrolled based on a Medical Research Council score ≤ 48/60. The patients randomly received two daily sessions; in the control group, conventional chest physiotherapy was performed, while in the intervention group, chest physiotherapy was associated with mechanical insufflation-exsufflation. The incidence of acute respiratory failure within 48 hours of extubation was evaluated. Similarly, the reintubation rate, intensive care unit length of stay, mortality at 28 days, and survival probability at 90 days were assessed. The study was stopped after futility results in the interim analysis. RESULTS: We included 122 consecutive patients (n = 61 per group). There was no significant difference in the incidence of acute respiratory failure between treatments (11.5% control group versus 16.4%, intervention group; p = 0.60), the need for reintubation (3.6% versus 10.7%; p = 0.27), mean length of stay (3 versus 4 days; p = 0.33), mortality at Day 28 (9.8% versus 15.0%; p = 0.42), or survival probability at Day 90 (21.3% versus 28.3%; p = 0.41). CONCLUSION: Mechanical insufflation-exsufflation combined with chest physiotherapy seems to have no impact in preventing postextubation acute respiratory failure in intensive care unit-acquired weakness patients. Similarly, mortality and survival probability were similar in both groups. Nevertheless, given the early termination of the trial, further clinical investigation is strongly recommended. CLINICAL TRIALS REGISTER: NCT 01931228

Background: COVID19-associated acute kidney injury frequency, severity and characterisation in critically ill patients has not been reported. Methods: Single-center cohort performed from March 3, 2020, to April 14, 2020 in 4 intensive care units in Bordeaux University Hospital, France. All patients with COVID19 and pulmonary severity criteria were included. AKI was defined using KDIGO criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterisation (transient vs. persistent acute kidney injury; proteinuria, hematuria and glycosuria), and short-term outcomes was evaluated. Results: 71 patients were included, with basal serum creatinine of 69 +/- 21 micromol/L. At admission, AKI was present in 8/71 (11%) patients. Median follow-up was 17 [12-23] days. AKI developed in a total of 57/71 (80%) patients with 35% Stage 1, 35% Stage 2, and 30% Stage 3 acute kidney injury; 10/57 (18%) required renal replacement therapy. Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median urine protein/creatinine of 82 [54-140] (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 +/- 20 indicating predominant tubulo-interstitial injury. Only 2 (4%) patients had glycosuria. At Day 7 onset of after AKI, six (11%) patients remained dependent on renal replacement therapy, nine (16%) had SCr > 200 micromol/L, and four (7%) died. Day 7 and day 14 renal recovery occurred in 28% and 52 % respectively. Conclusion: COVID19 associated AKI is frequent, persistent severe and characterised by an almost exclusive tubulo-interstitial injury without glycosuria

Background. Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. Methods. Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. Results. Seventy-one patients were included, with basal serum creatinine (SCr) of 69621 mmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12-23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54-140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23620, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 mmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively. Conclusion. Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria.

INTRODUCTION:Few studies described strategies to improve the use of diagnostic tests in intensive care units (ICU). No study assessed whether their impact was sustained or not. In this study, we assessed whether a multi-faceted intervention for more appropriate use of laboratory testing can decrease the number of tests, is sustainable, is not associated with additional morbidity and represents a potential cost saving.MATERIAL AND METHODS:An open-label prospective cohort study in two separated units of the same medical intensive care unit (ICU) including respectively 3315 and 2392 consecutive patients. After the observation period (2010), a reduction in ICU A of unnecessary diagnostics tests as part of a program including senior supervisory of juniors' orders, encouragements for orders containment at each everyday round discussions (period 2; 2011). Period 3 (2012) consisted in the prolongation of the protocol as a routine care without supervision; Period 4 (2013) was a new period of observation without intervention. No modification was implemented in ICU B in periods 2-4.RESULTS:After the intervention, a decrease in the overall number of tests per ICU-patient-days (37.3±5.5 (baseline) to 15.2±3.2 (- 59%); p<0.0001) was observed. The total cost of the tests decreased from 239±41 to 104±28 euros per ICU-patient days; p<0.0001. The effect on laboratory test orders was sustainable in period 3 (-49%) and 4 (-30%). No significant secondary effect of the intervention was observed in period 2. In ICU B, there was no significant change in the overall laboratory test orders in between the periods.CONCLUSIONS:Laboratory test containment is effective, likely safe and sustainable provided that an educational program is repeatedly promoted, that it makes sense for the whole team, that senior and junior physicians are both committed in the program, and that encouragements for laboratory orders containment at each everyday round discussions.

BACKGROUND:In a previous study of subjects suspected of having ventilator-associated pneumonia, a rapid susceptibility testing approach by using ETEST (BioMérieux) strips directly applied to bronchoalveolar lavage samples provided valuable information at hour 24. The primary objective of this study was to assess a new direct specimen testing by using an even more-rapid E-test approach (at hour 10), which could promote an early de-escalation of the antimicrobial therapy.METHODS:Twenty-eight subjects with ventilator-associated pneumonia admitted to a medical ICU were prospectively included. In parallel with standard routine methods, E-test strips were directly applied onto agar plates seeded with bronchoalveolar lavage samples and were analyzed after 10 h of incubation. E-test results were used to identify potential drug choices by simulating clinical decision making if the microscopy results had been available at the point of care. These choices were analyzed for concordance with the narrowest adequate antimicrobial therapy according to the Minimum Inhibitory Concentrations (MICs) provided by the reference method (ie, the laboratory routine diagnostic).RESULTS:At hour 10, direct specimen testing was readable in 18 of 28 bronchoalveolar lavage samples (64%). Total agreement between the 10-h direct specimen testing approach and the laboratory routine diagnostic approach was 90%, with a sensitivity of 83% and a specificity of 95%, with 8% major errors and 3% very major errors. The concordance between the 2 tests was very good (kappa = 0.79). If the 10-h E-test results were taken into account, then an early de-escalation strategy would have been possible in 10 of 18 cases (55%) at hour 10.CONCLUSIONS:This rapid susceptibility testing approach provided early (10 h) and valuable information that could lead to an early adjustment of empirical antimicrobial treatment in a ventilator-associated pneumonia setting. (ClinicalTrials.gov registration NCT01266863.).

BACKGROUND: In this study, we primarily sought to assess the ability of flow cytometry to predict early clinical deterioration and overall survival in patients with sepsis admitted in the ED and ICU. METHODS: Patients admitted for community-acquired acute sepsis from 11 hospital centers were eligible. Early (day 7) and late (day 28) deaths were notified. Levels of CD64(pos)granulocytes, CD16(pos) monocytes, CD16(di)(m) immature granulocytes (IGs), and T and B lymphocytes were assessed by flow cytometry using an identical, cross-validated, robust, and simple consensus standardized protocol in each center. RESULTS: Among 1,062 patients screened, 781 patients with confirmed sepsis were studied (age, 67 +/- 48 years; Simplified Acute Physiology Score II, 36 +/- 17; Sequential Organ Failure Assessment, 5 +/- 4). Patients were divided into three groups (sepsis, severe sepsis, and septic shock) on day 0 and on day 2. On day 0, patients with sepsis exhibited increased levels of CD64(pos) granulocytes, CD16(p)(os) monocytes, and IGs with T-cell lymphopenia. Clinical severity was associated with higher percentages of IGs and deeper T-cell lymphopenia. IG percentages tended to be higher in patients whose clinical status worsened on day 2 (35.1 +/- 35.6 vs 43.5 +/- 35.2, P = .07). Increased IG percentages were also related to occurrence of new organ failures on day 2. Increased IG percentages, especially when associated with T-cell lymphopenia, were independently associated with early (P < .01) and late (P < .01) death. CONCLUSIONS: Increased circulating IGs at the acute phase of sepsis are linked to clinical worsening, especially when associated with T-cell lymphopenia. Early flow cytometry could help clinicians to target patients at high risk of clinical deterioration.

Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders.

BACKGROUND: To assess the agreement between transpulmonary thermodilution (TPT) and critical care echocardiography (CCE) in ventilated patients with septic shock. METHODS: Ventilated patients in sinus rhythm requiring advanced hemodynamic assessment for septic shock were included in this prospective multicenter descriptive study. Patients were assessed successively using TPT and CCE in random order. Data were interpreted independently at bedside by two investigators who proposed therapeutic changes on the basis of predefined algorithms. TPT and CCE hemodynamic assessments were reviewed offline by two independent experts who identified potential sources of discrepant results by consensus. Lactate clearance and outcome were studied. RESULTS: A total of 137 patients were studied (71 men; age, 61 +/- 15 years; Simplified Acute Physiologic Score, 58 +/- 18; Sequential Organ Failure Assessment, 10 +/- 3). TPT and CCE interpretations at bedside were concordant in 87/132 patients (66%) without acute cor pulmonale (ACP), resulting in a moderate agreement (kappa, 0.48; 95% CI, 0.37-0.60). Experts' adjudications were concordant in 100/129 patients without ACP (77.5%), resulting in a good intertechnique agreement (kappa, 0.66; 95% CI, 0.55-0.77). In addition to ACP (n = 8), CCE depicted a potential source of TPT inaccuracy in 8/29 patients (28%). Lactate clearance at H6 was similar irrespective of the concordance of online interpretations of TPT and CCE (55/84 [65%] vs 32/45 [71%], P = .55). ICU and day 28 mortality rates were similar between patients with concordant and discordant interpretations (29/87 [36%] vs 13/45 [29%], P = .60; and 31/87 [36%] vs 16/45 [36%], P = .99, respectively). CONCLUSIONS: Agreement between TPT and CCE was moderate when interpreted at bedside and good when adjudicated offline by experts, but without impact on lactate clearance and mortality.

PURPOSE:To assess the ability of diaphragmatic ultrasound (US) to predict weaning failure in mechanically ventilated patients undergoing a first spontaneous breathing trial (SBT). METHODS:During a 4-month period, 67 consecutive patients eligible for a first SBT underwent US measurements of maximal diaphragmatic excursion (MDE) by a right anterior subcostal approach. Weaning failure was defined as either the failure of SBT or the need for resumption of ventilatory support for acute respiratory failure or death within 48h following successful extubation. The accuracy of diaphragmatic ultrasound and the Medical Research Council (MRC) score when predicting weaning failure was assessed via a receiver operating curve analysis. RESULTS:The feasibility rate for the ultrasound measurements was 63%. Mean values of MDE were significantly higher in patients who succeeded at their first weaning attempt (4.1±2.1 versus 3±1.8cm, P=0.04). Using a threshold of MDE≤2.7cm, the sensitivity and specificity of diaphragmatic ultrasound in predicting weaning failure were 59% [39-77%] and 71% [57-82%] with an AUC at 0.65 [0.51-0.78]. There was no significant difference between MDE values and MRC scores for predicting weaning failure (P=0.73). CONCLUSION:A decrease in MDE values may be associated with an unfavourable weaning outcome. Diaphragmatic excursion measured by ultrasound is however unable by itself to predict weaning failure at the bedside of patients undergoing a first spontaneous breathing trial and does not provide any additional value compared to the MRC score.

INTRODUCTION:High-flow nasal cannula (HFNC) can deliver heated and humidified gas (up to 100% oxygen) at a maximum flow of 60 L/min via nasal prongs or cannula. The aim of this study was to assess the short-term physiologic effects of HFNC. Inspiratory muscle effort, gas exchange, dyspnea score, and comfort were evaluated. METHODS:Twelve subjects admitted to the ICU for acute hypoxemic respiratory failure were prospectively included. Four study sessions were performed. The first session consisted of oxygen therapy given through a high-FIO2, non-rebreathing face mask. Recordings were then obtained during periods of HFNC and CPAP at 5 cm H2O in random order, and final measurements were performed during oxygen therapy delivered via a face mask. Each of these 4 periods lasted ∼20 min. RESULTS:Esophageal pressure signals, breathing pattern, gas exchange, comfort, and dyspnea were measured. Compared with the first session, HFNC reduced inspiratory effort (pressure-time product of 156.0 [119.2-194.4] cm H2O × s/min vs 204.2 [149.6-324.7] cm H2O × s/min, P < .01) and breathing frequency (P < .01). No significant differences were observed between HFNC and CPAP for inspiratory effort and breathing frequency. Compared with the first session, PaO2/FIO2 increased significantly with HFNC (167 [157-184] mm Hg vs 156 [110-171] mm Hg, P < .01). CPAP produced significantly greater PaO2/FIO2 improvement than did HFNC. Dyspnea improved with HFNC and CPAP, but this improvement was not significant. Subject comfort was not different across the 4 sessions. CONCLUSIONS:Compared with conventional oxygen therapy, HFNC improved inspiratory effort and oxygenation. In subjects with acute hypoxemic respiratory failure, HFNC is an alternative to conventional oxygen therapy. (ClinicalTrials.gov registration NCT01056952.).

L’objectif de cette étude était d’évaluer la capacité de l’échographie diaphragmatique à dépister précocement un échec de sevrage de ventilation mécanique. Après accord du comité local d’éthique, cette étude prospective, observationnelle et bicentrique était réalisée dans les services de réanimation médicale et de réanimation des urgences du CHU de Bordeaux et dans le service de réanimation polyvalente du CHR de Libourne entre novembre 2014 et mai 2015. Tout patient adulte ayant bénéficié de plus de 48 heures de ventilation mécanique et possédant les prérequis à une épreuve de sevrage était éligible. Avant réalisation de l’épreuve de sevrage, le score MRC était calculé (MRC < 48 en faveur d’une neuromyopathie acquise) associé à une mesure de capacité vitale en fonction des moyens disponibles (normale > 10 mL/kg). L’évaluation échographique de la cinétique diaphragmatique était réalisée en position semi-assise après déconnection du ventilateur pour mesure de l’excursion diaphragmatique expiratoire maximale (EDEmax) par voie sous-costale droite [1]. Le pourcentage de variabilité inter-observateur calculé au préalable sur dix patients était de 11,8 ± 5,6 %. Un sevrage simple était défini par un succès d’extubation à 48 heures de la première épreuve. Un échec de sevrage était défini par un échec d’épreuve de ventilation spontanée ou un échec d’extubation dans les 48 h suivant la première épreuve. Sur 80 patients initialement éligibles, 47 patients ont été inclus (faisabilité 59 %) et 26 ont bénéficié d’une mesure de CV (55 %). Trente-quatre patients ont présenté un sevrage simple (72 %) et 13 un échec de sevrage (28 %) après une première épreuve de ventilation spontanée. L’excursion diaphragmatique était significativement plus faible chez les sujets présentant un échec de sevrage (23,1 ± 12,1 vs 40,1 ± 20,7, p < 0,0005) alors que le score MRC n’était pas significativement différent dans les 2 groupes (40,7 ± 14,2 vs 48,4 ± 13,8, p = 0,093). La capacité vitale était significativement plus faible chez les sujets présentant un échec de sevrage (8,9 ± 4,4 vs 17,5 ± 9,5, p = 0,002) et il existait une corrélation significative entre EDEmax et CV (r2 = 0,369 ; p < 0,001). La capacité de l’échographie diaphragmatique à dépister un échec de sevrage en fonction des seuils d’EDEmax est résumée (Fig. 1) (aire sous la courbe = 0,761 [0,615–0,873]). Ainsi, un seuil d’EDEmax < 27 mm permettrait de prédire un échec de sevrage avec une sensibilité de 77 % [46–95] et une spécificité de 71 % [53–85]. Cette étude suggère qu’une diminution de l’excursion diaphragmatique en expiration forcée pourrait constituer un nouveau marqueur prédictif de sevrage difficile et témoigner d’une altération de la capacité vitale chez les patients de réanimation. Dans cette population, l’absence de neuromyopathie périphérique diagnostiquée par le score MRC ne témoigne pas de l’absence d’atteinte diaphragmatique diagnostiquée par échographie.

Background: Acute exacerbations of COPD are associated with increased bronchial inflammation and probably contribute to bronchial remodelling. Fibrocytes have emerged as key effector cells in diseases characterized by both chronic inflammation and remodelling, such as asthma or lung fibrosis. However, the recruitment of circulating fibrocytes to the lung and their involvement in bronchial remodelling during COPD exacerbations remain unknown. Methods: Circulating fibrocytes were quantified by flow cytometry in 33 COPD patients during an acute exacerbation and two months later in stable condition, and 26 age-matched control subjects. To address the mechanisms involved in fibrocyte migration to the lung during an acute exacerbation of COPD, COPD and control primary bronchial epithelial cells cultured under air-liquid condition were infected with rhinovirus RV16 to mimic in vitro such an exacerbation. The culture medium was then collected to induce fibrocyte migration. After 7 days of culture in serum free medium or serum free medium containing TNF-α, the cell morphology and α-smooth muscle actin expression as a marker of myofibroblast differentiation were both analyzed by immunocytochemistry. Results: The number of circulating fibrocytes is significantly increased during an acute exacerbation of COPD as compared to both controls and COPD in stable condition. RV16-infected COPD epithelium induces fibrocyte migration. Fibrocytes differentiate into myofibroblast-like cells expressing α-smooth muscle actin with an elongated shape in a TNF-α-dependent manner. Conclusion: These results strongly suggest that fibrocytes may play a crucial role in bronchial remodelling following COPD exacerbation.

Aminoglycoside nephrotoxicity has been reported in patients with sepsis, and several risk factors have been described. Once-daily dosing and shorter treatment have reduced nephrotoxicity risk, and simplified aminoglycoside monitoring. This review focuses on nephrotoxicity associated with aminoglycosides in the subset of patients with septic shock or severe sepsis. These patients are radically different from those with less severe sepsis. They may have, for instance, renal impairment due to the shock per se, sepsis-related acute kidney injury, frequent association with pre-existing risk factors for renal failure such as diabetes, dehydration and other nephrotoxic treatments. In this category of patients, these risk factors might modify substantially the benefit-risk ratio of aminoglycosides. In addition, aminoglycoside administration in critically ill patients with sepsis is complicated by an extreme inter- and intra-individual variability in drug pharmacokinetic/pharmacodynamic characteristics: the volume of distribution (Vd) is frequently increased while the elimination constant can be either increased or decreased. Consequently, and although its effect on nephrotoxicity has not been explored, a different administration schedule, i.e. a high-dose once daily (HDOD), and several therapeutic drug monitoring (TDM) options have been proposed in these patients. This review describes the historical perspective of these different options, including those applying to subsets of patients in which aminoglycoside administration is even more complex (obese intensive care unit [ICU] patients, patients needing continuous or discontinuous renal replacement therapy [CRRT/DRRT]). A simple linear dose adjustment according to aminoglycoside serum concentration can be classified as low-intensity TDM. Nomograms have also been proposed, based on the maximum (peak) plasma concentration (C-max) objectives, weight and creatinine clearance. The Sawchuk and Zaske method (based on the determination of C-max and an intermediate aminoglycoside assay before minimum plasma concentration) and the Bayesian method were both classified as high-intensity TDM programmes. Given the mean cost of aminoglycoside nephrotoxicity, these programmes may be cost-effective if its prevalence is above 10 %. However, none of these high-intensity TDM programmes have demonstrated a reduction of aminoglycoside-associated nephrotoxicity in patients with septic shock. Therefore, the questions remain as to, first, whether a TDM programme is relevant and, second, what intensity of TDM is achievable in the ICU, i.e. how it can be practically applied in the ICU setting where urgent care and high workload are substantial obstacles to a sophisticated, optimized aminoglycoside administration.

Hilbert, Gilles MD, PhD; Vargas, Frederic MD, PhD; Boyer, Alexandre MD; Bui, Hoang-Nam MD Author Information

In line with a rapid de-escalation of empirical antimicrobial therapy, this study assessed the validity of an E-test–based direct specimen testing method on bronchoalveolar lavage (BAL) samples from ventilator-associated pneumonia (VAP) patients. E-test strips were directly applied onto Mueller-Hinton agar plates seeded with BAL samples and read after 24 h of incubation. In parallel, the BAL samples were analyzed by the routine diagnostic laboratory. The microbroth dilution approach was used as a control method. In a cohort of 20 patients, 135 microorganism–antibiotic combinations were studied. Total agreement between the 2 methods was achieved for 88.9% combinations, with 1.5% very major errors (isolates susceptible by E-test and reported resistant by the diagnostic laboratory) and 9.6% major errors (isolates resistant by E-test and reported susceptible by the diagnostic laboratory). These results indicate that applying E-test directly on BAL samples is a promising method for obtaining susceptibility data after 24 h in critical patients with VAP.