Impact of recipient and donor pretransplantation body mass index on early postosperative complications after lung transplantation.

BACKGROUND: Prior studies have assessed the impact of the pretransplantation recipient body mass index (BMI) on patient outcomes after lung transplantation (LT), but they have not specifically addressed early postoperative complications. Moreover, the impact of donor BMI on these complications has not been evaluated. The first aim of this study was to assess complications during hospitalization in the ICU after LT according to donor and recipient pretransplantation BMI. METHODS: All the recipients who underwent LT at Bichat Claude Bernard Hospital, Paris, between January 2016 and August 2022 were included in this observational retrospective monocentric study. Postoperative complications were analyzed according to recipient and donor BMIs. Univariate and multivariate analyses were also performed. The 90-day and one-year survival rates were studied. P < 0.05 was considered to indicate statistical significance. The Paris-North Hospitals Institutional Review Board approved the study. RESULTS: A total of 304 recipients were analyzed. Being underweight was observed in 41 (13%) recipients, a normal weight in 130 (43%) recipients, and being overweight/obese in 133 (44%) recipients. ECMO support during surgery was significantly more common in the overweight/obese group (p = 0.021), as were respiratory complications (primary graft dysfunction (PGD) (p = 0.006), grade 3 PDG (p = 0.018), neuroblocking agent administration (p = 0.008), prone positioning (p = 0.007)), and KDIGO 3 acute kidney injury (p = 0.036). However, pretransplantation overweight/obese status was not an independent risk factor for 90-day mortality. An overweight or obese donor was associated with a decreased PaO2/FiO2 ratio before organ donation (p < 0.001), without affecting morbidity or mortality after LT. CONCLUSION: Pretransplantation overweight/obesity in recipients is strongly associated with respiratory and renal complications during hospitalization in the ICU after LT.

[Early outcomes following lung transplantation in patients aged 65 years and older]. / Résultats précoces de la transplantation pulmonaire chez les patients âgés de 65 ans et plus.

INTRODUCTION: The number of lung transplantations performed is increasing worldwide. With an improved experience and outcomes, the age of the recipient on its own has ceased to be an absolute contra-indication. We report our first experience with lung transplantation in patients aged 65 years or older. METHODS: From January 2014 to March 2019, the files of patients aged 65 years or older undergoing lung transplantation were retrospectively reviewed. RESULTS: During the study period, 241 patients underwent lung transplantation in Bichat hospital (Paris, France), including 25 recipients aged 65 years or older. Underlying diagnoses were interstitial (72%) and obstructive (28%) disease. The rate of single lung transplantation was 80%. Sixteen patients required ECMO assistance during the procedure. Early complications were mostly grade III primary graft dysfunction (12%) and cellular rejection (20%). Overall one-year survival rate was 76%. CONCLUSION: After a careful selection of the recipients, the early results of our retrospective single center series are encouraging. We continue to consider lung transplantation in rigorously selected recipients of aged 65 years and more.

Acute Kidney Injury After Lung Transplantation: Perioperative Risk Factors and Outcome.

BACKGROUND: Acute kidney injury (AKI) is associated with increased short-term and long-term mortality and morbidity after lung transplantation (LT). The primary objective of this study was to analyze the perioperative factors associated with AKI according to Kidney Disease: Improving Global Outcome (KDIGO) criteria during hospitalization in an intensive care unit (ICU) after LT. METHODS: This was a single-center, observational, prospective study. AKI was defined according to KDIGO criteria. Results are expressed as median, interquartile range, absolute numbers, and percentages. Statistical analyses were performed using χ2 test, Fisher exact test, and Mann-Whitney U test. P < .05 was considered to be significant. Multivariate analysis was performed to identify independent risk factors. RESULTS: Between January 2016 and April 2018, 94 patients underwent LT (70% bilateral LT). AKI occurred during ICU stay in 46 patients (49%). KDIGO 1 AKI was observed in 16 patients (17%), KDIGO 2 in 14 patients (15%), and KDIGO 3 in 16 patients (17%), including 12 patients (75%) who required renal replacement therapy. AKI occurred before the fifth day after surgery for 38 patients (82% of the AKI patients). On multivariate analysis, independent factors associated with AKI were bilateral LT and mechanical ventilation >3 days (odds ratio [OR] 4.26, 95% confidence interval [CI] [1.49; 13.63] P = .010 and OR 5.56 [1.25; 11.47] P = .018, respectively). AKI and the need for renal replacement therapy were significantly associated with ICU mortality, 28-day mortality, and 1-year mortality. CONCLUSION: AKI is common during ICU stay after LT, especially after bilateral LT, and is associated with prolonged mechanical ventilation and increased short-term and long-term mortality.

Impact of colonization pressure on acquisition of extended-spectrum ß-lactamase-producing Enterobacterales and meticillin-resistant Staphylococcus aureus in two intensive care units: a 19-year retrospective surveillance.

BACKGROUND: Colonization pressure is a risk factor for intensive care unit (ICU)-acquired multi-drug-resistant organisms (MDROs). AIM: To measure the long-term respective impact of colonization pressure on ICU-acquired extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) and meticillin-resistant Staphylococcus aureus (MRSA). METHODS: All patients admitted to two ICUs (medical and surgical) between January 1997 and December 2015 were included in this retrospective observational study. Rectal and nasal surveillance cultures were obtained at admission and weekly thereafter. Contact precautions were applied for colonized or infected patients. Colonization pressure was defined as the ratio of the number of MDRO-positive patient-days (PDs) of each MDRO to the total number of PDs. Single-level negative binomial regression models were used to evaluate the incidence of weekly MDRO acquisition. FINDINGS: Among the 23,423 patients included, 2327 (10.0%) and 1422 (6.1%) were colonized with ESBL-PE and MRSA, respectively, including 660 (2.8%) and 351 (1.5%) acquisitions. ESBL-PE acquisition increased from 0.51/1000 patient-exposed days (PEDs) in 1997 to 6.06/1000 PEDs in 2015 (P<0.001). In contrast, MRSA acquisition decreased steadily from 3.75 to 0.08/1000 PEDs (P<0.001). Controlling for period-level covariates, colonization pressure in the previous week was associated with MDRO acquisition for ESBL-PE (P<0.001 and P=0.04 for medical and surgical ICU, respectively), but not for MRSA (P=0.34 and P=0.37 for medical and surgical ICU, respectively). The increase in colonization pressure was significant above 100/1000 PDs for ESBL-PE. CONCLUSION: Colonization pressure contributed to the increasing incidence of ESBL-PE but not MRSA. This study suggests that preventive control measures should be customized to MDROs.

Fungal Isolation in Respiratory Tract After Lung Transplantation: Epidemiology, Clinical Consequences, and Associated Factors.

BACKGROUND: Fungus-positive respiratory samples (FPRS) are common in the intensive Care unit (ICU) and are usually considered to correspond to colonization. The management of FPRS during the early postoperative course after lung transplantation (LT) remains unclear. The epidemiology, clinical consequences, and prognosis of FPRS were assessed in LT recipients. METHODS: Over a 6-year period, we analyzed the postoperative ICU course of 176 LT recipients with a specific focus on microbiological results of routine respiratory samples and clinical course. The outcomes during the ICU stay at day 28 and at 1 year were compared in patients with or without FPRS. Results are expressed as median and interquartile range. RESULTS: In the pretransplantation period, Candida spp were reported in 17% of patients. No routine post-LT antifungal prophylaxis was initiated. In the post-LT period, at least 1 FPRS was observed in 69% of patients (93% Candida spp, 7% Aspergillus spp). Double LT (odds ratio = 4.15, 95% confidence interval [1.67-11.80], P = .0007) was the only risk factor associated with Candida spp in respiratory samples. Antifungal therapy was administered in 58% of patients with post-LT Candida-positive samples. Candida spp in post-LT respiratory samples were not associated with increased ICU, 28-day, or 1-year mortality rates. CONCLUSION: A high prevalence of FPRS is reported after LT, mainly with Candida spp. The lack of association between post-LT FPRS and mortality and morbidity suggests avoiding antifungal therapy in the absence of clinical signs of invasive infection.

Antibioprophylaxis in surgery and interventional medicine (adult patients). Update 2017.

Infection is a risk for any intervention. In surgery, for example, pathogenic bacteria are found in more than 90% of operative wounds during closure. This exists whatever the surgical technique and whatever the environment (the laminar flow does not entirely eliminate this risk). These bacteria are few in number but can proliferate. They find in the operative wound a favourable environment (haematoma, ischaemia, modification of oxido-reduction potential...) and the intervention induces anomalies of the immune defences. In the case of the installation of foreign material, the risk is increased. The objective of antibiotic prophylaxis (ABP) is to prevent bacterial growth in order to reduce the risk of infection at the site of the intervention. The preoperative consultation represents a privileged moment to decide on the prescription of a ABP. It is possible to define the type of intervention planned, the associated risk of infection (and therefore the necessity or not of ABP), the time of prescription before surgery and any allergic antecedents which may modify the choice of the selected antibiotic molecule.

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Pattern and consequences of cardiologic medications management for patients with elevated troponin I upon admission into an intensive care unit not linked to type 1 acute myocardial infarction: A prospective observational cohort study.

OBJECTIVES: No recommendations are currently available to help the clinician with the pharmacological management of intensive care unit (ICU) patients with elevated cardiac troponin (cTn) not linked to type 1 AMI. The aim of this study was to evaluate the pattern of cardiologic medications for patients with elevated cTnI in ICU not link to type 1 AMI and their effects on in-hospital mortality. MATERIAL AND METHODS: A prospective observational cohort study conducted in two ICU units. Patients with increased plasma concentration of cTnI at admission not linked to type 1 AMI were consecutively included. RESULTS: One hundred and ninety of the 835 patients admitted (23%) had an increased plasma concentration of cTnI not related to type 1 AMI. Antiplatelet therapy (AT) and statin were prescribed in 56 (29.5%) and 50 (26.3%) of patients, respectively. Others cardiologic medications were prescribed in less than 5% of all cases and were considered as contraindicated in more than 50% of cases. Antiplatelet therapy was the only cardiologic treatment associated with reduction of in-hospital mortality following uni- and multivariate analysis. The death rate was 23% and 40% in these patients treated with and without AT, respectively (aOR=0.39 [95% CI: 0.15-0.97]). CONCLUSIONS: Statin and AT were frequently prescribed to patients with a cTnI elevation not linked to type 1 AMI. This study suggests that AT in patients with an increased plasma concentration of cTnI, not related to type 1 AMI in ICU, could reduce in-hospital mortality.

Pharmacokinetic study of anidulafungin in ICU patients with intra-abdominal candidiasis.

Background: Only limited pharmacokinetic data are available for anidulafungin in ICU patients, especially in patients treated for severe intra-abdominal infection (IAI). Methods: This was a prospective multicentre observational study in ICU patients with suspected yeast IAI. All patients received an intravenous loading dose of 200 mg of anidulafungin, followed by 100 mg/day. Thirteen blood samples were drawn between day 1 and day 5 for pharmacokinetic analysis. Samples were analysed by an HPLC-tandem MS method. Demographics and SAPS2 and SOFA scores were recorded. Results: Fourteen patients with a median age (IQR) of 62 years (48-70) and with a mean BMI of 30.5 kg/m 2 were included from three centres; 57.1% were women. Their median (IQR) SAPS2 score was 54 (45-67) and their median (IQR) SOFA score was 8 (7-12). Six patients with community-acquired IAI and eight patients with nosocomial-acquired IAI were included. Twelve yeasts were isolated: six Candida albicans , two Candida glabrata , two Candida tropicalis , one Candida parapsilosis and one Candida krusei . Pharmacokinetic parameters were as follows [mean (% coefficient of variation)]: C max (mg/L) = 6.0 (29%); T max (h) = 1.6 (25.8%); C min (mg/L) = 3.2 (36.8%); AUC 0-24 (mg·h/L) = 88.9 (38.6%); t 1/2 (h) = 42.1 (68.2%); CL (L/h) = 1.2 (42.3%); and V (L) = 72.8 (87.8%). A two-compartment model best described the anidulafungin concentrations in the population pharmacokinetic study. Conclusions: The pharmacokinetic parameters of anidulafungin in critically ill ICU patients with complicated IAI are similar to those observed in the literature. However, an increased V and a longer t 1/2 were observed in this study. (EudraCT No. 2010-018695-25).

Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units.

OBJECTIVE: The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection. METHODS: Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF. RESULTS: In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score <7 if SAT was delayed by ≥6 days (p 0.04). Healthcare-associated CP (OR 3.82, 95% CI 1.52-9.64, p 0.004), SOFA ≥8 at ICU admission (OR 2.61, 95% CI 1.08-6.34; p 0.03), and SAPS II ≥45 at SAT initiation (OR 5.08, 95% CI 1.04-12.67; p 0.001) impacted the 28-day mortality. CONCLUSIONS: In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP.

Therapeutic management of peritonitis: a comprehensive guide for intensivists.

PURPOSE: The management of peritonitis in critically ill patients is becoming increasingly complex due to their changing characteristics and the growing prevalence of multidrug-resistant (MDR) bacteria. METHODS: A multidisciplinary panel summarizes the latest advances in the therapeutic management of these critically ill patients. RESULTS: Appendicitis, cholecystitis and bowel perforation represent the majority of all community-acquired infections, while most cases of healthcare-associated infections occur following suture leaks and/or bowel perforation. The micro-organisms involved include a spectrum of Gram-positive and Gram-negative bacteria, as well as anaerobes and fungi. Healthcare-associated infections are associated with an increased likelihood of MDR pathogens. The key elements for success are early and optimal source control and adequate surgery and appropriate antibiotic therapy. Drainage, debridement, abdominal cleansing, irrigation, and control of the source of contamination are the major steps to ensure source control. In life-threatening situations, a "damage control" approach is the safest way to gain time and achieve stability. The initial empirical antiinfective therapy should be prescribed rapidly and must target all of the micro-organisms likely to be involved, including MDR bacteria and fungi, on the basis of the suspected risk factors. Dosage adjustment needs to be based on pharmacokinetic parameters. Supportive care includes pain management, optimization of ventilation, haemodynamic and fluid monitoring, improvement of renal function, nutrition and anticoagulation. CONCLUSIONS: The majority of patients with peritonitis develop complications, including worsening of pre-existing organ dysfunction, surgical complications and healthcare-associated infections. The probability of postoperative complications must be taken into account in the decision-making process prior to surgery.

Epidemiology and risk factors of multidrug-resistant bacteria in respiratory samples after lung transplantation.

BACKGROUND: Multidrug-resistant (MDR) bacteria are a growing concern worldwide. The aim of this study was to describe the epidemiology and risk factors of MDR bacteria detected in respiratory invasive samples during hospitalization in the intensive care unit (ICU) after lung transplantation (LT). METHODS: This study was based on a retrospective analysis of 176 patients hospitalized in the ICU after LT in 2006-2012. Respiratory invasive samples were performed according to a routine protocol. MDR pathogens were defined according to in vitro susceptibility tests. RESULTS: A total of 1176 bacteria were cultured. Susceptibility testing was performed on 1046 strains and 404 (39%) MDR were detected in 90 (51%) patients. Pseudomonas aeruginosa, coagulase-negative staphylococci, and Enterobacteriaceae (mainly Enterobacter species) were the most common MDR pathogens. On multivariate analysis, an ICU stay >14 days, presence of a tracheostomy, and previous exposure to broad-spectrum antibiotics were associated with MDR acquisition (odds ratio [OR] 3.7; 95% confidence interval [1.69-8.12]; OR 3.28 [1.05-10.28]; and OR 2.25 [1.17-4.34], respectively). We consistently observed an increasing emergence of resistance to several antibiotics, from week 1 to week 4 of ICU hospitalization: for ticarcillin, piperacillin-tazobactam, ceftazidime, imipenem/cilastatin, amikacin, and ciprofloxacin in P. aeruginosa; and for piperacillin-tazobactam, cefepime, and amikacin in Enterobacteriaceae. CONCLUSION: A large proportion of MDR bacteria are detected on respiratory invasive samples in LT patients, and the risk of their emergence is mainly determined by the previous exposure to broad-spectrum antibiotics and the length of ICU stay. Adequate treatment requires broad-spectrum empiric antibiotic therapy.

Positive peritoneal fluid fungal cultures in postoperative peritonitis after bariatric surgery.

Postoperative peritonitis (POP) is a common surgical complication after bariatric surgery (BS). We assessed the importance of positive fungal cultures in these cases of POP admitted to the intensive care unit. Clinical features and outcome were compared in 25 (41%) Candida-positive patients (6 (22%) fluconazole-resistant Candida glabrata) and 36 patients without Candida infection. Candida infections were more commonly isolated in late-onset peritonitis and were often associated with multidrug-resistant bacteria. Risk factors for intensive care unit mortality (19.6%) were diabetes and superobesity. Candida infections, including fluconazole-resistant strains, are common in POP after BS. These data encourage the empirical use of a broad-spectrum antifungal agent.

Guidelines for management of intra-abdominal infections

Intra-abdominal infections are one of the most common gastrointestinal emergencies and a leading cause of septic shock. A consensus conference on the management of community-acquired peritonitis was published in 2000. A new consensus as well as new guidelines for less common situations such as peritonitis in paediatrics and healthcare-associated infections had become necessary. The objectives of these Clinical Practice Guidelines (CPGs) were therefore to define the medical and surgical management of community-acquired intra-abdominal infections, define the specificities of intra-abdominal infections in children and describe the management of healthcare-associated infections. The literature review was divided into six main themes: diagnostic approach, infection source control, microbiological data, paediatric specificities, medical treatment of peritonitis, and management of complications. The GRADE(®) methodology was applied to determine the level of evidence and the strength of recommendations. After summarising the work of the experts and application of the GRADE(®) method, 62 recommendations were formally defined by the organisation committee. Recommendations were then submitted to and amended by a review committee. After 2 rounds of Delphi scoring and various amendments, a strong agreement was obtained for 44 (100%) recommendations. The CPGs for peritonitis are therefore based on a consensus between the various disciplines involved in the management of these patients concerning a number of themes such as: diagnostic strategy and the place of imaging; time to management; the place of microbiological specimens; targets of empirical anti-infective therapy; duration of anti-infective therapy. The CPGs also specified the value and the place of certain practices such as: the place of laparoscopy; the indications for image-guided percutaneous drainage; indications for the treatment of enterococci and fungi. The CPGs also confirmed the futility of certain practices such as: the use of diagnostic biomarkers; systematic relaparotomies; prolonged anti-infective therapy, especially in children.(AU)

Performance and impact of a rapid method combining mass spectrometry and direct antimicrobial susceptibility testing on treatment adequacy of patients with ventilator-associated pneumonia.

Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. Using broad-spectrum antibiotics for 48 h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Performing AST directly on clinical respiratory samples would hasten the process by at least 24 h. Here, we analysed the diagnostic performance of a rapid method combining mass spectrometry and direct AST (DAST), and compared it with the conventional method (mass spectrometry with conventional AST (CAST)). Additionally, we assessed its potential impact on antimicrobial use in patients. Over a period of 18 months, the two methods were performed on 85 bronchoalveolar lavages obtained from intensive care unit patients with suspected VAP, and in which Gram-negative bacilli were observed on direct examination. Only the CAST results were reported to the clinicians. DAST produced useable results in 85.9% of the patients. The sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1%, (95% CI 93.3-101) and 97.4% (93.7-101), respectively) and amikacin (88.9% (81.7-96.1) and 96.4% (92.1-100.7), respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2-91.5) to 100%, and from 86.4 (78.5-94.2) to 100%, respectively. If the DAST results had been reported to the clinicians, treatment could have been optimized 24 h earlier in 35/85 (41.2%) patients, with 17 carbapenem patient-days saved. Overall, routine use of the DAST method could help optimize earlier antibiotic treatment in patients with suspected VAP.

Anaphylactic bronchospasm during general anesthesia is not related to asthma.

In the general population, a history of asthma (HA) is associated with a higher risk of mortality of anaphylactic shock (AS), but it is unknown whether this association remains valid for intra-operative AS. The goal of this retrospective study was to investigate whether a HA was associated with a higher risk of bronchospasm during intra-operative AS. We analyzed 106 patients (January 2009-December 2012) with intra-operative AS: 57% of them had a confirmed IgE-mediated reaction and 27% had a HA. On logistic regression, the only factor statistically associated with bronchospasm was a neuromuscular blocking drug, with both IgE- or non-IgE-mediated reactions. These results suggest that the mechanisms of bronchospasm in AS may be different from those of asthma and that, in the presence of bronchospasm during anesthesia, AS should be considered to be the most likely cause.

Alveolar and serum concentrations of imipenem in two lung transplant recipients supported with extracorporeal membrane oxygenation.

Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support. We report the cases of 2 patients supported with venovenous ECMO for refractory acute respiratory distress syndrome following single lung transplantation for pulmonary fibrosis, treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of Patient 2. Minimum inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L, respectively. Both patients were still alive on day 28. This is the first report, to our knowledge, of imipenem concentrations in lung transplantation patients supported with ECMO. This study confirms high variability in imipenem trough concentrations in patients on ECMO and with preserved renal function. An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended, where available. Population pharmacokinetic studies are indicated to develop evidence-based dosing guidelines for ECMO patients.

Risk factors for target non-attainment during empirical treatment with ß-lactam antibiotics in critically ill patients.

PURPOSE: Risk factors for ß-lactam antibiotic underdosing in critically ill patients have not been described in large-scale studies. The objective of this study was to describe pharmacokinetic/pharmacodynamic (PK/PD) target non-attainment envisioning empirical dosing in critically ill patients and considering a worst-case scenario as well as to identify patient characteristics that are associated with target non-attainment. METHODS: This analysis uses data from the DALI study, a prospective, multi-centre pharmacokinetic point-prevalence study. For this analysis, we assumed that these were the concentrations that would be reached during empirical dosing, and calculated target attainment using a hypothetical target minimum inhibitory concentration (MIC), namely the susceptibility breakpoint of the least susceptible organism for which that antibiotic is commonly used. PK/PD targets were free drug concentration maintained above the MIC of the suspected pathogen for at least 50 % and 100 % of the dosing interval respectively (50 % and 100 % f T (>MIC)). Multivariable analysis was performed to identify factors associated with inadequate antibiotic exposure. RESULTS: A total of 343 critically ill patients receiving eight different ß-lactam antibiotics were included. The median (interquartile range) age was 60 (47-73) years, APACHE II score was 18 (13-24). In the hypothetical situation of empirical dosing, antibiotic concentrations remained below the MIC during 50 % and 100 % of the dosing interval in 66 (19.2 %) and 142 (41.4 %) patients respectively. The use of intermittent infusion was significantly associated with increased risk of non-attainment for both targets; creatinine clearance was independently associated with not reaching the 100 % f T( >MIC) target. CONCLUSIONS: This study found that-in empirical dosing and considering a worst--case scenario--19 % and 41 % of the patients would not achieve antibiotic concentrations above the MIC during 50 % and 100 % of the dosing interval. The use of intermittent infusion (compared to extended and continuous infusion) was the main determinant of non-attainment for both targets; increasing creatinine clearance was also associated with not attaining concentrations above the MIC for the whole dosing interval. In the light of this study from 68 ICUs across ten countries, we believe current empiric dosing recommendations for ICU patients are inadequate to effectively cover a broad range of susceptible organisms and need to be reconsidered.