Lung Ultrasound in Emergency and Critically Ill Patients: Number of Supervised Exams to Reach Basic Competence.

BACKGROUND: Lung ultrasound is increasingly used in critically ill patients as an alternative to bedside chest radiography, but the best training method remains uncertain. This study describes a training curriculum allowing trainees to acquire basic competence. METHODS: This multicenter, prospective, and educational study was conducted in 10 Intensive Care Units in Brazil, China, France and Uruguay. One hundred residents, respiratory therapists, and critical care physicians without expertise in transthoracic ultrasound (trainees) were trained by 18 experts. The main study objective was to determine the number of supervised exams required to get the basic competence, defined as the trainees' ability to adequately classify lung regions with normal aeration, interstitial-alveolar syndrome, and lung consolidation. An initial 2-h video lecture provided the rationale for image formation and described the ultrasound patterns commonly observed in critically ill and emergency patients. Each trainee performed 25 bedside ultrasound examinations supervised by an expert. The progression in competence was assessed every five supervised examinations. In a new patient, 12 pulmonary regions were independently classified by the trainee and the expert. RESULTS: Progression in competence was derived from the analysis of 7,330 lung regions in 2,562 critically ill and emergency patients. After 25 supervised examinations, 80% of lung regions were adequately classified by trainees. The ultrasound examination mean duration was 8 to 10 min in experts and decreased from 19 to 12 min in trainees (after 5 vs. 25 supervised examinations). The median training duration was 52 (42, 82) days. CONCLUSIONS: A training curriculum including 25 transthoracic ultrasound examinations supervised by an expert provides the basic skills for diagnosing normal lung aeration, interstitial-alveolar syndrome, and consolidation in emergency and critically ill patients.

Human IgA binds a diverse array of commensal bacteria.

In humans, several grams of IgA are secreted every day in the intestinal lumen. While only one IgA isotype exists in mice, humans secrete IgA1 and IgA2, whose respective relations with the microbiota remain elusive. We compared the binding patterns of both polyclonal IgA subclasses to commensals and glycan arrays and determined the reactivity profile of native human monoclonal IgA antibodies. While most commensals are dually targeted by IgA1 and IgA2 in the small intestine, IgA1+IgA2+ and IgA1-IgA2+ bacteria coexist in the colon lumen, where Bacteroidetes is preferentially targeted by IgA2. We also observed that galactose-α terminated glycans are almost exclusively recognized by IgA2. Although bearing signs of affinity maturation, gut-derived IgA monoclonal antibodies are cross-reactive in the sense that they bind to multiple bacterial targets. Private anticarbohydrate-binding patterns, observed at clonal level as well, could explain these apparently opposing features of IgA, being at the same time cross-reactive and selective in its interactions with the microbiota.

T regulatory cells activation and distribution are modified in critically ill patients with acute respiratory distress syndrome: A prospective single-centre observational study.

BACKGROUNDS: Acute respiratory distress syndrome (ARDS) is a common and fatal inflammatory condition. Whether T regulatory cells (Tregs) are beneficial or detrimental remains controversial, and longitudinal studies are lacking. Phenotyping of Tregs activation markers has been poorly reported. We aimed to evaluate quantitative and functional alterations in blood and bronchoalveolar Treg phenotype of ARDS patients. METHODS: We performed a single-centre observational study in a French intensive care unit. The study enrolled 60 ARDS and 45 non-ARDS patients. Patients under 18years old or with immunosuppression (native or acquired) were excluded. Tregs phenotypes were assessed by flow cytometry, while cytokines were measured by multiplex-based assays in blood and bronchoalveolar samples collected over 3weeks after the onset of ARDS. RESULTS: Blood Tregs/CD4+ percentage (median %, 25-75% interquartile) was higher in ARDS patients than in non-ARDS patients: 12.1% [9.0-16.0] versus 9.9% [8.1-12.6], P=0.01. Alveolar Tregs/CD4+ percentage was lower in ARDS patients than in non-ARDS patients: 10.4% [6.3-16.6] versus 16.2% [12.4-21.1], P=0.03. In ARDS patients, Tregs activation was reduced in the blood and increased in the alveolus, compared to non-ARDS patients. ROC analysis revealed a threshold of 10.4% for the Tregs/CD4+ percentage in the blood collected within the first week of ARDS to discriminate between survivors and non-survivors (sensitivity: 75%; specificity 76%; area under the curve [95% confidence interval]: 0.72 [0.5-0.9]). CONCLUSIONS: Quantitative and functional alterations in Treg phenotype were observed in patients with ARDS. Whether rebalancing Tregs phenotype with therapeutic interventions would be beneficial deserves further investigations.

[Multidisciplinarity and early rehabilitation in intensive care]. / Pluridisciplinarité et réhabilitation précoce en réanimation.

Whatever the nature of the mobilisation of intensive care patients, it requires sufficient numbers of staff, time and adapted material resources. It forms part of the personalised treatment around the patient's care project. Mobilising patients as soon as possible in order to enable them to recover a minimum of muscle tone is the first stage before standing with a view to their early recovery of their lost autonomy. The in-bed cycle is one of the tools of this care project.

Unexpected good outcome in severe cerebral fat embolism syndrome.

In this case study, we report the longitudinal and multimodal follow-up of a catastrophic initial presentation of cerebral fat embolism syndrome. We show that despite the initial severity, the cognitive outcome was ultimately very good but with a highly nonlinear time-course and prolonged loss of consciousness (more than 2 months). Repeated clinical assessments and brain-imaging techniques (electroencephalography, event-related potential, 18-Fluoro-Deoxy-Glucose-PET and magnetic resonance imaging) allowed us to monitor and anticipate this dynamic, providing relevant information to guide decision making in front of withdrawal of life-sustaining therapy discussions. This case illustrates the value of multimodal functional imaging in devastating brain injuries.

Treating hepatic encephalopathy in cirrhotic patients admitted to ICU with sodium phenylbutyrate: a preliminary study.

Hepatic encephalopathy (HE) influences short-term and long-term prognoses. Recently, glycerol phenylbutyrate (PB), that lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion, has shown that it was effective in preventing the occurrence of HE in RCT. The aim was to assess the benefits of sodium PB in cirrhotic patients admitted to ICU for overt HE, in terms of ammonia levels decrease, neurological improvement, and survival. Cirrhotic patients who presented with overt HE, ammonia levels >100 µmol/L, and did not display any contra-indication were included. Sodium PB was administered at 200 mg/kg/day. Control group included historical controls treated by standard therapy, matched for age, sex, MELD score, and severity of HE. Eighteen patients were included and treated with sodium PB (age: 59 [45-68], male gender: 15 [83%], Child-Pugh B: 8 [44%], Child-Pugh C: 10 [56%], and MELD score: 16 [13-23]). Ammonia levels significantly decreased in the PB as compared to the control group from inclusion to 12 h and from inclusion to 48 h (P = 0.0201 and P = 0.0230, respectively). The proportion of patients displaying neurological improvement was only higher in the PB-treated group as compared to controls at ICU discharge (15 [83%] vs. 9 [50%], P = 0.0339). ICU discharge survival was significantly higher in patients treated with PB (17 [94%] vs. 9 [50%], P = 0.0017). In cirrhotic patients with overt HE, sodium PB could be effective in reducing ammonia levels and might be effective in improving neurological status and ICU discharge survival. More extensive data, especially a RCT, are mandatory.

Modification of Tracheal Cuff Shape and Continuous Cuff Pressure Control to Prevent Microaspiration in an Ex Vivo Pig Tracheal Two-Lung Model.

OBJECTIVES: Microaspiration of subglottic secretions plays a pivotal role in ventilator-associated pneumonia. Impact of endotracheal tube cuff material and shape on tracheal sealing performance remains debated. The primary objective was to compare the tracheal sealing performance of polyvinyl chloride tapered, cylindrical and spherical cuffs. Secondary objectives were to determine the impact of continuous cuff pressure control on sealing performance and pressure variability. DESIGN: Prospective randomized ex vivo animal study. SETTING: French research laboratory. SUBJECTS: Seventy-two ex vivo pig tracheal two-lung blocks. INTERVENTIONS: Blocks were randomly intubated with cylindrical (n = 26), tapered (n = 24), or spherical (n = 22) polyvinyl chloride endotracheal tube cuffs. Two milliliter of methylene blue were instilled above the cuff to quantify microaspirations, and lungs were ventilated for 2 hours. Continuous cuff pressure control was implemented in 33 blocks. MEASUREMENTS AND MAIN RESULTS: Cuff pressures were continuously recorded, and after 2 hours, a microaspiration score was calculated. Tapered cuffs improved cuff sealing performance compared with spherical cuffs with or without continuous cuff pressure control. Compared with spherical cuffs, tapered cuffs reduced the microaspiration score without and with continuous pressure control by 65% and 72%, respectively. Continuous cuff pressure control did not impact sealing performance. Tapered cuffs generated higher cuff pressures and increased the time spent with overinflation compared with spherical cuffs (median [interquartile range], 77.9% [0-99.8] vs. 0% [0-0.5]; p = 0.03). Continuous cuff pressure control reduced the variability of tapered and spherical cuffs likewise the time spent with overinflation of tapered and cylindrical cuffs. CONCLUSIONS: Polyvinyl chloride tapered cuffs sealing enhanced performance at the cost of an increase in cuff pressure and in time spent with overinflation. Continuous cuff pressure control reduced the variability and normalized cuff pressures without impacting sealing performance.

Comment on "Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination".

Analysis of antigen-specific T cells can be confounded by T cell activation in vitro.

Multidrug-resistant bacteria transmitted through high-density EEG in ICU.

PURPOSE: Prevention of multidrug resistant (MDR) bacterial contamination remains a major challenge in ICUs. Many hospital outbreaks involving MDR transmitted through environmental contamination have been reported. Bedside high-density EEG allow for dynamic cognitive evaluation in brain-injured patients and is used more and more frequently in clinical practice to evaluate brain function and predict outcome in severely neurologically impaired patients. Unfortunately, the material used for this procedure is not entirely disposable. METHOD: We performed a systematic analysis of MDR bacterial contamination in patients contaminated in our ICU using specific bacteriological methods. RESULTS: We report a proven case of cross-contamination of an extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae strain, and a possible case of cross-contamination of a carbapenem-resistant Acinetobacter baumannii strain. CONCLUSION: Cross-contamination of MDR bacteria is possible through high-density EEG material. However, appropriate procedures can decrease this risk.

Tapered-cuff Endotracheal Tube Does Not Prevent Early Postoperative Pneumonia Compared with Spherical-cuff Endotracheal Tube after Major Vascular Surgery: A Randomized Controlled Trial.

BACKGROUND: Patients undergoing major vascular surgery often develop postoperative pneumonia that impacts their outcomes. Conflicting data exist concerning the potential benefit of tapered-shaped cuffs on tracheal sealing. The primary objective of this study was to assess the efficiency of a polyvinyl chloride tapered-cuff endotracheal tube at reducing the postoperative pneumonia rate after major vascular surgery. Secondary objectives were to determine its impact on microaspiration, ventilator-associated pneumonia rate, and inner cuff pressure. METHODS: This prospective randomized controlled study included 109 patients who were randomly assigned to receive either spherical- (standard cuff) or taper-shaped (tapered cuff) endotracheal tubes inserted after anesthesia induction and then admitted to the intensive care unit after major vascular surgery. Cuff pressure was continuously recorded over 5 h. Pepsin and α-amylase concentrations in tracheal aspirates were quantified on postoperative days 1 and 2. The primary outcome was the early postoperative pneumonia frequency. RESULTS: Comparing the tapered-cuff with standard-cuff group, respectively, postoperative pneumonia rates were comparable (42 vs. 44%, P = 0.87) and the percentage (interquartile range) of cuff-pressure time with overinflation was significantly higher (16.1% [1.5 to 50] vs. 0.6% [0 to 8.3], P = 0.01), with a 2.5-fold higher coefficient of variation (20.2 [10.6 to 29.4] vs. 7.6 [6.2 to 10.2], P < 0.001). Although microaspiration frequencies were high, they did not differ between groups. CONCLUSION: For major vascular surgery patients, polyvinyl chloride tapered-cuff endotracheal tubes with intermittent cuff-pressure control did not lower the early postoperative pneumonia frequency and did not prevent microaspiration.

First experience of liver transplantation with type 2 donation after cardiac death in France.

Organ donation after unexpected cardiac death [type 2 donation after cardiac death (DCD)] is currently authorized in France and has been since 2006. Following the Spanish experience, a national protocol was established to perform liver transplantation (LT) with type 2 DCD donors. After the declaration of death, abdominal normothermic oxygenated recirculation was used to perfuse and oxygenate the abdominal organs until harvesting and cold storage. Such grafts were proposed to consenting patients < 65 years old with liver cancer and without any hepatic insufficiency. Between 2010 and 2013, 13 LTs were performed in 3 French centers. Six patients had a rapid and uneventful postoperative recovery. However, primary nonfunction occurred in 3 patients, with each requiring urgent retransplantation, and 4 early allograft dysfunctions were observed. One patient developed a nonanastomotic biliary stricture after 3 months, whereas 8 patients showed no sign of ischemic cholangiopathy at their 1-year follow-up. In comparison with a control group of patients receiving grafts from brain-dead donors (n = 41), donor age and cold ischemia time were significantly lower in the type 2 DCD group. Time spent on the national organ wait list tended to be shorter in the type 2 DCD group: 7.5 months [interquartile range (IQR), 4.0-11.0 months] versus 12.0 months (IQR, 6.8-16.7 months; P = 0.08. The 1-year patient survival rates were similar (85% in the type 2 DCD group versus 93% in the control group), but the 1-year graft survival rate was significantly lower in the type 2 DCD group (69% versus 93%; P = 0.03). In conclusion, to treat borderline hepatocellular carcinoma, LT with type 2 DCD donors is possible as long as strict donor selection is observed.

Diagnostic accuracy of the Bedside Lung Ultrasound in Emergency protocol for the diagnosis of acute respiratory failure in spontaneously breathing patients.

OBJECTIVE: Bedside lung ultrasound (LUS) is a noninvasive, readily available imaging modality that can complement clinical evaluation. The Bedside Lung Ultrasound in Emergency (BLUE) protocol has demonstrated a high diagnostic accuracy in patients with acute respiratory failure (ARF). Recently, bedside LUS has been added to the medical training program of our ICU. The aim of this study was to investigate the accuracy of LUS based on the BLUE protocol, when performed by physicians who are not ultrasound experts, to guide the diagnosis of ARF. METHODS: Over a one-year period, all spontaneously breathing adult patients consecutively admitted to the ICU for ARF were prospectively included. After training, 4 non-ultrasound experts performed LUS within 20 minutes of patient admission. They were blinded to patient medical history. LUS diagnosis was compared with the final clinical diagnosis made by the ICU team before patients were discharged from the ICU (gold standard). RESULTS: Thirty-seven patients were included in the analysis (mean age, 73.2 ± 14.7 years; APACHE II, 19.2 ± 7.3). LUS diagnosis had a good agreement with the final diagnosis in 84% of patients (overall kappa, 0.81). The most common etiologies for ARF were pneumonia (n = 17) and hemodynamic lung edema (n = 15). The sensitivity and specificity of LUS as measured against the final diagnosis were, respectively, 88% and 90% for pneumonia and 86% and 87% for hemodynamic lung edema. CONCLUSIONS: LUS based on the BLUE protocol was reproducible by physicians who are not ultrasound experts and accurate for the diagnosis of pneumonia and hemodynamic lung edema.

OBJETIVO: O ultrassom pulmonar (USP) à beira do leito é uma técnica de imagem não invasiva e prontamente disponível que pode complementar a avaliação clínica. O protocolo Bedside Lung Ultrasound in Emergency (BLUE, ultrassom pulmonar à beira do leito em situações de emergência) demonstrou elevado rendimento diagnóstico em pacientes com insuficiência respiratória aguda (IRpA). Recentemente, um programa de treinamento em USP à beira do leito foi implementado na nossa UTI. O objetivo deste estudo foi avaliar a acurácia do USP baseado no protocolo BLUE, quando realizado por médicos com habilidades básicas em ultrassonografia, para orientar o diagnóstico de IRpA. MÉTODOS: Ao longo de um ano, todos os pacientes adultos consecutivos respirando espontaneamente admitidos na UTI por IRpA foram prospectivamente inclusos. Após treinamento, 4 operadores com habilidades básicas em ultrassonografia realizaram o USP em até 20 minutos após a admissão na UTI, cegados para a história do paciente. Os diagnósticos do USP foram comparados aos diagnósticos da equipe assistente ao final da internação na UTI (padrão-ouro). RESULTADOS: Foram inclusos na análise 37 pacientes (média etária: 73,2 ± 14,7 anos; APACHE II: 19,2 ± 7,3). O diagnóstico do USP demonstrou concordância com o diagnóstico final em 84% dos casos (kappa total: 0,81). As causas mais comuns de IRpA foram pneumonia (n = 17) e edema pulmonar cardiogênico (n = 15). A sensibilidade e a especificidade do USP comparado ao diagnóstico final foram de 88% e 90% para pneumonia e de 86% e 87% para edema pulmonar cardiogênico, respectivamente. CONCLUSÕES: O USP baseado no protocolo BLUE foi reproduzível por médicos com habilidades básicas em ultrassonografia e acurado para o diagnóstico de pneumonia e de edema pulmonar cardiogênico.

Diagnostic accuracy of the Bedside Lung Ultrasound in Emergency protocol for the diagnosis of acute respiratory failure in spontaneously breathing patients, / Acurácia diagnóstica do protocolo de ultrassom pulmonar à beira do leito em situações de emergência para diagnóstico de insuficiência respiratória aguda em pacientes com ventilação espontânea

Objective: Bedside lung ultrasound (LUS) is a noninvasive, readily available imaging modality that can complement clinical evaluation. The Bedside Lung Ultrasound in Emergency (BLUE) protocol has demonstrated a high diagnostic accuracy in patients with acute respiratory failure (ARF). Recently, bedside LUS has been added to the medical training program of our ICU. The aim of this study was to investigate the accuracy of LUS based on the BLUE protocol, when performed by physicians who are not ultrasound experts, to guide the diagnosis of ARF. Methods: Over a one-year period, all spontaneously breathing adult patients consecutively admitted to the ICU for ARF were prospectively included. After training, 4 non-ultrasound experts performed LUS within 20 minutes of patient admission. They were blinded to patient medical history. LUS diagnosis was compared with the final clinical diagnosis made by the ICU team before patients were discharged from the ICU (gold standard). Results: Thirty-seven patients were included in the analysis (mean age, 73.2 ± 14.7 years; APACHE II, 19.2 ± 7.3). LUS diagnosis had a good agreement with the final diagnosis in 84% of patients (overall kappa, 0.81). The most common etiologies for ARF were pneumonia (n = 17) and hemodynamic lung edema (n = 15). The sensitivity and specificity of LUS as measured against the final diagnosis were, respectively, 88% and 90% for pneumonia and 86% and 87% for hemodynamic lung edema. Conclusions: LUS based on the BLUE protocol was reproducible by physicians who are not ultrasound experts and accurate for the diagnosis of pneumonia and hemodynamic lung edema. .

Objetivo: O ultrassom pulmonar (USP) à beira do leito é uma técnica de imagem não invasiva e prontamente disponível que pode complementar a avaliação clínica. O protocolo Bedside Lung Ultrasound in Emergency (BLUE, ultrassom pulmonar à beira do leito em situações de emergência) demonstrou elevado rendimento diagnóstico em pacientes com insuficiência respiratória aguda (IRpA). Recentemente, um programa de treinamento em USP à beira do leito foi implementado na nossa UTI. O objetivo deste estudo foi avaliar a acurácia do USP baseado no protocolo BLUE, quando realizado por médicos com habilidades básicas em ultrassonografia, para orientar o diagnóstico de IRpA. Métodos: Ao longo de um ano, todos os pacientes adultos consecutivos respirando espontaneamente admitidos na UTI por IRpA foram prospectivamente inclusos. Após treinamento, 4 operadores com habilidades básicas em ultrassonografia realizaram o USP em até 20 minutos após a admissão na UTI, cegados para a história do paciente. Os diagnósticos do USP foram comparados aos diagnósticos da equipe assistente ao final da internação na UTI (padrão-ouro). Resultados: Foram inclusos na análise 37 pacientes (média etária: 73,2 ± 14,7 anos; APACHE II: 19,2 ± 7,3). O diagnóstico do USP demonstrou concordância com o diagnóstico final em 84% dos casos (kappa total: 0,81). As causas mais comuns de IRpA foram pneumonia (n = 17) e edema pulmonar cardiogênico (n = 15). A sensibilidade e a especificidade do USP comparado ao diagnóstico final foram de 88% e 90% para pneumonia e de 86% e 87% para edema pulmonar cardiogênico, respectivamente. Conclusões: O USP baseado no protocolo BLUE foi reproduzível por médicos com habilidades básicas em ultrassonografia e acurado para o diagnóstico de pneumonia e de edema pulmonar cardiogênico. .

Early fluid loading in acute respiratory distress syndrome with septic shock deteriorates lung aeration without impairing arterial oxygenation: a lung ultrasound observational study.

INTRODUCTION: The study was designed to assess the impact of fluid loading on lung aeration, oxygenation and hemodynamics in patients with septic shock and acute respiratory distress syndrome (ARDS). METHODS: During a 1-year period, a prospective observational study was performed in 32 patients with septic shock and ARDS. Cardiorespiratory parameters were measured using Swan Ganz (n = 29) or PiCCO catheters (n = 3). Lung aeration and regional pulmonary blood flows were measured using bedside transthoracic ultrasound. Measurements were performed before (T0), at the end of volume expansion (T1) and 40 minutes later (T2), consisting of 1-L of saline over 30 minutes during the first 48 h following onset of septic shock and ARDS. RESULTS: Lung ultrasound score increased by 23% at T2, from 13 at baseline to 16 (P < 0.001). Cardiac index and cardiac filling pressures increased significantly at T1 (P < 0.001) and returned to control values at T2. The increase in lung ultrasound score was statistically correlated with fluid loading-induced increase in cardiac index and was not associated with increase in pulmonary shunt or regional pulmonary blood flow. At T1, PaO2/FiO2 significantly increased (P < 0.005) from 144 (123 to 198) to 165 (128 to 226) and returned to control values at T2, whereas lung ultrasound score continued to increase. CONCLUSIONS: Early fluid loading transitorily improves hemodynamics and oxygenation and worsens lung aeration. Aeration changes can be detected at the bedside by transthoracic lung ultrasound, which may serve as a safeguard against excessive fluid loading.

Imipenem, meropenem, or doripenem to treat patients with Pseudomonas aeruginosa ventilator-associated pneumonia.

Only limited data exist on Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) treated with imipenem, meropenem, or doripenem. Therefore, we conducted a prospective observational study in 169 patients who developed Pseudomonas aeruginosa VAP. Imipenem, meropenem, and doripenem MICs for Pseudomonas aeruginosa isolates were determined using Etests and compared according to the carbapenem received. Among the 169 isolates responsible for the first VAP episode, doripenem MICs were lower (P<0.0001) than those of imipenem and meropenem (MIC50s, 0.25, 2, and 0.38, respectively); 61%, 64%, and 70% were susceptible to imipenem, meropenem, and doripenem, respectively (P was not statistically significant). Factors independently associated with carbapenem resistance were previous carbapenem use (within 15 days) and mechanical ventilation duration before VAP onset. Fifty-six (33%) patients had at least one VAP recurrence, and 56 (33%) died. Factors independently associated with an unfavorable outcome (recurrence or death) were a high day 7 sequential organ failure assessment score and mechanical ventilation dependency on day 7. Physicians freely prescribed a carbapenem to 88 patients: imipenem for 32, meropenem for 24, and doripenem for 32. The remaining 81 patients were treated with various antibiotics. Imipenem-, meropenem-, and doripenem-treated patients had similar VAP recurrence rates (41%, 25%, and 22%, respectively; P=0.15) and mortality rates (47%, 25%, and 22%, respectively; P=0.07). Carbapenem resistance emerged similarly among patients treated with any carbapenem. No carbapenem was superior to another for preventing carbapenem resistance emergence.

Aerosolized antibiotics for ventilator-associated pneumonia: lessons from experimental studies.

The aim of this review is to perform a critical analysis of experimental studies on aerosolized antibiotics and draw lessons for clinical use in patients with ventilator-associated pneumonia. Ultrasonic or vibrating plate nebulizers should be preferred to jet nebulizers. During the nebulization period, specific ventilator settings aimed at decreasing flow turbulence should be used, and discoordination with the ventilator should be avoided. The appropriate dose of aerosolized antibiotic can be determined as the intravenous dose plus extrapulmonary deposition. If these conditions are strictly respected, then high lung tissue deposition associated with rapid and efficient bacterial killing can be expected. For aerosolized aminoglycosides and cephalosporins, a decrease in systemic exposure leading to reduced toxicity is not proven by experimental studies. Aerosolized colistin, however, does not easily cross the alveolar-capillary membrane even in the presence of severe lung infection, and high doses can be delivered by nebulization without significant systemic exposure.