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Abstract Rationale In experimental pneumonia, nebulization of antibiotics provides high lung tissue concentrations and rapid bacterial killing. Objectives To assess the efficacy and safety of nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Methods Forty patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa were included in a randomized comparative phase II trial. Twenty patients infected with susceptible or intermediate strains received nebulized ceftazidime (15 mg·kg−1·3 h−1) and amikacin (25 mg·kg−1·d−1). Seventeen patients infected with susceptible strains received intravenous ceftazidime (90 mg·kg−1·d−1, continuous administration) and amikacin (15 mg·kg−1·d−1). In three patients infected with intermediate strains, amikacin was replaced by ciprofloxacin (400 mg·12 h−1). Measurements and Main Results After 8 days of antibiotic administration, aerosol and intravenous groups were similar in terms of successful treatment (70 vs. 55%), treatment failure (15 vs. 30%), and superinfection with other microorganisms (15 vs. 15%). Antibiotic-induced changes in lung aeration, determined by computed tomography, were not different between groups (increase in gas volume, 159 ± 460 vs. 251 ± 583 ml; decrease in tissue volume, –58 [–77, 25] vs. –89 [–139, 5] ml). Acquisition of per-treatment antibiotic resistance was observed exclusively in the intravenous group. In the aerosol group, four patients infected with intermediate strains were successfully treated. Nebulization induced an obstruction of the expiratory filter in three patients. The obstruction caused cardiac arrest in one patient, who fully recovered after brief cardiopulmonary resuscitation. Conclusions Nebulization and intravenous infusion of ceftazidime and amikacin provide similar efficiency for treating ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Nebulization is efficient against intermediate strains and may prevent per-treatment acquisition of antibiotic resistance.

COVID-19 pneumonia typically begins with subpleural ground glass opacities with progressive extension on computerized tomography studies. Lung ultrasound is well suited to this interstitial, subpleural involvement, and it is now broadly used in intensive care units (ICUs). The extension and severity of lung infiltrates can be described numerically with a reproducible and validated lung ultrasound score (LUSS). We hypothesized that LUSS might be useful as a tool to non-invasively monitor the evolution of COVID-19 pneumonia at the bedside. LUSS monitoring was rapidly implemented in the management of our COVID-19 patients with RT-PCR-documented COVID-19. The LUSS was evaluated repeatedly at the bedside. We present a graphic description of the course of LUSS during COVID-19 in 10 consecutive patients admitted in our intensive care unit with moderate to severe ARDS between March 15 and 30th. LUSS appeared to be closely related to the disease progression. In successfully extubated patients, LUSS decreased and was lower than at the time of intubation. LUSS increased inexorably in a patient who died from refractory hypoxemia. LUSS helped with the diagnosis of ventilator-associated pneumonia (VAP), showing an increased score and the presence of new lung consolidations in all 5 patients with VAPs. There was also a good agreement between CT-scans and LUSS as for the presence of lung consolidations. In conclusion, our early experience suggests that LUSS monitoring accurately reflect disease progression and indicates potential usefulness for the management of COVID-19 patients with ARDS. It might help with early VAP diagnosis, mechanical ventilation weaning management, and potentially reduce the need for X-ray and CT exams. LUSS evaluation is easy to use and readily available in ICUs throughout the world, and might be a safe, cheap and simple tool to optimize critically ill COVID-19 patients care during the pandemic.

Purpose To assess the impact of lung ultrasound (LU) on clinical decision making in mechanically ventilated critically ill patients. Methods One hundred and eighty-nine patients took part in this prospective study. The patients were enrolled in the study when LU was requested by the primary physician for (1) unexplained deterioration of arterial blood gases and (2) a suspected pathologic entity [pneumothorax, significant pleural effusion (including parapneumonic effusion, empyema, or hemothorax), unilateral atelectasis (lobar or total), pneumonia and diffuse interstitial syndrome (pulmonary edema)]. Results Two hundred and fifty-three LU examinations were performed; 108 studies (42.7 %) were performed for unexplained deterioration of arterial blood gases, and 145 (57.3 %) for a suspected pathologic entity (60 for pneumothorax, 34 for significant pleural effusion, 22 for diffuse interstitial syndrome, 15 for unilateral lobar or total lung atelectasis, and 14 for pneumonia). The net reclassification index was 85.6 %, indicating that LU significantly influenced the decision-making process. The management was changed directly as a result of information provided by the LU in 119 out of 253 cases (47 %). In 81 cases, the change in patient management involved invasive interventions (chest tube, bronchoscopy, diagnostic thoracentesis/fluid drainage, continuous venous–venous hemofiltration, abdominal decompression, tracheotomy), and in 38 cases, non-invasive (PEEP change/titration, recruitment maneuver, diuretics, physiotherapy, change in bed position, antibiotics initiation/change). In 53 out of 253 cases (21 %), LU revealed findings which supported diagnoses not suspected by the primary physician (7 cases of pneumothorax, 9 of significant pleural effusion, 9 of pneumonia, 16 of unilateral atelectasis, and 12 of diffuse interstitial syndrome). Conclusion Our study shows that LU has a significant impact on decision making and therapeutic management.

Background The use of multiplex PCR to shorten time to identification of pathogens and their resistance mechanisms for patients with ventilator-associated pneumonia (VAP) is attractive, but poorly studied. The multiplex PCR–based Unyvero pneumonia cartridge assay can directly identify 20 bacteria and one fungus, amongst the most frequently causing VAP, and 19 of their resistance markers in clinical specimens (bronchoalveolar lavage or tracheal aspirate), with a turnaround time of 4–5 h. We performed this study to evaluate the concordance between the multiplex PCR–based Unyvero pneumonia cartridge assay and conventional microbiological techniques to identify pathogens and their resistance mechanisms in patients with VAP. Methods All patients suspected of having VAP (January 2016 to January 2019), who underwent fiberoptic bronchoscopy with bronchoalveolar lavage fluid (BALF) and whose BALF microscopy examination revealed intracellular bacteria, were included. BALF conventional cultures (gold standard), antimicrobial susceptibility testing and processing for the Unyvero pneumonia cartridge were done. Culture and Unyvero results were compared. Results Compared to cultures of the 93 samples processed for both techniques, Unyvero correctly identified pathogens in 68 (73%) proven VAP episodes, was discordant for 25 (27%), detected no pathogen in 11 and overdetected a not otherwise found pathogen in six. For the eight remaining discordant results, the pathogen responsible for VAP was not included in the Unyvero cartridge panel or it grew at a non-significant level in culture. Amongst the 31 (33%) resistance mechanism discordances observed, 22 were resistance detection failures and 24 concerned Pseudomonas aeruginosa . Conclusions Compared to conventional microbiological cultures, the Unyvero pneumonia cartridge had poor diagnostic performance: it correctly identified pathogens and their resistance mechanisms in 73% and 67% of VAP cases, respectively. The lack of performance on the resistance mechanism was more pronounced when the pathogen detected was a Pseudomonas aeruginosa .

In the coronavirus disease-2019 (COVID-19) era, point-of-care lung ultrasound (LUS) has attracted increased attention. Prospective studies on LUS for the assessment of pneumonia in adult patients were extensively carried out for more than 10 years before this era. None of these prospective studies attempted to differentiate bacterial and viral pneumonia in adult patients using LUS. The majority of studies considered the LUS examination to be positive if sonographic consolidations or multiple B-lines were observed. Significant differences existed in the accuracy of these studies. Some studies revealed that LUS showed superior sensitivity to chest X-ray. These results indicate that point-of-care LUS has the potential to be an initial imaging modality for the diagnosis of pneumonia. The LUS diagnosis of ventilator-associated pneumonia in intensive care units is more challenging in comparison with the diagnosis of community-acquired pneumonia in emergency departments due to the limited access to the mechanically ventilated patients and the high prevalence of atelectasis. However, several studies have demonstrated that the combination of LUS findings with other clinical markers improved the diagnostic accuracy. In the COVID-19 era, many case reports and small observational studies on COVID-19 pneumonia have been published in a short period. Multiple B-lines were the most common and consistent finding in COVID-19 pneumonia. Serial LUS showed the deterioration of the disease. The knowledge and ideas on the application of LUS in the management of pneumonia that are expected to accumulate in the COVID-19 era may provide us with clues regarding more appropriate management.

Ventilator-associated pneumonia (VAP) is a type of nosocomial pneumonia developing in patients who are mechanically ventilated for ≥48 hours. Lung ultrasound (LUS) has been shown to be useful in evaluating various pathologic pulmory conditions. We aimed to study the utility of chest ultrasound in the diagnosis of VAP in a critical care unit. This was a monocentric, prospective observatiol study carried out in the intensive care unit (ICU) of our institution. On clinical suspicion of VAP, patients were subjected to ultrasound chest (lung) examition, which was done in a supine position in six areas of each hemithorax on the same day, and endotracheal aspirate (ETA) for gram stain and aerobic culture was sent within 6 hours. The fil diagnosis of VAP was made when the ETA culture was positive (>105 CFU/mL). Days of mechanical ventilation, ICU stay, hospital stay, and mortality were separately recorded for monitoring outcomes. Diagnostic performance of risk factors for VAP was alyzed by parameters like sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio (positive and negative). Concerning LUS signs, subpleural consolidations >2 had a sensitivity of 96% and specificity of 63% with an odds ratio of 51.43 in predicting VAP. A dymic air bronchogram within consolidation was seen in 45% of patients with a sensitivity and specificity of 29% and 73%, respectively. A clinical LUS score >2 had a sensitivity of 100% in predicting VAP. LUS is a robust diagnostic tool with high sensitivity for diagnosing VAP. Clinical trials are needed to study whether LUS can be used as a tool for early diagnosis of VAP, which will help in the timely introduction of antibiotics.

Here, we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and P. aeruginosa specific, and bystander activated, which may have contributed to this patient’s persistent symptoms and radiological changes.

BackgroundVentilator-associated pneumonia (VAP) is a clinical form of hospital-associated pneumonia, which may develop within 48 h in patients on mechanical ventilation who had no pre-existing pneumonia at the time of intubation.ObjectiveThe objective of this study was to compare the incidence of VAP among patients who started receiving treatment with heat and moisture exchanger (HME) filters and heated humidifiers (HHs) for mechanical ventilation.MethodsPatients who were on the first day of intubation, did not have pre-intubation pneumonia, presented to the healthcare centre with no infections at the time of presentation, were not on antibiotic treatment for pulmonary infections and did not have evidence of infiltration with chest radiography were included in the study. Data were evaluated using Fischer’s exact, Mann–Whitney’s U and t tests.ResultsThe patients in the HME filter and HHs groups had a mean age of 47.9 ± 2.2 and 44.5 ± 2.1 years, respectively. Infiltration on chest radiography was identified on day 6.33 for the patients in the HME filter group and on day 5.8 in the HHs group. Patients using HME filters and HHs did not differ significantly with regard to the day of mechanical ventilation and number of days hospitalized (p > 0.5). Comparison of the two groups with regard to presence of fever during the first 24 h, however, demonstrated higher than expected values for the patients using HHs, with a significant difference (p = 0.001).ConclusionThere were no significant differences between the groups on HME filters and heated humidifiers in terms of infection development; although pulmonary radiography showed delayed average days to infiltration development for subjects using HME filters.

ObjectivesTo evaluate whether the performance of the modified Clinical Pulmonary Infection Score (CPIS) for diagnosis of ventilator-associated pneumonia (VAP) could be improved by incorporating procalcitonin (PCT), lactate and a standardised lung ultrasound score (LUS).DesignProspective observational study.SettingInternal medicine and respiratory intensive care units (ICUs) of a tertiary care centre in India over 18 months.Participants97 adult patients receiving invasive mechanical ventilation for 48 hours or more with suspected VAP.Primary and secondary outcome measuresThe primary outcome was the diagnostic accuracy (area under the receiver operating characteristic curve (AUC)) of the integrated score compared with a reference standard of quantitative bronchoalveolar lavage culture (>104 CFU/mL). Secondary outcomes included ICU length of stay and 14-day mortality.ResultsOf the 97 patients, 70 (72.2%) were culture positive. The modified CPIS alone demonstrated limited diagnostic utility (AUC 0.686). In contrast, the novel 4-point Lactate-Lung Ultrasound-Procalcitonin-Clinical Pulmonary Infection Score (LPCPIS) score (integrating CPIS >5, lactate >2.15 mmol/L, PCT >1.3 ng/mL and LUS >14) achieved excellent discriminatory ability (AUC 0.919, 95% CI 0.844 to 0.976). At a cut-off of ≥2, the score yielded 95.7% sensitivity and 77.8% specificity. Crucially, a 4-point LPCPIS bedside score of ≤1 was associated with a highly diminished probability of VAP, yielding a negative predictive value of 100% in this cohort. In comparison, a score ≥3 strongly indicated a high likelihood of VAP, with a positive predictive value of 96.5% and specificity of 92.6%, pending definitive microbiological confirmation.ConclusionsThe novel 4-point LPCPIS bedside score demonstrates significant diagnostic superiority over the traditional modified CPIS (AUC 0.919 vs 0.686). By integrating bedside lung ultrasound with biomarkers, this simplified pragmatic tool provides impressive discriminatory power, allowing clinicians in resource-limited settings to reliably assess probability of VAP and guide early antimicrobial decision-making while awaiting definitive microbiological cultures.

Lung ultrasonography (LUS) is a well-established technique in adult critical care, but remains insufficiently recognizedin children and infants. The purpose of this short review is to describe the rapidly growing field of point-of-care LUS in critically ill and injured children.