We evaluated the pharmacokinetic profile of ciprofloxacin and its penetration into bronchial secretions of critically ill patients with chronic obstructive pulmonary disease (COPD). Twenty-five mechanically ventilated patients with severe COPD who were suffering from an acute, infectious exacerbation were included in this prospective, open-label study. All subjects received a 1-hour intravenous infusion of 400 mg ciprofloxacin every 8 h. Serial blood and bronchial secretion samples were obtained at steady state, and concentrations were determined using high-performance liquid chromatography. The pharmacodynamic parameters that are associated with the efficacy of fluoroquinolones against Gram-negative pathogens were also calculated. The mean peak (maximum) concentration (C_max) and trough (minimum) concentration in plasma were 5.37 ± 1.57 and 1 ± 0.53 mg/liter, respectively. Mean values for volume of distribution, clearance, half-life, and area under the curve from 0 to 24 h (AUC_0–24) were 169.87 ± 84.11 liters, 26.96 ± 8.86 liters/h, 5.35 ± 2.21 h, and 47.41 ± 17.02 mg · h/liter, respectively. In bronchial secretions, a meanC_maxof 3.08 ± 1.21 mg/liter was achieved in 3.12 ± 1.01 h, and the penetration ratio was 1.16 ± 0.59. The target of AUC_0–24/MIC of ≥125 was attained in all patients, in the majority of them (76%), and in none at MICs of 0.125, 0.25, and 1 μg/ml, respectively. Slightly better results were obtained for the ratioC_max/MIC of ≥10. In conclusion, ciprofloxacin demonstrates excellent penetration into bronchial secretions. There is wide interindividual variability in its pharmacokinetic parameters in critically ill COPD patients and inadequate pharmacodynamic exposure against bacteria with MICs of ≥0.5 μg/ml.

The purpose of the study was to evaluate painful procedures in ICU patients and to investigate their effect as well as the role of analgesia in the outcome. We measured pain level and vital signs before, during and after potentially painful procedures by using the Behavioral Pain Scale (BPS) and the Critical Care Pain Observation Tool (CPOT). We analyzed the correlation of these measurements and of analgesia with the outcome. Twenty-eight patients were subjected to 160 stimuli. There were statistically significant differences in pain scores and most vital signs between the different timepoints (before-during, during-after). Most of them were significantly correlated with each other. Physiotherapy proved to be the most painful procedure. Regarding the outcome, the administration of extra analgesia predicted less days of mechanical ventilation (p = 0.015) and of ICU stay (p = 0.016). The higher change in BPS was correlated with more days of mechanical ventilation [B (95% CI) = 3.640 (1.001–6.280), p = 0.007] and of ICU stay [B (95% CI) = 3.645 (1.035–6.254), p = 0.006]. The higher change in CPOT and the nonuse of extra analgesia were related to increased mortality [OR (95% CI) = 1.492 (1.107–2.011), p = 0.009 and OR (95% CI) = 2.626 (1.013–6.806), p = 0.047]. Increased pain in ICU patients was successfully assessed by the BPS and CPOT and correlated to worse outcomes, which the administration of extra analgesia might improve.

(2018). Changes in the microbial flora in patients of a Greek intensive care unit over two decades. Infectious Diseases: Vol. 50, No. 9, pp. 722-724.

Background: We aimed to evaluate the pharmacokinetic profile of tigecycline in plasma and its penetration to sputum in moderately ill patients with an infectious acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods: Eleven patients hospitalized with acute respiratory failure due to an acute COPD exacerbation with clinical evidence of an infectious cause received tigecycline 50 mg twice daily after an initial loading dose of 100 mg. Blood and sputum samples were collected at steady state after dose seven. Results: In plasma, mean C_max pl was 975.95 ± 490.36 ng/mL and mean C_min pl was 214.48 ±140.62 ng/mL. In sputum, mean C_max sp was 641.91 ± 253.07 ng/mL and mean C_min sp was 308.06 ± 61.7 ng/mL. In plasma, mean AUC _0–12 pl was 3765.89 ± 1862.23 ng*h/mL, while in sputum mean AUC _{0–12 sp} was 4023.27 ± 793.37 ng*h/mL. The mean penetration ratio for the 10/11 patients was 1.65 ± 1.35. The mean Free AUC_{0–24 pl}/MIC ratio for Streptococcus pneumoniae and Haemophilus influenzae was 25.10 ± 12.42 and 6.02 ± 2.97, respectively. Conclusions: Our findings support the clinical effectiveness of tigecycline against commonly causative bacteria in COPD exacerbations and highlight its sufficient lung penetration in pulmonary infections of moderate severity.

Background: Sepsis remains a leading cause of late mortality in critically ill burn patients. The optimal hemodynamic strategy, including vasopressor combinations, corticosteroids, and landiolol therapy, remains incompletely defined in this population. Objective: To examine factors associated with landiolol therapy, vasopressor strategies, and corticosteroid use in burn patients with vasopressor-dependent sepsis, and to evaluate their relationship with organ dysfunction and clinical outcomes. Methods: We conducted a preliminary exploratory retrospective cohort study in a specialized burn intensive care unit (ICU) over a three-year period (2022–2024). All mechanically ventilated adult burn patients who developed sepsis requiring vasopressor support during ICU stay were included. The primary exposure of interest was landiolol therapy; five outcomes were assessed for this exposure (ventilator-free days at day 28 after sepsis onset, duration of mechanical ventilation after sepsis onset, ICU length of stay after sepsis onset, acute kidney injury [AKI] after sepsis, and ICU mortality). Hydrocortisone administration and dual vasopressor therapy with norepinephrine plus vasopressin were evaluated as secondary descriptive exposures. Results: Thirty-one patients were included (mean age 55.8 ± 15.3 years; mean TBSA 40.2 ± 13.3%). ICU mortality was 35.5% (11/31). Landiolol was administered in 41.9% of patients; all treated patients were in sinus tachycardia (heart rate 111–140 beats/min), whereas all untreated patients had heart rates 0.99), ICU length of stay after sepsis onset (41 [21–62] vs. 56 [15–106.25] days; multiplicity-adjusted p > 0.99), AKI (2/13 vs. 5/18; OR 0.47, 95% CI 0.08–2.93; multiplicity-adjusted p > 0.99), and ICU mortality (6/13 vs. 5/18; OR 2.23, 95% CI 0.50–10.00; multiplicity-adjusted p > 0.99). The shorter total mechanical ventilation duration in landiolol-treated patients (24 [7–38] vs. 53 [18.75–79.75] days) reflected shorter ventilation before sepsis onset (6 [3–16] vs. 16.5 [10–36.75] days) and the competing risk of early death (six of eleven deaths occurred within 28 days of sepsis onset). Dual vasopressor therapy (25.8%) and hydrocortisone (19.4%) identified phenotypes of greater shock severity. Conclusions: In this small preliminary retrospective cohort, protocolized landiolol therapy in sinus-tachycardic patients was feasible and achieved heart-rate targets, but was not associated with detectable differences in clinical outcomes. These exploratory findings warrant adequately powered prospective studies in this population.