Introduction: Although early use of broad-spectrum antimicrobials in critically ill patients may increase antimicrobial adequacy, uncontrolled use of these agents may select for more-resistant organisms. This study investigated the effects of early use of broad-spectrum antimicrobials in critically ill patients with hospital-acquired pneumonia. Methods: We compared the early use of broad-spectrum antimicrobials plus subsequent de-escalation (DE) with conventional antimicrobial treatment (non-de-escalation, NDE) in critically ill patients with hospital-acquired pneumonia (HAP). This open-label, randomized clinical trial was performed in patients in a tertiary-care center medical intensive care unit (MICU) in Korea. Patients (n = 54) randomized to the DE group received initial imipenem/cilastatin plus vancomycin with subsequent de-escalation according to culture results, whereas patients randomized to the NDE group (n = 55) received noncarbapenem, nonvancomycin empiric antimicrobials. Results: Between November 2004 and October 2006, 109 MICU patients with HAP were enrolled. Initial antimicrobial adequacy was significantly higher in the DE than in the NDE group for Gram-positive organisms (100% versus 14.3%; P < 0.001), but not for Gram-negative organisms (64.3% versus 85.7%; P = 0.190). Mean intensive care unit (ICU) stay, and 14-day, 28-day, and overall mortality rates did not differ in the two groups. Among culture-positive patients, mortality from methicillin-resistant Staphylococcus aureus (MRSA) pneumonia was higher in the DE group, even after early administration of vancomycin. Multidrug-resistant organisms, especially MRSA, were more likely to emerge in the DE group (adjusted hazard ratio for emergence of MRSA, 3.84; 95% confidence interval, 1.06 to 13.91). Conclusions: The therapeutic advantage of early administration of broad-spectrum antimicrobials, especially with vancomycin, was not evident in this study.

Purpose: Anticoagulation is mandatory for extracorporeal membrane oxygenation (ECMO), but systemic heparinization, which has been most widely used as an anticoagulant, has been associated with bleeding complications. The present study reviewed the usefulness and safety of nafamostat mesilate as a regional anticoagulant in patients with bleeding complication during ECMO. Methods: We retrospectively reviewed the record of 13 cases. The nafamostat mesilate dose was regulated to maintain the activated clotting time (ACT) or activated partial thromboplastin time (aPTT) values within an adequate range at the ECMO reinfusion route. ACT or aPTT values in blood samples from the ECMO circuit and from the patients were measured simultaneously and consecutively. Results: We measured the ACT value in 6 cases and aPTT in 7 cases. The bleeding complications were treated in 11 cases. When we compared the difference in 2 anticoagulation values (ACT and aPTT) between the 2 blood samples, one taken from ECMO and the other from patients, mean anticoagulation values of blood from patients were lower than those from ECMO circuit in 11 cases. With respect to the type of ECMO reinfusion mode, the difference was significant only in veno-arterial mode ECMO group (p<0.001). Conclusions: Nafamostat mesilate, with which we can reduce anticoagulation values of patient to a safe level without losing the ECMO anticoagulation values is expected to be useful as a regional anticoagulant in patients with bleeding complications or a high risk of bleeding during ECMO.

Background: Although there have been studies regarding the role of nebulized colistin as adjunctive therapy of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB), a paucity of information on the efficacy of nebulized colistin as monotherapy is available. Methods: We retrospectively reviewed 219 patients with VAP caused by CRAB treated with either intravenous (n=93) or nebulized colistin (n=126), from March 2010 to November 2015. Factors related to clinical failure was assessed using propensity-score-matched analysis. Results: Of 219 patients, 39 patients from each group (n=78) were matched after covariate adjustment using propensity score. There were no significant differences in baseline characteristics as well as the rates of clinical failure between the propensity-score-matched groups [Odds ratio (OR), 0.48; 95% confidence interval (CI), 0.19–1.19; P=0.11], while a significantly lower rate of acute kidney injury (AKI) during colistin therapy (18% vs. 49%, P=0.004) was observed in nebulized colistin group. In addition, multivariable analysis revealed that nebulized colistin did not significantly alter the rate of clinical failure [adjusted odds ratio (aOR), 0.36; 95% CI, 0.12–1.09; P=0.070]. Instead, medical intensive care unit (ICU) admission (aOR, 7.14; 95% CI, 1.60–32.00; P=0.010), and septic shock (aOR, 3.93; 95% CI, 1.27–12.17; P=0.018) were independent risk factors for clinical failure. Conclusions: Our findings suggest that nebulized colistin-based therapy, even without concurrent administration of intravenous colistin, may be an effective and safe treatment option for VAP caused by CRAB.

Background: Anticoagulation during extracorporeal membrane oxygenation (ECMO) usually is required to prevent thrombosis. The aim of this study was to investigate the usefulness of nafamostat mesilate (NM) as a regional anticoagulant during veno-arterial ECMO (VA-ECMO) treatment. Methods: We retrospectively reviewed the medical records of 16 patients receiving VA-ECMO and NM from January 2017 to June 2020 at Haeundae Paik Hospital. We compared clinical and laboratory data, including activated partial thromboplastin time (aPTT), which was measured simultaneously in patients and the ECMO site, to estimate the efficacy of regional anticoagulation. Results: The median patient age was 68.5 years, and 56.3% of patients were men. Cardiovascular disease was the most common primary disease (75.0%) requiring ECMO treatment, followed by respiratory disease (12.5%). The median duration of ECMO treatment was 7.5 days. Among 16 patients, seven were switched to NM after first using heparin as an anticoagulation agent, and nine received only NM. When comparing aPTT values in the NM group between patients and the ECMO site, that in patients was significantly lower than that at the ECMO site (73.57 vs. 79.25 seconds; P=0.010); in contrast, no difference was observed in the heparin group. Conclusions: NM showed efficacy as a regional anticoagulation method by sustaining a lower aPTT value compared to that measured at the ECMO site. NM should be considered as a safer regional anticoagulation method in VA-ECMO for patients at high risk of bleeding.

Sepsis is a life-threatening condition and remains a major cause of mortality. The aim of this study was to evaluate the role of biomarkers in the diagnosis of sepsis and septic shock in patients admitted to the emergency department (ED). Medical records of patients who underwent measurement of serum biomarkers including lactic acid, C-reactive protein, procalcitonin (PCT), and presepsin in the ED between May 2019 and May 2020 were retrospectively reviewed. Patients were subdivided into 3 groups; non-sepsis, sepsis, and septic shock according to the new definition using the sequential organ failure assessment score. The mean age was 69.3 years, and 55.8% of the study population was female. Of 249 subjects, 98 patients confined to sepsis group, and 35.7% of them were septic shock. In the multivariable analysis, a high level of PCT was an independent predictor of sepsis (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.006–1.051; P = .011) along with a simplified acute physiology score III (SAPS III) (OR, 1.082; 95% CI, 1.062–1.103, P < .001). PCT was also an independent risk factor for septic shock (OR, 1.043; 95% CI, 1.016–1.071, P = .02). In the receiver operating characteristic curve analysis, the area under the curve of PCT to predict sepsis and septic shock were 0.691 (P < .001) and 0.734 (P < .001), respectively. The overall 30-days mortality rate was 8.8%, and the mortality rate was significantly higher in the sepsis group (sepsis vs non-sepsis, 15.3% vs 4.6%; P = .004). In the multivariate Cox analysis, a higher level of lactic acid (hazard ratio [HR], 1.328; 95% CI, 1.061–1.663, P = .013), predisposing chronic pulmonary diseases (HR, 7.035; 95% CI, 1.687–29.341, P = .007), and a high SAPSIII value (HR, 1.046; 95% CI, 1.015–1.078, P = .003) were independent risk factors for mortality in sepsis patients. PCT was a useful biomarker for predicting sepsis and septic shock in the ED. A higher level of lactic acid, predisposing chronic pulmonary diseases, and a high SAPS III score were associated with a greater mortality risk in patients with sepsis.

Background: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with chronic, progressive lung fibrosis with a poor prognosis. Recent studies have reported a high prevalence of obstructive sleep apnea (OSA) in IPF patients and an association with poor prognosis. This study aimed to evaluate the prevalence, risk factors, and clinical effects on mortality of OSA in patients with IPF. Methods: Clinical data were retrospectively analyzed in 167 patients with IPF at Haeundae-Paik Hospital, Republic of Korea. A type 4 portable device was used to monitor OSA, and an apnea-hypopnea index of 5 events per sleep hour and above was diagnosed as OSA. Results: The mean follow-up period and age were 26.9 months and 71.4 years, respectively, with male predominance. OSA was confirmed in 108 patients (64.7%). Mild OSA was the most common (62.1%). Independent risk factors for OSA in the multivariate logistic regression analysis were age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02–1.13, p = 0.007), body weight (OR 1.05, 95% CI 1.02–1.09, p = 0.002), and risk based on the Berlin questionnaire (OR 2.76, 95% CI 1.12–6.80, p = 0.028). Shorter six-minute walk distance (6MWD) (hazard ratio [HR] 1.00, 95% CI: 1.00–1.00, p < 0.001), acute exacerbation (AE) (HR 13.83, 95% CI: 5.71–33.47, p < 0.001), and higher percentage of cumulative time with oxygen saturation below 90% in total sleep time (HR 1.08, 95% CI: 1.02–1.14, p = 0.007) were risk factors for mortality in IPF patients in the Cox regression analysis. Conclusion: Approximately two-thirds of the IPF patients had OSA. Older age, higher body weight, and high risk based on the Berlin questionnaire were independent risk factors for OSA in IPF patients. Shorter 6MWD, experience of AE, and night hypoxemia during sleep were associated with a higher risk of mortality in patients with IPF.