Kuo-Chen Cheng

In vitro efficacy of fosfomycin-containing regimens against methicillin-resistant Staphylococcus aureus in biofilms

OBJECTIVES To compare the in vitro antibacterial efficacy of antistaphylococcal antibiotics in combination with fosfomycin or rifampicin, using a biofilm model. METHODS The antibacterial activities of fusidic acid, linezolid, vancomycin, teicoplanin, rifampicin, minocycline, fosfomycin and tigecycline, individually and in fosfomycin or rifampicin combinations, were measured against planktonic or biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) with susceptible and resistant breakpoint concentrations (SBCs and RBCs, respectively), using the MTT-staining method and by counting the number of cfu in the biofilms. RESULTS Linezolid alone at its SBC, and fosfomycin, linezolid, minocycline and tigecycline at their RBCs, exhibited killing effects on biofilm-embedded MRSA (P < 0.0001). Of the eight fosfomycin combinations studied, fosfomycin combined with linezolid, minocycline, vancomycin or teicoplanin at their respective SBCs, exhibited enhanced antibacterial activities (P < 0.0001) when compared with the control group, and outperformed rifampicin combinations (P < 0.01). The killing effects of fosfomycin combinations at their respective RBCs were better than those at their respective SBCs (P < 0.05). Significantly enhanced killing effects were observed with fosfomycin in combination with vancomycin or teicoplanin, compared with vancomycin or teicoplanin alone. For 10 randomly selected MRSA isolates, the results of colony counting in biofilms were comparable with those of the MTT-staining method. CONCLUSIONS Fosfomycin enhanced the activities of linezolid, minocycline, vancomycin and teicoplanin. These combinatorial treatments were even better than rifampicin combination regimens, and may provide therapeutic advantages in catheter-related or prosthetic joint infections.

Epidemiology and mortality of hip fracture among patients on dialysis: Taiwan National Cohort Study

Chronic kidney disease increases the risk for hip fractures. Hip fractures are associated with increased mortality, decreased quality of life, and higher economic burden. To determine whether dialysis modality is associated with a higher incidence of hip fractures in patients with end-stage renal disease (ESRD), we used the Taiwan National Health Insurance Research Database to examine the records of 51,473 patients who began dialysis between 1999 and 2005. The patients were followed until death, transplantation, dialysis cessation, or 31 December 2008. The follow-up period was (mean±SD) 4.14±2.48 years. The cumulative incidence rate of hip fracture was calculated using Kaplan-Meier methods. Predictors of hip fracture were determined using Cox models. During the study period, 1903 patients had a hip fracture. The overall incidence rate of hip fracture was 89.21/10,000 patient-years. Patients on hemodialysis (HD) had a 31% higher incidence of hip fracture than those on peritoneal dialysis (PD) (HR 1.31, 95% CI: 1.01-1.70). Patients ≥65 years old had more than 13 times the risk of a hip fracture than did those 18-44 years old (HR: 13.65; 95% CI: 10.12-18.40). Other factors that increased the risk of a hip fracture were a prior hip fracture (HR: 1.44; 95% CI: 1.15-1.80), osteoporosis (HR: 1.24; 95% CI: 1.07-1.45), DM (HR: 1.66; 95% CI: 1.51-1.83), and liver cirrhosis (HR: 1.37, 95% CI: 1.15-1.64). The overall in-hospital mortality rate was 3.2%. The cumulative survival rates after a hip fracture were 74.6% at one year and only 29.6% at seven years. Our findings supported the notion that being on HD is a risk for hip fracture. Additionally, old age, female gender, a prior hip fracture, osteoporosis, DM and liver cirrhosis were also risk factors for hip fracture in patients with ESRD and undergoing dialysis.

The outcomes and prognostic factors of patients requiring prolonged mechanical ventilation

The aims of this study were to investigate the outcomes of patients requiring prolonged mechanical ventilation (PMV) and to identify risk factors associated with its mortality rate. All patients admitted to the respiratory care centre (RCC) who required PMV (the use of MV ≥21 days) between January 2006 and December 2014 were enrolled. A total of 1,821 patients were identified; their mean age was 69.8 ± 14.2 years, and 521 patients (28.6%) were aged >80 years. Upon RCC admission, the APACHE II scores were 16.5 ± 6.3, and 1,311 (72.0%) patients had at least one comorbidity. Pulmonary infection was the most common diagnosis (n = 770, 42.3%). A total of 320 patients died during hospitalization, and the in-hospital mortality rate was 17.6%. A multivariate stepwise logistic regression analysis indicated that patients were more likely to die if they who were >80 years of age, had lower albumin levels (<2 g/dl) and higher APACHE II scores (≥15), required haemodialysis, or had a comorbidity. In conclusion, the in-hospital mortality for patients requiring PMV in our study was 17%, and mortality was associated with disease severity, hypoalbuminaemia, haemodialysis, and an older age.

The Outcomes and Prognostic Factors of the Very Elderly Requiring Prolonged Mechanical Ventilation in a Single Respiratory Care Center

AbstractThis study investigated the outcomes and the prognostic factors among the very elderly (patients ≥80 years old) requiring prolonged mechanical ventilation (PMV).Between 2006 and 2014, all of the very elderly patients of age 80 or more transferred to respiratory care center (RCC) of a tertiary medical center were retrospectively identified, and only patients who used mechanical ventilation (MV) for >3 weeks were included in this study.A total of 510 very elderly patients undergoing PMV were identified. The mean age of the patients was 84.3 ± 3.3 years, and it ranged from 80 to 96 years. Male comprised most of the patients (n = 269, 52.7%), and most of the patients were transferred to RCC from medical ICU (n = 357, 70.0%). The APACHE II scores on RCC admission was 17.6 ± 6.0. At least 1 comorbidity was found in 419 (82.2%) patients. No significant differences of gender, disease severity, diagnosis, dialysis, laboratory examinations, comorbidities, and outcome were found between octogenarians (aged 80–89) and nonagenarians (aged ≥ 90). The overall in-hospital mortality rate was 21.8%. In the multivariate analysis, patients who had APACHE II score ≥ 15(odds ratio [OR], 2.30, 95% confidence interval [CI], 1.36–3.90), or albumin ⩽ 2 g/dL (OR, 3.92, 95% CI, 2.17–7.01) were more likely to have significant in-hospital mortality (P < 0.05).The in-hospital mortality rate of the very elderly PMV patients in our RCC is 21.8%, and poor outcomes in this specific population were found to be associated with a higher APACHE II score and lower albumin level.

Early Mobilization Reduces Duration of Mechanical Ventilation and Intensive Care Unit Stay in Patients With Acute Respiratory Failure

OBJECTIVE To evaluate the effects of a quality improvement program to introduce early mobilization on the outcomes of patients with mechanical ventilation (MV) in the intensive care unit (ICU). DESIGN A retrospective observational study. SETTING Nineteen-bed ICU at a medical center. PARTICIPANTS Adults patients with MV (N=153) admitted to a medical ICU. INTERVENTIONS A multidisciplinary team (critical care nurse, nursing assistant, respiratory therapist, physical therapist, patients family) initiated the protocol within 72 hours of MV when patients become hemodynamically stable. We did early mobilization twice daily, 5d/wk during family visits (30min each time), and cooperated with family, if possible. MAIN OUTCOME MEASURES MV duration, rate of successful weaning, and length of ICU and hospital stay. RESULTS We enrolled 63 patients in the before protocol group and 90 in the after protocol group. The 2 groups were well matched in age, sex, body height, body weight, body mass index, disease severity, cause of intubation, number of comorbidities, and most underlying diseases. After protocol group patients had shorter MV durations (4.7d vs 7.5d; P<.001) and ICU stays (6.9d vs 9.9d; P=.001) than did before protocol group patients. Early mobilization was negatively associated with the duration of MV (β=-.269; P<.002; 95% confidence interval [CI], -4.767 to -1.072), and the risk of MV for ≥7 days was lower in patients who underwent early mobilization (odds ratio, .082; 95% CI, .021-.311). CONCLUSIONS The introduction of early mobilization for patients with MV in the ICU shortened MV durations and ICU stays. A multidisciplinary team that includes the patients family can work together to improve the patients clinical outcomes.

The Ratio of Partial Pressure Arterial Oxygen and Fraction of Inspired Oxygen 1 Day After Acute Respiratory Distress Syndrome Onset Can Predict the Outcomes of Involving Patients.

AbstractThe initial hypoxemic level of acute respiratory distress syndrome (ARDS) defined according to Berlin definition might not be the optimal predictor for prognosis. We aimed to determine the predictive validity of the stabilized ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2 ratio) following standard ventilator setting in the prognosis of patients with ARDS.This prospective observational study was conducted in a single tertiary medical center in Taiwan and compared the stabilized PaO2/FiO2 ratio (Day 1) following standard ventilator settings and the PaO2/FiO2 ratio on the day patients met ARDS Berlin criteria (Day 0). Patients admitted to intensive care units and in accordance with the Berlin criteria for ARDS were collected between December 1, 2012 and May 31, 2015. Main outcome was 28-day mortality. Arterial blood gas and ventilator setting on Days 0 and 1 were obtained.A total of 238 patients met the Berlin criteria for ARDS were enrolled, and they were classified as mild (n = 50), moderate (n = 125), and severe (n = 63) ARDS, respectively. Twelve (5%) patients who originally were classified as ARDS did not continually meet the Berlin definition, and a total of 134 (56%) patients had the changes regarding the severity of ARDS from Day 0 to Day 1. The 28-day mortality rate was 49.1%, and multivariate analysis identified age, PaO2/FiO2 on Day 1, number of organ failures, and positive fluid balance within 5 days as significant risk factors of death. Moreover, the area under receiver-operating curve for mortality prediction using PaO2/FiO2 on Day 1 was significant higher than that on Day 0 (P = 0.016).PaO2/FiO2 ratio on Day 1 after applying mechanical ventilator is a better predictor of outcomes in patients with ARDS than those on Day 0.

Prognostic factors and outcomes of unplanned extubation

This study investigated the prognostic factors and outcomes of unplanned extubation (UE) in patients in a medical center’s 6 intensive care units (ICUs) and calculated their mortality risk. We retrospectively reviewed the medical records of all adult patients in Chi Mei Medical Center who underwent UE between 2009 and 2015. During the study period, there were 305 episodes of UE in 295 ICU patients (men: 199 [67.5%]; mean age: 65.7 years; age range: 18–94 years). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 16.4, mean therapeutic intervention scoring system (TISS) score was 26.5, and mean Glasgow coma scale score was 10.4. One hundred thirty-six patients (46.1%) were re-intubated within 48 h. Forty-five died (mortality rate: 15.3%). Multivariate analyses showed 5 risk factors—respiratory rate, APACHE II score, uremia, liver cirrhosis, and weaning status—were independently associated with mortality. In conclusion, five risk factors including a high respiratory rate before UE, high APACHE II score, uremia, liver cirrhosis, and not in the process of being weaned—were associated with high mortality in patients who underwent UE.

Establishing predictors for successfully planned endotracheal extubation

Abstract The aim of this study was to establish predictors for successfully planned extubation, which can be followed by medical personnel. The patients who were admitted to the adult intensive care unit of a tertiary hospital and met the following criteria between January 2005 and December 2014 were collected retrospectively: intubation > 48 hours; and candidate for extubation. The patient characteristics, including disease severity, rapid shallow breath index (RSBI), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), cuff leak test (CLT) before extubation, and outcome, were recorded. The CLT was classified as 2+ with audible flow without a stethoscope, 1+ with audible flow using a stethoscope, and negative (N) with no audible flow, even with a stethoscope. Failure to extubate was defined as reintubation within 48 hours. In total, 6583 patients were enrolled and 403 patients (6.1%) had extubation failures. Male patients dominated the patient cohort (4261 [64.7%]). The mean age was 64.5±16.3 years. The overall in-hospital mortality rate was 11.3%. The extubation failure rate for females was greater than males (7.7% vs 5.3%, P < 0.001). The group of patients who failed extubation were older (66.7 ± 14.4 vs 64.3 ± 16.4, P = 0.002), had higher APACHE II scores (16.8 ± 7.6 vs 15.9 ± 7.8, P = 0.023), lower coma scales (10.3 ± 3.7 vs 10.8 ± 3.7, P = 0.07), a higher RSBI (69.9 ± 37.3 vs 58.6 ± 30.3, P < 0.001), a lower MIP, and MEP (−35.6 ± 15.3 vs −37.8 ± 14.6, P = 0.0001 and 49.6 ± 28.4 vs 58.6 ± 30.2, P < 0.001, respectively), and a higher mortality rate (25.6% vs 10.5%, P < 0.001) compared to the successful extubation group. Based on multivariate logistic regression, a CLT of 2+ (odds ratio [OR] = 2.07, P < 0.001), a MEP ≥ 55 cmH2O (OR = 1.73, P < 0.001), and a RSBI < 68 breath/min/ml (OR = 1.57, P < 0.001) were independent predictors for successful extubation. This study identified 3 independent risk factors for successful extubation after a successful breathing trial, including a CLT of 2+, a MEP ≥ 55 cmH2O, and a RSBI < 68 breath/min/ml. Furthermore, a nomogram integrating these 3 parameters, which represented the combined consideration of the upper airway patentency, cough strength, and respiratory capacity, was developed to better predict extubation success.

The prognostic value of N-terminal proB-type natriuretic peptide in patients with acute respiratory distress syndrome

We investigated whether N-terminal proB-type natriuretic peptide (NT-proBNP) predicts the prognosis of patients with acute respiratory distress syndrome (ARDS). Between December 1, 2012, and May 31, 2015, this observational study recruited patients admitted to our tertiary medical center who met the Berlin criteria for ARDS and who had their NT-proBNP measured. The main outcome was 28-day mortality. We enrolled 61 patients who met the Berlin criteria for ARDS: 7 were classified as mild, 29 as moderate, and 25 as severe. The median APACHE II scores were 23 (interquartile range [IQR], 18–28), and SOFA scores were 11 (IQR, 8–13). The median lung injury score was 3.0 (IQR, 2.50–3.25), and the median level of NT-proBNP was 2011 pg/ml (IQR, 579–7216). Thirty-four patients died during this study, and the 28-day mortality rate was 55.7%. Patients who die were older and had significantly (all p < 0.05) higher APACHE II scores and NT-proBNP levels than did patients who survived. Multivariate analysis identified age (HR: 1.546, 95% CI: 1.174–2.035, p = 0.0019) and NT-proBNP (HR: 1.009, 95% CI: 1.004–1.013, p = 0.0001) as significant risk factors of death. NT-proBNP was associated with poor outcomes for patients with ARDS, and its level predicted mortality.

Critical care medicine in Taiwan from 1997 to 2013 under National Health Insurance

Background Monitoring of trends in the use of the intensive care unit (ICU) and the outcomes of ICU patients is essential for the assessment of the effective use of ICU. This study aims to investigate the incidence and outcome of critical care admissions in Taiwan from 1997 to 2013. Methods Patients >18 years who had ICU admission between January 1997 and December 2013 were identified from the National Health Insurance Research Database in Taiwan. The main outcomes including ICU mortality and ICU length of stay (LOS) were measured. Results A total of 3,451,157 patients with ICU admission were identified during the study period. The mean ICU LOS was 5.9±9.0 days and the overall ICU-mortality rate was 19.8%. The mean age of the patients was 65.4 years old, 58.0% were elderly (≥65 years old), 61.1% were male. Annual incidence of ICU admissions increased from 115,754 in 1997 (age-adjusted incidence: 1,130/100,000 population) to 244,820 in 2013 (incidence: 1,483/100,000 population) (P<0.0001). The admission rate was highest for patients 75-104 years old (8,074 per 100,000 population), and lowest for those 18-44 years old (298 per 100,000 population). Among ICU admission patients, the percentage of patients ≥75 years old significantly increased from 25.2% in 1997 to 38.3% in 2013 (P<0.0001). ICU LOS remained stable during the study period, but the annual mortality rate significantly decreased from 23.0% in 1997 to 16.3% in 2013. Conclusions ICU admissions significantly increased from 1997 to 2013, especially for elderly patients, in contrast, the mortality rate of ICU patients significantly declined with time. In addition, the ICU LOS did not change during the study period.