Ceftriaxone resistance and adequacy of initial antibiotic therapy in community onset bacterial pneumonia.

ABSTRACT: Much remains unknown about the impact of initial antibiotic adequacy on mortality in community onset bacterial pneumonia (COBP). Therefore, we performed a study to determine how the adequacy of initial antibiotic therapy affects in-hospital mortality for patients with COBP.We carried out a retrospective cohort study among the 11 BJC Healthcare community and academic hospitals in Missouri and Illinois. The electronic medical records for BJC Healthcare were queried to obtain a set of patient admissions with culture positive (respiratory or blood) COBP admitted from January 1, 2016 through December 31, 2019. Patients with COBP required an International Classification of Diseases (ICD)-10 diagnostic code for pneumonia, admission to the hospital through an emergency department, a chest radiograph with an infiltrate, an abnormal white blood cell count or temperature, an order for 1 or more new antibiotics, and a positive respiratory or blood culture. Antibiotic selection was deemed adequate if the patient had organisms susceptible to at least one of the antibiotics received according to in vitro testing using standard laboratory breakpoints.Among 36,645 screened pneumonia admissions, 1843 met criteria for culture positive COBP. Eight hundred nineteen (44.4%) had ceftriaxone-resistant (CTX-R) organisms and 1024 had ceftriaxone-sensitive (CTX-S) organisms. The most common CTX-R pathogens were methicillin resistant Staphylococcus aureus (46.9%), Pseudomonas species (38.4%), and Escherichia coli (4.5%). On the day of admission 71% of all patients were given adequate antibiotic treatment (62.2% of CTX-R and 77.9% of CTX-S). Unnecessarily broad initial treatment was administered to 57.1% of CTX-S patients. In a logistic regression model accounting for comorbidities and severity of illness, inadequate therapy on the day of admission was associated with higher in-hospital mortality (P = .005). Among CTX-S patients who were adequately treated, initial use of unnecessarily broad antibiotics was associated with increased in-hospital mortality (P = .003).Ceftriaxone resistance was common in this cohort of culture positive COBP patients. Inappropriate coverage on day of admission was associated with greater likelihood of in-hospital mortality.

Factors associated with tracheostomy decannulation in patients with severe traumatic brain injury.

OBJECTIVE: To assess variables associated with decannulation in patients with traumatic brain injury (TBI). PARTICIPANTS: 79 patients with TBI requiring tracheostomy and ICU admission from January 1st to December 31st, 2014. DESIGN: Retrospective analysis. MEASURES: Patients decannulated prior to 90 days were compared with patients who remained cannulated. Two Cox Proportional Hazards models were used to predict decannulation using variables prior to tracheostomy and throughout hospitalization. RESULTS: Median time to decannulation was 37 days (Interquartile Range [IQR] 29-67). Variables prior to tracheostomy associated with decannulation included diabetes (HR, 0.15; 95% CI, 0.03-0.84; p =.03), craniotomy (HR, 0.25; 95% CI, 0.06-1.02; p =.05) and acute kidney injury (AKI) (HR, 0.06; 95% CI, 0.01-0.48; p =.01). Variables present throughout hospitalization included age (HR, 1.12; 95% CI, 1.01-1.21; p =.03), ventilator days (HR, 0.74; 95% CI, 0.57-0.95; p =.02), reintubation (HR, 0.07; 95% CI, 0.01-0.64; p =.02), aspiration (HR, 0.01; 95% CI, 0.0-0.29, p =.01), craniotomy (HR, 0.004; 95% CI, 0.0-0.39; p =.02) and AKI (HR, 0.0; 95% CI, 0.0-0.21; p =.01). CONCLUSION: The presence of diabetes, craniotomy and acute kidney injury may inform the conversation surrounding chances for decannulation prior to tracheostomy.

Inpatient Complications Predict Tracheostomy Better than Admission Variables After Traumatic Brain Injury.

BACKGROUND: Data regarding who will require tracheostomy are lacking which may limit investigations into therapeutic effects of early tracheostomy. METHODS: We performed an observational study of adult traumatic brain injury (TBI) patients requiring intensive care unit (ICU) admission for ≥ 72 h and mechanical ventilation for ≥ 24 h between January 2014 and December 2014 at a level 1 trauma center. Patients who had life-sustaining measures withdrawn were excluded. Multivariable logistic regression analyses were used to assess admission and inpatient factors associated with receiving a tracheostomy and to develop predictive models. Inpatient complications prior to day 7 were used to standardize data collection for patients with and without tracheostomy. Patients who received tracheostomy prior to day 7 were excluded from analysis. RESULTS: In total, 209 patients (78% men, mean 48 years old, median Glasgow Coma Scale score (GCS) 8) met study criteria with tracheostomy performed in 94 (45%). Admission predictors of tracheostomy included GCS, chest tube, Injury Severity Score, and Marshall score. Inpatient factors associated with tracheostomy included the requirement for an external ventricular drain (EVD), number of operations, inpatient dialysis, aspiration, GCS on day 5, and reintubation. Multiple logistic regression analysis demonstrated that the number of operation room trips (adjusted odds ratio [AOR], 1.75; 95% CI, 1.04-2.97; P = 0.036), reintubation (AOR, 8.45; 95% CI, 1.91-37.44; P = .005), and placement of an EVD (AOR, 3.48; 95% CI, 1.27-9.58; P = .016) were independently associated with patients undergoing tracheostomy. Higher GCS on hospital day 5 (AOR, 0.52; 95% CI, 0.40-0.68; P < 0.001) was protective against tracheostomy. A model of inpatient variables only had a stronger association with tracheostomy than one with admission variables only (ROC AUC 0.93 vs 0.72, P < 0.001) and did not benefit from the addition of admission variables (ROC AUC 0.93 vs 0.92, P = 0.78). CONCLUSION: Potentially modifiable inpatient factors have a stronger association with tracheostomy than do admission characteristics. Multicenter studies are needed to validate the results.

Post-discharge adherence with venous thromboembolism prophylaxis after orthopedic trauma: Results from a randomized controlled trial of aspirin versus low molecular weight heparin.

BACKGROUND: Orthopedic trauma patients are often treated with venous thromboembolism (VTE) chemoprophylaxis with aspirin or low molecular weight heparin (LMWH) after discharge from their index admission, but adherence patterns are not known. We hypothesized that overall adherence would be moderate and greater with aspirin compared to LMWH. METHODS: We conducted a randomized controlled trial of adult trauma patients with an operative extremity fracture or any pelvic/acetabular fracture requiring VTE prophylaxis. Patients were randomized to receive either LMWH 30 mg BID or aspirin 81 mg BID. Patients prescribed outpatient prophylaxis were contacted between 10 and 21 days after discharge to assess adherence measured by the validated Morisky Medication Adherence Scale (MMAS-8). Adherence scores were compared between the two treatment arms with similar results for intention-to-treat and as-treated analyses. As-treated multivariable logistic regression was performed to determine factors associated with low-medium adherence scores. RESULTS: One hundred fifty patients (64 on LMWH, 86 on aspirin) on chemoprophylaxis at time of follow-up completed the questionnaire. As-treated analysis showed that adherence was high overall (mean MMAS 7.2 out of 8, SD 1.5) and similar for the two regimens (LMWH: 7.4 vs. aspirin: 7.0, p = 0.13). However, patients on LMWH were more likely to feel hassled by their regimen (23% vs. 9%, p = 0.02). In a multivariable model, low-medium adherence was associated with taking LMWH as the prophylaxis medication (aOR 2.34, CI 1.06-5.18, p = 0.04), having to self-administer the prophylaxis (aOR 4.44, CI 1.45-13.61, p < 0.01), being of male sex (aOR 2.46, CI 1.10-5.49, p = 0.03), and of younger age (aOR 0.72 per additional 10 years of age, CI 0.57-0.91, p < 0.01). CONCLUSIONS: Overall post-discharge adherence with VTE prophylaxis was high. Several factors, including prophylaxis by LMWH, were associated with decreased adherence. These factors should be considered when managing patients and designing efficacy trials. LEVEL OF EVIDENCE: Therapeutic, level II.

Targeting the binding interface on a shared receptor subunit of a cytokine family enables the inhibition of multiple member cytokines with selectable target spectrum.

The common γ molecule (γc) is a shared signaling receptor subunit used by six γc-cytokines. These cytokines play crucial roles in the differentiation of the mature immune system and are involved in many human diseases. Moreover, recent studies suggest that multiple γc-cytokines are pathogenically involved in a single disease, thus making the shared γc-molecule a logical target for therapeutic intervention. However, the current therapeutic strategies seem to lack options to treat such cases, partly because of the lack of appropriate neutralizing antibodies recognizing the γc and, more importantly, because of the inherent and practical limitations in the use of monoclonal antibodies. By targeting the binding interface of the γc and cytokines, we successfully designed peptides that not only inhibit multiple γc-cytokines but with a selectable target spectrum. Notably, the lead peptide inhibited three γc-cytokines without affecting the other three or non-γc-cytokines. Biological and mutational analyses of our peptide provide new insights to our current understanding on the structural aspect of the binding of γc-cytokines the γc-molecule. Furthermore, we provide evidence that our peptide, when conjugated to polyethylene glycol to gain stability in vivo, efficiently blocks the action of one of the target cytokines in animal models. Collectively, our technology can be expanded to target various combinations of γc-cytokines and thereby will provide a novel strategy to the current anti-cytokine therapies against immune, inflammatory, and malignant diseases.