Resource Over-Utilization in Hospitalized Patients With Uncomplicated Skin and Soft Tissue Infections.

BACKGROUND: Inpatient management of SSTIs utilizes considerable healthcare resources. The CREST+SEWS score categorizes patients with SSTIs into 4 severity classes. Hospitalizations can be avoided in Class I as they are treated as outpatients with oral antibiotics, whereas Class IV require hospitalization for intravenous antibiotics. OBJECTIVE: The purpose of this study was to perform a budget impact analysis on CREST+SEWS Class 1 patients, to compare the medical costs of current treatment, in the inpatient setting with intravenous antibiotics, with a proposed alternative of using oral antibiotics in the outpatient setting. Further, resource utilization in Class I was evaluated. METHODS: This was a retrospective study of adult patients hospitalized in 2015 for SSTIs who received >24 hours of antimicrobials. The CREST+SEWS scoring system was used to stratify patients into Class I to IV. Pharmacy and medical costs and resources associated with inpatient management of Class I SSTIs were derived from the itemized discharge records. RESULTS: Of the 252 patients who met the inclusion criteria, 61 (24%) were classified as Class I. The total cost of treating Class I SSTI patients in the inpatient setting was $281,816 (cost per patient: $4,619) in 2015 USD. In the hypothetical situation of treatment with oral antibiotics in the outpatient setting, the cost savings were estimated to be $4,398 per patient. Fifty-three percent of patients had blood cultures, and on average, each patient received 2 radiographic tests. CONCLUSIONS: Identifying outpatient candidates, and avoiding tests with low diagnostic can reduce the economic burden of SSTIs.

Ceftolozane/tazobactam for pulmonary exacerbation in a 63-year-old cystic fibrosis patient with renal insufficiency and an elevated MIC to Pseudomonas aeruginosa.

Cystic fibrosis (CF) is a progressive genetic disorder caused by mutations in a gene encoding the cystic fibrosis transmembrane regulator (CFTR) protein leading to persistent and difficult to treat lower airway infections. Multi-drug resistant Pseudomonas aeruginosa is becoming increasingly more common as a cause of pulmonary exacerbations, and newer agents such as ceftolozane/tazobactam (C/T) are being sought for treatment. There is currently little published data regarding its use in cystic fibrosis, particularly in the setting of reduced renal clearance. This report details the case of a 63-year-old female with cystic fibrosis and chronic kidney disease stage III (estimated creatinine clearance of 25-30 ml/min, Cockroft-Gault) who was successfully treated for a pulmonary exacerbation with C/T 3 g (2000 mg/1000 mg) infused intravenously every 8 h when the P. aeruginosa minimum inhibitory concentration (MIC) was elevated at 8 mcg/mL. Serum samples were collected to determine concentrations by a validated high-performance liquid chromatography assay. The steady state 1-hr post-infusion peak (Cmax) and trough (Cmin) concentrations for ceftolozane were 145.04 mcg/mL and 82.08 mcg/mL, and 15.93 mcg/mL and 3.20 mcg/mL for tazobactam, respectively. The patient's symptoms resolved and her lung function returned to baseline. She completed 14 days of therapy and tolerated the infusion well without any infusion-related or adverse events.

The Role of an Antimicrobial Stewardship Team in the Use of Rapid Diagnostic Testing in Acute Care: An Official Position Statement of the Society of Infectious Diseases Pharmacists.

Rapid diagnostic technologies can assist Antimicrobial Stewardship Programs (ASPs) in achieving the goals of reducing unnecessary antimicrobial exposure and optimizing patient care. The Society of Infectious Diseases Pharmacists supports all members of the ASP team as essential components of optimal use of these technologies for management of antibiotic prescribing and cost-reduction strategies. Infect Control Hosp Epidemiol 2018;39:473-475.

Comparative effectiveness of 3- versus 4-factor prothrombin complex concentrate for emergent warfarin reversal.

INTRODUCTION: Three- and 4-factor prothrombin complex concentrates (PCC) are routinely administered for emergent reversal of warfarin, but direct comparisons of clinical outcomes are lacking. The purpose of this study was to compare the safety and effectiveness of 3- and 4-PCC in patients requiring emergent warfarin reversal. MATERIALS AND METHODS: This was a single-center retrospective study in adult patients requiring administration of either 3-PCC or 4-PCC for emergent reversal of warfarin. RESULTS: One hundred sixty-five patients were included (3-PCC, n=109; 4-PCC, n=56). The most frequent indications for PCC were intracranial and gastrointestinal bleeding. Baseline median INR was 2.5 (2.0-3.2) and 2.4 (2.0-4.2) in the 3-PCC and 4-PCC groups. Thirty minutes after PCC administration, median INR decreased to 1.3 in both groups (p<0.001), and 87 (80%) versus 47 (84%) of patients had INR values≤1.5 (p=0.52) in the 3-PCC group versus the 4-PCC group. Thromboembolic events occurred in 7 patients (4%) and were similar between the 3-PCC (n=3, 3%) and 4-PCC (n=4, 7%) groups (p=0.23). Thirty-four (31%) patients in the 3-PCC group died compared to 5 patients (9%) in the 4-PCC group (p=0.001). INR>1.5 thirty minutes after PCC was associated with increased mortality (OR 4.3; 95% CI 1.8-10.4, p=0.001), and administration of a 4-PCC was associated with decreased mortality (OR 0.19; 95% CI 0.06-0.54, p=0.002). CONCLUSION: Patients who received 4-PCC, and those with INR≤1.5 regardless of type of PCC received were more likely to survive. Thromboembolic events were low in both groups and similar to previous studies.

Independent relationship between amyloid precursor protein (APP) dimerization and γ-secretase processivity.

Altered production of ß-amyloid (Aß) from the amyloid precursor protein (APP) is closely associated with Alzheimer's disease (AD). APP has a number of homo- and hetero-dimerizing domains, and studies have suggested that dimerization of ß-secretase derived APP carboxyl terminal fragment (CTFß, C99) impairs processive cleavage by γ-secretase increasing production of long Aßs (e.g., Aß1-42, 43). Other studies report that APP CTFß dimers are not γ-secretase substrates. We revisited this issue due to observations made with an artificial APP mutant referred to as 3xK-APP, which contains three lysine residues at the border of the APP ectodomain and transmembrane domain (TMD). This mutant, which dramatically increases production of long Aß, was found to form SDS-stable APP dimers, once again suggesting a mechanistic link between dimerization and increased production of long Aß. To further evaluate how multimerization of substrate affects both initial γ-secretase cleavage and subsequent processivity, we generated recombinant wild type- (WT) and 3xK-C100 substrates, isolated monomeric, dimeric and trimeric forms of these proteins, and evaluated both ε-cleavage site utilization and Aß production. These show that multimerization significantly impedes γ-secretase cleavage, irrespective of substrate sequence. Further, the monomeric form of the 3xK-C100 mutant increased long Aß production without altering the initial ε-cleavage utilization. These data confirm and extend previous studies showing that dimeric substrates are not efficient γ-secretase substrates, and demonstrate that primary sequence determinants within APP substrate alter γ-secretase processivity.