Retrospective Analysis of Adverse Drug Events Between Nafcillin Versus Cefazolin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections.

Background: Nafcillin or cefazolin are drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Prior studies indicate a higher incidence of acute kidney injury (AKI) with nafcillin, although AKI classification and time to occurrence is not well described. Objective: To characterize the incidence and time to adverse drug events for nafcillin versus cefazolin in the inpatient setting. Methods: A retrospective cohort study evaluated hospitalized, adult patients receiving intravenous nafcillin or cefazolin for treatment of MSSA infection. Incidence and time to AKI based on RIFLE criteria were measured. Secondary end points included antibiotic discontinuation and incidence of neutropenia, thrombocytopenia, elevated transaminases, and Clostridioides difficile infection (CDI). Results: Of 324 patients who received nafcillin (n = 119) or cefazolin (n = 205), higher rates of AKI were found for nafcillin versus cefazolin (19% vs 2%, respectively; P < 0.0001). Median time to AKI with nafcillin was 6.5 days (range, 3-14 days). The majority of patients were classified as RIFLE "Risk" stratum. Nafcillin treatment discontinuations were more frequent than for cefazolin (17.6% vs 0.9%, respectively; P < 0.0001). Nafcillin was an independent predictor of AKI (odds ratio = 12.4; 95% CI = 4.14-47.60, P < 0.0001). No differences in neutropenia, thrombocytopenia, elevated transaminases, or CDI were observed. Conclusion and Relevance: Nafcillin displayed higher rates of AKI at a median of 1 week of therapy, which provides a framework for clinician monitoring and consideration of antibiotic modification. Most patients developed "Risk" class AKI (RIFLE classification), which may be reversible with prompt intervention.

Impact of Procalcitonin Guidance on Management of Adults Hospitalized with Chronic Obstructive Pulmonary Disease Exacerbations.

BACKGROUND: Antibiotics are often prescribed for hospitalized patients with chronic obstructive pulmonary disease (COPD) exacerbations. The use of procalcitonin (PCT) in the management of pneumonia has safely reduced antibiotic durations, but limited data on the impact of PCT guidance on the management of COPD exacerbations remain. OBJECTIVE: To determine the impact of PCT guidance on antibiotic utilization for hospitalized adults with exacerbations of COPD. DESIGN: A retrospective, pre-/post-intervention cohort study was conducted to compare the management of patients admitted with COPD exacerbations before and after implementation of PCT guidance. The pre-intervention period was March 1, 2014, through October 31, 2014, and the post-intervention period was March 1, 2015, through October 31, 2015. PARTICIPANTS: All patients with hospital admissions during the pre- and post-intervention period with COPD exacerbations were included. Patients with concomitant pneumonia were excluded. INTERVENTION: Availability of PCT laboratory values in tandem with a PCT guidance algorithm and education. MAIN MEASURES: The primary outcome was duration of antibiotic therapy for COPD. Secondary objectives included duration of inpatient length of stay (LOS) and 30-day readmission rates. KEY RESULTS: There were a total of 166 and 139 patients in the pre- and post-intervention cohorts, respectively. There were no differences in mean age (66.2 vs. 65.9; P = 0.82) or use of home oxygenation (34% vs. 39%; P = 0.42) in the pre- and post-intervention groups, respectively. PCT guidance was associated with a reduced number of antibiotic days (5.3 vs. 3.0; p = 0.01) and inpatient LOS (4.1 days vs. 2.9 days; P = 0.01). Respiratory-related 30-day readmission rates were unaffected (10.8% vs. 9.4%; P = 0.25). CONCLUSIONS: Utilizing PCT guidance in the management of COPD exacerbations was associated with a decreased total duration of antibiotic therapy and hospital LOS without negatively impacting hospital readmissions.

HLA-A, -B, -C, -DR, and -DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival.

To enhance selection of appropriate deceased donors for pancreas transplants, we sought to determine whether HLA matching improved posttransplantation outcomes. In this single-center study of 1219 pancreas transplants, we correlated posttransplantation outcomes with HLA-A, -B, -C, -DR, and -DQ matches and mismatches. Rejection was linearly correlated with the number of mismatches. The individual number of HLA mismatches reached significance at four or more with a 2.3- to 2.9-fold increase in rejection. The effect was most predominant with HLA-B (1.8-fold with one mismatch and 2.0-fold with two mismatches) and -DR (1.9-fold with two mismatches) loci, whereas HLA-A, -C, and -DQ matches or mismatches did not independently predict acute rejection. The affect was strongest in solitary pancreas transplants, with little impact for simultaneous pancreas and kidney (SPK). In contrast, HLA matching did not affect graft or patient survival rates but was associated with a reduced risk of opportunistic infection. Avoidance of acute rejection saved an estimated $32 000 for solitary pancreas recipients and $52 000 for SPK recipients in hospital costs. Our data do not support the use of HLA matching for predicting pancreas graft survival but do support its significance for the reduction of acute rejection, particularly for solitary pancreas recipients.

Appropriateness of antibiotic management of uncomplicated skin and soft tissue infections in hospitalized adult patients.

BACKGROUND: Skin and soft tissue infections (SSTIs) are a leading cause for hospitalizations in the United States. Few studies have addressed the appropriateness of antibiotic therapy in the management of SSTIs without complicating factors. We aimed to determine the appropriateness of antibiotic treatment duration for hospitalized adult patients with uncomplicated SSTIs. METHODS: This was a retrospective analysis performed at two academic medical centers in Pittsburgh, Pennsylvania on patients aged 18 years and older with primary ICD-9 code for SSTIs admitted August 1st, 2014-March 31st, 2015. The primary outcome was the appropriateness of antibiotic treatment duration for uncomplicated SSTIs. Secondary objectives included the appropriateness of antibiotic agent spectrum, duration of inpatient length of stay (LOS), utilization of blood cultures and advanced imaging modalities, and re-hospitalization for SSTI within 30 days of discharge from the index admission. RESULTS: A total of 163 episodes were included in the cohort. The mean duration of total antibiotic therapy was 12.6 days. Appropriate duration was defined as receipt of total antibiotic duration of less than 10 days and occurred in 20.2% of patients. Twenty eight percent of patients received antibiotics for greater than 14 days. Seventy three (44.8%) patients received greater than 24 h of inappropriate extended spectrum gram-negative coverage; 65 (39.9%) received anaerobic coverage. CONCLUSIONS: In the majority of patients, treatment duration was excessive. Inappropriate broad spectrum antibiotic selection was utilized with regularity for SSTIs without complicating factors. The management of uncomplicated SSTIs represents a significant opportunity for antimicrobial stewardship.

High frequency of nonadherence to Clostridium difficile treatment guidelines.

OBJECTIVES: The 2010 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America treatment guidelines for Clostridium difficile infections (CDI) recommend oral metronidazole for mild-to-moderate disease and oral vancomycin for severe disease. Given that disease severity is easily determined by the peripheral white blood cell count and serum creatinine level, a computerized decision support (CDS) pathway to guide treatment is inherently appealing. Because providers often override or ignore the computer-based alerts, the proposed CDS pathway should be justified before implementation. METHODS: We undertook this study to ascertain the frequency of nonadherence to CDI guidelines. Between October 1, 2007 and September 30, 2008, a total of 229 cases were screened and 78 cases were included in the study, which took place at a 661-bed acute tertiary care teaching hospital. RESULTS: During the year-long study of CDI cases at our tertiary care hospital, 61.5% (48/78) of the patients received an antibiotic regimen that was not recommended by the 2010 guidelines. Among the 35 patients with mild-to-moderate CDI, 85.7% (30/35) received the recommended treatment of oral metronidazole monotherapy; in contrast, among the 43 patients with severe disease, none (0/43) received the recommended treatment of oral vancomycin monotherapy (P < 0.01). Moreover, 17.9% (14/78) of patients received concurrent oral metronidazole and vancomycin, a regimen that is not recommended anywhere in the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America guidelines and which may be associated with a poor outcome. Patients who received combination oral metronidazole and vancomycin were not more likely to have comorbidities or severe CDI compared with those who received a single antibiotic agent. CONCLUSIONS: As a result of this study, we plan to educate our providers on the treatment of CDI through a CDS pathway in an effort to increase guideline adherence, decrease inappropriate antibiotic use, and potentially improve patient outcomes.

The missing link between cancer stem cells and immunotherapy.

Cancer stem cells (CSCs) are cancer cells that can self-renew and give rise to tumors. The multipotency of CSCs enables the generation of diverse cancer cell types and their potential for differentiation and resilience against chemotherapy and radiation. Additionally, specific biomarkers have been identified for them, such as CD24, CD34, CD44, CD47, CD90, and CD133. The CSC model suggests that a subset of CSCs within tumors is responsible for tumor growth. The tumor microenvironment (TME), including Fibroblasts, immune cells, adipocytes, endothelial cells, neuroendocrine (NE) cells, extracellular matrix (ECM), and extracellular vesicles, has a part in shielding CSCs from the host immune response as well as protecting them against anticancer drugs. The regulation of cancer stem cell plasticity by cancer-associated fibroblasts (CAFs) occurs through specific signaling pathways that differ among various types of cancer, utilizing the IGF-II/IGF1R, FAK, and c-Met/FRA1/HEY1 signaling pathways. Due to the intricate dynamics of CSC proliferation, controlling their growth necessitates innovative approaches and much more research. Our current review speculates an outline of how the TME safeguards stem cells, their interaction with CSCs, and the involvement of the immune and inflammatory systems in CSC differentiation and maintenance. Several technologies have the ability to identify CSCs; however, each approach has limitations. We discuss how these methods can aid in recognizing CSCs in several cancer types, comprising brain, breast, liver, stomach, and colon cancer. Furthermore, we explore different immunotherapeutic strategies targeting CSCs, including stimulating cancer-specific T cells, modifying immunosuppressive TMEs, and antibody-mediated therapy targeting CSC markers.

Common and well-documented HLA alleles: 2012 update to the CWD catalogue.

We have updated the catalogue of common and well-documented (CWD) human leukocyte antigen (HLA) alleles to reflect current understanding of the prevalence of specific allele sequences. The original CWD catalogue designated 721 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, and -DPB1 loci in IMGT (IMmunoGeneTics)/HLA Database release 2.15.0 as being CWD. The updated CWD catalogue designates 1122 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1 loci as being CWD, and represents 14.3% of the HLA alleles in IMGT/HLA Database release 3.9.0. In particular, we identified 415 of these alleles as being 'common' (having known frequencies) and 707 as being 'well-documented' on the basis of ~140,000 sequence-based typing observations and available HLA haplotype data. Using these allele prevalence data, we have also assigned CWD status to specific G and P designations. We identified 147/151 G groups and 290/415 P groups as being CWD. The CWD catalogue will be updated on a regular basis moving forward, and will incorporate changes to the IMGT/HLA Database as well as empirical data from the histocompatibility and immunogenetics community. This version 2.0.0 of the CWD catalogue is available online at cwd.immunogenomics.org, and will be integrated into the Allele Frequencies Net Database, the IMGT/HLA Database and National Marrow Donor Program's bioinformatics web pages.

Perceptions of participating emergency nurses regarding an ED seasonal influenza vaccination program.

INTRODUCTION: Numerous professional organizations have recommended that emergency departments provide influenza vaccine to patients. However, no study has reported on the perceptions of participating emergency nurses regarding ED influenza vaccination programs. METHODS: We conducted an anonymous Web-based survey to assess the post-participation perceptions of emergency nurses regarding an ED influenza vaccination protocol. The vaccination protocol occurred at an urban, academic emergency department and was designed to be performed by emergency nurses without added staffing resources by using ED Electronic Medical Record technology. Data from the Web-based survey were analyzed using descriptive statistics and χ(2) analysis to assess significant associations of where emergency nurses believed the protocol was time inefficient. RESULTS: The ED influenza vaccination protocol was in effect from October 1-25, 2009, with 3091 eligible ED visits and 613 patients receiving ED seasonal influenza vaccination. Fifty-eight of 59 participating emergency nurses (98%) responded to the survey. Significant findings were that 59% of responding emergency nurses found the protocol too time consuming and believed it was inappropriate in the ED setting. Responding emergency nurses reported that protocol efficiency could be improved by adding staff, simplifying screening and vaccination documentation requirements, and improving vaccine supply and stocking procedures in the emergency department. CONCLUSION: A majority of surveyed emergency nurses who had participated in an ED influenza vaccination program reported that the protocol was too time consuming and inappropriate for the ED setting. Surveyed emergency nurses expressed the opinion that such protocols required added staff, simplified patient consent/vaccination documentation requirements, and improved vaccine supply and stocking processes.

Revisiting traditional risk factors for rejection and graft loss after kidney transplantation.

Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single-antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third-party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death-censored graft survival (DCGS) and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization.

Multidrug-resistant gram-negative infections. Bringing back the old.

Multidrug-resistant (MDR) gram-negative infections have become challenging to treat when there is only a limited armamentarium of anti-infectives that are commercially available. In particular, increasing resistance of gram-negative organisms such as Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species have become concerning. Carbapenems have been used to treat extended-spectrum-ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella species infections. However, because of carbapenemase-producing K pneumoniae strains, other MDR gram-negative infection treatment options are limited to antibiotics with in vitro spectrum of activity against these MDR pathogens and may include the use of tigecycline, polymyxin B, or polymxyin E (colistin). Because of the potential for nephrotoxicity or neurotoxicity with the polymyxins, clinicians should be vigilant in preventing its adverse effects. Clinicians are encouraged to support the Infectious Diseases Society of America's 10 × '20 Initiative in gaining global commitment to develop additional antimicrobials for the future.