Fluoroquinolone Prescribing for Diabetic Foot Infections following an FDA Drug Safety Communication for Aortic Aneurysm Risk.

In 2018, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication regarding fluoroquinolone-associated aortic aneurysm. This quasi-experimental study assessed antibiotic prescribing for 198 patients hospitalized with diabetic foot infection. Following the warning, median inpatient fluoroquinolone days of therapy (DOT) decreased from 3 to 0 days (P < 0.001), corresponding to increased beta-lactam DOT and outpatient parenteral antimicrobial therapy enrollment. FDA communications may influence antibiotic selection and transitions of care, representing opportunities for antimicrobial stewardship.

Proteomic Analysis of Infants Undergoing Cardiopulmonary Bypass Using Contemporary Ontological Tools.

BACKGROUND: Cardiopulmonary bypass (CPB) is essential for the repair of many congenital cardiac defects in infants but is associated with significant derangements in hemostasis and systemic inflammation. As a result, hemorrhagic complications and thrombosis are major challenges in the management of children requiring CPB or extracorporeal membrane oxygenation. Conventional clinical laboratory tests capture individual hemostatic derangements (low platelets, elevated fibrinogen) but fail to describe the complex, overlapping interactions among the various components of coagulation, including cellular interactions, contact activation, fibrinolysis, and inflammation. Given recent advances in analytic tools for identifying protein-protein interactions in the plasma proteome, we hypothesized that an unbiased proteomic analysis would help identify networks of interacting proteins for further investigation in pediatric CPB. MATERIALS AND METHODS: Infants up to 1 y of age were enrolled. Plasma samples were collected at 0, 1, 4, and 24 h after CPB. Mass spectrometry was used to identify proteins undergoing changes in concentration after CPB, and STRING and ToppGene tools were used to identify biological networks. Two-dimensional difference gel electrophoresis identified changes in protein concentrations. Inflammatory markers were assessed by enzyme-linked immunosorbent assay at the same time points. RESULTS: Ten infants with cardiac anomalies requiring surgery and CPB were enrolled; no major complications were recorded (median age, 127.5 d; interquartile range, 181.25 d). Using two-dimensional difference gel electrophoresis, >1400 individual protein spots were observed, and 89 proteins demonstrated change in concentration >30% with P < 0.02 when comparing 1, 4, or 24 h to baseline. Among protein spots with significant changes in concentration after CPB, 29 were identified with mass spectrometry (33%). In our interrogation of functional associations among these differentially expressed proteins, our results were dominated by the acute phase response, coagulation, and cell signaling functional categories. Among cytokines analyzed by enzyme-linked immunosorbent assay, IL-2, IL-8, and IL-10 were elevated at 4 h but normalized by 24 h, whereas IL-6 was persistently elevated. CONCLUSIONS: Infants manifest a robust response to CPB that includes overlapping, complex pathways. Further investigation of interactions among immune, coagulation, and cell signaling systems may lead to novel therapeutics or biomarkers useful in the management of infants requiring CPB.

Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the Murine Neutropenic Thigh Model.

Apramycin, an aminocyclitol aminoglycoside, was rapidly bactericidal against Acinetobacter baumannii In a neutropenic murine thigh infection model, treatment-associated A. baumannii CFU reductions of >4 log10 per thigh were observed for all exposures for which area under the curve (AUC)/MIC ratio was >50 and maximum concentration of drug in serum (Cmax)/MIC was ≈10 or higher. Based on these findings, we suggest that apramycin deserves further preclinical exploration as a repurposed therapeutic for multidrug-resistant Gram-negative pathogens, including A. baumannii.

Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections.

BACKGROUND: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. OBJECTIVE: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. METHODS: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. RESULTS: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. CONCLUSIONS: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.

Bezlotoxumab: Could This be the Answer for Clostridium difficile Recurrence?

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of bezlotoxumab (BEZ), a novel monoclonal antibody against Clostridium difficile toxin B. DATA SOURCES: A PubMed search was conducted for data between 1946 and April 2017 using MeSH terms bezlotoxumab, MK-6072, or MDX-1388 alone and the terms Clostridium difficile combined with monoclonal antibody or antitoxin. STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to English-language studies that described clinical efficacy, safety, and pharmacokinetics in humans and animals. Abstracts featuring prepublished data were also evaluated for inclusion. DATA SYNTHESIS: BEZ is indicated for adult patients receiving standard-of-care (SoC) antibiotics for C difficile infection (CDI) to prevent future recurrence. Two phase III trials-MODIFY I (n = 1452) and MODIFY II (n = 1203)-demonstrated a 40% relative reduction in recurrent CDI (rCDI) with BEZ compared with placebo (16.5% vs 26.6%, P < 0.0001). The most common adverse drug events associated with BEZ were mild to moderate infusion-related reactions (10.3%). CONCLUSIONS: In patients treated with SoC antibiotics, BEZ is effective in decreasing rCDI. BEZ has no apparent effect on treatment of an initial CDI episode. In light of increasing rates of CDI, BEZ is a promising option for preventing recurrent episodes. The greatest benefit has been demonstrated in high-risk patients, though the targeted patient population is yet to be defined.

Tissue engineered vascular grafts: Origins, development, and current strategies for clinical application.

Since the development of a dependable and durable synthetic non-autogenous vascular conduit in the mid-twentieth century, the field of vascular surgery has experienced tremendous growth. Concomitant with this growth, development in the field of bioengineering and the development of different tissue engineering techniques have expanded the armamentarium of the surgeon for treating a variety of complex cardiovascular diseases. The recent development of completely tissue engineered vascular conduits that can be implanted for clinical application is a particularly exciting development in this field. With the rapid advances in the field of tissue engineering, the great hope of the surgeon remains that this conduit will function like a true blood vessel with an intact endothelial layer, with the ability to respond to endogenous vasoactive compounds. Eventually, these engineered tissues may have the potential to supplant older organic but not truly biologic technologies, which are used currently.

Assessment of Fosfomycin for Complicated or Multidrug-Resistant Urinary Tract Infections: Patient Characteristics and Outcomes.

BACKGROUND: Bacterial resistance among uropathogens is on the rise and has led to a decreased effectiveness of oral therapies. Fosfomycin tromethamine (fosfomycin) is indicated for uncomplicated urinary tract infections (UTIs) and displays in vitro activity against multidrug-resistant (MDR) isolates; however, clinical data assessing fosfomycin for the treatment of complicated or MDR UTIs are limited. METHODS: We conducted a retrospective evaluation of patients who received ≥1 dose of fosfomycin between January 2009 and September 2015 for treatment of a UTI. Patients were included if they had a positive urine culture and documented signs/symptoms of a UTI. RESULTS: Fifty-seven patients were included; 44 (77.2%) had complicated UTIs, 36 (63.2%) had MDR UTIs, and a total of 23 (40.4%) patients had a UTI that was both complicated and MDR. The majority of patients were female (66.7%) and elderly (median age, 79 years). Overall, the most common pathogens isolated were Escherichia coli (n = 28), Enterococcus spp. (n = 22), and Pseudomonas aeruginosa (n = 8). Twenty-eight patients (49.1%) were clinically evaluable; the preponderance achieved clinical success (96.4%). Fifteen out of 20 (75%) patients with repeat urine cultures had a microbiological cure. CONCLUSIONS: This retrospective study adds to the limited literature exploring alternative therapies for complicated and MDR UTIs with results providing additional evidence that fosfomycin may be an effective oral option.

Computerized alcohol screening identified more at-risk drinkers in a level 2 than a level 1 trauma center.

BACKGROUND: Alcohol abuse is recognized as a significant contributor to injury. It is therefore essential that trauma centers implement screening and brief intervention (SBI) to identify patients who are problem drinkers. Although, the utility of SBI in identifying at-risk drinkers have been widely studied in level 1 trauma centers, few studies have been done in level 2 centers. This study evaluates the usefulness of SBI in identifying at-risk drinkers and to investigate the pattern of alcohol drinking among level 2 trauma patients. METHODS: This is a retrospective study of a convenience sample of trauma patients participating in computerized alcohol screening, brief intervention, and referral to treatment (CASI) in an academic level 1 trauma center and a nearby suburban community hospital level 2 trauma center. CASI utilized Alcohol Use Disorders Identification Test (AUDIT) to screen patients. We compared the pattern of alcohol drinking, demographic factors, and readiness-to-change scores between those screened in a level 2 and 1 trauma center. RESULTS: A total of 3,850 and 1,933 admitted trauma patients were screened in level 1 and 2 trauma centers respectively. There was no difference in mean age, gender, and language between the two centers. Of those screened, 10.2% of the level 1 and 14.4% of the level 2 trauma patients scored at-risk (AUDIT 8-19) (p < 0.005). Overall, 3.7% of the level 1 and 7.2% of the level 2 trauma patients had an AUDIT score consistent with dependency (AUDIT > =20) (p < 0.005). After adjusting for age, sex, education, and language, the odds of being a drinker at the level 2 center was two times of those at the level 1 center (p < 0.005). The odds of being an at-risk or dependent drinker at level 2 trauma center were 1.72 times of those at the level 1 center (p < 0.005). CONCLUSIONS: Findings suggest that SBI is effective in identifying at-risk drinkers in level 2 trauma center. SBI was able to identify all drinkers, including at-risk and dependent drinkers at higher rates in level 2 versus level 1 trauma centers. Further studies to evaluate the effectiveness of SBI in altering drinking patterns among level 2 trauma patients are warranted.

Quantifying the Risk of Spinal Injury in Motor Vehicle Collisions According to Ambulatory Status: A Prospective Analytical Study.

BACKGROUND: The association between ambulation at the scene of a motor vehicle collision (MVC) and spinal injury has never been quantified. OBJECTIVE: To evaluate the association between ambulation and spinal injury in patients involved in a MVC. METHODS: Prospective analytical-observational cohort study. Inclusion: patients sustaining traumatic injury in a MVC. Exclusion: < 18 years old, pregnancy. PRIMARY OUTCOME: spinal injury defined as injury to the cervical, thoracic, or lumbar spinal cord, bones, or ligaments. Secondary outcome: Injury resulting in neurological deficit, need for surgery, or death. A generalized linear model was used to evaluate the association between outcome and predictor variables. Risk ratios [RR] were reported with a point estimate and 95% confidence interval (CI). A two-tailed alpha of < 0.05 was the threshold for statistical significance. RESULTS: There were 704 patients analyzed. Nonambulatory patients were 2.29 times more likely to sustain a spinal injury, compared to ambulatory patients (RR 2.29, 95% CI 1.34-3.91). Patients ≥ 65 years of age were 3.27 times more likely to sustain a spinal injury (RR 3.27, 95% CI 1.66-6.45). Patients with a Glasgow Coma Scale score ≤ 8 were 4.93 times more likely to sustain a spinal injury (RR 4.93, 95% CI 1.86-13.10). CONCLUSION: In this prospective analytical-observational study evaluating the association between ambulatory status and spinal injury in patients involved in MVCs, we observed that those patients who were nonambulatory were more than two times as likely to have a spinal injury compared to those patients who were ambulatory at the scene.

Susceptibility of Multidrug-Resistant Gram-Negative Urine Isolates to Oral Antibiotics.

Increasing resistance among Gram-negative uropathogens limits treatment options, and susceptibility data for multidrug-resistant isolates are limited. We assessed the activity of five oral agents against 91 multidrug-resistant Gram-negative urine isolates that were collected from emergency department/hospitalized patients. Fosfomycin and nitrofurantoin were most active (>75% susceptibility). Susceptibilities to sulfamethoxazole-trimethoprim, ciprofloxacin, and ampicillin were ≤40%; empirical use of these agents likely provides inadequate coverage in areas with a high prevalence of multidrug-resistant uropathogens.

Race-related Healthcare Disparities Among California Workers: Public Health Considerations for Immigration Reform.

BACKGROUND: Healthcare disparities are prevalent in medicine and identifying them will provide healthcare professionals, administrators, and policy makers needed information to address this public health concern. OBJECTIVE: To evaluate racial and ethnic disparities in the rates of hospital admission and death among California workers. METHODS: We performed an analysis of hospital and emergency department (ED) data from the Office of Statewide Health Planning and Development (OSHPD). Data was collected from California licensed acute care hospitals from 2008-2010. INCLUSION CRITERIA: patients >15 years of age whose expected source of payment was worker's compensation. EXCLUSION CRITERIA: patients <15 years; had missing data for age, sex, race, or injury; or were injured by a suicide attempt, poisoning, or complication of medical procedure. Multivariate logistic regression was used to evaluate the relationship of race/ethnicity and admission/death rates. RESULTS: There were 393,298 patients discharged from the ED and 23,343 patients admitted from ED had workers compensation as their expected sources of payment and 150,277 met our inclusion criteria. The annual rate of ED treated injuries was 209/100,000 for Caucasians 343/100,000 for Hispanics, 258/100,000 for blacks and 97/100,000 for Asians. Compared to Caucasians, admission odds ratios (OR) were 1.15 (95% CI 1.07-1.25) for Hispanics, 1.08 (95% CI 0.87-1.33) for blacks, and 0.78 (95% CI 0.63-0.97) for Asians. CONCLUSION: We observed race and ethnicity related healthcare disparities among the occupationally injured in California, with Hispanics having the highest odds of admission and annual incidence of ED treated injuries. No difference in mortality rates was observed.

Arsenic and Its Methylated Metabolites Inhibit the Differentiation of Neural Plate Border Specifier Cells.

Exposure to arsenic in food and drinking water has been correlated with adverse developmental outcomes, such as reductions in birth weight and neurological deficits. Additionally, studies have shown that arsenic suppresses sensory neuron formation and skeletal muscle myogenesis, although the reason why arsenic targets both of these cell types in unclear. Thus, P19 mouse embryonic stem cells were used to investigate the mechanisms by which arsenic could inhibit cellular differentiation. P19 cells were exposed to 0, 0.1, or 0.5 µM sodium arsenite and induced to form embryoid bodies over a period of 5 days. The expression of transcription factors necessary to form neural plate border specifier (NPBS) cells, neural crest cells and their progenitors, and myocytes and their progenitors were examined. Early during differentiation, arsenic significantly reduced the transcript and protein expression of Msx1 and Pax3, both needed for NPBS cell formation. Arsenic also significantly reduced the protein expression of Sox 10, needed for neural crest progenitor cell production, by 31-50%, and downregulated the protein and mRNA levels of NeuroD1, needed for neural crest cell differentiation, in a time- and dose-dependent manner. While the overall protein expression of transcription factors in the skeletal muscle lineage was not changed, arsenic did alter their nuclear localization. MyoD nuclear translocation was significantly reduced on days 2-5 between 15 and 70%. At a 10-fold lower concentration, monomethylarsonous acid (MMA III) appeared to be just as potent as inorganic arsenic at reducing the mRNA levels Pax3 (79% vs84%), Sox10 (49% vs 65%), and Msx1 (56% vs 56%). Dimethylarsinous acid (DMA III) also reduced protein and transcript expression, but the changes were less dramatic than those with MMA or arsenite. All three arsenic species reduced the nuclear localization of MyoD and NeuroD1 in a similar manner. The early changes in the differentiation of neural plate border specifier cells may provide a mechanism for arsenic to suppress both neurogenesis and myogenesis.

Mycotic Saccular Abdominal Aortic Aneurysm in an Infant after Cardiac Catheterization: A Case Report.

Abdominal aortic aneurysms (AAAs) are a rare entity in the pediatric population. Children with mycotic (infectious) AAA in particular are at risk of life-threatening rupture due to their rapid expansion coupled with aortic wall thinning and deterioration. Here, we present the case of a 10-month-old infant with prior 2-staged repair for hypoplastic left heart syndrome that was incidentally discovered to have a mycotic AAA on abdominal ultrasound (US) for evaluation of renovascular hypertension. Before the time of evaluation with US, the infant had developed methicillin-resistant Staphylococcus aureus bacteremia 3 days after cardiac catheterization with percutaneous thoracic aortic balloon angioplasty. She had normal aortic contours on contrasted computed tomography scan of the abdomen approximately 2 weeks before the aforementioned US evaluation. This infant subsequently underwent open aneurysmorrhaphy with cryopreserved vein patch angioplasty with resolution of her aneurysmal segment.

A retrospective analysis of ethnic and gender differences in alcohol consumption among emergency department patients: a cross-sectional study.

BACKGROUND: Previous studies of alcohol use have recognized several trends in consumption patterns among gender and age yet few have examined ethnic differences. This study examines the intra- and inter-ethnic differences in alcohol consumption among a population of patients seen in the emergency department. METHODS: This is a cross-sectional study conducted in the emergency department in a large urban setting. Information on drinking behavior and ethnicity was collected using the Computerized Alcohol Screening and Brief Intervention (CASI) tool. We explored differences in drinking patterns using a multivariate multinomial logistic regression model. RESULTS: We analyzed the drinking habits of 2,444 patients surveyed between November 2012 and May 2014. The results indicate that when compared to non-Hispanic whites, Asians have the lowest odds of drinking within normal limits or excessively, followed by other Latinos, and Mexicans. Age and gender consistently showed statistically significant associations with alcohol-use. The odds of drinking within normal limits or excessively are inversely associated with age and were lower among females. The predicted probabilities show a marked gender-specific difference in alcohol use both between and within ethnic/racial groups. They also highlight an age-related convergence in alcohol use between men and women within ethnic groups. DISCUSSION: The results of this study show intra-racial/ethnic variability associated with sex and education. The highlighted differences within and between ethnic groups reinforce the need to use refined categories when examining alcohol use among minorities. CONCLUSION: The results of this study confirm some alcohol consumption trends among ethnic minorities observed in literature. It provides empirical evidence of the marked gender differences and highlights an age-related convergence for gender-specific alcohol use. Health-care personnel should be aware of these differences when screening and counseling.

Determining if Admission Thromboelastography can Predict the Development of Late Resolving Multiple Organ Failure in Trauma Patients.

BACKGROUND: Normal coagulation TEG values on admission negatively correlate with overall risk of multiple organ failure, but less is known about association between coagulation and late-resolving multiple organ failure (LRMOF) risk. Here, the relationship between TEG parameters and development of LRMOF was investigated. METHODS: We conducted a retrospective assessment of patients at high postinjury multiple organ failure risk at our center. The primary outcome was LRMOF. RESULTS: Analysis included 742 patients. Demographics were 76% male, mean age of 41, mean ISS of 23, 34% hypercoagulability, and 16% developed LRMOF. Patients with normal admission TEG developed LRMOF at significantly lower unadjusted rates than patients with coagulation disturbances (9 vs 16%-19%, P = 0.029); however, multivariable logistic regression demonstrated that neither coagulation profile nor individual admission TEG parameters showed association with LRMOF. CONCLUSIONS: In this series, we found no significant relationship between coagulation status and LRMOF development.

Association of volume of patient encounters with residents' in-training examination performance.

BACKGROUND: Patient care and medical knowledge are Accreditation Council for Graduate Medical Education (ACGME) core competencies. The correlation between amount of patient contact and knowledge acquisition is not known. OBJECTIVE: To determine if a correlation exists between the number of patient encounters and in-training exam (ITE) scores in internal medicine (IM) and pediatric residents at a large academic medical center. DESIGN: Retrospective cohort study PARTICIPANTS: Resident physicians at Mayo Clinic from July 2006 to June 2010 in IM (318 resident-years) and pediatrics (66 resident-years). METHODS: We tabulated patient encounters through review of clinical notes in an electronic medical record during post graduate year (PGY)-1 and PGY-2. Using linear regression models, we investigated associations between ITE score and number of notes during the previous PGY, adjusted for previous ITE score, gender, medical school origin, and conference attendance. KEY RESULTS: For IM, PGY-2 admission and consult encounters in the hospital and specialty clinics had a positive linear association with ITE-3 % score (ß = 0.02; p = 0.004). For IM, PGY-1 conference attendance is positively associated with PGY-2 ITE performance. We did not detect a correlation between PGY-1 patient encounters and subsequent ITE scores for IM or pediatric residents. No association was found between IM PGY-2 ITE score and inpatient, outpatient, or total encounters in the first year of training. Resident continuity clinic and total encounters were not associated with change in PGY-3 ITE score. CONCLUSIONS: We identified a positive association between hospital and subspecialty encounters during the second year of IM training and subsequent ITE score, such that each additional 50 encounters were associated with an increase of 1 % correct in PGY-3 ITE score after controlling for previous ITE performance and continuity clinic encounters. We did not find a correlation for volume of encounters and medical knowledge for IM PGY-1 residents or the pediatric cohort.

Impact of a pharmacy resident on a transitions of care rotation for inpatients enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program.

A novel pharmacy residency rotation was created to meet the needs of patients enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program but not yet discharged from the inpatient setting. This service resulted in a high number of antimicrobial stewardship interventions identified and accepted by the primary team(s).

Outcomes associated with empiric cefepime for bloodstream infections caused by ceftriaxone-resistant, cefepime-susceptible Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: Cefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L. METHODS: This single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours. RESULTS: Fifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2-6) days and 7 (5-10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016). CONCLUSION: Mortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.