New Gram-Positive Agents: the Next Generation of Oxazolidinones and Lipoglycopeptides.

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibit in vitro activity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstrate in vitro activity against VRE. These new Gram-positive agents are reviewed here.

Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship.

INTRODUCTION: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use. METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy. RESULTS: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027). CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.

Ridinilazole: a novel antimicrobial for Clostridium difficile infection.

Clostridium difficile (C. difficile) infection remains a global healthcare threat worldwide and the limited options available for its treatment are of particular concern. Ridinilazole is one potential future agent, as it demonstrates rapid bactericidal activity against C. difficile. Current studies show that ridinilazole has a lower propensity for collateral damage to the gut microbiome and appears to diminish the production of C. difficile toxins. Results from phase II studies demonstrate that patients receiving ridinilazole had a higher sustained clinical response compared with patients receiving vancomycin (66.7% vs. 42.4%; P=0.0004). Adverse reactions were similar between ridinilazole and vancomycin (40% vs. 56%, respectively), with most being gastrointestinal-related. Nausea (20%) and abdominal pain (12%) were the most commonly reported adverse reactions associated with ridinilazole. Phase II study results are promising and future availability of phase III trial results will help further delineate the role and value of ridinilazole.

An Evaluation of Guideline Concordance in the Management of Intra-Abdominal Infections.

Background: Optimal treatment of intra-abdominal infections (IAIs) is multifaceted, typically requiring surgical intervention and antimicrobial therapy. Treatment of IAIs aligned with the 2017 revised Surgical Infection Society (SIS) guidelines may improve patient outcomes. Here we compare clinical outcomes of patients who received guideline concordant and discordant therapy for treatment of IAIs. Patients and Methods: This was a retrospective observational study of patients admitted from January 2013 to June 2016 with IAIs. Guideline concordant treatment was based on three criteria: source control, antibiotic choice, and antibiotic duration. The primary outcome was a composite of in-hospital mortality and 30-day re-admission. Multivariable logistic regression was used to determine independent factors associated with the composite end point. Results: A total of 221 patients were included, with guideline concordant treatment occurring in 117 (53%) patients. In-hospital mortality or 30-day re-admission occurred in 15 (12.8%) patients in the guideline concordant group compared with 24 (23.1%) in the guideline discordant group (p = 0.046). Empiric antibiotic choice was the most common component of discordance to guidelines (61% of patients). In multivariable analysis, guideline concordant treatment was associated with a decrease in the composite outcome (adjusted odds ratio [aOR] = 0.461, p = 0.045). In contrast, the presence of empiric methicillin-resistant Staphylococcus aureus (MRSA)/vancomycin-resistant Enterococcus (VRE) coverage (aOR: 2.645, p = 0.030), and moderate-to-severe liver disease (aOR: 8.081, p = 0.027) were associated with an increased risk for the composite outcome. Conclusions: Concordance to recommendations from the 2017 revised SIS guidelines is of critical importance in the optimal management of IAIs and further investigation of interventions to improve concordance are warranted.

Learning Experiences Within Infectious Diseases Pharmacy Residency Programs in the United States: A Cross-Sectional Survey.

BACKGROUND: Pharmacists with residency training in infectious diseases (ID) optimize antimicrobial therapy outcomes in patients and support antimicrobial stewardship (AS) programs. Although most ID residencies are accredited and assessed by certain standards, the degree to which these programs are similar is not known. METHODS: A 19-item, cross-sectional, multicentered, electronic survey was distributed via e-mail to pharmacy residency program directors (RPDs) of all 101 second-year postgraduate (PGY-2) ID residency programs in the United States. RESULTS: Survey responses were collected from 71 RPDs (70.3%); 64.8% were associated with an academic medical center and 97.2% focused primarily in adult ID. Rotations in the microbiology laboratory, adult AS, and adult ID consult were required in 98.6% of residency programs. Only 28.2% of responding programs required pediatric AS and pediatric ID consult rotations. Programs at academic medical centers were more likely to offer immunocompromised host ID consult (P = .003), pediatric ID consult (P = .006), and hospital epidemiology (P = .047) rotations but less frequently offered outpatient AS (P = .003), viral hepatitis clinics (P = .001), and travel medicine clinics (P = .007) rotations compared to programs at nonacademic medical centers. Residents were frequently involved in AS committees (97.2%), pharmacokinetic dosing of antimicrobials (83.1%), precepting pharmacy trainees (80.3%), and performing research projects (91.5%). CONCLUSIONS: The PGY-2 ID pharmacy residency programs demonstrated consistency in required adult ID consult, antimicrobial management activities, committee service, and teaching and research opportunities. Pediatric experiences were less common. The PGY-2 ID residency programs prepare pharmacists to become antimicrobial stewards for adult patients.

What Is Old Is New Again: Delafloxacin, a Modern Fluoroquinolone.

Delafloxacin is a new fluoroquinolone antimicrobial approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults using dosage regimens of 300 mg intravenously every 12 hours, 450 mg orally every 12 hours, or switching from intravenous to oral regimens for a 5- to 14-day treatment duration. Dosage adjustments in patients with severe renal dysfunction (estimated glomerular filtration rate [eGFR] = 15-29 ml/min/1.73 m2 ) are not required for oral doses but should be decreased to 200 mg intravenously every 12 hours in patients requiring parenteral therapy. Due to insufficient data, use of delafloxacin is not recommended for patients on hemodialysis or with end-stage renal disease (eGFR < 15 ml/min/1.73 m2 ). Delafloxacin works through inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV, which are essential enzymes for bacterial DNA transcription, replication, repair, and recombination and exhibits bactericidal activity against gram-positive and gram-negative organisms through a concentration-dependent matter. Delafloxacin has a very broad spectrum of activity against atypical, anaerobic, and resistant gram-negative and gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. During phase 3 trials, the most common side effects associated with delafloxacin were gastrointestinal (nausea, diarrhea). Unlike other fluoroquinolones, there does not seem to be a risk of QTc prolongation or phototoxicity with delafloxacin. The availability of both parenteral and oral formulations for delafloxacin distinguishes it from many of the currently available agents approved for ABSSSIs. Phase 3 studies for the treatment of respiratory infections are currently under way, and future results of these studies will further help delineate the role of delafloxacin.

A single-institution experience with a brucellosis outbreak in the United States.

Human cases of brucellosis in the United States are primarily limited to imported infections or reservoirs. We describe a brucellosis outbreak involving 8 patients treated at a single hospital in the United States. Standardized precautionary microbiology processes and coordinated collaboration among hospital departments and local health departments assisted in optimally managing this disease at our institution.

Epidemiology, Co-Infections, and Outcomes of Viral Pneumonia in Adults: An Observational Cohort Study.

Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48  h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk.