Introduction: Catheter related bloodstream infections (CRBSIs) are bloodstream infections in a patient with a CVC receiving parenteral nutrition (PN) without an alternative source of infection. They represent a significant source of morbidity, mortality and cost for PN patients. Limited evidence exists to identify their incidence and risk factors. The aim of this study was to identify the incidence of CRBSIs in hospitalized patients requiring PN. The secondary objectives were to identify risk factors for CRBSIs and examine if nutrition prescription or weight class correlates with its incidence. Methods: Out of 600 PN patients who received care at UF Health Shands Hospital over 30 months, 423 met inclusion criteria for retrospective review. Results: As outlined in Table 1, the incidence of overall and PN-related CRBSI were 23.1% and 21.2% respectively. History of antibiotic lock within 90 days of admission, total number of immunosuppressants, central line-associated bloodstream infections (CLABSI), SBS or fistula were significantly associated with CRBSI. PN macronutrients and total calories were also associated with CRBSI. Patients weight or weight class did not correlate with the incidence of CRBSIs (Table 1). Conclusion: In our population, incidence of PN-related CRBSI was lower than previous reports for patients with CVC either not on PN therapy or on home PN. Adherence to published guidelines, catheter placement procedures and bundles, staff training and selective formulation and utilization of PN therapy may help reduce CRBSI incidence. Table 1. - Primary End Point (N= 423) CRBSI 97/420 (23.1) CRBSI related to PN 82/386 (21.2) SIRS Criteria or bacteremic on admission 58/404 (14.4) Treated as Catheter infection but Negative BC and Negative SIRS criteria 63/347 (18.2) BSI due to alternative sources AbdominalLungUrologyMultipleOthers 74/276 (26.8)31/276 (11.2)16/276 (5.8)47/276 (17)108/276 (39.1)

Objectives:Urinary Tract Infections (UTIs) are the most common bacterial infections encountered in the Emergency Department (ED). Objectives of this study are to describe the urological pathogens associated with UTIs in the ED, report antibiotic susceptibilities, and assess empiric antibiotic treatment.Methods:A retrospective chart review of 154 patients with positive urine cultures from January to June 2016 were reviewed for inclusion in the study. Patients were excluded if less than 18 years of age, hospitalized, discharged from the ED without antibiotics or diagnosed with pyelonephritis. Patient demographics, uropathogens isolated, in-vitro susceptibility to commonly prescribed oral antibiotics (nitrofurantoin, ciprofloxacin, and sulfamethoxazole/trimethoprim), and antibiotics selected for treatment were recorded.Results:One hundred patients were included in the final analysis. Of the 106 bacterial isolates,Escherichia coli, Klebsiella pneumoniae, and Group BStreptococcusaccounted for 62.5%, 8%, and 8% of pathogens, respectively. Overall susceptibilities were 88.1%, 87.9%, 85.4%, and 70.6% for nitrofurantoin, cefazolin, ciprofloxacin, and sulfamethoxazole/trimethoprim, respectively.Escherichia coliwas most susceptible to nitrofurantoin at 96.9% followed by cefazolin at 94%. Ciprofloxacin was the most prescribed antibiotic followed by cephalexin, nitrofurantoin and sulfamethoxazole/trimethoprim.Conclusions:Based on bacterial susceptibility patterns, nitrofurantoin and cephalexin are reasonable first line agents in the empiric treatment of urinary tract infections identified in the emergency department. The most frequently prescribed antibiotic was ciprofloxacin, highlighting the importance of implementing antimicrobial stewardship initiatives and designing specific tools and educational programs for the emergency department targeted at minimizing fluoroquinolone use.

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Chlorhexidine-related ventilator-associated events: Toward recognition?-CORRIGENDUM Centers for medicare and medicaid services hospital-acquired conditions policy for central line-associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) shows minimal impact on hospital reimbursement -CORRIGENDUM Blood culture utilization at an academic hospital: Addressing a gap in benchmarking -CORRIGENDUM

Management of micro-organisms harbouring AmpC β-lactamases remains challenging. Carbapenems are often considered first-line agents. Due to growing concern regarding carbapenem-resistant Enterobacteriaceae, integrating non-carbapenem treatment strategies is being explored for these pathogens. The primary objective of this study was to evaluate clinical outcomes in patients with bacteraemia secondary to AmpC-producing organisms treated with cefepime or piperacillin/tazobactam (TZP). A retrospective study of adult patients receiving cefepime or TZP for the treatment of AmpC -producing organisms with positive cefoxitin screen (i.e. Citrobacter, Enterobacter or Serratia spp. along with cefoxitin resistance) isolated from blood cultures was conducted. The primary endpoint was clinical cure at end of therapy (EOT). Secondary endpoints included microbiological eradication, frequency of susceptibility changes following treatment, and 7- and 30-day all-cause mortality. Clinical cure at EOT was 87.1%, with 93.2% of patients achieving microbiological eradication. The 7- and 30-day mortality rates were 3.8% and 10.6%, respectively. Organism susceptibility was exceptionally high, with minimum inhibitory concentrations (MICs) of ≤2 μg/mL in 90% of patients treated with cefepime (n = 108). Selection for resistance to third-generation cephalosporins or primary antimicrobial therapy was infrequent at 6.1% (8/132). In conclusion, use of cefepime or TZP for management of AmpC bloodstream infections was associated with clinical and microbiological cure with infrequent selection for resistance.

Background: The antibiotic armamentarium used to combat multi-drug resistant organisms (MDROs) include carbapenems. Continuous infusion (CI) dosing is frequently employed to maximize beta-lactam efficacy; however, use of meropenem CI has been limited due to concerns with product instability. Objective: The primary objective of this study was to quantify meropenem serum concentrations to reflect drug stability when administered as CI over 8- or 12-h exchanges. In addition, a stability experiment was performed to further establish meropenem integrity over 12 h. The secondary objectives were to assess the ability of meropenem to achieve target pharmacokinetic/pharmacodynamic (PK/PD) exposures relative to the minimum inhibitory concentration (MIC) of the pathogen, and to determine clinical cure. Methods: This was a retrospective, observational study on use of CI meropenem (infused either over 8- or 12- h) at a 1% concentration. The stability experiment was conducted on 1% meropenem at room temperature. Results: In 22 patients, a median meropenem daily dose of 6 g/day (range 2-6 g/day) resulted in a median serum concentration of 17.8 mg/L (interquartile range, 9.3-27.8 mg/L). In 95% of cases, meropenem delivered as CI resulted in free drug concentrations at or above the MIC of the pathogen for the entire dosing interval. Clinical cure was achieved in 80% of patients included in this review. The stability experiment revealed negligible drug degradation at the end of the 12-h dosing interval. Conclusions: The data from this study provides compelling evidence for the use of meropenem as CI utilizing either a 12- or 8-h exchange process.

Vancomycin-resistant enterococci (VRE) are a common cause of urinary tract infections (UTIs) and are typically multidrug resistant, including ampicillin. This retrospective study evaluated outcomes of 84 adult patients hospitalized between January 2007 and December 2015 with ampicillin-and vancomycin-resistant enterococcus isolates causing UTI and treated with ampicillin. Treatment response was classified as clinical cure and microbiological eradication. Clinical cure was achieved in 88.1% (74/84) of patients. In patients with follow-up cultures, microbiological eradication was achieved in 86% (50/58) of patients. Cure rates were similar in patients with indwelling urinary catheters (n = 45) receiving catheter exchange/removal (90.47%; 19/21) versus catheter retention (87.5%; 21/24). Presence of co-morbidities, such as diabetes and chronic kidney disease, were not associated with increased risk of treatment failure. Immunocompromised patients achieved lower cure rates of 78.1% (25/32) compared with 94.2% (49/52) among those without immune impairment (P = 0.038). Presence of an underlying urinary tract abnormality was also associated with a lower cure rate of 71.4% (15/21) compared with 93.7% (59/63) in those without urinary tract abnormalities (P = 0.0135). Overall cure rates remained high in all groups providing good evidence to support ampicillin for the treatment of complicated UTI caused by ampicillinand vancomycin-resistant enterococci. (c) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Objectives Voriconazole, a first-line agent for the treatment of invasive fungal infections (IFIs), is metabolized by CYP2C19. A significant proportion of patients fail to achieve therapeutic trough concentrations with standard weight-based voriconazole dosing, placing them at increased risk for treatment failure, which can be life threatening. We sought to test the association between the CYP2C19 genotype and subtherapeutic voriconazole concentrations in adults with IFIs. Patient and methods Adults receiving weight-based voriconazole dosing for the treatment of IFIs were genotyped for the CYP2C19*2, *3, and *17 polymorphisms, and CYP2C19 metabolizer phenotypes were inferred. Steady-state voriconazole trough plasma concentrations and the prevalence of subtherapeutic troughs (<2 mg/l) were compared between patients with the CYP2C19*17/*17 (ultrarapid metabolizer, UM) or *1/*17 (rapid metabolizer, RM) genotype versus those with other genotypes. Logistic regression, adjusting for clinical factors, was performed to estimate the odds of subtherapeutic concentrations. Results Of 70 patients included (mean age 52.5±18 years), 39% were RMs or UMs. Compared with patients with the other phenotypes, RMs/UMs had a lower steady-state trough concentration (4.26±2.2 vs. 2.86±2.3, P=0.0093) and a higher prevalence of subtherapeutic troughs (16 vs. 52%, P=0.0028), with an odds ratio of 5.6 (95% confidence interval: 1.64–19.24, P=0.0044). Conclusion Our findings indicate that adults with the CYP2C19 RM or UM phenotype are more likely to have subtherapeutic concentrations with weight-based voriconazole dosing. These results corroborate previous findings in children and support the potential clinical utility of CYP2C19 genotype-guided voriconazole dosing to avoid underexposure in RMs and UMs.

Background A local quality initiative to improve compliance with surgical antibiotic prophylaxis measures resulted in a high percentage of patients receiving antibiotics within minutes of surgical incision. Studies examining the association between timing of prophylaxis and the risk for surgical site infection (SSI) have produced heterogeneous results. Objective To examine risk factors for SSI, including “just in time” dosing of antibiotic prophylaxis (dose administered within 5 minutes of incision). Methods This was a retrospective matched case-control study. Case patients developed SSI in the 30 days following a clean or clean-contaminated surgical procedure. Control patients did not develop SSI following similar procedures and were matched to ensure comparable baseline risk. We assessed the rate of guideline-compliant antibiotic prophylaxis and calculated odds ratios (ORs) to determine the association of patient covariates with the risk for SSI. Results Forty case patients and 104 controls were included in the study. The rate of appropriate prophylaxis was high in both groups (98% and 94% for case and control groups, respectively). Approximately 15% of case and control patients received antibiotic prophylaxis within 5 minutes of incision, thus, “just in time” dosing did not appear to increase the risk for SSI (OR, 0.814; 95% CI, 0.274–2.415). There was a nonsignificant association between receipt of vancomycin and SSI (OR, 2.844; 95% CI, 0.926–8.737). Conclusion “Just in time” dosing of prophylactic antibiotics was not associated with increased risk for SSI. Further study is needed to clarify the impact of antibiotic choice on the risk for subsequent SSI.

The purpose of this study was to evaluate the impact of the FilmArray Blood Culture Identification (BCID) Panel on the management of patients with blood cultures growing gram positive cocci and Candida. We retrospectively compared clinical and economic outcomes between patients during the BCID testing period and a matched historical control group before BCID testing was introduced. A total of 84 BCID patients were matched to 252 historical controls. BCID identification of coagulase negative staphylococci contaminants resulted in shorter post-culture length of stay (P < 0.008) and saved roughly $30,000 per 100 patients tested. The BCID led to shorter duration of empirical vancomycin for patients with contaminated blood cultures (P = 0.005) and methicillin-susceptible Staphylococcus aureus bacteremia (P < 0.001). Patients with vancomycin-resistant enterococcal bacteremia received active therapy earlier than historical controls (P = 0.047). The BCID, coupled with antimicrobial stewardship intervention, was a cost effective tool to improve patient care.

Purpose: The purpose of this comparative review is to provide clinical information on the semisynthetic lipoglycopeptides (telavancin, oritavancin, and dalbavancin) for the management of gram-positive infections.Methods: A Pub Med search was conducted using the following terms: telavancin, dalbavancin, and oritavancin. Clinical trials evaluating pharmacokinetic properties, pharmacodynamic properties, clinical efficacy, and safety profiles were included in the review.Findings: The lipoglycopeptides are approximately 4- to 8-fold more potent than vancomycin against gram-positive organisms, including activity against vancomycin-intermediate or vancomycin-resistant strains of Staphylococcus and Enterococcus species. In addition, oritavancin maintains activity against Enterococcus species harboring vanA operon. Clinical trial data revealed equal efficacy to vancomycin in the management of acute bacterial skin and skin structure infections and, in the case of telavancin, hospital-acquired pneumonia. A benefit of oritavancin and dalbavancin is that a full course of therapy consists of a single- or 2-dose regimen, respectively. These agents are well tolerated with similar adverse event rates to vancomycin. Telavancin requires a thorough assessment before initiation of therapy to minimize the risk of acute kidney injury and teratogenicity. (C) 2015 Elsevier HS Journals, Inc. All rights reserved.

BACKGROUND:Appropriate de-escalation of empirical antimicrobial therapy is a fundamental component of antimicrobial stewardship. Concern for the late detection of bloodstream pathogens may undermine early streamlining efforts and subject patients to protracted courses of nonessential therapy.OBJECTIVE:To quantify the prevalence of bacterial bloodstream infection (BSI) detection after more than 48 hours of culture incubation. We also assessed the impact of antimicrobial therapy delivered prior to blood sample collection.METHODS:We retrospectively evaluated time to blood culture positivity (TTP) in adult patients at an academic tertiary care hospital. Microbiology reports were reviewed to identify the TTP for the first positive blood culture bottle for each episode of BSI occurring from February 1, 2011, to July 31, 2011. Isolates were classified as true pathogens or contaminants. Blood culture results after 48 hours of incubation were compared with results after 120 hours of incubation.RESULTS:The median TTP of 416 monomicrobial BSIs and 210 contamination episodes was 13.7 and 24.4 hours, respectively (P < .001). The median TTPs in those who received and did not receive prior antibiotics were 17.0 and 12.8 hours, respectively (P < .001). By 48 hours, 98% of aerobic Gram-positive and Gram-negative BSIs were detected. Culture results at 48 hours were 97% sensitive and had a negative predictive value of 99.8%.CONCLUSION:Few true BSIs are detected after more than 48 hours of culture incubation. Clinicians may adjust empirical antibiotic coverage at this time with little risk for subsequent bacterial pathogen detection.

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ABSTRACT The FilmArray blood culture identification (BCID) panel is a rapid molecular diagnostic test approved for use with positive blood culture material. We describe a fatal case of meningococcemia with central nervous system (CNS) involvement detected using the BCID test with culture-negative blood and cerebrospinal fluid.

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