Harvesting the low-hanging fruit? Comparative assessment of intravenous to oral route antimicrobial conversion policy implementation.

Policies that promote conversion of antibiotics from intravenous to oral route administration are considered "low hanging fruit" for hospital antimicrobial stewardship programs. We developed a simple metric based on digestive days of therapy divided by total days of therapy for targeted agents and a method for hospital comparisons. External comparisons may help identify opportunities for improving prospective implementation.

Conventional Antifungals for Invasive Infections Delivered by Unconventional Methods; Aerosols, Irrigants, Directed Injections and Impregnated Cement.

The administration of approved antifungals via unapproved formulations or administration routes (such as aerosol, direct injection, irrigation, topical formulation and antifungal-impregnated orthopedic beads or cement) may be resorted to in an attempt to optimize drug exposure while minimizing toxicities and/or drug interactions associated with conventional (systemic) administrations. Existing data regarding such administrations are mostly restricted to uncontrolled case reports of patients with diseases refractory to conventional therapies. Attribution of efficacy and tolerability is most often problematic. This review updates prior published summaries, reflecting the most recent data and its application by available prevention and treatment guidelines for invasive fungal infections. Of the various dosage forms and antifungals, perhaps none is more widely reported than the application of amphotericin B-containing aerosols for the prevention of invasive mold infections (notably Aspergillus spp.).

Impact of select risk factors on treatment outcome in adults with candidemia.

BACKGROUND: Studies examining relationships between patient-related factors and treatment outcome in patients with candidemia are limited and often based on all-cause mortality. OBJECTIVE: Our purpose was to examine the impact of concurrent renal replacement therapy (RRT) and other pre-specified factors on treatment outcome among adults with candidemia. METHODS: This Institutional Review Board (IRB)-approved, single-center, case-cohort study included patients over 18 years of age admitted to Duke University Hospital between Jun 1, 2013 and Jun 1, 2017 with a blood culture positive for Candida spp. Treatment-, patient-, and disease-specific data were collected, and outcome (success/failure) determined 90 days after the index culture. An odds ratio (OR) and 95% confidence interval (95%CI) were calculated for the following during therapy: receipt of RRT, fluconazole monotherapy regimen, intensive care unit (ICU) stay, and neutropenia. RESULTS: Among the 112 encounters (from 110 unique patients) included, treatment failure occurred in 8/112 (7.1%). Demographics were comparable between outcome groups. Among 12 patients receiving concomitant RRT, only 1 patient failed therapy. With regard to treatment failure, no significant differences were observed with RRT (OR, 1.21; 95%CI, 0.14 - 10.75), fluconazole monotherapy regimen (OR, 1.59; 95%CI, 0.3-8.27), ICU stay (OR, 1.43; 95%CI, 0.32-6.29), and neutropenia (0 treatment failures). CONCLUSIONS: Treatment failure, receipt of concomitant RRT, and neutropenia were infrequent in patients undergoing treatment for candidemia. In our cohort, exposure to RRT, a fluconazole monotherapy regimen, ICU stay, or neutropenia during treatment did not impact treatment outcome.

Impact of select risk factors on treatment outcome in adults with candidemia

Background: Studies examining relationships between patient-related factors and treatment outcome in patients with candidemia are limited and often based on all-cause mortality. Objective: Our purpose was to examine the impact of concurrent renal replacement therapy (RRT) and other pre-specified factors on treatment outcome among adults with candidemia. Methods: This Institutional Review Board (IRB)-approved, single-center, case-cohort study included patients over 18 years of age admitted to Duke University Hospital between Jun 1, 2013 and Jun 1, 2017 with a blood culture positive for Candida spp. Treatment-, patient-, and disease-specific data were collected, and outcome (success/failure) determined 90 days after the index culture. An odds ratio (OR) and 95% confidence interval (95%CI) were calculated for the following during therapy: receipt of RRT, fluconazole monotherapy regimen, intensive care unit (ICU) stay, and neutropenia. Results: Among the 112 encounters (from 110 unique patients) included, treatment failure occurred in 8/112 (7.1%). Demographics were comparable between outcome groups. Among 12 patients receiving concomitant RRT, only 1 patient failed therapy. With regard to treatment failure, no significant differences were observed with RRT (OR, 1.21; 95%CI, 0.14 - 10.75), fluconazole monotherapy regimen (OR, 1.59; 95%CI, 0.3-8.27), ICU stay (OR, 1.43; 95%CI, 0.32-6.29), and neutropenia (0 treatment failures). Conclusions: Treatment failure, receipt of concomitant RRT, and neutropenia were infrequent in patients undergoing treatment for candidemia. In our cohort, exposure to RRT, a fluconazole monotherapy regimen, ICU stay, or neutropenia during treatment did not impact treatment outcome

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Evaluation of a vancomycin dosing nomogram in obese patients weighing at least 100 kilograms.

BACKGROUND: There remains variability in both practice and evidence related to optimal initial empiric dosing strategies for vancomycin. OBJECTIVE: Our primary objective was to describe the percentage of obese patients receiving vancomycin doses consistent with nomogram recommendations achieving targeted initial steady-state serum vancomycin concentrations. Secondary objectives were to describe the primary endpoint in subgroups based on patient weight and estimated creatinine clearance, to describe the rate of supratherapeutic vancomycin accumulation following an initial therapeutic trough concentration, and to describe the rate of vancomycin-related adverse events. METHODS: This single-center, IRB-approved, retrospective cohort included adult patients ≥ 100 kilograms total body weight with a body mass index (BMI) >30 kilograms/m2 who received a stable nomogram-based vancomycin regimen and had at least one steady-state vancomycin trough concentration. Data collected included vancomycin regimens and concentrations, vancomycin indication, serum creatinine, and vancomycin-related adverse events. Patients were divided into two cohorts by goal trough concentration: 10-15 mcg/mL and 15-20 mcg/mL. RESULTS: Of 325 patients screened, 85 were included. Goal steady-state concentrations were reached in 42/85 (49.4%) of total patients. CONCLUSIONS: Achievement of initial steady-state vancomycin serum concentrations in the present study (approximately 50%) was consistent with the use of published vancomycin dosing nomograms.

Evaluation of a vancomycin dosing nomogram in obese patients weighing at least 100 kilograms

Background: There remains variability in both practice and evidence related to optimal initial empiric dosing strategies for vancomycin. Objective: Our primary objective was to describe the percentage of obese patients receiving vancomycin doses consistent with nomogram recommendations achieving targeted initial steady-state serum vancomycin concentrations. Secondary objectives were to describe the primary endpoint in subgroups based on patient weight and estimated creatinine clearance, to describe the rate of supratherapeutic vancomycin accumulation following an initial therapeutic trough concentration, and to describe the rate of vancomycin-related adverse events. Methods: This single-center, IRB-approved, retrospective cohort included adult patients ≥ 100 kilograms total body weight with a body mass index (BMI) >30 kilograms/m2 who received a stable nomogram-based vancomycin regimen and had at least one steady-state vancomycin trough concentration. Data collected included vancomycin regimens and concentrations, vancomycin indication, serum creatinine, and vancomycin-related adverse events. Patients were divided into two cohorts by goal trough concentration: 10-15 mcg/mL and 15-20 mcg/mL. Results: Of 325 patients screened, 85 were included. Goal steady-state concentrations were reached in 42/85 (49.4%) of total patients. Conclusions: Achievement of initial steady-state vancomycin serum concentrations in the present study (approximately 50%) was consistent with the use of published vancomycin dosing nomograms

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Influence of Reported Penicillin Allergy on Mortality in MSSA Bacteremia.

BACKGROUND: Penicillin allergy frequently impacts antibiotic choice. As beta-lactams are superior to vancomycin in treating methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, we examined the effect of reported penicillin allergy on clinical outcomes in patients with MSSA bacteremia. METHODS: In this retrospective cohort study of adults with MSSA bacteremia admitted to a large tertiary care hospital, outcomes were examined according to reported penicillin allergy. Primary outcomes included 30-day and 90-day mortality rates. Multivariable regression models were developed to quantify the effect of reported penicillin allergy on mortality while adjusting for potential confounders. RESULTS: From 2010 to 2015, 318 patients with MSSA bacteremia were identified. Reported penicillin allergy had no significant effect on adjusted 30-day mortality (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.29-1.84; P = .51). Patients with reported penicillin allergy were more likely to receive vancomycin (38% vs 11%, P < .01), but a large number received cefazolin regardless of reported allergy (29 of 66, 44%). Mortality rates were highest among nonallergic patients receiving vancomycin (22.6% vs 7.4% for those receiving beta-lactams regardless of reported allergy, P < .01). In multivariable analysis, beta-lactam receipt was most strongly associated with survival (OR, 0.26; 95% CI, 0.12-0.54). CONCLUSIONS: Reported penicillin allergy had no significant effect on 30- or 90-day mortality. Non-penicillin-allergic patients receiving vancomycin for treatment of MSSA bacteremia had the highest mortality rates overall. Receipt of a beta-lactam was the strongest predictor of survival. These results underscore the importance of correct classification of patients with penicillin allergy and appropriate treatment with a beta-lactam when tolerated.

Impact of automatic infectious diseases consultation on the management of fungemia at a large academic medical center.

PURPOSE: The impact of automatic infectious diseases (ID) consultation for inpatients with fungemia at a large academic medical center was studied. METHODS: In this single-center, retrospective study, the time to appropriate antifungal therapy before and after implementing a policy requiring automatic ID consultation for the management of fungemia for all patients with an inpatient positive blood culture for fungus was examined. The rates of ID consultation; the likelihood of receiving appropriate antifungal therapy; central venous catheter (CVC) removal rates; performance of ophthalmologic examinations; infection-related length of stay (LOS); rates of all-cause inhospital mortality, death, or transfer to an intensive care unit within 7 days of first culture; and inpatient cost of antifungals were also evaluated. RESULTS: A total of 173 unique episodes (94 and 79 in the control and intervention groups, respectively) were included. Candida species were the most frequently cultured organisms, isolated from over 90% of patients in both groups. No differences were observed between the control and intervention groups in time to appropriate therapy, infection-related LOS, or time to CVC removal. However, patients in the intervention group were more likely than those in the control group to receive appropriate antifungal therapy (p = 0.0392), undergo ophthalmologic examination (p = 0.003), have their CVC removed (p = 0.0038), and receive ID consultation (p = 0.0123). Inpatient antifungal costs were significantly higher in the intervention group (p = 0.0177). CONCLUSION: While automatic ID consultation for inpatients with fungemia did not affect the time to administration of appropriate therapy, improvement was observed for several process indicators, including rates of appropriate antifungal therapy selection, time to removal of CVCs, and performance of ophthalmologic examinations.

Role of isavuconazole in the treatment of invasive fungal infections.

Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug-drug interactions, and/or variable pharmacokinetic profiles. Isavuconazole, a second-generation triazole, was approved by the US Food and Drug Administration in March 2015 and the European Medicines Agency in July 2015 for the treatment of adults with invasive aspergillosis (IA) or mucormycosis. Similar to amphotericin B and posaconazole, isavuconazole exhibits a broad spectrum of in vitro activity against yeasts, dimorphic fungi, and molds. Isavuconazole is available in both oral and intravenous formulations, exhibits a favorable safety profile (notably the absence of QTc prolongation), and reduced drug-drug interactions (relative to voriconazole). Phase 3 studies have evaluated the efficacy of isavuconazole in the management of IA, mucormycosis, and invasive candidiasis. Based on the results of these studies, isavuconazole appears to be a viable treatment option for patients with IA as well as those patients with mucormycosis who are not able to tolerate or fail amphotericin B or posaconazole therapy. In contrast, evidence of isavuconazole for invasive candidiasis (relative to comparator agents such as echinocandins) is not as robust. Therefore, isavuconazole use for invasive candidiasis may initially be reserved as a step-down oral option in those patients who cannot receive other azoles due to tolerability or spectrum of activity limitations. Post-marketing surveillance of isavuconazole will be important to better understand the safety and efficacy of this agent, as well as to better define the need for isavuconazole serum concentration monitoring.

Challenges in Preparation of Cumulative Antibiogram Reports for Community Hospitals.

Knowledge of local antimicrobial resistance is critical for management of infectious diseases. Community hospitals' compliance with Clinical and Laboratory Standards Institute (CLSI) guidance for creation of cumulative antibiograms is uncertain. This descriptive cohort study of antibiogram reporting practices included community hospitals enrolled in the Duke Infection Control Outreach Network. Cumulative antibiograms from 2012 were reviewed for criteria on reporting practices and compliance with CLSI guidelines. Microbiology personnel were sent a voluntary, electronic survey on antibiogram preparation practices. Data were compiled using descriptive statistics. Thirty-two of 37 (86%) hospitals provided antibiograms; 26 of 37 (70%) also provided survey responses. Twelve (38%) antibiograms specified methods used for compiling data and exclusion of duplicates. Eight (25%) reported only species with >30 isolates. Of the 24 that did not follow the 30-isolate rule, 3 (13%) included footnotes to indicate impaired statistical validity. Twenty (63%) reported at least 1 pathogen-drug combination not recommended for primary or supplemental testing per CLSI. Thirteen (41%) separately reported methicillin-resistant and -susceptible Staphylococcus aureus. Complete compliance with CLSI guidelines was observed in only 3 (9%) antibiograms. Survey respondents' self-assessment of full or partial compliance with CLSI guidelines was 50% and 15%, respectively; 33% reported uncertainty with CLSI guidelines. Full adherence to CLSI guidelines for hospital antibiograms was uncommon. Uncertainty about CLSI guidelines was common. Alternate strategies, such as regional antibiograms using pooled data and educational outreach efforts, are needed to provide reliable and appropriate susceptibility estimates for community hospitals.

Sulfonylurea Prescribing Patterns After the Introduction of DPP-4 Inhibitors and GLP-1 Receptor Agonists.

PURPOSE: Although newer agents (dipeptidyl peptidase [DPP]-4 inhibitors and glucagon-like peptide [GLP]-1 receptor agonists) are available for the treatment of hyperglycemia in patients with type 2 diabetes mellitus (T2DM), the impact of the availability of these agents on the use of second-generation sulfonylureas (SUs) is unknown. This article presents percentages of patients prescribed SUs, using data from the National Ambulatory Medical Care Survey (NAMCS). The associations between SU prescribing and prespecified variables of interest were also explored. METHODS: The NAMCS database was queried for visits of patients aged ≥18 years with an International Classification of Diseases, Ninth Revision diagnostic code relevant to T2DM. χ(2) tests were conducted to assess the associations between SU use and year-group (2003-2004, 2007-2008, or 2009-2010) and other variables of interest. A multivariate logistic regression model was constructed to jointly assess the value of these variables in predicting SU use. All analyses were weighted using procedures recommended by the National Center for Health Statistics. FINDINGS: Data from 7042 eligible visits were included, representing an extrapolated national estimate of 280,733,405 patient visits. The percentages of patients who received a prescription for an SU, by study year, were 25.7%, 23.4%, and 23.7% in 2003 to 2004, 2007 to 2008, and 2009 to 2010, respectively (P = 0.57). In the multivariate model, age ≥70 years, male sex, nonwhite race, primary care physician seen, and concurrent DPP-4 inhibitor use were significantly associated with SU use. IMPLICATIONS: No significant decrease in the use of SUs was observed after the introduction of DPP-4 inhibitors and GLP-1 receptor agonists. However, patient-specific factors (eg, select demographic variables, site of care, and concurrent medication use) were associated with SU use.

Risk factors associated with unfavorable short-term treatment outcome in patients with documented Pseudomonas aeruginosa infection.

BACKGROUND: Invasive infections with Pseudomonas aeruginosa (PA) are associated with significant morbidity and mortality. While risk factors for mortality have been identified, their influence on short-term outcomes impacting treatment selection has not been reported. OBJECTIVES: The objective of this study was to evaluate the relationship between select patient- and treatment-related factors and short-term outcomes in patients with PA pneumonia and/or bacteremia. SETTING: Large academic medical center in the United States. METHODS: This IRB-approved single-center, retrospective case-cohort study included patients >18 years of age with culture-confirmed PA bacteremia and/or pneumonia receiving antimicrobial agent(s) active against PA. MAIN OUTCOME MEASURE: Risk of unfavorable short-term treatment result. RESULTS: The population consisted of 117 patients (40 [34 %] and 77 [66 %] in the unfavorable and not-unfavorable groups, respectively). Baseline characteristics including age (mean of 63 years), gender (55 % male), Charlson score, creatinine clearance, and body mass index were comparable between groups. Piperacillin/tazobactam was the most common monotherapy antibiotic (46 and 33 % in unfavorable and not-unfavorable groups, respectively). Combination therapy primarily consisted of a beta-lactam plus ciprofloxacin in both unfavorable (10 %) and not-unfavorable (20 %) outcome groups. The preliminary regression model indicated that SIRS, direct ICU admission, and vasopressor therapy were associated with an unfavorable outcome. In addition, patients who received more than two active antimicrobials had a reduced risk of an unfavorable outcome. The final regression model revealed that vasopressor therapy (odds ratio [OR] 6.0; 95 % confidence interval [95 % CI] 2.3, 17) was associated with an unfavorable outcome, while receipt of greater than two active antibiotics was associated with a reduced risk of an unfavorable outcome (OR 0.26; 95 % CI 0.07, 0.83). CONCLUSIONS: Treatment with more than two agents with activity against PA was associated with a reduced risk of an unfavorable short-term treatment outcome in patients with bacteremia and/or pneumonia.

Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam.

STUDY OBJECTIVES: To determine whether the addition of piperacillin-tazobactam leads to an increased incidence of nephrotoxicity in patients receiving vancomycin and to explore potential confounding factors that may increase the risk of vancomycin-induced nephrotoxicity. DESIGN: Single-center, retrospective cohort study. SETTING: Large, academic, tertiary-care hospital. PATIENTS: One hundred ninety-one adults hospitalized between July 1, 2009, and July 1, 2012, with normal baseline renal function who received a minimum of 48 hours of vancomycin for any indication were included in the analysis. Of these patients, 92 received a minimum of 48 hours of intravenous piperacillin-tazobactam concurrently with vancomycin, with piperacillin-tazobactam being initiated within 48 hours of the initiation of vancomycin (combination group); 99 received vancomycin without piperacillin-tazobactam (vancomycin group). MEASUREMENTS AND MAIN RESULTS: A univariate analysis was performed to assess the effect of the following risk factors on the incidence of nephrotoxicity within the first 7 days of vancomycin treatment: concomitant nephrotoxic agents, advanced age, steady-state vancomycin trough concentration of 15 µg/ml or greater, elevated Charlson Comorbidity Index, and a total daily vancomycin dose of 4 g or greater. A multivariate model was constructed to compare the incidence of the primary end point of nephrotoxicity, defined as a minimum 1.5-fold increase in serum creatinine concentration, between groups. Nephrotoxicity developed in 8 (8.1%) of 99 patients in the vancomycin group and in 15 (16.3%) of 92 patients in the combination group (1-sided χ(2) test, p=0.041). In the univariate analysis, only vancomycin trough concentration of 15 µg/ml or greater (odds ratio 3.67) was associated with an increased risk of developing nephrotoxicity. In the multivariate analysis, patients with piperacillin-tazobactam added to vancomycin exhibited an increased incidence of nephrotoxicity, with an odds ratio of 2.48 (1-sided χ(2) test, p=0.032). CONCLUSION: We observed an increased incidence of nephrotoxicity in vancomycin-treated patients who received concomitant piperacillin-tazobactam. A steady-state vancomycin trough concentration of 15 µg/ml or greater was also associated with an increased risk of the development of nephrotoxicity. These findings should be confirmed in larger, randomized studies.

Clinical effectiveness of posaconazole versus fluconazole as antifungal prophylaxis in hematology-oncology patients: a retrospective cohort study.

In preventing invasive fungal disease (IFD) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), clinical trials demonstrated efficacy of posaconazole over fluconazole and itraconazole. However, effectiveness of posaconazole has not been investigated in the United States in real-world setting outside the environment of controlled clinical trial. We performed a single-center, retrospective cohort study of 130 evaluable patients ≥18 years of age admitted to Duke University Hospital between 2004 and 2010 who received either posaconazole or fluconazole as prophylaxis during first induction or first reinduction chemotherapy for AML or MDS. The primary endpoint was possible, probable, or definite breakthrough IFD. Baseline characteristics were well balanced between groups, except that posaconazole recipients received reinduction chemotherapy and cytarabine more frequently. IFD occurred in 17/65 (27.0%) in the fluconazole group and in 6/65 (9.2%) in the posaconazole group (P = 0.012). Definite/probable IFDs occurred in 7 (10.8%) and 0 patients (0%), respectively (P = 0.0013). In multivariate analysis, fluconazole prophylaxis and duration of neutropenia were predictors of IFD. Mortality was similar between groups. This study demonstrates superior effectiveness of posaconazole over fluconazole as prophylaxis of IFD in AML and MDS patients. Such superiority did not translate to reductions in 100-day all-cause mortality.

Recent advances in the treatment of life-threatening, invasive fungal infections.

INTRODUCTION: Invasive fungal infections (IFIs) pose significant morbidity and are often life-threatening to many high-risk patients. Timely diagnosis and treatment of these infections with optimal therapy is imperative. AREAS COVERED: Advances have been made in diagnostic biomarkers such as peptide nucleic acid fluorescent in situ hybridization, ß-D-glucan and galactomannan, although more research is needed in this area to assist with both diagnosis and monitoring for improvement of IFI management. Novel antifungal agents (azole antifungals and echinocandins) are being investigated that have activity against Candida spp. and Aspergillus spp. Optimizing the pharmacodynamics (PD) of our current antifungal therapies through such strategies as continuous infusion of amphotericin B and dose escalation of echinocandins and liposomal formulations of amphotericin B have also been investigated with mixed results. Therapeutic drug monitoring (TDM) shows promise as evident from data with such agents as flucytosine, itraconazole, voriconazole and posaconazole. EXPERT OPINION: The goal for the future of biomarkers in IFIs will be to have excellent sensitivity and specificity to ideally identify a particular fungus causing the infection or eliminate its existence to prevent unnecessary costs, resistance and antifungal usage. In addition, further developments of new antifungals are needed and judicious use of the current regimens needs to be optimized through antifungal PD properties and TDM.

Utility of a clinical risk factor scoring model in predicting infection with extended-spectrum ß-lactamase-producing enterobacteriaceae on hospital admission.

OBJECTIVE: To validate the utility of a previously published scoring model (Italian) to identify patients infected with community-onset extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-EKP) and develop a new model (Duke) based on local epidemiology. METHODS: This case-control study included patients 18 years of age or more admitted to Duke University Hospital between January 1, 2008, and December 31, 2010, with culture-confirmed infection due to an ESBL-EKP (cases). Uninfected controls were matched to cases (3:1). The Italian model was applied to our patient population for validation. The Duke model was developed through logistic-regression-based prediction scores calculated on variables independently associated with ESBL-EKP isolation. Sensitivities and specificities at various point cutoffs were determined, and determination of the area under the receiver operating characteristic curve (ROC AUC) was performed. RESULTS: A total of 123 cases and 375 controls were identified. Adjusted odds ratios and 95% confidence intervals for variables previously identified in the Italian model were as follows: hospitalization (3.20 [1.62-6.55]), transfer (4.31 [2.15-8.78]), urinary catheterization (5.92 [3.09-11.60]), ß-lactam and/or fluoroquinolone therapy (3.76 [2.06-6.95]), age 70 years or more (1.55 [0.79-3.01]), and Charlson Comorbidity Score of 4 or above (1.06 [0.55-2.01]). Sensitivity and specificity were, respectively, more than or equal to 95% and less than or equal to 47% for scores 3 or below and were less than or equal to 50% and more than or equal to 96% for scores 8 or above. The ROC AUC was 0.88. Variables identified in the Duke model were as follows: hospitalization (2.63 [1.32-5.41]), transfer (5.30 [2.67-10.71]), urinary catheterization (6.89 [3.62-13.38]), ß-lactam and/or fluoroquinolone therapy (3.47 [1.91-6.41]), and immunosuppression (2.34 [1.14-4.80]). Sensitivity and specificity were, respectively, more than or equal to 94% and less than or equal to 65% for scores 3 or below and were less than or equal to 58% and more than or equal to 95% for scores 8 or above. The ROC AUC was 0.89. CONCLUSION: While the previously reported model was an excellent predictor of community-onset ESBL-EKP infection, models utilizing factors based on local epidemiology may be associated with improved performance.

Constructing unit-specific empiric treatment guidelines for catheter-related and primary bacteremia by determining the likelihood of inadequate therapy.

This study aimed to determine the feasibility of using likelihood of inadequate therapy (LIT), a parameter calculated by using pathogen frequency and in vitro susceptibility for determination of appropriate empiric antibiotic therapy for primary bloodstream infections. Our study demonstrates that LIT may reveal differences in traditional antibiograms.

Addressing current medical needs in invasive fungal infection prevention and treatment with new antifungal agents, strategies and formulations.

Introduction: Morbidity and mortality associated with invasive fungal infections (IFIs) remains unacceptably high. Such diseases represent a substantial burden to the healthcare system. New options are needed to address antifungal resistance in existing and emerging pathogens and improve treatment outcomes while minimizing drug-related toxicities and interactions. Awareness of new and potential future options is of great value for those healthcare professionals who care for patients with IFIs. Areas covered: A search of PubMed, infectious diseases conference abstracts and reference lists from relevant publications was conducted and relevant information abstracted. This review describes the limitations of existing systemic antifungal therapies (e.g., resistance, drug-drug interactions, drug-related toxicities) and summarizes data regarding several emerging antifungal compounds including (but not limited to) new triazoles (e.g. isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin Z. Agents in clinical trials such as (but not limited to) new triazoles (e.g., isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin are included. New formulations of existing drugs including reformulations of miconazole, posaconazole and amphotericin B are also reviewed. Finally, new or novel administration strategies for existing drugs such as combination antifungal therapy, antifungal dose escalation, adjunctive use of iron chelators and preemptive therapy are discussed. Expert opinion: All present antifungal agents have some deficiencies in antifungal spectra, toxicity, pharmacokinetics and/or drug-drug interactions, making them less than ideal for some fungal infections. Therefore, there remains an urgent need to find safe, effective, rapidly fungicidal, broad-spectrum antifungal agents with excellent pharmacodynamics to effectively eliminate the fungus from the body with short antifungal courses.

Ceftaroline fosamil for treatment of community-acquired pneumonia: findings from FOCUS 1 and 2 and potential role in therapy.

Cephalosporins have been widely used over the last few decades (often as first-line antibiotic therapy) for numerous infections, owing primarily to their broad spectrum of microbiologic activity and favorable safety profile. Current Infectious Diseases Society of America guidelines identify a third-generation cephalosporin in combination with a macrolide antibiotic as an option for treatment of hospitalized adult patients with community-acquired pneumonia (CAP) outside the intensive care unit setting. Although ceftriaxone is a frequently used agent for CAP, increasing incidence of multidrug-resistant Streptococcus pneumoniae and concerns regarding poor outcomes associated with ineffective therapy have prompted the search for a well-tolerated treatment alternative that is effective against bacteria that can cause CAP. Ceftaroline fosamil, the prodrug of ceftaroline, is a new extended-spectrum cephalosporin that exhibits time-dependant bactericidal activity against numerous Gram-negative and Gram-positive organisms, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. pneumoniae. Notable exceptions include Pseudomonas spp. and Gram-negative organisms that produce extended-spectrum ß-lactamases or carbapenemases. Two large Phase III clinical trials (FOCUS 1 and 2) reported that ceftaroline fosamil was well tolerated, with a clinical cure rate of CAP that was noninferior to that with ceftriaxone in nonintensive care unit adult inpatients with moderately severe (Pneumonia Outcomes Research Team score of III or IV) community-acquired pneumonia.