Ferric Carboxymaltose for Anemic Perioperative Populations: A Systematic Literature Review of Randomized Controlled Trials.

IMPORTANCE: Perioperative anemia is a common comorbid condition associated with increased risk of morbidity and mortality in patients undergoing elective surgical procedures. OBJECTIVE: We conducted a systematic literature review (SLR) to determine the efficacy and safety of the use of intravenous ferric carboxymaltose (FCM) for the treatment of perioperative anemia in preoperative, intraoperative, and postoperative elective surgical care. EVIDENCE REVIEW: Studies meeting inclusion criteria for the SLR reported on treatment efficacy in an adult study population randomly allocated to FCM for the treatment of perioperative anemia during the perioperative period. After screening, 10 of 181 identified studies from searches in MEDLINE and EMBASE databases were identified for inclusion in this review. FINDINGS: Preoperative treatment was reported in six studies, intraoperative treatment in one study, postoperative treatment in two studies, and both pre- and postoperative treatment in one study. Together, 1975 patients were studied, of whom 943 were randomized to FCM, of whom 914 received FCM treatment. The 10 studies reported elective surgical populations for colorectal, gastric, orthopedic, abdominal, urologic, plastic, neck, gynecologic, and otolaryngologic procedures. Given the clinical and methodological heterogeneity of the studies, the analyses were limited to qualitative assessments without meta-analyses. All 10 studies reported statistically greater changes in hemoglobin concentration, serum ferritin, and/or transferrin saturation with FCM treatment compared with comparators (placebo, oral iron, standard care, or a combination of these). Two studies reported statistically significant differences in transfusion rate and 2 studies reported significant differences in length of hospital stay between FCM and its comparator(s). CONCLUSIONS AND RELEVANCE: This SLR adds to existing data that administration of FCM in preoperative and postoperative settings improves hematologic parameters. Several studies in the review supported the beneficial effects of FCM in reducing transfusion rate and length of stay. Larger, well-designed, longer-term studies may be needed to further establish the efficacy and safety of FCM in elective surgery patients with perioperative anemia.

Randomized Placebo-Controlled Trial of Ferric Carboxymaltose in Heart Failure With Iron Deficiency: Rationale and Design.

BACKGROUND: Iron deficiency (ID) has a prevalence of ≈40% to 50% among patients in heart failure (HF) with reduced ejection fraction and is associated with worse prognosis. Several trials demonstrated that intravenous ferric carboxymaltose leads to early and sustained improvement in patient-reported outcomes and functional capacity in patients with HF with reduced ejection fraction with ID, yet morbidity and mortality data are limited. METHODS: The objective of the HEART-FID trial (Ferric Carboxymaltose in Heart Failure With Iron Deficiency) is to assess efficacy and safety of ferric carboxymaltose compared with placebo as treatment for symptomatic HF with reduced ejection fraction with ID. HEART-FID is a multicenter, randomized, double-blind, placebo-controlled trial enrolling ≈3014 patients at ≈300 international centers. Eligible patients are aged ≥18 years in stable chronic HF with New York Heart Association functional class II to IV symptoms, ejection fraction ≤40%, ID (ferritin <100 ng/mL or ferritin 100-300 ng/mL with a transferrin saturation <20%), and documented HF hospitalization or elevated N-terminal pro-brain natriuretic peptide. Consented patients are assigned to ferric carboxymaltose or placebo at baseline, with repeated visits/assessments every 6 months for additional study drug based on hemoglobin and iron indices for the trial duration. The primary end point is a hierarchical composite of death and HF hospitalization at 12 months and change from baseline to 6 months in the 6-minute walk test distance. CONCLUSIONS: The HEART-FID trial will inform clinical practice by clarifying the role of long-term treatment with intravenous ferric carboxymaltose, added to usual care, in ambulatory patients with symptomatic HF with reduced ejection fraction with ID. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037931.

Outcomes of extended-spectrum beta-lactamases producing Enterobacteriaceae colonization among patients abdominal surgery patients.

Preoperative enteric screening for extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae was conducted in 360 patients prospectively observed for surgical site infection (SSI). ESBL colonization (adjusted odds ratio [aOR], 2.4) and dirty wound classification (aOR, 3.6) were associated with SSI; no association between carbapenem prophylaxis and reduction in SSI was detected.

Phase 3 adaptive trial design options in treatment of complicated urinary tract infection.

New antimicrobial drugs for treatment of complicated urinary tract infection (cUTI) are generally assessed in randomized, double-blind, noninferiority clinical trials. Robust historical data for the active comparator inform on treatment effect estimation, yet typically do not substitute for the active comparator data in the proposed trial. We report design options for a phase 3 trial of cUTI using a Bayesian hierarchical model and historical data from 2 well-executed phase 3 registrational trials of doripenem. The methodology is directly applicable to other phase 3 noninferiority settings. In addition to the research design application, we provide a novel methodology for assessing the robustness of type I error control. The model borrows heavily from the prior data when the current active comparator parameter estimate approximated the historical estimate. In contrast, the model had restricted borrowing when the 2 estimates were very different. The alternative trial design, with or without the inclusion of futility stopping criteria, provides a framework for future cUTI phase 3 trials.

Community-Acquired Pneumonia Case Validation in an Anonymized Electronic Medical Record-Linked Expert System.

An electronic anonymized patient portal analysis using radiographic reports and admission and discharge diagnoses had sensitivity, specificity, positive predictive value, and negative predictive value of 84.7%, 78.2%, 75%, and 87%, respectively, for community-acquired pneumonia validated against a blinded expert medical review. This approach can help to track antimicrobial use and resistance.

Design and analysis of a pharmacist-enhanced antimicrobial stewardship program in Thailand.

BACKGROUND: The purpose of this study was to design and evaluate the enhancement of an antibiotic stewardship program (ASP) with trained hospital-based infectious diseases clinical pharmacists (IDCPs). METHODS: The IDCP training entailed a 12-hour course by 3 pharmacists. From January 1, 2012-September 30, 2012, all patients consecutively admitted with presumptive infections to 6 medicine units were prospectively followed to discharge. Standard of care (SoC) included ASP measures with or without infectious diseases consultations (IDCs). Physician teams had the option to request IDCs, IDCPs, or both. The IDCP support included pharmacist participation in daily rounds to inform on antibiotic use. Outcomes examined were inappropriate antibiotic use, antibiotic de-escalation, duration of antibiotic use, and hospital length of stay (LOS) stratified by patient groups who received SoC versus adjunctive IDCPs with and without IDCs. RESULTS: There were 150 patients in the SoC group, 104 in the IDCP group, and 320 in the IDCP plus IDC group. Most antibiotic prescriptions were for empirical therapy (n = 373, 65%), and the top-ranked indications were infections of the respiratory tract (n = 287, 50%) and urinary tract (n = 165, 29%). By multivariate analysis, compared with SoC, the 2 other groups were less likely to be prescribed inappropriate antibiotic use (P < .001), had de-escalation of antibiotics (P < .001), received antibiotics <7 days (P < .001), and had subjects with shorter hospital LOSs (P < .001). There were no group differences in mortality. CONCLUSION: Our study suggests measurable treatment benefits associated with international IDCP training and the integration of adjunct IDCP services into hospital-based ASPs.

Systematic Review and Meta-Analysis To Estimate Antibacterial Treatment Effect in Acute Bacterial Skin and Skin Structure Infection.

A systematic literature review and meta-analysis were conducted to estimate the antibacterial treatment effect for linezolid and ceftaroline to inform on the design of acute bacterial skin and skin structure infection (ABSSSI) noninferiority trials. The primary endpoints included an early clinical treatment response (ECTR) defined as cessation of lesion spread at 48 to 72 h postrandomization and the test-of-cure (TOC) response defined as total resolution of the infection at 7 to 14 days posttreatment. The systematic review identified no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12 linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95% confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0% (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for nonantibacterial treatment. The early clinical treatment effect could not be estimated, given no available placebo or proxy for placebo data for this endpoint. Clinical, methodological, and statistical heterogeneity influenced the selection of trials for the meta-analysis of the TOC treatment effect estimation. The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to 55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid, and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The antibacterial treatment effect estimation at TOC will inform on the design and analysis of future noninferiority ABSSSI clinical trials.

Behavior-based interventions to improve hand hygiene adherence among intensive care unit healthcare workers in Thailand.

OBJECTIVE: To evaluate behavioral-based interventions to improve hand hygiene (HH) among healthcare workers (HCWs) at a Thai tertiary care center. METHODS: A quasi-experimental study was performed in 6 intensive care units with computer-generated allocation. Baseline demographic characteristics, self-reported stage of HH behavioral commitment, and observed HH adherence were examined from January 1, 2012, through December 31, 2012 (preintervention), and from January 1, 2013, through December 31, 2013 (postintervention). Self-reported HH was categorized by the stages construct from the Transtheoretical Model of Health Behavior Change. The intensive care unit group randomization was to either standard-of-care HH education every 3 months (S1), intensified HH interventions (S2), or intensified HH interventions plus increased availability of alcohol-based handrub throughout the unit (S3). RESULTS: Among 125 HCWs from 6 intensive care units (42 in S1, 41 in S2, 42 in S3) there were 1,936 total HH observations; most HCWs (100 [ 80%]) were nurses or nurse assistants. Compared with preintervention, overall postintervention HH adherence improved in HCWs assigned to S2 (65% vs 85%; P=.02) and S3 (66% vs 95%; P=.005) but not S1 (68% vs 71%; P=.84). Improvement in HH adherence was demonstrated among HCWs who reported lower stages of HH commitment in S2 (21% vs 84%; P<.001) and S3 (24% vs 89%; P<.001) and in HCWs who self-reported higher stages of commitment in S3 (78% vs 96%; P<.001). CONCLUSIONS: HCW HH programs may benefit from stage-based tailored strategies to promote sustained HH adherence.

Tuberculin skin test and QuantiFERON-TB Gold In-tube Test for latent tuberculosis in Thai HIV-infected adults.

BACKGROUND AND OBJECTIVE: Limited data exist for the performance of QuantiFERON-TB Gold In-tube Test (QFT-IT) in comparison to tuberculin skin test (TST) for detecting latent tuberculosis (LTB) in patients with human immunodeficiency virus (HIV) infection from tuberculosis (TB)-endemic Asia-Pacific countries. METHODS: A cohort study of Thai HIV-infected patients without history of TB or LTB treatment was conducted from March 2012 through March 2013. Each patient underwent simultaneous TST and QFT-IT. RESULTS: Among the 150 enrolled subjects, the median age was 40 years (range 17-65), 53% were male, and the median CD4 count was 367 cells/µL (range 8-1290). Reactive TST and positive QFT-IT were 16% and 13%, respectively, with low concordance between tests (kappa = 0.26); correlation between TST reaction size and level of interferon-γ was moderate (r = 0.34). Independent factors associated with discordant results were long-term smoking (adjusted odds ratio (aOR) 5.74; P = 0.002) for TST-reactive, QFT-IT-negative subjects, and age greater than 52 years (aOR 5.56; P = 0.02) and female gender (aOR 4.40; P = 0.04) for TST non-reactive, QFT-IT-positive subjects. The level of agreement between both tests improved when using a TST cut-off of ≥ 10 mm (kappa = 0.39). CONCLUSIONS: In our setting where QFT-IT is available but has limited use due to cost, TST with a cut-off of 10 mm for reactivity should be the initial LTB test. HIV-infected women and persons older than 52 years with non-reactive TST and long-term smokers with reactive TST may benefit from subsequent QFT-IT.

Retapamulin prescriptions and monitored off-label use.

INTRODUCTION: Retapamulin, a topical pleuromutilin that selectively inhibits bacterial protein synthesis, is approved for treatment of impetigo and secondarily infected traumatic lesions in adults and in children older than 9 months of age. OBJECTIVE: A 5-year study was conducted to monitor prescription use in children younger than 9 months of age. METHODS: Annual prescription events were monitored in the UK Clinical Practice Research Datalink (CPRD) and the Clinformatics™ DataMart Multiplan (IMPACT), a product of OptumInsight Life Sciences, Inc. (Eden Prairie, MN, USA), from the USA. RESULTS: In the CPRD, of 148 prescriptions, three (2 %) were identified in children aged less than 9 months between years 2008 and 2011. In IMPACT, of 59,210 claims for retapamulin in children, 1,951 (3.3 %) were categorized as definitive, or uncertain for, less than 9 months of age between 2007 and 2011. CONCLUSION: Retapamulin prescription events in children aged less than 9 months were relatively low compared with other recent estimations of off-label pediatric medicines. Our report provides a framework for future investigations and discussions that may facilitate off-label reporting schemes and promote pediatric drug safety.

Colistin-based treatment for extensively drug-resistant Acinetobacter baumannii pneumonia.

Data for treatment and outcomes of extensively drug-resistant Acinetobacter baumannii (XDR-AB) pneumonia are limited. A retrospective cohort study of 236 adult patients with XDR-AB pneumonia was conducted between January 2009 and December 2012. The median age of subjects was 70 years (range 17-95 years), 53% were male, 55% had ventilator-associated pneumonia and 42% had been admitted to the intensive care unit. All XDR-AB isolates were susceptible only to tigecycline and colistin; 52 (22%) of the 236 subjects did not receive an agent active against XDR-AB, with an associated 28-day survival of 0%. Colistin-based two-drug combination treatment was prescribed to 166 subjects (70%); regimens included (i) colistin and high-dose sulbactam (n=93); (ii) colistin and tigecycline (n=43); and (iii) colistin and high-dose prolonged infusion of a carbapenem (n=30). The 28-day survival rate and mean length of hospital stay were not statistically different between these three regimens (65%, 53% and 60% and 39, 39 and 38 days, respectively). Predictors of mortality included Acute Physiology and Chronic Health Evaluation (APACHE) II score [adjusted odds ratio (aOR)=1.11; P<0.001 for each point increase], duration from infection onset to receipt of active regimen (aOR=1.01; P=0.002 for each hour delay), underlying malignancy (aOR=3.46; P=0.01) and chronic kidney disease (aOR=2.85; P=0.03). These findings suggest that the three colistin-based two-drug combination regimens may be treatment options for XDR-AB pneumonia.

Asymptomatic eosinophilia due to gnathostomiasis.

The diagnosis of gnathostomiasis typically includes a triad of eosinophilia, migratory skin lesions, and exposure risk. The cutaneous manifestations are protean yet often involve intermittent migratory swellings and creeping skin eruptions with abscesses or nodules, which vary in onset and duration. We report the first case of gnathostomiasis presenting as fever and eosinophilia without cutaneous migratory and internal organ involvement.