Wild-type MIC distributions and epidemiological cutoff values for amphotericin B, flucytosine, and itraconazole and Candida spp. as determined by CLSI broth microdilution.

Clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs) have been established for several Candida spp. and the newer triazoles and echinocandins but are not yet available for older antifungal agents, such as amphotericin B, flucytosine, or itraconazole. We determined species-specific ECVs for amphotericin B (AMB), flucytosine (FC) and itraconazole (ITR) for eight Candida spp.

Evaluation of postprescription review and feedback as a method of promoting rational antimicrobial use: a multicenter intervention.

Objective: To evaluate the impact of postprescription review of broad-spectrum antimicrobial (study-ABX) agents on rates of antimicrobial use.

Design: Quasi-experimental before-after study.

Setting: Five academic medical centers.

Engaging children in genomics research: decoding the meaning of assent in research.

This article considers how to approach assent from children for genomics research. We examine the "protection" rationale for assent, which emerged in the context of a historical debate regarding whether it was ever acceptable to subject children to risks of research for the benefit of others. We also consider the "development" rationale for assent, which has been articulated for pediatric clinical practice, as an alternative approach for addressing this issue.

Adolescent refusal of lifesaving treatment: are we asking the right questions?

In life-threatening situations, whether and under what conditions a minor should be allowed to refuse a lifesaving intervention is an important question. This article addresses the issue of whether adolescents, as a rule, possess capacity of sufficient quality that it should be respected even in the case of life-altering medical decisions. After reviewing the traditional approach to determining when adolescents should have their decisions respected, an approach that focuses on establishing capacity under a traditional informed consent model, the article reviews our evolving understanding of adolescent brain development and explores the implications for adolescent decision-making capacity.

Activities of E1210 and comparator agents tested by CLSI and EUCAST broth microdilution methods against Fusarium and Scedosporium species identified using molecular methods.

Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques.

Finding the proper balance between freedom and justice: why we should not eliminate personal belief exemptions to vaccine mandates.

Lantos and colleagues (this issue) propose to eliminate personal belief exemptions from school vaccine mandates, particularly for those vaccines that target deadly contagious childhood disease. They argue that not doing so would be unjust. In this counterpoint, we argue that, for reasons grounded in both health policy and morality, a just vaccine policy need not prohibit parents from claiming personal belief exemptions.

Detection of Staphylococcus aureus isolates with heterogeneous intermediate-level resistance to vancomycin in the United States.

The prevalence of heterogeneous intermediate-level resistance to vancomycin (hVISA) in Staphylococcus aureus was assessed by screening a large collection of recent isolates. Susceptibility testing by the Clinical and Laboratory Standards Institute broth microdilution method and the Etest GRD (glycopeptide resistance detection) method (bioMérieux) was performed on 4,210 clinically significant S. aureus isolates obtained in 2009 from 43 U.

Current practice in Staphylococcus aureus screening and decolonization.

We surveyed infectious disease physicians to determine their preoperative Staphylococcus aureus screening and decolonization practices. Sixty percent reported preoperative screening for S. aureus.

Wild-type MIC distributions and epidemiologic cutoff values for fluconazole, posaconazole, and voriconazole when testing Cryptococcus neoformans as determined by the CLSI broth microdilution method.

When clinical susceptibility breakpoints (CBPs) are absent, establishing wild-type (WT) MIC distributions and epidemiologic cutoff values (ECVs) provides a sensitive means for detecting emerging resistance to antimicrobials. We determined species-specific ECVs for fluconazole (FLC), posaconazole (PSC), and voriconazole (VRC) using a large global collection of Cryptococcus neoformans (CNEO) isolates obtained from the ARTEMIS and SENTRY Antimicrobial Surveillance Programs. From 2006 to 2009, 285 invasive clinical isolates of CNEO were collected from 61 centers worldwide (178 isolates from ARTEMIS and 107 from SENTRY) and susceptibility testing was performed against FLC, PSC, and VRC using Clinical and Laboratory Standards Institute M27-A3 broth microdilution method (72 h of incubation).

Triazole and echinocandin MIC distributions with epidemiological cutoff values for differentiation of wild-type strains from non-wild-type strains of six uncommon species of Candida.

When clinical susceptibility breakpoints (CBPs) are absent, establishing wild-type (WT) MIC distributions and epidemiological cutoff values (ECVs) provides a sensitive means for detecting emerging resistance. We determined species-specific ECVs for anidulafungin (ANF), caspofungin (CSF), micafungin (MCF), fluconazole (FLC), posaconazole (PSC), and voriconazole (VRC) for six rarer Candida species (819 strains) using isolates obtained from the ARTEMIS Program and the SENTRY Antimicrobial Surveillance Program, all tested by a reference broth microdilution method. The calculated ECVs, expressed in μg/ml (and the percentages of isolates that had MICs less than or equal to the ECVs), for ANF, CSF, MCF, FLC, PSC, and VRC, respectively, were 0.

Plasmid-borne vga(A)-encoding gene in methicillin-resistant Staphylococcus aureus ST398 recovered from swine and a swine farmer in the United States.

We report a novel vga(A) detected in 3 methicillin-resistant Staphylococcus aureus ST398 recovered from swine and a swine caretaker in the United States. Strains were wild type for L3 and L4, but positive for vga(A) and tet(M). vga(A) was plasmid-located (ca.

Revisiting the best interest standard: uses and misuses.

The best interest standard is the threshold most frequently employed by physicians and ethics consultants in challenging a parent's refusal to provide consent for a child's medical care. In this article, I will argue that the best interest standard has evolved to serve two different functions, and that these functions differ sufficiently that they require separate standards. While the best interest standard is appropriate for choosing among alternative treatment options for children, making recommendations to parents, and making decisions on behalf of a child when the legal decision makers are either unable to make a decision or are in dispute, a different standard is required for deciding when to seek state interference with parental decision-making authority.

Activity of ceftaroline and epidemiologic trends in Staphylococcus aureus isolates collected from 43 medical centers in the United States in 2009.

A Staphylococcus aureus surveillance program was initiated in the United States to examine the in vitro activity of ceftaroline and epidemiologic trends. Susceptibility testing by Clinical and Laboratory Standards Institute broth microdilution was performed on 4,210 clinically significant isolates collected in 2009 from 43 medical centers. All isolates were screened for mecA by PCR and evaluated by pulsed-field gel electrophoresis.

Azole resistance in Aspergillus fumigatus isolates from the ARTEMIS global surveillance study is primarily due to the TR/L98H mutation in the cyp51A gene.

We surveyed 497 isolates of Aspergillus fumigatus collected from 2008 to 2009 as part of the ARTEMIS global surveillance study for elevated MIC values to itraconazole, voriconazole, and posaconazole. Sequencing of the cyp51A gene revealed that 8/29 isolates with elevated MIC values to one or more triazoles, all originating in China, contained the TR/L98H mutation associated with resistant European isolates of A. fumigatus.

Prevalence and genetic relatedness of methicillin-susceptible Staphylococcus aureus isolates detected by the Xpert MRSA nasal assay.

Methicillin-susceptible Staphylococcus aureus (MSSA) isolates lacking mecA yet testing positive on the Xpert MRSA assay were recovered from culture for 7.7% of 248 Xpert-positive nasal samples. These "false-positive" Xpert results may be attributed to staphylococcal cassette chromosome (SCC) elements without the mecA gene.

Clinical breakpoints for voriconazole and Candida spp. revisited: review of microbiologic, molecular, pharmacodynamic, and clinical data as they pertain to the development of species-specific interpretive criteria.

We reassessed the Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) for voriconazole. We examined i) the essential (EA: ±2 dilutions) and categorical agreement between 24-h CLSI and EUCAST methods for voriconazole testing of Candida, ii) wild-type (WT) MICs and epidemiologic cutoff values (ECVs) for voriconazole by both CLSI and EUCAST methods, and iii) correlation of MICs with outcomes from previously published data using CLSI methods. We applied these findings to propose new 24-h species-specific CLSI CBPs.

Pediatric ethics guidelines for hereditary medullary thyroid cancer.

Hereditary medullary thyroid cancer is an aggressive cancer for which there is no standard effective systemic therapy, but which can be prevented through genetic screening and prophylactic thyroidectomy. Although this cancer accounts for roughly 17% of all pediatric thyroid cancers, a significant percentage of affected families do not "accept" screening, while many gene carriers delay or refuse prophylactic thyroid surgery for their children. Current genetic screening practices in medullary thyroid cancer are inadequate; more than 50% of index patients with hereditary medullary thyroid cancer present with a thyroid mass; up to 75% have distant metastasis.

Multicenter comparison of the Vitek 2 antifungal susceptibility test with the CLSI broth microdilution reference method for testing caspofungin, micafungin, and posaconazole against Candida spp.

The performance of the automated Vitek 2 (bioMérieux, Inc., Marcy l'Etoile, France) antifungal susceptibility system was compared to that of broth microdilution (BMD) for the determination of MICs of various antifungal drugs. A total of 112 challenge strains and 755 clinical isolates of Candida spp.

Clinical significance of positive cranial bone flap cultures and associated risk of surgical site infection after craniotomies or craniectomies.

Object: The risk of surgical site infection (SSI) after craniotomies or craniectomies in patients in whom contaminated bone flaps have been reimplanted has not been determined. The objectives of this study were to identify the prevalence of bone flaps with positive cultures--especially those contaminated with Propionibacterium acnes--to assess the risk of SSI after reimplanting (either during the initial operation or subsequently) bone flaps with positive cultures, and to identify risk factors for SSI following the initial craniotomies or craniectomies.

Methods: The authors conducted a retrospective review of cases in which patients underwent craniotomy/craniectomy procedures between January and October 2007 in the neurosurgery department at the University of Iowa Hospitals and Clinics.

Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria.

The CLSI established clinical breakpoints (CBPs) for caspofungin (CSF), micafungin (MCF) and anidulafungin (ANF) versus Candida. The same CBP (susceptible (S): MIC ≤ 2 mcg/ml; non-S: MIC > 2 mcg/ml) was applied to all echinocandins and species. More data now allow reassessment of these CBPs.

Validation of 24-hour posaconazole and voriconazole MIC readings versus the CLSI 48-hour broth microdilution reference method: application of epidemiological cutoff values to results from a global Candida antifungal surveillance program.

We performed 24- and 48-h MIC determinations of posaconazole and voriconazole against more than 16,000 clinical isolates of Candida species. By using the 24- and 48-h epidemiological cutoff values (ECVs), the categorical agreement between the 24-h and reference 48-h broth microdilution results ranged from 97.1% (C.

Multilaboratory testing of two-drug combinations of antifungals against Candida albicans, Candida glabrata, and Candida parapsilosis.

There are few multilaboratory studies of antifungal combination testing to suggest a format for use in clinical laboratories. In the present study, eight laboratories tested quality control (QC) strain Candida parapsilosis ATCC 22019 and clinical isolates Candida albicans 20533.043, C.