Intention-to-treat and transparency of related practices in randomized, controlled trials of anti-infectives.

BACKGROUND: Intention-to-treat (ITT) analysis is commonly recommended for use, due to its benefits on external validity, in randomized, controlled trials (RCTs). No published reports describe how ITT analysis, as well as alternative approaches, are used in anti-infective RCTs. The purpose of this study is to describe the extent to which ITT analysis and alternative data approaches are used, the practices used to handle missing subject data, and whether non-inferiority trials present both ITT and per protocol (PP) analyses. Results of this analysis will help guide end users of infectious diseases primary drug literature. METHODS: A cross-sectional study of RCTs of anti-infectives published from January 1, 2013 through December 31, 2014 was conducted. A PubMed search identified relevant articles published in five specialty infectious diseases journals and four general medical journals. Each article was reviewed by two independent investigators with discrepancies resolved by consensus. Descriptive statistics were used to quantify results. RESULTS: One hundred four articles met study criteria. The most common medication classes represented in the RCTs were hepatitis C antivirals (26 %), antibacterials (25 %), and antiretrovirals (21 %). Thirty studies (29 %) were non-inferiority trials. Most studies (77 %) described use of ITT or modified ITT (mITT) in their methods. Of the ITT and mITT studies, most (73 %) did not describe practices used to handle missing data. Most (97 %) non-inferiority trials described use of ITT, mITT, or both; however, only 15 (50 %) also described use of PP. CONCLUSIONS: RCTs of anti-infectives commonly employ ITT and mITT. Most do not describe how missing data were addressed. Non-inferiority trials of anti-infectives do not consistently employ both ITT and PP populations.

Prolonged infusions of ß-lactam antibiotics: implication for antimicrobial stewardship.

The optimal dosage and administration of antibiotics are not only important measures to combat antimicrobial resistance, but they are also integral to antimicrobial stewardship. In light of a diminishing antibiotic pipeline and an alarming rise in resistance, the optimal dosage and administration of antimicrobial agents have been under a great deal of scrutiny. Prolonged infusions of ß-lactam antibiotics have been proposed as an alternate dosing strategy. To summarize the evidence on prolonged infusions of ß-lactam agents and provide their clinical implications for antimicrobial stewardship, we performed a MEDLINE search (1950-2011) of all relevant articles. This article provides a review of data from Monte Carlo simulations, clinical outcome analyses, and pharmacoeconomic studies. Furthermore, protocol implementation strategies are discussed to address antimicrobial stewardship.

Detection of SHV-type extended-spectrum beta-lactamase in Enterobacter isolates.

One hundred four Enterobacter isolates were tested by standard CLSI disk diffusion methods for detecting extended-spectrum beta-lactamases (ESBLs) and with cefepime-clavulanate disk combinations. SHV-12 was produced by 8.7% of isolates. The cefepime-clavulanate combination provided 88% sensitivity and 91% specificity for the detection of SHV-12 ESBL.