BACKGROUND: Penicillin skin testing (PST) is a simple and reliable way of diagnosing penicillin allergy. After being off the market for 4 years, penicilloyl-polylysine was reintroduced in 2009 as PRE-PEN. We describe the negative predictive value (NPV) of PST and the impact on antibiotic selection in a sample of hospitalized patients with a reported history of penicillin allergy.

Intravenous (IV) minocycline is increasingly used to treat infections caused by multi-drug resistant (MDR)-Acinetobacter baumannii. Despite being approved nearly 50 years ago, published information on its pharmacokinetic (PK) prolife is limited. This multi-center study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of IV minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200 mg IV dose of minocycline. Plasma PK samples were collected pre-dose and 1, 4, 12, 24, 36, and 48 hours after initiation of minocycline. Total and unbound minocycline concentrations were determined at each timepoint. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (fAUC:MIC of 12 and 18, respectively) were evaluated. A two-compartment population PK model with zero-order IV input and first-order elimination, which estimated a constant fraction unbound (fub) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area [associated with central volume of distribution] and albumin (associated with fub). In the PK-PD target attainment analyses, minocycline 200 mg IV Q12H was predicted to result in a suboptimal PK-PD profile for patients with A. baumannii infections with MIC values ≥ 1 mg/L. These findings cast uncertainty on the appropriateness of the current minocycline FDA susceptibility breakpoints and suggest that clinicians should strongly consider only combination antibiotic therapy with IV minocycline for all patients with serious Acinetobacter sp. infections.

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BackgroundProspectively identifying patients at highest risk for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) by implementing a risk assessment scoring tool may help focus prevention efforts, optimize the screening process to improve clinical trial feasibility, and enhance development of new antibacterial agents.MethodsWithin the intensive care units (ICU) of 28 US hospitals, between February 6, 2016 and October 7, 2016, patients hospitalized >48 hours and receiving high levels of respiratory support were prospectively followed for meeting the definition of HABP/VABP recommended in US FDA draft guidance. Patient demographics, medical comorbidities, and treatment exposures were recorded. The association between candidate risk factors and odds of developing HABP/VABP was evaluated with a multivariable logistic regression model. Risk factors were selected using backward selection with α = 0.1 for model inclusion. A web-based scoring system was developed to estimate the risk of HABP/VABP from the risk factors identified.ResultsA total of 5,101 patients were enrolled, of whom 1,005 (20%) developed HABP/VABp. 4,613 patients were included in the model, excluding 488 (10%) with HABP/VABP at or before enrollment. There are 15 variables included in the model. APACHE II admission score >20 (P < 0.001, OR 2.14, 95% CI 2.00–2.29), admission diagnosis of trauma (P < 0.001, OR 3.31, 95% CI 1.90–5.74), frequent oral or lower respiratory tract suctioning (P < 0.001, OR 2.33, 95% CI 1.81–2.99), and receipt of enteral nutrition (P < 0.001, OR 2.31, 95% CI 1.69–3.16) were the key drivers of increased pneumonia risk. The model demonstrated excellent discrimination (bias-corrected C-statistic 0.861, 95% CI 0.843–0.880). The web-based scoring system can be accessed via this link: https://ctti-habpvabp.shinyapps.io/web_based_tool/.ConclusionUsing a web-based scoring system, ICU patients at highest risk for developing HABP/VABP can be accurately identified. Prospective implementation of this tool may assist in focusing additional prevention efforts on the highest risk patients and enhance new drug development for HABP/VABP.Disclosures S. P. Bergin, CTTI: Investigator and Scientific Advisor, Research support and Travel to study related meetings. A. Coles, CTTI: Investigator and Scientific Advisor, Salary. S. B. Calvert, CTTI: Employee, Salary. M. J. Zervos, CTTI: Investigator, Research support. A. C. Bardossy, CTTI: Investigator, Research support. M. Kollef, CTTI: Investigator, Research support. M. J. Durkin, CTTI: Investigator, Research support. M. Sims, CTTI: Investigator, Research support. C. Greenshields, CTTI: Investigator, Research support. B. A. Kabchi, CTTI: Investigator, Research support. H. K. Donnelly, CTTI: Collaborator and Scientific Advisor, Research support and Salary. P. Tenaerts, CTTI: Employee, Salary. P. Gu, CTTI: Collaborator, Research support and Salary. V. G. Fowler Jr., CTTI: Investigator and Scientific Advisor, Research support and Salary. Merck: Consultant, Grant Investigator...

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