Stewardship / Resistance Scan for Jan 02, 2018

Antimicrobial resistance in the ICU
Trial of new UTI antibiotic

Experts issue call for action on antimicrobial resistance in ICU patients

Intensive care and infectious disease experts from the Antimicrobial Resistance in Critical Care (ANTARCTICA) coalition have released a statement in Intensive Care Medicine calling for increased awareness and action to reduce antimicrobial resistance (AMR) in intensive care units (ICUs).

The statement comes out of discussions held at a 2016 meeting in Milan on AMR in the ICU organized by the European Society of Intensive Care Medicine, the European Society of Clinical Microbiology and Infectious Diseases, and the World Alliance Against Antimicrobial Resistance. Recognizing that ICU patients are particularly at risk of acquiring AMR infections, that action is urgently required, and that multiple aspects of the problem need to be covered, the members of the coalition released a set of recommendations for investigating AMR in critically ill patients and developing guidance for treating these patients, along with priorities for improved management of multidrug-resistant (MDR) infections in different domains.

Recommendations from the coalition include committing to making AMR a priority in guideline development and research activities, documenting the global prevalence of gram-negative AMR infection and colonization, developing clinical guidance on specific topics such as antibiotic dosing and duration in the ICU and optimization of empiric treatment, collecting data on treatment and outcomes for extensively- and pan-drug-resistant infections, and assembling a consortium for collaborative research on AMR in the ICU.

Priorities were categorized into four domains (risk stratification, diagnosis, therapy, and prevention) and include identifying MDR pathogen-specific risk factors, developing tools for early diagnosis of sepsis and rapid identification of pathogens and resistance patterns, elucidating the role of combination therapy in MDR infections, and defining optimal use of barrier precautions.

The coalition also proposed a number of immediate interventions that can be taken to reduce AMR in the ICU, including enforcing infection control practices, developing an antimicrobial stewardship team, applying smart antibiotic dosing, and reviewing antibiotics daily.
Dec 29 Intensive Care Med paper

New candidate for multidrug-resistant UTIs shows promise in human trial

Biopharmaceutical company Achaogen today announced positive top-line results from a phase 1 clinical trial of C-Scape, an oral antibacterial candidate being developed for treatment of MDR gram-negative infections.

C-Scape is a combination of two previously approved drugs, the third-generation cephalosporin ceftibuten and the beta-lactamase inhibitor clavulanate. Achaogen is developing the combination therapy as a potential oral treatment for patients who have complicated urinary tract infections (cUTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, which are often resistant to currently available oral antibiotics and require intravenous carbapenem therapy. In preliminary non-clinical studies, C-Scape showed potent in vitro activity against ESBL-producing Enterobacteriaceae and rapid bactericidal activity.

The phase 1 trial was a double-blind, randomized, placebo-controlled, parallel group study to assess the safety, tolerability, and clinical pharmacology of C-Scape in 41 healthy subjects. According to a company press release, the results showed that the combination of ceftibuten and clavulanate was well tolerated when administered for 14 days and did not demonstrate any drug-drug interactions or serious side effects. The most commonly reported adverse events included vascular access site bruising, headache, diarrhea, gastroenteritis, and nausea.

"The positive top-line results from this first-in-human clinical trial for C-Scape are supportive of further evaluation and we continue to plan for Phase 3 in 2018," Kenneth Hillan, MBChB, Achaogen's president of research and development, said in the press release.

In January 2017 the US Food and Drug Administration awarded C-Scape Qualified Infectious Disease Product (QIDP) status for the treatment of cUTI. The QIDP designation, created to provide incentives for new antibiotic treatments, includes priority review and an additional 5 years of marketing exclusivity.
Jan 2 Achaogen press release

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