Insights into Early Stage of Antibiotic Development in Small and Medium-Sized Enterprises: A Survey of Targets, Costs, and Durations

Antibiotic innovation has dwindled to dangerously low levels in the past 30 years. Since resistance continues to evolve, this innovation deficit can have perilous consequences on patients. A number of new incentives have been suggested to stimulate greater antibacterial drug innovation. To design effective solutions, a greater understanding is needed of actual antibiotic discovery and development costs and timelines. Small and medium-sized enterprises (SMEs) undertake most discovery and early phase development for antibiotics and other drugs. This paper attempts to gather a better understanding of SMEs’ targets, costs, and durations related to discovery and early phase development of antibacterial therapies

Nitrofurantoin revisited: a systematic review and meta-analysis of controlled trials

The available evidence supports first-line treatment of lower urinary tract infections with nitrofurantoin as clinical efficacy is similar to that seen for trimethoprim/sulfamethoxazole, ciprofloxacin and amoxicillin, rates of microbiological cure are good, short- term toxicity is generally mild and acquired resistance is still relatively rar

Impact of availability of guidelines and active surveillance in reducing the incidence of ventilator-associated pneumonia in Europe and worldwide

Background: To analyse whether the availability of written standards for management of mechanically ventilated patients and/or the existence of a surveillance system for cases of ventilation-associated pneumonia (VAP) are positively associated with compliance with 6 well-established VAP prevention measures. Methods: Ecological study based on responses to an online-questionnaire completed by 1730 critical care physicians. Replies were received from 77 different countries, of which the majority, i.e. 1351, came from 36 European countries. Results: On a cross-country level, compliance with VAP prevention measures is higher in countries with a large number of prevention standards and/or VAP surveillance systems in place at ICU level., Likewise, implementation of standards and VAP surveillance systems has a significant impact on self-reported total compliance with VAP prevention measures (both p < 0.001). Moreover, predictions of overall prevention measure compliance show the effect size of the availability of written standards and existence of surveillance system. For instance, a female physician with 10 years of experience in critical care working in a 15-bed ICU in France has a predicted baseline level of VAP prevention measure compliance of 63 per cent. This baseline level increases by 9.5 percentage points (p < 0.001) if a written clinical VAP prevention standard is available in the ICU, and by another 4 percentage points (p < 0.001) if complemented by a VAP surveillance system. Conclusions: The existence of written standards for management of mechanically ventilated patients in an ICU and the availability of VAP surveillance systems have shown to be positively associated with compliance with VAP prevention measures and should be fostered on a policy level

Forgotten antibiotics : a follow-up inventory study in Europe, the USA, Canada and Australia

The objective of this study was to update a 2011 survey, conducted on behalf of the ESCMID Study Group for Antibiotic Policies (ESGAP), studying the availability of old but clinically useful antibiotics in North America, Europe and Australia. This follow-up survey was performed in 2015 in 40 countries among specialists from the pharmaceutical, infectious diseases and microbiology sectors in North America, Europe and Australia in order to assess the availability through usual marketing processes of 36 systemic antibiotics (addition of 3 antibiotics compared with the 2011 survey) selected for their ability to treat infections caused by resistant bacteria and their unique value for specific criteria. The questionnaire was sent by e-mail to national contacts belonging to ESGAP and ReAct networks. In all, 39 of the 40 countries participated in this survey. The number of available antibiotics differed considerably from one drug to another as well as from one country to another (e.g. 7 antibiotics available in Estonia, 24 in France). Overall, 25/36 selected antibiotics were marketed in 20/39 countries or less. From 2011 to 2015 (data available for both periods in 37 countries for 33 antibiotics), the number of available selected antibiotics increased in 13 countries and decreased in 17. In conclusion, despite the ongoing bacterial resistance crisis, the situation regarding the availability of ‘forgotten antibiotics’ has worsened since 2011. Urgent measures are needed to ensure better availability of these antibiotics on a global scale as a conservation measure to ensure sustainable and responsible use of antibiotics.peer-reviewe

Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria

Objectives: The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death. Methods: Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) 2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03–1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19–1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen. Discussion: The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations