New strategies for individualized and rational use of antibiotics in difficult-to-treat infections

Antibiotic overuse and misuse are main drivers of the emerging multidrug-resistant (MDR) bacteria. It has been estimated that as much as 50% of antibiotic prescriptions are inappropriate. Much of the last-resort antibiotics are used in hospitals where decisions on therapy for bacterial infections are typically complex due to underlying diseases, organ failures and other patient-specific factors. Digital decision support systems and stewardship interventions are needed to promote rational use of available drugs. Also, a shift from one-size-fits-all to individualized precision medicine in severe bacterial infections is required. This PhD project includes an international multicenter randomized trial where a smartphone app for digital decision support is developed and introduced using a stepped-wedge cluster design in hospitals in Uppsala, Geneva and Rotterdam.

A prospective multicenter national study is conducted to capture real-life data on how recently introduced antibiotics with activity against MDR pathogens are used. Clinical and microbiological outcomes including resistance development after 7 days of therapy is recorded and the bacterial isolates are collected for genotypic and phenotypic characterization as well as synergy testing for antibiotic combinations. Finally, a prospective multicenter national study is conducted to assess pharmacokinetics (PK) in patients with infective endocarditis who receive prolonged and high-dose beta-lactam treatments. The data will be used to develop a mathematical PK model that can simulate and predict optimal dosing in this patient group to ensure therapeutic effect but avoid toxicity.

Researchers at UU

Lisa Faxén

Clinical assistant at Department of Medical Sciences, Basic Education

Email:
lisa.faxen[AT-sign]medsci.uu.se

PhD student at Uppsala Antibiotic Center

Thomas Tängdén

Associate professor at Department of Medical Sciences, Infection medicine

Email:
Thomas.Tangden[AT-sign]medsci.uu.se

Related published research

1. Davey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E, Gould IM, Ramsay CR, Michie S. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2017 Feb 9;2(2):CD003543.

2. Helou RI, Catho G, Peyravi Latif A, Mouton J, Hulscher M, Teerenstra S, Conly J, Huttner BD, Tängdén T, Verbon A. Study protocol for an international, multicentre stepped-wedge cluster randomised trial to evaluate the impact of a digital antimicrobial stewardship smartphone application. BMJ Open. 2020 Jun 4;10(6):e033640. 

3. Paul M, Carrara E, Retamar P, Tängdén T, Bitterman R, Bonomo RA, de Waele J, Daikos GL, Akova M, Harbarth S, Pulcini C, Garnacho-Montero J, Seme K, Tumbarello M, Lindemann PC, Gandra S, Yu Y, Bassetti M, Mouton JW, Tacconelli E, Rodríguez-Baño J. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli. Clin Microbiol Infect. 2022 Apr;28(4):521-547.

4. Wistrand-Yuen P, Olsson A, Skarp KP, Friberg LE, Nielsen EI, Lagerbäck P, Tängdén T. Evaluation of polymyxin B in combination with 13 other antibiotics against carbapenemase-producing Klebsiella pneumoniae in time-lapse microscopy and time-kill experiments. Clin Microbiol Infect. 2020 Sep;26(9):1214-1221.

5. Tängdén T, Ramos Martín V, Felton TW, Nielsen EI, Marchand S, Brüggemann RJ, Bulitta JB, Bassetti M, Theuretzbacher U, Tsuji BT, Wareham DW, Friberg LE, De Waele JJ, Tam VH, Roberts JA; Infection Section for the European Society of Intensive Care Medicine, the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases, the International Society of Anti-Infective Pharmacology and the Critically Ill Patients Study Group of European Society of Clinical Microbiology and Infectious Diseases. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections. Intensive Care Med. 2017 Jul;43(7):1021-1032.

Last modified: 2022-06-28