Bacterial temporal dynamics enable optimal design of antibiotic treatment.

ABSTRACT

There is a critical need to better use existing antibiotics due to the urgent threat of antibiotic resistant bacteria coupled with the reduced effort in developing new antibiotics. ß-lactam antibiotics represent one of the most commonly used classes of antibiotics to treat a broad spectrum of Gram-positive and -negative bacterial pathogens. However, the rise of extended spectrum ß-lactamase (ESBL) producing bacteria has limited the use of ß-lactams. Due to the concern of complex drug responses, many ß-lactams are typically ruled out if ESBL-producing pathogens are detected, even if these pathogens test as susceptible to some ß-lactams. Using quantitative modeling, we show that ß-lactams could still effectively treat pathogens producing low or moderate levels of ESBLs when administered properly. We further develop a metric to guide the design of a dosing protocol to optimize treatment efficiency for any antibiotic-pathogen combination. Ultimately, optimized dosing protocols could allow reintroduction of a repertoire of first-line antibiotics with improved treatment outcomes and preserve last-resort antibiotics.