The population dynamics of antimicrobial chemotherapy

Abstract

We present and analyze a series of mathematical models for the emergence of resistance during antibiotic treatment of an infected host. The models consider the population dynamics of antibiotic-sensitive and -resistant bacteria during the course of treatment and addresses the following problems: (i) the probability of obtaining a resistant mutant during the course of treatment as a function of antibiotic exposure; (ii) the conditions under which high, infrequent doses of an antibiotic are predicted to succeed in preventing the emergence of resistance; (iii) the conditions for the success of multiple drug treatment in suppressing the emergence of resistance and the relationship between antibiotic synergism and suppression of resistance; and (iv) the conditions under which nonadherence to the prescribed treatment regimen is predicted to result in treatment failure due to resistance. We analyze the predictions of the model for interpreting and extrapolating existing experimental studies of treatment efficacy and for optimizing treatment protocols to prevent the emergence of resistance.

Optimal Use of Modern Antibiotics: Emerging Trends

“…Will the use of smaller yet effective doses of an antibiotic for highly susceptible bacteria result in greater or lesser resistance? Since the use of any dose of an antibiotic will select for resistant strains, the magnitude of dose most likely determines which organisms are selected [57,58]. Widespread use of lower yet effective doses and a shorter duration of therapy than currently recommended (below) is probably desirable from the point of view of resistance, because the selective pressure exerted by the antibiotic, presumably reflecting the overall tonnage of drug in the environment, will be reduced.…”

The rising impact of mathematical modelling in epidemiology: antibiotic resistance research as a case study

“…Sebille et al [19] Infect Control Hosp Epidemiol 1997 9 Kepler & Perelson [20] Proc Natl Acad Sci USA 1998 10 Lipsitch & Levin [21] Int J Tuberc Lung Dis 1998 11 Stewart et al [22] Theor Popul Biol 1998 12 Austin & Anderson [23] Philos Trans R Soc Lond B Biol Sci 1999 13 Austin et al [24] Proc Natl Acad Sci USA 1999 14 Austin et al [10] Proc Natl Acad Sci USA 1999 15 Dye & Williams [25] Proc Natl Acad Sci USA 2000 16 Levin et al [26] Genetics 2000 17 Lipsitch et al [27] Proc Natl Acad Sci USA 2000 18 Bonten et al [ provide general information on the scientific area of specialization of articles published in them. We summarized this information by dividing these subject categories into the following six scientific classes: clinical medicine, biology, mathematics/statistics/ informatics, other basic science (e.g.…”

A model of the complex response of Staphylococcus aureus to methicillin

“…Some models of drug-resistance group individuals into two subpopulations (susceptible and resistant) to account for variation in the population (Lipsitch and Levin, 1997). Nikolaou and Tam (2006) modeled heterogeneous populations by considering the resistance of a population to be distributed over a range of values, rather than just two subpopulations.…”