Switching to Second-Line Drugs to Curb Resistance

Using mathematical deterministic models of the epidemiology of hospital-acquired infections and antibiotic resistance, it has been shown that the rates of hospital-acquired bacterial infection and frequency of antibiotic infections can be reduced by restricting the admission of patients colonized with resistant bacteria, increasing the rate of turnover of patients, reducing transmission by infection control measures, and the use of second-line drugs for which there is no resistance.

In an effort to explore the generality and robustness of the predictions of these deterministic models to the real world of hospitals, where there is variation in all of the factors contributing to the incidence of infection, Haber, et al. (2010) developed and used a stochastic model of the epidemiology of hospital-acquired infections and resistance. In their analysis of the properties of this model they gave particular consideration to different regimes using second-line drugs in this process. Their research was published in BMC Infectious Diseases.

The researchers report that they developed a simple model that describes the transmission of drug-sensitive and drug-resistant bacteria in a small hospital. Colonized patients may be treated with a standard drug, for which there is some resistance, and with a second-line drug, for which there is no resistance. They then ran deterministic and stochastic simulation programs, based on this model, to predict the effectiveness of various treatment strategies.

Haber, et al. (2010) say the results of the analysis using their stochastic model support the predictions of the deterministic models; not only will the implementation of any of the aforementioned listed measures substantially reduce the incidences of hospital-acquired infections and the frequency of resistance, the effects of their implementation should be seen in months rather than the years or decades anticipated to control resistance in open communities. They add that how effectively and how rapidly the application of second-line drugs will contribute to the decline in the frequency of resistance to the first-line drugs depends on how these drugs are administered. The earlier the switch to second-line drugs, the more effective this protocol will be. Switching to second-line drugs at random is more effective than switching after a defined period or only after there is direct evidence that the patient is colonized with bacteria resistant to the first antibiotic.

The researchers conclude that incidence of hospital-acquired bacterial infections and frequencies of antibiotic resistant bacteria can be markedly and rapidly reduced by different readily implemented procedures. The efficacy using second line drugs to achieve these ends depends on the protocol used for their administration.

Reference: Haber MJ, Levin BR and Kramarz P. Antibiotic Control of Antibiotic Resistance in Hospitals: A Simulation Study. BMC Infectious Diseases 2010, 10:254doi:10.1186/1471-2334-10-254.