[Analysis of patient flows: basis for regional control of antibiotic resistance]. / Analyse van patiëntstromen. De basis voor regionale bestrijding van gevaarlijke infecties.

Antibiotic resistance is a worldwide threat to health care as it impairs the effective treatment of bacterial infections. Measures against the spread of resistance are mainly focused on individual health care institutions as these are viewed as the main source of resistance. However, health care institutions are not completely independent in their control of the prevalence of resistance, as movement of patients between hospitals and care institutions can induce movement of resistant micro-organisms. In other words, antibiotic resistance follows the flow of patients. Mapping this flow of patients results in a network that includes all health care institutions, and has a distinctive modular structure. Patients are moved primarily within regions, much less so between regions. We argue that the structure of this health care network should be used to design efficient and effective control strategies. To this end, we advocate (a) regional coordination of control measures, (b) differentiation of investment in infection prevention according to the network position of the institution, and

Small regulatory RNA-induced growth rate heterogeneity of Bacillus subtilis.

Isogenic bacterial populations can consist of cells displaying heterogeneous physiological traits. Small regulatory RNAs (sRNAs) could affect this heterogeneity since they act by fine-tuning mRNA or protein levels to coordinate the appropriate cellular behavior. Here we show that the sRNA RnaC/S1022 from the Gram-positive bacterium Bacillus subtilis can suppress exponential growth by modulation of the transcriptional regulator AbrB. Specifically, the post-transcriptional abrB-RnaC/S1022 interaction allows B. subtilis to increase the cell-to-cell variation in AbrB protein levels, despite strong negative autoregulation of the abrB promoter. This behavior is consistent with existing mathematical models of sRNA action, thus suggesting that induction of protein expression noise could be a new general aspect of sRNA regulation. Importantly, we show that the sRNA-induced diversity in AbrB levels generates heterogeneity in growth rates during the exponential growth phase. Based on these findings, we hypothesize that the resulting subpopulations of fast- and slow-growing B. subtilis cells reflect a bet-hedging strategy for enhanced survival of unfavorable conditions.

Efficient surveillance for healthcare-associated infections spreading between hospitals.

Early detection of new or novel variants of nosocomial pathogens is a public health priority. We show that, for healthcare-associated infections that spread between hospitals as a result of patient movements, it is possible to design an effective surveillance system based on a relatively small number of sentinel hospitals. We apply recently developed mathematical models to patient admission data from the national healthcare systems of England and The Netherlands. Relatively short detection times are achieved once 10-20% hospitals are recruited as sentinels and only modest reductions are seen as more hospitals are recruited thereafter. Using a heuristic optimization approach to sentinel selection, the same expected time to detection can be achieved by recruiting approximately half as many hospitals. Our study provides a robust evidence base to underpin the design of an efficient sentinel hospital surveillance system for novel nosocomial pathogens, delivering early detection times for reduced expenditure and effort.

Infection prevention in a connected world: the case for a regional approach.

Results from microbiological and epidemiological investigations, as well as mathematical modelling, show that the transmission dynamics of nosocomial pathogens, especially of multiple antibiotic-resistant bacteria, is not exclusively amenable to single-hospital infection prevention measures. Crucially, their extent of spread depends on the structure of an underlying "healthcare network", as determined by inter-institutional referrals of patients. The current trend towards centralized healthcare systems favours the spread of hospital-associated pathogens, and must be addressed by coordinated regional or national approaches to infection prevention in order to maintain patient safety. Here we review recent advances that support this hypothesis, and propose a "next-generation" network-approach to hospital infection prevention and control.