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.patient referrals | network T here is a worldwide concern about the recent emergence, and rapid widespread dissemination, of novel strains of existing nosocomial pathogens as well as of new genetic determinants of virulence and resistance (1-5). Local and national surveillance is considered an important component of the strategy to control these strains (6-8). However, surveillance is costly in monetary terms, effort, and facilities and it is important to consider ways in which surveillance systems can be made more efficient both at the hospital and the national level. Although this is widely recognized (9, 10), there is still no good evidence base to inform the design of efficient surveillance systems at the national level. A key question is how many hospitals should be included in enhanced surveillance programs.Reflecting this, existing surveillance programs are markedly diverse. For example, in The Netherlands the national antibiotic resistance surveillance system (11) consists of 30 participating laboratories serving ∼50% of hospitals beds in the country. In Britain, the most prominent surveillance schemes include the voluntary reporting of all bacteraemias (90% of clinical laboratories in England, Wales, and Northern Ireland), mandatory bacteraemia surveillance (all acute health trusts in England), and the British Society for Antimicrobial Chemotherapy Resistance Surveillance Project (20-25 collecting laboratories covering the United Kingdom and Ireland) (12). Here, we consider a single, simple, generic approach to this problem that is applicable to a range of nosocomial pathogens including, importantly, novel pathogens or variants whose epidemiology is, by definition, unknown. The only condition is that the major transmission route is the movement of patients between hospitals.The movement of patients between hospitals in a national healthcare system plays an important role in the spread of healthcare-associated infections (HCAIs) (13-17). Patient movements have also been suggested as an important...