Geographic distribution of Staphylococcus aureus causing invasive infections in Europe: a molecular-epidemiological analysis

Abstract

Background: Staphylococcus aureus is one of the most important human pathogens and methicillin-resistant variants (MRSAs) are a major cause of hospital and community-acquired infection. We aimed to map the geographic distribution of the dominant clones that cause invasive infections in Europe.

Methods and findings: In each country, staphylococcal reference laboratories secured the participation of a sufficient number of hospital laboratories to achieve national geo-demographic representation. Participating laboratories collected successive methicillin-susceptible (MSSA) and MRSA isolates from patients with invasive S. aureus infection using an agreed protocol. All isolates were sent to the respective national reference laboratories and characterised by quality-controlled sequence typing of the variable region of the staphylococcal spa gene (spa typing), and data were uploaded to a central database. Relevant genetic and phenotypic information was assembled for interactive interrogation by a purpose-built Web-based mapping application. Between September 2006 and February 2007, 357 laboratories serving 450 hospitals in 26 countries collected 2,890 MSSA and MRSA isolates from patients with invasive S. aureus infection. A wide geographical distribution of spa types was found with some prevalent in all European countries. MSSA were more diverse than MRSA. Genetic diversity of MRSA differed considerably between countries with dominant MRSA spa types forming distinctive geographical clusters. We provide evidence that a network approach consisting of decentralised typing and visualisation of aggregated data using an interactive mapping tool can provide important information on the dynamics of MRSA populations such as early signalling of emerging strains, cross border spread, and importation by travel.

Conclusions: In contrast to MSSA, MRSA spa types have a predominantly regional distribution in Europe. This finding is indicative of the selection and spread of a limited number of clones within health care networks, suggesting that control efforts aimed at interrupting the spread within and between health care institutions may not only be feasible but ultimately successful and should therefore be strongly encouraged.

Conflict of interest statement

DH is one of the developers of the Ridom StaphType software and the SpaServer mentioned in the manuscript. The client software is distributed and sold by the company Ridom GmbH, which is partially owned by him. All other authors have declared that no competing interests exist.

Figures

Figure 1. Locations of participating laboratories.

Figure 2. Age distribution and all-cause mortality of patients 14 d after diagnosis of invasive S. aureus infections in Europe.

Age divided in bands of 5 y, except for infants under 1 y (−1).

Figure 3. Estimates of country-specific genetic diversity expressed as Simpson's index of diversity of spa types (as a percentage) for MSSA (light blue diamonds) and MRSA (dark blue diamonds) and 95% CIs (bars).

Only countries for which spa type information for more then ten MRSA isolates were available were included in this figure.

Figure 4. Location of laboratories isolating S. aureus of spa types t067, t041, t032, and t003, which are the four most significant regional clusters on SRL-Maps.

The numbers within each placemark represent the number of isolates and the colours represent resistance phenotypes: red, MRSA; green, MSSA; yellow, a mixture of MRSA and MSSA.

Figure 5. Location of laboratories isolating S. aureus spa type t067 (as shown in Figure 4) viewed using SRL-Maps.

Isolates from LAB ES056 in Madrid, Spain, and the distribution of all other t067 isolates are shown (n = 62). Each placemark indicates whether isolates are MSSA (green), MRSA (red), or a mixture (yellow) and the selected laboratory is blue. The numbers of isolates are indicated inside the placemark. The pie charts on the right show the proportion of MRSA/MSSA and all-cause mortality after 14 d, and the bar chart displays patient age distribution.