Antibiotics have been used in clinical practice for about 80 years and, throughout that period, the problems posed by resistant bacteria have escalated at a pace that has forced near-continuous development of new antibacterial drugs. We now face an immediate future in which pharmaceutical companies can offer few options for some of the multi-drug-resistant bacteria encountered ever more frequently by the clinicians and microbiologists of the 21st century.
Travelers have aided the international spread of infectious diseases since antiquity. Though it is a more recent pairing, travel is also inextricably linked with antibiotic resistance. Importation of resistant strains of Neisseria gonorrhoeae, for example, has for many years been associated with travel to countries in the Far East. Indeed, the two original penicillinase plasmids of this species were described as “Asian” and “African” to reflect their epidemiological associations.1 Moreover, international surveillance systems often illustrate dramatic differences between countries in the prevalence of resistance for many clinical pathogens and hospital opportunists. Countries of high prevalence have the potential to serve as reservoirs for further dissemination.
Much recent attention has been focused on Escherichia coli, which is a normal component of our gut flora, but also a major cause of community-acquired and healthcare-associated infections. It is now also one of the more antibiotic-resistant species of the Enterobacteriaceae. Exposure to resistant bacteria overseas may lead to infection or to “harmless” colonization. Antibiotic use while overseas or after travel will select for the resistant bacteria, with consequences for the individual and for wider society. The causes of rising rates of resistance, including in the community setting, are multi-factorial, but foreign travel must represent a substantial contributor, providing a continual influx of resistant strains. If those strains are able to persist in an individual, they can spread to other family members and beyond through the indirect oral–fecal route, and there may also be horizontal spread of resistance genes to other strains in the gut.
Antibiotic resistance is now rarely far from the media spotlight, as recently evidenced by global interest in NDM-1, a newly recognized β-lactamase that joins the substantial ranks of those causing current clinical concern. It is a “carbapenemase,” one of a diverse group of enzymes that can degrade carbapenems, the most powerful members of the β-lactam antibiotic class.2 The media furor over NDM-1 was sparked by epidemiological evidence that many, though not all, patients affected in the UK had traveled to, or had healthcare contact in the Indian subcontinent,3 where the enzyme is distributed among many bacterial species.4 It was further fueled by the initial response in India; political and media campaigns over the naming of the new enzyme served to polarize attitudes, and attention moved away from the real issue, of the threat to public health and modern medicine. Multi-resistance, including that shown by bacteria with NDM-1 carbapenemase, undermines the effectiveness of antibiotics, reduces our ability to treat infections effectively, and so causes increased mortality.
This issue includes three papers that address different aspects of the resistance/travel conjunction. First, Peirano et al.5 extend the previous work done in Calgary, Canada,6 to show the link between carriage of E coli with CTX-M-type extended-spectrum β-lactamases (ESBLs) and travel, especially to either India or Africa. The cohort studied was not screened before travel, so some may already have been colonized, but the difference (>five-fold) between carriage by travelers and non-travelers was significant. India is known to have an extremely high prevalence of ESBL-producing E coli,7 and a recent Swedish study confirmed similar high rates of acquisition by prescreened volunteers after travel to India.8 Longitudinal studies are needed to follow up such cohorts and to determine the length of carriage of resistant strains, the proportion of colonized patients who go on to develop infections and, although more difficult to achieve, the extent of transfer of resistance genes to other strains in their gut flora.
In the second paper, Hussenet et al.9 present three case reports of infections caused by multi-resistant Acinetobacter baumannii in patients repatriated to France from hospitals in Algeria, Thailand, and Turkey. This species is also a significant pathogen or colonist of casualties repatriated to Europe and the United States from conflict zones.10
Since, as the third paper by Lepelletier et al.11 stresses, resistant bacteria have no respect for international boundaries, we must take steps to limit the consequences of spread. These must include (1) prompt and accurate detection in the diagnostic laboratory (phenotypic methods and molecular diagnostics); (2) appropriate treatment of infected patients; (3) screening to define the extent of onwards transmission (carriage or infection); and (4) implementation of infection control procedures to limit further spread and, ideally, to remove the problem. Advice on detection, control, and treatment of carbapenemase-producing bacteria has recently been issued in the UK (http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/CarbapenemResistance/GuidanceOnCarbapenamProducers/), and in many other European countries.12 Lepelletier et al.11 describe the guidelines introduced to identify carriage of glycopeptide-resistant enterococci or carbapenemase-producing Enterobacteriaceae by French or foreign nationals who need hospital treatment in France after hospital admission overseas. Guidelines are the first step, but it is essential also to promote awareness and uptake of them.
For many gram-negative pathogens the balance has tipped toward multi-resistance and away from a pipeline of promising new antibiotics in development. Acquired carbapenemases, such as NDM-1, confer resistance to almost all β-lactams. We must prevent the loss of our most frequently used antibiotic class, and must preserve all antibacterial agents that are available to us. The entire international community must accept shared responsibility for this global crisis. We should view antibiotics, β-lactams in particular, as a potentially endangered “species”; there will be “poachers” who disregard the conservation efforts of others, but concerted international efforts may make a difference.