Traditional thinking suggested that CF patients with chronic lung infections harboured their own unique organisms and could not transmit these to similar individuals.6
However, this was shown to be incorrect with the outbreak of the Burkholderia cepacia
complex (Bcc) epidemic in CF patients attending summer camps in the USA in the late 1980s.27
Not only could these organisms spread to Bcc naïve patients,28,29
but we also showed that different Bcc strains could spread to patients already infected to their detriment.30
Subsequent stringent segregation of infected patients by the CF healthcare community halted this epidemic,31
and now few CF patients harbour these organisms.
However, at that time whether Psa might possess a similar ability was controversial since strains are indistinguishable by phenotypic methods alone. Although an increase in the incidence and prevalence of multiresistant Psa was noted in a Danish CF centre in the 1980s,32
and following phenotypic cohort segregation there was a fall in the annual incidence of new infections, other control measures (early eradication therapy for Psa infection and elective intravenous treatment for those with chronic infection) were also employed. These, coupled with a lack of genotypic identification of the resistant Psa isolates, meant the link between cohort segregation and improving clinical outcomes could not be made.
Transmissible strains may be more antibiotic resistant and have been shown to confer a worse prognosis with increased treatment requirements,13,21
inpatient hospital stays, worsening lung function and nutritional state,14
and will ultimately cause excess mortality.33
Prevention of infection of CF patients with these strains is therefore paramount: since they do not survive long in the environment and nosocomial reservoirs have not been found, patient-to-patient contact is the likely source of their acquisition, such that patient segregation becomes the most important infection control measure.
Unfortunately, CF care is complex and requires the coordinated efforts of a multidisciplinary team: while the grouping of patients together at dedicated centres is associated with improved outcomes, it also means that they are potentially exposed to pathogens, in particular transmissible Psa strains.34
However, the degree of contact necessary between CF individuals to allow transmission of organisms is unknown: although we have shown that LES-infected patients produce an aerosol of viable infected droplets that can be detected for several hours in the environment, and this clone also has an enhanced ability to survive on hard surfaces compared with other strains,35
the amount of exposure necessary for host acute infection/colonization with Psa in general remains unclear. Contact density must be an important factor in predicting cross-infection: in adult patients, the limited contact possible within the environment of an outpatient visit is unlikely to be sufficient, and where cross-infection has been documented, this has followed an inpatient stay.8,13
Nevertheless, complete avoidance of patient-to-patient contact is the gold standard to prevent the passage of organisms from one individual to another: under these circumstances, for inpatient care, all CF patients would be accommodated in separate areas on different wards, and for outpatient care in separate clinics at separate times of the week.
As regards outpatient care, it is impossible to review all patients entirely separately and some units use the approach whereby each patient remains in a single clinic room and is visited in turn by members of the CF multidisciplinary team (MDT),36
thereby ensuring that patient-to-patient contact within the clinic should not occur. However, such a strategy is time consuming, limits the number of patients that can be seen in any one session and even if patients adhere strictly to appointment times, since they are invited to attend the hospital at the same time, some mixing cannot be prevented. Furthermore, it is irrational to stringently segregate outpatients but not inpatients, where the risk of cross-infection is much greater.
Similarly as regards inpatient care, due to limited healthcare resources such segregation is difficult for most units, and many adopt the policy of admitting patients to the same facility, but in different rooms and with agreed rules of conduct while on the ward. However, children and young adults are gregarious and some mixing is inevitable, especially at those social times in the evening and weekends which are difficult to police, and it has been shown that this strategy ultimately results in cross-infection.37
Many adult CF clinics therefore use cohort segregation as the most practicable way of limiting cross-infection. However, Psa strains cannot be separated on phenotypic or antibiogram patterns38
such that policies which rely on these criteria will inevitably allow cross-infection to occur. These include ones that segregate solely on multiresistance or the separation of Psa-positive from Psa-negative patient groups. In the latter, those with sporadic strains cannot by definition cross-infect, and therefore their separation from those who are Psa negative is illogical, but they can in turn become super-infected by those in the Psa-positive group with transmissible strains with the potential for consequent clinical deterioration.8
It therefore follows that in order for any cohorting policy to be effective, the clinician needs to be aware of the strains of Psa in their CF clinic population in realtime. This can only be achieved by Psa genotyping on a regular basis, allowing those with transmissible strains to be segregated from all other individuals.
It is this policy we adopted in 2003 in our developing adult CF clinic, where increasing numbers of patients already infected with transmissible Psa (LES) were arriving from the local paediatric centre as they reached adulthood, and a cross-sectional survey had shown a high prevalence among our patients. Our results show that by using regular genotypic surveillance of Psa strains and segregating patient groups accordingly, we have prevented infection by nosocomial contact. The very few patients who have developed super-infection all did so through well-documented social contact outside the hospital environment, despite advice to the contrary. It is of note that other units undertaking Psa genotypic analysis, but without effective patient segregation measures in place, have noted a high cross-infection rate with LES during this period.37
Furthermore, although we have not separated those without Psa infection from those infected with sporadic Psa strains, there has been only one new case of chronic Psa infection in this group (with a unique strain), underlining that it is unnecessary to separate these patient cohorts. A further six cases of acute Psa infection with unique strains occurred, all of which were successfully eradicated – although previous studies4,39,40
reported a higher incidence of such acute infections, these were carried out in a largely paediatric population where the prevalence of chronic Psa infection is much lower.
There are financial consequences to adopting this genotypic surveillance protocol: each test costs approximately £20, and with the addition of technician time the yearly cost to our clinic is currently £22,000. This is likely to increase further, since although the relative numbers of patients infected with Psa strains is diminishing with time due to better cross-infection control and eradication therapy (particularly in paediatric practice), the absolute numbers continue to grow as more patients live longer. Nevertheless, we believe that not only is the cost of this testing outweighed by the clinical benefit, but there are strong economic arguments for its use. Firstly, segregating patient by other methods would necessitate an alteration in clinic and ward infrastructure, which would be costly and for some units impossible, and secondly cross-infection with transmissible strains has been shown to confer an increased healthcare cost burden.41
Finally, the emerging medicolegal consequences of allowing cross-infection between CF patients within the hospital environment, which can be costly, are also avoided.
In conclusion, we recommend the use of genotypic surveillance of Psa strains, to allow rational segregation of CF patients. Using such a method, we have halted the epidemic in our clinic of LES, the most prevalent and important transmissible Psa strain within the CF community.