METHODS

Patients with chronic P aeruginosa infection who attend the Manchester Adult CF Centre were included in the study if they had received inpatient treatment with intravenous antibiotics during the year 2000. Patients were grouped on the basis of typing results of P aeruginosa isolates from sputum samples as outlined in our previous study.⁵ Briefly, bacterial fingerprinting of P aeruginosa isolates by pyocin typing and pulsed field gel electrophoresis identified a number of patients at our centre who harboured a highly transmissible strain. This strain was genomically distinct from another strain of P aeruginosa associated with cross infection at other UK CF centres.^4,6 The patients with CF were divided into two groups: those who harbour unique P aeruginosa strains (group 1) and those who harbour the Manchester epidemic P aeruginosa (group 2).⁵ Patients co-infected with Burkholderia cepacia or other highly transmissible strains of P aeruginosa such as the Alder Hey epidemic strain⁴ were excluded.

The results of antibiotic sensitivity patterns of P aeruginosa from disc sensitivity tests were noted. Multiresistance for P aeruginosa was defined as resistance to at least two of the three major classes of usual antipseudomonal antibiotics (β-lactam antibiotics, aminoglycosides, quinolones).

The regime for treating an exacerbation with intravenous antibiotics was identical for both groups. Patients were treated with a combination of at least two antibiotics with ceftazidime and tobramycin used as first line treatment; however, adjustments were made to the regime on the basis of in vitro sensitivity of the isolate and the patient’s allergies to antibiotics. The duration of treatment was based upon clinical response.

The age, percentage predicted forced expiratory volume in one second (FEV₁), percentage predicted forced vital capacity (FVC), and body mass index (BMI) were calculated at the patient’s first visit of the year 2000 to the CF centre. The number of days of intravenous antibiotic treatment (inpatient and home combined), number of infective pulmonary exacerbations requiring treatment with oral or intravenous antibiotics, and the number of clinic visits were calculated for the year 2000. The numbers of inpatient episodes and total number of inpatient days were also recorded, but hospital admissions for causes unrelated to respiratory exacerbations were excluded.

Statistical analysis was performed using SPSS statistical package version 9.0 (SPSS Inc, Chicago, Illinois, USA). The two groups were compared using a two sample t test and the Mann-Whitney U test.

RESULTS

There were 56 patients (33 male) and 22 patients (10 male) in groups 1 and 2, respectively; two patients died in group 1 and three in group 2. A multiresistant P aeruginosa isolate was identified in sputum samples on at least one occasion during the year 2000 for 28 (50%) of the 56 patients in group 1 and 20 (91%) of the 22 patients in group 2. There was no difference between the two groups in mean age, % predicted FEV₁, % predicted FVC, and body mass index. There were, however, significant differences between the two groups in median number of days receiving intravenous antibiotics (p=0.01), inpatient episodes (p=0.005), inpatient days (p=0.003), and mean number of respiratory exacerbations (p=0.01; table 1).

DISCUSSION

This study has examined the differences in treatment requirements between patients with CF who have chronic P aeruginosa infection with their own unique strains and those who harbour a highly transmissible strain. Patients who harbour the highly transmissible P aeruginosa strain had more respiratory exacerbations and a greater requirement for intravenous antibiotics and inpatient treatment.

The emergence and spread of highly transmissible strains of P aeruginosa is, at present, a topic of great concern and controversy among CF physicians.⁸ Isolates of highly transmissible strains may display unusual phenotypic features, including antibiotic resistance.^4–6 Most (20/22) of the isolates from patients in group 2 were found to be multiresistant; however, P aeruginosa strains from 50% (28/56) of the patients in group 1 were also found to exhibit antibiotic resistant phenotypes. Although the increased morbidity seen in patients in group 2 may be a reflection of the difficulty in treating a multiresistant strain, it is also possible that highly transmissible strains possess other properties that allow adaptation to and spread among CF patients, and which make them more difficult to treat. We have previously described two “Pseudomonas naïve” patients who acquired initial infection with the highly transmissible P aeruginosa strain.⁵ In both cases the recommended eradication regimes failed and the patients developed chronic infection.⁹ There are also reports of superinfection by a highly transmissible strain at another UK CF centre.⁶ In addition, there is a suggestion from an Australian CF centre that another highly transmissible strain may be associated with increased virulence.¹⁰

The two groups in the current study were well matched in terms of spirometric parameters and body mass index. However, it is still not clear whether infection by the highly transmissible strain is the cause of the increase in treatment requirements or a marker for CF patients who require a high intensity of treatment. The contact density of cases may be important in determining the risk of cross infection, therefore highly transmissible strains may be more likely to spread among inpatients, selecting CF patients who already have increased treatment requirements. We therefore limited the patients in the study to those who have received inpatient treatment with intravenous antibiotics during the year 2000.

The CF Trust advocates surveillance for highly transmissible strains of P aeruginosa.¹¹ This study shows that there may be resource implications associated with spread of infection by multiresistant highly transmissible P aeruginosa strains and an increased morbidity for the CF patient. These findings support the need for microbiological surveillance for P aeruginosa cross infection and the implementation of cross infection control measures to limit spread of highly transmissible strains.