Regional Adult Cystic Fibrosis Center, Belfast City Hospital, Belfast, Northern Ireland, BT9 7AB, UK
Department of Bacteriology, Belfast City Hospital, Belfast, Northern Ireland, BT9 7AB, UK
Abstract
Background
Patients with cystic fibrosis [CF] have frequent pulmonary exacerbations associated with the isolation of bacterial organisms from sputum samples. It is not clear however, if there are differences in the types of additional organisms isolated from patients who are infected with
Methods
Adult patients attending the regional CF unit were followed over a two year period and patients were assigned to three groups depending on whether they were known to be chronically infected with BCC, PA or NI. We compared the numbers and types of organisms which were isolated in each of these groups.
Results
Information was available on a total of 79 patients; BCC 23, PA 30 and NI 26. Total numbers of organisms isolated, expressed as median and IQR for each group, [P = 0.045] and numbers of co-infecting organisms [P = 0.003] were significantly higher in the BCC group compared to PA, and in the PA group [P < 0.001, p = 0.007 respectively] compared to NI patients. The pattern of co-infecting organisms was similar in all three groups.
Conclusions
Total numbers of organisms isolated and numbers of co-infecting organisms were significantly higher in the BCC group compared to PA, and in the PA group compared to NI patients. Types of co-infecting organisms are similar in all groups of patients.
Introduction
Patients with CF experience frequent exacerbations of their symptoms; contributing factors include infections which may be bacterial or viral in nature
This study examines the bacterial organisms cultured from an adult CF population, subdividing them into three groups; BCC, PA and those who were not infected with either of these organisms [NI] and to correlate with several clinical parameters. We hypothesized that those patients with BCC have more co-infection with other bacteria and this contributes to the greater morbidity in these patients.
Materials and Methods
Study Design and Eligibility
Data were collected on all patients [>18 years old] attending the regional adult CF unit at the Belfast City Hospital for two consecutive years. Sputum specimens were obtained for each patient at regular clinic attendances [patients were reviewed at 3 monthly intervals] as well as twice during hospital admissions. BCC was cultured from sputum employing selective agar (Columbian Agar Base cat no: CM331, Oxoid Ltd., Hampshire + 5% Defibrinated Horse Blood E & O Laboratories, Bonnybridge, Scotland). All isolates were grouped into cultural phenotypes displaying similar visual characteristics and one colony from each phenotype identified by API. Sputum samples were well taken samples following physiotherapy.
Sputum culture results were retrieved from the Bacteriology database for all samples submitted over the study time period. Patients were then divided into three groups using the following criteria; BCC if there was ever any sputum culture positive for these organisms. PA, if this bacterium was identified on two or more occasions over a twelve month period, and NI for all other patients who were not chronically infected with either of these organisms. It was noted as to whether the positive culture consisted of one organism or if there were additional organisms identified. In the BCC and PA groups, when more than one organism was identified from a sputum culture the additional organism [s] where recorded as 'co-infecting', as where all organisms in cultures of two or more infecting organisms in the NI group. Co-infecting organisms were divided into groups;
Spirometry [Vitalograph α ,Buckingham, UK] and oxygen saturation measurements were noted at the start and end of the study as well as the best measurement for each year. Weight was recorded at the beginning and end of the two year period. Other measurements included; smoking history, use of prophylactic and number of courses of intravenous antibiotics and a history of diabetes mellitus.
Statistical Analysis
Statistical analyses were performed using the SPSS version 11 package. The Chi-square test was used to analyse differences in the sex, smoking status and incidence of diabetes mellitus between groups. The Kruskal-Wallis and Mann Whitney test were used to compare antibiotic use and organisms isolated across groups. Lung Function and Oxygen saturation means were compared by one-way analysis of variance followed by the Student-Newman-Keuls method. A probability (P) value of less than 0.05 was considered statistically significant.
Results
Information was available on a total of 79 patients, mean [Standard Deviation] age 26 [7.9] years. Numbers in each group were as follows; BCC 23 [2
Use of oral and intravenous antibiotics; median [Interquartile Range].
Antibiotic Courses
Patient Group
BCC
PA
NI
No. of Patients
23
30
26
Oral
0 [0–2.0]
1 [0–2.0]
1 [0–2.3]
Intravenous
3 [1.0–11.0]
3 [2.0–5.0]
0 [0–2.0]
The changes between the best FEV1 measured each year, the change in FEV1 between the start and end were not significant between the groups. Oxygen saturation measured at the end of the study tended to be lower in the BCC and PA groups when compared to the NI group; however there were no significant differences for the best SaO2 values for each year.
Median and interquartile ranges of organism numbers [total numbers and numbers of co-infecting organisms] and specimen numbers in each group are shown in table
Median [Interquartile Range] of numbers of sputum specimens, total numbers of organisms and numbers of co-infecting organisms [per patient] in each group. Mean ± SD numbers of individual co-infecting organisms isolated per patient in each group.
Measurement
Patient Group
BCC
PA
NI
No. of Patients
23
30
26
Total No. of Specimens / patient
24 [9.0–59.0]
19.5 [5.5–34.5]
0 [0–9.8]
Total No. of Organisms / patient †
32 [16.0–79.0]
24 [7.8–46.3]
0 [0–11.3]
No. of Co-infecting Organisms / patient ‡
15 [8.0–20.0]
3.5 [0.8–11.3]
0 [0–4.3]
P. aeruginosa co-infection
14.4 ± 19.7
-
0.1 ± 0.3
S. aureus co-infection
3.6 ± 4.8
2.0 ± 4.1
3.7 ± 7.5
H. influenza co-infection
1.8 ± 2.9
0.7 ± 1.6
1.1 ± 3.1
S. pneumonia co-infection
0.6 ± 1.2
0.2 ± 0.5
0.4 ± 1.0
S. maltophilia co-infection
0.9 ± 1.5
2.6 ± 6.6
1.7 ± 6.3
Other organism co-infection
1.4 ± 1.9
3.1 ± 5.9
1.7 ± 3.2
† Total number of different bacterial organisms isolated in that group of patients during the study period.
‡ Number different bacterial organisms isolated excluding those isolates for BCC or PA in those patients who are colonized with these bacteria.
Discussion
This study identified individuals with BCC and PA more frequently require courses of IV antibiotic therapy in comparison to CF adults in whom neither pathogen was identified [NI]. This is in keeping with previous findings in which patients colonized with BCC
The BCC group were also noted to have significant weight loss over the study period, again this has been shown to act as an independent predictor of survival in this group
On comparison of PA and BCC patients to those in the NI group, investigators have previously demonstrated higher morbidity
It is well documented that CF patients experience a more rapid decline in their lung function
Investigators have shown evidence of this type of risk taking behaviour in these patients, however it is actually lower when compared than their peer group
Conclusion
Patients with BCC and PA infection have a similar use of antibiotics. Total numbers of organisms isolated and numbers of co-infecting organisms are significantly higher in the BCC group compared to PA, and in the PA group compared to NI patients. Types of co-infecting organisms are similar in all groups of patients.
Abbreviations
BCC Burkholderia cepacia complex
CF Cystic fibrosis
FEV1 Forced expiratory volume in one second
NI 'Neither Isolated' group
No. Number
P Probability
PA Pseudomonas aeruginosa
SAO2 Oxygen Saturation
SD Standard Deviation
SE Standard Error
SPSS Statistical Package for the Social Sciences
SPECIAL CHARACTERS:
< Less than
α Alpha
Competing Interests
The authors' declare that they have no competing interests.
Authors' Contributions
TMcM
Collected data relating to the study and drafted the paper.
AMcD
Participated in the analysis of clinical specimens and contributed to the manuscript content.
JEM
Participated in the study design and coordination.
JSE
Conceived of the study and participated in its design and coordination.
All authors read and approved the final manuscript
Acknowledgements
Dr Chris Patterson [Department Of Epidemiology, Queens University Belfast] performed the statistical analysis of all data.