Case report

A 47 year old non-smoking woman with an unremarkable previous medical history presented to her GP with persistent right pleuritic chest pain in September 1995. A chest radiograph showed vague shadowing in the right upper zone and she was treated with analgesia and oral co-amoxiclav. A repeat chest radiograph showed little change and, although her symptoms remained, no immediate further action was taken. Three months later she was referred to her local district general hospital complaining of increasing malaise and more chest pain. A further chest radiograph showed progression of the right upper zone shadowing and a diagnosis of tuberculosis was considered. She was not producing sputum and fibreoptic bronchoscopy was carried out in order to obtain microbiological samples. This revealed an inflamed right upper lobe orifice, washings from which grew a fully sensitive strain of Haemophilus influenzae. She had a two week course of co-amoxiclav with no benefit. Direct smear examination of the washings showed no evidence of tuberculosis.

One month later she presented to the local accident and emergency department complaining of progressive malaise, weight loss, and pyrexia and a further chest radiograph showed marked worsening of the right lung shadowing (fig 1). She was transferred to our unit because of the possibility that she was suffering from tuberculosis. On admission she was pyrexial (38.5°C), tachypnoeic, and mildly hypoxaemic (Pao ₂ 9.6 kPa). She had lost 6 kg in weight over the preceding two months. There were crackles over the right upper lobe. Her white cell count was 15 400 (82% neutrophils, rest of differential count normal). A Mantoux test was negative and she was unable to produce sputum. An HIV test was negative, serum immunoglobulins showed a non-specific polyclonal increase, IgG subclasses showed no isolated deficiencies, autoantibodies were negative, ANCA test was negative, and blood sugar and ACE levels were in the normal range. She was commenced speculatively on quadruple antituberculous chemotherapy and oral steroids and intravenous cefotaxime. However, she continued to deteriorate and a chest CT scan showed extensive consolidation in the right upper and middle lobes, now with peripheral consolidation in the left lung. She underwent rigid bronchoscopic examination and an open right lung biopsy specimen was taken. The surgeon who undertook this noted that the whole of the right lung was very inflamed, typical of an acute infective process. Histological examination of the open lung biopsy specimen merely revealed an acute inflammatory process. Washings taken at rigid bronchoscopy, however, grew only Burkholderia cepaciawhich was intermediately sensitive to ceftazidime and co-trimoxazole but resistant to all other antibiotics tested. Subsequently, sputum culture grew B cepacia.

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Figure 1

Chest radiograph showing patchy consolidation in the right upper and middle lobes and peripheral consolidation in the left lung.

Anti-tuberculous chemotherapy was stopped and she was commenced on high dose intravenous ceftazidime and co-trimoxazole. Following this her pyrexia gradually settled and her appetite and weight increased. All microbiological samples sent for tuberculous culture were ultimately negative. After six weeks in hospital she was discharged home on a reducing course of steroids and oral co-trimoxazole. All subsequent sputum cultures have grown B cepacia and a further CT scan in July 1996 showed bronchiectasis in the right middle and upper lobes. She has since required one further hospital admission for an exacerbation of B cepacia infection and this organism continues to be the only one in her limited daily sputum sample. Although she remains well, simple spirometric tests are now only 70% predicted.

This patient has had nine children, two of whom suffer from cystic fibrosis. She has been intimately involved in the care of these children, preparing and administering their nebulised antibiotics and bronchodilators and helping them with their physiotherapy. Both children became colonised by B cepacia in 1991. Microbiological screening of the rest of the family has failed to reveal any other members colonised by this organism. Genetic testing revealed both children to be DF508/621+1(G>T) and the mother to be heterozygous for DF508. Extensive DNA screening tests have failed to reveal a further cystic fibrosis gene for the mother, and her sweat chloride level is only 8 mmol/l (low normal range).

Pulse field gel electrophoresis of genomic cepacia DNA has been shown to give different patterns for organisms from different sources6 and this method has become accepted as the gold standard for epidemiological typing of B cepacia.7 It was therefore chosen to identify the relationship of the patient’s strain to those of her children with cystic fibrosis. The patterns derived from the three strains were identical, proving them to be from the same source (fig 2). Polymerase chain reaction (PCR) for the cable pilus also established that all three strains possessed the gene for the pilus and were therefore related to the “epidemic” strain (data not shown).

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Figure 2

Pulse field gel electrophoresis of several Burkholderia cepacia strains obtained from 10 patients. Those of the siblings (lane 4 and 5) and mother (lane 6) are identical.

Discussion

In patients with cystic fibrosis the transmission of B cepacia depends on many factors. High numbers of B cepacia (>10⁸ cfu/ml) are present in the saliva of colonised patients and it has been shown that indirect spread via contaminated fomites is possible.3 Whilst airborne dissemination may present a small risk of acquisition,8the highest risk occurs in the direct exchange of respiratory secretions associated with kissing and the intimate social contact which occurs between family members.9 Different B cepacia strains differ greatly in their rates of transmission. In the UK a very transmissible strain of B cepacia has been identified which is identical to a strain from Ontario, Canada.10 This strain, labelled ET 12 or UK “epidemic strain”, has a unique form of pilus designated “cable pilus” due to its length (2 μm) and intertwining properties. Up to 40% of patients in UK cystic fibrosis centres are colonised by B cepacia, 38% of which is due to the “epidemic strain”, involving 50% of cystic fibrosis centres.11 Transient colonisation can occur with some strains of B cepacia, but individuals who acquire the epidemic strain invariably remain chronically colonised.

In non-cystic fibrosis patients B cepacia pneumonia is characteristically a hospital acquired infection in the intubated or immunocompromised. There are rare case reports of community acquiredB cepacia pneumonia occurring in previously healthy individuals12 but there are no reported cases of chronic respiratory colonisation.

This patient appears to have developed chronic respiratory colonisation with the epidemic strain of B cepacia following an acute infection with the organism acquired from one of her two affected offspring. Whilst it is still possible that she is a “forme fruste” of cystic fibrosis, we have been unable to detect a second gene despite extensive first and second level screening (ruling out 99% of cystic fibrosis genes) and she has a negative sweat test. Furthermore, she has had nine children and reached the age of 47 years without exhibiting any other symptoms. We are not aware of any other such cases, either where B cepacia has been transmitted from cystic fibrosis patients to immunocompetent adult individuals or where chronic colonisation and lung damage with the organism has been the end result. Thisis a potentially worrying development for the parents, siblings, and partners of individuals with cystic fibrosis who are necessarily intimately exposed to the microbiological pathogens carried by cystic fibrosis patients.