Stenotrophomonas maltophilia in cystic fibrosis

Stenotrophomonas maltophilia - questions and answers

Miles Denton. May, 2001. Stenotrophomonas maltophilia-questions and answers [online]. Leeds University Teaching Hospitals, Leeds, UK. Available from http://www.cysticfibrosismedicine.com

What is Stenotrophomonas maltophilia?

Stenotrophomonas maltophilia is a ubiquitous environmental gram negative bacillus. It was first isolated in 1943 in the UK and called 'Bacterium bookeri'. It was formally classified as Pseudomonas maltophilia in 1961, renamed Xanthomonas maltophilia after further taxonomic analysis in 1981, and finally reclassified as Stenotrophomonas maltophilia in 1993.

Where can it be found?

It is ubiquitous. It can be found in aquatic environments, in soils, and on vegetation and even on some animals. It is widespread in the home and hospital environments, including those of patients with cystic fibrosis, particularly in sites related to water and plumbing. Common sites of isolation include taps, plugholes, showerheads, potable water, dishwashers, washing machines, sponges, toothbrushes, flannels, dishwashing paraphernalia, flowers (and vase water), plants, fruit, salads, and vegetables. It has also been isolated from respiratory equipment used by cystic fibrosis patients, including nebulisers used to deliver aerosolized antibiotics.

Is it unique to cystic fibrosis patients?

No. S. maltophilia has been isolated from other patient groups, particularly those with immunocompromise. Patients with haematological malignancy, and those being managed on intensive care units are particularly susceptible to infections with this organism. The most commonly encountered infections are bacteraemia, particularly in association with intravascular catheters, and ventilator-associated pneumonia. However, a wide variety of other infections have been reported, particularly in association with prosthetic devices, implant, and foreign bodies in patients with varying degrees of immunocompromise.

How common is it in cystic fibrosis patients?

The reported prevalence of S. maltophilia in cystic fibrosis patients varies widely from country to country and from centre to centre. There is no doubt that the prevalence has been increasing during the 1990s. Some centres in the UK and Denmark report a prevalence of around 20%, and one centre in Spain reported a prevalence of over 30%. Figures from the US have generally been lower with one recent study reporting a prevalence of around 10%. The reported prevalence can be influenced by the methodology and reporting practices employed by the local microbiology laboratory. A recent study suggested that the use of a selective medium specifically to look for S. maltophilia increased prevalence by over 5%. Some patients were found to harbour the organism for months or even years before it was detected using conventional culture methods.

What are the risk factors for acquiring S. maltophilia?

Identified risk factors for the acquisition of S. maltophilia by patients with cystic fibrosis include poor clinical condition, increasing age, female sex, co-colonisation with Burkholderia cepacia, hospitalisation, and previous antibiotic therapy, including oral ciprofloxacin, nebulised aminoglycosides, and intravenous anti-pseudomonal antibiotics. No individual agent used for intravenous therapy, including carbapenems, has been shown to be associated with a greater risk of S. maltophilia colonisation of patients with cystic fibrosis.

Is it only found in patients with poor clinical condition?

No. It has also been isolated from patients with good lung function too. A study carried out in the Paediatric CF Unit in Leeds revealed that only 10 (25%) of CF patients were chronically infected with Pseudomonas aeruginosa when S. maltophilia was first isolated (unpublished data).

Is it clinically significant?

This is the most controversial issue surrounding S. maltophilia in cystic fibrosis at the present time, due mainly to the paucity of well-designed clinical trials assessing the impact of S. maltophilia colonisation on the respiratory function and clinical well-being of patients with cystic fibrosis. Recently a matched parallel cohort study used data from the US CF Foundation National Registry to assess the impact of S. maltophilia acquisition on survival. Data from 19,255 patients collected between 1991 and 1997 were analysed. 1,721 (8.9%) patients were positive for S. maltophilia and followed up for a median of 4 years. Patients positive for S. maltophilia had lower predicted FEV1 (63% vs 73%, p<0.001), were older (18.9 vs 16.6, p=0.001), more likely to be female (50% vs 46%, p<0.003), and more likely to be B. cepacia-positive (5.7% vs 3.5%, p=0.001). During the study 175 (10.2%) S. maltophilia-positive patients died compared to 1,096 (7.3%) of the S. maltophilia-negative patients. There were no differences in survival when patients were stratified according to FEV1 % predicted. Other anecdotal reports have given rise to mixed results. Gladman et al reported that S. maltophilia had been isolated from 23 of 216 (10.6%) children at one UK centre between 1983 and 1990. Median age at first isolation was 6.1 years. All were alive at the end of the study period and none had experienced unexpected deterioration in clinical condition since the acquisition of S. maltophilia. Demko et al reported that S. maltophilia had been isolated from 211 of 773 CF patients over a 12 year period (1982-1994) in one US centre. Only 24 (11%) of these remained chronically infected. When stratified by FEV1, the two-year survival for S. maltophilia-positive patients was similar to that of non-colonised patients. Karpati et al isolated S. maltophilia from 25 of 150 Swedish CF patients between 1983 and 1992, twelve (48%) of whom were chronically colonised. No clinical deterioration could be documented up to two years after chronic colonisation was established, but these patients did have significantly worse lung function than controls colonised with P. aeruginosa (p<0.05) at follow-up 2-7 years later.

S. maltophilia may act as a pathogen in individual patients. Ballestero et al report one such patient from Spain who was persistently colonised with numbers of S. maltophilia in excess of 105/ gram of sputum. We have seen patients in Leeds, chronically colonised with high numbers of S. maltophilia, who have had exacerbations unresponsive to conventional anti-pseudomonal therapy but who have improved when iv cotrimoxazole has been started. Most conventional culture methods will only be positive for S. maltophilia when the organism is present in numbers >105/ gram of sputum. Therefore those patients with recurrent positive cultures for S. maltophilia may be those most likely to suffer symptoms attributable to its presence.

How can it be treated?

S. maltophilia is resistant to many of the antibiotics used to treat P. aeruginosa. They are inherently resistant to carbapenems (imipenem, meropenem) and most strains are also resistant to aztreonam (>90%), tobramycin (75%), amikacin (70%), piperacillin-tazobactam (>50%), and colistin (>50%). Strains have even been shown to survive exposure to concentrations of tobramycin used in nebulisers, which are well in excess of the MIC (minimum inhibitory concentration). Although many strains may appear susceptible to ciprofloxacin on laboratory testing, clinical experience suggests that resistance emerges rapidly and therapeutic failure, particularly of monotherapy, is common. Ceftazidime is probably the most active of commonly used anti-pseudomonal antibiotics against S. maltophilia. The majority of strains are susceptible on initial testing. However, resistance can emerge during therapy. Timentin, a combination of ticarcillin and clavulanate, has good in vitro activity against S. maltophilia, although clinical experience is lacking. The agent of choice for treatment of S. maltophilia infections is cotrimoxazole (Septrin) and most strains are susceptible (>95%). However, experience of efficacy in CF patients is limited and the agent is associated with significant toxicity. Another agent with promise is minocycline. Virtually all strains are susceptible in vitro but again, reported clinical experience is limited. Also, being a tetracycline, its use in children is contra-indicated. There may be some value to treating significant S. maltophilia infections with combination therapy. A number of regimens have shown evidence of synergy in vitro. These include ceftazidime plus tobramycin, ceftazidime plus ciprofloxacin, cotrimoxazole plus ticarcillin-clavulanate, and ciprofloxacin plus gentamicin.

Should CF patients colonised with S. maltophilia be isolated?

There is no evidence of patient-to-patient transmission of S. maltophilia between CF patients. An epidemiological study carried out in Leeds, using molecular typing techniques, revealed that most patients had independent strains of S. maltophilia. The organism was widespread, both in the home and hospital environment, and the authors hypothesis was that CF patients were most likely to have acquired their strains from their environment. As there was no evidence that CF patients contaminated their environment, there appeared to be no benefit attached to segregating patients on the basis of their S. maltophilia status alone.

Other issues

S. maltophilia has recently been associated with line infections in patients with cystic fibrosis. Presentation has generally been indolent and patients have so far responded to line removal and appropriate antibiotic therapy.

Key points

S. maltophilia is ubiquitous in our environment, especially in those sites associated with water and its delivery. It is found in the home as well as in the hospital.

It is not unique to CF patients. It is becoming increasingly common in CF centres all over the world Risk factors for acquisition include antibiotic usage and poorer lung function It can also be found in CF patients with good lung function.

The clinical significance of S. maltophilia remains uncertain. However individuals chronically colonised with significant numbers (>105 organisms/gram of sputum) do appear to suffer from symptoms associated with its presence.

Available evidence suggests cotrimoxazole is the agent of choice for treating significant infections with S. maltophilia Isolation of S. maltophilia-colonised CF patients does not seem to be of value.

For more details see CF (UK) Trust antibiotic consensus section

References

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