Prophylactic antibiotic therapy for Staphylococus aureus

The Leeds Method of Management. April, 2008. Prophylactic antibiotic therapy for Staphylococus aureus [online]. Leeds Regional Adult and Paediatric Cystic Fibrosis Units, St James's University Hospital, Leeds, UK. Available from http://www.cysticfibrosismedicine.com

Prophylactic antibiotic therapy for Staphylococus aureus

If Staphylococcus aureus grows repeatedly from respiratory secretions, antibody studies suggest that it is almost certainly present in the lower airways (Strandvik et al, 1990). Comparison of cultures from the throat and bronchial tubes of the same patients with cystic fibrosis (CF) supports this finding. When patients are receiving long term prophylactic flucloxacillin, S. aureus is no longer a significant problem and is cultured infrequently (Southern et al, 1993; Littlewood et al, 1995).

A comparison of screened infants with CF in East Anglia on long term flucloxacillin or episodic antibiotics from the time of diagnosis showed those on long term flucloxacillin had significantly less cough, fewer S. aureus isolates, less often required in-patient treatment, had shorter hospital admisions and needed fewer courses of additional antibiotics (Weaver et al, 1994). Although the CF Foundation's 4-year trial of cephalexin failed to demonstrate clinical differences between the treated and control children, the treated group had fewer positive cultures for S. aureus, 6% vs 30% but more P. aeruginosa, 25% vs 6% (Stutman & Martell, 1992). A recent systematic review of the diversity of treatments for S. aureus found that anti-staphylococcal treatment achieved sputum clearance of S. aureus and concluded that prophylactic treatment in young children is likely to be of clinical benefit (McCaffery et al, 1999).

Some CF clinics (e.g. Copenhagen) do not recommend long term flucloxacillin, but perform regular throat swabs or sputum cultures. Any potentially harmful organisms isolated from the cultures, including S. aureus, are treated with a course of an appropriate antibiotic. Further cultures are taken in two or three weeks to ensure the organism has cleared (Szaff & Hoiby, 1982). A major disadvantage of this approach is that throat cultures are an insensitive method of detecting organisms in the lower airways. Recent studies comparing throat/sputum cultures and cultures obtained at bronchoscopy revealed many potential pathogens in the lower airways which had not been detected by cultures from the upper respiratory tract (Wood, 1989; Ramsey et al, 1991; Armstrong et al, 1995; Armstrong et al, 1996). Also cultures are performed infrequently in some clinics and therefore S. aureus or other pathogens are not identified and thus not treated.

No clinical trial has yet answered the question whether prophylactic or intermittent anti-staphylococcal therapy results in improved lung function tests or chest x-rays, an increase in bacterial resistance or earlier P. aeruginosa infection (McCaffrey et al, 1999).

Our present policy is to recommend long term prophylactic flucloxacillin and this is continued indefinitely (50-100mg/kg/day in divided doses to a maximum of 1 gram four times a day in adults). Experience of patients referred to Leeds for CF assessments indicates that S. aureus continues to be a cause of significant lung damage in some individuals with CF who have not received, or have failed to comply with, such preventative treatment. We believe that the lungs of treated patients have some protection from S. aureus infection. When patients are receiving long term prophylactic flucloxacillin, S. aureus is cultured infrequently (Southern et al, 1993; Littlewood et al, 1995).

If S. aureus grows repeatedly from a patient who is prescribed long term flucloxacillin one should first confirm that the drug is being taken. Another anti-staphylococcal antibiotic should be added for two weeks e.g. fucidin or rifampicin. Before accepting that it is not possible to eradicate S. aureus, the patient should receive a two week course of intravenous antibiotics e.g. flucloxacillin.

Some older patients have entrenched S. aureus for many years. It is reasonable to treat them with long term flucloxacillin to minimise tissue damage. Some clinics will not specifically treat the S. aureus unless its appearance is associated with an obvious change in symptoms and signs. In Leeds we do not agree with that policy.

 

Key points

•If Staphylococcus aureus grows repeatedly from respiratory secretions, antibody studies suggest that it is almost certainly present in the lower airways

• Prompt and effective antibiotic treatment of respiratory infection has played a major part in the improved prognosis for people with CF

• No clinical trial has yet answered the question whether prophylactic or intermittent anti-staphylococcal therapy results in improved lung function tests or chest x-rays, an increase in bacterial resistance or earlier P. aeruginosa infection

• It is our policy to prescribe prophylactic flucloxacillin from diagnosis and continue indefinitely

 

References

Armstrong DS, Grimwood K, Carzino R, et al. Lower respiratory tract infection and inflammation in infants with newly diagnosed cystic fibrosis. BMJ 1995; 310: 1571-1572. [PubMed]

Armstrong DS, Grimwood K, Carlin JB, et al. Bronchoalveolar lavage and oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis. Pediatr Pulmonol 1996; 21: 267-275. [PubMed]

Littlewood JM, Littlewood AE, McLaughlin S, et al. 20 years continuous neonatal screening in one hospital; progress of the 37 patients and their families. Pediatr Pulmonol 1995; Suppl 12: 374.

McCaffery K, Olver RE, Franklin M, Mukhopadhyay S. Systemic review of anti-staphylococcal antibiotic therapy in cystic fibrosis. Thorax 1999; 54: 380-383. [PubMed]

Ramsay BW, Wentz KR, Smith AL, et al. Predictive value of oropharyngeal cultures for identifying lower airway bacteria in cystic fibrosis patients. Am Rev Respir Dis 1991; 144: 331-337. [PubMed]

Southern KW, Littlewood AE, Littlewood JM. The prevalence and significance of chronic Staphylococcus aureus infection in patients with cystic fibrosis on long term flucloxacillin. In: Escobar H, Baquero CF, Svarez L, editors. Clinical Ecology of Cystic Fibrosis. Elsevier Science Publ. 1993: 129-130.

Strandvik B, Hollsing A, Mollby R, et al. Anti-staphylococcal antibodies in cystic fibrosis. Infection 1990; 18: 170-172. [PubMed]

Stutman HR, Marks MI. Antibiotic Prophylaxis Study Group. Cephalexin prophylaxis in newly diagnosed infants with cystic fibrosis. Sixth Annual North American Cystic Fibrosis Conference; 1992 Washington DC.

Szaff M, Hoiby N. Antibiotic treatment of S. aureus infection in cystic fibrosis. Acta Paediatr Scand. 1982; 71: 82182-6. [PubMed]

Wood RE. Treatment of CF lung disease in the first two years. Third Annual North American Cystic Fibrosis Conference. Pediatr Pulmonol 1989; Suppl 4: 68

Weaver LT, Green MG, Nicholson K, et al. Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period. Arch Dis Child 1994; 70: 84-89. [PubMed]

 

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