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Positive S.aureus on a cough swab or sputum sample should initially be managed with a two week course of flucloxacillin at treatment dose before therapy is escalated.

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What is S.aureus?

S. aureus is a ubiquitous gram positive coccus bacterium. It is a commensal of the human skin, especially anterior nares and skin creases in patients with or without cystic fibrosis (CF).

S. aureus is normally considered an aerobic bacterium but can also behave as facultative anaerobe and is capable of biofilm formation (Goss C et al, 2011 PMID: 21719362).

Chronic S. aureus infection in CF lung may occur as biofilms which are associated with higher in vitro antibiotic resistance. Aktas, N et al, 2013, PMID: 24240049). S. aureus shows increased mutation rates during CF lung infection compared to nasal colonisation in healthy subjects. S. aureus isolates, like P.aeruginosa, have clearly been shown to persist in CF patients over years. (Goss C et al, 2011 PMID: 21719362)
 
Why is it important?

If S. aureus grows repeatedly from respiratory secretions, antibody studies suggest that it is almost certainly present in the lower airways (Strandvik et al, 1990, PMID: 2365469). S.aureus is a lung pathogen. Early infection with S.aureus is associated with bronchiectasis at age six on CT scan. [B]

How common is Staphylococcus aureus?

Bacterial infection due to S. aureus is one of the earliest bacteria detected in infants and children with CF, and it may be found in CF infants as early as three months of age (Armstrong 1995, PMID: 7787647). In one study, 78 bronchoscopies were performed on 38 patients. The average age at the time of bronchoscopy was 2.7 years (range 0.3-7.0 year). A significant organism was detected in 58 (74.5%) bronchoalveolar lavages (BAL). Haemophilus influenzae was detected in 27 (34.6%) samples, 16 (20.5%) samples had S. aureus, and nine (11.5%) had P. aeruginosa.  (Linanne B 2015, PMID: 25408378)

S. aureus  is the most prevalent organism among US CF children with a peak prevalence between ages 11–15 years. Cross sectional studies show that in those under 10 years, 25−30% of patients culture S. aureus from sputum. This may be an underestimate as cough swabs in children unable to expectorate are often negative. Many adults are chronically infected. Nasal carriage rates of S. aureus are significantly higher in patients with CF (66%) than in patients without CF (32%), (Goerke et al, 2000, PMID: 10720521).

Is it serious?

There continues to be debate about the significance of S. aureus in the pathogenesis of CF lung infection. There is evidence that S. aureus can result in scarring, bronchiectasis, tissue destruction and progressive airway obstruction, predisposing to acute P. aeruginosa infection. Co-infection with P. aeruginosa and S. aureus may be associated with a more rapid decline in lung function (Rosenbluth et al, 2004, PMID: 15302726)
For this reason, as well as for its own pathogenic potential, early treatment and eradication (if possible) of S. aureus infection is recommended.

Can it be prevented?

A recent Cochrane review concluded that, “Fewer children receiving anti-staphylococcal antibiotic prophylaxis had one or more isolates of S. aureus. There was no significant difference between groups in infant or conventional lung function. We found no significant effect on nutrition, hospital admissions, additional courses of antibiotics or adverse effects. There was no significant difference in the number of isolates of P. aeruginosa between groups, though there was a trend towards a lower cumulative isolation rate of P. aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years. As the studies reviewed lasted six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis.” (Smyth A et al. 2014; PMID: 25419599). [A]

It is recognised that there are different policies regarding prophylaxis throughout the UK, and indeed the world. This reflects the lack of good evidence to guide management.

Currently it is standard practice in Leeds for people with cystic fibrosis to have flucloxacillin prophylaxis into adulthood. This may change as new evidence becomes available.

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What are the symptoms?

There is no way of differentiating lower respiratory tract infection with S. aureus from any other infection. Indeed, infection may be asymptomatic, and for the majority, can be effectively treated with antibiotics.

How is it diagnosed?

Children often are not sputum producers; therefore, oropharyngeal (“cough”) swabs are frequently obtained. Studies have compared oropharyngeal swabs with specimens obtained by bronchoalveolar lavage; cultures obtained from the upper airway correlated with lower airway infection (Rosenfeld M, 1999, PMID: 10536062 ). [B]

Ramsey et al (1991, PMID: 1859056) reported a 91% positive predictive value [95% confidence interval (CI) 59-100] for S. aureus identified by oropharyngeal swab compared with bronchial cultures and an 80% negative predictive value (95% CI 52-96). This suggests that oropharyngeal swabs with positive cultures are highly predictive, but negative cultures do not rule out the presence of a pathogen. [B]

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Cough or oropharyngeal swabs are the first line investigation for children who are unable to expectorate. For everyone else a sputum sample is preferred. Either a cough swab or sputum sample is obtained  at every routine clinic visit. Other investigations include induced sputum or bronchoalveolar lavage at bronchoscopy.

If S. aureus grows repeatedly from respiratory secretions, antibody studies suggest that it is almost certainly present in the lower airways (Strandvik et al, 1990, PMID: 2365469). Comparison of cultures from the throat and bronchial tubes of the same patients supports this finding.
Ramsey et al (1991, PMID: 1859056) reported a 91% positive predictive value [95% confidence interval (CI) 59-100] for S. aureus identified by oropharyngeal swab compared with bronchial cultures and an 80% negative predictive value (95% CI 52-96). This suggests that oropharyngeal swabs with positive cultures are highly predictive, but negative cultures do not rule out the presence of a pathogen. [B]

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Patients with cystic fibrosis infected with S. aureus should be treated with anti-staphylococcal antibiotics for two weeks at treatment dose. This should be flucloxacillin in most patients (exceptions would include, for example, penicillin allergic patients).  In culture positive patients, anti-staphylococcal treatment for at least two weeks results in an eradication rate of 75% and only a few patients harbour S. aureus for more than six months thereafter. [B]

If S. aureus grows repeatedly from a patient one should first confirm that the drug is being taken appropriately, with consideration of adherence, suitable dose and taking it on an empty stomach. [C] Another anti-staphylococcal antibiotic should be added in combination to flucloxacillin for two weeks e.g. sodium fusidate 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, vancomycin or teicoplanin, after discussion with a microbiologist.[D]

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S.aureus Eradication Protocol

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