How much patient-to-patient spread of S. aureus occurs? Apparently, not much

I recently posted an article on surprising finds of a study suggesting that horizontal transmission of C. difficile from known symptomatic cases may be less common that we thought. A group of researchers from Oxford, Brighton and London in the UK applied similar methodology to Staphylococcus aureus transmission with similar findings: only a fifth of S. aureus acquisitions could be attributed to patient-to-patient transmission.

All patients admitted to a 16 bed ICU in Brighton were screened on admission and weekly to detect S. aureus colonization and acquisition. Each isolate was typed by spa and whole genome sequencing (WGS). The number of acquisitions that could be linked using conventional methods (spa typing combined with an analysis of overlapping stays) vs. WGS was evaluated.

Overall, 185 (16.7%) of 1109 admissions carried S. aureus; 59 carried MRSA (5.3%). 680 patients were on the unit for long enough to have a weekly screen and hence were eligible for assessing acquisition. Of these, 44 S. aureus (22 MRSA) acquisitions were detected in 41 patients. 35 of these acquisitions were in patients who were screen-negative on admission and 9 were acquisitions of different strains in patients who were already colonized on admission.

Only 14% (5/36) of the acquisitions available for typing were of the same spa type as another patient on the unit at the same time. All of these were MRSA. WGS discounted three of these apparent occurrences of patient-to-patient transmission, confirmed two and identified a further five (3 MRSA, 2 MSSA). So, in total, 7 / 36 (19%) of acquired isolates (5 MRSA and 2 MSSA) were linked to isolates from other patients (Figure).

Price MRSA WGSFigure: Source of S. aureus acquisitions identified through WGS.

The paper raises some interesting questions:

  • Principally, if almost 80% of patients did not acquire their S. aureus from other patients on the unit, where on earth did they acquire them from? In the C. difficile study, unrecognized importation of diverse strains from the community that would not be detected on admission since admission screening was not performed represents a plausible explanation for the surprisingly low incidence of horizontal transmission from known cases. This is not the case in this study, where all patients were screened on admission for S. aureus. So where were the diverse isolates acquired from? Staff carriers? Contaminated surfaces? S. aureus has the capacity to survive on surfaces for very long periods (more than 1 year), so an ancient environmental reservoir is possible. Furthermore, there was no ‘lead in’ period to the study, so it could be that S. aureus on the unit in the months before the study left an environmental reservoir that led to acquisition in some cases, which would not have been captured by this study. The fact that 4/7 patient-to-patient transmissions acquired the same strain of S. aureus without sharing time on the ICU together supports this, although could also be explained by staff carriers. It was a shame that 16% of the 329 S. aureus isolates (including 16% (7/44) of the acquired isolates) were not available for sequencing, which represents a substantial reservoir from which patient-to-patient transmission likely occurred in some cases.
  • It was interesting that some 20% (9/44) acquisitions that were detected occurred in patients who were already colonized on admission; these would have been missed altogether if molecular typing was not performed. I wonder how much ‘silent’ acquisition of this type occurs?
  • Assuming temporal relationship between strains assumes a constant mutation rate. The ‘speed of the mutation clock’ was assessed in this study through repeated sampling of the same patient. This exercise demonstrated minimal diversity, as was the case for C. difficile.
  • WGS is rapidly becoming the gold standard for transmission mapping. In this study, the conventional approach of evaluating spa typing with overlapping stays lacked both sensitivity and specificity for identifying transmitted isolates.

In summary, the major finding is that only 20% of patients who acquired S. aureus appeared to acquire it through horizontal spread from other patients. The next frontier of transmission mapping must be a more comprehensive evaluation of other potential sources: contaminated surfaces, contaminated air, nurses, doctors, cleaners, tea-tray deliverers and the list goes on…

Article citation: Price JR, Golubchik T, Cole K, Wilson DJ, Crook DW, Thwaites GE, Bowden R, Walker AS, Peto TE, Paul J, Llewelyn MJ. Whole-genome sequencing shows that patient-to-patient transmission rarely accounts for acquisition of Staphylococcus aureus in an intensive care unit. Clin Infect Dis 2014. Jan 9. [Epub ahead of print].

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6 thoughts on “How much patient-to-patient spread of S. aureus occurs? Apparently, not much

  1. Thanks for a very interesting analysis. Your comments mention the possible contribution of environmental sources, which is fair enough, but your principal question seems to downplay the likely role of hospital staff as a source. The findings of this study strike me as entirely compatible with a human source for almost all “acquisitions” – even if the prevalence of carriage among staff was as low as that among patients, you only need four times as many staff-patient as patient-patient interactions to confer a four-fold higher risk of acquiring S aureus from a staff member than a fellow patient.

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    • Mark, you’re right that the human reservoir of staff and visitors is the most likely source for MSSA acquisition, since around 30% of healthy humans carry S. aureus. However, in this study, 50% of acquisitions were MRSA and the staff / visitor reservoir is a less plausible source for MRSA. Here, I suspect an ‘ancient’ environmental reservoir may be relatively more important.

      Another possibility is ‘delayed emergence’, where patients who are colonised on admission are not detected due to poor sensitivity of the sampling or suppression by antistaphylococcal agents such as chlorhexidine.

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  2. Very interesting paper and well reviewed. These two papers on C.diff and S. aureus are really groundbreaking in working out transmission models for micro-organisms and I am sure more will follow. Agree that WGS will become the Gold Standard for this type of research.

    I must admit I always thought environmental survival for S.aureus on dry surfaces was more like days than months. I will need to go and do some further reading on this….

    Michael

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  3. These findings are counter-intuitive from what we experence by ribotyping all C difficile or investigating S.aureus. Previous iterations of typing were oversensitive and allowed for single differences e.g. Robert Williams and Tom Parker’s development of phage-typing in S.aureus and the early days of PFGE. These required additional controls beyond one on the organism alone e.g. mutation rates and these were constructed by comparing unrelatable and potentially common environment strains. Presumably all large bacterial populations include minorities which culture based methodologies without selection (by enrichment) underestimate and infection by mutiple geno/phenotypes is probably commoner than we observe when quantal methodologies in routine work are considered. We know from Gram negatives (think CRE/ESBLs) that organisms persist in patients but there is little quantitative work on this diversity. In MRSA repeat screening on sequential admissions suggest carriage persists for many years (?10 within my experience). I am not molecularly sufficeintly competent to pursue the argument but we cannot afford to be wrong with such fundamental work. I agree staff and environment are “let out clauses” that are credible and part of a cross infection rather than “creationist” theory of infection but we need to better explore diversity in a patient milieu controlled by degrees of unrelated patients/family to be sure. Given we know little about what biologically allows carriers the model used by De Bano of family eating and not eating in the same household is a good one to make spatial separation quantitative.

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