PLoS One. 2015 Nov 10;10(11):e0142320. doi: 10.1371/journal.pone.0142320.

From the Skin to the Brain: Pathophysiology of Colonization and Infection of External Ventricular Drain, a Prospective Observational Study.
 

Mounier R1, Lobo D1, Cook F1, Martin M1, Attias A1, Aït-Mamar B1, Gabriel I1, Bekaert O2, Bardon J1, Nebbad B3, Plaud B4, Dhonneur G1.
  • 1Department of Anesthesia and Surgical Intensive Care, Henri Mondor University Hospital of Paris, Paris XII school of medicine, Créteil, France.
  • 2Department of Neurosurgery, Henri Mondor University Hospital of Paris, Paris XII school of medicine, Créteil, France.
  • 3Department of Microbiology, Henri Mondor University Hospital of Paris, Paris XII school of medicine, Créteil, France.
  • 4Department of Anesthesiology and Surgical Intensive Care, Saint-Louis University Hospital of Paris, Paris VII school of medicine, Paris, France.

 

Abstract

Ventriculostomy-related infection (VRI) is a serious complication of external ventricular drain (EVD) but its natural history is poorly studied. We prospectively tracked the bacteria pathways from skin towards ventricles to identify the infectious process resulting in ventriculostomy-related colonization (VRC), and VRI. We systematically sampled cerebrospinal fluid (CSF) on a daily basis and collected swabs from both the skin and stopcock every 3.0 days for microbiological analysis including in 101 neurosurgical patient. Risk factors for positive event defined as either VRC or VRI were recorded and related to our microbiological findings. A total of 1261 CSF samples, 473 skin swabs, and 450 stopcock swabs were collected. Skin site was more frequently colonized than stopcock (70 (60%) vs 34 (29%), p = 0.023), and earlier (14 ±1.4 vs 24 ±1.5 days, p<0.0001). Sixty-one (52%) and 32 (27%) skin and stopcock sites were colonized with commensal bacteria, 1 (1%) and 1 (1%) with pathogens, 8 (7%) and 1 (1%) with combined pathogens and commensal bacteria, respectively. Sixteen positive events were diagnosed; a cutaneous origin was identified in 69% of cases. The presence of a pathogen at skin site (6/16 vs 4/85, OR: 11.8, [2.5-56.8], p = 0.002) and CSF leakage (7/16 vs 6/85, OR 10 [2.4-41.2], p = 0.001)) were the two independent significant risk factors statistically linked to positive events occurrence. Our results suggest that VRC and VRI mainly results from an extra-luminal progression of pathogens initially colonizing the skin site where CSF leaks.

PMID: 26555597

 

Supplements:

Ventriculostomy related infection (VRI) is not fully understood. Pathophysiology, clinical and biological features and diagnosis remain subject to debate. Thus, prevention and treatment are not consensual.

Some risk factors for this redoubtable complication are well established (infusion through external ventricular drain, CSF leaks, opening the closed system). However, others such as daily CSF sampling are still debated. Confusion comes from literature which does not discriminate the respective risks of sampling, with that of sampling combined to infusing. Interestingly, studies assessing more specifically the drainage system did not evidence that sampling was a risk factor [1–3].

In the same time, difficulties to obtain a control group of good quality (temporal time point) have led to many false postulates suggesting that VRI was mainly asymptomatic and that CSF monitoring (biochemistry and bacteriology) did not help to diagnosis.

A dynamic approach of CSF monitoring, comparing patients with and without VRI (but that showed positive CSF culture with a good outcome despite no antibiotics treatment) have shown an obvious feature for VRI [4]. Furthermore, daily CSF monitoring may help to hasten diagnosis and avoid unnecessary and harmful antibiotics treatment [4].

For consolidating our finding, a specific focus was made on the route of colonization of the EVD. Several studies assessing risk factors for VRI have been published. But most of them use the same methodology, and none of them focused on pathophysiology of infection. Thus risk factors studied are heterogeneous, without clear comprehensible links.

We chose to specifically look at the route of colonization of the drainage system. We aimed to seek if an intra-luminal route of colonization could highlight a possible role of CSF sampling in VRI installation. On the other hand, an extra-luminal route could be in favour of the skin role. Assessing positive infectious events (EVD-colonization and VRI) in the light of local skin and stopcock sampling, revealed the importance of extra-luminal route of colonization. This result was very similar to those from others studies assessing pathophysiology of short-term central venous catheter-related infection. As median duration of drainage using EVD was of below 15 Days, the hypothesis of extra-luminal route was thus reinforced.

The second important finding of this study was that a major risk factor to develop VRI was the presence at skin insertion of the drainage system of a pathogen (OR: 11.8, [2.5-56.8], p=0.002). The presence of the normal cutaneous microbiota seems to act as a local site protector, just like if the insertion place was sterile, thus preventing VRI risk to increase. It is obvious that no increase in VRI risk existed if the bacteria type at skin site was commensal. However, the presence of a foreign material may lead in fine to material associated-colonization and possibly infection over time. Interestingly, pathogens did not promote such infection dynamics.

Thus, 2 assumptions could be proposed to explain our observations

Firstly, a dynamic approach in which the duration of drainage system exposure to bacterial species affects the incidence of VRI and virulence factors determines the phenotype of the infection. In other words, the time duration elapsing between colonization and infection could be shorter in case of pathogenic bacteria, compared to that of commensal bacteria. In this model, long exposure to commensal bacteria could finally ends in achieving colonization and infection depending upon host immune-competency.

Secondly, our data could result from normal microbiota effect at generating a barrier effect very similar to a bio-film, preventing VRI. Indeed, these bacteria that do not carry virulence gene are ipso facto not keen in triggering infection. However, inflammation episodes caused by “phagocytosis frustration” could explain some CSF alterations we evidenced [5].

 

The importance of this study is three-fold. 

Firstly, it shows that the major route of infection is the skin, especially in case of short-duration drainage. This information lead to better preventing VRI procedures regarding skin disinfection, drainage  system handling and more rigorous CSF monitoring analysis.

Secondly, it demonstrates that the presence of a pathogen at the skin site of the drainage system insertion is important risk factors for VRI development. Clinics depend upon the virulence factors carried by the pathogen. Traditionally thinking suggests that prompt antibiotic’s treatment must be started and our finding is strong argument favouring the implantation of antibiotics impregnated devices.

Thirdly, our data opens a new field of research in the domain of infection/colonization of foreign material entering the human body. Should the absence of bacteria at the site of insertion the main targeted goal? Should we target strictly sterile cutaneous site: the eukaryotic cell dream? This is probably not possible and certainly not desirable. No pathogen does not mean sterile!  We showed that commensal bacteria present at the site of skin insertion exerted a kind of protective effect against VRI. The futurist strategy would be to first elucidate the conditions a natural barrier resulting from a “biofilm” induced by commensal bacteria installs, second to understand the conditions under which this shield lose its protective function and finally propose a more rational VRI preventive strategy based upon a natural process exploiting natural properties of the cutaneous environment without the need of antibiotics.

 

References:

  1.            Bogdahn U, Lau W, Hassel W, Gunreben G, Mertens HG, Brawanski A. Continuous-pressure controlled, external ventricular drainage for treatment of acute hydrocephalus–evaluation of risk factors. Neurosurgery. 1992;31: 898–903; discussion 903–904.
  2.            Mayhall CG, Archer NH, Lamb VA, Spadora AC, Baggett JW, Ward JD, et al. Ventriculostomy-related infections. A prospective epidemiologic study. N Engl J Med. 1984;310: 553–559. doi:10.1056/NEJM198403013100903
  3.            Aucoin PJ, Kotilainen HR, Gantz NM, Davidson R, Kellogg P, Stone B. Intracranial pressure monitors. Epidemiologic study of risk factors and infections. Am J Med. 1986;80: 369–376.
  4.            Mounier R, Lobo D, Cook F, Fratani A, Attias A, Martin M, et al. Clinical, biological, and microbiological pattern associated with ventriculostomy-related infection: a retrospective longitudinal study. Acta Neurochir (Wien). 2015; doi:10.1007/s00701-015-2574-6
  5.            Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284: 1318–1322.

 

 

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