Coagulase-negative staphylococci and hydrocephalus shunt infections

47 1

629th MEETING, LONDON Dasgupta. M. K., Hardy, E L., Zuberbuhler, P. C. & Brown. P. C. ( 1986) I’ediatr. Res. 20,293A. Doggett, R. G. (1969)Appl. Microbiol. 18,936-937 Doig. P., Smith, N. R., Todd. T. & Irvin, R. T. ( 1 987) Infecf. Immun. 5 5 , 15 17-1 522 Ellen, R. P. ( 1985) in Molecular Basis of Oral Microbial Adhesion (Mergenhagen, S. E. & Rosan, B., eds.), pp. 33-39, American Society for Microbiology, Washington, DC Franklin, A. L., Todd, T., Gurman, G., Black, D., Mankinen-Irvin. P. M. & Irvin, R. T. ( 1 987) Infect. Immun. 5 5 , 1523- I525 Gacesa, P. & Russell, N. J. (eds.) ( 1989) fseudornonas Infection and A lginates: Structures, Properties and Function, Ellis Honvood, Chichester Geers, T. & Baker, N. R. (1987) J. Anfimicrob. C‘hemother. 19. 56 1-568 Goodchild, M. C. & Dodge, J. A. (1985) C’ystic Fibrosis. Manual of Diagnosis and Management, Bailliere Tindall, London Govan, J. R. W. & Harris, G. S. ( 1986) Microbiol. Sci. 3,302-308 Govan, J. R. W., Fyfe, J. A. M. & Baker, N. R. (1983) Rev. Infect. Dis. 5 (Suppl. 51,874-879 Govan, J. R. W., Fyfe, J. A. M., Doherty, C. & McCrae, W. M. (1984) in Cystic Fibrosis: Horizons (Lawson, D., ed.), p. 373, Wiley, Chichester Komiyama, K., Habbick, B. F. & Gibbons, R. J. ( 1987) Can. J . Microbiol. 33 , 2 7- 3 2 Krivan, H. C., Ginsburg, V. & Roberts, D. D. ( 1988) Archiv. Riochem. Biophys. 260,493-496 Lam, J., Chan, R., Lam, K. & Costerton, J. R. W. (1980) Itlject. Immun. 28,546-556 McAvoy, M. J., Newton, V., Paull, A,, Morgan, J., Gacesa, P. & Russell, N. J. (1988) J. Med. Microbiol. 28, 183- 189 McCarthy, V. P., Rosenberg, G. & Rosenstein, B. J. ( 1 986) I’aediatr. Infect. Dis. 5,256-258

McEachran. D. W. & Irvin. R. T. (1986) C‘un. J. Micmhiol. 31. 563-569 Marcus, H. & Baker, N . R. ( 1 985) Infect. Irnmirn. 47,723-729 Mearns, M. B. ( 1980) in I’erspectives in C’ystic. Fibrosis (Sturgess, J. M., ed.), pp. 325-334, Canadian Cystic Fibrosis Foundation, Toronto Normark, S., Baga. M., Giiransson, M., Lindberg, F. P.. Lund, B., Norgren, M. & Uhlin, B. E. ( 1 986) in Microbial Lectins and Agglutinins (Mirelman, D.. ed.). pp. 1 13- 143, Wiley, New York Patterson, H., Irvin, R., Costerton, J. W. & Cheng, K. J. (1’975) J . Ructeriol. 122,278-287 Ramphal, R. & Pier. G. ( 1985) Infect. Immun. 47, 1-4 Ramphal, R. & Pyle. M. ( 1 9 8 3 ~Infect. ) Immun. 41.339-344 Ramphal, R. & Pyle, M. (1983b) Infect. Irnmun. 41,345-35 1 Ramphal, R.. Small. P. A,. Shands, J. W., Jr, Fischlsweiger. W. & Small, P. A,, Jr ( 1980)1nfi.c.t. Immun. 2 7 , 6 14-6 1 Y Ramphal, R., Saddoff, J. C., Pyle, M. & Silipingi, J. D. ( 1984) Infect. Immun. 44, 38-40 Reid, L. (1980) in I’erspectives in Cystic Fibrosis (Sturgess, J. M., ed.). pp. 198-2 14, Canadian Cystic Fibrosis Foundation. Toronto Russell, N. J. & Gacesa, P. ( 1988) Mot. Aspects Med. 10, 1-9 I Schintz, P. 0.(1982) Actci I’uediatr. Scand. (Suppl. 301), 55-62 Sturgess, J. H. ( 198 1 ) Monogr. I’aediatr. 14,60-74 Vishwanath, S. & Ramphal, R. ( 1 985) Infect. Immirn. 48, 33 1-335 Woods, D. E., Straus, D. C., Johanson, W. G., Jr & Bass, J. A. ( 1 98 1 ) J . Infect. l1i.s. 143, 784-790 Woods, D. E., Straus, D. C., Johanson, W. G., Jr & Bass, J. A. ( 1 983) Rev. Infect. Dis. 5 (Suppl. 5). 846-85 1

Received 19 Decemher 1988

Coagulase-negative staphylococci and hydrocephalus shunt infections Non-return valves

R. BAYSTON Department of Paediatric Surgery, Institute of Child Ileulth, University of L o n d o n , 30 Guildford Street, L o n d o n W C I N IEH, U.K.

1 1

Introduction

Hydrocephalus is caused by accumulation of cerebrospinal fluid in the cerebral ventricular system, and is controlled by diverting or shunting the fluid around the obstruction and into a suitable body cavity. The most common drainage site is the peritoneal cavity, but some shunts drain into the right cardiac atrium and other sites. Shunts are inserted surgically and are totally enclosed within the body. They are made wholly or partly from silicone elastomer (Fig. 1). The commonest cause of failure of this treatment is colonization of the shunt by microorganisms [ 11. The published incidence varies between 1% and 39% [ 2 , 3 ]with a national average of about 15% of operations. The consequences of shunt colonization depend on the site of drainage, but include ventriculitis, septicaemia, peritonitis, abscesses and renal failure. In addition, while the infection is being treated the hydrocephalus cannot be controlled satisfactorily. The estimated cost of an episode of shunt infection, not including personal expenses, loss of earnings, dependant’s travel to hospital and state benefits, is f6000 in the U.K. Aetiology

Shunt infections can usefully be classified as internal and external 141. The latter consist largely of infection of the Abbreviation used: ESS, extracellular slime substance.

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Direction of flow

Fig. 1. Holter hydrocephalus shun;

A Holter hydrocephalus shunt consisting of (left to right) ventricular catheter, Rickham reservoir, two valves in a steel housing and a long distal catheter leading in this case into the heart. tissue around the outside of the shunt which is enhanced by the presence of the shunt as a foreign body. Internal shunt infections are more common and consist of colonization of the luminal surfaces of the shunt tubing and valves. The causative organisms almost always gain access to the shunt when it is being inserted or revised, and originate on the patient’s skin [5].Despite thorough preparation of the skin preoperatively, resident organisms from the deeper layers crnerge after a few minutes and are found in large numbers in most surgical incisions during operation [6]. In most cases they do not cause harm, except when a surgical implant such as a shunt is inserted.

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BIOCHEMICAL SOCIETY TRANSACTIONS

As the causative organisms originate mainly on the skin, most infections are due to coagulase-negative staphylococci which reside here in large numbers. Other members of the skin flora such as coryneforms, Acinerohacrer sp. and I’ropionibucteriitm sp. also cause shunt infections though much less frequently. The coagulase-negative staphylococci can be divided into several species [ 71. Staphylococcus epidermidis is the commonest both o n the skin and as a cause of shunt colonization.

I)etermiriutivefactors in colonization The process by which a coagulase-negative staphylococcus comes into proximity with the shunt surface and subsequently colonizes it can be divided into two phases. The first phase involves the organism being attracted to the shunt surface and adhering to it. Van der Waals forces, hydrophobicity and sometimes chemical bonding play a part, but perhaps the most important is hydrophobicity [8]. Hydrocephalus shunts are made from silicone elastomer which is very hydrophobic. The outer surfaces of organisms can undergo modification depending on the genetically determined capabilities of the organism. For instance, Klehsiellu aerogenes. a Gram-negative rod which normally has a hydrophilic capsule, will not adhere well to silicone elastomer, but a genetic variant which cannot produce the capsular material will [9].Absence of the capsule means the hydrophobic proteins on the cell surface are exposed. Coagulase-negative staphylococci also have hydrophobic proteins on their surfaces which make them adhere. Adherence to silicone elastomer occurs within seconds of close contact under experimental conditions. On completion of phase I, resulting in adherence, phase I I begins. If nutrients are present, as in cerebrospinal fluid, the cells begin t o divide and to produce an extracellular glycosaminoglycan called extracellular slime substance (ESS) [ 10, 111. At first this appears as a rugose coating over the small groups of cells (Fig. 2), but then it appears t o become fully

Fig. 3. Cocci embedded in u linear network of ESS Original magnification: x 1 5 000 scanning electron micrograph. hydrated and extends several cell diameters. After dehydration for electron microscopy, it appears as a linear network in which the cells are embedded (Fig. 3).The rate at which this process occurs is governed by availability of nutrients, but is usually about 24 h, with a stage of cell division before ESS production of 1-4 h. .Yricc/ies i r i

iirro

Dehydrated. purificd ESS consist\ o f 27”,, protein \\ith the remaining polys;icch:iridc containing uronic acids and other monosaccharide components 11 21. I t has been found to have ii wricty of effect5 i r i iirro o n components o f the immune system. such ;is lethality to 13-lymphocytes and inhibition o f killing by polymorphonuclear Icucocytes. though the role of thew i r i i i i ~is ;IS yet unclear 11 31. I t clearly enhances adherence of staphylococcal cells to each other. though not to silicone elastomer. and :iIlo\v\ them to develop morc dense niicrocolonics. The mo\t important effect of ESS is the protection it atfords t o c o l o n i h g organisms from antimicrobials 114. 151. Whether the ESS itself functions as a molecule o r charge barrier. or u,hcther the \beer density o f the microcolonic5 protects those cocci in the core from the drug action remains unclear. Houevcr. laboratory studies on colonized catheters show that ESS-producing organisms are very much more resistant to antimicrobials which in convcntional tests are lethal. Also. in the early part o f phase I I . alter adhcrcncc. but betore ESS production. organisms are normally susceptible t o the antimicrobials and progression to microcolony formation and f 3 S production can be aborted. ( ‘linicalrc~lriwicc~

Fig. 2. Production of ESS in the early stages ofphase I1 The ESS is dense and rugose and is possibly poorly hydrated at this stage. Original magnification: x 3200 scanning electron micrograph.

The characteristics of coagulase-negative staphylococci and their chemical affinity for silicone elastomer make them an important source of morbidity and a major problem in modern medicine. 1989

623th MEETING, LONDON Once a hydrocephalus shunt has become colonized and ESS production has begun, attempts to eradicate the organisms using antimicrobials almost always fail and the shunt must be removed. After further treatment to eradicate the organisms from the tissues, another shunt is inserted, but there is a risk of this becoming colonized. Experimental work has led to the development of a regimen for treatment which increases the chances of success, but the device must still be removed [ 11. The early part of phase 11 before ESS production, when the organisms are still vulnerable to conventional levels of antimicrobials, might allow antimicrobials given during the operation to prevent colonization, and a multicentre trial to evaluate this is proceeding. Another approach to prevention is the processing of implants to make them less susceptible to colonization, either by changing their surface characteristics or by bonding antimicrobials to the surface to kill adherent bacteria. Several processes are now available and one suitable for hydrocephalus shunts has been described [ 161. 1. Bayston, R., Hart, C. A. 6t Barnicoat, M. (1987) J. .“wrol. Neurosirrg. I’sychiutr. 50. 11 19- 1123 2. Tabard. Z . & Forrest, D. M. ( 19x2) Z. Kinderchir. 37. 1 S6- I S X 3. Wald, S. & McLaurin, R. L. ( 19x0) J. Nectrosctrg. 52.4 1-46

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473 ~ h u l 1tific.tioti.s. ~rs Chapman 4. Bayston. R. ( I9XX) t t ~ ~ l r ~ c l ~ e ~Shirrit

and Hall, London 5. Bayston. R. & Lari. J. ( 1974) I k v . Med. C’hilcl Ncirrol. 3 2 . 16-22

6 . Raahave, D. ( I 974) Rc/rr C’hir. Scund. 140,585-593 7. Goodfellow, M. ( 1 987) Zhl. Rukt. (Suppl. 16), 1-14 8 . H o g , A. H., Dankert, J. & Feijen. J. ( 1 9x7) Zhl. Rukr. (Suppl. 16). 113-131 9, Denoya, C. D.. Trevisan, A. R. & Zorzopulos, J. ( 19x6) J. Mrd. Microbiol. 21.225-231

10. Bayston. R. & Penny. S. R. [ 1972) &I,.

hfrd. C’hiltl Nzirrol. 27,

25-28

I I . Peters. G.. Locci. R. ti Pulverer. G. (19x1) Zhl. Hukt. 173, 293-299

12. Peters. G.. Schumacher-Perdreau, F.. Jansen. €3.. Bey. M. & Pulverer, G. (19x7) Zhl. Rukt. (Suppl. 16). 15-32 13. Gray, E. D., Peters, G., Verstegen, M. & Regclmann, W. E. ( 1 984) Luncct i. 365-367 14. Sheth, N. K., Franson, T. R. & Sohnle, P. G. ( I 9x5) Luncrt ii, 1266- 126X I S . Bayston, R., Zdroyewski. V. & Barsham. S. ( 19XX) J. Infict. 16. 141- 146 16. Bayston. R.. Grove. N.. Sicgel, J.. Lawellin. I>. & Barsham. S. ( 1989~ J. h’crrrol. Mvtrotrtrg. /’.syc/7io/r. in the press

Received I9 I>ecemhcr I UXX