1219

were not

reported:

our

aim

was a

randomised trial with

rate

of

infection rather than level of cutaneous colonisation as the criterion for antiseptic efficacy. We did explain why chlorhexidine seemed to protect against septicaemias due to contaminated hubs or infusate. All 4 bacteraemias due to contaminated infusate or a contaminated hub were in the alcohol and povidone-iodine groups. They "originated from a second catheter placed over a guidewire in the site of a previous catheter; in each case, the first catheter or skin of the insertion site was shown to have been colonised when the second catheter was inserted". Because replacing catheters over a guidewire is widely practised, organisms present on skin of the insertion site or in the old tract can be introduced into the hub or can contaminate infusate in the lumen of the catether at the time of insertion; thus a more effective cutaneous antiseptic could be expected to protect against such bacteraemias. We stand by our statement that, in an analysis of infusion-related bacteraemias from all sources in the two groups, chlorhexidine conferred significant protection against infusion-related septicaemia (odds ratio 0-16, p = 0-04). We do agree that strategies beyond more effective cutaenous antiseptics must be sought to reduce further the incidence of infection due to intravascular devices, and progress is being made. Studies point to the benefit of more stringent barrier precautions during insertion of central venous catheters,1 of the use of topical mupirocin’ or povidone-iodine5 at insertion sites, and the use of subcutaneous silver-impregnated cuffS,6,7anovel contaminationresistant catheter hub,8 and catheters coated with antimicrobial agents9 or impregnated with antiseptics.3 Department of Medicine, University of Wisconsin, Madison, Wisconsin 53792, USA

DENNIS G. MAKI

1. Mermel

LA, McCormick RD, Springman SR, Maki DG. The pathogenesis and epidemiology of catheter-related infection with pulmonary artery swan-ganz catheters: a prospective study utilizing molecular subtyping. Am J Med 1991; 91:

197-205. 2. Alvarado CJ, Stolz SM, Maid DG. Nosocomial infections from contaminated endoscopes, a flawed automated endoscope washer: an investigation using molecular epidemiology. Am J Med 1991; 91: 272-80. 3. Maki DG, Wheeler SJ, Stolz SM, Mermel LA. Clinical trial of a novel antiseptic central venous catheter. In: Program and abstracts of Thirty-first Interscience Conference in Antimicrobial Agents and Chemotherapy (Oct 1, 1991, Chicago). Washington, DC: American Society for Microbiology, 1991: 461. 4. Hill RLR, Fisher AP, Ware RJ, Wilson S, Casewell MW. Mupirocin for the reduction of colonization of internal jugular cannulae: a randomised controlled trial. J Hosp Infect 1990; 15: 311-21. 5. Levin A, Mason AJ, Jindal KK, Golstein MB, Fong IW. The value of topical povidone-iodine ointment in the prevention of hemodialysis related sepsis. In: Program and abstracts of Twenty-ninth Interscience Conference on Antimicrobial Agents and Chemotherapy (September, 1989, Houston). Washington, DC: American Society for Microbiology, 1989: 1078. 6. Maki DG, Cobb L, Garman JK, Shapiro J, Ringer M. An attachable silverJ impregnated cuff for prevention of infection with central venous catheters. Am Med 1988; 85: 307-15. Farr BM. 7. Flowers RH, Schwenzer KJ, Kopel RF, Fisch MJ, Tucker SI, Efficacy of an attachable subcutaneous cuff for the prevention of intravascular catheter-related infection: a randomized, controlled trial. JAMA 1989; 261: 878-83. 8. Stotter AT, Ward H, Waterfield AH, Hilton J, Sim AJW. Junctional care: the key to prevention of catheter sepsis in intravenous feeding. J Parenter Enterol Nutr 1987; 11: 159-62. 9. Kamal GD, Pfaller MA, Rampe LE, Jebson PJR. Reduced intravascular catheter infection by antibiotic bonding: a prospective, randomized, controlled trial. JAMA 1991; 265: 2364-68.

Catheters were inserted by house-officers and the frequency of infection may be related to technical skill and to the care taken by doctors inserting the cannulas. For example, increased trauma on insertion may encourage infection.1 In a study at this hospital we are comparing infection rates associated with two types of intravascular catheter. Only three doctors are inserting the cannulas. They are evaluating complications quantitatively by looking at factors such as localised pain (tensionometry) and area of inflammation (direct measurement). The results so far indicate that with strict attention to insertion technique and quantitative assessment of complications, studies limited to just a few doctors may permit more accurate comparisons of cannula infection rates. Department of Clinical Microbiology, Queen Elizabeth Hospital, Birmingham B15 2TH, UK 1. Elliott

TSJ.

Intravascular device infecttons.

T. S. J. ELLIOTT S. E. TEBBS J Med Microbiol 1988; 27: 161-67.

Renal intratubular crystallisation of calcium oxalate and naftidrofuryl oxalate SIR,-Drug-induced acute renal failure (ARF) may result from as cell toxicity of the drug or its metabolites, immunological injury, tubular obstruction, and cell damage by intraluminal precipitates of drug microcrystals. This last mechanism cannot be definitely demonstrated without precise identification of the crystalline material. We report two patients with ARF who had crystals in renal tubules with a suspected drug origin. Two men, aged 62 (patient 1) and 64 (patient 2) years, had arteritis, and patient 2 also had diabetes mellitus. They were admitted because of ARF without previous renal impairment. various mechanisms, such

Clinical and biochemical examinations were inconclusive. In 1 renal biopsy showed abundant crystals in tubules, associated with interstitial nephritis and diffuse sclerosis (figure). The patient required haemodialysis for three weeks and eventually recovered partial renal function (plasma creatinine 450 pmol/1). From the onset of urinary output, urine sediment contained many monohydrate (Cl) and dihydrate (C2) calcium oxalate crystals. In patient 2, renal biopsy revealed acute tubular necrosis associated with obstruction of numerous tubules by crystals. The patient required two haemodialysis sessions to recover partial renal function (plasma creatinine 160 umol/1). Shortly after diuresis started again, urine contained Cl crystals. In both patients, the intratubular crystals seen on renal biopsy were directly identified as Cl by Fourier-transformed infrared microscopy (FTIRM)

patient

SIR,-Dr Maki and colleagues’ study was on arterial and central catheters, the latter showing a greater propensity to infection. In studies such as this consideration should be given to the number of infusions or withdrawals via a line, since this may venous

influence the rate of catheter contamination. In central lines we find that intraluminal contamination is more likely with arterial than with

venous catheters, probably because arterial manipulated more often--eg, for blood sampling.

catheters

are

Maki and colleagues also report that coagulase-negative staphylococci on the skin at the insertion site may have been the origin of 8 cases of catheter-related bacteraemia. Coagulasenegative staphylococci are skin commensals. The source in these 8 cases could have been the patient’s own flora or that of medical attendants. Typing of bacteria from the catheter and patient’s skin would have provided additional evidence as to

source.

Microcrystals in renal biopsy specimen (arrows).

1220

(Bruker A590 infrared microscope with an IFS25 infrared spectrometer) and a calcium fluoride plate. Because Cl crystallisation is mainly dependent on hyperoxaluria,l we searched for the origin of oxalate in these patients. Neither patient had a known cause of secondary hyperoxaluria, such as an enteric hyperoxaluria or an overload of oxalate precursors. None of the drugs the patients received contains oxalate or its known precursors. Patient 2 had received enalapril and frusemide for more than 18 months without effect on renal function. Dietary oxalate intake was normal. We noted, however, that both patients had received oral naftidrofuryl oxalate (’Praxilene’) (2 x 200 mg daily) during the twenty days preceding ARF. In addition, patient 1 received a daily intravenous (iv) infusion in 5 % dextrose of 3x 400 mg naftidrofuryl oxalate for 20 days before ARF, and patient 2 a daily iv infusion of 2 x 400 mg for 10 days before ARF. The commercial form of naftidrofuryl is a salt of oxalic acid that provides an oxalate load of 76 mg for 400 mg of drug. Intestinal absorption of oxalate is low, and thus the contribution of dietary oxalate or oral oxalate-containing drugs would be unimportant. No case of nephrotoxicity induced by this drug has been reported so far to the French Pharmacovigilance Service or to the manufacturer (Laboratoire Oberval, Lyon). Our findings emphasise the value of FTIRM in the identification of renal crystal deposits,2,3 especially in biopsy specimens. Since high amounts of oxalate are delivered in iv naftidrofuryl treatment, the risk of renal damage should be noted and iv use of this drug should be carefully defmed. Department of Nephrology, CHRU Dupuytren, 87042 Limoges, France

CHRISTIAN MOESCH MICHEL RINCE

Department of Nephrology, Hôpital Necker, Paris

MICHEL DAUDON

INSERM U90,

Department of Nephrology, Dupuytren

CHRU

calculated for 1988, 1989, and 1990 and compared with numbers of donated in October of the same year. Comea-only donation in October, 1989, the month of the television appeals, virtually doubled compared with the mean rate in January to June, 1989: corneas

*5 SD

a

higher than average donation

rate

in

January-June, 1989.

Thus, against a slowly rising cornea-only donation rate, there was striking jump in October, 1989, during a period of intense

publicity, albeit one focusing initially on liver transplantation. This suggests that many more potential cornea donors are available than are retrieved, which is important in view of the continuing rise in demand for corneas and transplantation.2 Although cornea-only donation rates gradually fell after October, 1989, they did stabilise at a new high level. No other explanation for this finding exists apart from the apparent positive effect of publicity, supporting Gore and colleagues results.’ Public appeals of this nature for organs cannot be advocated as routine policy. Nevertheless, every such event can be regarded as an educational opportunity to make the case for patients awaiting organ transplants at a time when both lay public and medical professions are especially receptive. Department

of

Ophthalmology,

Bristol University, Bristol Eye Hospital, Bristol BS1 2LX, UK, and UK Transplant Support Service Authority, Bristol

W. J. ARMITAGE C. A. ROGERS M. J. RIGGULSFORD B. A. BRADLEY S. J. Moss D. L. EASTY

JEAN-CLAUDE ALDIGIER CLAUDE LEROUX-ROBERT

SM, Taylor RMR, Wallwork J. Availability of transplantable organs from brain dead donors in intensive care units. Br Med J 1991; 302: 149-53. 2. Armitage WJ, Moss SJ, Easty DL, Bradley BA. Supply of corneal tissue in the United Kingdom. Br J Ophthalmol 1990; 74: 685-87. 1. Gore

stem

1. Daudon M, Réveillaud RJ, Levasseur H, Jungers P. Combined influence of urinary calcium and oxalate concentrations on crystal formation in stone formers. Urol Res 1988; 16: 223. 2. Daudon M, Marfisi C, Lacour B, Bader C. Investigation of urinary crystals by Fourier transform infrared microscopy. Clin Chem 1991; 37: 83-87. 3. Levison DA, Croker PR, Allen SD. Applications of infrared microscopy to clinical diagnosis. Eur Spectroscopy News 1985; 62: 18-20.

Cornea donation boosted by positive publicity for transplantation SIR,- In their audit of organ donation from intensive care units (ICUs) in England, Gore et all reported that a period of intense publicity in October and November, 1989, following appeals on television and in national newspapers for livers for two patients, influenced the numbers of organs offered and retrieved from brainstem-dead, heart-beating donors. During this period, both refusal of relatives to give consent and failure of hospital staff to discuss donation with relatives were much reduced compared with January to June, 1989, leading to increased offers of organs. Although retrievals of hearts, livers, lungs, and corneas from heart-beating cadaveric donors in ICUs did not change appreciably during this period, there was a 17% increase in kidney retrieval. Cornea donation is not restricted to heart-beating cadavers. Furthermore corners are often retrieved from donors over 70 years old and up to 24 h post mortem-yet in the UK there is a shortage of corneas for transplantation. This prompted us to study cornea donation, as reported to the UK Transplant Service, to see if cornea donation from asystolic donors was also influenced by the publicity surrounding the liver appeals. Gore et all reported 151 heart-beating cadaveric cornea donors in ICUs in England during January to June, 1989. During the same period, the number of cadaveric cornea donors from the whole of the UK and Republic of Ireland reported to the UK Transplant Service was 589, of which 188 were multi-organ donors and 401 were cornea-only donors. A few cornea-only donors are heartbeating cadaveric donors but the great majority were asystolic donors, forming in the main a distinct and larger group of cornea donors from that analysed by Gore et aU Mean (and SD) average monthly cornea-only donation rates during January to June were

Treatment of septic shock SiR,—We would add a few points to Dr Cohen and Professor Glauser’s review (Sept 21, p 732) of septic shock. It is a sad commentary on current clinical practice that in many patients with sepsis, features of shock develop while they are being treated in hospital. At best they may have received intravenous fluids and broad spectrum antibiotics and some of these patients will probably recover, but the outcome for many clearly remains unacceptable. For the past ten years the pathophysiology of septic shock has been investigated in some detail and the messages from these studies are clear: clinical features such as pulse, blood pressure, and temperature provide no guide to management, and the addition of central venous pressure measurements and arterial blood gas estimations contribute little.1 Indices of cardiac output and oxygen transport provide not only prognostic information but also data on which therapeutic action can be based. Both morbidity and mortality have been reduced by application of the principles of oxygen transport support to the patient with septic shock.2 However, this practice is still viewed with scepticism by some because of the increased resources this type of monitoring requires, and by others who believe that the cure for sepsis (the "magic bullet") is just around the comer. The detection of at-risk patients at a stage when resuscitation can prevent shock should not be beyond an experienced doctor’s ability and may be aided by a system for rapid detection of endotoxaemia.3 The role of tumour necrosis factor (TNF) in septic shock is becoming increasingly confused. That we should have evolved an immune system intent on self-destruction when confronted by gram-negative bacteria seems strange, and Cohen and Glauser suggest a potentially protective effect. Using a sensitive ELISA for TNF we not only have been unable to find TNF in the plasma often patients with advanced septic shock and multiple organ failure (studied for 4-10 days) but also have found TNF-neutralising activity in these samples as shown by the apparent loss of immunoreactivity of human recombinant TNF suggesting the