7734

Saturday 20 November 1971

ALTERNATIVE FORMS OF LOCALTREATMENT FOR BURNS

E. J. L. LOWBURYH. A. LILLY

J. S. CASON

D. M. JACKSONJ. P. BULL

J. W. L. DAVIESPAMELA M. FORD

Medical Research Council Industrial Injuries and Burns Unit,Birmingham Accident Hospital, Birmingham 15

Summary In a controlled trial of three alternativemethods for local treatment of severe

burns, a significantly lower incidence of bacterialcolonisation was recorded in burns treated with localchemoprophylactic agents than in those treated byexposure in warm, dry air. Of the local chemoprophy-lactic methods, compresses of 0.5% silver-nitratesolution gave better protection in general against bac-terial colonisation than 11.2% mafenide (’ Sulfamylon’)acetate cream with exposure of burns, but infection withPseudomonas œruginosa occurred about as often inburns treated with silver-nitrate compresses as inthose treated with mafenide cream. Miscellaneouscoliform bacilli colonised similar proportions ofburns in the three treatment groups. The mean ofthe highest respiration-rates per patient was signifi-cantly higher in patients treated by exposure in warm,dry air than in those treated with silver-nitrate com-presses. The mean respiration-rate of patients treatedwith mafenide was slightly higher than that of patientsin the silver-nitrate group, and slightly lower thanthat of patients in the group treated by exposure inwarm, dry air; the mean temperature of patientstreated with mafenide was slightly lower than that ofthe patients treated by exposure, but not apparentlydifferent from that of patients treated with silver-nitrate compresses. Mortality in each group was

slightly, but not significantly, lower than that expectedon a probability chart based on findings in the unitduring the years 1965-70. Most of the patients treatedwith mafenide did not complete the course of treat-ment because of pain; acidosis occurred only in onepatient treated with this agent. Side-effects of silver-nitrate treatment were noted in some patients, includ-ing low serum-sodium, acidosis, and diarrhœa. Atrial of 1% silver-sulphadiazine cream on smallerburns showed that daily reapplication of the creamgave significantly better protection than reapplicationevery three or four days; the prophylactic effects ofthis treatment were similar, whether burns were

covered with dressings or exposed.

Introduction

LOCAL treatment of burns is a subject of muchcontroversy, and conflicting claims have been putforward for treatment by exposure or cover, for wetor dry conditions, and for the use or avoidance ofantibacterial applications. A major consideration hasbeen the effect of such treatment on the developmentof sepsis, and evidence for the value of various formsof topical chemoprophylaxis has been shown in con-trolled trials reported from this unit.1-4 Local treat-ment is relevant also to the success of early excisionand grafting, to the survival of undamaged tissue inthe burned area, to fluid loss, and to metabolism. In

selecting a form of treatment for routine use each ofthese factors must be considered.

In the past few years special claims for 0-5%silver-nitrate solutions, 4-7 mafenide cream,8-11 andsilver sulphadiazine 12-14 have been supported bystudies in the United States and Europe. Good resultswith low mortality have been reported also in patientstreated by exposure in a warm, dry atmosphere, theprimary object of which was to conserve the patient’smetabolic activity.15-17

In this paper we report a comparison, by controlledtrial, of 0-5% silver-nitrate solution, 11-2% mafenide(’ Sulfamylon’) acetate cream, and exposure in warm,dry air as methods of local treatment for extensivelyburned patients. We report also a trial of silver-sulphadiazine cream on smaller burns, in which thevalue of more frequent dressings and of continuousexposure of the treated area are assessed.

Patients and Methods

EXTENSIVE BURNS

Patients under seventy years of age with fresh burnsinvolving 0-1 or more expectation of mortality on theprobability grid described by Bull 11 were examined onadmission to assess their eligibility for the trial; if eligibleand suitable on clinical grounds, they were allocated inrotation to three groups, for treatment with 0-5% silver-nitrate compresses, 11-2% mafenide acetate cream, or

exposure in warm, dry air.Silver-nitrate CompressesThis treatment was carried out as in previous trials.4. s

Gauze dressings soaked in warm 0-5% silver nitrate wereapplied daily and kept in position by cotton bandages. Thedressings were kept continuously moist by applicationevery two hours of fresh 0-5% silver-nitrate solution. Thedressings were changed every day until the burns wereconsidered ready for skin-grafting, or healed and ready forexposure. Supplements of electrolytes were given bymouth. 4,5 5 Room temperature was maintained at about

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25 °C unless a cooler environment was asked for by thepatient.

Afafenide Acetate CreamThe cream was applied directly with a gloved hand to

the surface of the burn, in a layer thick enough to concealthe burn; the burns were left exposed, and the cream wasremoved in a warm bath or by washing, and replaced withfresh cream every day. Some sites had to be covered withcream several times a day. In patients, especially smallchildren, who could not be restrained from rubbing orscratching the treated area, the cream was applied on asingle layer of gauze, which was held in position by cottonbandages. Treatment was continued, when possible, untilthe burns were ready for skin-grafting or healed; only thosewho could be treated for at least 7 days were included inthe bacteriological analysis of the trial. Five patientsadmitted to the trial were withdrawn after 1-3 days becauseof complaints of severe pain at the site of application. Thisgroup also was treated at about 25 °C unless they found ittoo warm.

Warm, Dry AirPatients were treated by exposure to warm, dry air on a

Harrison and Jones Rotaire’ force-ventilated bed 19 in asingle-bed side-room. It was intended to maintain thetemperature at 30-32°C and the relative humidity at

between 20 and 30%. These environmental conditions,however, could not always be maintained; the temperaturesometimes fell when the door to the room was openedfrequently, and the relative humidity rose to more than40% on occasions because of the limited drying capacity ofthe dehumidifying equipment. Failure to maintain therelative humidity at less than 30% occurred when a patientwith extensive burns, who might lose up to 3 litres of waterper day by evaporation from the burned surface, wasnursed in the room, or when the relative humidity of theair outside the hospital was high, or when there werefrequent visits to the patient by nursing and medical staff.

All patients received 7-10 days’ treatment with erythro-mycin (250 mg. 6-hourly) or cloxacillin (250 mg. 6-hourly)as prophylaxis against tetanus and Streptococcus pyogenes.

SMALLER BURNS

To assess the possible advantage of exposure or of dress-ings and of more frequent application in the local prophylac-tic treatment of burns with silver-sulphadiazine cream,patients with burns of moderate extent (over 5%, but withno expectation of death on the mortality grid 18) wereallocated in rotation to three groups:

(a) Treatment with 1% silver-sulphadiazine cream coveredwith dressings of gauze, cotton-wool, and crepe bandage; the

dressings were changed daily.(b) Treatment with silver-sulphadiazine cream with no dress-

ings, or with only a single layer of gauze kept in place by a cottonbandage; the cream was reapplied daily after baths. Themethod was modelled on that used for mafenide cream (see above).

(c) Treatment with 1 % silver-sulphadiazine cream coveredwith dressings which were changed every three or four days.This, the control treatment, was identical with that comparedin a previous trial with silver-nitrate cream.14

BACTERIOLOGICAL ASSESSMENTS

In both trials the frequency and approximate amountof bacterial colonisation of burns in the treatment andcontrol groups were assessed from the results of culture ofbacteriological samples taken from burns on swabs mois-tened with peptone water.4 4 Swabs were taken from allburns on admission of the patient, at every change ofdressing, at operations, and daily if the burns were treatedby the exposure method. Swabs were inoculated on horse-blood agar (with 4% New Zealand agar to prevent swarmingof Proteus spp.), on a selective medium, cetrimide agar, forPseudomonas aruginosa 20 and in cooked meat broth, whichwas subcultured to the same solid media after overnightincubation at 37 °C. Plates were examined after eighteen totwenty-four hours’ incubation and colonies were picked forgram-stain morphology and for a limited confirmation ofgenus and species.4, Zo, 21 Tests were made for carry-over " of antimicrobial agents from burns to swabs and toculture media when no bacterial growth was obtained.

Sloughs excised from a number of burns were examinedby a quantitative method for numbers of bacteria. Thesamples of slough were weighed, homogenised in a Biihlertop-drive homogeniser, and viable counts of total bacteria,Staph. aureus, Ps. aeruginosa, and coliform bacilli were madeby the method of Miles et al.22 on horse-blood agar with4% New Zealand agar in the medium; the details of themethod will be reported elsewhere. 23 Presumptive Staph.aureus and Ps. aruginosa colonies were picked and con-firmatory tests were used for identification.

Sensitivity of Strep. pyogenes, Staph. aureus, Ps. aeruginosa,and miscellaneous gram-negative bacilli to antimicrobialagents used in local treatment was assessed by a ditch-platemethod and, for silver compounds and mafenide, by aplate-dilution test. 4,24,25

CLINICAL ASSESSMENT

The mean morning and evening temperature and

respiration-rate and the mean highest temperature andrespiration-rates of patients were assessed from the tempera-ture charts in the trials of silver-nitrate compresses,mafenide cream, and exposure in warm, dry air. Tempera-ture and respiration-rate were carefully measured by a nurse.The mortality in these three groups was also compared

with the expected mortality, using Bull’s revised mortalityprobability grid based on all cases treated in this unitduring 1965-70.2g Each of the three treatments hadcertain disadvantages, but once a patient was allocated to atreatment group, that treatment was continued unless achange was clearly in the patient’s interest; when thetreatment was changed the reasons were noted.

Results

EXTENSIVE BURNS

BacteriologyTable I shows that no bacterial growth in solid or

liquid medium (N.G.) or bacterial growth only in

liquid medium (v.s.G., very scanty growth) was muchmore common in samples from patients treated withtopical antibacterial applications than in those treated

TABLE I-BACTERIAL GROWTH

* Significantly lower than corresponding control frequencies (p < 0-001). f Significantly lower than corresponding mafenide frequency (p 0-001).t Not significantly different from corresponding control frequency (p > 0-05).

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TABLE II-ISOLATION OF STAPH. AUREUS, PS. ARUGINOSA, PROTEUS SPP., AND COLIFORM BACILLI

* Significantly greater than corresponding control frequencies (p < 0-001). t Significantly greater than corresponding mafenide frequencies (p < 0 001).Other differences not significant (P > 0-05).

by exposure in warm, dry air. Those treated withsilver-nitrate compresses had more N.G. results (35%)than those treated with mafenide cream (13%).

Staph. aureus, Ps. ceruginosa, and Proteus spp. wereisolated from a smaller proportion of swabs takenfrom burns treated with antibacterial applications thanfrom those treated by exposure method in warm, dryair (table 11). Staph. aureus and Proteus spp., but notPs. ceruginosa, were isolated less often from the patientstreated with silver-nitrate compresses than from thosetreated with mafenide cream. There was no appre-ciable difference in the incidence of isolation ofcoliform bacilli (i.e., miscellaneous gram-negativebacilli other than Pseudomonas or Proteus) from thethree groups. Strep. pyogenes was not isolated fromany patient in the trial.Table ill shows the numbers of patients and of

burns acquiring heavy growth (+ + +), moderategrowth (+ + or +), and very scanty growth ofbacteria. The proportion of isolations of Staph. aureusgraded as + + + was much higher in the patientstreated by exposure than in those treated with silver-

nitrate compresses or mafenide cream. Gram-negativebacilli, presumably because of their greater sensitivityto the lethal effects of drying, were present on exposedburns in smaller proportions than Staph. aureus.The semiquantitative grading of bacterial density

used in our routine bacteriology of burns (table ill)was found to give a useful indication of the numbersof bacteria present. Table iv shows that there was a

rough correlation between the viable counts per g. ofexcised slough from burns treated with dressings andthe grading as + + +, + +, +, or v.s.G. Individual

discrepancies occurred, some burns showing largernumbers of bacteria than were indicated by thegrading of swabs, probably because of a selectiveinhibition of growth by antibacterial agents appliedon the surface of the burns. Swab grading of Ps.ceruginosa and Proteus spp. in burns also showed arough correspondence with viable counts, though thenumbers examined were small..

In a separate study of burns treated by the exposuremethod, some swabs showing + or smaller numbers ofbacteria came from burns yielding very large numbers

TABLE III-DENSITY OF BACTERIAL GROWTH IN BURNS

* The numbers under patients and burns represent one or more swabs from which the density of growth was that shown at the head of the column;swabs represents the total number of swabs showing that density of growth.

TABLE IV-DENSITY OF BACTERIAL GROWTH FROM SWABS IN RELATION TO VIABLE COUNTS FROM BURN SLOUGH

* The burns were treated with creams and covered with dressings.

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TABLE V-MEAN (&plusmn;S.E.M.) MORNING AND EVENING TEMPERATURE AND RESPIRATION-RATE

* t=2’17; 0.05> p > 002.

of gram-negative bacilli on viable counts from excisedslough. This finding is consistent with our earlier

report of scanty surface flora associated with abundantdeeper colonisation of excised sloughs from burnstreated by exposure."Clinical AssessmentsTable v shows the mean and the mean highest

morning and evening temperature and respiration-ratein the three groups of patients included in the trial ofprophylaxis for extensive burns. The mean highestrespiration-rate in patients treated with silver-nitratecompresses was significantly lower than that of patientstreated by exposure in warm, dry air. Other differenceswere not significant, though mean temperature andrespiration-rates were almost all higher in the patientstreated by exposure in warm, dry air than in thosetreated with either form of topical chemoprophylaxis;mean respiration-rates were higher in the patientstreated with mafenide than in those treated withsilver-nitrate compresses, but there was little apparentdifference in mean morning and evening temperatures.The actual mortality (with the expected mortality

in parentheses) was as follows: silver-nitrate com-

presses 1 (3-5), mafenide cream 3 (3-7), and warm, dryair 3 (3-5). The causes of death were: acute renalfailure associated with septicaemia (coliform bacilliwere found in the spleen) in the patient given silver-nitrate compresses; bronchopneumonia with acute

renal failure, pulmonary embolus with septicaemia,and pulmonary embolus in the patients on mafenide;and septicaemia with acute bronchopneumonia (2 cases)and septicaemia with tracheobronchitis and renal failurein the patients exposed to warm, dry air.

All patients in the trial received the test treatmentfor at least seven days. Treatment was terminatedbecause of pain in 10 of the 15 cases treated withmafenide and in 1 case in each of the other groups.Silver-nitrate treatment was changed in 3 cases becausethe burns became colonised with Ps. aruginosa, and4 were changed to creams to hasten slough separation.

In 3 cases the warm, dry air treatment was changed forthe same reason. When clinicians learn the particularadvantages of different methods they naturally wish touse them consecutively at different stages of the

patient’s progress.Side-effects and Complications

In the silver-nitrate group there was 1 case ofacidosis with confusion, hyperventilation, and sodiumretention; 1 case of diarrhoea probably due to oral

supplements of electrolytes; and 1 patient had a

serum-sodium below 125 meq. per litre, falling to aslow as 116 meq. per litre. In the mafenide group 1 casehad acidosis with hyperventilation; on two occasionsthe base deficit was -7-0 and -9-3 meq. per litre, andon both occasions this was readily corrected withoral sodium bicarbonate.

Pain caused by application of mafenide in somepatients was sufficiently severe to indicate change oftreatment. To investigate this pain, we did experi-ments on a healthy volunteer based on the technique ofArmstrong et al.2a Solutions of substances under testwere applied to opened blisters raised by cantharides.The intensity of pain sensation was recorded via afive-position switch and pen recorder, so that thetime course and severity of pain could be analysed.The subject did not know which type or concentrationof agent was being applied. Solutions of mafenideacetate (2-5, 5, and 10%) were compared with sodiumchloride (1-5, 3, and 6%). Potassium chloride solu-tions (0-1, 0-2, 0-4, and 0-8%) were used as a basis forcomparison of pain production.

All the potassium chloride and all the mafenidesolutions caused some discomfort or pain. By contrast,only the highest concentration (6 %) of sodium chloridecaused pain. The pain from any of the applicationswas readily relieved by an immediate rinse withsaline. The pain from mafenide was of gradual onset(30-45 seconds), was of moderate severity, and lastedfor four or more minutes. Pain due to potassiumchloride of 0-2% or more was more rapid in onset and

TABLE VI-CONTROLLED TRIAL OF SILVER-SULPHADIAZINE CREAM: BACTERIAL COLONISATION OF BURNS

* Significantly different from cream every 2-4 days with dressings (p < 0-001).

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declined sooner. The pain from 6% sodium chloridehad a time course similar to that of mafenide.

Neither the acidity (the pH was 6-85) nor the hyper-tonicity of the mafenide seemed to be sufficient causefor its painful effect. 3% sodium chloride is more

hypertonic than 10% mafenide and yet causes nopain, and even 2-5% mafenide, which is almost iso-tonic, causes some pain. The effect may perhaps berelated to the relatively high toxicity of mafenide toskin cells. The 11-2% cream corresponds to ten timesthe E.D.50 for inhibition of the respiration of skin-tissue culture.29 We had hoped that a more dilutepreparation, possibly reinforced with another anti-bacterial agent, might have produced equivalent thera-peutic action without causing pain, but this seemsunlikely.

SMALLER BURNS

Table vi summarises the main bacteriological find-ings in this trial. The prophylactic efficacy of silver-sulphadiazine cream, as judged by the frequency of nobacterial growth and of staphylococcal infection, wasgreater when it was applied daily than when it wasapplied every two to four days. Infection with Ps.aeruginosaJ Proteus spp., and coliform bacilli was in-frequent in all groups of the trial; the incidence ofinfection with these gram-negative bacilli was lowest inthe patients treated with daily applications of thecream and exposure or minimum cover.

Of the 43 patients treated with silver-sulphadiazinecream, 3 had skin rashes and 8 complained of irritationat the site of application. It was uncertain whetherthese complications were caused by silver sulphadia-zine, but local treatment was changed when theyoccurred. Very young children in this trial were lessoften treated by exposure than with dressings, becausethey had been known to eat the cream when theirfingers could reach it.

Physiotherapy with active movements of burnedhands was greatly facilitated when the cream was leftexposed.No patients complained of pain. There was very

little staining of bedclothes, and acidosis and hyper-ventilation were not observed.

COMPARABILITY OF GROUPS

Table vn shows that, except for those treated withsilver sulphadiazine and exposure, the patients in thetreatment and control groups of each trial fell withina similar range in respect of age and area of burn.

BACTERIOLOGY

Sensitivity of BacteriaThe strains of bacteria tested for sensitivity to silver

nitrate by the plate-dilution method showed a patternsimilar to that of strains isolated before the currenttrials, 3 and there was no evidence of an increasedresistance of any group of bacteria. As before, nostrain of Ps. aeruginosa grew on medium made up with160 {ig. or more of silver nitrate per ml., and Staph.aureus and Proteus spp. were inhibited on mediumcontaining half that amount of silver nitrate: of the427 strains of coliform bacilli, however, 55 grew on

TABLE VII-COMPARABILITY OF PATIENTS IN TWO TRIALS

plates made up with more than 5000 g. per ml. ofsilver nitrate-a proportion similar to that found byLowbury and Jackson. 3 0

There was a slight increase in resistance to mafenide,as judged by tests on strains isolated in the first andlast months of the trial of mafenide; the range ofM.l.c.s (in mg. per ml.) of Staph. aureus rose from0-5 (23 strains) to 1-0-5-0 (45 strains), that of Ps.aeruginosa rose from 0,5-5’0 (23 strains) to 5’0-10,0(47 strains), and that of coliform bacilli rose from5-10 (49 strains) to 10-20 (28 strains). The highestconcentration of mafenide acetate (1%) allowinggrowth in vitro was considerably lower than theconcentration of mafenide in the cream applied to theburns.

Tests for" Carry OverNo inhibition of added test organisms was found on

blood-agar plate cultures of burns yielding no growth;of these, 241 cultures from silver-nitrate-treated burnsin 15 patients and 50 cultures from 10 burns treatedwith mafenide cream were examined.

Discussion

Effective prophylaxis against bacterial contaminationis an important part of the treatment for patients withextensive burns in whom infection, especially withPs. aruginosa, is a major cause of death. This studycompares three different methods of local treatment forextensive burns, each of which has been stronglyadvocated in separate studies. The use of silver-nitratecompresses and of mafenide cream has been reportedto cause a reduction in the bacterial flora of burns andin mortality. Exposure treatment in warm, dry air hasalso been associated with a reduced mortality; thismethod, which was designed to conserve the patient’smetabolic activity, probably owes its clinical success tothis property rather than to the control of bacterialinfection. Though antibacterial compounds are notapplied to the burns in the exposure treatment, it hasbeen thought that the dry condition of the exposedburn might have contributed to the good clinicalresult by suppressing bacterial growth 15-in particu-lar the growth of gram-negative bacilli, which aremore prone than other bacteria to die on evaporationof the medium in which they have grown.31Our results show that silver-nitrate compresses were

more effective than mafenide cream, and each of these

applications was more effective than the exposuremethod in keeping burns free from bacterial colonisa-tion. Staph. aureus, Ps. ceruginosa, and Proteus spp.were isolated more often from burns treated by expo-

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Contact-plate culture on blood agar from burn treated byexposure in warm, dry air.

In spite of the dry surface, large numbers of bacteria ofdifferent types were present.

sure than from burns treated by the other methods;the figure gives an example of the heavy growth ofbacteria which may be found on extensive burns treated

by exposure. Ps. aeruginosa appeared approximately asoften in burns treated with mafenide cream as in thosetreated with silver-nitrate compresses. In view of the

large prophylactic effect of silver-nitrate compressesagainst Ps. ceruginosa shown in an earlier trial, in whichthe controls were treated with penicillin cream,4 itseemed that mafenide cream gave protection of asimilar order against these bacteria while giving lessprotection against some other bacteria. In an earlier

trial,32 mafenide cream applied with dressings wasfound no more effective as a prophylactic agent than0-5% silver-nitrate cream; since 0-5% silver-nitratecompresses gave much greater prophylaxis than 0-5%silver-nitrate cream, it appeared that mafenide creamwas much more effective when applied daily withexposure than when applied every two to four dayswith dressings.

A comparison of different methods of applying silver-sulphadiazine cream showed that daily re-applicationof this preparation gave better protection than appli-cation of the cream every 2-4 days; a similar resulthad been obtained in a previous trial with silver-nitratecream. 3 Unlike mafenide cream, silver-sulphadiazinecream did not give better protection when used withexposure (or minimal cover) and daily baths thanwhen used with dressings; this result was not unexpec-ted, because silver-sulphadiazine cream on exposedburns remained moist, unlike mafenide cream, whichwithin a few hours formed a dry incrustation on theexposed surface.There was evidence of clinical benefit from topical

chemoprophylaxis in the significantly lower meanrespiration-rate of patients treated with silver nitrateor mafenide than in those treated by exposure, and asuggestion that treatment with silver-nitrate compresses

was giving lower respiration-rates than treatment withmafenide cream. The absence of a significant differencein mean morning and evening temperature betweenpatients treated with silver-nitrate compresses andthose treated by exposure in warm, dry air was incontrast with earlier findings of a significantly highertemperature of patients treated with penicillin creamthan in those treated with silver-nitrate compresses &deg;

and with neomycin-chlorhexidine tulle gras,33 both ofwhich had good prophylactic effects against somegram-negative bacilli. This suggests that the exposuremethod was associated with less pyrexia and probablyless clinical infection than would have been found ontreatment with a cream inactive against hospital flora(especially gram-negative bacilli). Although the burnstreated by exposure usually had much heavier bacterialcolonisation than those treated with silver-nitratecompresses or mafenide cream, still larger amounts ofbacterial growth and growth products would befound in the burns and dressings of patients treatedwith creams (e.g., penicillin cream) inactive againstgram-negative bacilli and other common hospitalorganisms. Low humidity and raised temperature ofthe environment, which were imperfectly maintainedin the room occupied by the Harrison-Jones bed,probably contributed little towards the limited inhi-bition of bacterial growth on burns treated by exposurein this study.Each of the three methods used in severe burns had

serious drawbacks. The disadvantages of silver nitratewere staining, electrolyte loss, and the need for

electrolyte supplements, which could cause diarrhoea;also, silver nitrate was prophylactic only. Applicationof mafenide cream was painful, except on areas of full-thickness skin loss, and this tends to rule it out as aroutine prophylactic agent for children and someadults, since there are painless preparations that areas effective. Mafenide cream also tended to causeacidosis and can produce skin-sensitivity reactions.When patients were treated exposed on the specialbed with warm, dry air, it was difficult to maintainthe body and limbs in the best position to preventpressure necrosis and contractures; also, the dry airmade it difficult to provide humid conditions for thetreatment of respiratory-tract damage.The relatively small clinical effect shown in this

controlled trial by methods which caused a largereduction in bacterial contamination was not unexpec-ted, because invasive infection, even in extensivelyburned patients, occurs sporadically. Heavy growth ofbacteria, including Ps. aruginosa, is often found withoutobvious clinical infection (though it often causes somefailure of skin-grafts and delay in healing).1 I Thehazards of infection vary greatly in different burnsunits, and may be related to:

(1) The number of patients treated, which will deter-mine the amount of cross-infection and influence theselection of more virulent and more communicablestrains;

(2) the proportion of severely burned patients, who aremore likely to acquire and to disseminate bacteria;

(3) the ratio of nurses to patients, the isolation facilities,and other measures for controlling cross-infection;

(4) the age-range of patients, which will be related to

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susceptibility and possibly to hazards of acquisition anddissemination;

(5) the direct admission of freshly burned patients, inwhom prophylactic means have the best chance of succeed-ing, or of patients transferred from other hospitals, inwhom infection is likely to have been acquired beforeprophylaxis begins; and

(6) details of treatment which may enhance the patients’resistance to invasion by bacteria.

Differences in one or more of these categoriesexist between the Karolinska Hospital, Stockholm,where a low mortality and little sepsis occurred withoutuse of topical chemoprophylaxis, 16,17 our unit, wherea reduced mortality and very little sepsis (e.g., noPs. ceruginosa septicaemia for several years) was achievedonly after introducing effective topical chemopro-phylaxis, 6, 7,26 and the Shriners Burns Institute in

Cincinnati, where an appreciable amount of sepsis(including pseudomonas septicaemia) was still presentafter the introduction of topical chemoprophylaxis,pseudomonas vaccines, and good control of environ-mental flora. 34, 3;; In Stockholm, a relatively smallnumber of adult patients with fresh burns were treatedby exposure method in an isolation ward with single-bed rooms and a high nurse/patient ratio. The Bir-

mingham unit admitted a larger number of patientswith burns of slightly smaller average severity thanthose treated in Stockholm, but including children aswell as adults, and only a few transferred from otherhospitals with burns already infected on admission;patients were in a subdivided ward. In the unit atCincinnati the patients were all children, with a higherproportion severely burned than in the Birminghamunit, and almost all transferred from other hospitalsand likely to be infected on admission. These differen-ces might well account for the different findings in thethree centres.

No form of topical chemoprophylaxis is entirelysatisfactory, and the possible emergence of drug-resistant bacteria must be anticipated even after yearsin which all strains have been sensitive (e.g., as in theemergence of neomycin-resistant staphylococci, whichhappened in the early 1960s after many years in whichneomycin and related antibiotics had been extensivelyused). The availability of alternative prophylacticagents is therefore welcome; none of the three testedin this study has as yet presented a problem of resis-tance among burn pathogens. With most other anti-microbial agents, however, resistance, if it has not

already emerged, must be anticipated, and prophylacticuse of such agents should be avoided. This caution

applies to gentamicin, against which moderately in-sensitive strains of Ps. aeruginosa have been found inthis hospital and elsewhere. Gentamicin is a valuableantibiotic for systemic and topical treatment of pseu-domonas sepsis, and in a burns unit it should, withrare exceptions, be reserved for such uses.These trials confirmed our previous experience that

there are advantages in using different forms of treat-ment consecutively as circumstances change. For

instance, silver-nitrate compresses are a good initialtreatment for patients with severe burns, but thetreatment should be changed (e.g., to mafenide orsilver sulphadiazine or, in some cases, to gentamicin

or polymyxin cream) if sensitive gram-negative bacilliappear in large numbers, because these agents havebeen shown to have some therapeutic, as well as

prophylactic, value. 1, 14 Gentamicin cream has beenkept as a last reserve among our topical applications,and systemic gentamicin and cephaloridine or cephalo-thin have not been used unless heavy colonisation of anextensive burn or positive blood cultures suggestedimminent or actual invasion.With this schedule of treatment we usually find

only one or two of the patients in a 40-bed unitcolonised with Ps. ceruginosa; extensively burned

patients now commonly remain free from the organismwhich formerly colonised almost all extensive burns 3 sand caused more severe infection than other bacteria. 1

We thank Sterling-Winthrop Group Ltd. for supplies ofmafenide acetate cream; Dr. C. R. Ricketts, Miss R. A. Jenkins,and Smith and Nephew Ltd. for supplies of silver-sulpha-diazine cream; Mr. M. D. Wilkins for statistical help; the

laboratory staff for technical assistance; and the medical andnursing staff for cooperation in the trials.

Requests for reprints should be addressed to E. J. L. L.

REFERENCES

1. Jackson, D. M., Lowbury, E. J. L., Topley, E. Lancet, 1951, ii, 137.2. Jackson, D. M., Lowbury, E. J. L., Topley, E. ibid. p. 705.3. Lowbury, E. J. L. Br. med. J. 1960, i, 994.4. Cason, J. S., Jackson, D. M., Lowbury, E. J. L., Ricketts, C. R.

ibid. 1966, ii, 1288.5. Moyer, C. A., Brentano, L., Gravens, D. L., Margraf, H. W.,

Monafo, W. W. Archs Surg., Chicago, 1965, 90, 812.6. Cason, J. S., Lowbury, E. J. L. Lancet, 1968, i, 651.7. Carter, R. G. M.SC. thesis, University of Birmingham, 1968.8. Lindberg, R. B., Moncrief, J. A., Switzer, W. E., Order, S. E.,

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