Hospital Infection Yesterday and Today

J Clin Pathol: first published as 10.1136/jcp.14.1.2 on 1 January 1961. Downloaded from

J. clin. Path. (1961), 14, 2.

Hospital infection yesterday and today

MARY BARBER From the Postgraduate Medical School ofLondon

HISTORICAL BACKGROUND nique was first applied in 1865. The dramatic effect and the consequent revolution in surgery are well BEFORE LISTER known. In the years that follo ved, asepsis largely super- Cross infection has been a problem throughout the ceded antisepsis and enormous improvements in ages wherever the sick have been housed. It was hospital, particularly theatre, hygiene were intro- particularly rife in some of the larger hospitals of duced. By about the 1930s the conquest over hospital Europe in the centuries before Lister, making all but infection seemed almost complete and operations the most imperative operations unthirljable. Pare in which would not have been contemplated in the days the sixteenth century complained that infection at the of Lister became everyday occurrences. Admittedly Hotel Dieu in Paris was so frightful that no operation 'clean' operations still sometimes became infected, could rightly be contemplated in that institution. but this occurred so much less frequently and with The graphic accounts of John Bell at the beginning so much less severity than formerly that little atten- of the nineteenth century paint a horrifying picture. tion was paid, and few, if any, surgeons kept a record of the incidence. 'There is no hospital,' he wrote (1801), 'however small, airy or well regulated, where this epidemic ulcer In the last 20 years antiseptics of a new type have is not to be found at times; and then no operation dare appeared on the scene, namely antibiotics. Unlike the be performed! every cure stands still! every wound old-fashioned antiseptics, which are general proto- becomes a sore, and ever sore is apt to run into plasmic poisons, antibiotics have a selective toxicity gangrene: but in great hospitals especially, it prevails for certain cells and are relatively harmless to others. at all times and is a real gangrene; it has been named This important property is, of course, the basis of http://jcp.bmj.com/ the Hospital Gangrene; and such were its ravages at their therapeutic activity, since they will kill bacteria the HMtel Dieu of Paris (that great storehouse of cor- in doses which do not affect the cells of the human ruption and disease) that the surgeons did not dare to body. But the corollary is that no antibiotic yet dis- call it by its true name.' covered attacks all species of pathogenic microbe John Bell saw no solution to the problem. and among sensitive species individual strains may develop new metabolic pathways which bypass the

'What then, is the surgeon to do?' he continues. 'Is drug's action. Nevertheless the arrival of penicillin in on October 2, 2021 by guest. Protected copyright. he to seek for washes or dressings to cure such a 1940 seemed at first to be the final answer to hospital disease as this? Is he to expend butts of wine, contend- cross infection, since it was the death warrant of the ing, as it were, against the elements? No! Let him bear two organisms at that time largely responsible, i.e., this always in mind, that no dressings ever have been Strep. pyogenes and Staph. pyogenes. found to stop this ulcer; that no quantities of wine or bark which a man can bear have ever retarded this gangrene; let him bear in mind that this is a hospital TWENTY YEARS AFTER disease; that without the circle of the infected walls the men are safe; let him, therefore, hurry them out of this house of death ... let him lay them in a schoolroom, a Unfortunately, early hopes with antibiotics have not church, on a dunghill or in a stable ... let him carry been fulfilled. The streptococcus has, indeed, lost them anywhere but to their graves.' much of its menace but not so the more adaptable staphylococcus. So far, as will be discussed below, FROM ANTISEPTICS TO ANTIBIOTICS strains of this organism have become resistant to all the antibiotics in common use and appear to flourish This hopeless attitude towards hospital sepsis in hospitals as never before. Furthermore, cross in- persisted for another 50 years, until Lister demon- fection with Gram-negative bacilli is becoming an strated its microbial origin and proved to the world increasing problem. There is in fact much evidence to that it was a preventable disease. His antiseptic tech- suggest that the situation has changed for the worse. 2 J Clin Pathol: first published as 10.1136/jcp.14.1.2 on 1 January 1961. Downloaded from

Hospital infection yesterday and today 3 INCIDENCE, SEVERITY, BACTERAEMIADUE TO GRAM-POSITIVE COCCI Like other AND BACTERIOLOGY OF investigators Finland et al. (1959) noted an increase in the incidence of staphylococcal septicaemia. Thus HOSPITAL INFECTION there were 70 cases in 1935, about twice this number TODAY in 1941, and over 200 in each of the years 1955 and 1957. The increasing incidence occurred throughout The exact position with regard to the incidence of the period, except for the early years of penicillin hospital cross infection is difficult to assess, because (1941-47) during which time there was a slight it is subject to wide fluctuations, not only in different decline. hospitals and wards, but even in a single ward in the The number of cases due to haemolytic strepto- absence of any obvious changes in technique. Never- cocci was approximately 50 in 1935 but fell sharply theless there seems little room for doubt that hospital between 1935 and 1941 and remained very low until infection with Staph. pyogenes and certain coliform 1957 when there was a slight rise. The pneumococcus bacilli, particularly Ps. pyocyanea, has increased in was the most frequent aetiological agent in 1935 incidence and severity in the last 15 to 20 years (see when it was responsible for about 100 cases. There- Hassall and Rountree, 1959; Finland, Jones, and after the incidence of pneumococcal bacteraemia Barnes, 1959). remained high and although there was a slight fall in There are many reasons why this should be so. To 1955 and 1957, in each of these years there were more begin with, in the first flush of antibiotic triumph, than 50 cases. Only minor fluctuations were noted in pathogenic bacteria appeared to be defeated and in relation to Strep. viridans. Finally, enterococci were many, perhaps most, hospitals aseptic technique was isolated from no cases in 1935, but from 23 to 36 relaxed and isolation wards were put to other pur- cases each year after 1947. poses. Secondly, patients in hospital today are peculiarly susceptible to infection. They tend to BACTERAEMIA DUE TO GRAM-NEGATIVE BACILLI The be older and many are kept alive for long periods incidence of bacteraemia due to various Gram- with conditions, such as leukaemia, which predispose negative bacilli showed even more striking changes. towards infection. Moreover, many of the new life- In 1935 the total number of such cases was less than prolonging procedures, such as major operations, 40, and about three-quarters of them were due to intravenous therapy, the prophylactic administration Bact. coli. In 1947 the total number was about 180, of antibiotics and treatment with corticosteroids and of which 70 were due to Bact. coli, 45 to Bact. antimitotic drugs, themselves help to create favour- had not been isolated from any

aerogenes (which http://jcp.bmj.com/ able conditions for bacteria. Thirdly, some of the cases in 1935), and 40 to Proteus. In all the subse- drug-resistant organisms, which at present flourish quent years of study these three species were each in our hospitals, appear to be of enhanced virulence. responsible for from 45 to 60 cases per year. Thus our hospitals are full of patients who are highly Bacteraemia due to Pseudomonas pyocyanea was rare susceptible to infection and of microbes which lose no in 1935, but the number rose steadily, reaching 20 time in taking advantage of the situation. cases in 1957. A general picture of the incidence of post- operative sepsis in British hospitals is given in a on October 2, 2021 by guest. Protected copyright. recent survey by the Public Health Laboratory DRUG-RESISTANT STAPHYLOCOCCI Service (1960). In a total of 21 hospitals the average IN HOSPITAL incidence was 9 7 %, and ranged from 4-7 to 21-8 % in different hospitals. Staph. pyogenes was the com- EMERGENCE OF RESISTANT STRAINS monest aetiological agent; it was isolated from 60% of the septic wounds and was the only pathogen in PENICILLIN AND TETRACYCLINES The story of the 45%. Coliform bacilli were isolated together with emergence of drug-resistant staphylococci in hos- staphylococci from 13% and alone from 17%. pitals over the past 20 years is well known. Phage- The severity of hospital infection today is indicated typing studies have shown that, whatever the ulti- by the high incidence of bacteraemia. The most ex- mate mode of origin of such strains, selection has tensive study is that of Finland et al. (1959) from the been the major factor in their increasing incidence in Boston City Hospital, Massachusetts. They recorded hospital (see Barber, Hayhoe, and Whitehead, 1949; a total increase in the incidence of all types of Rountree and Thomson, 1949). With the widespread bacteraemia since 1935 and an increase in mortality use first ofpenicillin in the 1940s and then ofthe tetra- since 1947. Analysis of the bacteria responsible cyclines in the 1950s the hospital staphylococci have showed a remarkable change during the period and in fact been passaged from patient to patient in the the results are summarized below. presence of these antibiotics one after the other. J Clin Pathol: first published as 10.1136/jcp.14.1.2 on 1 January 1961. Downloaded from

4 Mary Barber Staphylococci do not readily become resistant to ERYTHROMYCIN was introduced into hospitals after either penicillin or the tetracyclines and both cross we had become aware of the problem of drug- infection and the widespread use of these drugs have resistance and in most places has been kept in played a part in the emergence of strains of staphylo- reserve. This has had the desired effect and staphylococci resistant to them. Even with both factors cocci resistant to erythromycin are not very common. operating, penicillin-resistant staphylococci were un- But since staphylococci develop resistance to erythro- common until penicillin had been freely available in mycin more readily than to any other antibiotic hospitals for several years. By 1946, however, they except streptomycin (Hobson, 1954; Garrod and were becoming quite frequent (Barber, 1947) and a Waterworth, 1956), erythromycin-resistant strains are few years later in hospitals all over the world they by no means unknown, even in hospitals where the outnumbered penicillin-sensitive strains (see Barber drug has been used sparingly. Where it has been and Rozwadowska-Dowzenko, 1948; Rountree and widely used the spread of erythromycin-resistant Thomson, 1949; Nichols and Needham, 1949 and strains in the hospital has been rapid in the extreme many others). Today penicillin-resistant staphylo- (Lepper, Moulton, Dowling, Jackson, and Kofman, coccal infection is common even in hospital out- 1953). patients (MacFarlane, Murrell, Shooter, and Curwen, 1960). ERYTHROMYCIN-LIKE ANTIBIOTICS Several antibio- The story was more or less repeated with the tetra- tics closely similar to erythromycin are in use, of cyclines except that by the time the latter were intro- which the most important are spiramycin and duced, most hospital staphylococci were already oleandomycin. With all three there is considerable resistant to penicillin and it was these penicillin- cross-resistance. Between spiramycin and oleando- resistant strains which became resistant to the tetra- mycin this appears to be complete, but Garrod (1957) cyclines. Thus by 1952, in many hospitals at least, a has shown that cross-resistance between these two few strains of Staph. pyogenes resistant to penicillin and erythromycin may be dissociated. Thus while and the tetracyclines were responsible for most of strains habituated to erythromycin in vitro always the staphylococcal infections (Clarke, Dalgleish, and show cross-resistance to spiramycin and oleando- Gillespie, 1952; Rountree and Thomson, 1949; mycin this is not always the case with erythromycin- Lowbury, Topley, and Hood, 1952; Kirby and resistant strains isolated from patients. With another Ahern, 1953). related drug, E129, resistance is more slowly developed but once again there is some cross- and STREPTOMYCIN The story with streptomycin resistance with erythromycin. http://jcp.bmj.com/ chloramphenicol, both of which were introduced into hospitals between penicillin and the tetra- NOVOBIOCIN Staphylococci become resistant to cyclines, has been rather different, simply because novobiocin almost, but not quite, as readily as to for different reasons the use of both drugs has been erythromycin, and resistant strains have been re- limited. In the case of streptomycin, this was because corded both in vitro (Lin and Coriell, 1956; Garrod early studies proved that nearly all species of bacteria and Waterworth, 1956) and in vivo (Nichols and could become resistant to its action with unparalleled Finland, 1956). rapidity. It is not surprising, therefore, that in spite on October 2, 2021 by guest. Protected copyright. of restriction in its use, many hospital staphylococci MULTIPLE RESISTANCE Erythromycin and novo- are resistant to streptomycin as well as to penicillin biocin-resistant staphylococci encountered in hos- and the tetracyclines. pitals are usually also resistant to penicillin and tetracycline, since the former antibiotics are mainly CHLORAMPHENICOL has been kept in reserve, because used in the treatment of infections resistant to the of its potential danger to the bone marrow. Before two latter. this danger was appreciated chloramphenicol- resistant staphylococci were emerging in many CELBENIN (BRL 1241) This antibiotic is a 'penicillin' hospitals, particularly in the U.S.A., but when the which is resistant to staphylococcal penicillinase use of the antibiotic was no longer widespread the although it stimulates production of the enzyme. trend was reversed (see Kirby and Ahern, 1953) and Staphylococci resistant to benzyl penicillin (penicillin until very recently chloramphenicol-resistant staphy- G) are sensitive to it (Rolinson, Stevens, Batchelor, lococci were uncommon. In the last year or two, Wood, and Chain, 1960), and early reports indicate however, chloramphenicol has been used more ex- that staphylococci are not readily rendered resistant tensively on account of its antistaphylococcal pro- to it by passage in vitro (Rolinson et al., 1960; Knox, perties, and chloramphenicol-resistant strains are 1960). It is moreover argued on theoretical grounds beginning to appear. that since the only form of resistance to benzyl J Clin Pathol: first published as 10.1136/jcp.14.1.2 on 1 January 1961. Downloaded from

Hospital infection yesterday and today S penicillin shown by fully virulent staphylococci is pletely lost the capacity (Barber, 1949; Bondi, that associated with penicillinase production, Kornblum, and De Saint Phalle, 1953; Fairbrother, celbenin-resistant staphylococci will not become a Parker, and Eaton, 1954). This loss in enzyme pro- clinical problem. duction is sudden and complete and suggests Two lines, of objection can be raised to this argu- spontaneous mutation. It seems likely, therefore, ment. First staphylococci might produce a new or that the gain in enzyme production also occurs by adapted enzyme which inactivates celbenin. This spontaneous mutation, but since the change has not possibility is supported by the fact that celbenin is been inequivocally demonstrated in vivo or in vitro not wholly resistant to the penicillinase of B. cereus. the mutation must be a rare one. Secondly, celbenin is not equivalent to penicillinase- On the other hand, staphylococcal penicillinase is resistant benzyl penicillin, since penicillin-sensitive an adaptive enzyme, in the sense that the enzyme bacteria, including staphylococci, are 20 to 50 times production of penicillinase-producing strains is in- less sensitive to celbenin than to benzyl penicillin. creased by the presence of the substrate penicillin, Thus is it possible that the mode of action of celbenin although penicillin does not initiate penicillinase pro- differs in some way from that of benzyl penicillin and duction de novo by penicillin-sensitive staphylococci. that bacteria may develop different pathways of Thus the effect of penicillin on the emergence of resistance. penicillinase-producing organisms cannot be entirely Whatever the theoretical arguments, in preliminary overlooked. experiments I have trained two penicillinase-producing staphylococci to be resistant to from 50 to DRUG TOLERANCE With all other antibiotics, 100 ,tg./ml. celbenin; neither strain inactivates the resistant mutants are capable of growing in the antibiotic, but unlike staphylococci trained in vitro to presence of unchanged antibiotic. Such strains al- be tolerant to benzyl penicillin they have retained the most certainly arise by single or multi-step mutation typical cultural appearances of Staph. pyogenes and (see Luria and Delbruck, 1943; Demerec, 1945, full coagulase and alpha-toxin activity. Whether 1948; Lederberg and Lederberg, 1952). With strepto- celbenin-resistant strains will appear in vivo remains mycin, gross resistance is the result of a single muta- to be seen, but it is too early to assume that this tion, and the rate of mutation is very high (of the cannot happen. order of 1 in 109 or 1010 cell generations). With the other antibiotics in common use against the staphylo- OTHER ANTIBIOTICS Two relatively recent anti- coccus, gross resistance is the result of multi-step staphylococcal antibiotics, vancomycin and risto- mutation involving a number of genes. With erythro- http://jcp.bmj.com/ cetin, so far have a clean record with regard to mycin and novobiocin the resistant mutants are so resistance. This may be partly due to the fact that frequent that a gross change in sensitivity develops since both drugs have to be given intravenously and after only a few passages in the antibiotic in vitro and are toxic to the eighth nerve they have been used is often seen in a strain during the treatment of a sparingly, but, at least with vancomycin, laboratory single patient. With chloramphenicol and the tetra- studies have shown that resistance is not readily cycline antibiotics the mutation rates are much achieved (Garrod and Waterworth, 1956). Another lower. With and vancomycin ristocetin resistant on October 2, 2021 by guest. Protected copyright. new antibiotic, kanamycin, is closely related to mutants either do not occur or are very rare. streptomycin, and although staphylococci do not develop resistance quite so readily to kanamycin as VIRULENCE OF MULTIPLE RESISTANT STAPHYLOCOCCI to streptomycin there is some cross-resistance between the two antibiotics. Drug-resistant strains isolated in vitro often show an associated reduction in rate of growth and some- MODE OF ORIGIN AND FREQUENCY times virulence, so that they may be at a competitive OF DRUG-RESISTANT STAPHYLOCOCCI disadvantage with drug-sensitive cultures. But the drug-resistant staphylococci selected in hospitals are DRUG DESTRUCTION Penicillin-resistant staphylo- those which have survived in the tissues of infected cocci isolated from infective processes almost patients and which have been passaged in the invariably owe their resistance to the production of hospital community. They are thus likely to be of the enzyme penicillinase which inactivates all the enhanced virulence and with some strains at least penicillins available for therapy (benzyl penicillin, this appears to be the case. Certainly all strains phenoxymethyl penicillin, broxil) except celbenin. responsible for epidemics in hospitals today are drug- Penicillinase production is a relatively permanent resistant and in the large experience of Williams property, but many penicillinase-producing strains (1959) usually belong to only about six phage types. tend to yield a proportion of cells which have com- Thus all hospitals appear to have become breeding J Clin Pathol: first published as 10.1136/jcp.14.1.2 on 1 January 1961. Downloaded from

6 Mary Barber grounds for a few highly virulent strains of staphylo- More severe outbreaks of neonatal infection are, cocci, and in devising preventive measures it is however, sometimes due to multiple resistant staphy- important to concentrate on these strains. The recent lococci of phage group III (Beavan and Burry, 1956) observation of Moore (1960) that these strains tend or type 80 (Rountree and Freeman, 1955). to be mercury resistant, if confirmed, offers a quick method for their detection. SOURCES OF PATHOGENIC STAPHYLOCOCCI

STAPHYLOCOCCI IN SURGICAL WARDS PRIMARY SOURCE The most important source of pathogenic staphylococci in hospitals is staphylococ- Many studies of post-operative infection over the cal sepsis. Staphylococci in open lesions are more last five years have shown that the staphylococci readily disseminated than carrier strains, and, as in- responsible for nearly all cases of surgical cross- dicated by studies in surgical wards, tend to be of infection are strains resistant to penicillin and tetra- greater virulence. Nevertheless staff carriers repre- cycline and belonging to phage group III or type 80, sent an important source, particularly in maternity although such strains are relatively uncommon units. In most cases the main site of carriage is the among staff carriers (Alder, Gillespie, and Thomp- anterior nares, but in some cases Staph. pyogenes son, 1955; Barber and Burston, 1955; Shooter, may be persistently present on skin sites, particularly Smith, Griffiths, Brown, Williams, Rippon, and in the perineal region, in the absence of nasal Jevons, 1958; Williams, 1959). Often a few strains carriage (Hare and Ridley, 1958). appear to be responsible for nearly all the infections in a given hospital. Thus in a study by Shooter and SECONDARY SOURCES From infected patients and his colleagues (1958) of a surgical ward over a period carriers staphylococci are readily spread to the en- of eight months 186 different types of Staph. aureus vironment. Patients with staphylococcal lesions in- were isolated but only 13 caused disease and only three variably contaminate their bedding and during bed were responsible for sepsis in more than one patient. making the staphylococci are widely disseminated In a recent investigation of the surgical wards at throughout the ward. Equally members of the staff Hammersmith Hospital (Barber, et al., 1960) lasting who have lesions or are carriers contaminate their more than two and a half years and involving over clothing, their handkerchiefs, and their hands. More- 5,000 patients, evidence was accumulated to indicate over nurses' and doctors' hands or uniform may that some of the multiple resistant strains of Staph. become contaminated from contact with an infected pyogenes in the hospital had enhanced virulence, patient or his bedding. both in their capacity to initiate infection and in the From any or all ofthese sources staphylococci may http://jcp.bmj.com/ severity of the infection produced. Thus the ratio of get into the air and dust of wards and operating infections caused by staphylococci sensitive to all theatres. As might be expected staphylococci are far antibiotics or resistant to penicillin only was 1-4 more prevalent in the atmosphere of wards than that whereas with strains resistant to penicillin and tetra- of operating theatres and wounds are far more often cycline it was 2-0 and with strains resistant to penicil- infected in wards than in the operating theatre. On lin, tetracycline, and erythromycin it was 3 0. More- the other hand the important studies of Gillespie and over all but five of 49 generalized infections seen and his colleagues at Bristol have shown that theatre in- on October 2, 2021 by guest. Protected copyright. all but one of the 24 fatal cases were due to multiple fection when it does occur is liable to be more severe resistant strains, although such strains were only (Gillespie, Alder, Ayliffe, Bradbeer, and Wypkema, responsible for 50 % ofthe total number of infections. 1959).

STAPHYLOCOCCI IN MATERNITY WARDS GRAM-NEGATIVE BACILLI IN HOSPITAL Staphylococcal infection in babies in maternity wards differs from that in surgical wards in that the INCREASING INCIDENCE OF infecting strains are usually penicillin-resistant GRAM-NEGATIVE INFECTIONS staphylococci of phage group I. Such strains also predominate among nurse nasal carriers (Alder et al., Long before the age of antibiotics it was known that 1955; Barber and Burston, 1955). In maternity units wounds in hospital might become contaminated with they are responsible for infection of the anterior nares Gram-negative bacilli. Meleney (1948) in a Treatise and skin of healthy babies as well as for most cases on Surgical Infections analysed the incidence of of mild neonatal sepsis (Barber, Wilson, Rippon, various bacteria in clean operation wounds during and Williams, 1953; Barber and Burston, 1955; a period ofeight years largely before the introduction Anderson and Williams, 1956). of antibiotics. Staph. aureus was the commonest in- J Clin Pathol: first published as 10.1136/jcp.14.1.2 on 1 January 1961. Downloaded from

Hospital infection yesterday and today 7 vader and was found in 36 % of the infected wounds. incidence of Proteus and Pseudomonas infections. Gram-negative bacilli were isolated from 10%, and Thus a comparison of the Gram-negative bacilli consisted of 'Coli' group 6%, Proteus 3 %, Pseudo- isolated from specimens received in the bacterio- monas 1 %. logical laboratory of a large general hospital in the In 1944, Miles drew attention to the possible U.S.A. in June, 1948, and January, 1951, showed increase in importance of coliform infections now that the proportion of Bact. coli fell from 50 to 20%, that efficient weapons (sulphonamides and penicillin) whereas that of Proteus rose from 8 to 32 and had been found for fighting pyogenic cocci. Three Pseudomonas from 15 to 30. The same investigation years later Florey, Ross, and Turton (1947) pub- recorded 28 infections, including four bacteraemias lished an important study of the incidence and sig- due to Pseudomonas, and 19, with two bacteraemias, nificance of Gram-negative bacilli in wounds of air- due to Proteus, occurring in patients under anti- borne casualties admitted to the Radcliffe Penicillin biotic therapy. Finland et al. (1959) noted a similar Unit. All the patients had received prophylactic in- increase in the incidence ofProteus and Ps. pyocyanea jections of penicillin for up to three weeks after in patients with bacteraemia and meningitis. wounding, so that pyogenic cocci were relatively uncommon. A total of 1,164 swabs were taken at intervals from 63 deep and 10 superficial wounds. INCREASING INCIDENCE OF The percentage of the swabs yielding various bacteria PS. PYOCYANEA IN HOSPITALS was as follows: Superficial Among the Gram-negative bacilli, Ps. pyocyanea is Deep Wounds Wounds the most serious menace and is beginning to rival Bact. coli 35.4 11-5 Staph. pyogenes as the hospital scourge. Not only is Proteus 36-1 17-2 it being found with increasing frequency in all kinds Ps. pyocyanea 39-2 17-2 Staph. aureus 14-9 44-8 of infections in hospital, but the infections tend to Strep. haemolyticus 4-3 0-6 be severe and, since there is no reallyeffectivechemo- Clostridia 11-3 0*0 Indifferent cocci 12-4 21-9 therapy, have a high mortality, reaching almost Sterile 11-7 17-8 100% in cases of established septicaemia. The frequency with which burns become infected The presence of coliform organisms appeared to be with Ps. pyocyanea is well known (Colebrook, the result of cross infection in the unit. Bact. coli was Duncan, and Ross, 1948; Jackson, Lowbury, and the earliest invader and was present in 50% of all Topley, 1951; Markley, Gurmendi, and Chavez, wounds examined in their first week. Proteus ap- 1957). Apart from the resultant delay in healing and http://jcp.bmj.com/ peared most often in the second week and Ps. the failure of skin grafts, in extensive burns, Ps. pyocyanea in the third. By the end of six weeks, in pyocyanea is liable to invade the blood stream and is spite of a no-touch dressing technique, all but one of a common cause of death (Liedberg, Reiss, and Artz, the 38 still unhealed wounds had been infected with 1954; Markley et al., 1957). Bact. coli and all but six with Ps. pyocyanea. The incidence of Ps. pyocyanea in operation Of a number of agents used for local treatment wounds has not often been recorded. but many

streptomycin was the most effective against all three bacteriologists have the impression that it is on the on October 2, 2021 by guest. Protected copyright. species, although Eusol and Milton were almost as increase. Figure I shows the number of patients in a effective as streptomycin against Ps. pyocyanea. An large London hospital from whom Ps. pyocyanea interesting observation was the effect of contamina- was isolated from specimens of sputum or pus tion with Staph. aureus. In many instances there was (mainly infected wounds) between 1958 and 1960. a steady disappearance of Gram-negative bacilli after The analysis was undertaken because a very large the appearance of staphylococci in the wound. If not increase in the number of specimens yielding Ps. removed, the main effects of coliform organisms in pyocyanea was noted in the first quarter of 1958. The the wound were lysis of surrounding clot, persistence biggest change was the number of patients in the of discharge, and consequent delay in bony and soft medical wards with Ps. pyocyanea in the sputum. tissue repair. Thus in the first quarter of 1958 there were two such patients, whereas in the first quarter of 1959 there CHANGING PATTERN OF GRAM-NEGATIVE INFECTIONS were 39. During the same period the incidence of wounds infected with Ps. pyocya'zea in the surgical Since the arrival of the broad-spectrum antibiotics wards rose from two to 21. In the summer, as might there has been a qualitative change in the type of be expected, the number of patients with Ps. pyo- Gram-negative bacilli responsible for infections. Yow cyanea in the sputum fell; in the following winter as early as 1952 noted a relative increase in the the number again increased, but probably because J Clin Pathol: first published as 10.1136/jcp.14.1.2 on 1 January 1961. Downloaded from

8 Mary Barber

SPUTA

40 .PUS. - - from wounds etc.

< 30

X 20

JAN. JAN. APRI L J U LY OCT. JAN. APRIL MAR. MAR. JUNE SEPT. DEC. MAR. JUNE 1958. 1959 1960

FIG. 1. Infections due to Ps. pyocyanea in a large general hospital. the weather was much less severe, only to half the to the staphylococcus as the aetiological agent. number of the previous winter. Wound infections in Williams, Williams, and Hyams (1960) recorded

the surgical wards have remained between 20 and three septicaemias, one chest infection, and one in- http://jcp.bmj.com/ 30 since the sharp rise in the first quarter of 1959. testinal infection due to Ps. pyocyanea, all occurring Many of the medical patients with pseudomonas in a single general medical ward between May and chest infections were patients with chronic bronchitis, September, 1958. All five patients died and infection who had had various forms of chemotherapy and with Ps. pyocyanea in all cases materially contributed were admitted to the wards already infected with Ps. to their death. Of the three patients with septicaemia, pyocyanea. Since isolation facilities were not avail- two had leukaemia and the third marrow aplasia. All able they were admitted to open wards and it seems five patients had previously been treated with broad- on October 2, 2021 by guest. Protected copyright. possible that they acted as a reservoir of infection in spectrum antibiotics and all had received corti- the hospital. costeroids.

PSEUDOMONAS SEPTICAEMIA IN MEDICAL WARDS PRIMARY AND SECONDARY In recent years pseudomonas septicaemia has been SOURCES OF PS. PYOCYANEA IN HOSPITAL becoming an increasing problem in medical wards, particularly in units devoted to patients under PRIMARY SOURCE The most important primary modern forms of treatment for leukaemia. Forkner, source of Ps. pyocyanea, as of Staph. pyogenes, is Frei, Edgcomb, and Utz (1958) recorded 23 patients infected patients. Unlike the staphylococcus, Ps. with pseudomonas septicaemia between 1954 and pyocyanea is rarely carried in the nose or on the skin 1957, of whom 22 died. Sixteen of the patients had of healthy individuals, but Lowbury and Fox (1954) leukaemia, and of 13 who were studied more care- isolated Ps. pyocyanea from the stools of two out of fully, 10 had had previous treatment with antibiotics, 64 medical students. eight with steroids, and nine with antimetabolite drugs. The same authors analysed the bacteria SECONDARY SOURCES Lowbury and Fox (1954) responsible for 63 septicaemias in the leukaemia ser- made an extensive study of the distribution of Ps. vice and found that Ps. pyocyanea was second only pyocyanea in the environment of a burns unit. They J Clin Pathol: first published as 10.1136/jcp.14.1.2 on 1 January 1961. Downloaded from

Hospital infection yesterday and today 9 isolated the organism from the nose and skin of a mind that at present it is being wasted. In a recent small proportion of the staff and patients of burns survey by the Public Health Laboratory Service wards, but not from the staff of other wards. (1960) it was estimated that the cost ofpost-operatiN e Of the inanimate sources, dust seems to be the sepsis to the National Health Service is some £5 mil- most important; 94% of samples from the burns lion per annum, quite apart from the value of any wards and 16 % from other surgical wards contained lives lost. To return to the words of John Bell Ps. pyocyanea. The percentage of air samples yield- (1801): ing the organism was 86% during the dressing of an 'No expense should be spared ... you would infected wound in the burns dressing station, 27 % in willingly expend your own future in such a cause-then the burns ward during bed making, and 25 % when do not grudge to employ the revenue of the state for it the ward was at rest. Ps. pyocyanea was also fre- is employing it and not abusing it! ... if in the course quently isolated from the outside of bandages and of a few weeks sixty men die of the disease in your the bedclothes of infected patients, and less fre- hospital, government has lost a sum which would trebly quently from objects brought to the patients, such buy your hospital itself.' as bedpans, wash basins, food trays, and toys. In a recently described outbreak, involving eight Cross-infection in hospital has remained a problem patients in an orthopaedic ward, infection was traced yesterday and today. If enough people take it to contaminated cellulose wadding used for padding seriously there is no reason why it should continue plaster casts applied to fractures (Sussman and tomorrow. Stevens, 1960). REFERENCES

PREVENTION Alder, V. G., Gillespie,W. A., and Thompson, M. E. M. (1955). J. Path. Bact., 70, 503. Anderson, E. S., and Williams, R. E. 0. (1956). J. clin. Path., 9, 94. As pointed out by Lister, hospital infection is a Barber, M. (1947). J. Path. Bact., 59, 373. preventable disease. That it has not yet been pre- . (1949). J. gen. Microbiol., 3, 274. in the _- and Burston, J. (1955). Lancet, 2, 578. vented is largely a reflection on the fact that , Dutton, A. A. C., Beard, M. A., Elwes, P. C., and Williams, past we have underestimated the enemy. If we are to R. (1960). Brit. med. J., 1, 11. succeed we must attack the problem on many fronts. , Hayhoe, J. E. M., and Whitehead, J. E. M. (1949). Ibid., 2, 1120. -, and Rozwadowska-Dowzenko, M. (1948), Ibid., 2, 641. Different modes of attack and their effects are Wilson, D. B. R., Rippon, J. E., and Williams, R. E. 0. (1953). described in detail in the subsequent articles of this J. Obstet. Gynaec. Brit. Emp., 60, 476. Beavan, D. W., and Burry, A. F. (1956). Ibid., 2, 21 1. series. Here it is only possible to outline the Bell, John. (1801). The Principles ofSurgery, Vol. 1, Ch. 3. Edinburgh. http://jcp.bmj.com/ strategy. Bondi, A., Kornblum, J., and De Saint Phalle, M. (1953). Proc. Soc. The first line of attack must be on the primary exp. Biol. (N. Y.), 83, 527. Clarke, S. K. R., Dalgleish, P. G., and Gillespie, W. A. (1952). Lancet, human reservoirs of infection. Infected patients must 1, 1132. be excluded from open general wards and the infec- Colebrook, L., Duncan, J. M., and Ross, W. P. D. (1948). Ibid., 1, 893. Demerec, M. (1945). Proc. nat. Acad. Sci. (Wash.), 31, 16. tion controlled, where possible, by means of intel- -. (1948). J. Bact., 56, 63. ligent chemotherapy. With staphylococci, nasal and Fairbrother, R. W., Parker, L., and Eaton, B. R. (1954). J. gen. have to what Microbiol., 10, 309. skin carriers also got be considered. To Finland, M., Jones, W. F., and Barnes, M. W. (1959). J. Amer. med. on October 2, 2021 by guest. Protected copyright. extent this would remain necessary once the cycle of Ass., 170, 2188. cross infection had been broken by the strict isolation Florey, M. E., Ross, R. W. N. L., and Turton, E. C. (1947). Lancet, 1, 855. of infected patients remains to be determined. But at Forkner, C. E., Jr., Frei, E., Edgcomb, J. H., and Utz, J. P. (1958). present there is no doubt that carriers, at any rate Amer. J. Med., 25, 877. of multiple resistant staphylococci, can be a source Garrod, L. P. (1957). Brit. med. J., 2, 57. , and Waterworth, P. M. (1956). Ibid., 2, 61. of danger. Gillespie, W. A., Alder, V. G., Ayliffe, G. A. J., Bradbeer, J. W., and Staph. pyogenes, Ps. pyocyanea, and other drug- Wypkema, W. (1959). Lancet, 2, 781. Hare, R., and Ridley, M. (1958). Brit. med. J., 1, 69. resistant coliform bacilli in the hospital environment Hassall, J. E., and Rountree, P. M. (1959). Lancet, 1, 213. must also be dealt with. This entails rigorous aseptic Hobson, D. (1954). Brit. med. J., 1, 236. Jackson, D. M., Lowbury, E. J. L., and Topley, E. (1951). Lancet, technique in wards as well as in theatres, clean air, 2, 137. clean bedding, and hygienic methods ofdust removal. Kirby, W. M. M., and Ahern, J. J. (1953). Antibiot. and Chemother., 3, 831. Last, but not least, some control of the use of Knox, R. (1960). Brit. med. J., 2, 690. antibiotics in hospitals is essential both to prevent Lederberg, J., and Lederberg, E. M. (1952). J. Bact., 63, 399. the emergence of drug-resistant bacteria and also to Leppcr, M. H., Moulton, B., Dowling, H. F., Jackson, G. G., and Kofman, S. (1953). Antibiot. Ann., 19534, p. 308. avoid rendering patients more susceptible to infection Liedberg, N. C. F., Reiss, E., and Artz, C. P. (1954). Surg. Gynec. by such bacteria, through elimination of the normal Obstet., 99, 151. Lin, F. K., and Coriell, L. L. (1956). Artis. Med., 2, 268 flora. Lowbury, E. J. L., and Fox, J. (1954). J. Hyg. (Camb.), 52, 403. Money will have to be spent, but let us bear in -, Topley, E., and Hood, A. M. (1952). Lancet, 1, 1036. J Clin Pathol: first published as 10.1136/jcp.14.1.2 on 1 January 1961. Downloaded from

10 Mary Barber

Luria, S. E., and Delbruck, M. (1943). Genetics, 28, 491. Rolinson, G. N., Stevens, S., Batchelor, F. R., Wood, J. C., and MacFarlane, D. A., Murrell, J. S., Shooter, R. &., and Curwen, M. P. Chain, E. B. (1960). Lancet, 2, 564. (1960). Brit. Med. J., 2, 900. Rountree, P. M., and Freeman, B. M. (1955). Med. J. Aus., 2, 157. Markley, K., Gurmendi, G., and Chavez, P. M. (1957). Ann. Surg., and Thomson, E. F. (1949). Lancet, 2, 501. 145, 175. Shooter, R. A., Smith, M. A., Griffiths, J. D., Brown, M. E. A., Meleney, F. L. (1948). Treatise on Surgical Infections, pp. 134-135. Williams, R. E. O., Rippon, J. E., and Jevons, M. P. (1958). Oxford Univ. Press, New York. Brit. med. J., 1, 607. Miles, A. A. (1944). Lancet, 1, 809. Sussman, M., and Stevens, J. (1960). Lancet, 2, 734. Moore, B. (1960). Ibid., 2, 453. Williams, R. E. 0. (1959). Ibid., 1, 190. Nichols, D. R.,and Needham, G. M. (1949). Proc. Mayo Clin., 24, 309 Williams, R., Williams, E. D., and Hyams, D. E. (1960). Ibid., 1, Nichols, R. L., and Finland, M. (1956). Antibiot. Med., 2, 241. 376. Public Health Laboratory Service. (1960). Ibid., 2, 659. Yow, E. M. (1952). J. Amiter. nmed. Ass., 149, 1184. http://jcp.bmj.com/ on October 2, 2021 by guest. Protected copyright.