THE PRESENT STAPHYLOCOCCAL PROBLEM

B y Vernon Knight Department rf Medicine, School of Medicine, Vanderbilt Uniuersity, Nashville, Tenn.

The problem of staphylococcal infection today is one that is limited princi- pally to hospitals. I t refers to infections there with StaphyZococci resistant at least to penicillin, streptomycin, and the tetracyclines, and to their lysis by phages 80/81 or by those of phage group 111.

It seems to be agreed that the drug resistance of these Staphylococci has arisen through repeated exposure to antimicrobial drugs in the hospital in the course of therapy of patients who were staphylococcal carriers. The strains are disseminated by the carriers either directly or through intermediary agencies to the patients who become infected. There is nearly as much agreement that the high incidence of lysis of these strains by phages 80/81 or those of phage group I11 is also a drug effect.

It is a currently popular and rather ominous concept that staphylococcal infections are more frequent in hospitals now than they were a few years ago, and that this increase is due, a t least in part, to an increased capacity of these drug-selected strains to cause infection; that is, they have increased virulence.

A more conservative view holds that any increased occurrence of staphylococ- cal infection can be accounted for by the effect of the multiple factors that influence the care of patients in present-day hospitals, with the further impli- cation that these drug-resistant strains have not increased their virulence as a result of drug exposure. If the first point of view is correct, then urgent meas- ures are need to alleviate the situation by an attempt to control the spread of these dangerous organisms and to interrupt the processes by which they are produced. If the second concept is correct, although a problem of control re- mains, the situation is less threatening.

The suggestion of increased virulence has generally been applied to drug- resistant 80/81 phage types rather than to those of phage group 111. This has occurred because of the increasingly frequent appearance of this strainas a cause of acute outbreaks of staphylococcal infections in many hospitals in the United States and in Canada. I n contrast, strains of phage group I11 have more often been the cause of continuing endemic infections in hospitals. Phage type 80/81 has been the most common recent cause of infections in the newborn and in nursing mothers, but it has also caused other kinds of staphylococcal infection.'

The fact that this organism can cause serious outbreaks of infection would not, without further substantiation, constitute sufficient evidence of greater than usual virulence of strains of this phage type, for outbreaks of staphylococ- cal infection have occurred on many occasions predominantly caused by strains of one or another phage type. However, the continued occurrence of phage type 80/81 outbreaks has lent considerable support to this view. More recent support for the concept of increased virulence of strains of this phage type has been found in observations of an outbreak of staphylococcal infection in an institution for feeble-minded children ( I. Bennett, personal communication).

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From this point there is increasing diversity of opinion.

Knight: The Staphylococcal Problem 2 75 There, a large majority of cases were caused by a drug-resistant strain of 80/81 phage type, while only a small per cent of a collection of cultures from carriers in that environment were of this type. This suggested that the 80/81 strain possessed greater virulence than others in the environment. This type of analysis of outbreaks may be one of the few methods available that will permit estimates of the virulence of Staphylococci, for present tests of virulence are very unsatisfactory.

This evidence must be employed with caution, however, for we have ob- served how tetracycline can cause patients to acquire drug-resistant strains from the hospital environment, while untreated patients at their side continue to carry drug-susceptible strains for long periods? Thus the casual use of tetracyclines, as in the treatment of upper respiratory infections, could lead to implantation of a drug-resistant strain such as a phage type 80/81, which might later cause infection. This would imply that these phage types, which are sometimes sparsely distributed in the environment, were either the most available of the drug-resistant strains, or that they had the greatest avidity for drug-treated carriers.

While we are attracted to the possibility that strains of phage type 80/81 are more virulent, we have not yet adopted this point of view. We have no clear explanation as to why this strain has either had multifocal origin, or has spread over the country from a single source to cause outbreaks of infection in nurseries and other hospital areas, except that we believe such a thing could occur independently of the effect of antibiotics.

An increased occurrence of the endemic type of staphylococcal infections in hospital wards can be more readily explained, for it is possible to describe several factors that favor the development in hospitals of infections today, which were not present, or were less influential, in the period before antibiotics were so heavily used. It is further apparent that these factors will need to be considered in attempting to control the frequency of these infections, whatever the relationship between virulence and antimicrobial therapy.

These factors are well known and will only be listed here. (1) Loss of the antistaphylococcal effect of penicillin, the tetracyclines, and

streptomycin because of the development of drug resistance. Thus, many staphylococcal infections, which would have been prevented or cured promptly, now occur.

(2) Increased opportunity for drug-resistant Staphylococci to cause infections in patients who would formerly have had infections with Pnezmococci, group A Streptococci, and other drug.susceptible bacteria.

(3) The increasing age of hospital patients today, with a consequent greater amount of degenerative diseases and more opportunities for infections to develop.

(4) Interference with host resistance to infection by use of rigorous medical and surgical procedures, such as more extensive surgery, greater use of cutdowns, indwelling catheters, radiation, steroids, and treatment with antineoplastic agents.

( 5 ) Longer survival of patients with terminal illness due to better control of fluid and electrolyte imbalances, nutrition, and other metabolic alterations

They are:

276 Annals New York Academy of Sciences common in serious illness, thus preserving the patients in a state highly sus- ceptible to infection.

I t is our view then, that the problem of control of staphylococcal infection is twofold: firit, there is the necessity for reducing or preventing the spread of any microorganism in hospital populations that have disease-producing potential; second, there is a need to develop a means of diminishing the drug resistance of Staphylococci.

The changes in hospital patient populations and the exceeding hazard of infection attendant upon the complex methods employed in their treatment have created a demand for procedures for preventing the spread in hospitals of infections that we believe are not possible, even under the most exacting application of present methodology. We do feel, however, that improved results will follow a more energetic enforcement of the available regulations. Thus, we feel that medical progress has carried us to a point where new develop- ments in control of spread of infection are necessary to permit other kinds of advance in medical care. The present problem with staphylococcal infection has served to jolt us out of a feeling of complacency that resulted from false confidence in the protective effect of antibiotics, and we are in hearty agree- ment with the vigorous efforts that have recently been undertaken to devise and improve procedures for control of spread of infections in hospitals.

The presence of reservoirs of drug-resistant Slaphylococci is obviously dis- advantageous by any concept of their role, but especially if we hold that in- creased virulence has rewlted from the action of antibiotics. An attempt to reduce these reservoirs is thus a worthy objective, and its accomplishment will surely depend upon some method of control of the use of antimicrobial drugs in hospitals and, conceivably, in whole communities. No suitable programs are available for such a project now, but there is a t least a theoretical promise of its accomplishment. Investigation in this field will be required. Furthermore, implementation of almost any program will involve a measure of control over the decisions of physicians who prescribe antimicrobial treatment-a very weighty problem indeed. I t is to be hoped that some strategy will be devised that will satisfy all requirements.

One point that seems quite definite is that increasing numbers of new, differ- ent, and potent antibiotics would simplify the design of such a program. It is, therefore, very appropriate for us to contemplate the staphylococcal problem as we learn more of the properties of the new agent, kanamycin, which has already shown great promise in the treatment of these infections.]

References 1 BLAIR, J. E. & M. CARR. 1958. Staphylococci in hospital-acquired infections. J. Am

2. KNIGIIT, V. & A. C. WHITE. 1956. Drug-resistant staphylococci. I. Their distribution Med. Assoc. 166: 1192.

in hospital patients. Southern Med. J. 49: 1176.