Clinical aspects of staphylococcus and staphylophage

JEN-YAH HSIE, Ph.D., Des Moines, Iowa After strict aseptic technic was universally ob- served, postoperative mortality was cut to less than 1 per cent. However, since preoperative and post- The etiologic relationship of abscesses and Staphy- operative prophylactic antibiotic therapy became lococcus aureus was not ascertained until 1880, by widely used, resulting in the laxity of strict asepsis, Pasteur.' In 1871, "micrococci" were found in the the wound rate has been increasing in kidneys of a pyemic patient by von Recklinghausen2 many hospitals. For instance, Howe (1954) 8 re- in miliary cardiac and renal abscesses, and also in ported that in Massachusetts Memorial Hospitals peritoneal pus in puerperal sepsis by Waldeyer. the wound sepsis rate was 1 per cent in 1949. Over Likewise, in 1872 Birch-Hirschfeld3 found cocci in a period of 5 years the rate gradually increased the abscesses and blood of a pyemic patient. Klebs to 4 per cent in 1953, with a peak of 10 per cent ( 1872 ) 4 suggested that infected thrombi were re- in early 1954. Similar high incidence, requiring sponsible for the metastatic abscesses in pyemia. closure of the hospital, has been reported by Hueter (1872 ) 5 also regarded the cocci found in others.° pus as the most important irritant causing inflam- The present status of staphylococcal disease in mation. In 1880, Pasteur isolated staphylococci from hospitals may be assessed according to the recent furuncles and reproduced abscesses in rabbits from surveys on (1) the incidence of staphylococcal dis- which staphylococci could be recovered. He also ease, ( 2) staphylococcal found at autop- found staphylococci in osteomyelitic pus and cul- sy, and (3) the carrier rate of -positive tivated them in broth. staphylococci among hospital patients and person- In 1881, Ogston6 reported that pus-containing nel. cocci, when injected into animals, set up septicemia from local suppuration. Following this, many pio- neers inoculated themselves with virulent staphy- Present status of lococci and developed abscesses from which staphy- staphylococcal disease in hospitals lococci were isolated. Thus, the etiologic role of Staphylococcus aureus in human disease was es- Incidence • The incidence of staphylococcal dis- tablished according to the procedure of Koch's ease in hospitals, spot-surveyed by Finland and postulate. Jones (1956) 1° in Boston, and by Godfrey and Before listerian carbolic-spray technic was wide- Smith (1958) 11 in Iowa City, and shown in Table I, ly accepted, surgical wound infections with pyo- varies from around 11 per cent to 15 per cent. It genic bacteria were generally directly proportional was found that more than half of these staphylo- to the size of the hospital. For example, in Parisian coccal infections were acquired after admission to hospitals with over 600 beds, the postoperative the hospital. The most frequently encountered mortality rate was 60 per cent. At that time in staphylococcal infections are infected wounds and English hospitals with 300 to 600 beds, it was 41 burns, decubitus ulcers, and abscesses, as shown in per cent; with 100 to 200 beds, 23 per cent; with 25 Table II. Next in order of frequency are osteo- to 100 beds, 14 per cent; and in isolated houses in myelitis, bacteremia and septicemia, sinusitis and the village, 10 per cent.7 cellulitis, urinary tract infections, endocarditis, and Presented before the Midwestern Study Conference of the American suppurative otitis. A similar frequency distribution College of Osteopathic Internists, Kansas City, March 24, 1961. Dr. Ilsie is chairman of the Department of and pattern of staphylococcal infections was observed Immunology at the College of Osteopathic and . by Godfrey and Smith" and many other clinicians °Address, 720-722 Sixth Ave. and investigators in other parts of the country.

102 TABLE I—INCIDENCE OF STAPHYLOCOCCAL DISEASE IN HOSPITALS staphylococcal infection rate may be as high as about 30 per cent of the autopsied cases, but the No. cases of Percentage direct cause of death due to staphylococci is ap- No. patients Staphylococcal of persons surveyed disease infected Investigators proximately 4 per cent, and the indirect cause of death attributable to staphylococci is approximately 1,172 15.5 Finland 181 ( 68 found 13 per cent. at time of and Jones admission) ( 1956 )" Carrier rates • The crucial problem of staphylo- 634 70 11.1 Godfrey (first survey) and Smith coccal disease in hospitals today lies in the emer- (1958)" gence of antibiotic-resistant strains of certain phage 206 29 14.1 Godfrey types carried by hospital personnel and patients. (second survey) and Smith This is demonstrated by the data of Barber and (1958)" Burston (1955) 12 as shown in Table IV, and the data of many other investigators. It has been re-

TABLE II—FREQUENCY OF THE VARIOUS CLINICAL peatedly demonstrated", 13-19 (Table V) that about STAPHYLOCOCCAL DISEASES IN HOSPITALS° one third to one half of hospital personnel harbor Disease No. cases coagulase-positive staphylococci on the nasal mu- cosa when studied at a single point in time. It is Infected burns, wounds, and ulcers 75 Furuncles, carbuncles, and abscesses 70 well known that during an endemic period in hos- Pneumonia and/or empyema, and other respiratory pitals, most of the carriers harbored antibiotic- tract infections resistant strains susceptible to phage groups I and 13 Osteomyelitis 6 III; and lately, more strains have been found sus- Bacteremia 4 ceptible to phage types 80 and/or 81.20 Sinusitis and cellulitis 3 Urinary tract infections 3 Endocarditis 2 Chronic suppurative otitis 2 TABLE IV—COMPARISON OF STAPHYLOCOCCUS Postoperative meningitis 1 AUREUS STRAINS OBTAINED FROM HOSPITAL AND FROM COMMUNITY° Postoperative subphrenic abscess 1 1 No. positive for Phage Data of Finland and Jones (1956) 1" )" regrouped and rearranged by the present author. Personnel and Staphylococcus No. of penicillin- type patients aureus resistant strains 52A Maternity Staphylococcal infections found at autopsy • nurses ( 31 ) 17 14 8 Mothers on The magnitude of the current status of staphy- admission ( 62 ) 17 3 1 lococcal disease in hospitals is further revealed by Mothers on the autopsy studies as shown in Table III. Godfrey discharge ( 62) 30 15 12 Babies on discharge (62) 57 55 28 °Data of Barber and Burston (1955 )" TABLE III—STAPHYLOCOCCAL INFECTIONS FOUND IN AUTOPSIED CASES

Per cent of No. of cases of positive There are two schools of thought concerning the carrier state of coagulase-positive staphylococci in No. of Staphylococcus staphylococcal autopsies found cultures Investigators hospital personnel and the community population 914 266 29.1 Finland at large. One school of thought is represented by and Jones Miles, Williams, and Clayton-Cooper 13 (also see ( 1956 )' McDermott21 and Knight, White, and Hemmerly19) 534 89 16.6 Godfrey who maintain that "the nasal carrier state varies, ( Direct cause and Smith of death, 20; (1958)" not with the environment of the person, but with contributory the person himself. There is a marked tendency cause of for persons to be persistent carriers or persistently death, 69) free from nasal Staph. aureus." The second school of thought adheres to the common concept that environments are the all-important factor determin- and Smith" reported that among the 159 cases ing the carrier state of the individuals of a popula- positive for Staphylococcus aureus among 534 au- tion. topsied patients, 20 were diagnosed by the patholo- The truth probably lies in the appreciation of gists as having died from staphylococcal disease, the interaction of the host-microbe relationship. and 69 more had suffered severe staphylococcal The outcome of the carrier state is probably a disease which the pathologists considered had con- function of three factors: the physiologic state of tributed to death. The remaining 70 cases positive the host in terms of resistance, the virulence of the for Staphylococcus aureus appeared to the patholo- staphylococci controlled by their genomes, and the gists not to be related to death. Generally, the environment in terms of chance contacts or exposure

JOURNAL A.O.A., VOL. 61, OCT. 1961 103 TABLE V—INCIDENCE OF COAGULASE-POSITIVE age. In either case, the chance contacts or the STAPHYLOCOCCI IN NOSE CULTURES exposure dosage is a codeterminant, at least when Per cent the prevailing staphylococcal flora is virulent. Groups of persons of When one's environment is kept relatively con- studied (and positive number of cultures) cultures Investigators stant or varied only within certain limits, such as in a relatively stable environment of prevailing Outpatients (479) 47.6 Miles, 'Williams, mild staphylococcal flora, then the carrier state of Ward patients on and Clayton-Cooper admission (536) 49.4 ( 1944 )" an individual may indeed be mainly or solely de- Ward patients with termined by the physiologic state of the host's con- weekly cultures (1,456) 54.5 stitution, resulting in his being either a persistent Nursing staff (612) 64.1 carrier or free from nasal Staphylococcus aureus,

Blood donors ( 200) 45.0 Rountree and Thomson as suggested by Miles, Williams, and Clayton- Cooper" and McDermott.21 Unfortunately, such Hospital nurses and ( 1949)" doctors (200) 52.5 an "equilibrium" condition usually prevails only in the community at large. In hospitals, under great Second-year medical Denton, Kalz, and Foley fluctuation of patients infected with virulent.staphy- students ( 50) 20.0 ( 1950 )" Science students, nurses, lococci, and coupled with debilitated patients, sus- and interns not at ceptible newborns, and open surgical wounds, the maternity center (484) 28.7 environmental factors are quite different from those Fourth-year medical of the community at large. students (50) 46.0 Lacking precise knowledge of staphylococcal Infants, mothers, and pathogenicity and the defensive mechanism of the staff at maternity center (375) 64.0 host, the so-called epidemic strain of staphylococci usually can be defined only after an outbreak has Student nurses entering Rountree and Barbour occurred and the staphylococcal culture has been training (127) 53.5 (1951)'" identified by phage typing and antibiotic tests. At Student nurses before entering ward (116) 52.6 this juncture, an account of the common staphy- lococcal phage patterns and the correlated anti- Student nurses after 5 weeks on ward (112) 71.4 biotic-resistant patterns seems warranted. Student nurses after 10 weeks on ward (104) 68.3 Staphylococcal strains most commonly

Healthy school Saint-Martin ( 1953 )" encountered in endemics and among children (2,762) 30.5 hospital personnel

Blood donors (200) 49.0 Rountree, Freeman, and Today, our knowledge of the speciation of Staphy- Patients on Barbour (1954)" admission (153) 34.0 lococcus aureus is still very limited. Serologic Patients on studies by Cowan (1939) 22 established three types, discharge (153) 40.5 designated as I, II, and III. This has proved to be of some value in epidemiologic problems, but it is Hospitalized Knight, White, and adults (2,439) 19.2 Hemmerly ( 1958 )" difficult to distinguish strains causing various forms of infections. In 1942, Fisk 23,24 used staphylophages Psychopathic-hospital Godfrey and Smith isolated from lysogenic staphylococci for phage staff (46) 33 ( 1958 )" typing purposes. Hobbs (1948) 25 reported that Psychopathic-hospital there is a broad correlation between susceptibility patients (42) 36 Hospital-school staff (68) 40 to various phages and Cowan's serologic types. Hospital-school However, this correlation is by no means com- patients (53) 57 plete.26 The staphylophages used today for routine General hospital typing are listed in Table VI. staff (95) 61 General hospital patients ( 206) 42 TABLE VI—STAPHYLOCOCCUS PHAGES USED FOR TYPING

Hospital staff (165) 31.5 Present series ( unpub- Group Phages lished data of 1960) 29, 52, 52A, 79, 80 (29A, 31, 31A, 44, 44A)° II 3A, 3B, 3C, 55, 71 (39, 523)* dosage. If the virulence of the staphylococci is rela- HI 6, 7, 42E, 47, 53, 54, 73, 75, 77, 83(VA4) tively constant, then the carrier state will be partly (42B, 47B, 47C, 70, 76)* determined by host resistance and partly by expo- IV 42D Miscel- 81, 187 (42C, 47A, 142)* sure dosage. On the other hand, if the physiologic laneous: state of the host is relatively constant, then the °Excluded in routine phage typing. outcome of the carrier state will be partly deter- mined by the virulence of the prevailing staphylo- They are classified into five groups. Groups I, II, coccal flora and, again, partly by the exposure dos- and III correspond to Cowan's serologic Types I,

104 II, and III, respectivoy.23,24,27,2s phage Type 42D TABLE VII-COMPARISON OF MEAN RECOVERY RATES OF THE VARIOUS STAPHYLOPHAGE TYPES WHEN is classified under Group IV, and phages 81, 187, FILTERED THROUGH SEITZ PADS 42C, 47A, and 142 are classified under a "miscel- Staphylophage no. Recovery rate laneous" group. That the 23 staphylophages used for routine typing represent a heterogeneous group 3A 0.77 x 10-0 3C 3.68x 10-13 is shown by their plaque morphology (Fig. 1). 73 0.46 x 10-0 The wide range of recovery rate of the various phage types (Table VII) after filtration through 29 1.06 x 40-1 Seitz filter pads implies that their size and shape, 39 1.4 x 10-1 52A 2.9 x 10-1 with or without a tail, also vary considerably.29,3° 55 1.0 x 10-1 Generally, the greater the average size of the 80 0.78 x 10-1 plaques, the greater is the recovery rate. Some exceptions were also noted. 83 1.1 x 10-2 A "halo phenomenon" of the phage plaques was 6 1.75 x 10 -2 7 1.7 x 10-2 noted occasionally in Types 7, 47, 3C, and 42D, as 42B 3.68 x 10 -2 shown in Figure 2. The mechanism of "halo" for- 42D 7.7 x 10-2 mation remains to be explored. It may involve 47 0.68 x 10-2 prophage formation caused by a mutated phage particle. An alternative explanation is that one of 52 3.5 x 10 -3 53 0.59 x 10-3 the susceptible staphylococcal progenies might have 54 5.1 x 10 -3 become an unstable lysogenic mutant. Theoretically, 70 0.85 x 10-3 an unstable prophage-harboring lysogenic staphy- 81 1.13 x 10-3 lococcus may continue to grow, reproduce, and 77 2.24 x 10-4 develop into a fairly large colony. Under unfavor- 75 0.77 x 10-5 able conditions such as aging, depletion of nutri- 187 1.7 x 10-7

Fig.

JOURNAL A.O.A., VOL. 61, OCT. 1961 105 vestigators, but were generally very sensitive to 741114 I/11"s chloramphenicol and the newer antibiotics such as kanamycin, ristocedin, , and oleando- mycin and, not infrequently, were also sensitive to erythromycin and magnamycin. It is Interesting to note that after so many years of popular use of chloramphenicol for penicillin-resistant staphylo- coccal infections, most of the pathogenic strains of staphylococci remained sensitive to this drug.31-35

Recent advances in the search for control measures 7 4 7 3C 42D Fig. 2 The three main sources of staphylococcal infections are: (1) patients with frank staphylococcal disease; ents, or accumulation of some metabolic products, (2) healthy carriers among the hospital personnel the unstable lysogenic mutant colony may start and visitors; and (3) fomites in the air, bedding, being lysed by the prophage, starting in the center linen, blankets, curtains, and other objects in con- of the colony and gradually spreading out peripher- tact with patients and carriers. ally. The first two sources are the breeding "hot beds" and therefore require special attention in detection The common phage patterns and correlated and . The last source requires sanitation antibiotic-resistant patterns • Most strains of control, including disinfection and sterilization Staphylococcus aureus are susceptible to more than measures. one type of staphylophage. For example, phage The most likely places for spreading staphylo- pattern 80/81 may include the staphylococcal coccal disease are: (1) operating rooms and dress- strains susceptible not only to phage types 80 and ing rooms where the integument barriers are open 81, but, in some strains, also to phage types 52, for staphylococcal assault; (2) nurseries where the 42B, and so forth. As an example, the common newborns' umbilical wounds and immature reticulo- phage patterns encountered in hospital endemics endothelial systems are helpless; and (3) surgical and carriers are listed in Table VIII. Generally and medical wards where the patients have become speaking, most of the antibiotic-resistant "epidemic" debilitated. Here, rigorous aseptic technic, sanita- strains of staphylococci belong to phage groups tion ( especially in terms of air flow), and the III and I. In recent years, the unclassified phage judicial use of antibiotics constitute the most im- group, so-called 80/81, has been encountered fre- portant triad of measures. quently in hospital endemics" and healthy carriers. Many experiments have been carried out along the lines just mentioned. These experimental results should serve as a guide for future planning in the TABLE Vol-THE COMMON PHAGE PATTERNS ENCOUNTERED IN HOSPITALS prevention of staphylococcal disease in hospitals. Group Common phage patterns Studies on the control of carriers • The carriers I 52A, 52/52A, 29/52, 29/52/80/83, of virulent staphylococci may be healthy hospital 29/31/44/52, 44/44A, 44A, 52A/79 personnel as well as patients. Spink (1956) 38 re- II 523, 3A, 3C, 3B/3C, 3A/3B/3C/39 HI 6/47/83, 6/47, 47, 6/83, 7, 7/53, 42B, ported a series of 10 surgical wound infections that 47/47C/83, 53/77/83, 83, 53, 47/53/75, occurred within Di months, which were found to 57/53/54/75, 53/83, 47/3C, 42B/47C, originate from a scrub nurse who had been in at- 47/53/54/77/83 tendance during all of the operations. After the IV 42D Unclassified 80/81, 7/42C/42E/52/52A/54, 3A/44A, removal of the scrub nurse from the operating 3A/7/54, E23/42B/44A/55/75, room, no further infections occurred. 523/42B/44A/54, 3A13B/44A Likewise, McDonald and Timbury (1957)37 °Modified after Williams and Rippon, Fusillo and his associates, and Blair and Carr traced a staphylococcal disease outbreak to a sur- geon who had a septic lesion. Similar experiences were reported by many other investigators. Last summer my colleagues and I made a survey Gould and Allan (1954) 38 treated all the staphy- of typable staphylococci from carriers among the lococcal nasal carriers on the staff of a small hos- personnel in our two teaching hospitals in Des pital with a tetracycline cream for 1 week and Moines. It was found that about 39 per cent belong found that the incidence of hospital infection de- to group III, 27 per cent belong to the unclassified creased strikingly following that treatment. Gil- group 80/81, and the rest belong to the other phage lespie" applied an antibiotic cream to the patients' patterns of unclassified group and groups H and I. nasal mucosa at the time of their admission to the The strains of 80/81 were all resistant to penicillin ward and throughout their stay. With this regimen, and tetracyclines, as reported by many other in- the frequency of recovering staphylococci from

106 open wounds dropped from 15 per cent to about 3 rate in relation to the ventilating system of an per cent. operating room over a period of 8 months. They It is the consensus today that the antibiotics for found that when the air was sucked into the oper- topical application should exclude penicillin, eryth- ating room from adjoining corridors, and ultimately romycin, and so forth, in favor of those more toxic from the wards, 9 per cent of clean surgical wounds compounds such as bacitracin, tyrothricin, neo- developed postoperative sepsis. After adjustment of mycin, or the synthetic compound 1:6-di-4'-chloro- the ventilation to provide a positive pressure within phenyl-diguanidohexeon (Hibitane), as suggested the operating room, the incidence of sepsis de- by Barber and Burston ( 1955 ).12 creased from 9 per cent to 1 per cent. There was The advisability of the topical application of also a striking reduction in the number of bacteria antibiotic cream to nasal carriers has been chal- in the air of the operating room. As a result of the lenged by Knight, White, and Hemmerly (1958 ).19 studies of Blowers and associates9 and Bourdillon They reported that "treatment of carriers with and Colebrook,43 it is now generally accepted that active agents temporarily suppressed the carrier when operating rooms are built within the structure state in a ward where few resistant strains were of the hospital, they need to be ventilated under available for replacement, but these persons re- positive pressure to make sure that contaminated gained staphylococci after treatment was stopped." air from the wards is kept out. Lepper (1958 ) 40 further suggested that "wholesale It is also recognized that the rate of air change treatment of carriers, which would allow accumula- must be sufficiently rapid that any contamination tion of resistant strains, may be dangerous." How- liberated at one operation is cleared up before ever, the emergence of antibiotic-resistant strains the next operation is commenced. This usually may be prevented by using combined antibiotics. implies a rate of 10 to 20 air changes per hour. As a hypothetical example, if the mutation rate of According to Williams, 4I "Dr. Blowers has been -9 investigating the best ways of getting the required a staphylococcus to bacitracin is 10 , and that to rate of air changes with the least expenditure of neomycin is 10 8, then the chance of the emergence energy, and he has shown that one can get a con- of a resistant mutant to both of the antibiotics siderable advantage by bringing the air in at the -17 simultaneously is 10 . For practical purposes, this ceiling in such a way that it tends to descend is a very unlikely event. This principle has been through the room in a 'piston' fashion, rather than widely applied to tuberculosis therapy with the by inducing turbulent mixing." combination of streptomycin, para-aminosalicylate, Blowers44,45 also showed, in one instance, that and isoniazid. Apparently, more critical experiments special training of the surgical staff to avoid all unnecessary movement in the operating room re- along this line are needed before re-evaluating the duced the bacterial count as much as did improving merits of topical application of antibiotic creams. the ventilation. From the economic point of view, combined anti- Kelley and Brown" reported that the combina- biotics cream might be applied only to the carriers tion of lithium chloride solutions and the "Kathabar of epidemic virulent strain as identified by phage Unit" design, made by Surface Combustion Cor- typing during endemic periods. poration, will consistently reduce the population of airborne bacteria from as high as 140 to 150 per Studies on the control of patients with frank cubic foot to less than 5 per cubic foot. This is an staphylococcal disease • Williams,4' being im- indication that air-conditioning engineers are grad- pressed by the ability of some infected patients to ually paying attention to the sanitary and micro- disperse their germs, initiated a rigorous plan for biologic aspects of ventilation as well as to human isolation in a separate room of any patient with comfort in terms of humidity, temperature, and what appeared to be infection caused by a danger- dust particles. ous staphylococcus. The physical isolation was Hare and his colleagues ,47,48 after studying the further supported by a very strict barrier-nursing dispersal of staphylococci from contaminated cloth- system. Great care was taken that no material which ing of nasal and skin carriers, stressed the impor- had been near the patient was used again in the tance of a rule that the persons working in the ward without sterilization. In 2 years of this regime, operating room should change all their clothing or his group was able to isolate all persons (both wear some special protective suit. Howe49 suggests patients with septic lesions and healthy carriers ) double masking and changing of masks every hour known to be infected with supposedly dangerous or two during long operations. types, on six separate occasions. He suggested that It is now the consensus that the widespread use hospital administrators can make a valuable con- of prophylactic antibiotics has resulted in a false tribution toward solving the problem of cross in- sense of security and a laxity of rigorous aseptic fection by providing really isolated facilities on all technic. This has also contributed to the increasing wards, with the equipment that is needed to sim- trend to , postoperative infections. plify the routine of barrier-nursing. Studies on control in nurseries • Jellard5° studied Studies on control in surgical units • Shooter cross infection with Staphylococcus aureus in a and coworkers42 studied the postoperative sepsis maternity unit. He found that if the umbilical

JOURNAL A.O.A., VOL. 61, OCT. 1961 107 stump was painted daily with an dye, ing prolonged oral medication of broad spectrum staphylococci seemed to spread less rapidly through antibiotics. the nursery. Gillespie36 has had a similar experi- Cellulitis at the site of venipuncture may lead to ence; he used hexachlorophene dusting powder for staphylococcal septicemia. 36,56 Physicians adminis- the umbilical stump. Shaffer 51 and Baldwin and tering steroid or corticotropin compounds to ward his coworkers52 have demonstrated the effective- patients must be constantly aware of the fact that ness of bathing infants with hexachlorophene in dissemination of staphylococcal infection with rap- reducing the skin and nasal colonization. Shaffer51 idly fatal septicemia may happen.57 pointed out that any measure which effectively prevents nasal or skin colonization is desirable in Studies on sanitation • Besides the air sanitation, infants, because implantation of pathogenic staphy- as previously mentioned, regular sterilization of all lococci may occur without warning during the early bedding at weekly intervals and between patients days of life and be followed by overt infection has been advocated. But no study on its effect days or weeks later. He goes on to emphasize seri- upon staphylococcal infection rates is as yet avail- ous public health implications of this long period able.45 Several methods for the sterilization of of latency; dissemination of an antibiotic-resistant, woolen blankets with quaternary ammonium com- virulent strain of Staphylococcus aureus from the pounds have been suggested.58,59 hospital to the community may occur in this man- Spring interior mattresses may be disinfected by ner. hot formalin vapor. 60 Mattress covers and other With good hygienic practices, hexachlorophene cotton bedding may be boiled or autoclaved. Patho- bathing of infants, and detection and control of genic bacteria present in floor dust can be pre- asymptomatic nasal carriers among hospital per- vented from floating into the air by treating the sonnel, Shaffer51 was able to maintain the staphy- floor with a light spindle oi1. 61 The amount required lococcal infection rate at less than 0.5 per cent for application is about 1 gallon per 800 to 1,000 of the infants in a children's hospital. square feet. The addition of certain and detergents has also been advocated62,63 and prac- Studies on general medical services • Rogers and ticed in some hospitals. Bennett" reported that, in contrast to reports of pediatric or surgical experience, many staphylo- coccal infections on medical services are produced The unknowns of staphylococcal disease by strains in phage group III. They found infec- According to Dr. Carl C. Dauer, Medical Advisor tions caused by strain 80/81 to be less common, to the Chief, National Office of Vital Statistics,64 and that the medical patient without influenza during the 11-year period from 1949 through 1959 rarely develops life-threatening staphylococcal in- in the United States, "the number of deaths from fection if there is no advanced debilitating disease. staphylococcal septicemia increased seven-fold..." Staphylococcal infection, according to these authors, This is an alarming trend, reflecting our inadequate usually arises in the following groups of hospital- understanding about this ubiquitous, successful ized medical patients: colonizer of human bodies. More basic research 1. Patients with certain types of systemic disease, work, therefore, is urgently needed in the fields notably those with leukemia, Hodgkin's disease, of: ( 1 ) identification of epidemic strains of Staphy- metastatic carcinoma, diabetes, disseminated lupus lococcus aureus; (2) its ecologic relationship with erythematosus, renal failure, and chronic pulmonary other microbes and vertebrate hosts; (3) recog- disease. nition of the determinants of host susceptibility and 2. Patients with certain local alterations in re- resistance; and (4) more exact and efficient control sistance, notably those with exfoliative dermatitis, measures to avert this rising trend. influenza, or any local surgical procedure such as tracheotomy, an indwelling urinary catheter, intra- The various staphylophages and their propagating venous "cut-down," prolonged intravenous infu- strains of staphylococci were kindly supplied by sions, or multiple parenteral injections. Dr. I. E. Blair. The technical assistance of Messrs. 3. Patients receiving certain types of therapy, S. Grobman and T. Chambers is gratefully acknowl- notably those receiving steroids or corticotropins, edged. The author is also indebted to Mr. L. Bald- nitrogen mustards, radiation, folic acid antagonists, win for preparing the photographs. and probably those receiving broad-spectrum anti- microbial therapy. 1. Pasteur, L.: De lextension de la theorie des germes A lStiologie de quelques maladies communes. C. R. Acad. Sc. Paris 90:1033-1044, It is well known that staphylococcal broncho- 1880. pneumonia may be contracted by recuperating 2. von Recklinghausen, F. D.: Cited by von Lingelsheim, W.: Atiologie und Therapie der Staphylokokken infectionen. Urban patients in hospital wards. Pulmonary edema is Schwarzenberg, Berlin, 1900. believed to be a predisposing factor. 54 This dreaded 3. Birch-Hirschfeld, F. V.: Die neuem pathologisch-anatomischen Untersuchungen fiber krankmachende Schmarotzerpilze. Schmidts fb. complication with its high mortality rate may be 155:97-109, 1872. prevented or minimized by strict isolation manage- 4. Klebs, T. A. E.: Beitraege zur patbologischen anatomie der Schusswunde. Vogel, Leipzig, 1872, pp. 104-122. ment and proper sterilization of bedding, linen, 5. Rueter, C.: Zur Aetiologie und Therapie der Metastasirenden blankets, and so forth. Another dreaded complica- Pyaenie. Dtsch z. Chir. 1:91-125, 1872. 6. Ogston, A.: Report upon micro-organisms in surgical diseases. tion is pseudomembranous enterocolitis55 follow- Brit. M. J. 1:369-375, 1881.

108 7. Hare, R.: Pomp and pestilence, infectious disease, its origins 33. Kenney, M., Johnson, P. M., and Tatz, J. S.: Four-year study and conquest. Victor Gollancz, London. of bacterial sensitivity of 5 antibiotics using qandardized paper-disk 8. Howe, C. W.: Prevention and control of postoperative wound method. Antibiotics Chemother. 3:1221-1234, Dec. 1953. infections owing to Staphylococcus aureus. New England J. Med. 34. Kutscher, A. H., et al.: Cross-correlation of bacterial sensitivity 255:787-794, Oct. 25, 1958. to carbomycin and erythromycin compared with other antibiotics. 9. Blowers, R., et al.: Control of wound infection in thoracic Antibiotics Chemother. 4:1023-1036, Oct. 1954. • surgery unit. Lancet 2:786-794, Oct. 15, 1955. 35. Altemeier, W. A., et al.: Critical reevaluation of antibiotic 10. Finland, M., and Jones, W. F., Jr.: Clinical staphylococcal therapy in surgery. J. Am. M. A. 157:305-309, Jan. 22, 1955. infections; staphylococcal infections currently encountered in large 36. Spink, W. W.: Clinical problem of antimicrobial resistant municipal hospital: some problems in evaluating antimicrobial therapy staphylococci. Ann. New York Acad. Sc. 65:175-190, 1956. in such infections. Ann. New York Acad. Sc. 65:191-205, 1956. 37. McDonald, S., and Timbury, M. C.: Unusual outbreak of 11. Godfrey, M. E., and Smith, I. M.: Hospital hazards of staphy- staphylococcal postoperative wound infection. Lancet 2:863-864, lococcic sepsis. J. Am. M. A. 166:1197-1201, March 8, 1958. Nov. 2, 1957. 12. Barber, M., and Burston, J.: Antibiotic-resistant staphylococcal 38. Gould, J. C., and Allan, W. S. A.: Staphylococcus pyogenes infection; study of antibiotic sensitivity in relation to bacteriophage cross-infection; prevention by treatment of carriers. Lancet 2:988-989, types. Lancet 2:578-583, Sept. 17, 1955. Nov. 13, 1954. 13. Miles, A. A., Williams, R. E. 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