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 infection 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 infections found at autop- found staphylococci in osteomyelitic pus and cul- sy, and (3) the carrier rate of coagulase-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 Medical Microbiology and pattern of staphylococcal infections was observed Immunology at the College of Osteopathic Medicine and Surgery. 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 Peritonitis 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