Clinical Laboratory and Epidemiological Investigations of a ...

Vol. 19, No. 3

JOURNAL OF CLINICAL MICROBIOLOGY, Mar. 1984, p. 366-370

0095-1137184/030366-05$02.00/0 Copyright ©3 1984, American Society for Microbiology

Clinical Laboratory and Epidemiological Investigations of a Streptococcus pyogenes Cluster Epidemic in a Newborn Nursery HENRY D. ISENBERG,'* VICTOR TUCCI,' PHILIP LIPSITZ,2 AND RICHARD R. FACKLAM3 Divisions of Microbiology' and Neonatology,2 Schneider Children's Hospital, Long Island Jewish-Hillside Medical Center, New Hyde Park, New York 11042, and Centers for Disease Control, Atlanta, Georgia 303333 Received 30 September 1983/Accepted 8 December 1983

Streptococcus pyogenes, nontypable with available M antisera, T type 12, and reactive in the serum opacity test, produced various lesions in 10 newborn infants during a 2-month period. All infants except one were discharged from the nursery before overt disease manifestations. Colonization studies of newborn infants showed a streptococcal carrier rate of 19% (27 of 140). Only 1 of 154 staff members yielded the same streptococcus from the throat, but it could not be implicated as the source for the outbreak. Cohorting of infants and chlorhexidine gluconate hand washing by staff members helped in terminating this cluster epidemic.

Isolation and identification of bacteria. All bacteria, from clinical specimens, were isolated on routine media which included 5% sheep blood agar consisting of Trypticase soy agar (BBL Microbiology Systems, Cockeysville, Md.), staphylococcus 110 agar (BBL); a special broth medium previously described (9); enterococcal agar (BBL), and media for the isolation and identification of other bacteria not pertinent to this report. Beta-hemolytic colonies, morphologically suggesting streptococci, were transferred to an additional sheep blood agar plate and exposed to Taxo A (BBL) and trimethoprim sulfamethoxazole (BBL) disks in accordance with the presumptive identification scheme suggested by Facklam (6). All bacitracin-susceptible, trimethoprim sulfamethoxazole-resistant beta-hemolytic streptococci were subcultured to sheep blood agar slants for storage and transferred to Todd-Hewitt broth (BBL). After incubation overnight, the broths were centrifuged and the pellets were extracted with hot acid and grouped by the capillary precipitin reaction (6). All bacteria identified as group A streptococci were sent to the Centers for Disease Control, Atlanta, Ga. M precipitation, T agglutination (21), and serum opacity reaction (28) were performed to establish the type of S. pyogenes involved. All staphylococci isolated on blood agar plates and staphylococcus 110 media were tested for free coagulase production as advocated by Kloos and Smith (11). Each staphylococcal isolate was maintained on Trypticase soy agar (BBL) for bacteriophage typing with the international set of staphylophages. Surveillance cultures. The periumbilical areas of newborns were cultured with 0.9% NaCl-moistened swabs and inoculated onto 5% sheep blood agar and staphylococcus 110 media; the swabs were then immersed in the special broths, and all material was transported to the laboratory immediately. The culture plates were streaked, and the agars and broths were incubated overnight. If the agar plates were negative after this incubation, the broths were inspected macroscopically and subcultured to sheep blood agar and staphylococcus 110 agar, incubated once more overnight, and screened the following day for the presence of either streptococci or staphylococci. The throats of all medical house staff members and nursing staff on the maternity floor, including labor and delivery

Streptococcus pyogenes, assumed to have been the major agent of puerperal sepsis and infections in newborns (17), has yielded its dominant role to Streptococcus agalactiae during the past decades. This shift cannot be attributed only to the action of antibiotic drugs, since both species of Streptococcus have remained constant in their susceptibility to penicillin, the agent of choice in the treatment of both types of disease. The last group A streptococcal epidemic involving newborns was reported from Sweden in 1978. This report summarizes our experience with an S. pyogenes outbreak in a newborn nursery and the measures required for its control. MATERIALS AND METHODS

Epidemiological surveillance. The Long Island JewishHillside Medical Center has practiced surveillance for nosocomial infections since 1974. This surveillance consists of routine ward rounds and daily, in-depth evaluation of all microbiology requests by the hospital epidemiologist. This surveillance system identified the initial S. pyogenes infections of the newborns. The maternity department of the medical center consists of a labor and delivery suite, a 48-crib newborn nursery divided into four distinct and separate nurseries, and a 41bed postpartum division, all located on the third floor of the institution. Only healthy newborns are kept in the third floor nursery. Premature and ill newborn infants are cared for in the neonatal unit located on the first floor of the facility. The nursing staff of the newborn nursery is completely distinct from the labor-delivery and postpartum nursing staff. After delivery, an infant is transported immediately to the newborn nursery in a transport incubator, sanitized after each use. The first bathing of the newborn takes place in the nursery. Routine infant care at the time of the cluster epidemic consisted of washing the infant with castile soap, without any special treatment for the umbilicus. Gloves were not worn by the staff, and hand washing with either castile soap or a hexachlorophene formulation (pHisoHex, Winthrop Laboratories, New York) was the routine on arrival and between contact with each baby. Residents of the pediatric service routinely examine newborns. These house officers also care for infants in the neonatal unit. *

Corresponding author.

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TABLE 1. S. pyogenes infections in Newborn Infants: M:NT, T-12, serum opacity reactive Onset and culture

Patient no.

Sex

Date of birth

Anatomical site(s) involved

1 2 3 4 5 6 7 8 9 10

F M F M M M F M M M

10/21/81 10/21/81 10/30/81 10/17/81 11/2/81 11/4/81 10/25/81 11/16/81 12/8/81 12/19/81

Axillary pustule Umbilicus Umbilicus Umbilicus, finger lesion Umbilicus Umbilicus Umbilicus Umbilicus Throat, thumb lesion Umbilicus

rooms, the newborn nursery, and the postpartum areas, were cultured for the presence of S. pyogenes by inoculating sheep blood agar plates. These plates were transported immediately to the laboratory, where they were streaked and incubated for inspection the following day. Reincubation of the plates for an additional day was practiced on all sheep blood agars that did not reveal the presence of beta-hemolytic streptococci. All colonies on surveillance agar plates suggestive of either S. pyogenes or Staphylococcus aureus were treated in the fashion described above. All infections involving S. pyogenes were identified as nosocomial by using the criteria defined by the National Nosocomial Infection Survey (Centers for Disease Control). RESULTS Ten infants delivered at this institution between 21 October and 19 December 1981 developed S. pyogenes infections (Table 1). Of these infected children, only one (no. 1) developed an axillary pustular lesion on day 5 of life while in the neonatal unit (premature nursery). Only one infection became manifest while an infant resided in the newborn nursery (infant no. 3). All other infants had been discharged before overt manifestations of the infections. Seven were seen in the emergency room after their discharge. It was necessary to admit five of the infants to the neonatal unit; the other two were treated and discharged without readmission. The most common infection in these infants was omphalitis, involved eight times. Pustules became manifest in one infant, and two developed finger lesions. All yielded streptococci on culture. In only one of these infants (no. 9) could S. pyogenes be recovered from the throat. S. aureus was isolated as a companion organism from the same lesions in seven of the infants. However, distinct and TABLE 2. Distribution of S. aureus recovered during colonization studies Staphylophage type

94/96 3A/3C

29/52/52A/79/80/84/83A

No. of infants' with S. aureus of the type in column 1 during the period: 12/22/81-1/29/82 12/4/81-12/21/81

50 (52.6) 6 (6.3) 6 (6.3)

9 (9.5) 79/81 19 (20.0) No type 5 (5.3) Other a the indicate in Numbers parentheses recovered during each period.

9 (3.3) 13 (4.8) 44 (16.1) 35 (12.8) 72 (26.4) 100 (36.6) percentage of the total

Date Date

10/26 11/5 11/6 11/10 11/13 11/13 11/24 11/27 12/26 1/6/82

age Age (days)

5 15 7 24 11 9 31 11 18 17

Associated S. aureus

Assocteriophageus bacteriophage type

29/52A/52/80/75/84/85/95 94/96 3C/71 No type 83/3C/42E/47/54/77/75 Not isolated Not isolated Not isolated No type 83A/81

different staphylophage patterns were manifested by each of the staphylococci. The lesions developed from day 5 through day 31 after delivery, with an average of 14.8 days. All of the streptococci isolated from these lesions reacted with the group-specific polysaccharide antiserum. None reacted with M antisera, but all isolates typed out as T-12 and were serum opacity reactive. These findings suggested strongly that a common source led to this cluster epidemic. A total of 154 staff members were screened once for throat carriage of the group A Streptococcus. None of them manifested overt symptoms at the time of culture; however, three (1.9%) yielded 3-hemolytic streptococci. Typing of these three isolates indicated that one individual, a newborn nursery nurse, carried M:NT, T-12, serum opacity reactive Streptococcus. The second isolate was a group G Streptococcus, and the third was identified as S. pyogenes of a different type. A colonization study of the newborn infants was begun on 4 December 1981 and continued through 29 January 1982. The periumbilical areas of the infants were cultured upon discharge from the newborn nursery, usually after a 3-day stay. During the first 2 weeks, the periumbilical area was also cultured on admission to the nursery; since none of the infants carried organisms on admission, this practice was discontinued. The fact-finding period of this study, a total of 16 days (December 4 through 21, 1981), involved 140 newborn infants, of whom 27 (19%) carried the epidemic S. pyogenes. S. aureus was present in 95 (67.9%) of these babies. On 21 December 1981, the epidemilogical control measures discussed below were initiated. Between December 22 and 26, 47 infants were discharged from the newborn nursery, of whom 5 (11%) were positive for S. pyogenes and 17 (36.2%) were positive for S. aureus. For the next 33 days, of 314 infants discharged from the newborn nursery, none carried S. pyogenes. Of these 314 newborn infants, 121 (38.5%) harbored S. aureus in their periumbilical areas. Table 2 lists the bacteriophage patterns of the staphylococci during this study. It is noteworthy that in the initial period, 58.8% of the staphylococci belonged to staphylophage type 94/96. This number was reduced to 3.3% after the control measures were instituted. Epidemiology. Suspicion of a cluster epidemic involving S. pyogenes arose during November 1981 when six infants previously discharged were seen in the emergency room with draining umbilical stumps. Of these, five were readmitted to the neonatal unit. The isolation of the group A Streptococcus from this drainage led to an epidemiological investigation. A retrospective review of all group A streptococci isolated from newborn and premature infants during

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the previous 3 months yielded the index case. It was a 5-dayold infant transferred from the newborn nursery to the premature nursery at 3 days of age with an axillary pustule that yielded group A Streptococcus. A working group which included, beside the microbiologist and epidemiologist, the chief of the neonatal service, the chairman of the Department of Obstetrics and Gynecology, various nursing department representatives, and administrators, agreed to a surveillance of the newborn nursery. The periumbilical areas of all babies were cultured upon discharge from the nursery. These efforts also included surveillance for staphylococci. The finding that 19% of the infants were colonized with S. pyogenes upon discharge from the nursery during an approximately 2-week period led to the institution of the following measures. All permanent personnel working in the newborn nursery, the labor and delivery room suite, and the postpartum floor, as well as the pediatric, neonatal, and obstetrics and gynecology house officers, were screened for carriage of group A streptococci. (Actually, this surveillance was begun on 17 December 1981, 4 days before the institution of control measures.) All newborn babies and mothers were cohorted. All nursing staff in the newborn nursery and on the postpartum floor were cohorted. All sibling visitations were discontinued. All employees with demonstrated carriage of group A streptococci were to receive treatment under the supervision of the Employee Health Service. All nursing personnel in the newborn nursery were treated on a voluntary basis with a course of oral antibiotic, regardless of culture results. Chlorhexidine gluconate (Hibiclens, Stuart Pharmaceuticals, Wilmington, Del.) was instituted as the sole agent for hand washing in the newborn nursery. Dry skin care for the newborns was instituted. The surveillance of periumbilical cultures upon discharge was continued. The Divisions of Epidemiology and of Maternal and Child Welfare of The New York City Department of Health were notified. The next follow-up meeting of this working committee (28 December 1981) noted the success of the control measures which led to a dramatic decline in the colonization of the newborn infants. In addition, the results of employee surveillance showed that only 3 of 154 employees carried betahemolytic streptococci. All three staff members were negative in a follow-up performed 5 days after the initial culture. The working committee therefore decided that the cohorting of the newborn infants, nurses, and mothers, surveillance cultures of the newborn infants, and restriction of sibling visits would be continued. One week later, the same working committee decided to continue permanently the cohorting of infants but elected to discontinue the cohorting of mothers and postpartum care nurses and to permit sibling visitation. Surveillance cultures were continued until the end of January 1982. The 10 infants with streptococcosis recovered uneventfully after appropriate therapy.

DISCUSSION The introduction of serogrouping by Lancefield (14) established S. pyogenes as the major agent of puerperal sepsis (27). However, a decline in the frequency and severity of puerperal group A infections was observed even before the availability of antimicrobial agents (8). The English language literature since 1933 contains only a moderate number of reports of puerperal and neonatal group A streptococcosis (2, 3, 5, 7, 8, 10, 12, 15, 17-20, 22, 23, 26). The group A Streptococcus has been replaced by S. agalactiae, a bacteri-

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um that is part of the normal vaginal microbiota in an appreciable number of women of childbearing age (13). Nevertheless, the diseases and sequelae S. pyogenes can evoke in the human host must lead to the mobilization of stringent methods to control its spread in maternity and newborn services, despite its diminished effect during the newborn period (24). This cluster epidemic resembled most of the other outbreaks. A common nosocomial source obviously initiated the sequence but could not be identified. The index patient with an axillary pustule was transferred to the neonatal unit on the third postpartum day before lesions became apparent. None of the other infants manifested infections while in the hospital; symptoms did not become apparent until 7 to 31 days after birth. The newborn nursery nurse, the only staff member from whom the identical Streptococcus strain could be recovered, is an unlikely candidate as the source since her throat culture was not performed until 2 months after the birth of the index patient at a time when a considerable number of infants were colonized with this particular Streptococcus strain. In retrospect, throat cultures of personnel

may have been an inadequate screening procedure for determining the spread of the organism. Hand cultures might have helped in explaining the transmission from infant to infant, in view of the observations of Rammelkamp et al. (25) that streptococcal infections are transmitted mainly by direct and intimate contact with an infected individual, not by the airborne route or by contact with environmental deposits. However, these investigators were concerned exclusively with streptococcal respiratory disease. Streptococcal skin infections may be initiated by a different mechanism. Almost 20% (27 of 140) of the infants in the nursery were colonized with the identical bacterium during the initial phase of the investigation; only one manifested with omphalitis during the same time, indicating that clinical manifestation was related to the response of an individual infant to the microbial challenge. Omphalitis was the most common (80%) manifestation of this outbreak, in agreement with earlier observations of streptococcal nursery epidemics (2). According to Chamberlain (4), the umbilicus represents a ready portal of entry for microorganisms during the perinatal period. Even benignappearing lesions such as blennorrhea (moist umbilicus) may have grave consequences. Chamberlain's report emphasizes the role of Streptococcus hemolyticus, which accounted for 15 of 33 fatal cases he reported. Unfortunately, the lack of grouping and typing of the streptococci mars the significance of his observation, although it emphasizes the importance of this site as a potential threat to newborns. It is difficult to interpret the role of S. aureus in the outbreak. This bacterium was recovered as a companion in 7 of the 10 sick infants, but bacteriophage types were different in all instances. For the past 5 years, ongoing colonization studies of newborn infants in this institution indicate 60 to 80% staphylococcal colonization of the umbilicus by day 3 of life. Although shifts in the predominant bacteriophage types occur at approximately 6- to 8-month intervals, the incidence of staphylococcal disease of newborns, manifested mainly as pustulosis, has remained constant at a very low level. It seems plausible that this bacterium did not play a major part in this streptococcal cluster epidemic. It is of interest to note that most epidemics involve streptococci with readily determined M protein. Geil et al. (7) reported on two epidemics with T-28 and T-11/9 group A streptococci, M-nontypable with available antisera, and Nelson and co-workers (22) described a streptococcal epidemic

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caused by a bacterium that initially reacted only with T-12 antibodies but later was shown to possess an M protein provisionally identified as M66. The Streptococcus sp. organisms in this outbreak also did not react with M protein antibodies including M12, M62, and M66, proteins frequently shared by T-12 streptococci. Its positive serum opacity reaction helped in the epidemiological definition of the organism and suggests that it may have an M antigen for which no antisera are avalable (M22 or provisional M76) or that it may be associated with an as yet undefined M protein (16). Maxted and Widdowson (16) also noted that the greatest number of serum opacity reactive streptococci are associated with skin infections. The recent work by Beachey's group (1) assigns an important function to M protein, which in combination with lipoteichoic acid insures adhesions of S. pyogenes to a specific receptor on pharyngeal or laryngeal epithelial cell membranes, thought to consist of a protein or glycoprotein containing specific fatty acid binding sites for lipoteichoic acid. It may be that the attachment to skin epithelial cells involves a mechanism that utilizes the serum opacity-producing factor. None of the infants with overt streptococcal infections presented with sequelae, confirming the conclusions of Powers and Boisvert (24). The various measures instituted to control this outbreak reflect those used by previous investigators. In our opinion, cohorting of the infants and their nurses and the use of chlorhexidine gluconate for hand washing were the most helpful. The nurseries at Long Island Jewish-Hillside Medical Center are divided into four units on the postpartum floor as an easy means of bringing infants to their mothers. As soon as the problem became apparent, this distribution of infants ceased. All infants were accommodated in one nursery, and all personnel were permanently assigned. All other nurseries were terminally cleaned before the admission of new infants. Thereafter, infants were admitted to one nursery at a time until it was fully occupied when the next nursery was opened. No infant was admitted to a nursery until all previous occupants were discharged and the nursery was again terminally cleaned. As soon as this type of cohorting was instituted, no additional carriers of Streptococcus were encountered, although the colonization surveillance continued for more than a month. Since none of the colonized infants were treated with antibiotic, this barrier to exposure seems to have interrupted the dissemination of the Streptococcus organisms. In addition, chlorhexidine gluconate hand washing may have had a beneficial effect, since staphylococcal colonization of the infants was reduced appreciably and has been maintained at a lower level. It is unlikely that the cohorting of mothers and the probibition of sibling visits affected the outcome. The one-time screening of throats of personnel indicated that individuals in close contact with infants may acquire their organisms and that carriage of related and different microorganisms is a fact of life that must be taken into account whenever personal contact with a susceptible individual occurs. It should be standard practice, but constant educational insistence on ordinary ablutions between patients cannot be overemphasized. The streptococci in the throats of three employee contacts were eliminated by day 5 of treatment. The effect of oral penicillin prophylaxis for nursery personnel could not be determined since it was learned after the study that those without positive cultures did not comply with the directive. S. pyogenes is a rare organism in newborn nurseries. When introduced, it can colonize a large number of infants and produce disease, often delayed in its manifestations until

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after discharge, as was the case in this outbreak and in several earlier descriptions of nursery epidemics. The preponderence of males over females emphasized by others (4, 15) has no ready explanation. The absence of disease in the many infants colonized by S. pyogenes and the mild symptoms observed in those affected must not be allowed to obscure the potential severity of streptococcal infections of newborn infants. ACKNOWLEDGMENT We are grateful to the nursing department of Long Island JewishHillside Medical Center for the cooperation of its members in implementing the control measures. LITERATURE CITED 1. Beachey, E. H., B. I. Eisenstein, and I. Ofek. 1982. Bacterial adherence in infectious disease. The Upjohn Co., Kalamazoo,

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