Factors affecting neonatal E. coli K1 rectal colonization

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Brief cfinical and laboratory observations

lower the frequency of this complication '° but does not completely eliminate it. Wiley and Hutchins" recently reported the case of a patient on central parenteral nutrition who developed Candida septicemia followed by SVC obstruction owing to a thrombus with vegetations. In our five patients, infection was not usually associated with the development of a thrombus. The displacement of the end of the catheter by the infant's movements may damage the vessel wall and play an important role in the pathogenesis of the thrombosis and obstruction. The modified technique for catheter placement, because it avoids the ligation of the internal jugular vein and allows a better localization and fixation of the tip of the catheter which lies in the SVC, may contribute to the decrease in frequency of these complications. The authors express their appreciation to Mr. Steven Dale for statistical analysis and to Mrs. Martha Newbold for secretarial assistance. REFERENCES 1. Cashore WJ, Sedaghatian MR, and Usher RH: Nutritional supplements with intravenously administered lipid, protein hydrolysate, and glucose in small premature infants, Pediatrics 56:8, 1975.

The Journal of Pediatrics November 1978

2. Winters RW: Total parenteral nutrition in pediatrics: The Borden Award Address, Pediatrics 56:17, 1975. 3. Boeckman CR, and Krill CE Jr: Bacterial and fungal infection complicating parenteral alimentation in infants and children, J Pediatr Surg 5:117, 1970. 4. Ryan JA Jr, Abel RM, Abbot WM, et al: Catheter complications in total parenteral nutrition, N Engl J Med 290:757, 1974. 5. Smith W, and Balistreri W: Caviting pulmonary infarct: An unusual complication of parenteral alimentation, J PEDIATR 83:1021, 1973. 6. Wilmore DW, and Dudrick SJ: Growth and development of an infant receiving all nutrients exclusively by vein, JAMA 203:140, 1968. 7. Zumbro GL, Mullin MJ, and Nelson TG: Catheter placement in infants needing total parenteral nutrition utilizing common facial vein, Arch Surg 102:71, 1971. 8. Bell MJ, and Martin LW: A method of central venous alimentation catheter placement for use in small infants, Am Surg 39:323, 1973. 9. Wigger HJ, Bransilver BR, and Blanc WA: Thromboses due to catheterization in infants and children, J PEDIATR76:1, 1970. 10. Filler RM: A new method of fixation of silicone rubber catheters for long-tern" hyperalimentation, J Pediatr Surg 8:395, 1975. 11. Wiley EL, and Hutchins GM: Superior vena cava syndrome secondary to Candida thromboflebitis complicating parenteral alimentation, J PEDIATR91:977, 1977.

Factors affecting neonatal E. coli K1 rectal colonization Georges Peter, M.D.,* Providence, R.L, and Jeffrey S. Nelson, M.D., Berkeley, Calif.

ALTHOUGH at least 100 different K capsular antigens of Escherichia coli have been identified, approximately 75% of the E. coli cerebrospinal fluid isolates from newborn infants with meningitis possess the K1 capsular polysaccharide.' Previous epidemiologic studies of E. coli K1 strains in newborn nurseries have demonstrated asymptoFrom the Department of Pediatrics, Rhode Island Hospital and the Department of Medicine, Roger Williams General Hospital; and the Section of Reproductive and Developmental Medicine, Brown University' Program in Medicine. Supported by Contract No. 223-75-1204from the Food and Drug Administration, Department of Health, Education and Welfare, U.S. Public Health Service. Presented in part at the Eastern Section Meeting, American Federationfor Clinical Research, January 14, 1977, Boston, Mass. *Reprint address: Division of lnfeetious Diseases, Rhode Island Hospital, 593 Eddy St., Providence, RI 02902.

matic rectal carriage of this potential pathogen in approximately 20% of infants, and neonatal acquisition either by vertical transmission from mother-to-infant in the perinatal period or, less commonly, by infant-to-infant transmission within the nurseries. 2 Host immune factors have been implicated in the protection of the infants whose acquisition of the organism results in colonization and not invasive disease. Nevertheless, acquisition of this pathogen remains the initiating event in the pathophysiology of E. co6 K1 meningitis. Sarff et al -~ demonstrated the importance of maternal carriage in neonatal acquisition of E. coli K1 strains, and the temporal and geographic variations in the rate of rectal colonization. The factors responsible for the variable prevalence rates within and among nurseries have not been identified, although (brskov and Screnson ~ did demonstrate decreased fecal recovery of E. coli K1 strains among breast-fed infants in comparison to those in bottle-fed infants. To investigate further the factors affect-

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ing neonatal prevalance ofE. coli K1 strains, the following studies were performed.

Brief clinical and laboratory observations

867

•

NORMAL

Ioo I 80 70

Abbreviation used ICN: intensivecare nursery

I

MATERIAL AND METHODS During a 14-month period at Women and Infants Hospital of Rhode Island, rectal swabs for the identifications of E. coli K1 strains were obtained from the following groups of infants: (1) Infants discharged from the normal infant nurseries on weekdays for seven consecutive weeks. (2) Weekly surveys of all infants in the intensive care nursery for ten consecutive weeks (including the seven weeks of the preceding survey). (3) Fortythree maternal-infant pairs, from whom maternal swabs after delivery and daily swabs from their infants until discharge were obtained. These pairs were selected at random from women with uncomplicated deliveries of term infants. (4~ Daily cultures from 50 consecutive infants admitted to the ICN for the first 14 days of life or until discharge from this nursery. (5) After the ICN was moved to a newly renovated location in the hospital, prevalence surveys of both this nursery and the previously surveyed normal infant nurseries were repeated. The identification of E. coli K1 strains in these rectal swabs was performed by the antiserum agar technique, as described by Sarff et al/These agar plates were prepared with equine meningococcal group B antisera (kindly provided by Dr. John Robbins, Bureau of Biologics, Bethesda, Md.). The group B meningococcal capsular antigen is immunologically indistinguishable from the K1 antigen? The swabs were initially streaked on the antisera agar plates, incubated at 37°C overnight, and inspected for precipitation halos the following morning and again after 24 hours incubation at 4°C. The specificity of this method was demonstrated by complete concordance in the typing of 20 random E. coli K1 strains (K1 and non-K1) between the antiserum agar technique in our laboratory and immunodiffusion and slide agglutination assays kindly performed by Dr. Lowell S. Young (UCLA Medical Center, Los Angeles). RESULTS In the initial survey of infants at discharge from the normal infant nurseries, 61 of 223, or 27%, were E. coli K1 carriers. During the seven weeks of this study the weekly prevalence of carriers varied between 18 and 32%. Age at discharge, but not the mode of feeding, affected the rate of rectal colonization among these healthy, term neonates. The carriage rate of 50% (12 of 24) for infants

% Kt

D ICN

r .-p
50 40 50 20 IO O-Td

8-14d

15-28d

40 29-56d

Figure. Escherichia coli K1 rectal colonization in newborn infants of varying ages in both the ICN and normal infant nurseries. The number at the bottom of each bar represents the number of infants cultured in each group. Infant age is shown below the horizontal axis. The difference in colonization rate for infants 0 to 7 days of age and those 8 to,14 days of age is statistically significant for infants in the ICN as well as for those in the normal infant nurseries. seven days of age or more was significantly (P < 0.01) greater than that of 25% (49 of 199) for infants less than seven days of age. Of 154 bottle-fed infants, 38 (24%) were E. coli K1 carriers, whereas rectal swabs from 23 of 69 breast-fed infants (33%) yielded K1 strains; these differences were not statistically significant. In both groups, rectal carriage was greater for infants seven days or more in age than that of those younger than seven days. Rectal colonization was similar in infants born by cesarean section to that of those born by the vaginal route. Six of the 17 infants born by the former were E. coli K1 carriers at discharge, in comparison to eight K1 positive infants among the 20 delivered by the latter. Infants from both groups were between six and eight days of age. In the surveys of the ICN populations, 232 rectal swabs from 94 infants yielded 131 cultures positive for E. coli K1. Weekly prevalence rates ranged from 37.5% to 67%, were less than 50% during only two weeks, and consistently exceeded the weekly prevalence of E. coli K1 carriage in the regular nurseries. Sixty percent of the ICN infants (57 of 94) were rectal carriers, in comparison to the 27% carrier rate for infants discharged from the normal nurseries. However, as shown in the Figure, these differences disappeared when culture results were grouped according to infant age. In the first week of life, 25% of normal infants and 21% of ICN infants were carriers, in comparison to 50% of normal nursery infants and 54% of those in the ICN in the second week of life. Among the ICN infants, rectal carriage rates continued to rise with increasing age; 80% of cultures from infants four to eight weeks of age yielded K1 strains. Rectal swabs from maternal-infant pairs confirmed the role of maternal E. coli K1 carriage in the subsequent acquisition by their offspring. Nineteen of 45 (44%) of the

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Brief clinical and laboratory observations

Table I. Escherichia coli K1 rectal colonization in ICN infants according to age and parentera! administration of antibiotics; colonization is expressed as the number of E. coli K 1 positive cultures (numerator) and total number of rectal swabs (denominator) m

Antibiotic ] recipient

I

0-141

Age (days) 0-718-14

Yes No

3/115 (3%)* 19/t70(11%)*

3/91 (3.3%) 13/123(10.6%)

0/24 (0%) 6/47(12.8%)

Total no. of cultures

22/285 (8%)

16/214 (7%)

6/71 (8%)

Table II. Prevalence of rectal colonization with E. coli K 1 strains in different nurseries from November, 1975, to December, 1976; prevalence is expressed as the number of carriers (numerator) and the total number of infants cultured (denominator); in June, 1976, the ICN was moved to a new, renovated site

November, December, May, 1976 June, 1976 November, December,

1975 1975

1976 1976

found earlier. No change in the pattern of antibiotic use, handwashing practices, the ratio of infants to nurses, or daily infant census in the ICN following its relocation could be retrospectively identified. However, the new quarters provided slightly more floor space than the previous location, more effective use of floor space with resulting greater distance between infant incubators, and more limited access for hospital personnel. During the 14 months that these studies encompassed, only two instances of E. coli K1 meningitis and three of E. coli K1 sepsis occurred in the hospital's nurseries. DISCUSSION

*Significantdifferencesbetween colonizationrates.

Date

The Journal of Pediatrics November 1978

ICN (%)

Normal nurseries (%)

14/27 (52%) 18/27 (67%) 11/22 (50%) 1/11 (9.1%) 2/23 (8.7%) 3/32 (9.4%)

7/33 (21%) 7/26 (27%) 17/56 (30%) 9/27 (33%)

mothers were rectal carriers. Twelve (63%) of their infants developed rectal colonization before discharge, in contrast to only seven of 24 (29%) of the infants born of K1 negative mothers (P < 0.05). By day three of life, 11 of 12 of the former group and four of seven of the latter were K1 positive. The role of parenteral use of antibiotics in explaining the wide variation of weekly ICN prevalence rates were examined. As listed in Table I, the occurrence of K1 positive cultures was significantly ( P < 0 . 0 2 5 ) less common in infants receiving antibiotics (usually ampicillin and either kanamycin or gentamicin) than in infants who were not. These differences did not achieve statistical significance in either the first or second week of life. The low incidence of Kt positive cultures in this later ICN study was noted, in retrospect, to follow relocation of the ICN to renovated facilities. Subsequently, in three separate surveys of the ICN at its new site, the prevalence ofE. coli K1 colonization was less than 10% (Table II). In contrast, maternal colonization and that of infants in the regular nurseries (33%), did not differ from the rates

Previous studies have shown that the majority of infants colonized with strains of E. coli acquire these strains from their own mothers. 5 Sarff et al 2 demonstrated similar findings with E. coli K1 strains in that two-thirds of infants born to E. coli K1 mothers became K1 rectal carriers, most of which were identical by O and H serotyping with the maternal strains. The mothers of 83% of the colonized infants were also rectal carriers. These findings have been confirmed and extended in our study, in which the importance of maternal carriage, neonatal age, antibiotic administration, and probably also intranursery transmission was demonstrated. Although the prevalence of neonatal carriers was higher in the ICN than in the normal nurseries, the difference between the nurseries disappeared when infants of similar age were compared. This colonization rate probably is explained by cross-infection within the ICN. The marked drop in prevalence of E. coli K1 rectal carriage that occurred when the ICN moved into new, less crowded facilities supports this explanation. Possibly, the move to new facilities led to improved handwashing, and reduced the horizontal transmission of bacteria. ~, 7 Parenteral administration of antibiotics also was associated with reduced E. coli K1 rectal colonization, but no evidence could be found that antibiotic utilization increased in association with the precipitous fall in carrier rates after the ICN move. Breast-feeding in our study did not affect E. coli K1 rectal carriage. This finding conflicts with that of ~brskov and SCrenson. 3 Colostral anti-K1 IgA has been suggested as the explanation for this latter difference in colonization and as a possible protective factor in E. coli K1 neonatal disease. 2 However, our study and that of ~rskov and SCrenson are not comparable, since the latter involved infants under ten days of age. Our findings do not support a role for anti-Kl colostral IgA in the prevention of initial colonization, but do not exclude a possible role of colostral antibody in the prevention of invasive E. coli Kt disease. The low incidence of disease among colonized

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Brief clinical and laboratory observations

infants in this study, however, does support the role of host immune factors, such as colostral or circulating antibody, in the pathogenesis of neonatal E. coli K1 meningitis. The authors thank Lee Rotundo for her assistance in the organization and performance of this study. We also thank Katherine S. Elias, Janet S. Bissell, and Richard B. Provonchee for their technical assistance, Dr. William Oh for his advice and encouragement, and the Pediatric Nursing Staff of the Women and Infants Hospital of Rhode Island for their cooperation during the study.

3.

4.

5.

6. REFERENCES

1. Glode MP, Sutton A, Robbins JB, McCracken GH, Gotschlich EC, Kaijser B, and Hanson LA: Neonatal bacterial meningitis and enteric diseases of infants and children. Neonatal meningitis due to Escherichia coli K1, J Infect Dis 136:$93, 1977. 2. Sarff LD, McCracken GH .Jr, Schiffer MS, Golde MP, Robbins JB, Orskov I, and Orskov F: Epidemiology of

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Escherichia coli K1 in healthy and diseased newborns, Lancet 1:1099, 1975. Orskov F, and SCrensen KB: Escherichia coli serogroups in breast-fed and bottle-fed infants, Acta Pathol Microbiol Scand B, 83:25, 1975. Kasper DL, Winkelhake JL, Zollinger WD, Brandt BL, and Artenstein MS: Immunochemical similarity between polysaccharide antigens of Escherichia coli 07:K1 (L) NM and group B Neisseria meningitidis, J Immunol 110:262, 1973. Bettelheim KA, Teoh-Chan CH, Chandler ME, O'Farrell SM, Rahamin L, Shaw EJ, and Shooter RA: Further studies of Escherichia coli in babies after normal delivery, J Hyg 73:277, 1974. Eisenach KD, Reber RM, Eitzman DV, and Baer H: Nosocomial infections due to kanamycin-resistant, R factor carrying enteric organisms in an intensive care nursery, Pediatrics 50:395, 1972. Adler JL, Shulman JA, Terry PM, Feldman DB, and Skaity P: Nosocomial colonization with kanamycin-resistant Klebsiella pneumoniae, types 2 and I 1, in a premature nursery, J PEDIATR77:376, 1970.

Commentary: The tragedy of stillbirth

OUR COLLEAGUES on the other side of the Atlantic deserve credit for recently describing the natural history of stillbirth and the potential long-term psychologic consequences in the parents, especially during subsequent pregnancies and in surviving children, a When the diagnosis is made in utero, physician anxiety is often generated in deciding whether to inform the mother, as welt as the father. During delivery the labor room becomes a somber scene, with depressed medical attendants making feeble attempts to encourage the bereaved or unsuspecting mother. The delivery itself is characterized by an absence of joy and a feeling of failure as the limp baby is quickly wrapped in a receiving blanket and removed from the delivery room. A similar scene evolves when stillbirth is unexpected, except for an initial flurry of activity as frantic attempts are made at resuscitation. This activity is gradually replaced by an oppressive silence, most often best appreciated by the anxious mother straining to hear her infant's cry and barely noticing the hurried exit of her

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dead child in the arms of a well-meaning medical attendant. Following delivery the bereaved mother is often heavily sedated and isolated physically from the other mothers and children. Medical personnel visit infrequently and characteristically avoid meaningful communication. Such physical isolation exaggerates the mother's feelings of failure, guilt, and misery. Hospital discharge is often premature to facilitate a "return to normalcy." Friends and relatives often avoid visiting the bereaved parents, adding further to the mother's feelings of isolation. The mother's immediate postpartum reaction may be characterized by depression associated with frigidity and phobic states. Some mothers, seemingly untouched at the time of delivery, may be at increased risk of a breakdown during a subsequent pregnancy. Postpartum matrimonial disturbances are not uncommon and psychosomatic symptoms may occur in the husband. Far reaching psychologic effects have also been described in surviving children.