Of the 61 infected patients, 37 were symptomatic (60.7%) and 24 asymptomatic (39.3%). Thus, the incidence of nosocomial symptomatic rotavirus infection was 16.8%, and that of asymptomatic infection was 10.9%; the difference is not significant (P = 0.098). Of the 61 infections, 26 cases occurred during hospitalization (incidence rate = 11.8%), while 35 occurred after discharge (incidence rate = 15.9%); the difference is not significant (P = 0.268).
We detected 15 cases (13.2%) of symptomatic infection in patients receiving LGG versus 22 cases (20.8%) in the placebo group. Even if we assessed a lower risk of symptomatic infection in the treated group (RR = 0.63), the difference is not significant (P = 0.132). The higher risk of asymptomatic infection in the treated group (RR = 1.30) is not significant either (P = 0.499).
Of the 26 cases with infection during hospitalization, 12 belonged to the treated group and 14 to the placebo group (RR = 0.80); of the 35 cases identified in the period after discharge, 17 belonged to the treated group and 18 to the placebo group (RR = 0.98). The differences are not significant.
The total number of days spent in hospital by the enrolled patients was 1,144. The mean duration of hospital stay in the treated group was 5.33 days, while in the placebo group it was 5.1 days. The difference is not significant.
Forty-seven of 220 infants (21.4%) were breast-fed (at least 2 meals a day), and 173 of 220 (78.6%) were non–breast-fed. Only 5 of 47 breast-fed infants (10.6%) developed nosocomial rotavirus infection, versus 56 of 173 non–breast-fed infants (32.4%) (Table 5); the difference is significant (P = 0.003). Of the five breast-fed infants who developed infection, two belonged to the treated group and three to the placebo group; the lower risk found for the treated group (RR = 0.49) is not significant (P = 0.404). Among the 56 non–breast-fed children with rotavirus infection, 27 were in the treated group and 29 in the placebo group. Also in this case, the lower risk assessed (RR = 0.92) is not significant (P = 0.706).
LGG is a physiologic constituent of gut microflora. It is unaffected by gastric acid (35) (it survives up to pH 3) and adheres to intestinal mucosa (36), a necessary condition for stable intestinal colonization. Colonization of the stool has been shown to be dosage-dependent and occurs in all patients if given at a dose of 1010 colony-forming units per day for at least 48 hours (30).
One source of error in this study could be the concomitant use of antibiotics. However, owing to randomization, antibiotic treated patients were homogeneously distributed into the treated group and the placebo group. Moreover, LGG is resistant to the most widely used antibiotics, as reported in the first studies by Goldin et al. (35), where LGG was recovered in the feces of 20 of 23 patients who were concurrently receiving ampicillin. Recently, LGG proved to be resistant to a group of antibiotics, including cefoxitin, aztreonam, amikacin, gentamicin, kanamycin, streptomycin, norfloxacin, nalidixic acid, sulphametoxazole, trimethoprim, cotrimoxazole, metronidazole, polymixin, and colistin sulphate (37). LGG was susceptible to tetracycline, chloramphenicol, and rifampicin, which were not used in the study patients. Finally, LGG has proved to be effective in the prevention of antibiotic-associated diarrhea (38).
1. Haffejee IE. The epidemiology of rotavirus
infections: A global perspective. J Pediatr Gastroenterol Nutr 1995; 20:275–86.
2. Berner R, Schumacher RF, Hameister S, Forster J. Occurrence and impact of community-acquired and nosocomial rotavirus
infection: A hospital-based study over 10 years. Acta Paediatr Suppl 1999; 426:48–52.
3. Dennehy PH, Tente WE, Fischer DJ, Veloudis BA, Peter G. Lack of impact of rapid identification of rotavirus
infected patients on nosocomial rotavirus
infection. Pediatr Infect Dis J 1989; 8:290–6.
4. Garner JS. Guidelines for isolation precautions in hospitals. The Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1996; 17:53–80.
5. Ford-Jones EL, Mindorff CM, Gold R, Petric M. The incidence of viral-associated diarrhea after admission to a pediatric hospital. Am J Epidemiol 1990; 131:711–8.
6. Cone R, Mohan K, Thouless M, Corey L. Nosocomial transmission of rotavirus
infection. Pediatr Infect Dis J 1998; 7:103–9.
7. Koopmans M, Van Asperen I. Epidemiology of rotavirus
infections in The Netherlands. Acta Paediatr Suppl 1999; 426:31–7.
8. Dennehy PH, Peter G. Risk factors associated with nosocomial rotavirus
infection. Am J Dis Child 1985; 139:935–9.
9. Tufvesson B, Johnsson T. Occurrence of reo-like calf viruses in young children
with acute gastroenteritis: Diagnoses established by electron microscopy and complement fixation, using the reo-like virus as antigen. Acta Pathol Microbiol Scand [B] 1976; 84:22–8.
10. Kapikian AZ, Flores J, Hoshino Y, et al. Prospects for development of a rotavirus
vaccine against rotavirus
diarrhea in infants and young children
. Rev Infect Dis 1989; 3(suppl):539–46.
11. Saavedra JM, Bauman NA, Oung I, Perman JA, Yolken RH. Feeding of Bifidobacterium bifidum
and Streptococcus thermophilus
to infants in hospital for prevention
of diarrhea and shedding of rotavirus
. Lancet 1994; 344:1046.
12. Oksanen PJ, Salminen S, Saxelin M, et al. Prevention
of traveller's diarrhoea by Lactobacillus GG. Ann Med 1990; 22:53–6.
13. Siitonen S, Vapaatalo H, Salminen S, et al. Effect of Lactobacillus GG yoghurt in prevention
of antibiotic associated diarrhoea. Ann Med 1990; 22:57–9.
14. Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T. A human Lactobacillus
strain (Lactobacillus Casei
strain GG) promotes recovery from acute diarrhea in children
. Pediatrics 1991; 88:90–7.
15. Pant AR, Graham SM, Allen SJ, et al. Lactobacillus GG and acute diarrhoea in young children
in the tropics. J Trop Pediatr 1996; 42:162–5.
16. Guarino A, Canani RB, Spagnuolo MI, Albano F, Di Benedetto L. Oral bacterial therapy reduces the duration of symptoms and of viral excretion in children
with mild diarrhea. J Pediatr Gastroenterol Nutr 1997; 25:516–9.
17. Szajevska H, Kotowska M, Mrukovicz JZ, Armanska M, Mikolajezyk W. Efficacy of Lactobacillus GG in prevention
of nosocomial diarrhea in infants. J Pediatr 2001; 138:361–5.
18. Weinberg RJ, Tipton G, Klish WJ, Brown MR. Effect of breast-feeding
on morbidity in rotavirus
gastroenteritis. Paediatrics 1984; 74:250–3.
19. Glass RI, Stoll BJ, Wyatt RG, Hoshino Y, Banu H, Kapikian AZ. Observation questioning a protective role for breast-feeding
in severe Rotavirus
diarrhea. Acta Paediatr Scand 1986; 75:713–8.
20. Duffy LC, Riepenhoff-Talty M, Byers TE, et al. Modulation of rotavirus
enteritis during breast-feeding
: Implications on alterations in the intestinal bacterial flora. Am J Dis Child 1986; 140:1164–8.
21. Clemens J, Rao M, Ahmed F, et al. Breast-feeding
and the risk of life-threatening rotavirus
or postponement? Pediatrics 1993; 92:680–5.
22. Gurwith M, Weirman W, Hinde D, et al. A prospective study of rotavirus
infection in infants and young children
. J Infect Dis 1981; 114:218–24.
23. Berger R, Hadziselimovic F, Just M, Reigel F. Influence of breast milk on nosocomial rotavirus
infections in infants. Infection 1984; 12:171–4.
24. Howie PW, Forsyth JS, Ogston SA, Clark A, Florey CD. Protective effect of breast-feeding
against infection. Br Med J 1990; 300:11–6.
25. Cunningham AS. Breast-feeding
and health. J Pediatr 1987; 110:658–9.
26. Blake PA, Ramos S, Mac Donald KL, et al. Pathogen specific risk factors and protective factors for acute diarrheal disease in urban Brasilian infants. J Infect Dis 1993; 167:627–32.
27. Totterdell BM, Chrystie IL, Banatvala JE. Rotavirus
infections in a maternity unit. Arch Dis Child 1976; 51:924–8.
28. Chrystie IL, Totterdell BM, Banatvala JE. Asymptomatic endemic rotavirus
infections in the newborn. Lancet 1978; 1:1176–8.
29. Eiden JJ, Verleur DG, Vonderfecht SL, Yolken RH. Duration and pattern of asymptomatic rotavirus
shedding by hospitalized children
. Pediatr Infect Dis J 1988; 7:564–9.
30. Saxelin M, Elo S, Vapaatalo H. Dose response colonisation of faeces after oral administration of Lactobacillus
casei strain GG. Microb Ecol Health Dis 1991; 4:209–14.
31. Armitage P, Berry G. Statistical methods in medical research.
Oxford, Blackwell Scientific, 1987, pp 172–5.
32. Pickering LK, Bartlett AV, Reves RR, Morrow A. Asymptomatic excretion of rotavirus
before and after rotavirus
diarrhea in children
in day care centers. J Pediatr 1988; 112:361–5.
33. Walther FJ, Bruggeman C, Daniëls-Bosman MSM, et al. Symptomatic and asymptomatic rotavirus
infections in hospitalized children
. Acta Paediatr Scand 1983; 72:659–63.
34. Champsaur H, Questiaux E, Prevot J, et al. Rotavirus
carriage, asymptomatic infection, and disease in the first two years of life: I. Virus shedding. J Infect Dis 1984; 149:667–74.
35. Goldin BR, Gorbach SL, Saxelin M, Barakat S, Gualtieri L, Salminen S. Survival of Lactobacillus species (strain GG) in human gastrointestinal tract. Dig Dis Sci 1992; 37:121–8.
36. Chauviere G, Coconnier MH, Kerneis S, Fourniat J, Servin AL. Adhesion of human Lactobacillus acidophilus strain LB to human enterocyte-like Caco-2 cells. J Gen Microbiol 1992; 138:1689–96.
37. Charteris WP, Kelly PM, Morelli L, Collins JK. Antibiotic susceptibility of potentially probiotic Lactobacillus species. J Food Prot 1998; 61:1636–43.
38. Arvola T, Laiho K, Torkkeli S, et al. Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children
with respiratory infections: A randomized study. Pediatrics 1999; 104:1121.
39. Newburg DS, Peterson JA, Ruiz-Palacios GM, et al. Role of human-milk lactadherin in protection against symptomatic rotavirus
infection. Lancet 1998; 351:1160–4.