OBJECTIVE: To study risk factors for the highly variable local colonization rates with unrelated Enterobacter species strains previously found in 22 Swedish neonatal units (0% to 32.4% of the infants). PATIENTS AND SETTING: The fecal Enterobacter species carriage rates among 953 infants in the 22 special-care neonatal units were correlated with variables related to the ward (size, crowding, staffing, work load, antibiotic usage, level of care, hygienic precautions), and the hospital (temperature of water supplied, geographical location). RESULTS: The average Enterobacter species carriage rate was highest at seven days of age (17% of the infants) and then declined to 3%. Only location of the hospital in an area with warmer climate according to horticultural zone showed an association with Enterobacter species carriage in multivariate analysis (P = 0.005). CONCLUSION: Although Enterobacter species mainly cause nosocomially acquired infections, the occurrence of the organism in special-care neonatal units seemed to be determined more by extrahospital than by intrahospital factors.
Enterobacter cloacae strains dominated the aerobic faecal flora of 8.3% of 953 infants discharged from 32 Swedish neonatal intensive care units and the susceptibility of these strains to seven beta-lactam antibiotics was determined. Isolates from infants treated with cefuroxime showed slightly increased MICs only to ampicillin, cephalexin and cephalothin as compared to isolates from untreated infants matched for ward and time of sampling (P = 0.02). In contrast, E. cloacae isolates from ampicillin treated infants showed markedly elevated MICs of all agents tested including piperacillin, cefuroxime, cefotaxime and ceftazidime as compared to those from control neonates (P values between 0.001 for ampicillin and 0.017 for cefotaxime). Thus, E. cloacae with cefotaxime MICs as high as 512 mg/L were isolated only after ampicillin therapy. The resistant strains were negative in a colony DNA hybridization assay using gene probes for the plasmid beta-lactamases TEM-1, OXA-1 and SHV-1. The resistant strains also showed only one beta-lactamase band when crude cell sonicates were analysed by isoelectric focusing, and were not found in other infants in the same ward. The results indicate that the selection of chromosomal E. cloacae mutants, presumably with stably derepressed beta-lactamase production, in the faecal flora of neonates is rare during treatment with cefuroxime and more common during ampicillin therapy.
Both ampicillin and cefuroxime therapy of neonates selected drug- and species-dependent beta-lactam resistance patterns in fecal strains of Escherichia coli and Klebsiella spp. This was in contrast to our previous findings that ampicillin, but not cefuroxime, contributed to the emergence of beta-lactam resistance also by the promotion of nosocomial spread of resistant strains.
Among 953 infants in 22 neonatal care units studied, 23% (median value, range 0-78) were found to be faecally colonized with one of 21 distinct nosocomial strains of Escherichia coli, Klebsiella or Enterobacter spp. Lower birth weight was associated with such colonization, particularly with nosocomial phenotypes of E. coli. Caesarean section followed by prolonged incubator care, and hospital stay, were additional factors associated with colonization by such strains of E. coli. Antibiotic therapy of the infant and type of feeding were not found to be associated with acquisition of nosocomial strains of enteric bacteria among neonates.
TEM-1, OXA-1, SHV-1, and related beta-lactamases in fecal isolates from 953 infants in 22 Swedish neonatal intensive care units were studied by DNA hybridization. TEM-1- and OXA-1-positive isolates were always Escherichia coli and represented 86 and 8%, respectively, of the ampicillin-resistant isolates of this species. SHV-1 was found in 16% of the Klebsiella sp. (mainly Klebsiella pneumoniae) isolates. TEM-1 and SHV-1 occurred in 14 and 16 units and in up to 64 and 26% of the neonates, respectively. On average, two to four different biochemical phenotypes per species per ward were positive for each beta-lactamase. All but 1 of the 33 E. coli phenotypes found to be TEM-1 positive were uniformly positive for the beta-lactamase gene, whereas some of the phenotypes found to be positive for OXA-1 (2 of 3) and SHV-1 (6 of 70) were occasionally negative for the respective genes. The occurrence of the three beta-lactamases studied tended to be associated with local ampicillin usage (correlation coefficient, 0.31 to 0.39; P greater than 0.05). Of the neonates receiving ampicillin, 30% carried TEM-1-positive E. coli, compared with 13% for cephalosporin-treated neonates and 15% for untreated neonates (P less than or equal to 0.001). The corresponding rates for SHV-1 in Klebsiella spp. were 18, 13, and 9% (P less than or equal to 0.01). Ampicillin is thus a significant risk factor for the maintenance of the most prevalent gram-negative plasmid-mediated beta-lactamases in hospitalized neonates.
Gram-negative bacteria are an important cause of invasive infection among neonates. In this study a novel fingerprinting method was used for the first time to assess the importance of various potential reservoirs of the major gram-negative enterobacteria that colonized 46 consecutive infants in three neonatal special care units during a three to four week period. Such bacteria were isolated from the oropharynx, umbilical cord and faeces in 24%, 33% and 100% of the infants, respectively. Klebsiella/Enterobacter spp. dominated over Escherichia coli and spreading (shared) over sporadic strains. Sixty-one percent of the neonates were colonized with at least one and up to six different strains shown to exist in the ward, mainly in other infants. Environmental reservoirs and the faecal flora of mothers and staff were of minor importance. Vertical transmission occurred in 12% of vaginally delivered infants and in 0% of those delivered by caesarean section.
The aerobic faecal flora of 953 infants aged over 5 days was studied on discharge from 22 neonatal wards in Swedish hospitals. Klebsiella/enterobacter was isolated from 74% of infants and dominated the aerobic gram-negative flora in 19 wards. Escherichia coli was carried by 42% and showed a slight dominance in two wards. Initially klebsiella/enterobacter dominated the flora but became increasingly mixed with and taken over by E. coli, carriage increasing from 21% in infants discharged after 5-7 days to 57% after 3 weeks or later. Among infants with E. coli, P-fimbriated strains were demonstrated in 23% (range 0-67) and were independent of age. Occasional clustering of such strains was observed in 3/22 wards during the study period. It is postulated that the general and local colonization patterns observed reflect differences between individual strains of E. coli and klebsiella in both their capacity for transmission and their persistence in the newborn gut. The role of P-fimbriae in intestinal colonization of neonates by E. coli was, however, not supported.
The influence of previous antibiotic therapy on the aerobic faecal flora, including P-fimbriated Escherichia coli, was studied in 953 neonates at discharge from 22 neonatal wards in Sweden. Antibiotics, mainly ampicillin (with or without gentamicin) or cefuroxime, had been received by 37% of the infants. Treatment with ampicillin (with or without gentamicin) increased Klebsiella/Enterobacter and reduced Esch. coli colonization. Cephalosporin therapy (71% cefuroxime) reduced the frequency of colonization with both Esch. coli and Klebsiella/Enterobacter spp. but doubled the isolation rate of other Gram-negative bacteria (Citrobacter, Pseudomonas, Proteus and Acinetobacter spp.) and tripled the incidence of specimens yielding no aerobic Gram-negative growth. Gentamicin showed no significant ecological impact. The selection of Klebsiella/Enterobacter and P-negative Esch. coli strains by ampicillin was correlated with their resistance to this agent, while the association between P-fimbriated Esch. coli and cefuroxime therapy was not related to cefuroxime resistance.
All episodes of Clostridium difficile associated diarrhea (CDAD) diagnosed in a defined population of 274,000 including one tertiary and two primary hospitals and their catchment areas were studied during 12 months. The annual CDAD incidence in the county was 97 primary episodes per 100,000, and 78% of all episodes were classified as hospital associated with a mean incidence of 5.3 (range, 1.4 to 6.5) primary episodes per 1,000 admissions. The incidence among hospitalized individuals was 1,300-fold higher than that in the community (33,700 versus 25 primary episodes per 100,000 persons per year), reflecting a 37-fold difference in antibiotic consumption (477 versus 13 defined daily doses [DDD]/1,000 persons/day) and other risk factors. Three tertiary hospital wards with the highest incidence (13 to 36 per 1,000) had CDAD patients of high age (median age of 80 years versus 70 years for other wards, P