Cronobacter Support
02-19-2009, 06:44 PM
Enterobacter sakazakii kills 40%–80% of infected infants and has been associated with powdered formula. We analyzed 46 cases of invasive infant E. sakazakii infection to define risk factors and guide prevention and treatment. Twelve infants had bacteremia, 33 had meningitis, and 1 had a urinary tract infection. Compared with infants with isolated bacteremia, infants with meningitis had greater birthweight (2,454 g vs. 850 g, p = 0.002) and gestational age (37 weeks vs. 27.8 weeks, p = 0.02), and infection developed at a younger age (6 days vs. 35 days, p<0.001). Among meningitis patients, 11 (33%) had seizures, 7 (21%) had brain abscess, and 14 (42%) died. Twenty-four (92%) of 26 infants with feeding patterns specified were fed powdered formula. Formula samples associated with 15 (68%) of 22 cases yielded E. sakazakii; in 13 cases, clinical and formula strains were indistinguishable. Further clarification of clinical risk factors and improved powdered formula safety is needed.
Enterobacter sakazakii, a gram-negative bacillus, is a rare cause of bloodstream and central nervous system infections (1–8). The organism has also been associated with necrotizing enterocolitis; however, it has not been firmly established as a causative agent (8–10). Reported outcomes are often severe: seizures; brain abscess; hydrocephalus; developmental delay; and death in as many as 40%–80% of cases (11). Premature infants are thought to be at greater risk than more mature infants, other children, or adults, and outbreaks of disease have occurred in hospital units for newborns (1,2,4,6,8–10,12). Infant infections with E. sakazakii have been associated with contaminated powdered formula products, but other environmental sources of contamination are possible (1,3,9,10,13). In this analysis, we attempt to more clearly define the host risk factors and disease course to refine prevention and treatment efforts.
Methods
We reviewed the literature for reports of E. sakazakii disease in infants. Using medical subject heading terms "E. sakazakii" or "Enterobacter" in combination with "newborn," "infant," or "meningitis," we searched PubMed and examined the bibliographies of resulting articles. Finally, we reviewed E. sakazakii case consultations conducted by the Centers for Disease Control and Prevention (CDC) from 1998 to 2005 and reviewed results of a French outbreak reported to CDC in 2005 (14).
We defined a case as an infant (<12 months of age) with E. sakazakii cultured from an area of the body that is normally sterile: tissue, blood, cerebrospinal fluid, or urine aspirated through the bladder wall. Infants with cultures of cerebrospinal fluid or brain abscesses yielding E. sakazakii were considered to have meningitis. Because bacteremia is usually an intermediate step during the process of developing meningitis, patients with both bacteremia and meningitis were included in the meningitis group. Bacteremia was defined as E. sakazakii grown from the blood of a case-patient without evidence of meningitis.
Infants with gestational ages <37 weeks, or those reported to be premature, were considered premature. A gestational age of 40 weeks was assigned to 3 (27%) of 11 infants with bacteremia and 4 (14%) of 28 infants with meningitis who were reported as born following term gestation without a specific gestational age mentioned. We defined birthweight <2,500 g as low birthweight (LBW), <1,500 g as very low birthweight (VLBW), and <1,000 g as extremely low birthweight (ELBW).
Descriptive analysis was performed by using SAS software (SAS Institute, Cary, NC, USA). Groups were compared by using 2-tailed Fisher exact test.
Results
Forty-six infants met the case definition (Table 1). Reported onset years ranged from 1958 to 2005; 32 (70%) cases were reported during the second half of this period. Cases were reported in 7 countries in North America, Europe, and the Middle East. Thirty-three (72%) infants had meningitis, 12 (26%) had bacteremia, and 1 (2%) had a urinary tract infection.
Clinical characteristics were available for a subset of cases (Table 2). Eight (40%) of 20 infants for whom data were available were delivered by cesarean section. Twenty-nine (69%) of 42 infants experienced disease onset within a hospital. Gestational duration was available for 38 infants; 21 (55%) were born prematurely, and the median gestational age overall was 36 weeks (range 23.5–40 weeks). The median birthweight was 2,063 g (range 540–3,401); 18 (56%) of 32 infants had LBW; 9 (28%) of these met the definition for VLBW, and 7 (22%) met the definition for ELBW. Median age at the time of infection onset was 8.5 days (range 2–300).
Figure
http://www.cdc.gov/ncidod/EID/vol12no08/images/05-1509_t.gif
Figure. Box plot with each box indicating range (vertical lines), first and third quartiles (lower and upper boundaries of box, respectively), and median value...
Although the proportion of infants who experienced nosocomial disease onset was not significantly different between the meningitis and bacteremia groups, other infant characteristics differed by site of infection (Figure). The median gestational ages of infants with meningitis and bacteremia were 37 and 27.8 weeks, respectively (p = 0.02). Median birthweights were 2,454 g and 850 g, respectively (p = 0.002). However, median age at infection onset was 6 days in the group with meningitis and 35 days in the group with bacteremia (p < 0.0001). Thirty (94%) of 32 infants with meningitis, but only 2 (18%) of 11 infants with bacteremia, were <28 days old when infection was detected. One infant (8%) with bacteremia died; this infant also had necrotizing enterocolitis. The single infant with a urinary tract infection recovered without complication. In contrast, 14 (42%) of 33 infants with meningitis died. Of 19 surviving infants, only those with meningitis suffered adverse outcomes, including brain abscess (21%, p = 0.2), developmental delays (53%, p = 0.004), motor impairment (21%, p = 0.3), and ventricular shunt placement (42%, p = 0.01); 74% experienced at least one of these outcomes.
Feeding practices were described for 26 infants. Twenty-four (92%) received a powdered formula product, including an infant who received powdered breast milk fortifier but no powdered infant formula; 1 additional infant received formula of an unspecified type. E. sakazakii was cultured from formula associated with 15 (68%) of 22 cases investigated. Isolates were obtained from prepared formula, opened formula tins, and previously unopened formula tins associated with 2, 6, and 7 cases, respectively. Thirteen (87%) of the 15 formula isolates were indistinguishable from the corresponding clinical strain by biotype or genotype; multiple formula manufacturers were implicated. In one of the remaining cases, multiple E. sakazakii strains were recovered from powdered formula, but none matched the clinical isolate by pulsed-field gel electrophoresis (CDC, unpub. data). In the other case, 2 E. sakazakii strains were isolated from blood and from rectal swabs; a third strain, as determined by arbitrarily primed PCR, was recovered from the powdered infant formula (9).
Continued...
Bowen AB, Braden CR. Invasive Enterobacter sakazakii disease in infants. Emerg Infect Dis [serial on the Internet]. 2006 Aug publication [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no08/05-1509.htm
Enterobacter sakazakii, a gram-negative bacillus, is a rare cause of bloodstream and central nervous system infections (1–8). The organism has also been associated with necrotizing enterocolitis; however, it has not been firmly established as a causative agent (8–10). Reported outcomes are often severe: seizures; brain abscess; hydrocephalus; developmental delay; and death in as many as 40%–80% of cases (11). Premature infants are thought to be at greater risk than more mature infants, other children, or adults, and outbreaks of disease have occurred in hospital units for newborns (1,2,4,6,8–10,12). Infant infections with E. sakazakii have been associated with contaminated powdered formula products, but other environmental sources of contamination are possible (1,3,9,10,13). In this analysis, we attempt to more clearly define the host risk factors and disease course to refine prevention and treatment efforts.
Methods
We reviewed the literature for reports of E. sakazakii disease in infants. Using medical subject heading terms "E. sakazakii" or "Enterobacter" in combination with "newborn," "infant," or "meningitis," we searched PubMed and examined the bibliographies of resulting articles. Finally, we reviewed E. sakazakii case consultations conducted by the Centers for Disease Control and Prevention (CDC) from 1998 to 2005 and reviewed results of a French outbreak reported to CDC in 2005 (14).
We defined a case as an infant (<12 months of age) with E. sakazakii cultured from an area of the body that is normally sterile: tissue, blood, cerebrospinal fluid, or urine aspirated through the bladder wall. Infants with cultures of cerebrospinal fluid or brain abscesses yielding E. sakazakii were considered to have meningitis. Because bacteremia is usually an intermediate step during the process of developing meningitis, patients with both bacteremia and meningitis were included in the meningitis group. Bacteremia was defined as E. sakazakii grown from the blood of a case-patient without evidence of meningitis.
Infants with gestational ages <37 weeks, or those reported to be premature, were considered premature. A gestational age of 40 weeks was assigned to 3 (27%) of 11 infants with bacteremia and 4 (14%) of 28 infants with meningitis who were reported as born following term gestation without a specific gestational age mentioned. We defined birthweight <2,500 g as low birthweight (LBW), <1,500 g as very low birthweight (VLBW), and <1,000 g as extremely low birthweight (ELBW).
Descriptive analysis was performed by using SAS software (SAS Institute, Cary, NC, USA). Groups were compared by using 2-tailed Fisher exact test.
Results
Forty-six infants met the case definition (Table 1). Reported onset years ranged from 1958 to 2005; 32 (70%) cases were reported during the second half of this period. Cases were reported in 7 countries in North America, Europe, and the Middle East. Thirty-three (72%) infants had meningitis, 12 (26%) had bacteremia, and 1 (2%) had a urinary tract infection.
Clinical characteristics were available for a subset of cases (Table 2). Eight (40%) of 20 infants for whom data were available were delivered by cesarean section. Twenty-nine (69%) of 42 infants experienced disease onset within a hospital. Gestational duration was available for 38 infants; 21 (55%) were born prematurely, and the median gestational age overall was 36 weeks (range 23.5–40 weeks). The median birthweight was 2,063 g (range 540–3,401); 18 (56%) of 32 infants had LBW; 9 (28%) of these met the definition for VLBW, and 7 (22%) met the definition for ELBW. Median age at the time of infection onset was 8.5 days (range 2–300).
Figure
http://www.cdc.gov/ncidod/EID/vol12no08/images/05-1509_t.gif
Figure. Box plot with each box indicating range (vertical lines), first and third quartiles (lower and upper boundaries of box, respectively), and median value...
Although the proportion of infants who experienced nosocomial disease onset was not significantly different between the meningitis and bacteremia groups, other infant characteristics differed by site of infection (Figure). The median gestational ages of infants with meningitis and bacteremia were 37 and 27.8 weeks, respectively (p = 0.02). Median birthweights were 2,454 g and 850 g, respectively (p = 0.002). However, median age at infection onset was 6 days in the group with meningitis and 35 days in the group with bacteremia (p < 0.0001). Thirty (94%) of 32 infants with meningitis, but only 2 (18%) of 11 infants with bacteremia, were <28 days old when infection was detected. One infant (8%) with bacteremia died; this infant also had necrotizing enterocolitis. The single infant with a urinary tract infection recovered without complication. In contrast, 14 (42%) of 33 infants with meningitis died. Of 19 surviving infants, only those with meningitis suffered adverse outcomes, including brain abscess (21%, p = 0.2), developmental delays (53%, p = 0.004), motor impairment (21%, p = 0.3), and ventricular shunt placement (42%, p = 0.01); 74% experienced at least one of these outcomes.
Feeding practices were described for 26 infants. Twenty-four (92%) received a powdered formula product, including an infant who received powdered breast milk fortifier but no powdered infant formula; 1 additional infant received formula of an unspecified type. E. sakazakii was cultured from formula associated with 15 (68%) of 22 cases investigated. Isolates were obtained from prepared formula, opened formula tins, and previously unopened formula tins associated with 2, 6, and 7 cases, respectively. Thirteen (87%) of the 15 formula isolates were indistinguishable from the corresponding clinical strain by biotype or genotype; multiple formula manufacturers were implicated. In one of the remaining cases, multiple E. sakazakii strains were recovered from powdered formula, but none matched the clinical isolate by pulsed-field gel electrophoresis (CDC, unpub. data). In the other case, 2 E. sakazakii strains were isolated from blood and from rectal swabs; a third strain, as determined by arbitrarily primed PCR, was recovered from the powdered infant formula (9).
Continued...
Bowen AB, Braden CR. Invasive Enterobacter sakazakii disease in infants. Emerg Infect Dis [serial on the Internet]. 2006 Aug publication [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no08/05-1509.htm