A total of 358 newborns were admitted to the NICU during the study period. Of these, 294 neonates were analysed and 64 were excluded due to lack of data. There was a slight predominance of males (58.2%) and most neonates (94.2%) were inborn with a total of 61.6% c-section deliveries.
The median gestational age was 35 weeks (interquartile range [IQR] 32–38 weeks) with a prematurity rate of 61.2%, 8.2% being extremely preterm. The median birth weight was 2175 grams (IQR 1498.8 g–3090 g). The median length of stay in the NICU was 9.5 days (minimum 0 days, maximum 110 days). Half of the infants (50.3%) needed at least 1 central line during hospital stay - umbilical venous catheter (n = 141), umbilical arterial catheter (n = 21), epicutaneo-caval catheter (n = 70), femoral vein catheter (n = 1) and internal jugular vein catheter (n = 1). In 68 infants (23.1%), invasive mechanical ventilation was needed, for a median of 2.5 days (minimum 1 day, maximum 51 days) and in 145 infants (58.7%), antibiotics were administered on admission for a median of 5 days (minimum 1 day, maximum 14 days). Enteric feeding was started, on average, on day 1.6 of life with MOM (57.5%).
Regarding maternal data, 32.8% of mothers received antibiotics prior to childbirth and its main indications were confirmed or highly suspected maternal infection (31.5%), preterm premature rupture of membranes (31.5%) and group B Streptococcus (GBS) colonization (15.7%). The most common antibiotic administered was ampicillin, either in monotherapy (37.1%) or in association with other antibiotics, such as erythromycin (18.0%), gentamicin (7.9%) and clarithromycin (4.5%). Over one-fifth of the mothers (21.8%) were admitted more than 1 week prior to childbirth. Most frequent hospital admission causes were risk of preterm birth (28.8%), preeclampsia/HELLP syndrome (17.0%), preterm premature rupture of membranes (15.3%), vaginal bleeding (11.9%) and intrauterine growth restriction (8.5%).
During the study period, 896 nasal swabs and 1637 rectal swabs were performed. A total of 83 infants (28.2%) were colonized during hospital stay (group A). From the 83 colonized neonates, 73.5% were colonized by 1 MDRB, 20.5% by 2 MDRB and 6% by 3 (Table 1). Regarding the neonates colonized with 1 agent, the most frequent MDR colonization agent was ESBL-producing Enterobacteriaceae (n = 27), followed by MRSA (n = 15), Serratia marcescens (n = 15) and CPE (n = 4). In the neonates colonized by more than 1 MDR organism, the most frequent association was ESBL-producing Enterobacteriaceae and MRSA colonization (n = 8). The most frequent overall MDR colonization agent was ESBL-producing Enterobacteriaceae (n = 48), followed by MRSA (n = 28), Serratia marcescens (n = 21) and CPE (n = 9).
Table 1
Group A: distribution of MDR colonization agents.
Category
|
n
|
Colonized with 1 agent
|
61
|
MRSA
|
15
|
ESBL-producing Enterobacteriaceae
|
27
|
CPE
|
4
|
Serratia marcescens
|
15
|
Colonized with 2 agents
|
17
|
ESBL-producing Enterobacteriaceae + MRSA
|
8
|
ESBL-producing Enterobacteriaceae + Serratia marcescens
|
4
|
ESBL-producing Enterobacteriaceae + CPE
|
4
|
MRSA + Serratia marcescens
|
1
|
Colonized with 3 agents
|
5
|
ESBL-producing Enterobacteriaceae + MRSA + S. marcescens
|
4
|
ESBL-producing Enterobacteriaceae + CPE + S. marcescens
|
1
|
Median time from admission to colonization was 10 days (minimum 0 days, maximum 50 days).
Among the colonized neonates, 12% were colonized upon admission in the NICU. In this subgroup, median time between birth and admission in the NICU was 1 day (minimum 0 days, maximum 5 days). The most frequent MDR colonization agent was ESBL-producing Enterobacteriaceae (n = 8), followed by MRSA (n = 1), Serratia marcescens (n = 1) and CPE (n = 1).
Their median gestational age and mean birth weight were respectively 37.5 weeks (IQR 37–38.75 weeks) and 2907.5 grams (IQR 2637.5–3416.25 g). Most (60%) were born by vaginal birth, 90% were inborn and initially admitted with their mothers in the obstetric ward. Only 1 (10%) was born at home and later admitted in the NICU in the first 24h of life. None of these neonates were, subsequently, infected.
When comparing groups A (colonized infants) and B (non-colonized infants), colonized infants had a lower gestational age (median of 31 vs. 36 weeks, p < 0.001) and a lower birth weight (median of 1490g vs. 2445g, p < 0.001), versus non-colonized ones. Also, colonized infants were more likely to be born via caesarean delivery (69.9% vs. 58.3%, p = 0.660) and had a longer hospitalization in the NICU (median of 31 vs. 6 days, p < 0.001). Mothers of group A infants were more likely to have received antibiotics (39.8% vs. 31.8%, p = 0.235) and to have been admitted, at least, 1 week prior to delivery (34.9% vs. 19.4%, p = 0.009).
Upon admission to the NICU, most group A infants received antibiotic therapy (68.7% vs. 41.7%, p < 0.001); were more likely to have been submitted to invasive ventilation (39.8% vs. 16.6%, p < 0.001) and to have had a central line (78.3% vs. 39.3%, p < 0.001). Enteric feeding was started later in group A infants (mean 2.2 vs. 1.3 days). In both groups, most newborns started with MOM (group A 66.3% vs. group B 54.0%, p = 0.056).
In Table 2 we display the frequency of colonized and non-colonized newborns, with or without symptomatic infection.
Colonized infants were further divided into colonized-only and colonized and infected for analysis. Among the colonized infants, 31.3% (26/83) developed LOS and it occurred at a median of 9 days of live. During hospital stay, 30 episodes of LOS were diagnosed in 26 infected infants (4 patients had 2 episodes of LOS). In 13 of them, the agent was the same as the colonization agent. Therefore, in total, 13 colonized infants developed a LOS concordant with the colonizing pathogen (15.7%) (Table 3).
Table 2
Distribution of the infants of our cohort, according to their colonization and infection status.
Category
|
n
|
Total number of patients screened
|
294
|
Colonized infants (Group A)
|
83
|
Without infection
|
57
|
With infection
|
26
|
Non-colonized infants (Group B)
|
211
|
With infection
|
11
|
Without infection
|
200
|
Table 3
Frequency of organisms causing LOS in group A infants.
MDR organism
|
n
|
Klebsiella pneumoniae ESBL
|
8
|
Staphylococcus haemolyticus MR
|
6
|
Staphylococcus capitis MR
|
5
|
MRSA
|
3
|
Serratia marcescens
|
2
|
Staphylococcus epidermidis
|
1
|
Staphylococcus warneri MR
|
1
|
Non-isolated agent
|
4
|
Amongst the colonized infants, when comparing the infected and the non-infected infants, we found that they had a lower gestational age (median of 28 vs. 33 weeks, p < 0.001), a lower birth weight (942.5g vs. 1680g, p < 0.001), and a longer hospitalization (54.5 vs. 25 days, p < 0.001). Furthermore, they were more likely to be born via cesarean delivery (76.9% vs. 66.7%, p = 0.345) and their mothers were more likely to have received antibiotics (46.2% vs. 36.8%, p = 0.457) and to have been admitted, at least, 1 week prior to delivery (38.5% vs. 33.3%, p = 0.649). Colonized and infected infants were also more likely to have been submitted to invasive ventilation (69.2% vs. 26.3%, p < 0.001) and to have had a central line (100% vs. 68.4%, p = 0.001). These infants started enteral feeding on average on day 3.3 of life, in contrast with the non-infected ones, who started on day 1.8. Enteric feeding was started with MOM in most newborns of both subgroups (88.5% in colonized and infected and 57.9% in colonized non-infected newborns).
When comparing the volume of ingested MOM between the colonized-only vs. the colonized and infected infants, we found that: 1) at the time of sepsis, 80.8% of the colonized and infected infants’ intake was with, at least, 50% of MOM; 2) 61.4% of colonized-only infants at day 9 of life or at discharge if length of stay didn’t last that long, had, at least, 50% of MOM comprising total fluid intake (80.8% vs. 61.4%, p = 0.81).
Regarding the whole cohort, 11 infants (3.7%) died at the NICU. During hospital stay, 8 infants died from LOS, 3 being colonized by the same MDR pathogen responsible for sepsis (Klebsiella pneumoniae ESBL n = 2 and Serratia marcescens n = 1); 1 died from multiorgan failure in the context of symptomatic congenital syphilis. The remaining 2 infants died in their first 72 hours of life, non-colonized and with early-onset sepsis. Mortality rate was similar between groups A and B.