Late-onset neonatal sepsis (LOS) remains an important cause of death, morbidity and long-term complications among premature infants, which are associated with prolonged hospital stay and increased health-care costs.1 It is of great interest to know the incidence and the strategies that are effective for preventing LOS in neonatal intensive care units (NICUs).2–4

The most common infections seen in neonates are central line-associated bloodstream infections (CA-BSIs), which substantially contribute to the burden and cost of neonatal care.5 One proposed approach to achieve low CA-BSI rates is implementation of catheter care bundles.6

Besides the classic risk factors for LOS, neonates requiring intensive care in developing countries are at high risk due to structural factors such as overcrowding, shortages of nursing and medical staff, lack or improper use of basic supplies and equipment, excessive use of antibiotics, insufficient knowledge and difficulties in the implementation of infection control practices.7–9

The aim of this study was to evaluate the changes in LOS incidence rates in a reference NICU at a Brazilian hospital considering different time periods: staff vacation period, relocation of the unit to a temporary site, and the effect of implementation of an evidence based care bundle.

Out of 551 neonates admitted in the NICU during the study period, 112 neonates developed sepsis (20.3%) with a total of 178 episodes (32.3%); 139 (25.2%) was defined as LOS and only 38 (6.8%) as early onset sepsis (EOS). For LOS, 76.9% (107/139) of episodes had late positive blood culture (Table 1). The overall incidence rate of LOS in the study was 16.1/1000 patient-days and 23.0/1000 CVC-days. The mean length of stay was 18.8 days and CVC utilization density rate was 0.7. Univariate and multivariate analyses of potential risk factors for LOS are displayed in Table 2. Overall, gestational age<37 weeks (p=0.01) birth weight<1500g (p=0.001), use of CVC (p<0.001), parenteral nutrition (p<0.001), and mechanical ventilation (p<0.001) were risk factors for LOS in univariate analysis. The following risk factors remained independently associated with LOS: use of CVC (p<0.001), parenteral nutrition (p=0.05), and mechanical ventilation (p<0.001) (Table 2). Our data have shown that 66.3% (71/107) of LOS were caused by Gram-positive cocci, 25.1% (27/107) by Gram-negative bacilli, and 8.4% (9/107) by Candida sp. Staphylococcus epidermidis was the most frequent agent (37.9%), followed by Staphylococcus aureus (12.9%). Among Gram-negative bacilli, Klebsiella pneumoniae was the most frequent (8.3%). The pathogens isolated from LOS are shown in Table 3.

Our monthly rates of LOS/1000 patient-days reveal fluctuations over the study period (Fig. 1), with incidence rates of these infections during staff vacation periods (January 2011 and 2012) significantly higher (59.6/1000 patient-days) when compared with rates during other months (16.6/1000 patient-days) [IRR=3.59; p<0.001]. In contrast, the incidence rates of LOS during the relocation period were lower (10.3/1000 patient-days) when compared with rates of the baseline period (26.7/1000 patient-days) [IRR=2.59; p=0.007]. Table 4 shows that post-intervention rates (14.7/1000 patients-days) decreased in relation to pre-intervention rates (23.4/1000 patient-days) [IRR=1.59; p=0.04]. Nonetheless, there was no significant difference in gestational age, SNAPPE-II score, low birth weight, and APGAR<5 at five minutes, in all these periods.

Fig. 1.

Monthly rates of late onset-sepsis per 1000 patient-days and per 1000 CVC-days from October 2010 to August 2012. LOS, late-onset sepsis; UAL, upper alert limit; UCL, upper control limit.

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The present study demonstrates that through infection control measures, LOS can be successfully controlled temporally, even in a NICU with high endemic levels of S. epidermidis. Although the overall incidence of LOS in our NICU was higher than rates reported in developed countries12 they are similar to rates reported in developing countries including other settings in Brazil.13,14

Our approach placed great emphasis and value on local context, considering that the technical intervention on CVC insertion reduces infection rates, its introduction and application reflect the different conditions among staff of each NICU.

The main aim of this study was to evaluate the effectiveness of a care bundle designed to reduce LOS in the unit. Over the surveillance period, we identified two events that significantly increased and reduced, respectively, the rates of LOS: staff vacations (months of January) and the unit relocation to a temporary nursery. According to literature, there is an association between nurse staffing and outcome of healthcare-associated infections in infants. Ensuring that staff receives infection control training is important to guarantee that the NICU is adequately staffed.15,16 In the months of January there was less trained nurse staff in the unit, due to their vacation period, with a subsequent increase of bloodstream infections rates. We hypothesize that inadequate nurse staffing and increased workload in an intensive care unit, can result in low hand-hygiene compliance, breaks in aseptic technique, or compromises in practice that might increase the risk of infection. Other studies from western countries have demonstrated a direct link between staffing levels and infection rates in NICUs, mainly due shortage of trained healthcare workers.16,17

It should also be pointed out the decrease of infection rates observed in this study when the unit was transferred to an improvised area, probably because of more isolation facilities, more space per cot, and enforcement of hand washing compliance during in that temporary place. These aspects have also been shown in other studies with impact on infection rates.18,19

Despite some unexpected events during the study period, we could demonstrate an important reduction in LOS rate among the neonates after a sustained effort in February 2012 that were maintained at lower rates over five months, probably due the implementation of the bundle. Our results are consistent with previous reports showing reductions in overall NI multifaceted interventions, and especially those related to central lines.20,21 We have shown that specific education and a protocol adopting the recommended procedures for CVC insertion and care besides feedback to healthcare workers (HCWs) can result in significant reduction of CA-BSI rates. In our NICU, earlier approach by our team, using simple and inexpensive intervention to increase compliance with evidence-based infection control practices, decrease CA-BSI rates.4 After implementation of these measures, the overall CA-BSI rate declined from 32% to 19.6%, and from 37.3% to 15.2% in low birth weight neonates.

All these strategies described so far were based on our findings from the surveillance study that detected high incidence of LOS in the unit associated to S. epidermidis, a major causative agent of these infections in our NICU. From our data it was possible to design a case–control study to detect the main risk factors associates to LOS in critical neonates. Thus, in this report the multivariate analysis identified low birth weight, length of stay in the unit >7 days, use of CVC, mechanical ventilation, and parenteral nutrition as independent risk factors for BSI, similar to those found in other studies.22,23 The central venous catheters and low birth weight placed infants at a higher risk of developing LOS, as has been shown in other studies.22

The organisms causing neonatal infections often differ from one place to another and may change over time within the same setting. In this study most of LOS was microbiologically confirmed, and S. epidermidis was identified as a major cause of LOS in the unit. Gram-positive bacteria, particularly coagulase negative Staphylococci, are the most common cause of LOS in many industrialized as well as in some developing countries.24 Gram-negative bacillary and Candida infections have become another major cause of neonatal sepsis, as seen in our study when around one-fourth of the episodes were caused by BGN, mainly K. pneumoniae, with a high case fatality and long-term complications.14,25

Our study has several limitations. First, we had two main events, summer outbreaks and unit relocation that interfered in the analysis of the baseline period of intervention. Second, we were not able to ensure the adoption of the checklist to achieve stable compliance in order to evaluate the real adherence and ascertain the full impact of the bundle. Third, our study was performed at a single unit, although representative of Brazilian teaching hospitals, but the results may not be applicable to other units. Finally, both the intervention and post-intervention periods has lasted only one and six months, respectively, and efforts of short duration may not be as successful as years of sustained strategies reduce LOS.

In conclusion, the incidence of LOS in our NICU is high, in both overall as well as in low birth weight neonates, reflecting the situation in resource-poor countries and show that application of evidence-based practices can lead to significant reduction in LOS rate. Additionally, the analysis of trends over a period of 22 months showed an increase of LOS rates during staff vacation months and a reduction of LOS rates during the relocation of the unit. Finally, these infections are preventable, and their elimination presents an opportunity to improve patient outcomes and reduce costs in the unit. Lessons learned about the importance and feasibility of an individualized local approach on specific techniques to decrease CA-BSI as evidenced in our proposed bundle that describes simple and inexpensive practices that lead to the reduction of these infections in the NICU.

The authors declare no conflicts of interest.