Late-onset Bacterial Infection Research Articles

Association between Congenital Anomalies and Late-Onset Bacterial Infections in Neonates Admitted to Neonatal Intensive Care Units in Australia and New Zealand: A Population-Based Cohort Study

Introduction: Compromised neonatal intensive care unit neonates are at risk of acquiring late-onset infections (late-onset sepsis [LOS]). Neonates born with congenital anomalies (CAs) could have an additional LOS risk. Methods: Utilising the population-based Australian and New Zealand Neonatal Network data from 2007 to 2017, bacterial LOS rates were determined in very preterm (VPT, <32 week), moderately preterm (MPT, 32–36 weeks), and term (FT, 37–41 weeks) neonates with or without CA. Stratified by major surgery, the association between CA and bacterial LOS was evaluated. Results: Of 102,808 neonates, 37.7%, 32.8%, and 29.6% were born VPT, MPT, and FT, respectively. Among these, 3.4% VPT, 7.5% MPT, and 16.2% FT neonates had CA. VPT neonates had the highest LOS rate (11.1%), compared to MPT (1.8%) and FT (1.8%) neonates. LOS rates were higher in CA neonates than those without (8.2% versus 5.1% adjusted relative risk [aRR] 1.67, 95% confidence interval [CI]: 1.45–1.92). Neonates with surgery had a higher LOS rate (14.2%) than neonates without surgery (4.4%, p < 0.001). Among the neonates without surgery, CA neonates had consistently higher LOS rates than those without CA (VPT 14.3% vs. 9.6% [aRR 1.32, 95% CI: 1.11–1.57]; MPT 4% vs. 0.9% [aRR 4.45, 95% CI: 3.23–6.14]; and FT 2% vs. 0.7% [aRR 2.87, 95% CI: 1.97–4.18]). For the neonates with surgery, CAs were not associated with additional LOS risks. Conclusion: Overall, we reported higher rates of LOS in neonates with CA compared to those without CA. Regardless of gestation, CA was associated with an increased LOS risk among non-surgical neonates. Optimisation of infection prevention strategies for CA neonates should be explored. Future studies are needed to evaluate if the infection risk is caused by CA or associated complications.

Efficacy of periodic surveillance culture in a neonatal intensive care unit in the presumption of causative pathogens of late-onset bacterial infection.

Surveillance cultures have been recommended for infection control of resistant bacteria in neonatal intensive care units (NICUs). However, the utility of surveillance cultures in the presumption of causative bacteria in late-onset bacterial infection has been controversial. The aim of the present study was to investigate the relationship between the causative pathogens of late-onset bacterial infection and the results of periodic surveillance cultures in a NICU. A retrospective study was performed on 600 patients hospitalized in the NICU of a large metropolitan hospital from 2010-2013. The correspondence of the results of surveillance cultures with causative pathogens was analyzed in patients who developed late-onset bacterial infection. Staphylococcus species and enterobacterium were the most prevalent in the samples obtained from the oropharynx and rectum, respectively, during the investigation period. Twenty patients (3.3%) developed late-onset bacterial infection. The causative pathogens in 15 patients (75%) were also detected from the final surveillance cultures; these patients tended to be older than the other 5 patients (P = .003). Surveillance cultures might be useful for the presumption of causative pathogens of late-onset bacterial infection in patients with risk factors for the development of nosocomial bacterial infection.

Symptomatic Postnatal Cytomegalovirus Testing among Very Low-Birth-Weight Infants: Indications and Outcomes.

Objective The objective of this study was to describe the indications for postnatal cytomegalovirus (CMV) testing among very low-birth-weight (VLBW, birth weight [BW] < 1,500 g) infants, clinical characteristics of infected infants, and adverse outcomes associated with CMV infection. Study Design This is a single-center, retrospective study of 2,132 VLBW infants from 1999 to 2013. Results In this study, 145 (6.8%) infants out of 2,132 were evaluated for postnatal CMV infection and 27 (18.6%) infants out of 145 were infected. CMV-tested infants were of significantly lower gestational age and BW compared with untested VLBW infants (p < 0.001). Respiratory decompensation and thrombocytopenia were the findings most commonly associated with infection. CMV-infected infants had significantly more exposure to mechanical ventilation and longer duration of hospitalization. Adjusting for multiple predictors of respiratory morbidity, the incidence of bronchopulmonary dysplasia (BPD) was significantly elevated among infants diagnosed with postnatal CMV infection (odds ratio, 4.0 [95% confidence interval, 1.3-12.4); p, 0.02.) Conclusion Symptomatic postnatal CMV infection was diagnosed in 1.3% of VLBW infants, most commonly among infants with BW < 1,000 g with respiratory instability and thrombocytopenia. Similar to late-onset bacterial infection, symptomatic postnatal CMV infection may be an independent contributor to the development of BPD. This possibility should be addressed in a prospective study of extremely low BW infants.

Age-specific percentile-based reference curve of serum procalcitonin concentrations in Japanese preterm infants.

Procalcitonin (PCT) levels are elevated early after birth in newborn infants; however, the physiological features and reference of serum PCT concentrations have not been fully studied in preterm infants. The aims of the current study were to establish an age-specific percentile-based reference curve of serum PCT concentrations in preterm infants and determine the features. The PCT concentration peaked in infants at 1 day old and decreased thereafter. At 1 day old, serum PCT concentrations in preterm infants <34 weeks’ gestational age were higher than those in late preterm infants between 34 and 36 weeks’ gestational age or term infants ≥37 weeks’ gestational age. Although the 50-percentile value in late preterm and term infants reached the adult normal level (0.1 ng/mL) at 5 days old, it did not in preterm infants. It took 9 weeks for preterm infants to reach it. Serum PCT concentrations at onset in late-onset infected preterm infants were over the 95-percentile value. We showed that the physiological feature in preterm infants was significantly different from that in late preterm infants, even in those <37 weeks’ gestational age. To detect late-onset bacterial infection and sepsis, an age-specific percentile-based reference curve may be useful in preterm infants.

Diagnostic Value of an Interleukin-6 Bedside Test in Term and Preterm Neonates at the Time of Clinical Suspicion of Early- and Late-Onset Bacterial Infection

Background: For quick detection or exclusion of neonatal early-onset bacterial infection (EOBI) or late-onset bacterial infection (LOBI), interleukin (IL)-6 is used. Its clinical use is sometimes limited due to prolonged recall times. Therefore, an IL-6 bedside test was established. Objective: To compare the diagnostic value of plasma IL-6 and an IL-6 bedside test at the time of clinical suspicion in the course of EOBI and LOBI. Methods: Eighteen term (mean gestational age 40.2 weeks, SD 1.3) and 88 preterm (mean gestational age 30.1 weeks, SD 4.2) neonates with clinical and serological signs of bacterial infection were analysed. Eight had an EOBI, and 24 had a LOBI, of whom 13 were blood culture positive. Twelve term and 62 preterm neonates with risk factors but without proven EOBI/LOBI served as a non-infected group. Results: At the time of clinical suspicion, the sensitivity of the IL-6 bedside test in comparison to plasma IL-6 was 69 versus 75% (p = 0.7744, McNemar’s test), and specificity was 77 versus 81% (p = 0.6476, McNemar’s test; cutoff level 50 ng/l). For LOBI, both the sensitivity (75%) and specificity (82%) of the bedside test exceeded values calculated for EOBI (sensitivity 50%, specificity 75%). Conclusion: No significant difference between the bedside and established plasma IL-6 test was detected for LOBI. For detection of EOBI, the bedside test was not sensitive enough. Larger studies are needed to verify our findings before IL-6 bedside tests can be recommended routinely.

Very late onset infections in the neonatal intensive care unit

ObjectiveWe sought to determine the risk factors, incidence, and mortality of very late onset bacterial infection (blood, urine, or cerebrospinal fluid culture positive occurring after day of life 120) in preterm infants. Study designA retrospective observational cohort study of all very low birth weight infants cared for between day of life 120 and 365 in 292 neonatal intensive care units in the United States from 1997 to 2008. ResultsWe identified 3918 infants who were hospitalized beyond 120days of life. Of these, 1027 (26%) were evaluated with at least 1 culture (blood, urine, or cerebrospinal fluid), and 276 (27%) of the evaluated infants had 414 episodes of culture-positive infection. Gram-positive organisms caused most of the infections (48%). The risk of death was higher in infants with positive cultures (odds ratio; 10.5, 95% confidence interval [7.2–15.5]) or negative cultures (4.8, [3.5–6.7]) compared to infants that were never evaluated with a culture (p<0.001). Mortality was highest with fungal infections (8/24, 33%) followed by Gram-positive cocci (40/142, 28%). ConclusionsImportant predictive risk factors for early and late onset sepsis (birth weight and gestational age) did not contribute to risk of developing very late onset infection. Evaluation for infection (whether positive or negative) was a significant risk factor for death. GPC and fungal infections were associated with high mortality.

Procalcitonin and valuable clinical symptoms in the early detection of neonatal late‐onset bacterial infection

To evaluate which clinical symptoms indicate proven neonatal bacterial infection (NBI) and whether measuring procalcitonin aside from C-reactive protein and interleukin 6 improves sensitivity and specificity in diagnosis. In a prospective observational study, clinical symptoms and procalcitonin, C-reactive protein and interleukin 6 were simultaneously determined from the 4th day of life in 170 preterm and term neonates at the first time of suspicion of NBI. Proven NBI was defined as a positive culture of otherwise sterile body fluids or radiologically verified pneumonia in combination with elevated inflammatory markers. Fifty-eight (34%) patients were diagnosed with proven late-onset NBI. In case of proven NBI, odds ratio and 95% confidence intervals were 2.64 (1.06-6.54) for arterial hypotension, 5.16 (2.55-10.43) for feeding intolerance and 9.18 (4.10-20.59) for prolonged capillary refill. Sensitivity of combined determination of C-reactive protein (>10 mg/L) and interleukin 6 (>100 pg/mL) was 91.4%, specificity 80.4%, positive predictive value 70.7% and negative predictive value 94.7%. The additional determination of procalcitonin (>0.7 ng/mL) resulted in 98.3%, 65.2%, 58.8% and 98.6%, respectively. Arterial hypotension, feeding intolerance and especially prolonged capillary refill indicate proven neonatal late-onset bacterial infection, even at the time of first suspicion. Additional measurement of procalcitonin does indeed improve sensitivity to nearly 100%, but is linked to a decline in specificity. Nevertheless, in the high-risk neonatal population, additional procalcitonin measurement can be recommended because all infants with NBI have to be identified.

Quality Transformation Efforts: No Quick Fixes

The authors of 3 articles in this issue of Pediatrics describe the impact of efforts to improve the quality of neonatal care across multiple institutions.1,–,3 Each article reports improved neonatal outcomes, namely reductions in neonatal infections, late-onset bacterial infections, and central-line–associated bloodstream infections, respectively. All 3 projects were “success stories.” Examined together, however, an intriguing aspect is the varying methodologies used to educate and instill reliable behavior change in participating providers and the resulting varying degrees of outcome improvement. Wirtschafter et al1 studied 27 participant institutions, compared with 27 control institutions, at which participant status meant that staff member(s) participated in at least 1 workshop or Webcast to learn about best practices and how to implement them. Toolkits that clearly defined best practices were freely available to both participant and control institutions. All institutions reported their neonatal infection rates as the main study outcome for a 2-year evaluation period; data on compliance with best practices were not assessed. Kaplan et al2 evaluated 24 institutions that participated in 3 day-long learning sessions and monthly Webinars to educate on best … Address correspondence to Marlene R. Miller, MD, MSc, Departments of Pediatrics and Health Policy and Management, Johns Hopkins University, 200 N Wolfe St, Room 2094, Baltimore, MD, 21287. E-mail: mmille21{at}jhmi.edu

Ohio Statewide Quality-Improvement Collaborative to Reduce Late-Onset Sepsis in Preterm Infants

We aimed to reduce late-onset bacterial infections in infants born at 22 to 29 weeks' gestation by using collaborative quality-improvement methods to implement evidence-based catheter care. We hypothesized that these methods would result in a 50% reduction in nosocomial infection. We conducted an interrupted time-series study among 24 Ohio NICUs. The intervention began in September 2008 and continued through December 2009. Sites used the Institute for Healthcare Improvement Breakthrough Series quality-improvement model to facilitate implementation of evidence-based catheter care. Data were collected monthly for all catheter insertions and for at least 10 observations of indwelling catheter care. NICUs also submitted monthly data on catheter-days, patient-days, and episodes of infection. Data were analyzed by using statistical process control methods. During the intervention, NICUs submitted information on 1916 infants. Of the 242 infections reported, 69% were catheter associated. Compliance with catheter-insertion components was >90% by April 2009. Compliance with components of evidence-based indwelling catheter care reached 80.4% by December 2009. There was a significant reduction in the proportion of infants with at least 1 late-onset infection from a baseline of 18.2% to 14.3%. There was a 20% reduction in the incidence of late-onset infection after the intervention, but the magnitude was less than hypothesized, perhaps because compliance with components of evidence-based care of indwelling catheters remained <90%. Because nearly one-third of infections were not catheter associated, improvement may require attention to other aspects of care such as skin integrity and nutrition.

IP-10 Is an Early Diagnostic Marker for Identification of Late-Onset Bacterial Infection in Preterm Infants

Very low birth weight (VLBW) infants with suspected late-onset infection requiring sepsis screening were enrolled in a prospective study to evaluate the diagnostic utilities of a comprehensive panel of key chemokines and cytokines, both individually and in combination, to identify diagnostic markers for early recognition of bacterial sepsis and necrotizing enterocolitis (NEC). Plasma chemokines interleukin (IL)-8, interferon-gamma-inducible protein 10 (IP-10), monokine induced by interferon-gamma (MIG), monocyte chemoattractant protein 1 (MCP-1), growth-related oncogene-alpha (GRO-alpha), and regulated upon activation of normal T cell expressed and secreted (RANTES) and cytokines IL-1beta, IL-6, IL-10, IL-12p70, and tumor necrosis factor alpha (TNF-alpha) were measured at the onset of sepsis (0 h) and 24 h later. Of 155 suspected infection episodes, 44 were classified as infected. Concentrations of all studied inflammatory mediators (except IL-1beta and RANTES) were significantly higher in the infected than in the noninfected group at 0 h, but the levels decreased precipitously by 24 h. IP-10 with a plasma cutoff concentration > or = 1250 pg/mL could identify all septicemic and NEC cases and had the highest overall sensitivity (93%) and specificity (89%) at 0 h. We conclude that preterm infants have the ability to induce a robust chemokine and cytokine response during sepsis, and IP-10 is a sensitive early marker of infection.

Les infections à entérovirus du nourrisson de moins de trois mois

Enterovirus infections in childhood (echoviruses, coxsackie viruses A and B, unclassified enteroviruses) are varied, nonspecific and benign (except for poliovirus infections). However, in infants, they may lead to severe neurological or cardiac lesions. In neonates, enterovirus infections are difficult to distinguish from late-onset bacterial infection. Maternal-fetal or postnatal transmission can induce early spontaneous abortions or severe neonatal infections. Diagnosis is usually based on viral cultures and, in recent years, on PCR techniques. At the present time, no potential effective drug is available: intravenous immunoglobulins, immunization or anti-proteases may be of interest.

Predictors and outcome of early- versus late-onset major bacterial infections in liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression.

Major bacterial infections and the predictors of early (within 100 days of transplantation) versus late onset (after 100 days post-transplant) bacterial infections were prospectively assessed in 130 consecutive liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression. The median follow-up period was 38 months. Overall, 35% (45/130) of the patients developed 67 episodes of major bacterial infections (0.52 episodes/patient). Sixty-three percent of the major bacterial infections occurred early, and 37% occurred in the late post-transplant period. Eighty-four percent of the abdominal infections occurred early, whereas 38% of the cases of pneumonia, 60% of the cases of primary bacteremia, and 50% of the biliary infections occurred late. By logistic regression analysis, portal vein thrombosis was the most significant independent risk factor for early-onset major bacterial infection (odds ratio 4.1; 95% CI 1.4-12.2), and recurrent hepatitis C was the most significant independent predictor of late-onset major bacterial infections (odds ratio 6.21; 95% CI 1.9-20.2). Thus, sources and risk factors differ for early versus late-onset bacterial infections after liver transplantation. Knowledge of the differences in the potential sources, the pathogens, and the predictors of early versus late-onset bacterial infections can be valuable in the evaluation and empiric treatment of liver transplant recipients with bacterial infections.