Staphylococcus lugdunensis Bacteremia with an Infected Aortic Thrombus in a Preterm Infant

Staphylococcus lugdunensis is a rare cause of late-onset sepsis in preterm infants. To our best knowledge, we report the fourth case of a male preterm infant who developed fulminant late-onset sepsis due to Staphylococcus lugdunensis with persistent bacteremia secondary to an infected aortic thrombus confirmed with two positive blood cultures. Our patient was an extremely low birth weight growth-restricted infant born at 27 weeks gestation and initially required an umbilical arterial catheter for blood pressure and blood gas monitoring. The course of this neonate was complicated by severe respiratory distress syndrome that evolved into chronic lung disease along with multiple episodes of tracheitis. Hemodynamically, the infant had a significant patent ductus arteriosus, and an episode of medical necrotizing enterocolitis followed by Staphylococcus lugdunensis septicemia. He was diagnosed with an infected aortic thrombus, probably the occult focus responsible for the persistent bacteremia. After a 6-week course of intravenous antibiotics and 4-week course of anticoagulant therapy, the infant responded and recovered without complications.

Nutritional Factors Associated with Late-Onset Sepsis in Very Low Birth Weight Newborns

Background: Delayed onset of minimal enteral nutrition compromises the immune response of preterm infants, increasing the risk of colonization and clinical complications (e.g., late-onset sepsis). This study aimed to analyze associations between late-onset sepsis in very low birth weight infants (<1500 g) and days of parenteral nutrition, days to reach full enteral nutrition, and maternal and nutritional factors. Methods: A cross-sectional study was carried out with very low birth weight infants admitted to a neonatal intensive care unit (NICU) of a reference maternity hospital of high-risk deliveries. Data regarding days of parenteral nutrition, days to reach full enteral nutrition, fasting days, extrauterine growth restriction, and NICU length of stay were extracted from online medical records. Late-onset sepsis was diagnosed (clinical or laboratory) after 48 h of life. Chi-squared, Mann–Whitney tests, and binary logistic regression were applied. Results: A total of 97 preterm infants were included. Of those, 75 presented late-onset sepsis with clinical (n = 40) or laboratory (n = 35) diagnosis. Maternal urinary tract infection, prolonged parenteral nutrition (>14 days), and extrauterine growth restriction presented 4.24-fold, 4.86-fold, and 4.90-fold higher chance of late-onset sepsis, respectively. Conclusion: Very low birth weight infants with late-onset sepsis had prolonged parenteral nutrition and took longer to reach full enteral nutrition. They also presented a higher prevalence of extrauterine growth restriction than infants without late-onset sepsis.

The concomitant use of vancomycin and piperacillin-tazobactam is associated with acute kidney injury (AKI) in extremely low birth weight infants (ELBW)

BACKGROUND: Late-onset sepsis is common in extremely low birth weight (ELBW) infants, and it leads to the use of antibiotics to cover resistant organisms, which can be nephrotoxic. Here we have investigated the role of vancomycin plus piperacillin-tazobactam on the rate of acute kidney injury (AKI). METHODS: In a retrospective case-control study, medical records of all ELBW infants who were admitted to our Neonatal Intensive Care Unit (NICU) with late onset sepsis who were prescribed vancomycin plus piperacillin-tazobactam were reviewed for demographics, clinical characteristics, use of potential nephrotoxic medications and outcomes. RESULTS: During the study period, 264 patients were admitted, of whom 28.4%(75/264) received vancomycin plus piperacillin-tazobactam and were matched with 64 controls. There were no differences in gestational age or birth weight between cases and controls [688±160 vs. 689±162 grams (p = 0.99), and 24.7±1.8 vs. 24.7±1.6 weeks (p = 0.99) respectively]. There was no difference in the rate of sepsis between cases and controls [76%(55/72) vs. 64%(41/64) respectively, p = 0.11]. Infants exposed to vancomycin plus piperacillin-tazobactam had a higher percentage of concomitant use of vasopressors and amphotericin. To adjust for confounders, a logistic regression analysis was conducted with AKI as the dependent variable. Use of vasopressors and vancomycin plus piperacillin-tazobactam were the only risk factors associated with AKI with an adjusted OR (95%CI) of 4.08 (1.90–8.74), p < 0.001; and 2.87 (1.26–6.53), p = 0.01 respectively. CONCLUSION: The use of vancomycin plus piperacillin-tazobactam in ELBW infants is associated with an increased risk for AKI.

A Prospective Study on Neonatal Sepsis in a Tertiary Hospital, Nepal

About 20 % of neonates develop sepsis and among them approximately 1% die due to sepsis-related causes. Bacterial pathogens are the commonest cause of neonatal sepsis which is either early-onset (<72 hours of age) or late-onset (>72 hours). Little is known about the epidemiology and antimicrobial susceptibility pattern of sepsis causing bacterial pathogens in Nepal. A prospective study was carried out among neonates suspected to have sepsis and admitted to Tribhuwan University Teaching Hospital from January to December 2016. Clinical suspicion of sepsis was made based on clinical findings and laboratory parameters, later confirmed by isolation of organisms in blood culture. Drug resistance pattern of Gram-positive and Gram-negative bacteria were studied by standard methods. Meropenem resistant Gram-negative bacteria were processed for the detection of β-lactamases and resistant genes were detected by X-pert Carba-R (Cepheid) Assays. Of 372 neonates with clinically suspected sepsis, 132 (35.4%) had blood culture positivity, with 47% early-onset and 53% late-onset sepsis. Coagulase-negative Staphylococcus aureus (CONS) was the most common (37.9%) etiological agent followed by Klebsiella pneumoniae (12.9%). Of all 132 isolates, 81 (61.3%) were Gram-positive of which 22 (27.2%) were multi-drug resistant (MDR), three (3.7%) were methicillin-resistant S. aureus (MRSA), and 14 (17.2%) were methicillin-resistant CoNS; and 50 (37.8%) were Gram-negative of which 26 (52%) were MDR and 29 (58%) were resistant to β-lactamases. The blaKPC gene was detected in four isolates of K. pneumoniae, two of E. coli, one ABC (Acinetobacter baumanii complex), and one Enterobacter aerogenes whereas blaNDM gene was detected in one isolate of K. pneumoniae, two of E. coli, two Pseudomonas aeruginosa, one Acinetobacter baumanii complex, and one Enterobacter aerogenes. Overall mortality due to sepsis-related causes was 7.6% (10 of 132). One-third of clinically suspected neonatal sepsis cases were culture positive. Late-onset sepsis was more common than early onset. CoNS was the predominant bacterial isolate followed by Klebsiella pneumoniae, with high rates of multi-drug resistance.

Validity of Serum And Urinary Hepcidin As Biomarkers of Late-Onset Sepsis of Premature Infants

Background: Sepsis remains one of the leading causes of neonatal morbidity and mortality particularly among premature infants. Blood culture is the “gold standard” for diagnosis of neonatal sepsis but is associated with several pitfalls. Adjunctive diagnostic tests, including biological markers should be used to aid in antibiotic -starting decision in presumed septic preemies until culture results are availableAim of the work: We aim to evaluate the validity of measuring serum hepcidin concentration as diagnostic biomarker for late-onset sepsis in preemies and to quantify its cut-off value that differentiate truly septic from non-septic symptomatic premature infants. In addition, to examine the correlation between serum hepcidin (Hep-S) and urinary hepcidin (Hep-U) and to find out if measuring Hep-U can be used as an alternative safe, non-invasive biomarker for late-onset sepsis diagnosis, without exposure to frequent phlebotomy and its risks.Patients and Methods: The current case-control study included seventy-three (73) cases of clinically and laboratory confirmed late-onset sepsis as "case group" and fifty (50) non-septic premature infants of comparable age and gender as "control group". All participants were evaluated as per unit protocol to rule out sepsis by complete blood count, CRP, blood, urine, CSF and other cultures as indicated, plus different radiologic modalities as needed. Acute serum and urinary hepcidin concentration were evaluated by ELISA for all participants at enrollment "acute sample". After one week of treatment, convalescent samples for serum and urine hepcidin were collected and compared with the acute samples.Results: Statistically significant higher concentration of both serum and urinary hepcidin were recorded among cases as compared with non-septic peers (t=44.2&p=0.0001, t=23.8 &p=0.0001 for serum and urine hepcidin respectively). Similarly, Significant reduction of hepcidin at different body fluids was recoded after one week of treatment as compared with acute samples (paired t =18.1&p=0.001, paired t =14.1&p=0.001 for serum and urine hepcidin respectively). Significant direct correlations were reported between acute serum hepcidin levels and CRP, urinary hepcidin, and total leucocyte count. While significant negative correlation was recorded with platelets count. AUC of serum hepcidin ROC is 0.93, A cut off value of ≥94.8ng/ml of S. hepcidin showed sensitivity (88%), specificity (94%), PPV (95%) and NPV (84%) respectively with accurately diagnosing 90.2% of presenting cases as septic or not. While urinary hepcidin showed slightly less discriminating ability with AUC of 0.87. At cut-off value of ≥ 264 ng/mg of urinary hepcidin/urinary creatinine showed sensitivity (85%), specificity (90%), PPV (92.5%) and NPV (81%) respectively with accurately diagnosing 84.5% of presenting cases as septic or not.Conclusions: Hepcidin concentration in different body fluid can function as promising accurate and rapid surrogate test, with blood culture, that guide empiric antibiotics –starting decision or withholding it safely until the culture results is ready in symptomatic presumed septic preemies. Urinary hepcidin has advantages over serum hepcidin as; it is non-invasive, no hazards of phlebotomy, and less variable throughout the day.

Protocol: Pentoxifylline optimal dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial)

Background Late onset sepsis is a leading cause of death and morbidity in preterm infants. Despite optimal antibiotic treatment, sepsis related mortality and morbidity is still high. Pentoxifylline (PTX) is a methylxanthine with promising immunomodulatory properties, which can be used as an additional therapy next to antibiotics in preterm infants. PTX is increasingly used off-label in neonatal intensive care units, however up till now no dose finding study has been done for PTX in this specific population. The aim of this study (PTX-trial) is to determine the optimal dose of PTX in preterm infants (gestational age < 30 weeks) with (suspected) late onset sepsis. Dose finding in this particular population is unique, since for most drugs used in neonates the optimal dosage has not been investigated in phase II dose-seeking studies. Methods The PTX-trial is a prospective open label sequential dose-optimization study with an adapted continual reassessment method. An up-and-down dose-response design will be used, with dose step-up and step-down titration after every 3 patients. The PTX starting dosage will be 30 mg/kg/day in 6 hours as described in most previous neonatal studies. Efficacy is defined by means of biochemical and clinical parameters. Toxicity in these vulnerable patients is unwarranted. The optimal dose is defined as the ED75 (i.e., clinically and chemically effective dose for 75% of patients) in preterm neonates with late onset sepsis. We plan to include 30 neonates to determine the optimal dose using this study design. Subsequently, the optimal dose will be validated in 10 additional preterm neonates. In parallel, pharmacokinetics of PTX and its metabolites will be described as well as longitudinal evaluation of metabolomics and proteomics. Discussion The study has been approved by the Regional Medical Ethics Board of Erasmus Medical Center University Rotterdam (MEC 2019-0477) and registered at Clinicaltrials.gov (NCT04152980). Results of the main trial and each of the secondary endpoints will be submitted for publications in peer-reviewed journals. Trial registration Clinicaltrials.gov, NCT04152980, Registered November 6th, 2019

Recurrent late-onset neonatal sepsis traced to breast milk: A case report

Breast milk feeding is an important late-onset sepsis reduction strategy in the Neonatal Intensive Care Unit (NICU). However, multiple studies have reported transfer of bacteria-contaminated breast milk to infants. We describe a case of culture-positive breast milk resulting in persistent Enterococcus bacteremia in an infant. Beyond the development of an infant’s innate and specific immunity as well as colonization of the gastrointestinal (GI) tract with commensal organisms, the risk of bacterial translocation from the GI tract into the bloodstream is shaped and modified by maternal health, birth history, and an infant’s NICU course. While freezing and/or pasteurizing breast milk reduces or eliminates its bacterial load, it also diminishes its immunologic and nutritional benefits.

Dual-site blood culture yield and time to positivity in neonatal late-onset sepsis

ObjectiveTo determine whether culture yield and time to positivity (TTP) differ between peripheral and central vascular catheter-derived blood cultures (BCx) in neonatal intensive care unit (NICU) patients evaluated for late-onset sepsis.DesignSingle-centre, retrospective, observational study.SettingLevel IV NICU.ParticipantsThe study included infants >72 hours old admitted to NICU in 2007–2019 with culture-confirmed bacteraemia. All episodes had simultaneous BCx drawn from a peripheral site and a vascular catheter (‘catheter culture’).Main outcome measuresDual-site culture yield and TTP.ResultsAmong 179 episodes of late-onset bacteraemia (among 167 infants) with concurrently drawn peripheral and catheter BCx, the majority (67%, 120 of 179) were positive from both sites, compared with 17% (30 of 179) with positive catheter cultures only and 16% (29 of 179) with positive peripheral cultures only. 66% (19 of 29) of episodes with only positive peripheral BCx grew coagulase-negative Staphylococcus, while 34% (10 of 29) were recognised bacterial pathogens. Among 120 episodes with both peripheral and catheter BCx growth, catheter cultures demonstrated bacterial growth prior to paired peripheral cultures in 78% of episodes (93 of 120, p<0.001). The median TTP was significantly shorter in catheter compared with peripheral cultures (15.0 hours vs 16.8 hours, p<0.001). The median elapsed time between paired catheter and peripheral culture growth was 1.3 hours.ConclusionConcurrently drawn peripheral and catheter BCx had similar yield. While a majority of episodes demonstrated dual-site BCx growth, a small but important minority of episodes grew virulent pathogens from either culture site alone. While dual-site culture practices may be useful, clinicians should balance the gain in sensitivity of bacteraemia detection against additive contamination risk.