The infant initially received conventional mechanical ventilation and empirical ampicillin plus ceftazidime after an early episode of Escherichia coli bacteremia. On day 41 of life, while enteral feeding had been advanced to 60 mL/kg/day, he developed pulmonary hemorrhage and disseminated intravascular coagulation with scattered ecchymoses. His white blood cell count reached 2.5 × 10⁹/L, platelet count 29 × 10⁹/L and hemoglobin level 89 g/L. Blood metagenomic next-generation sequencing detected K. pneumoniae with 10 reads, and a rectal swab was positive for carbapenem-resistant K. pneumoniae.

Clinicians changed treatment to polymyxin B, administered with a loading dose of 25,000 IU/kg, equivalent to 2.5 mg/kg, followed by 15,000 IU/kg, or 1.5 mg/kg, every 12 hours, together with aztreonam at 30 mg/kg every 8 hours. Procalcitonin declined to a nadir of 0.25 ng/mL, but the pancytopenia did not improve substantially. On day 56, at a weight of 1.41 kg, the infant developed progressive abdominal distension, gastric retention, fever up to 37.7 °C, abdominal tenderness and absent bowel sounds, with fresh blood detected on digital rectal examination. His white blood cell count was 1.2 × 10⁹/L, C-reactive protein was 31.8 mg/L and procalcitonin was 7.13 ng/mL.

Imaging showed ascites and pneumatosis intestinalis. Exploratory laparotomy confirmed neonatal necrotizing enterocolitis with appendiceal perforation. Surgeons performed partial resection of necrotic bowel, appendectomy and terminal ileostomy. Postoperative blood mNGS detected K. pneumoniae with high confidence at 3,087 species-specific reads, while ascitic-fluid mNGS detected the organism at 259,429 reads. Ascitic-fluid testing also identified the NDM β-lactamase gene with 101 reads, SHV with 40 reads, APH(3′)-Ia with three reads and tet(A) with three reads. Enterococcus faecium was detected with moderate confidence at nine reads, although blood and ascitic-fluid cultures were negative.

After surgery, the infant received vancomycin at 15 mg/kg every 8 hours in combination with polymyxin B and aztreonam. Low-molecular-weight heparin was also used for thromboprophylaxis under an institutional protocol for critically ill neonates with infectious peritonitis. By day 60, erythema, swelling and progressive dark discoloration had developed over the anterior chest, abdominal wall and right lower limb. The right leg became indurated and tense while the dorsalis pedis artery remained palpable. With C-reactive protein at 13.3 mg/L and persistently low platelets, the lesions raised concern for sepsis-associated skin involvement and possible necrotizing fasciitis. Necrotizing fasciitis remained a suspected diagnosis because it was not confirmed surgically and the lesions resolved with antibiotic therapy alone.

Following multidisciplinary review, a risk-benefit assessment and guardian consent, the clinicians replaced aztreonam with off-label aztreonam–avibactam at 40 mg/kg every 8 hours, comprising aztreonam at 30 mg/kg and avibactam at 10 mg/kg, with each dose infused over three hours. Linezolid at 10 mg/kg every eight hours was added for Gram-positive coverage. On day 64 of life—the fourth day of aztreonam–avibactam therapy—the infant showed marked improvement, including substantial resolution of ecchymoses and abdominal distension, recovery of bowel sounds and a decline in C-reactive protein to 3.7 mg/L.

On day 66, the sixth day of treatment, blood mNGS was negative, linezolid was discontinued and enteral feeding was restarted. By day 70, the tenth treatment day, the ecchymoses and right-leg induration had completely resolved, enteral nutrition was advancing smoothly and C-reactive protein had fallen to 0.6 mg/L. Aztreonam–avibactam was continued for 24 days through day 84 because of the complicated intra-abdominal infection. No dose adjustment was required, and the clinicians identified no adverse events considered attributable to aztreonam–avibactam. The infant transitioned to non-invasive ventilation on day 84, reached full enteral feeding with stable weight gain by day 89 and was discharged after 117 days of hospitalization weighing 2,320 g.

Aztreonam–avibactam combines aztreonam, a monobactam stable against metallo-β-lactamase hydrolysis, with avibactam, which inhibits class A, C and some class D serine β-lactamases and can protect aztreonam from degradation by co-produced enzymes. The report states that the combination was approved in China on 30 June 2025 for complicated intra-abdominal infections and hospital-acquired pneumonia, including ventilator-associated pneumonia, in adults with limited or no alternative options, but had no approved neonatal indication. A phase IIa pediatric trial involving neonates and infants younger than nine months had been initiated in 2024 to provide pharmacokinetic and safety data.

The case has important limitations. The neonatal dose was selected through multidisciplinary consultation and extrapolation from standard neonatal aztreonam dosing, without systematic pharmacokinetic assessment or therapeutic drug monitoring, so optimal pharmacokinetic and pharmacodynamic targets were not established. Pathogen identification relied primarily on mNGS because cultures were negative, and standardized surveillance after treatment withdrawal was not performed to confirm durable pathogen clearance. Concomitant vancomycin, linezolid and surgery also limit attribution of the improvement to aztreonam–avibactam alone. As a retrospective single-patient report without a comparison group, the findings document an observed clinical response and apparent tolerability in one extremely preterm infant, but do not establish the regimen’s efficacy or support broad neonatal recommendations. Prospective pharmacokinetic, safety and efficacy data are needed to define its role in critically ill neonates.

Subject of Research: Off-label aztreonam–avibactam salvage treatment of NDM-producing Klebsiella pneumoniae in an extremely preterm infant

Article Title: From sepsis to necrotizing enterocolitis with appendiceal perforation: a case report of successful salvage therapy with aztreonam–avibactam in an extremely preterm infant with NDM-producing Klebsiella pneumoniae

Article References: He, Y., Huang, J., Du, B., Chen, Z., Huang, L., Shi, J., Zhang, M., Zhang, L., & Tang, J. (2026). From sepsis to necrotizing enterocolitis with appendiceal perforation: a case report of successful salvage therapy with aztreonam–avibactam in an extremely preterm infant with NDM-producing Klebsiella pneumoniae. Frontiers in Pharmacology, 17, Article 1919037. https://doi.org/10.3389/fphar.2026.1919037

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1919037

Keywords: aztreonam–avibactam, NDM-producing Klebsiella pneumoniae, extremely preterm infant, salvage therapy, neonatal sepsis, necrotizing enterocolitis, appendiceal perforation, metagenomic sequencing, case report, surgical source control, sepsis, necrotizing

The clinical story began with what seemed, at first, to be a routine neonatal complaint. According to the case report, the infant had shown skin jaundice for two days before admission, and in the three hours before she was brought to the hospital she had decreased her milk intake and cried persistently. These are among the most common reasons newborns are evaluated by pediatricians, and none of them points specifically toward sepsis. That ambiguity is precisely what makes the case instructive, the authors argue: neonatal Edwardsiella tarda septicemia presents with non-specific clinical manifestations, which makes early diagnosis exceptionally challenging. A delayed or missed diagnosis of bacterial sepsis in a newborn can be fatal, so the stakes of recognizing unusual pathogens are high.

Blood culture provided the decisive answer. Culturing the infant’s blood allowed the laboratory to identify Edwardsiella tarda as the organism circulating in her bloodstream, confirming the diagnosis of neonatal septicemia. Blood culture remains the diagnostic gold standard for neonatal sepsis, because the clinical signs of infection in newborns, from temperature instability to poor feeding and lethargy, overlap so heavily with other neonatal illnesses that laboratory confirmation is essential before targeted therapy can be chosen. In this case, the identification of an organism that most pediatricians will never encounter in a newborn blood culture immediately placed the infant’s care in uncommon territory.

Edwardsiella tarda is a Gram-negative bacterium in the family Enterobacteriaceae, and its natural history is dominated by aquatic environments and cold-blooded animals. It is a well-documented pathogen of fish, causing disease in farmed and wild species, and it can also colonize reptiles and amphibians. Human infections are uncommon and typically occur through exposure to contaminated water or aquatic food sources, most often producing gastrointestinal illness. When the bacterium does invade the bloodstream, the consequences can be severe; the authors note that Edwardsiella tarda bacteremia can be a fatal disease in humans. Its appearance in the blood of a five-day-old infant is an event rare enough that the Jiangyou team combined their case with a review of the published literature to map what is known about this infection in newborns.

One of the most striking elements of the case involved a finding that extended beyond the bloodstream infection itself. During hospitalization, the infant was found to have a subgaleal hematoma over the left parietal region of her skull, a collection of blood between the scalp and the skull covering that had been present on imaging. That hematoma progressed to abscess rupture during her hospital stay, meaning the blood collection became infected and broke down. A subgaleal abscess in a newborn represents a serious complication, because the potential space between the galea aponeurotica and the skull can allow blood and pus to spread widely across the scalp, and infection in this compartment can seed the underlying structures. The progression of a sterile hematoma into an abscess in the setting of bacteremia illustrates how a circulating infection and a local collection of blood can reinforce one another, with bacteria seeding the hematoma and the hematoma providing a protected environment in which the bacteria can proliferate beyond the reach of circulating antibiotics.

Treatment combined two complementary strategies. The infant received meropenem, a broad-spectrum carbapenem antibiotic active against many Gram-negative organisms, including Enterobacteriaceae such as Edwardsiella tarda. Carbapenems are typically reserved for severe infections or for situations in which resistance to narrower agents is a concern, and their use here reflects the gravity of neonatal septicemia and the need to achieve rapid, reliable bacterial killing. Alongside the antibiotic, the clinicians administered adjunctive intravenous immunoglobulin, or IVIG, a blood-derived product concentrated with antibodies that can support the immature immune system of a newborn. Neonates have limited capacity to produce their own antibodies and to opsonize encapsulated and Gram-negative bacteria effectively, and IVIG is sometimes used as adjunctive therapy in severe neonatal sepsis to supplement the infant’s antibody repertoire while antibiotics address the underlying infection.

Supportive care completed the therapeutic picture. Newborns with septicemia require meticulous management of fluid balance, nutrition, temperature, and organ function, because the physiological reserves of a five-day-old are minimal and the systemic inflammatory response to bacterial sepsis can rapidly destabilize multiple organ systems. In this infant, the combination of meropenem, IVIG, and supportive measures succeeded in clearing the infection and resolving the local complication. The subgaleal abscess, despite its rupture during hospitalization, did not prevent a full recovery, and the authors report that the infant was discharged without long-term complications, an outcome that stands in welcome contrast to the potentially fatal trajectory of untreated Edwardsiella tarda bacteremia.

The rarity of this infection in newborns is what gives the case report its scientific value. By pairing their single case with a literature review, the authors have assembled a reference point for clinicians who may encounter similar presentations. The published record of Edwardsiella tarda infections in neonates is sparse, and each documented case contributes to a collective understanding of how the infection is acquired, how it manifests, and how it responds to treatment. The authors emphasize that awareness of potential environmental or aquatic exposures may be helpful when considering Edwardsiella tarda infection in neonates, a recommendation that reflects the bacterium’s ecology. In practice, this means that when a newborn presents with sepsis and cultures yield an unexpected aquatic-associated organism, clinicians should think to ask about the environments the mother and infant have contacted, from household water sources to contact with fish or aquatic animals.

The case also highlights the role of maternal exposure in the chain of transmission. The article’s keywords include maternal exposure, underscoring the authors’ interest in how a newborn so young, with no independent contact with the outside world beyond the delivery environment, could acquire a bacterium associated with water and aquatic animals. Possible routes in such cases include contamination during labor and delivery, contact in the home environment after discharge, or transmission from a colonized mother. The report does not resolve this question definitively for this infant, but by flagging maternal and environmental exposure as a consideration, it gives pediatricians a concrete line of inquiry when the unusual diagnosis arises.

For the wider medical community, the takeaways are practical. First, neonatal sepsis remains a diagnosis in which the clinical picture can deceive: jaundice and poor feeding, two of the most ordinary findings in a newborn, were the opening signs of a life-threatening bloodstream infection. Second, blood cultures must be obtained promptly whenever sepsis is suspected, because identifying the organism is the only way to move from empiric coverage to targeted therapy, particularly when the pathogen involved is as unusual as Edwardsiella tarda. Third, unusual organisms demand unusual histories, and asking about aquatic and environmental exposures can illuminate infections that would otherwise remain unexplained. Finally, the case demonstrates that even a rare and potentially fatal neonatal infection can have a good outcome when it is diagnosed by culture, treated with appropriate broad-spectrum antibiotics and adjunctive immunotherapy, and monitored closely for local complications such as the infected subgaleal hematoma that complicated this infant’s course. The authors, Qinnan Shao, Haixia Xie, Haixia Liu, and Hong Lin, all of the Department of Pediatrics at Jiangyou People’s Hospital, published the case as an open-access report so that clinicians elsewhere can draw on the experience when the same rare pathogen next appears in a newborn’s blood culture.

Subject of Research: Neonatal septicemia caused by Edwardsiella tarda

Article Title: Neonatal septicemia caused by Edwardsiella tarda: a case report and literature review

Article References: Shao, Q., Xie, H., Liu, H., & Lin, H. (2026). Neonatal septicemia caused by Edwardsiella tarda: a case report and literature review. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07819-x

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07819-x

Keywords: Edwardsiella tarda, neonatal sepsis, bloodstream infection, blood culture, meropenem, intravenous immunoglobulin, subgaleal hematoma, abscess, aquatic exposure, maternal exposure, neonatology, bacterial infection

The clinical half of the study drew on 366 hospitalized neonates born between 2018 and 2023 at Sun Yat-sen Memorial Hospital. What makes this dataset unusual is the timing of the blood work: every infant had serum 25-hydroxyvitamin D, or 25(OH)D, the standard laboratory marker of vitamin D status, measured within 72 hours of birth and, crucially, before any vitamin D supplementation had been given. That timing matters because it captures the vitamin D status the infant acquired in utero, through placental transfer of the vitamin from the mother, rather than any status achieved after birth through feeding or supplementation. The researchers then tracked which of these infants went on to be diagnosed with neonatal sepsis during their hospitalization.

The numbers that emerged were striking. The median 25(OH)D concentration across the cohort was just 37.7 nanomoles per liter, a figure that sits well below the 50 nanomoles per liter threshold generally considered sufficient in pediatric practice. Nearly eight in ten infants fell short of that mark: 28.4 percent were frankly deficient, with concentrations below 30 nanomoles per liter, and another 49.5 percent were insufficient, landing between 30 and 50. In other words, vitamin D inadequacy was the norm rather than the exception in this population of hospitalized newborns, a pattern consistent with the widespread vitamin D deficiency documented among pregnant women in many parts of the world, since the newborn’s stores largely mirror the mother’s.

When the researchers ran the statistical analysis, they prespecified the 235 term neonates in the cohort as the primary analysis population, a decision that reflects the clinical reality that preterm infants face a fundamentally different risk landscape for sepsis, with immature skin barriers, invasive procedures, and prolonged hospital stays all playing outsized roles. Among those term infants, the association was clear: every 10-nanomole-per-liter increase in 25(OH)D was associated with roughly 30 percent lower odds of neonatal sepsis, with an adjusted odds ratio of 0.70 and a 95 percent confidence interval of 0.54 to 0.90, reaching statistical significance at p equals 0.006. The adjustment accounted for potential confounders, meaning the relationship held even after accounting for other factors that might independently influence sepsis risk.

But an observational association, however carefully adjusted, always leaves open the possibility of reverse causation or residual confounding. Perhaps sepsis-prone infants are simply sicker in ways that also depress their vitamin D levels, or perhaps some unmeasured factor, from maternal nutrition to socioeconomic circumstances, drives both. This is where the second half of the study comes in. The team turned to Mendelian randomization, a technique that exploits the random allocation of genetic variants at conception to approximate a randomized trial. Because single-nucleotide polymorphisms, or SNPs, that influence vitamin D levels are fixed at conception and generally not confounded by later environmental exposures or disease processes, they can serve as proxies for lifelong vitamin D status, allowing researchers to ask whether genetically predicted higher 25(OH)D is associated with disease outcomes in ways that are harder to dismiss as mere correlation.

Using summary statistics from large genome-wide association studies, the researchers performed a two-sample Mendelian randomization analysis examining whether genetically predicted vitamin D status relates to sepsis outcomes. The result was intriguing but deliberately cautious in its interpretation: genetically predicted higher 25(OH)D was nominally associated with lower odds of streptococcal septicemia, with an odds ratio of 0.96 per unit increase and a confidence interval of 0.924 to 0.996, yielding a p value of 0.029. The word nominal is doing important work here. In the context of multiple genetic instruments and multiple outcomes, a p value just under the conventional 0.05 threshold does not constitute strong evidence, and the authors were explicit that this exploratory estimate, while directionally consistent with the cohort finding, does not establish causality. The effect size, roughly a 4 percent reduction in odds per genetically predicted increase in 25(OH)D, is modest, and the confidence interval grazes the null value at its upper bound.

Still, the convergence of two very different lines of evidence is what gives the study its interest. The retrospective cohort captures real-world clinical variation in vitamin D status at a moment, the first 72 hours of life, when intervention might theoretically still be possible through maternal supplementation during pregnancy or early neonatal dosing. The genetic analysis, for all its limitations, offers a triangulation point that is immune to the reverse-causation problem, since a newborn’s germline variants cannot be altered by the sepsis that follows. That the two approaches point in the same direction, with the genetic signal specifically implicating streptococcal septicemia, a major bacterial cause of neonatal sepsis, lends biological plausibility to the association, even if neither line alone can settle the question.

The mechanistic backdrop is also worth understanding. Vitamin D is not merely a bone-regulating hormone; its active form binds to the vitamin D receptor expressed on immune cells, including macrophages and dendritic cells, and modulates the production of antimicrobial peptides such as cathelicidin, which play a direct role in killing bacteria. In the neonatal period, when the innate immune system is still maturing and the adaptive arm is largely naive, this antimicrobial pathway may be particularly consequential. Animal models and in vitro studies have long suggested that vitamin D deficiency impairs antibacterial responses, and the neonatal context, with its immature immune defenses and high vulnerability to bloodstream infection, is precisely where such a deficit might matter most.

The authors are careful about what their study cannot say. This was a selected cohort of hospitalized neonates who had clinician-directed 25(OH)D testing, which means the sample may overrepresent infants already suspected of having problems, and the retrospective design means sepsis diagnoses were drawn from clinical records rather than standardized prospective criteria. The cohort was also drawn from a single center in southern China, and vitamin D status varies substantially across populations, seasons, and latitudes, so the generalizability of the 37.7 nanomole-per-liter median and the magnitude of the association remain open questions. The Mendelian randomization analysis, meanwhile, relied on genetic instruments developed primarily in European-ancestry populations, which can limit the precision and transportability of the estimates when applied to other populations.

What the study does establish is a well-defined hypothesis worth testing prospectively: that early neonatal vitamin D status, established largely in utero, is associated with sepsis risk in term infants, and that the relationship may be at least partially causal. The authors call for prospective multicenter validation, which would mean following newborns forward from birth with standardized 25(OH)D measurements and sepsis surveillance, ideally across diverse populations. If such studies confirm the association and the genetic signal strengthens, the implications could be significant for a condition where prevention options remain limited. Maternal vitamin D supplementation during pregnancy is already recommended in many guidelines for skeletal health, and if the immune benefits extend to sepsis prevention, the case for ensuring adequate maternal and neonatal vitamin D status would become considerably stronger. For now, the message is one of cautious promise: a cheap, widely available nutrient, a common deficiency in newborns, and a serious infection, all linked by evidence that is suggestive but not yet definitive.

Subject of Research: The association between early neonatal vitamin D status and neonatal sepsis, examined through a retrospective cohort and Mendelian randomization

Article Title: Early neonatal vitamin D status and neonatal sepsis: a retrospective cohort study complemented by Mendelian randomization

Article References: Xie, X., Chen, Y., Jin, N., Sha, S., Zhou, R., Bamo, A., Chen, J., Yu, Z., & Ouyang, Y. (2026). Early neonatal vitamin D status and neonatal sepsis: a retrospective cohort study complemented by Mendelian randomization. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07678-6

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07678-6

Keywords: neonatal sepsis, vitamin D, 25-hydroxyvitamin D, Mendelian randomization, newborns, term neonates, Sun Yat-sen University, retrospective cohort, genetic analysis, streptococcal septicemia, neonatology, immune regulation

DNA methylation is chemically simple: a methyl group is attached to cytosine bases, most often at cytosine-guanine dinucleotides known as CpG sites, catalysed by enzymes called DNA methyltransferases. Yet the consequences are profound. Methylated promoters can silence genes, methylation patterns define chromatin states, and the overall methylation landscape helps keep the genome structurally stable. As the editors of the Research Topic, Pietro Salvatore Carollo of the University of Enna Kore, Andrea Fuso of Sapienza University of Rome and Viviana Barra of the University of Palermo, frame it, DNA methylation acts as the critical software that executes precise cellular programs within the genome’s hardware. When that software is corrupted, the result can be inappropriate silencing or activation of genes, altered chromatin, genomic instability or the disruption of developmental programs, which is why methylation patterns are increasingly treated as predictors of health rather than mere byproducts of it.

Crucially, methylation is not a static feature of the genome. It responds to developmental environment and cellular cues, adapting dynamically and profoundly affecting cellular function and identity. That dynamism cuts both ways: depending on the biological context, a change in methylation may be the initiator of a pathological cascade or simply the consequence of a cell that has already gone awry. Disentangling cause from effect is one of the central challenges of modern epigenetics, and it is precisely the question that unites the six contributions gathered in this collection, which the editors organise into three strands: the enzymology of active demethylation, the methylation-based measurement of biological age, and methylation signatures in inflammatory and chronic disease.

The first strand centres on TET2, a member of the Ten-Eleven Translocation family of enzymes that mediate active DNA demethylation. While methyltransferases write the mark, TET enzymes erase it, and the process is far more intricate than simple reversal. TET2 catalyses the first step of the cascade, oxidising 5-methylcytosine, the canonical methylated base, into 5-hydroxymethylcytosine, an intermediate that carries its own regulatory meaning and can be further oxidised or passively diluted through cell division. In a review by Tang and colleagues, the authors survey how wild-type TET2 maintains cellular physiology and genetic stability, while somatic mutations in the gene are implicated in a striking range of pathologies, from inflammatory disorders to cancers. Because demethylation involves complex multi-step enzymatic cascades whose fine-tuning is still being worked out, understanding TET2’s behaviour in pathological contexts is viewed as a promising route to new therapeutic strategies, exploiting the fact that methylation, unlike the underlying DNA sequence, is chemically reversible.

The second strand turns to time. In 2013, Steve Horvath introduced the concept of the epigenetic clock, showing that variations in DNA methylation patterns across human tissues and cell types correlate with ageing phenotypes. Since then, a family of epigenetic clocks has been developed, and they can now be applied not only to individual tissues but to populations and to specific pathological contexts. Chen and colleagues review the mechanistic basis of these methylation-based age estimates and their expanding implications for ageing research, health monitoring and disease prediction. The idea that a blood sample can yield a molecular readout of biological age, one that may diverge from chronological age and predict disease risk, has moved epigenetics from the laboratory bench into preventive medicine, and the review charts both the technical progress and the open questions in the field.

The third strand delivers some of the collection’s most concrete clinical findings. In rheumatoid arthritis, an autoimmune disease characterised by chronic joint inflammation and erosion, Delgado-Cruzata and colleagues examined cell-free DNA, fragments of genetic material circulating in plasma, from 27 patients. Using pyrosequencing, a quantitative method that reads methylation levels at individual CpG sites, they found that patients displayed lower methylation of the DUSP22 gene promoter at one specific site compared with healthy controls. More strikingly, decreased methylation levels in circulating DNA were associated with increased joint space narrowing, a radiographic marker of disease progression. The result points toward cell-free DNA methylation as a new, non-invasive biomarker for rheumatoid arthritis, potentially allowing clinicians to track erosive disease from a simple blood draw.

Hypertension tells a similar story of methylation as a disease mirror. Zhu and colleagues used Illumina Infinium Methylation EPIC BeadChips, arrays capable of interrogating hundreds of thousands of CpG sites across the genome, to profile methylation in peripheral leukocytes from 179 patients with high blood pressure. Their epigenome-wide analysis uncovered associations between altered methylation patterns and inflammation biomarkers, reinforcing the emerging view that hypertension is not solely a vascular or haemodynamic disorder but one with a measurable inflammatory and epigenetic dimension. Patterns like these could eventually help stratify patients who respond differently to treatment, or flag individuals at risk before blood pressure becomes chronically elevated.

Inflammation also takes centre stage in neonatal medicine. Sankar and colleagues studied newborns with late-onset neonatal sepsis, a devastating bacterial infection that strikes after the first days of life. Infants with the condition displayed a distinctive methylation signature: pro-inflammatory genes were hypomethylated, a state generally permissive of gene expression, while anti-inflammatory genes were hypermethylated, relative to healthy newborns. The expression of key cytokines, including TNF-α, IFN-γ, IL-10 and TGF-β, was accordingly shaped by methylation status. Because neonatal sepsis is notoriously difficult to diagnose quickly, a methylation-based signature could improve both diagnostics and therapy, identifying which infants mount a runaway inflammatory response and guiding interventions before organ damage occurs.

The final study demonstrates how methylation profiles can capture the interplay of disease, sex and geography. Miranda-Morales and colleagues performed bisulfite pyrosequencing on leukocyte DNA from Parkinson’s disease patients and age- and sex-matched healthy individuals in the Mexican Mestizo population, targeting CpG sites within two genes central to the disease: MAPT, which encodes the tau protein, and SNCA, which encodes alpha-synuclein, the main component of the protein aggregates that define the disorder. Patients showed reduced methylation in the MAPT promoter region and in intron one of SNCA. Intriguingly, the methylation differences were sex-specific: men displayed significant differences in MAPT methylation, while women showed significant differences at SNCA. Patterns also varied with regional location within the population, establishing that sex- and geography-specific methylation signatures exist in Parkinson’s disease, with implications for how epigenetic risk is assessed across diverse populations.

Taken together, the six studies converge on a common theme that is reshaping biomedical research: DNA methylation is a dynamic, responsive layer of genome regulation whose disturbances both reflect and drive human disease. By combining multi-omic and clinical data, the field is evolving from the identification of individual methylation loci toward an integrated view of disease biology, one that clarifies the mechanisms underlying disease heterogeneity and uncovers molecular signatures with value for diagnostics, prognosis and therapy. And because methylation is reversible in a way that genetic mutations are not, aberrant patterns represent an inviting therapeutic target. From the demethylase activity of TET2 to the ticking of epigenetic clocks and the methylation signatures circulating in a drop of blood, the software of the genome is proving to be not just a record of disease, but a place where disease might be rewritten.

Subject of Research: The role of DNA methylation in human diseases, including TET2-mediated demethylation, epigenetic clocks, and methylation biomarkers in inflammatory and neurodegenerative conditions.

Article Title: Editorial: Discussing the implication of DNA methylation in human diseases

Article References: Carollo, P. S., Fuso, A., & Barra, V. (2026). Editorial: Discussing the implication of DNA methylation in human diseases. Frontiers in Molecular Biosciences, 13, Article 2015661. https://doi.org/10.3389/fmolb.2026.2015661

Image Credits: AI Generated

DOI: 10.3389/fmolb.2026.2015661

Keywords: DNA methylation, epigenetics, TET2, epigenetic clock, cell-free DNA, rheumatoid arthritis, hypertension, neonatal sepsis, Parkinson's disease, biomarkers, ageing, gene expression

The analogy, borrowed from astronomy, where the Goldilocks zone describes the orbital band around a star in which liquid water can survive, is more than a catchy framing device. It captures a genuine clinical dilemma. Neonatal sepsis, defined as life-threatening organ dysfunction caused by bacterial, viral or fungal infection, remains a leading cause of neonatal mortality worldwide and can leave survivors with serious neurodevelopmental sequelae. Yet the clinical presentation of sepsis in a newborn is notoriously nonspecific, and blood culture, the diagnostic cornerstone, has well-recognised limitations, particularly for early-onset sepsis. Antibiotics therefore remain the mainstay of treatment, and clinicians frequently must decide whether to start them in infants whose risk of infection is uncertain.

The stakes of that decision are amplified in preterm infants. These babies are immunologically immature, have thin skin and invasive lines, and are frequently exposed to maternal and neonatal risk factors that make infection plausible. Empiric antibiotics are started liberally, often within the first hours of life, and are continued for days in many infants who never have a positive culture. Recent studies quantifying this practice have found substantial variation in antibiotic exposure among culture-negative preterm infants, both within single centres over a decade and across international cohorts of late-preterm and term newborns. The question is no longer whether antibiotics are overused in this population, but how to measure the exposure precisely and what the consequences of that exposure actually are.

Those consequences have been examined in a growing body of observational research. Several large cohort studies have reported associations between prolonged duration of initial empiric antibiotic therapy and increased rates of necrotising enterocolitis and death in extremely low birth weight infants. Other analyses have linked extended early antibiotic exposure to subsequent development of late-onset sepsis, and to bronchopulmonary dysplasia in very preterm infants at low risk of early-onset sepsis. Multicentre cohort work has also associated longer empiric courses with necrotising enterocolitis and late-onset sepsis in preterm infants. These findings have fuelled calls for shorter empiric courses and more rapid discontinuation when cultures remain negative.

Yet the picture is not straightforward. Not every study points in the same direction. Some analyses, including a large international cohort of very low birth weight infants, have reported that early antibiotic use was associated with a lower incidence of necrotising enterocolitis, while a single-centre retrospective study found no association between early antibiotic exposure and short-term adverse outcomes in very preterm infants. Additional population-based and single-centre cohort analyses have produced mixed results regarding early empiric antibiotics and adverse clinical outcomes. The authors of the Pediatric Research commentary emphasise that this heterogeneity reflects real methodological complexity: confounding by indication, differences in gestational age, centre-level prescribing culture, and the difficulty of measuring what antibiotics are actually being given, at what dose, for how long, and against which suspected organisms.

Quantifying antibiotic use is itself a technical problem. A systematic review and international multidisciplinary consensus procedure has produced metrics for measuring antibiotic consumption in the hospital setting, recognising that simple days-of-therapy counts may obscure differences in spectrum, dose intensity and route. In neonatal intensive care, where weight-based dosing changes daily and renal clearance matures rapidly, the same number of days may represent very different cumulative exposures in different infants. The commentary argues that stewardship programmes must therefore move beyond crude consumption metrics toward precision prescribing, in which treatment is given to infants likely to benefit while unnecessary exposure is avoided in infants unlikely to have infection.

Achieving that precision requires better diagnostics as much as better prescribing habits. Inflammatory markers such as C-reactive protein and procalcitonin have been proposed as adjuncts to guide antibiotic decisions in early-onset sepsis, but their performance remains debated, with some experts questioning whether they are game changers or gimmicks. The absence of an accepted consensus definition of neonatal sepsis further hinders standardisation of registries, outcome measures, clinical trials and the evaluation of new diagnostics and therapeutics. Progress in developing advanced diagnostics and therapeutics for neonatal sepsis has been slow, which is precisely why antibiotics continue to carry such a heavy clinical load.

Where diagnostics fall short, pharmacology may help. Population pharmacokinetic models and simulation studies are being used to optimise vancomycin dosing in neonates, and a digital twin framework has been proposed for optimal aminoglycoside dosing in neonates with suspected sepsis, allowing clinicians to model individual drug exposure before administering it. Rapid point-of-care genotyping has been deployed in neonatal intensive care to identify infants at risk of aminoglycoside-induced ototoxicity, offering a way to personalise therapy at the genetic level. Best-evidence dosing recommendations for term and preterm neonates have been developed through dedicated projects, and considerations for drug dosing in premature infants continue to evolve as understanding of developmental pharmacology matures. Neonatal drug formularies are also being catalogued on a global scale to support safer prescribing.

The commentary also highlights the NANO trial, a randomised multicentre clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants, as an example of the kind of prospective evidence needed to move the field beyond observational associations. Randomised data are scarce in this population, partly because of ethical and logistical constraints, but without them the field risks perpetuating prescribing patterns based on weak evidence. The authors call for multidisciplinary antimicrobial stewardship programmes that bring together neonatologists, pharmacists, infectious disease specialists and microbiologists to define the optimal duration, spectrum and intensity of antibiotic exposure for preterm infants.

The goal, the authors stress, is not simply less antibiotic use. It is the right antibiotic, for the right infant, for the right duration, guided by evidence rather than habit or fear. In an era of rising antimicrobial resistance and growing recognition of the long-term consequences of early-life microbiome disruption, the Goldilocks zone of neonatal antibiotic prescribing is not a metaphorical luxury. It is a clinical target with measurable outcomes, and the tools to reach it, from precision metrics to pharmacokinetic modelling to point-of-care genotyping, are finally coming within grasp. What remains is the will to test them rigorously in the infants who need them most.

Subject of Research: Antimicrobial stewardship in preterm infants

Article Title: The Goldilocks zone of optimal antimicrobial stewardship in preterm infants

Article References: Molloy, E. J., Johnson, L., Klebanoff, M., Tingay, D., & Wynn, J. L. (2026). The Goldilocks zone of optimal antimicrobial stewardship in preterm infants. Pediatric Research. https://doi.org/10.1038/s41390-026-05558-4

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05558-4

Keywords: neonatology, antimicrobial stewardship, preterm infants, neonatal sepsis, antibiotic exposure, microbiome, necrotizing enterocolitis, precision prescribing, Goldilocks, zone, optimal, antimicrobial

The study, published in BMC Infectious Diseases by a team at the Medical Center, University of Freiburg, examined every blood culture-positive episode occurring in neonates hospitalized at the tertiary neonatal intensive care unit between 2014 and 2024. Of 3,246 blood cultures, 232 were positive — a positivity rate of just 7.1 percent. After accounting for follow-up and parallel cultures and other exclusions, the researchers distilled 189 unique culture-positive episodes. Treating teams, in their original documentation from the time of the episode, attributed 125 of these (66.1 percent) to infection and 64 (33.9 percent) to contamination.

The technical heart of the problem is a group of bacteria called coagulase-negative staphylococci, or CoNS. These organisms are common residents of human skin, which makes them frequent hitchhikers on sampling needles and catheter hubs. But CoNS can also cause genuine, sometimes dangerous infections, particularly in extremely premature infants with central venous catheters. Unlike unambiguous pathogens such as Staphylococcus aureus or Enterobacterales, CoNS carry no intrinsic signal of whether they represent real disease or a laboratory artifact. The clinician must infer intent from context.

The Freiburg data make that ambiguity vivid. Among the 189 episodes, CoNS appeared in 114 — 60.3 percent of the total — and their attribution varied more than any other organism. All 13 CoNS-positive episodes in the early-onset period, meaning within the first days of life, were classified as contamination. Yet among late-onset episodes, CoNS-positive cultures were attributed as infection in 64 of 101 cases, or 63.4 percent. The same microbe, in the same unit, flipped from near-certain artifact to majority true infection depending on the timing and clinical setting.

By contrast, other organisms behaved almost predictably. Enterobacterales, Enterococcus faecalis, Staphylococcus aureus, and Candida species were nearly always attributed as infection, reflecting their established pathogenic role. Bacillus species and other environmental organisms were predominantly dismissed as contamination, consistent with their origin in skin flora and hospital dust. In other words, microbiology laboratories do much of the interpretive work implicitly: the identity of the organism sets a prior probability, and the clinical team then adjusts it.

To quantify what drives that adjustment, the researchers ran descriptive analyses and exploratory logistic regression, focusing on late-onset episodes. The strongest signal by far was the maximum C-reactive protein value, an established blood marker of systemic inflammation. Higher peak CRP showed the strongest association with attribution as infection, both in univariable and multivariable analyses, with an adjusted odds ratio of 4.41 (95 percent confidence interval 2.59 to 7.51). In practical terms, a pronounced inflammatory response made clinicians far more likely to believe the culture.

Other candidate markers told a more complicated story. Time to positivity — how quickly the culture broth signals bacterial growth, with faster growth traditionally suggesting a heavier bacterial load and hence true infection — was associated with attribution, but the association weakened and became imprecisely estimated after adjustment for other factors. The same pattern held for CoNS detection itself and for the presence of a central vascular catheter, a known risk factor for catheter-related bloodstream infection. Once CRP and organism identity were accounted for, these features added comparatively little statistical certainty.

The authors are careful about what this study does and does not show. Because attribution was extracted from routine documentation made during the index episodes, the analysis describes real-world clinical attribution, not diagnostic accuracy. There is no gold standard against which the clinicians’ judgments can be graded, and the retrospective single-center design limits generalizability to other units with different case mixes and sampling practices. The logistic regression was explicitly exploratory. What the data capture instead is a decade of collective clinical reasoning under uncertainty — a portrait of practice, not a validated rule.

Even so, the implications for antimicrobial stewardship are substantial. Neonatal sepsis is among the leading causes of newborn death worldwide, and the standard response to a suspicious clinical picture is prompt empiric antibiotics, a strategy that saves lives when infection is real. But CoNS-driven uncertainty pushes in the opposite direction: overtreatment exposes fragile infants to unnecessary drug toxicities, disrupts the developing microbiome, and fuels resistance, while undertreatment of a genuine bloodstream infection can be catastrophic. The finding that a full third of culture-positive episodes were ultimately called contamination illustrates how much antibiotic therapy in neonatal care rides on judgments that current tools cannot reliably settle.

The study’s clearest conclusion is a call for more reproducible criteria. As the researchers note, CoNS-positive late-onset episodes represented the greatest diagnostic uncertainty, and clinical attribution depended on a combined consideration of organism plausibility, inflammatory response, time to positivity, and clinical context rather than on any single decisive test. Future work — whether refined biomarker panels, molecular diagnostics that quantify bacterial load, or standardized attribution algorithms — will need to target exactly this gray zone. Until then, the decision of whether a positive blood culture in a preemie means infection or contamination remains what it has always been: a judgment call, made under pressure, in the smallest and most vulnerable patients on the ward.

Subject of Research: Clinical attribution of blood culture-positive episodes as infection or contamination in neonatal intensive care

Article Title: Infection or contamination – Clinical attribution of blood culture-positive episodes in neonatal intensive care: an 11-year retrospective single-center study

Article References: Schnee, S. V., Lohrmann, F., Matheisl, D., Schneider, H., Hufnagel, M., Fuchs, H., & Kuntz, M. (2026). Infection or contamination – Clinical attribution of blood culture-positive episodes in neonatal intensive care: an 11-year retrospective single-center study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14605-8

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14605-8

Keywords: neonatal sepsis, blood cultures, contamination, coagulase-negative staphylococci, neonatal intensive care, C-reactive protein, antimicrobial stewardship, bloodstream infection, time to positivity, clinical microbiology, epidemiology, Infection

The study, published in BMC Infectious Diseases, analyzed clinical records from infants admitted to the hospital’s neonatal intensive care unit between May 2023 and February 2025. All of the patients were preterm, and the median age at which sepsis first appeared was just sixteen days, though the range stretched remarkably wide, from seven days to 223 days after birth. That timing matters. Late-onset sepsis, meaning infection that develops after the first seventy-two hours of life, is a leading cause of illness and death in preterm infants, and the usual suspects are well-known organisms such as coagulase-negative staphylococci. Bacillus cereus rarely tops the list of clinical suspicions, and that is precisely the problem the researchers set out to illuminate.

The clinical picture that emerged from the nineteen cases was strikingly non-specific, which helps explain why the organism is so easy to overlook. Every single infant, one hundred percent of the cohort, presented with poor responsiveness, a vague sign that overlaps with countless other conditions in fragile newborns. Fever was present in fourteen patients, or 73.9 percent, and apnea, the temporary cessation of breathing, occurred in twelve infants, accounting for 63.2 percent. None of these findings would immediately point a clinician toward Bacillus cereus. In fact, the study’s authors note that positive blood cultures for this organism are frequently dismissed as contamination, since Bacillus species are common environmental organisms that can inadvertently seed a culture bottle during sampling. Distinguishing true invasive infection from a stray contaminant requires clinical judgment, and the stakes of getting that call wrong are now considerably clearer.

One of the most consequential findings of the study concerned breathing. Among the sixteen infants who had not been receiving invasive mechanical ventilation before the onset of sepsis, ten, or 62.5 percent, required escalation to a higher level of respiratory support once the infection took hold. The researchers report this figure with a 95 percent confidence interval of 35.4 percent to 84.8 percent, a wide range that reflects the modest sample size but still signals a consistent pattern. In practical terms, a sudden deterioration in respiratory status in a preterm infant, manifesting as new or worsening apnea and increased oxygen requirements, may be one of the earliest and most reliable signals that sepsis is developing. For neonatal clinicians, the message is that a step up in respiratory support should trigger a careful search for infection, including blood cultures, rather than being attributed to the infant’s underlying prematurity alone.

The microbiology added its own sobering lessons. Every strain isolated in the cohort was resistant to penicillin and ampicillin, the beta-lactam antibiotics that form the backbone of empiric therapy for many neonatal infections. This resistance is a hallmark of Bacillus cereus, which produces beta-lactamase enzymes that dismantle penicillin-class drugs. The good news is that all strains remained susceptible to meropenem, vancomycin, and linezolid, giving clinicians effective options once the organism is identified. But the resistance pattern underscores a diagnostic trap: if Bacillus cereus is not considered and the infant is treated with ampicillin alone, the infection may continue to progress even as treatment appears to be under way. Timely identification of the organism and rational adjustment of the antimicrobial regimen are therefore not optional refinements but essential steps in managing these patients.

The most alarming dimension of the study concerns the central nervous system. Two of the nineteen infants, or 10.5 percent, developed purulent meningitis, the bacterial infection of the membranes surrounding the brain, and one of those cases progressed to a brain abscess, a localized collection of pus within brain tissue itself. The researchers provided a detailed account of this abscess case and then cast a wider net, searching the published literature for other reported cases of neonatal Bacillus cereus brain abscess. Combining their own patient with the literature yielded fifteen cases in total. Among those fifteen infants, five deaths were reported, a mortality rate of 33.3 percent. And the toll did not end with survival: some of the children who lived were left with neurological sequelae, lasting damage to brain function that can shape development for a lifetime.

The outcome of the Quanzhou abscess case illustrates both the gravity of the complication and the possibility of rescue through aggressive intervention. The infant survived after undergoing surgical drainage of the abscess combined with long-term antimicrobial therapy, a regimen that must be sustained for weeks to eradicate bacteria sequestered within an abscess cavity, where antibiotic penetration is poor and the blood-brain barrier complicates drug delivery. Yet survival came with a caveat. At twenty months of age, the child exhibited mild neuromotor developmental delay, a reminder that even successfully treated central nervous system infection in a preterm infant can leave subtle but meaningful traces on the developing brain. The developing nervous system of a premature infant is uniquely vulnerable, and inflammatory injury during critical windows of brain maturation can disrupt processes that unfold over months and years.

Overall mortality in the cohort was 5.3 percent, meaning one of the nineteen infants died, with a 95 percent confidence interval of 0.1 percent to 26.0 percent. That figure, while far lower than the mortality seen in the brain abscess literature, still represents a death toll from an organism that many clinicians would regard as a nuisance contaminant. The authors argue that their findings justify a more proactive diagnostic pathway. In their view, any preterm infant with a positive blood culture for Bacillus cereus should undergo lumbar puncture to examine the cerebrospinal fluid and cranial imaging as soon as possible, rather than waiting for neurological signs to appear. By the time seizures, bulging fontanelles, or other overt signs of central nervous system involvement emerge, an abscess may already be forming. Serial neuroimaging and long-term neurodevelopmental follow-up round out the recommended approach, ensuring that survivors are monitored for delays that may only become apparent as they grow.

Where does the bacterium come from in the first place? The study points to potential sources that are uncomfortably close to the infant’s bedside: contaminated environmental surfaces, medical equipment, and nutritional products, including breast milk and formula. Bacillus cereus is a spore-forming organism, and its spores are notoriously resistant to heat, drying, and disinfectants, allowing it to persist on surfaces and in equipment long after cleaning. This resilience is what makes the bacterium such a formidable opportunist in hospital settings. The authors emphasize that prevention rests on disciplined fundamentals: strict hand hygiene among staff and caregivers, regular and thorough disinfection of the environment and medical devices, and careful handling of breast milk and formula to prevent bacterial growth. These measures are neither glamorous nor technologically novel, but they target the routes by which spores travel from the environment into the bloodstream of an infant whose immune defenses are still under construction.

The significance of this study lies less in any single statistic than in the cumulative picture it paints. Bacillus cereus sepsis in preterm infants is rare enough that most evidence has previously been limited to isolated case reports or small series, leaving clinicians without a clear sense of the typical presentation, the likely course, or the full range of complications. By assembling nineteen cases from a single center and pairing them with a systematic review of the brain abscess literature, the Quanzhou team has transformed a scattered collection of anecdotes into a coherent clinical profile: a non-specific onset marked by poor responsiveness, fever, apnea, and escalating respiratory support; universal beta-lactam resistance demanding prompt antimicrobial adjustment; and a real, quantifiable risk of meningitis and brain abscess with lasting developmental consequences. For the neonatologists and infection-control teams who staff the world’s intensive care nurseries, the study is a call to take this soil-dwelling organism seriously, to investigate positive cultures rather than dismissing them, and to look beyond the bloodstream toward the brain before it is too late.

Subject of Research: Invasive Bacillus cereus sepsis and neurological complications in hospitalized preterm infants

Article Title: Invasive Bacillus cereus infection in hospitalized preterm infants: clinical characteristics, outcomes, and neurological complications from a single-center retrospective case series

Article References: Xue’e, Z., Zhiyong, L., Xialin, Y., Jiangbin, C., Jingyang, Z., Tianfeng, C., Ruiquan, W., Lianqiang, W., Weifeng, Z., Jinglin, X., Dongmei, C., & Hongyuan, Y. (2026). Invasive Bacillus cereus infection in hospitalized preterm infants: clinical characteristics, outcomes, and neurological complications from a single-center retrospective case series. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14504-y

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14504-y

Keywords: Bacillus cereus, preterm infants, neonatal sepsis, brain abscess, meningitis, neonatal intensive care, antimicrobial resistance, meropenem, vancomycin, neurodevelopmental delay, healthcare-associated infection, infection control

Scrub typhus is caused by Orientia tsutsugamushi, an obligate intracellular bacterium transmitted to humans through the bite of infected larval mites, commonly called chiggers. The disease is a major public health problem across the Asia-Pacific region, from Japan and Korea through Southeast Asia to northern Australia and the Indian subcontinent, with an estimated one million cases annually. Classically, infection produces a fever, headache, and a distinctive skin lesion known as an eschar, a dark, necrotic scab that forms at the site of the mite bite. The eschar is one of the most useful diagnostic signs in older children and adults. But in neonates, as the new report makes clear, the lesion may be entirely absent, stripping clinicians of the single most recognizable feature of the disease and leaving a nonspecific picture of fever and sepsis-like deterioration that can easily be mistaken for bacterial sepsis or meningitis.

The three infants described in the series all presented during the second to fourth week of life, an age when neonatal sepsis is a constant concern in any neonatal intensive care unit. Each of them showed involvement of multiple organ systems, and each displayed neurological manifestations, ranging in severity from encephalitic signs to seizures. Notably, none of the three had a typical eschar, which is precisely the feature that usually allows clinicians in endemic regions to suspect scrub typhus at the bedside. Without that sign, the infants’ illnesses looked like any number of other neonatal emergencies, and the correct diagnosis might have remained elusive without advanced molecular testing.

An intriguing epidemiological thread runs through all three cases. In retrospect, all three mothers reported having been diagnosed with scrub typhus during their pregnancies. However, the authors are careful to note that none of these maternal histories could be independently verified, because the original medical records and laboratory results from the mothers’ illnesses were unavailable. This distinction matters enormously for what the cases can and cannot tell us about how the babies were infected. A maternal history of scrub typhus during pregnancy raises the possibility of transplacental transmission of Orientia tsutsugamushi from mother to fetus, a route of infection that has been suggested in the literature but remains difficult to prove. The authors explicitly state that their data do not establish transplacental transmission, and they emphasize that postnatal acquisition, through mite bites after birth, cannot be excluded. In other words, the shared maternal histories are an important clue, but not a demonstration of congenital infection.

One of the three cases offers a particularly striking natural experiment. The affected infant was one member of a dichorionic diamniotic twin pair, meaning the twins developed from two separate fertilized eggs with separate placentas and separate amniotic sacs. While one twin fell gravely ill, the co-twin remained completely asymptomatic, and targeted genetic testing of both blood and cerebrospinal fluid from the healthy twin came back negative for Orientia tsutsugamushi. This discordance is fascinating from a transmission standpoint. If the infection had been acquired transplacentally, one might have expected both twins to be at risk, although separate placentas could in principle lead to separate outcomes. If the infection was acquired postnatally through a mite bite, discordance would be less surprising. The twin case therefore illustrates exactly why the authors resist drawing firm conclusions about the route of transmission from their small series.

The neurological dimension of these cases deserves particular attention. Two of the three infants had strong evidence of central nervous system involvement, while the third developed seizures in the context of severe systemic illness accompanied by major metabolic disturbances, a situation in which seizures can arise from metabolic derangement rather than direct infection of the brain. Central nervous system involvement in scrub typhus is recognized in older patients, where the organism can cause meningitis or encephalitis, but documenting it in neonates is exceptionally rare. The report suggests that when scrub typhus strikes newborns, the brain may be a frequent target, and that neurological signs in a febrile neonate from an endemic region should prompt consideration of this diagnosis alongside the usual suspects.

Establishing the diagnosis in these cases depended on next-generation sequencing, a family of molecular techniques that can detect the genetic material of pathogens in clinical samples without requiring the organism to be cultured or targeted with specific tests. In one patient, Orientia tsutsugamushi was detected using blood metagenomic next-generation sequencing, an unbiased approach that sequences all genetic material in a sample and identifies pathogens by matching the results against databases. In the other two patients, the diagnosis came from targeted next-generation sequencing of blood and, in some cases, cerebrospinal fluid. This technological angle is one of the most important practical lessons of the report. Routine investigations in neonatal sepsis, including blood cultures, are often unrevealing in scrub typhus because Orientia is an intracellular bacterium that is difficult to culture, and serological tests, the mainstay of diagnosis in adults, may be unreliable in the earliest days of infection. Molecular testing may establish an etiological diagnosis precisely when conventional methods come up empty.

The outcomes in the series were starkly divided. One infant recovered after treatment with azithromycin followed by doxycycline, the macrolide and tetracycline-class antibiotics that are the standard therapies for scrub typhus. The other two infants died after progressive multiorgan dysfunction. The survival of the treated infant underscores a point that infectious disease specialists have long emphasized for scrub typhus in general: the infection is treatable, and early appropriate antibiotic therapy can be lifesaving, but delays in diagnosis allow the organism to drive escalating inflammation, coagulopathy, liver injury, and organ failure. In neonates, where clinical deterioration can be rapid and nonspecific, the window for effective intervention may be especially narrow, which makes clinical suspicion and rapid diagnostic workup all the more critical.

The authors draw a clear set of practical conclusions for clinicians working in endemic areas. Neonatal scrub typhus can cause life-threatening multisystem disease and may involve the central nervous system. In regions where the disease circulates, it should be considered in any neonate with unexplained fever, sepsis-like illness, thrombocytopenia, which is a low platelet count, coagulopathy, liver injury, or neurological manifestations, even in the complete absence of an eschar. This expanded case definition is significant because it shifts scrub typhus from a diagnosis that depends on a visible skin lesion to one that depends on pattern recognition and laboratory confirmation. A retrospectively reported maternal history of scrub typhus during pregnancy, even when unverifiable, should be treated as an important epidemiological clue that lowers the threshold for molecular testing.

Beyond the immediate clinical lessons, the case series highlights gaps that future research will need to fill. The question of whether Orientia tsutsugamushi can cross the placenta and infect the fetus remains open, and well-documented twin pregnancies, prospective maternal cohorts in endemic regions, and systematic molecular testing of neonates with sepsis-like illness could all help resolve it. The report also illustrates the growing role of metagenomic and targeted sequencing in neonatal intensive care, where rapid, unbiased pathogen detection can make the difference between a correct diagnosis and a fatal blind spot. For now, the message from Yunnan is straightforward: in the mite-endemic belt that spans much of Asia, the youngest and most vulnerable patients can fall victim to scrub typhus, and the absence of the disease’s most famous sign should never be taken as reassurance.

Subject of Research: Neonatal scrub typhus with neurological manifestations caused by Orientia tsutsugamushi

Article Title: Neonatal scrub typhus with neurological manifestations: a case series from an endemic region

Article References: Yu, X., Li, J., Yang, P., Song, Y., Xi, M., Cui, S., Zhanghuang, C., & Liu, L. (2026). Neonatal scrub typhus with neurological manifestations: a case series from an endemic region. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14578-8

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14578-8

Keywords: scrub typhus, Orientia tsutsugamushi, neonates, central nervous system infection, next-generation sequencing, Yunnan Province, neonatal sepsis, eschar, transplacental transmission, doxycycline, azithromycin, case series

The research team, led by Hanni Lin of Shenzhen Luohu People’s Hospital and Jinan University together with colleagues across four Shenzhen tertiary neonatal intensive care units, analyzed data from 434 neonates who received delivery room PPV resuscitation and were admitted to one of the participating NICUs within 24 hours of birth during 2024. The cohort was deliberately balanced: exactly half of the infants, 217, were preterm, and half were full-term. Among the preterm babies, 148, or 68.2 percent, were managed with PPV alone, while 69, or 31.8 percent, required intubation. Full-term infants were far less likely to need the invasive route, with 187, or 86.2 percent, receiving PPV and only 30, or 13.8 percent, undergoing ETI. All families provided informed consent, and the study was approved by the Clinical Research Ethics Committee of Shenzhen Luohu People’s Hospital and conducted in accordance with the Declaration of Helsinki.

One of the central challenges in studying neonatal resuscitation is that babies who are intubated are, almost by definition, sicker to begin with. They tend to be born earlier, weigh less, and arrive with more compromised physiology. If researchers simply compare outcomes between intubated and non-intubated infants, the results can be badly distorted by these baseline differences, a problem known in epidemiology as confounding by indication. The Shenzhen team tackled this head-on using a statistical technique called propensity score weighting, abbreviated PrSW, which mathematically reweights the two groups so that measured baseline characteristics, such as gestational age, birth weight, antenatal steroid exposure, premature rupture of membranes, and mode of delivery, are balanced between them. The analysis was stratified by gestational age, meaning preterm and full-term infants were evaluated in separate strata, and stratified multiple binary logistic regression was then used to estimate both crude and weighted-adjusted odds ratios for a battery of in-hospital adverse events.

Before adjustment, the picture was stark. Neonates who required intubation displayed markedly poorer baseline profiles, and their crude rates of complications were correspondingly higher across nearly every endpoint the team measured, from respiratory distress syndrome to sepsis to metabolic disturbances. But the propensity-weighted analysis told a more nuanced story. Most of the crude excess risk in the ETI group lost statistical significance after weighting, indicating that a large share of the apparent harm reflected underlying illness rather than the procedure itself. Yet a set of associations survived the adjustment, and these residual, independently associated risks followed patterns that differed by gestational age in ways the authors describe as gestational-age dependent.

For preterm infants, intubation in the delivery room was independently associated with elevated odds of five distinct adverse outcomes. The adjusted odds ratio for pneumonia was 2.482, with a 95 percent confidence interval of 1.134 to 5.431 and a P value of 0.023. Pulmonary hemorrhage showed one of the strongest signals in the entire study, with an adjusted odds ratio of 12.476, though the confidence interval of 1.413 to 110.158 was wide, reflecting the small number of events. Respiratory distress syndrome carried an adjusted odds ratio of 6.156, with a confidence interval of 2.06 to 18.397 and a P value of 0.001. Sepsis was associated with an adjusted odds ratio of 2.354, and hyperglycemia with an adjusted odds ratio of 4.075, the latter with a P value below 0.001. Taken together, the preterm findings point to a cluster of pulmonary, infectious, and metabolic risks that travel with delivery room intubation even after accounting for how sick the babies were at baseline.

The full-term stratum produced a different and, in some respects, more surprising risk profile. In these infants, intubation was not significantly associated with the pulmonary complications that dominated the preterm analysis. Instead, the adjusted analysis revealed markedly elevated odds of sepsis, with an adjusted odds ratio of 12.773 and a confidence interval of 2.739 to 59.573, and an extraordinary association with hyperglycemia, whose adjusted odds ratio reached 46.268 with a confidence interval of 9.067 to 236.114 and a P value below 0.001. Full-term intubated infants were also far more likely to experience composite adverse events, with an adjusted odds ratio of 8.899. The authors suggest that because full-term infants rarely need intubation, those who do may represent an especially vulnerable subgroup, and the metabolic signal in particular may reflect the profound physiological stress of a difficult resuscitation in a baby whose lungs were otherwise mature.

The mechanistic logic behind these associations is plausible, though the study’s retrospective design means it can establish association rather than causation. Intubation bypasses the upper airway, which normally filters, warms, and humidifies inspired gas, and the procedure can introduce microtrauma and colonizing organisms into the trachea, pathways that could plausibly contribute to pneumonia and sepsis. Positive pressure delivered through a tube also generates different pressure distributions within the immature lung than mask ventilation, which may help explain the pulmonary hemorrhage and respiratory distress signals in preterm infants. Hyperglycemia, meanwhile, is a well-recognized stress response in critically ill neonates, and the strength of the metabolic associations in both strata suggests that the need for intubation may serve as a marker for a level of physiological derangement that conventional baseline variables do not fully capture.

The authors are careful about the limits of their work. As a retrospective cohort study relying on data collected through a pre-specified standardized case-report form, it cannot exclude residual confounding by unmeasured factors, such as the precise indication for intubation, the skill and experience of the resuscitating team, or the duration of the procedure. The single-year, single-city design, drawing on four tertiary NICUs within the Shenzhen Neonatal Data Network, may also limit generalizability to settings with different resources or case mixes. Long-term developmental outcomes were not available and were explicitly excluded from this analysis; the team states that follow-up data on longer-term events will be reported once that phase of the study is complete. The wide confidence intervals around some estimates, particularly for rare events like pulmonary hemorrhage, further underscore the need for cautious interpretation.

Even with those caveats, the study carries practical weight for a field in which delivery room decisions must be made in seconds. Current international resuscitation guidelines already emphasize that intubation should be reserved for infants who fail adequate PPV or who have specific indications, precisely because the procedure is technically demanding and carries its own risks. The new findings add gestational-age-specific texture to that principle: for preterm infants, the associated burden clusters in the lungs and in infection and metabolic control, while for full-term infants the dominant signals are sepsis, hyperglycemia, and overall composite morbidity. The authors argue that standardized delivery room resuscitation protocols and targeted post-resuscitation risk monitoring, tailored to gestational age, could help reduce these morbidities, for example by flagging intubated preterm infants for heightened surveillance of pulmonary complications and infection, and by monitoring glucose closely in any full-term infant who required a tube.

For clinicians and researchers alike, the study is a reminder that the first minutes of life cast long shadows across the entire hospital stay, and that the tools used to save a newborn’s breath are not clinically neutral. As neonatal care continues to improve survival at ever earlier gestations, disentangling the harms of underlying illness from the harms of the interventions themselves becomes both harder and more important. The Shenzhen team’s propensity-weighted, gestational-age-stratified approach offers a template for that disentangling, and their forthcoming long-term follow-up data will be watched closely by neonatologists eager to know whether the short-term signals documented here translate into lasting differences in neurodevelopment and health. In the meantime, the message for the delivery room is measured but clear: when it comes to intubating a newborn, less may often be more, and every tube placed deserves a plan for the risks that follow.

Subject of Research: Gestational-age-specific associations between delivery room endotracheal intubation versus positive pressure ventilation and short-term in-hospital adverse outcomes in neonates

Article Title: Short-term neonatal in-hospital associations following delivery room ETI versus PPV resuscitation: a multicenter retrospective cohort study

Article References: Lin, H., Yu, Z., Tu, H., Zhang, A., Zhang, F., Li, G., Yuan, S., Fang, X., & Liu, J. (2026). Short-term neonatal in-hospital associations following delivery room ETI versus PPV resuscitation: a multicenter retrospective cohort study. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07726-1

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07726-1

Keywords: neonatal resuscitation, endotracheal intubation, positive pressure ventilation, preterm infants, full-term infants, neonatal sepsis, hyperglycemia, respiratory distress syndrome, propensity score weighting, delivery room, NICU, retrospective cohort study

The research team, led by Abeya Fufa Worke of Mattu University together with colleagues from the university’s departments of midwifery and nursing, reviewed the medical records of 512 newborns admitted with sepsis to the hospital’s Neonatal Intensive Care Unit between January 2022 and December 2023. The two-year window captured a broad cross-section of cases in a region where specialized neonatal care is scarce and every day of hospitalization carries both clinical and economic weight for families.

The headline result is strikingly encouraging. Of the 512 neonates included in the final analysis, 497, or 95.2 percent, recovered from their infection. The median time to recovery was just six days, with an interquartile range of five to seven and a half days, meaning half of the surviving newborns were well enough to leave intensive care within roughly a week of admission. For a hospital operating in a resource-constrained corner of Southwest Ethiopia, those numbers suggest that the NICU’s standard care pathway is working.

But the study’s deeper contribution lies in its statistical machinery. Rather than simply comparing averages, the researchers deployed survival analysis techniques, beginning with Kaplan-Meier curves to visualize how recovery probability changed day by day, and then fitting a Weibull regression model to identify which clinical characteristics independently accelerated or delayed recovery. The Weibull distribution, a flexible parametric approach, is particularly well suited to time-to-event data like hospital recovery, where the hazard of recovery can rise or fall over the course of illness. Model selection was guided by the Akaike and Bayesian Information Criteria, and the team checked for multicollinearity using variance inflation factors, a level of methodological rigor that strengthens confidence in the final estimates.

The regression model surfaced a cluster of clinical predictors associated with slower recovery. Newborns presenting with leukopenia, an abnormally low white blood cell count, took longer to recover, a biologically plausible finding since a depleted immune cell arsenal limits the body’s capacity to clear infection. Respiratory distress and apnea, the latter referring to pauses in breathing that are common and dangerous in septic newborns, also predicted prolonged recovery, as did poor feeding, which can compound weakness and delay the return to normal growth.

Two additional factors stood out. Late-onset sepsis, defined as infection occurring between the eighth and twenty-eighth days of life, was linked to slower recovery compared with early-onset disease acquired within the first week. And newborns who received a clinical diagnosis of meningitis, an infection of the membranes surrounding the brain, faced a markedly longer road back to health. Meningitis in the neonatal period is notoriously difficult to treat, as antibiotics must penetrate the blood-brain barrier, and it often signals a more severe or disseminated infection.

The distinction between early-onset and late-onset sepsis carries practical implications. Early-onset infections typically stem from organisms acquired from the mother during delivery, while late-onset cases more often arise from the hospital or community environment. The finding that late-onset disease predicts slower recovery underscores the importance of infection prevention measures within NICUs themselves, from rigorous hand hygiene to careful management of invasive devices, as well as prompt recognition of illness in babies who have already gone home.

For clinicians working under the World Health Organization’s Integrated Management of Neonatal and Childhood Illness framework, the study offers a practical triage signal. A newborn with sepsis who also shows respiratory distress, apnea, poor feeding, or low white blood cell counts is not just sicker on arrival but statistically likely to occupy a NICU bed longer. Anticipating that trajectory could guide earlier escalation of care, closer monitoring, and more proactive nutritional support, potentially shaving critical days off recovery time.

The authors are careful to frame the findings within the limits of a retrospective, record-based design. Because the analysis relied on de-identified medical records rather than prospective follow-up, the predictors reflect associations observed in routine clinical documentation, and the diagnosis of meningitis was made clinically rather than confirmed by lumbar puncture in every case. The ethics committee of Mattu University’s Institutional Health Research Ethics Review Committee approved the study under the Declaration of Helsinki and formally waived individual informed consent given the retrospective use of de-identified data.

Even with those caveats, the study delivers a message of cautious optimism. A 95.2 percent recovery rate and a median stay of six days indicate that effective neonatal sepsis care is achievable far from the well-resourced hospitals of high-income countries. The path forward, the researchers conclude, lies in targeting the specific complications that slow recovery, particularly respiratory problems, meningitis, and feeding difficulties. For the thousands of Ethiopian families whose newborns face this infection each year, closing that gap could mean the difference between a one-week scare and a far longer, more dangerous ordeal.

Subject of Research: Time to recovery and predictors of neonatal sepsis in a Southwest Ethiopian neonatal intensive care unit

Article Title: Time to recovery and predictors of neonatal sepsis in Southwest Ethiopia, 2024

Article References: Balcha, M. L., Worke, A. F., Tesfaye, H., & Bidira, K. (2026). Time to recovery and predictors of neonatal sepsis in Southwest Ethiopia, 2024. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14576-w

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14576-w

Keywords: neonatal sepsis, Ethiopia, recovery time, survival analysis, Weibull regression, Kaplan-Meier, NICU, leukopenia, apnea, respiratory distress, meningitis, late-onset sepsis