Phage therapy is an experimental therapeutic approach used to target multidrug-resistant bacterial infections. A lack of reliable data with regard to its efficacy and regulatory hurdles hinders a broad application. Here we report, for the first time, a case of vancomycin-resistant Enterococcus faecium abdominal infection in a one-year-old, critically ill, and three times liver transplanted girl, which was successfully treated with intravenous injections (twice per day for 20 days) of a magistral preparation containing two Enterococcus phages. This correlated with a reduction in baseline C-reactive protein (CRP), successful weaning from mechanical ventilation and without associated clinical adverse events. Prior to clinical use, phage genome was sequenced to confirm the absence of genetic determinants conferring lysogeny, virulence or antibiotic resistance, and thus their safety. Using a phage neutralization assay, no neutralizing anti-phage antibodies in the patient’s serum could be detected. Vancomycin-susceptible E. faecium isolates were identified in close relation to phage therapy and, by using whole-genome sequencing, it was demonstrated that vancomycin-susceptible E. faecium emerged from vancomycin-resistant progenitors. Covering a one year follow up, we provide further evidence for the feasibility of bacteriophage therapy that can serve as a basis for urgently needed controlled clinical trials.

Introduction: Electrical velocimetry (EV) is a type of impedance cardiography, and is a non-invasive and continuously applicable method of cardiac output monitoring. Transthoracic echocardiography (TTE) is non-invasive but discontinuous. Methods: We compared EV with TTE in pediatric intensive care patients in a prospective single-center observational study. Simultaneous, coupled, left ventricular stroke volume measurements were performed by EV using an Aesculon® monitor and TTE (either via trans-aortic valve flow velocity time integral [EVVTI], or via M-mode [EVMM]). H₀: bias was less than 10% and the mean percentage error (MPE) was less than 30% in Bland–Altman analysis between EV and TTE. If appropriate, data were logarithmically transformed prior to Bland–Altman analysis. Results: A total of 72 patients (age: 2 days to 17 years; weight: 0.8 to 86 kg) were analyzed. Patients were divided into subgroups: organ transplantation (OTX, n =28), sepsis or organ failure (SEPSIS, n =16), neurological patients (NEURO, n =9), and preterm infants (PREM, n =26); Bias/MPE for EVVTI was 7.81%/26.16%. In the EVVTI subgroup analysis for OTX, NEURO, and SEPSIS, bias and MPE were within the limits of H₀, whereas the PREM subgroup had a bias/MPE of 39.00%/46.27%. Bias/MPE for EVMM was 8.07%/37.26% where the OTX and NEURO subgroups were within the range of H₀, but the PREM and SEPSIS subgroups were outside the range. Mechanical ventilation, non-invasive continuous positive airway pressure ventilation, body weight, and secondary abdominal closure were factors that significantly affected comparison of the methods. Conclusions: This study shows that EV is comparable with aortic flow-based TTE for pediatric patients.

Hypothermia in pediatrics is mainly about small body size. The key thermal factor here is the large surface-to-volume ratio. Although small mammals, including human infants and children, are adapted to higher heat losses through their elevated metabolic rate and thermogenic capacity, they are still at risk of hypothermia because of a small regulatory range and an impending metabolic exhaustion. However, some small mammalian species (hibernators) use reduced metabolic rates and lowered body temperatures as adaptations to impaired energy supply. Similar to nature, hypothermia has contradictory effects in clinical pediatrics as well: In neonates, it is a serious risk factor affecting respiratory adaptation in term and developmental outcome in preterm infants. On the other hand, it is an important self-protective response to neonatal hypoxia and an evidence-based treatment option for asphyxiated babies. In children, hypothermia first enabled the surgical repair of congenital heart defects and promotes favorable outcome after ice water drowning. Yet, it is also a major threat in various prehospital and clinical settings and has no proven therapeutic benefit in pediatric critical care. All in all, pediatric hypothermia is an ambiguous issue whose harmful or beneficial effects strongly depend on the particular circumstances.

Advances in neonatology now enable increasing numbers of very low birth weight neonates (R<1500 g) to survive into early adulthood and beyond. What are the implications for their long-term care? Selective literature search on the outcome of very low birth weight neonates in adulthood (“adults born preterm”). Robust data are available on the pulmonary, metabolic, cardiovascular, renal, neurocognitive, sensory-visual, social-emotional, mental, reproductive, and musculoskeletal long-term risks. On the somatic level, elevated rates have been documented for asthma (odds Ratio [OR] 2.37), diabetes mellitus (OR 1.54), and chronic renal disease (hazard ratio [HR] 3.01), along with the cardiovascular and cerebrovascular sequelae of a tendency toward arterial hypertension. On the psychosocial level, the main findings are deficits in romantic partnerships (OR 0.72) and a lower reproduction rate (relative risk [RR] male/female 0.24/0.33). The affected women also have an elevated risk of preterm delivery. A risk profile with both somatic and psychosocial aspects can be discerned for adults who were born prematurely, even if some of these risks are present in low absolute numbers. As the ability to compensate for latent deficits declines with age, such adults may suffer from “premature aging as the late price of premature birth.” A holistic approach to care with personalized prevention strategies—which for most of them was discontinued at discharge from pediatric follow-up—therefore seems appropriate in adulthood as well.

Background: Nasal continuous positive airway pressure (CPAP) applies positive end-expiratory pressure (PEEP) and has been shown to reduce the need for intubation and invasive mechanical ventilation in very low birth weight infants with respiratory distress syndrome. However, CPAP failure rates of 50% are reported in large randomized controlled trials. A possible explanation for these failure rates is the application of insufficient low levels of PEEP during nasal CPAP treatment to maintain adequate functional residual capacity shortly after birth. The optimum PEEP level to treat symptoms of respiratory distress in very low birth weight infants has not been assessed in clinical studies. The aim of the study is to compare two different PEEP levels during nasal CPAP treatment in preterm infants. Methods: In this randomized multicenter trial, 216 preterm infants born at 26 + 0–29 + 6 gestational weeks will be allocated to receive a higher (6–8 cmH₂O) or a lower (3–5 cmH₂O) PEEP during neonatal resuscitation and the first 120 h of life. The PEEP level within each group will be titrated throughout the intervention based on the FiO₂ (fraction of inspired oxygen concentration) requirements to keep oxygenation within the target range. The primary outcome is defined as the need for intubation and mechanical ventilation for > 1 h or being not ventilated but reaching one of the two pre-defined CPAP failure criteria (FiO₂ > 0.5 for > 1 h or pCO₂ ≥ 70 mmHg in two consecutive blood gas analyses at least 2 h apart). Discussion: Based on available data from the literature, the optimum level of PEEP that most effectively treats respiratory distress syndrome in preterm infants is unknown, since the majority of large clinical trials applied a wide range of PEEP levels (4–8 cmH₂O). The rationale for our study hypothesis is that the early application of a higher PEEP level will more effectively counteract the collapsing properties of the immature and surfactant-deficient lungs and that the level of inspired oxygen may serve as a surrogate marker to guide PEEP titration. Finding the optimum noninvasive continuous distending pressure during early nasal CPAP is required to improve CPAP efficacy and as a consequence to reduce the exposure to ventilator-induced lung injury and the incidence of chronic lung disease in this vulnerable population of very preterm infants. Trial registration: drks.de DRKS00019940. Registered on March 13, 2020