Backgrounds:

We aim to describe outcomes (focusing on hearing and neurological findings) and transfer of maternal antibodies in infants born from mothers with SARS-CoV-2 infection during pregnancy.

Methods:

Observational prospective study performed in a tertiary hospital in Madrid (Spain). Infants born from mothers with SARS CoV-2 infection during pregnancy from March to September 2020 were included. SARS-CoV-2 RT-PCT on nasopharyngeal swab (NPS) was performed at birth to infants born from mother with acute infection at delivery. A follow-up visit with physical and neurological examination, SARS-CoV-2 RT-PCR on NPS, SARS-CoV-2 serology, and a cranial ultrasound (cUS) was performed within 3 months of life. Automated auditory brainstem response (A-ABR) exams were performed at birth, and auditory steady-state response (ASSR) at six months of life.

Results:

95 infants born from 94 mothers were included. Median gestational age was 39+3 (IQR 38-40) and 10 (10.5%) were preterm. Thirteen (13.7%) newborns required hospital admission after birth, none of them with a COVID-19 infection. Rates of vertical (1/28; 3.6%) and horizontal (1/93; 1.1%) transmitted infections were low, with mild symptoms. In follow-up visit, neurological examination was normal in all infants. Cranial ultrasound was normal in 81/85 (95.3%) infants, with mild abnormalities in four infants. 47/ 95 (50%) infants had a positive serology. Serology result was not related to the severity of the maternal infection, skin-to-skin care at birth or breastfeeding. There was a progressive decrease in SARS-CoV-2 antibody titers with the age (figure 1). No hearing loss was detected.

Conclusions/Learning Points:

In this cohort, most infants born from mothers with SARS-CoV-2 infection during pregnancy had normal cUS, hearing screening and neurological examinations in the follow-up. There is a rapid decrease in transferred maternal antibodies in the first months of life.

Backgrounds:

Initial antibiotic treatment in appendicitis/peritonitis significantly reduces wound infection and intra-abdominal abscess formation in patients with gangrenous or perforated appendicitis. Randomized controlled trials have shown that the use of lower-spectrum antibiotic combinations is as effective in preventing abscesses or surgical wound infections as broad-spectrum regimens.

Methods

Observational, retrospective study of patients <16 years of age admitted for appendicitis and/or peritonitis from Jan/2014 to Dec/2019 in a tertiary university hospital in Madrid, Spain. Three study periods were established: P1 2014-2015 (before Antimicrobial Stewardship Programme (ASP)), P2 2016-2018 (ASP implemented) and P3 Jan/2019-Dec/2019 (ASP and implementation of an appendicitis/peritonitis protocol with electronic prescription, including lower-spectrum antibiotic combinations and selected and clinically guided use after surgery). Antimicrobial use was analysed with the days of therapy/1000 admissions days (DOT/1000) and start of treatment/1000 hospital admissions (SOT/1000).

Results:

During the study period a total of 1619 patients met inclusion criteria. The proportion of patients without antibiotic therapy after surgery during P1, P2 and P3 was 5.6%, 3.7%, and 38.6% respectively. [C1] The evolution of antibiotic use expressed by DOT / 1000 is shown in Figure 1. SOT/1000 of ampicillin, gentamicin and metronidazole rose from 162, 190 and 190 in 2014 to 386, 402 and 409 in 2019. DOT/1000 of meropenem drop to 64.85 in 2014 to 0 in 2019.

Conclusions/Learning Points:

The implementation of an ASP and a low-spectrum antibiotic protocol with electronic prescribing, reduced the antimicrobial use in children with appendicitis/peritonitis. The proportion of patients without antibiotic therapy after surgery increased and the use of carbapenems and other broad-spectrum antibiotics was reduced after the intervention. These improvements were observed when an electronically available protocol was added to the ASP implementation.

Backgrounds:

Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of CNS infection in young infants. They have been implicated in neurodevelopmental delay, limited data are available. The aim of this study is to describe clinical outcome and to assess and compare medium-term neurodevelopment following EV and HPeV-CNS-infections.

Methods

A multicentre observational ambispective study was conducted between May-2013 and March-2018. Children under 3 months with EV or HPeV CNS-infection excluding encephalitis were included. Infants were contacted one year after acute infection. Their neurological development was evaluated using ASQ-3-test. If any area was abnormal during first round, a second round was completed later.

Results:

Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) EV and 15 (31.3%) HPeV. At first assessment 14/29 (48.3%) EV and 3/15 (20%) HPeV positive cases presented some developmental concern in the ASQ-3-test. EV-positive infants showed mild and moderate alteration in all domains analysed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (p=0.016). At second assessment 4/13 (30.8%) EV-positive patients showed mild to moderate concerns in communication and gross motor function and 3/13 (23.1%) showed significant concern in fine motor function.

Conclusions/Learning Points:

Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months, 48.3% of the EV-infected infants and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3-test. We recommend monitor neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation if necessary.

Backgrounds:

Multisystem inflammatory syndrome in children (MIS-C) is a condition characterized by a dysregulated response of the immune system 2-6 weeks after a SARS-CoV-2 infection. Some authors hypothesized that the COVID-19 vaccine could trigger a new exaggerated response in these children.

Our aim was to assess the proportion of vaccinated children and the incidence of new MIS-C or myocarditis after vaccination in adolescents with previous MIS-C.

Methods

From the Epidemiological Study of COVID-19 in Children of the Spanish Pediatric Association, we contacted researchers from centers with ≥3 MIS-C patients aged 12-18 years old by October 31, 2021, hospitalized from March 2020, through October 2021 and fulfilling WHO criteria for MIS-C.

We performed a semi-structured telephonic interview with the caregivers and/or the adolescents, about vaccination acceptance and adverse events after vaccination.

Results:

An interview was possible in 42/48 (87.5%) selected adolescents, being mainly male (30/42, 71.4%) and, at MIS-C diagnosis, their median age was 13.1 years old. 32/42 (76.2%) patients had received COVID-19 vaccine. The median time between MIS-C diagnosis and vaccination was 42 weeks and the telephonic interview took place after a median of 10.0 weeks (range 5.3-19.7) post-vaccination. After vaccination, 22/32 (68.8%) patients reported adverse events, being 86.7% mild and 3.3% moderate (Table1). No new MIS-C or myocarditis or pericarditis episodes were reported.

Conclusions/Learning Points:

In this study, we describe a high acceptance and low incidence of relevant adverse events after COVID-19 vaccines in a population of adolescents with a previous MIS-C diagnosis. No new MIS-C episodes or myocarditis occurred after a median of 10 weeks post-vaccination. The results of this study are reassuring and may help to decide for patients with previous MIS-C who are considering COVID-19 vaccination.

Backgrounds:

There is a need to assess the immunogenicity and duration of immune response to SARS-CoV-2 mRNA vaccination in HIV-infected patients. Scarce data exist on HIV-infected adolescents.

Methods

A prospective ongoing observational study is being conducted in HIV-infected patients > 12 years of age after the introduction of mRNA vaccination in Spain. Blood samples were drawn 3-10weeks after the first or second dose (according to prior SARS-CoV2 infection) of BNT162b2 (Pfizer/BioNTech) and CoV-2-mRNA-1273 (Moderna) vaccines in 20 HIV-infected adolescents and compared to 20 matched healthy-control subjets. Humoral response was assesed by detection of SARS-CoV-2 antibodies by chemiluminescent-microparticle-immunoassay (CMIA) (Alinity® Quant assay-Abbott) to detect IgG against S1-region of the spike-protein of SARS-CoV-2 (≥50U/mL considered reactive). T-Cell response to SARS-CoV-2 was measured by an interferon-gamma-released-assay (IGRA,Euroimmun) of S1 peptide-stimulated T-cells in whole blood (≥200mlU/ml considered reactive).

Results:

Blood samples from 20 HIV-infected adolescents were drawn after vaccination (15 Pfizer/BioNTech, 5 Moderna), see figure one. Mean age was 16.7±3.9 and 14.3±3.9 years in patients and controls, respectively (p:0.06). Mean intervals since last vaccine dose in HIV-infected and controls were 44.0±15.1 and 38.5±12.6 days,(p>0.05). Two HIV-infected patients and 6 controls had documented past SARS-CoV-2 infection.

All patients and controls had reactive humoral and celular responses. HIV-infected subjects had lower anti-Spike antibodies titers (mean 14251±8270 U/mL) than controls (mean 27716±15768 U/mL)(p:0.013). Likewise, cellular immune responses were lower in HIV-infected adolescents (mean 1609±418 mlU/ml) than in controls (mean 1777±356 mlU/ml),(p:0.024).

Conclusions/Learning Points:

Perinatally HIV-infected adolescents with good immunologic and virological status elicit appropriate specific antispike-antibody levels and cellular immune responses against SARS-CoV-2 shortly after mRNA vaccination, but of lower amount than healthy control subjects. More prolonged studies are underway to determine the evolution of humoral and cellular immune responses after vaccination.

Backgrounds:

Multidrug resistant bacteria (MDRB) infections are a rising concern, especially those associated with healthcare environments. The aims of this study were to describe the characteristics of MDRB colonizations in paediatric patients admitted to a Haemato-Oncology ward and to establish the risk of having a MDRB infection in a patient previously colonised.

Methods

Multicentre prospective observational study from May 2021-March 2022 in Spain. Patients < 18 years with diagnosis of cancer or hematopoietic stem cell transplantation (HSCT) admitted to Hemato-Oncology wards, were included. Rectal and nasal swabs for MDRB detection were performed at inclusion and periodically during a 90-day follow-up period. Active infection surveillance was performed during follow-up.

Data of colonization at baseline is presented.

Results:

111 patients were included: Median age was 8 (±5,5) years and 60 (54,1%) were women. Most common diagnosis were leukemia (52;46.8%), solid tumour (43;38.7%), sickle cell disease (SCD) (6;5.4%) and lymphoma (4;3.6%). 20 (18%) had undergone a HSCT.

14 (12.6%) had a MDRB colonization at baseline and 3 (2.7%) a double colonization. MDRB detected were ESBL-producing enterobacteria (7;50%), carbapenemase-producing enterobacteria (6;42.9%), MDR-Pseudomonas (2;14.3%) and MRSA (1;7.1%). No MDR-Acinetobacter or vancomycin-resistant Enterococcus were detected. The main ESBL-producing enterobacteria was E. coli (75%) and the main carbapenemase detected, VIM (66.7%). Risk factors for MDRB colonization were SCD diagnosis (p=0.03) and a previous colonization (p<0.01). Children with colonizations were more likely to have a HSCT and their father’s were more likely to have been born abroad, with no statistical significance.

Conclusions/Learning Points:

Rates of ESBL and carbapenemase-producing enterobacteria colonization in a cohort of paediatric patients with cancer or SCT in Spain was high.

Children with SCD and a previous colonization have a higher risk

Backgrounds:

Gram-negative bacteremia (GNB) is associated with a significant rate of morbidity and mortality in adults. Moreover, resistances to antibiotics are increasingly described in surveillance reports. However, the epidemiology and outcomes of GNB in children are not well known. We aimed to analyze GNB bacteremia in pediatric patients in a tertiary hospital over a three years period.

Methods

A retrospective, observational study of bacteremia episodes caused by Enterobacteriaceae or non-fermentative GNB in pediatric patients between January of 2018 and December 2020 in a Tertiary Hospital from Madrid, Spain, was carried out through microbiology charts and clinical records. Demography, comorbidities, risk factors and infection characteristics were recorded, and bacterial strain and antibiotic resistance were registered. Three primary endpoints were defined: mortality, bacteremia persistence and recurrence. A statistical analysis was applied to assess differences in these outcomes according to the risk factors. A multivariable logistic regression analysis was used to assess the association between bacteria resistance and mortality.

Results:

One hundred eighteen cases of GNB in one hundred and seven patients were included. The characteristics of the patients are shown in Table 1. In fifty-three cases (44.9%) GNB presented resistance to at least one group of antibiotic and in nine (7.6%) were multidrug-resistant (Table 1). The incidence of resistance rates by years were stable. Indwelling urinary catheterization was a risk factor associated to mortality [OR 3.48 (1.20-10.6)] and parenteral nutrition was related to persistent bacteremia [OR 7.69 (1.1-209)]. No relation between drug resistance and mortality was observed in multivariable analysis.

Conclusions/Learning Points:

GNB represented an important problem in our institution, mainly related to neonatal intensive care and heart surgery. Antibiotic resistance was common. Patients that carried invasive care devices presented higher rates of bacteremia persistence and mortality.