Pseudomonas aeruginosa bloodstream infections in children and adolescents: risk factors associated with carbapenem resistance and mortality.

BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug resistant and 6.6% extensively drug resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, P<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, P=0.002) than BSIs caused by carbapenem-susceptible P. aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (aOR) 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.

Is it in their eyes? Correlation between microorganisms isolated from bronchial aspirates and conjunctival swabs in a Pediatric Intensive Care Unit.

OBJECTIVE: Our observational, retrospective study aimed to determine the correlation between bacteria isolated from bronchial aspirates of pediatric ICU patients (PICU) with respiratory infections and those obtained from conjunctival swabs of the same patients exhibiting clinical conjunctivitis. METHODS: Throughout the period from 2015 to 2022, we reviewed all clinically significant bronchial aspirates (≥105 CFU/mL) and positive conjunctival swabs obtained from PICU patients. These records were retrieved from the microbiology database, cross-referencing the data to identify patients who tested positive for both during the same clinical episode. RESULTS: The median age of the patients was 5 months (interquartile range: 1-7). Among the cohort, twenty-one patients exhibited positivity in both bronchial aspirate and conjunctival swab samples, showcasing a microbial match in 85.71% of cases (18 out of 21). The most frequently isolated microorganisms were Haemophilus influenzae (55.6%), followed by Pseudomonas aeruginosa (14.3%), Klebsiella aerogenes (9.5%), and Escherichia coli, Stenotrophomonas maltophilia, and Enterobacter cloacae, each accounting for 4.8% of the isolates. CONCLUSIONS: Our study demonstrates a strong concordance between the isolated microorganisms from both samples in patients presenting clear symptoms of clinical conjunctivitis. These findings provide a basis for future prospective studies that may leverage conjunctival swabs as a predictive tool for identifying microorganisms involved in respiratory infections.

Simulating the impact of non-pharmaceutical interventions limiting transmission in COVID-19 epidemics using a membrane computing model.

Epidemics caused by microbial organisms are part of the natural phenomena of increasing biological complexity. The heterogeneity and constant variability of hosts, in terms of age, immunological status, family structure, lifestyle, work activities, social and leisure habits, daily division of time and other demographic characteristics make it extremely difficult to predict the evolution of epidemics. Such prediction is, however, critical for implementing intervention measures in due time and with appropriate intensity. General conclusions should be precluded, given that local parameters dominate the flow of local epidemics. Membrane computing models allows us to reproduce the objects (viruses and hosts) and their interactions (stochastic but also with defined probabilities) with an unprecedented level of detail. Our LOIMOS model helps reproduce the demographics and social aspects of a hypothetical town of 10 320 inhabitants in an average European country where COVID-19 is imported from the outside. The above-mentioned characteristics of hosts and their lifestyle are minutely considered. For the data in the Hospital and the ICU we took advantage of the observations at the Nursery Intensive Care Unit of the Consortium University General Hospital, Valencia, Spain (included as author). The dynamics of the epidemics are reproduced and include the effects on viral transmission of innate and acquired immunity at various ages. The model predicts the consequences of delaying the adoption of non-pharmaceutical interventions (between 15 and 45 days after the first reported cases) and the effect of those interventions on infection and mortality rates (reducing transmission by 20, 50 and 80%) in immunological response groups. The lockdown for the elderly population as a single intervention appears to be effective. This modeling exercise exemplifies the application of membrane computing for designing appropriate multilateral interventions in epidemic situations.

Fosfomycin in the pediatric setting: Evidence and potential indications.

To date, there has been little experience in using fosfomycin in children. However, its broad spectrum of action and excellent safety profile have renewed interest in this antibiotic, especially for treating infections by multidrug-resistant bacteria. The main indication for fosfomycin in pediatrics is currently community-acquired lower urinary tract infection. Given its good activity against bacteria, fosfomycin can also be useful in urinary infections caused by extended-spectrum beta-lactamase-producing enterobacteria. Fosfomycin presents very good dissemination to tissues including bone and is therefore an option in the combined therapy of osteomyelitis, especially in cases produced by methicillin-resistant Staphylococcus aureus (MRSA) or in cases with beta-lactam allergies. Fosfomycin can also be employed in combination for multidrug-resistant Gram-negative bacteremia (especially carbapenemase-producing enterobacteria), S. aureus (if there is a high suspicion of MRSA or complicated infections) and vancomycin-resistant Enterococcus spp. Other infections in which fosfomycin could be part of a combined therapy include staphylococcal endocarditis (in case of beta-lactam allergy or MRSA), central nervous system infections (mainly by MRSA, S. epidermidis, Listeria and resistant pneumococcus), nosocomial pneumonia and infections associated with mechanical ventilation.

[Update on congenital and neonatal herpes infections: infection due to cytomegalovirus and herpes simplex]. / Actualizacion en infecciones herpeticas congenitas y neonatales: infeccion por citomegalovirus y herpes simple.

Newborn infants are a population which is especially susceptible to viral infections that frequently affect the central nervous system. Herpes infections can be transmitted to the foetus and to the newborn infant, and give rise to severe clinical conditions with long-term sensory and cognitive deficits. Two thirds of newborn infants with encephalitis due to herpes simplex virus and half of the children with symptomatic congenital infection by cytomegalovirus develop sequelae, which results in high community health costs in the long term. Fortunately, the better knowledge about these infections gained in recent years together with the development of effective antiviral treatments have improved the patients' prognosis. Valganciclovir (32 mg/kg/day in two doses for six months) prevents the development of hypoacusis and improves the neurological prognosis in symptomatic congenital infection due to cytomegalovirus. Acyclovir (60 mg/kg/day in three doses for 2-3 weeks) prevents the development of severe forms in skin-eyes-mouth herpes disease, and lowers the rate of mortality and sequelae when the disease has disseminated and is located in the central nervous system.

TITLE: Actualizacion en infecciones herpeticas congenitas y neonatales: infeccion por citomegalovirus y herpes simple.Los neonatos son una poblacion especialmente susceptible a las infecciones viricas que frecuentemente afectan al sistema nervioso central. Las infecciones herpeticas pueden transmitirse al feto y al recien nacido, y ocasionar cuadros clinicos graves con deficits sensoriales y cognitivos a largo plazo. Dos terceras partes de los neonatos con encefalitis por virus herpes simple y la mitad de los niños con infeccion congenita sintomatica por citomegalovirus desarrollan secuelas, lo cual supone un alto coste sociosanitario a largo plazo. Afortunadamente, el mejor conocimiento de estas infecciones en los ultimos años y el desarrollo de tratamientos antivirales efectivos han mejorado el pronostico de los pacientes. El valganciclovir (32 mg/kg/dia en dos dosis durante seis meses) previene el desarrollo de hipoacusia y mejora el pronostico neurologico en la infeccion congenita sintomatica por citomegalovirus. El aciclovir (60 mg/kg/dia en tres dosis durante 2-3 semanas) previene el desarrollo de formas graves en la enfermedad herpetica cutanea-ocular-oral, y disminuye la mortalidad y las secuelas en la enfermedad diseminada y localizada en el sistema nervioso central.

Septic pulmonary emboli detected by 18F-FDG PET/CT in children with S. aureus catheter-related bacteremia.

PURPOSE: The role of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in the diagnosis of metastatic infectious foci in children with catheter-related blood stream infection has been hardly studied, although some authors have reported it benefit in the screening of metastatic foci in adult population. Septic pulmonary emboli are among the most difficult to identify, because many cases do not present pulmonary complaints or abnormal chest radiography. However, diagnosis of these foci has important therapeutic consequences. The purpose of this article is to describe the role of 18F-FDG PET/CT in the diagnosis of septic pulmonary embolism in children with S. aureus catheter-related bacteremia. METHODS: We report 3 children with S. aureus catheter-related bacteremia and normal chest X-ray at admission, in whom 18F-FDG PET/CT led to the diagnosis of unsuspected septic pulmonary emboli, with an impact on clinical management. RESULTS: All patients had hemophilia and implantable venous access ports and presented with fever and normal lung auscultation. Only 1 reported non-specific symptoms (undifferentiated left chest pain). All patients had normal chest X-ray on admission. Catheters were removed within 48 h after admission in 2 cases, and 5 days after admission in the last case, subsiding fever. In 2 children, paired blood cultures were not able to identify bacteremia. However, in all cases catheter tip and subcutaneous port cultures yielded S. aureus and PET/CT detected unsuspected pulmonary metastatic emboli. CONCLUSIONS: 18F-FDG PET/CT should be considered as a useful tool to diagnose septic pulmonary embolism in S. aureus catheter-related bacteremia, especially if conventional diagnostic imaging techniques have failed to reveal possible metastatic foci. Further studies are needed to clarify the usefulness of PET/CT performance in children with CRBSI.

[SEIP-AEPAP-SEPEAP consensus document on the aetiology, diagnosis and treatment of bacterial skin infections in out-patients]. / Documento de consenso SEIP-AEPAP-SEPEAP sobre la etiología, el diagnóstico y el tratamiento de las infecciones cutáneas bacterianas de manejo ambulatorio.

Skin infections are a common cause for dermatological consultations in the paediatric setting. A review is presented of the clinical manifestations, diagnosis and treatment of the main bacterial skin infections, as well as the diagnosis and treatment of super-infected puncture and bite wounds. The most prevalent bacteria in skin infections are Staphylococcus aureus and Streptococcus pyogenes. Treatment is usually empirical, since microbiological studies are only recommended under certain circumstances or lack of improvement with common therapies. Superficial skin infections can be treated with local antiseptics or antibiotics (mupirocin or fusidic acid). Systemic treatment is usually reserved for patients with extensive or severe disease or with other risk factors. Systemic treatment depends on the suspected infecting bacteria, with penicillin, amoxicillin, amoxicillin-clavulanic acid and first or second generation cephalosporin being the most frequently used drugs. Due to the low incidence of community-acquired methicillin-resistant infection by S. aureus in Spain, the use of clindamycin or co-trimoxazole is only recommended after severe disease, relapses or a clear epidemiological background.

[Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (i): Epidemiology and diagnosis. Congenital tuberculosis]. / Guía de la Sociedad Española de Infectología Pediátrica sobre tuberculosis en la embarazada y el recién nacido (I): epidemiología y diagnóstico. Tuberculosis congénita.

Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death.

[Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment]. / Guía de la Sociedad Española de Infectología Pediátrica sobre tuberculosis en la embarazada y el recién nacido (ii): profilaxis y tratamiento.

In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended.

[Imported dengue: an emerging arbovirosis in Spain]. / Dengue importado: arbovirosis emergente en España.

Dengue is caused by one of 4 serotypes of dengue virus. Only imported cases have been reported in Spain. The main clinical findings are fever and exanthema, although there may be severe forms, particularly in secondary infections. Five children with a primary, non severe dengue infection are presented. The diagnosis was based on clinical suspicion and epidemiological history, and confirmed by immunochromatography and ELISA tests. The outcome was favourable in all cases. It is important to consider this diagnosis in international travellers that present with fever within the 14 days of returning from an endemic area, in order to get an early diagnosis, adequate treatment and a good prognosis.

[Consensus document on the aetiology, diagnosis and treatment of sinusitis]. / Documento de consenso sobre etiología, diagnóstico y tratamiento de la sinusitis.

The Spanish National Consensus (Spanish Society of Pediatric Infectious Diseases, Spanish Association of Primary Care Pediatrics, Spanish Society of Pediatric Outpatient and Primary Care, Spanish Society of Otorhinolaryngology and Cervical-Facial Pathology) on Sinusitis is presented. Rhinosinusitis is a difficult to diagnose and often unrecognised disease. The document discusses the aetiology, the clinical signs and symptoms, and the diagnostic criteria. A proposal for treatment is made based on the epidemiological situation in our country. Oral amoxicillin is the treatment of choice (80mg/kg/day divided every 8hours). Alternative treatment is proposed in special cases and when amoxicillin is not sufficient. The main complications are reviewed.

[The Spanish Society of Pediatric Infectious Diseases Guidelines for the diagnosis and treatment of congenital toxoplasmosis]. / Guía de la Sociedad Española de Infectología Pediátrica para el diagnóstico y tratamiento de la toxoplasmosis congénita.

Congenital toxoplasmosis is the result of transplacental fetal infection by Toxoplasma gondii after the primary maternal infection. The severity of the disease depends on the gestational age at transmission. First trimester infections are more severe, but less frequent, than third trimester infections. Acute maternal infection is diagnosed by seroconversion or by the detection of IgM antibodies and a low IgG avidity test. In these cases, spiramycin should be initiated to prevent transmission to the fetus. For identification of fetal infection, polymerase chain reaction (PCR) testing of amniotic fluid after 18 weeks gestation should be performed. If fetal infection is confirmed, the mothers should be treated with pyrimethamine, sulfadiazine and folinic acid. Most infants infected in utero are born with no obvious signs of toxoplasmosis, but up to 80% developed learning and visual disabilities later in life. Neonatal diagnosis with IgM/IgA antibodies or blood/cerebrospinal fluid PCR may be difficult because false-negative results frequently occur. In these cases diagnosis is possible by demonstrating a rise in IgG titers during follow-up or by the detection of antibodies beyond one year of age. Early treatment with pyrimethamine and sulfadiazine may improve the ophthalmologic and neurological outcome. Congenital toxoplasmosis is a preventable disease. Pre-pregnancy screening and appropriate counseling regarding prevention measures in seronegative women may prevent fetal infection.

[Consensus document on the aetiology, diagnosis and treatment of acute otitis media]. / Documento de consenso sobre etiología, diagnóstico y tratamiento de la otitis media aguda.

This is the consensus document on acute otitis media (AOM) of the Sociedad Española de Infectología Pediatrica (SEIP), Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria (SEPEAP), Sociedad Española de Urgencias Pediátricas (SEUP) and Asociación Española de Pediatría de Atención Primaria (AEPAP). It discusses the aetiology of the disease and its potential changes after the introduction of the pneumococcal 7-valent, 10-valent and 13-valent vaccines. A proposal is made based on diagnostic classification of otitis media as either confirmed or likely. AOM is considered confirmed if 3 criteria are fulfilled: acute onset, signs of occupation of the middle ear (or otorrhea) and inflammatory signs or symptoms, such as otalgia or severe tympanic hyperaemia. Oral amoxicillin is the antibiotic treatment of choice (80mg/kg/day divided every 8hours). Amoxicillin-clavulanate (80mg/kg/day) is indicated in the following cases: when the child is under 6 months, in infants with severe clinical manifestations (fever>39°C or severe pain), there is family history of AOM sequels, and after amoxiciline treatment failure.

[Recommendations from the Spanish Society of Paediatric Infectious Diseases on the diagnosis and treatment of non-tuberculous mycobacterial cervical lymphadenitis]. / Recomendaciones de la Sociedad Española de Infectología Pediátrica sobre el diagnóstico y tratamiento de las adenitis por micobacterias no tuberculosas.

Non-tuberculous mycobacteria (NTM) have been increasingly isolated over the last 20 years in Spain. However, as NTM disease is not a notifiable condition, there is no national registry, thus the true prevalence and incidence of these infections in children are difficult to estimate. Cervical adenitis is the most common clinical manifestation of NTM infection in immunocompetent children. The clinical course can be sub-acute or chronic, and is often associated with fluctuation, fistulisation, and scarring at a later stage. Although much less common, it is important to consider Mycobacterium tuberculosis in the differential diagnosis, as the management and the epidemiological implications of tuberculous lymphadenitis are completely different. Diagnosis of NTM cervical lymphadenitis is based on a high level of clinical suspicion, supported by results of the tuberculin skin test and interferon-gamma release assays (IGRA). Fine needle aspiration or excisional biopsy is usually required for histological and microbiological confirmation. Complete surgical excision of the affected nodes is the treatment of choice. Incision and drainage is not recommended, due to the high risk of chronic fistulisation and recurrence rate. Antibiotic treatment or conservative wait-and-see therapy may be indicated in certain circumstances.