Clinical Outcome of Discordant Empirical Therapy and Risk Factors Associated to Treatment Failure in Children Hospitalized for Urinary Tract Infections.

With the spread of antibiotic resistance in pediatric urinary tract infections (UTIs), more patients are likely to be started empirically on antibiotics to which pathogens are later found to be resistant (discordant therapy). However, in-vivo effectiveness may be different from in-vitro susceptibility. Aims of this study were to describe clinical outcomes of discordant empirical treatments in pediatric UTIs and to investigate risk factors associated to treatment failure. This observational, retrospective study was conducted on children hospitalized for febrile UTIs with positive urine culture and started on discordant empirical therapy. Failure rates of discordant treatments and associated risk factors were investigated. A total of 142/1600 (8.9%) patients were treated with inadequate empirical antibiotics. Clinical failure was observed in 67/142 (47.2%) patients, with no fatal events. Higher failure rates were observed for combinations of penicillin and beta-lactamase inhibitors (57.1%). Significant risk factors for failure of discordant treatment were history of recurrent UTIs (95% CI: 1.13-9.98, OR: 3.23, p < 0.05), recent use of antibiotics (95% CI: 1.46-21.82, OR: 5.02, p < 0.01), infections caused by Pseudomonas aeruginosa (95% CI: 1.85-62.10, OR: 7.30, p < 0.05), and empirical treatment with combinations of penicillin and beta-lactamase inhibitors (95% CI: 0.94-4.03, OR: 1.94, p = 0.05). This study showed that discordant empirical treatments may still be effective in more than half of pediatric UTIs. Clinical effectiveness varies between different discordant antibiotics in pediatric UTIs, and patients presenting risk factors for treatment failure may need a differentiated empirical approach.

Antibiotic Resistance in Paediatric Febrile Urinary Tract Infections.

Febrile urinary tract infection (UTI) is currently considered the most frequent cause of serious bacterial illness in children in the first 2 years of life. UTI in paediatrics can irreversibly damage the renal parenchyma and lead to chronic renal insufficiency and related problems. To avoid this risk, an early effective antibiotic treatment is essential. Moreover, prompt treatment is mandatory to improve the clinical condition of the patient, prevent bacteraemia, and avoid the risk of bacterial localization in other body sites. However, antibiotic resistance for UTI-related bacterial pathogens continuously increases, making recommendations rapidly outdated and the definition of the best empiric antibiotic therapy more difficult. Variation in pathogen susceptibility to antibiotics is essential for the choice of an effective therapy. Moreover, proper identification of cases at increased risk of difficult-to-treat UTIs can reduce the risk of ineffective therapy. In this review, the problem of emerging antibiotic resistance among pathogens associated with the development of paediatric febrile UTIs and the best potential solutions to ensure the most effective therapy are discussed. Literature analysis showed that the emergence of antibiotic resistance is an unavoidable phenomenon closely correlated with the use of antibiotics themselves. To limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be made. An increased use of antibiotic stewardship can be greatly effective in this regard.

Retrospective 8-Year Study on the Antibiotic Resistance of Uropathogens in Children Hospitalised for Urinary Tract Infection in the Emilia-Romagna Region, Italy.

The development and spread of antibiotic resistance is an increasingly important global public health problem, even in paediatric urinary tract infection (UTI). In light of the variability in the data, it is necessary to conduct surveillance studies to determine the prevalence of antibiotic resistance in specific geographical areas to optimize therapeutic management. In this observational, retrospective, multicentre study, the medical records of 1801 paediatric patients who were hospitalised for UTI between 1 January 2012, and 30 June 2020, in Emilia-Romagna, Italy, were analysed. Escherichia coli was the most frequently detected pathogen (75.6%), followed by Klebsiella pneumoniae (6.9%) and Pseudomonas aeruginosa (2.5%). Overall, 840 cases (46.7%) were due to antimicrobial-resistant uropathogens: 83 (4.7%) extended spectrum beta-lactamase (ESBL)-producing, 119 (6.7%) multidrug resistant (MDR) and 4 (0.2%) extensively drug resistant (XDR) bacteria. Empirical antibiotic therapy failed in 172 cases (9.6%). Having ESBL or MDR/XDR uropathogens, a history of recurrent UTI, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate were significantly associated with treatment failure, whereas first-line therapy with third-generation cephalosporins was associated with protection against negative outcomes. In conclusion, the increase in the resistance of uropathogens to commonly used antibiotics requires continuous monitoring, and recommendations for antibiotic choice need updating. In our epidemiological context, amoxicillin/clavulanate no longer seems to be the appropriate first-line therapy for children hospitalised for UTI, whereas third-generation cephalosporins continue to be useful. To further limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be implemented.

Whole Exome Sequencing Is the Minimal Technological Approach in Probands Born to Consanguineous Couples.

We report on two siblings suffering from different pathogenic conditions, born to consanguineous parents. A multigene panel for brain malformations and microcephaly identified the homozygous splicing variant NM_005886.3:c.1416+1del in the KATNB1 gene in the older sister. On the other hand, exome sequencing revealed the homozygous frameshift variant NM_005245.4:c.9729del in the FAT1 gene in the younger sister, who had a more complex phenotype: in addition to bilateral anophthalmia and heart defects, she showed a right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. These features have been never reported before in patients with pathogenic FAT1 variants and support the role of this gene in the development of limb buds. Notably, each parent was heterozygous for both of these variants, which were ultra-rare and rare, respectively. This study raises awareness about the value of using whole exome/genome sequencing rather than targeted gene panels when testing affected offspring born to consanguineous couples. In this way, exomic data from the parents are also made available for carrier screening, to identify heterozygous pathogenetic and likely pathogenetic variants in genes responsible for other recessive conditions, which may pose a risk for subsequent pregnancies.

Encephalitis due to herpes zoster without rash in an immunocompetent 12-year-old girl: case report and review of the literature.

BACKGROUND: Neurological complications due to reactivation of varicella-zoster virus (VZV) are very uncommon in immunocompetent patients. Generally a vesicular rash is present on one or more dermatomes, preceding or following the main manifestation. Few cases are reported in the international literature, but they concern mainly adult or elderly patients. CASE PRESENTATION: A 12-year-old girl was referred to our hospital for persisting headache, cough and rhinitis for six days. After first examination, diagnosis of anterior sinusitis was made by nasal endoscopy. The day after, the girl developed psychotic symptoms and altered mental status. Computed tomography (CT) scan was immediately performed but was unremarkable; lumbar puncture revealed leukocytosis with lymphocytic predominance and cerebrospinal fluid polymerase chain reaction (PCR) detected varicella-zoster virus DNA. The diagnosis of acute VZV encephalitis was made. The patient was promptly treated with acyclovir infused intravenously and her clinical conditions rapidly improved. Tests made did not show any condition of immunosuppression. CONCLUSIONS: Although if rare, reactivation of VZV can occur in immunocompetent children and its complications can involve central nervous system. Among these complications, meningitis is more common, but cerebral parenchyma can also be involved leading to a severe medical condition that is defined meningoencephalitis. In rare cases vesicular rash may be absent; therefore high level of suspicion is required even in those patients in which suggestive clinical features are not present to guide the diagnosis. Intravenous acyclovir represents the treatment of choice to obtain a fast clinical response and to prevent the onset of late-term complications.

Best practice guidelines for idiopathic nephrotic syndrome: recommendations versus reality.

BACKGROUND: The optimal therapeutic regimen for managing childhood idiopathic nephrotic syndrome (INS) is still under debate. We have evaluated the choice of steroid regimen and of symptomatic treatment adopted by pediatricians and pediatric nephrologists in a large number of centers as the first step towards establishing a shared protocol METHODS: This was a multicenter, retrospective study. A total of 231 children (132 admitted to pediatric units) aged 6 months to <15 years who presented with onset of nephrotic syndrome to 54 pediatric units and six pediatric nephrology units in Italy between 2007 and 2009 were eligible for entry into the study. RESULTS: Median steroid dosing was 55 (range 27-75) mg/m(2)/day. The overall median cumulative dose regimen for the first episode was 3,440 (1,904-6,035) mg/m(2), and the median duration of the therapeutic regimen was 21 (9-48) weeks. The total duration and cumulative steroid dose were significantly higher in patients treated by pediatricians than in those treated by pediatric nephrologists (p = 0.001 and p = 0.008). Among the patient cohort, 55, 64 and 22 % received albumin infusions, diuretics and acetyl salicylic acid treatment, respectively, but the laboratory and clinical data did not differ between children treated or not treated with symptomatic drugs. Albumin and diuretic use did not vary between patients in pediatric units and those in pediatric nephrology units. CONCLUSIONS: This study shows major differences in steroid and symptomatic treatment of nephrotic syndrome by pediatricians and pediatric nephrologists. As these differences can influence the efficacy of the treatments and the appearance of side-effects, shared guidelines and their implementation through widespread educational activities are necessary.

Prognostic value of glomerular collagen IV immunofluorescence studies in male patients with X-linked Alport syndrome.

BACKGROUND AND OBJECTIVES: X-linked Alport syndrome (X-AS) is caused by mutations of the COL4A5 gene, which encodes for the collagen IV α5 chain (α5[COLIV]), resulting in structural and functional abnormalities of the glomerular basement membrane (GBM) and leading to CKD. The aim of the present study was to evaluate the prognostic value of residual collagen IV chain expression in the GBM of patients with X-AS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The medical records of 22 patients with X-AS from 21 unrelated families collected between 1987 and 2009 were reviewed (median age at last follow-up, 19.9 years; range, 5.4-35.1 years); GBM expression of α1, α3, and α5(COLIV) chains was assessed by immunofluorescence microscopy. RESULTS: GBM distribution of the α5(COLIV) chain was diffuse in 1 and segmental or absent in 21 of the 22 patients; the expression of the α3(COLIV) chain was diffuse in 5 of 22 patients and segmental or absent in 17 of 22 patients. Patients with diffuse staining for the α3(COLIV) chain presented with proteinuria significantly later (median age, 16.9 versus 6.1 years; P=0.02) and reached an estimated GFR < 90 ml/min per 1.73 m(2) at an older age (median age, 27.0 versus 14.9 years; P=0.01) compared with patients with segmental or absent staining. Two thirds of patients with abnormal α3(COLIV) expression by immunofluorescence studies had null or truncating COL4A5 mutations, as opposed to none of the 4 tested patients with diffuse α3(COLIV) chain glomerular distribution. CONCLUSIONS: These results indicate that maintained expression of the α3(COLIV) chain is an early positive prognostic marker in patients with X-linked Alport symdrome.