Multisystem inflammatory syndrome in children: a case series.

OBJECTIVE: To describe a case series of multisystem inflammatory syndrome in children (MIS-C) in a pediatric tertiary hospital. METHODS: Patients under the age of 18 years who met MIS-C criteria of the Brazilian Ministry of Health (MH) and/or the Royal College of Paediatrics and Child Health (RCPCH) were included. A retrospective analysis was carried out by reviewing medical records and complementary exams. RESULTS: Six pediatric patients with mean age of 126 months were admitted with fever associated with multisystem involvement: all of them had abdominal pain and diarrhea and two underwent appendectomy; 100% had coagulopathy and increased inflammatory markers; 83% had cardiovascular impairment and 60% required vasoactive drugs; 83% had mucocutaneous symptoms and 50% required ventilatory support by invasive mechanical ventilation or non-invasive ventilation. One patient showed coronary artery dilation on echocardiogram. All patients received empiric antibiotic therapies. SARS-CoV-2 IgG testing was positive in five patients. Treatment was performed after excluding infectious causes: five patients (83%) received intravenous immunoglobulin, five patients (83%) pulse methylprednisolone therapy and one (16%) Tocilizumab. One patient died. The average length of stay in Pediatric Intensive Care Unit (PICU) was seven days. CONCLUSIONS: These cases are added to the literature in construction of this emerging condition. Early diagnosis should be considered due to its potential severity.

Pharmacodynamic Evaluation of Fosfomycin against Escherichia coli and Klebsiella spp. from Urinary Tract Infections and the Influence of pH on Fosfomycin Activities.

Fosfomycin is widely used for the treatment of uncomplicated urinary tract infection (UTI), and it has recently been recommended that fosfomycin be used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacilli. Whether urine acidification can improve bacterial susceptibility to fosfomycin oral dosing regimens has not been analyzed. The MIC of fosfomycin for 245 Gram-negative bacterial isolates, consisting of 158 Escherichia coli isolates and 87 Klebsiella isolates which were collected from patients with urinary tract infections, were determined at pH 6.0 and 7.0 using the agar dilution method. Monte Carlo simulation of the urinary fosfomycin area under the concentration-time curve (AUC) after a single oral dose of 3,000 mg fosfomycin and the MIC distribution were used to determine the probability of target attainment (PTA). Fosfomycin was effective against E. coli (MIC90 ≤ 16 µg/ml) but not against Klebsiella spp. (MIC90 > 512 µg/ml). Acidification of the environment increased the susceptibility of 71% of the bacterial isolates and resulted in a statistically significant decrease in bacterial survival. The use of a regimen consisting of a single oral dose of fosfomycin against an E. coli isolate with an MIC of ≤64 mg/liter was able to achieve a PTA of ≥90% for a target pharmacodynamic index (AUC/MIC) of 23 in urine; PTA was not achieved when the MIC was higher than 64 mg/liter. The cumulative fractions of the bacterial responses (CFR) were 99% and 55% against E. coli and Klebsiella spp., respectively, based on simulated drug exposure in urine with an acidic pH of 6.0. A decrease of the pH from 7.0 to 6.0 improved the PTA and CFR of the target pharmacodynamic index in both E. coli and Klebsiella isolates.