A case report of hepatic abscesses with soft tissue infection caused by methicillin resistant Staphylococcus aureus in a young child.

RATIONALE: Pyogenic hepatic abscess in children is a rare clinical condition. Hepatic abscesses caused by methicillin resistant Staphylococcus aureus are extremely rare. PATIENT CONCERNS: A 6-year-old boy was referred to a tertiary children's hospital for a 6-day history of right lower abdominal pain and fever. Radiographic findings showed hepatic abscesses and soft tissue abscesses around the left femur. DIAGNOSES: Bacteriology of blood, hepatic abscesses, and soft tissue abscesses showed methicillin resistant Staphylococcus aureus. INTERVENTIONS: Our patient received adequate drainage of MRSA abscesses and a complete course of antibiotics. OUTCOMES: The hepatic abscesses were healed and no recurrence has been founded until now. LESSONS: This report describes an extremely rare case of hepatic abscesses with soft tissue infection caused by MRSA. Adequate drainage and appropriate systemic antibiotics should be considered as a standard treatment of MRSA abscesses in order to reduce the mortality rate and improve the quality of life.

[Progress in the biomarker discovery for drug-induced liver injury].

The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.

The inhibition of hepatic bile acids transporters Ntcp and Bsep is involved in the pathogenesis of isoniazid/rifampicin-induced hepatotoxicity.

Co-treatment of isoniazid (INH) and rifampicin (RFP) is well known for clinically apparent liver injury. However, the mechanism of INH/RFP-induced liver injury is controversial. Emerging evidence shows links between inhibition of bile acids transporters and drug-induced liver injury (DILI). The present study investigates whether sodium taurocholate cotransporting polypeptide (NTCP/Ntcp; SLC10A1) and bile salt export pump (BSEP/Bsep; ABCB11) are involved in the anti-tuberculosis medicines induced liver injury. ICR female mice were intragastrically treated with INH (50 or 100 mg/kg), RFP (100 or 200 mg/kg), or the combination of INH/RFP (50 + 100 mg/kg or 100 + 200 mg/kg) for 14 consecutive days. Liver histopathological examination, serum biochemical and liver malondialdehyde tests were evaluated. Apparent histopathological alterations and hepatic oxidative stress showed in INH (100 mg/kg), RFP (200 mg/kg) and their combination group. The hepatoxic effect was also indicated by increased serum biomarkers, such as aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBil), total bilirubin (TBil) and total bile acids (TBA). Both doses of INH/RFP administration significantly down-regulated the expression of Ntcp and Bsep in liver. Furthermore, the combination of INH and RFP displayed stronger effect on the expression of Ntcp compared with the corresponding dose of INH or RFP alone. In conclusion, down-regulated expression of hepatic Ntcp and Bsep might play an important role in the development of INH and RFP induced liver injury.

Elevated serum ApoE levels are associated with bacterial infections in pediatric patients.

BACKGROUND/PURPOSE(S): We aimed to determine the variations in serum apolipoprotein E (ApoE) levels in pediatric patients with a variety of infectious diseases, and to investigate the potential mechanism of elevated ApoE serum levels during infection. METHODS: A total of 279 pediatric patients with a variety of infections and 58 normal controls were enrolled in this study. Serum ApoE levels were detected using an immunoturbidimetric assay. A mouse sepsis model was established to evaluate the expression of ApoE and its receptors by real-time polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: Serum ApoE was markedly increased in cases with bacterial infections including sepsis, bacterial meningitis, and bacterial pneumonia, compared to healthy controls. No significantly elevated serum ApoE levels were observed in aseptic meningitis patients or mycoplasma pneumonia patients. The mice sepsis models showed a similar pattern of increased serum ApoE levels in the early stage of infections. We found reduced expression of ApoE and its receptors in the liver tissues in these mice models. CONCLUSION: Serum ApoE may represent a novel indicator for diagnosis of bacterial infections, especially sepsis, in pediatric patients. The decreased expression of low-density lipoprotein receptor (LDLR), LDL receptor-related protein (LRP), and heparin sulfate proteoglycan (HSPG) syndecan-1 (SDC1) may contribute to reduced ApoE clearance and accumulation in the blood.

An apolipoprotein E mimetic peptide with activities against multidrug-resistant bacteria and immunomodulatory effects.

Apolipoprotein E (apoE) mimetic peptides derived from the low-density lipoprotein receptor-binding region of apoE with both activities against multidrug-resistant bacteria and immunomodulatory effects have not previously been reported. We identified an apoE mimetic peptide analogue of the receptor-binding region of apoE (abbreviated as apoE23) with the sequence of LRKLRKRLVRLASHLRKLRKRLL, which exhibited high antibacterial effects. The minimal inhibitory concentration of apoE23 against multidrug-resistant Acinetobacter baumannii was 6 µg/ml. The antimicrobial activity of apoE23 depended on its amphipathic α-helical conformation. Moreover, apoE23 downregulated the expression of tumour necrosis factor-α, interleukin-6 and interleukin-10 in lipopolysaccharide-induced THP-1 cells. ApoE23 exhibits potential in future clinical applications.

[Clinical features and molecular characteristics of methicillin-resistant Staphylococcus aureus in children].

OBJECTIVE: To study the clinical and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) infection in children. METHOD: A total of 37 MRSA strains were isolated from hospitalized patients in Children's Hospital of Fudan University from March 2009 to November 2011. The clinical characteristics were investigated by a cohort study. Furthermore, the mecA, Panton-Valentine leucocidin (PVL) genes were detected by polymerase chain reaction (PCR), and the genotypes of SCCmec were determined by multiplex PCR. RESULT: (1) Among the 37 MRSA isolates, infections with 21 were acquired from hospital (HA-MRSA), and 16 isolates were acquired from community (CA-MRSA). (2) In the study, MRSA frequently caused respiratory tract infection, and most of the strains were isolated from intensive care unit (ICU). (3) CA-MRSA was most frequently associated with skin and soft tissue infections (SSTI), suppurative tonsillitis, even pneumonia and septicemia. HA-MRSA infection was more aggressive, most frequently associated with pneumonia, septicemia, and central nervous system (CNS) infections, such as meningitis. In children with fever caused by HA-MRSA or CA-MRSA infection, HA-MRSA showed a longer duration of fever, for 10.5 days. C-reactive protein (CRP) level caused by HA-MRSA (63.00 mg/L) was higher than CA-MRSA (9.50 mg/L) , and there were statistically significant differences between the groups (t = 2.5670, P < 0.05). However, there were no statistically significant differences between the groups in white blood cell count (WBC) or procalcitonin (PCT) level. (4) Among 37 MRSA isolates, the whole isolates were mecA gene positive (100%). SCCmec genotyping results showed that the most frequent SCCmec types were type III, 17 isolates, the others including type IV 8 isolates, type II1 isolates, nontypable 11 isolates, type I and type V were not found in this group. Therein, among 21 HA-MRSA isolates, SCCmec III was the most common, 15 isolates, type IV 1 isolates, nontypable 5 isolates; among 16 CA-MRSA isolates, SCCmec type IV was the most common, 7 isolates, type III 2 isolates, type II 1 isolate, nontypable 6 isolates. (5) Among the 37 MRSA isolates, 28 were PVL gene positive; and among 21 HA-MRSA isolates, 17 were PVL gene positive; Among 16 CA-MRSA isolates, 11 were PVL gene positive; There were no statistically significant differences between the groups (χ(2) = 0.735, P > 0.05) . CONCLUSION: Compared with CA-MRSA, HA-MRSA infection was more aggressive, and induced higher C reactive protein; the dominant epidemic strains of CA-MRSA was SCCmec type IV, and HA-MRSA was SCCmec type III; the positive rate of PVL gene was high.