[A multicentric study on clinical characteristics and antibiotic sensitivity in children with methicillin-resistant Staphylococcus aureus infection].

Objective: To investigate the clinical characteristics of pediatric methicillin-resistant Staphylococcus aureus (MRSA) infection and the antibiotic sensitivity of the isolates. Methods: The clinical data of children with MRSA infection and antibiotic sensitivity of the isolates from 11 children's hospitals in Infectious Diseases Surveillance of Paediatrics (ISPED) group of China between January 1, 2018 and December 31, 2018 were collected retrospectively. The children's general condition, high-risk factors, antimicrobial therapy and prognosis, differences in clinical disease and laboratory test results between different age groups, and differences of antibiotic sensitivity between community-acquired (CA)-MRSA and hospital-acquired (HA)-MRSA were analyzed. The t test and Wilcoxon rank sum test were used for statistical analysis of the quantitative data and Chi-square test were used for comparison of rates. Results: Among the 452 patients, 264 were males and 188 were females, aged from 2 days to 17 years. There were 233 cases (51.5%) in the ≤1 year old group, 79 cases (17.5%) in the>1-3 years old group, 29 cases (6.4%) in the >3-5 years old group, 65 cases (14.4%) in the >5-10 years old group, and 46 cases (10.2%) in the>10 years old group. The main distributions of onset seasons were 55 cases (12.2%) in December, 47 cases (10.4%) in February, 46 cases (10.2%) in November, 45 cases (10.0%) in January, 40 cases (8.8%) in March. There were 335 cases (74.1%) CA-MRSA and 117 (25.9%) cases HA-MRSA. Among all cases, 174 cases (38.5%) had basic diseases or long-term use of hormone and immunosuppressive drugs. During the period of hospitalization, 209 cases (46.2%) received medical interventions. There were 182 patients (40.3%) had used antibiotics (ß-lactams, glycopeptides, macrolides, carbapenems, oxazolones, sulfonamides etc) 3 months before admission. The most common clinical disease was pneumonia (203 cases), followed by skin soft-tissue infection (133 cases), sepsis (92 cases), deep tissue abscess (42 cases), osteomyelitis (40 cases), and septic arthritis (26 cases), suppurative meningitis (10 cases). The proportion of pneumonia in the ≤1 year old group was higher than the >1-3 years old group,>3-5 years old group,>5-10 years old group,>10 years old group (57.5% (134/233) vs. 30.4% (24/79), 31.0% (9/29), 38.5% (25/65), 23.9% (11/46), χ(2)=17.374, 7.293, 7.410, 17.373, all P<0.01) The proportion of skin and soft tissue infections caused by CA-MRSA infection was higher than HA-MRSA (33.4% (112/335) vs. 17.9% (21/117), χ(2)=10.010, P=0.002), and the proportion of pneumonia caused by HA-MRSA infection was higher than CA-MRSA (53.0% (62/117) vs. 42.1% (141/335), χ(2)=4.166, P=0.041). The first white blood cell count of the ≤1 year old group was higher than that children > 1 year old ((15±8)×10(9)/L vs. (13±7)×10(9)/L, t=2.697, P=0.007), while the C-reactive protein of the ≤1 year old group was lower than the 1-3 years old group,>5-10 years old group,>10 years old group (8.00 (0.04-194.00) vs.17.00 (0.50-316.00), 15.20 (0.23-312.00), 21.79(0.13-219.00) mg/L, Z=3.207, 2.044, 2.513, all P<0.05), there were no significant differences in procalcitonin (PCT) between different age groups (all P>0.05). After the treatment, 131 cases were cured, 278 cases were improved, 21 cases were not cured, 12 cases died, and 10 cases were abandoned. The 452 MRSA isolates were all sensitive to vancomycin (100.0%), linezolid (100.0%), 100.0% resistant to penicillin, highly resistant to erythromycin (85.0%, 375/441), clindamycin (67.7%, 294/434), less resistant to sulfonamides (5.9%, 23/391), levofloxacin (4.5%, 19/423), gentamicin (3.2%, 14/438), rifampicin (1.8%, 8/440), minocycline (1.1%, 1/91). The antimicrobial resistance rates were not significantly different between the CA-MRSA and HA-MRSA groups (all P>0.05). Conclusions: The infection of MRSA is mainly found in infants under 3 years old. The prevalent seasons are winter and spring, and MRSA is mainly acquired in the community. The main clinical diseases are pneumonia, skin soft-tissue infection and sepsis. No MRSA isolate is resistant to vancomycin, linezolid. MRSA isolates are generally sensitive to sulfonamides, levofloxacin, gentamicin, rifampicin, minocycline, and were highly resistant to erythromycin and clindamycin. To achieve better prognosis. clinicians should initiate anti-infective treatment for children with MRSA infection according to the clinical characteristics of patients and drug sensitivity of the isolates timely and effectively.

[A multicentric clinical study on clinical characteristics and drug sensitivity of children with pneumococcal meningitis in China].

Objective: To understand clinical characteristics of children with pneumococcal meningitis (PM) in China and to analyze the drug sensitivity of Streptococcus pneumoniae isolates and associated impacts on death and sequelae. Methods: The clinical data, follow-up results and antimicrobial sensitivity of isolated strains of 155 children (including 98 males and 57 females, age ranged from 2 months to 15 years) with PM in 10 tertiary-grade A class hospitals of Infectious Diseases Surveillance of Pediatrics (ISPED) from 2013 to 2017 were collected and analyzed retrospectively. Patients were divided into different groups according to the following standards: ≤1 year old group,>1-3 years old group and >3 years old group according to age; death group and non-death group according to the death within 30 days after PM diagnosis; complication group and non-complication group according to the abnormal cranial imaging diagnosis; sequelae group and no-sequelae group according to the follow-up results. Bonfereoni chi-square segmentation and Kruskal-Wallis H test were used for statistical analysis. Results: There were 64 cases (41.3%) in the ≤1 year old group, 39 cases in the >1-3 years old group (25.2%), and 52 cases (33.5%) in the >3 years old group. The most common clinical manifestation was fever (151 cases, 97.4%). The mortality was 16.8% (26/155) during hospitalization. The neurological complication rate was 49.7% (77/155) during hospitalization, including the most common complication, subdural effusion and (or) empyema in 50 cases (32.3%) and hearing impairment in 6 cases. During follow-up after discharge, no death was found and focal neurological deficits were found in 47 cases (30.3%), including the frequent neurological sequelae: cognitive and mental retardation of different degree in 22 cases and hearing impairment in 14 cases (9.0%). The rate of cure and improvement on discharge was 74.8% (116/155) and the lost to follow-up rate was 8.4% (13/155). The proportions of died cases, neurological complications during hospitalization and proportions of peripheral white blood cell count <12 × 10(9)/L before admission in ≤1 year old group were significantly higher than those in >3 years old group (25.0% (16/64) vs. 5.8% (3/52), 75.0% (48/64) vs. 25.0% (13/52), 48.4% (31/64) vs. 15.4% (8/52), χ(2)=7.747, 28.767, 14.044; P=0.005, 0.000, 0.000). The proportions of headache, vomiting, neck resistance and high risk factors of purulent meningitis in >3 years old group were significantly higher than those in ≤ 1 year old group (67.3%(35/52) vs. 1.6%(1/64), 80.8% (42/52) vs. 48.4% (31/64), 69.2% (36/52) vs. 37.5% (24/64), 55.8% (29/52) vs. 14.1%(9/64), χ(2)=57.940, 12.856, 11.568, 22.656; P=0.000, 0.000, 0.001, 0.000). Streptococcus pneumoniae isolates were completely sensitive to vancomycin (100.0%, 152/152), linezolid (100.0%, 126/126), moxifloxacin (100.0%, 93/93) and ofloxacin (100.0%,41/41); highly sensitive to levofloxacin (99.3%, 142/143) and ertapenem (84.6%, 66/78); moderately sensitive to ceftriaxone (48.4%, 45/93), cefotaxime (40.0%, 44/110) and meropenem (38.0%, 38/100); less sensitive to penicillin (19.6%, 27/138) and erythromycin (4.2%, 5/120). The proportions of non-sensitive strains of penicillin (21/21) and meropenem (17/18) in the death group were significantly higher than those (90/117, 45/82) in the survived group(χ(2)=4.648 and 9.808, P=0.031 and 0.002). Conclusions: The children's PM is mainly found in infants under 3 years old in China. Death and neurological complications are more common in PM children under 1 year old. The clinical manifestations and peripheral blood inflammatory markers of PM patients under 1 year old are not typical. Fever is the most common clinical manifestation and subdural effusion and (or) empyema is the most common complication. Long-term hearing impairment is common in PM and the follow-up time must be prolonged. The dead PM cases had high in sensitive rates to penicillin and meropenem.

Myosin VI is an actin-based motor that moves backwards.

Myosins and kinesins are molecular motors that hydrolyse ATP to track along actin filaments and microtubules, respectively. Although the kinesin family includes motors that move towards either the plus or minus ends of microtubules, all characterized myosin motors move towards the barbed (+) end of actin filaments. Crystal structures of myosin II (refs 3-6) have shown that small movements within the myosin motor core are transmitted through the 'converter domain' to a 'lever arm' consisting of a light-chain-binding helix and associated light chains. The lever arm further amplifies the motions of the converter domain into large directed movements. Here we report that myosin VI, an unconventional myosin, moves towards the pointed (-) end of actin. We visualized the myosin VI construct bound to actin using cryo-electron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. Thus, it appears that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement.