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Biomedical subjects

Youning Liu

Publications and source records attributed to Youning Liu.

11 recordsLinked to original sources

The mutant selection window in rabbits infected with Staphylococcus aureus.

BACKGROUND: The mutant selection window hypothesis, originally based on agar plate assays, may lead to new antimicrobial dosing strategies that severely restrict the acquisition of resistance. However, it has not been directly tested in an animal model of infection. METHODS: Local infection with Staphylococcus aureus was established in rabbits, and the infected animals were treated orally with various doses of levofloxacin. Changes in levofloxacin concentration, levofloxacin susceptibility, and counts of total and resistant viable bacteria were monitored at the site of infection. RESULTS: S. aureus lost levofloxacin susceptibility when drug concentrations at the site of infection fluctuated between the lower and upper boundaries of the window, defined in vitro as the minimum inhibitory concentration (MIC)(99) and the mutant prevention concentration (MPC), respectively. The upper boundary of the selection window in vivo was estimated as an AUC(24)/MPC value of ~25 h, where AUC(24) is the area under the drug concentration time curve in a 24-h interval. The lower boundary was estimated as an AUC(24)/MIC value of ~20 h. CONCLUSIONS: The mutant selection window exists in vivo, and its boundaries fit well with those determined in vitro. Maintenance of antimicrobial concentrations above the window is expected to suppress the outgrowth of resistant mutant subpopulations.

Administration, Oral↗

Selection of rifampicin-resistant Staphylococcus aureus during tuberculosis therapy: concurrent bacterial eradication and acquisition of resistance.

BACKGROUND AND OBJECTIVES: Acquired antimicrobial resistance is commonly attributed to regimens that expose bacteria to subinhibitory concentrations; consequently, eradication of susceptible cells is advocated. The mutant selection window hypothesis predicts that resistance can be acquired even when inhibitory concentrations are exceeded and susceptible bacteria are eradicated. The objective was to test that prediction clinically. METHODS: Tuberculosis patients (n = 372) were sampled for nasal colonization by Staphylococcus aureus at the beginning of anti-tuberculosis therapy with rifampicin-containing regimens and again after 2 and 4 weeks. Rifampicin susceptibility of S. aureus was determined, and S. aureus isolates from patients developing acquired resistance were examined by molecular strain typing. Diabetes patients (n = 200) served as untreated controls. RESULTS: Nasal colonization was 17% and 20% for the tuberculosis and diabetes patients, respectively. Four patients were initially colonized with rifampicin-resistant S. aureus and were excluded from further sampling. Initiation of anti-tuberculosis therapy eradicated S. aureus nasal colonization in 53/58 tuberculosis patients while allowing acquisition of rifampicin resistance in 5/58. Pulsed-field gel electrophoresis (PFGE) band patterns and protein A repeat sequence determination differed in S. aureus isolated from different patients but was identical in isolates obtained from the same patient before and after acquisition of resistance. No resistance was acquired in untreated control patients, which differed statistically from treated patients (P = 0.025). CONCLUSIONS: Acquired resistance and eradication of susceptible bacteria can occur concurrently; restricting acquired resistance may require direct suppression of mutant growth and viability in addition to elimination of susceptible bacteria.

Adolescent↗

Dynamic changes of serum SARS-coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge.

OBJECTIVE: The intent of this study was to examine the recovery of individuals who had been hospitalized for severe acute respiratory syndrome (SARS) in the year following their discharge from the hospital. Parameters studied included serum levels of SARS coronavirus (SARS-CoV) IgG antibody, tests of lung function, and imaging data to evaluate changes in lung fibrosis. In addition, we explored the incidence of femoral head necrosis in some of the individuals recovering from SARS. METHODS: The subjects of this study were 383 clinically diagnosed SARS patients in Beijing, China. They were tested regularly for serum levels of SARS-CoV IgG antibody and lung function and were given chest X-rays and/or high resolution computerized tomography (HRCT) examinations at the Chinese PLA General Hospital during the 12 months that followed their release from the hospital. Those individuals who were found to have lung diffusion abnormities (transfer coefficient for carbon monoxide [DLCO] < 80% of predicted value [pred]) received regular lung function tests and HRCT examinations in the follow-up phase in order to document the changes in their lung condition. Some patients who complained of joint pain were given magnetic resonance imaging (MRI) examinations of their femoral heads. FINDINGS: Of all the subjects, 81.2% (311 of 383 patients) tested positive for serum SARS-CoV IgG. Of those testing positive, 27.3% (85 of 311 patients) were suffering from lung diffusion abnormities (DLCO < 80% pred) and 21.5% (67 of 311 patients) exhibited lung fibrotic changes. In the 12 month duration of this study, all of the 40 patients with lung diffusion abnormities who were examined exhibited some improvement of lung function and fibrosis detected by radiography. Of the individuals receiving MRI examinations, 23.1% (18 of 78 patients) showed signs of femoral head necrosis. INTERPRETATION: The lack of sero-positive SARS-CoV in some individuals suggests that there may have been some misdiagnosed cases among the subjects included in this study. Of those testing positive, the serum levels of SARS-CoV IgG antibody decreased significantly during the 12 months after hospital discharge. Additionally, we found that the individuals who had lung fibrosis showed some spontaneous recovery. Finally, some of the subjects developed femoral head necrosis.

Antibodies, Viral↗

Follow-up study on pulmonary function and lung radiographic changes in rehabilitating severe acute respiratory syndrome patients after discharge.

OBJECTIVES: To follow-up on the changes in lung function and lung radiographic pictures of severe acute respiratory syndrome (SARS) patients discharged from Xiaotangshan Hospital in Beijing (by regularly receiving examination), and to analyze retrospectively the treatment strategy in these patients. METHODS: Surviving SARS patients were seen at least twice within 3 months after discharge and underwent SARS-associated coronavirus (SARS-CoV) IgG antibody testing, pulmonary function testing, and chest radiography and/or high-resolution CT (HRCT) examinations at Chinese PLA General Hospital. The treatments received at Xiaotangshan Hospital were analyzed retrospectively and were correlated to later status. RESULTS: Positive SARS-Co virus IgG antibody results were seen in 208 of 258 patients, with 21.3% (55 of 258 patients) still having a pulmonary diffusion abnormality (D(LCO) < 80% of predicted). By comparing the 155 survivors with positive SARS-CoV IgG antibody results and D(LCO) > or = 80% predicted with the 50 patients with negative SARS-CoV IgG results, we found that 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality had endured a much longer course of fever and received larger doses of glucocorticoid, as well as higher ratios of oxygen inhalation and noninvasive ventilation treatment. For these patients, 51 of 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality underwent pulmonary function testing after approximately 1 month. D(LCO) improved in 80.4% of patients (41 of 51 patients). Of the patients with a lung diffusion abnormality, 40 of 51 patients showed lung fibrotic changes in the lung image examination and 22 patients (55%) showed improvement in lung fibrotic changes 1 month later. CONCLUSION: These findings suggest that lung fibrotic changes caused by SARS disease occurred mostly in severely sick patients and may be self-rehabilitated. D(LCO) scores might be more sensitive than HRCT when evaluating lung fibrotic changes.

Adolescent↗

An Asian study on the prevalence of atypical respiratory pathogens in community-acquired pneumonia.

BACKGROUND: In many parts of Asia, the inaccessibility and high cost of diagnostic tests have hampered the study of community-acquired pneumonia (CAP) caused by atypical respiratory pathogens. OBJECTIVE: This surveillance study examined the frequency of infection with Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila in 1756 patients presenting with signs and symptoms of CAP at 12 medical centres in Asia, using standardised laboratory techniques and interpretation criteria in all participating centres. METHODS: Diagnosis of current infection was based on significant changes in antibody titer or persisting high antibody titers, together with the presence of bacterial DNA in respiratory secretions, in the case of M. pneumoniae and C. pneumoniae infections, or bacterial antigen in urine, in the case of L. pneumophila serogroup 1 infection. RESULTS: Using these criteria, results from 1374 patients with paired sera showed that, overall, 23.5% of CAP cases were associated with infection with atypical respiratory pathogens, with M. pneumoniae, C. pneumoniae, and L. pneumophila being found in 12.2%, 4.7%, and 6.6% of cases, respectively. Persisting high antibody titers indicative of past exposure to M. pneumoniae, C. pneumoniae, and L. pneumophila were seen in 10.2%, 4.8%, and 18.9% of patients, respectively. CONCLUSION: These data reflect the overall high prevalence of these atypical pathogens among Asian patients with CAP.

Adolescent↗

Inhaling beta(2)-agonist with heliox-driven in bronchial asthma.

OBJECTIVE: To evaluate the effectiveness of a helium-oxygen mixture (79%He- 21%O(2)) as an aerosolizing compressed gas for beta(2)-agonist therapy in patients with an asthma exacerbation. METHODS: Twenty-four patients in the outpatient department with a mild to moderate exacerbation of asthma were enrolled. The patients were randomly divided into an experimental group (13 cases) and a control group (11 cases). The experimental group inhaled Berotec with heliox-driven, and the control group inhaled Berotec with compressed air-driven. Eight hospitalized patients in the respiratory department with severe exacerbation of asthma were enrolled. The patients inhaled Berotec with heliox-driven or compressed air-driven in a random order. RESULTS: The results of spirometric parameters and arterial blood-gas analysis were measured. In the mild to moderate asthma patients, no statistical differences between the two groups for forced vital capacity (FVC), forced expired volume in one second (FEV(1)), and expiratory flow in 50% forced vital capacity (FEF(50)) were presented. But the severe patients showed significant differences between heliox-driven and compressed air-driven for FVC, FEV(1), FEF(50) and partial pressure of oxygen (PaO(2)). CONCLUSIONS: Compared with the traditional inhalation of beta(2)-agonist therapy using compressed air-driven, the method of inhaling beta(2)-agonist with heliox-driven has more obvious benefits for those suffering from severe asthma. This is likely due to the cooperative effects between inhaling heliox on its physical gas properties and improving delivery of beta(2)-agonist in the treatment of exacerbation of severe asthma.

Adrenergic beta-Agonists↗

[Respiratology].

Explore the source record for details and available documents.

Asthma↗

[The expression of AmpC and extended-spectrum beta-lactamases among clinical isolates of enterobacter cloacae and its impact on antibiotics susceptibility].

OBJECTIVE: To investigate the expression of AmpC beta-lactamases and ESBL among clinical isolates of E. cloacae and its impact on antibiotic susceptibility. METHODS: Antibiotic susceptibility was determined by standard agar dilution procedures. beta-lactamases of the isolates with decreased susceptibilities to ceftazidime, cefotaxime, ceftriaxon or aztreonam were investigated by three-dimensional extract tests, isoelectric focusing overlay technique, conjugation experiments and PCR. RESULTS: Among 106 E. cloacae isolates, 16.0% produced only high-level AmpC beta-lactamases, 10.4% produced only ESBL, 13.2% produced both high-level AmpC beta-lactamases and ESBL. 18 isolates (17.0%) carried CTX-M-type ESBL and 7 isolates (6.6%) carried SHV-type ESBL. All carbapenems showed high activity against E. cloacae strains (MIC90 <or= 2 micro g/ml). More than 70% of the isolates producing only high-level AmpC beta-lactamases were susceptible to cefepime, amikacin, gentamicin or ciprofloxacin. More than 60% of the isolates producing only ESBL were susceptible to piperacillin/tazobactam, cefoperazone/sulbactam, ciprofloxacin or amikacin. The susceptible rates of the isolates producing both high-level AmpC beta-lactamases and ESBL to tested antimicrobial agents other than carbapenems were all lower than 25%. CONCLUSION: CTX-M-type ESBL was prevalent among clinical isolates of E. cloacae. Resistance to expanded-spectrum cephalosporins in E. cloacae was mediated not only by AmpC beta-lactamases but also by ESBL. Expression of ESBL in high-level AmpC beta-lactamases producing strains resulted in a significant rise in resistance level.

Anti-Bacterial Agents↗