A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate versus levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3 multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin versus levofloxacin for treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: The eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at test of cure (TOC) visit in the modified intent-to-treat (mITT) population. The efficacy and safety were also compared between nemonoxacin and levofloxacin in terms of secondary efficacy and safety endpoints. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n=349) or levofloxacin (n=176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P> 0.05). The clinical efficacy of nemonoxacin was noninferior to levofloxacin in treatment of CAP. Nemonoxacin achieved microbiological success rate of 88.8% (95/107), while levofloxacin achieved 87.8% (43/49) (P > 0.05) at TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in nemonoxacin group and 22.2% in levofloxacin group, mostly local reactions at the infusion site, nausea, elevated ALT/AST, and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and noninferior to levofloxacin for treating CAP in adult patients.

Efficacy and Safety of Sea Salt-Derived Physiological Saline Nasal Spray as Add-On Therapy in Patients with Acute Upper Respiratory Infection: A Multicenter Retrospective Cohort Study.

BACKGROUND The purpose of this study was to assess the effects of seawater on nasal congestion and runny nose symptoms in adults with an acute upper respiratory infection (URI). MATERIAL AND METHODS This was a multicenter retrospective cohort trial of patients with acute URI and symptoms of nasal congestion and runny nose. The patients were assigned to 2 groups and were administered regular non-drug supportive treatment or supportive treatment with nasal irrigation with sea salt-derived physiological saline. The primary efficacy endpoint was the effective rate (percentage of patients with ≥30% symptom score reduction from baseline for nasal congestion and runny nose). RESULTS In total, 144 patients were enrolled, including 72 in each group, and 143 patients completed the study. Both groups had similar demographics and vital signs. The effective rates for nasal congestion and runny nose were significantly increased in the seawater group compared with patients in the control group (87.3% vs 59.7% for nasal congestion; 85.9% vs 61.1% for runny nose; both P<0.001). In addition, the 2 groups showed markedly different degrees of patient symptom score improvement in sleep quality and appetite (both P<0.01), but not in cough and fatigue (both P>0.05). There were no adverse events in either group. CONCLUSIONS The sea salt-derived physiological saline nasal spray device satisfactorily improved nasal congestion, runny nose, sleep quality, and appetite in adults with URI, with no adverse effects.

Heat shock protein B8 promotes proliferation and migration in lung adenocarcinoma A549 cells by maintaining mitochondrial function.

Heat shock protein B8 (HSPB8) impacts on tumor proliferation and migration of malignancy. However, the role of HSPB8 in lung adenocarcinoma (LUAC) remains unclear. The aim of this study, therefore, was to clarify whether HSPB8 could bring benefits to proliferation and migration of LUAC and its underlying mechanisms. The expression of HSPB8 was first evaluated by immunohistochemistry in 35 LUAC samples. Then, A549 lung adenocarcinoma cells were transfected with pcDNA-HSPB8 or si-HSPB8 to induce HSPB8 overexpression and silence. Cellular activity was evaluated with a Cell Counting Kit-8 (CCK-8) assay. Cell proliferation and migration were observed by EdU assay and scratch assay. Mitochondria-specific reactive oxygen species (mtROS) and membrane potential were measured using MitoSOX Red probe and JC-1 staining. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) level were measured using commercial kits, respectively. HSPB8 protein, mitochondrial fusion protein MFN2 and mitochondrial fission protein p-Drp1/Drp1 were measured using western blot. Compared with the normal tissues, the expression of HSPB8 protein was higher in LUAC tissues and upregulation of HSPB8 protein was related to tumor size and tumor location. Furthermore, HSPB8 overexpression aggravated cell proliferation and migration of A549 cells. Mechanistically, HSPB8 suppressed mitochondrial impairment, leading to promoting the progress of A549 lung adenocarcinoma cells. These data demonstrate that HSPB8 plays an important role in progression of LUAC and may be a new target to treat LUAC.

Maternal embryonic leucine zipper kinase: A novel biomarker and a potential therapeutic target in lung adenocarcinoma.

Maternal embryonic leucine zipper kinase (MELK), is an adenosine monophosphate-activated protein kinase-related kinase that serves important roles in tumourigenesis in multiple malignant tumours. However, to the best of our knowledge, the effect of MELK in lung adenocarcinoma (LUAD) has not been elucidated. The present study aimed to explore the clinical significance of MELK in the prognosis of LUAD. Data from Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) were selected to predict the differential mRNA expression levels of MELK mRNA in LUAD and normal tissues. Subsequently, LUAD and adjacent normal tissue samples were collected from 75 patients with the disease, and immunohistochemistry was used to detect the protein expression of MELK. In addition, the Kaplan-Meier Plotter database, GEPIA and TCGA were used to verify the effect of MELK expression on clinical prognosis in patients with LUAD. MELK was significantly upregulated in LUAD tissues compared with that in normal tissues based on Oncomine, GEPIA and TCGA data (P<0.05). In addition, the results from immunohistochemistry demonstrated that the MELK protein level in LUAD tissues was significantly higher compared with that in matched normal tissues (P<0.05). Prognostic analysis performed using the Kaplan-Meier plotter, GEPIA and TCGA suggested that the expression of MELK was negatively associated with the overall survival time of patients with LUAD (P<0.05). In conclusion, MELK was highly expressed in LUAD based on bioinformatics and immunohistochemistry analysis, and increased expression of MELK was associated with a poor patient prognosis. MELK may serve as a potential diagnostic marker and therapeutic target for LUAD.

Novel Coronavirus Pneumonia Outbreak in 2019: Computed Tomographic Findings in Two Cases.

Since the 2019 novel coronavirus (2019-nCoV or officially named by the World Health Organization as COVID-19) outbreak in Wuhan, Hubei Province, China in 2019, there have been a few reports of its imaging findings. Here, we report two confirmed cases of 2019-nCoV pneumonia with chest computed tomography findings of multiple regions of patchy consolidation and ground-glass opacities in both lungs. These findings were characteristically located along the bronchial bundle or subpleural lungs.

The expression and prognostic significance of Drp1 in lung cancer: A bioinformatics analysis and immunohistochemistry.

BACKGROUND: Dynamin-related protein 1 (Drp1) plays important roles in tumorigenesis, including lung cancer. However, the effect of Drp1 in lung cancer remains unclear. The present study was aimed to investigate the clinical significance and effect of Drp1 on prognosis of lung cancer. METHODS: Oncomine and The Cancer Genome Atlas (TCGA) databases were selected to predict the differential expression levels of Drp1 in lung cancer. Then, 70 cases of lung cancer and normal tissues were collected and immunohistochemistry was used to detect the expression of Drp1. In addition, Kaplan-Meier Plotter database and TCGA database were used to verify the correlation between Drp1 expression and the clinical prognosis in lung cancer patients. RESULTS: Drp1 was significantly overexpressed in lung cancer tissues based on Oncomine and TCGA databases (P < .05). Moreover, results from immunohistochemistry showed that Drp1 protein level in lung cancer was also significantly higher than that in the matched normal tissues (P < .05). Prognostic analysis from Kaplan-Meier Plotter database with the chosen probe IDs of 203105_s_at suggested that Drp1 was negatively correlated to overall survival (OS) of lung cancer patients (HR = 1.16, 95% CI: 1.02-1.31; P = .025), but not in the probe IDs of 226154_at (HR = 0.86, 95% CI: 0.73-1.01; P = .069). However, prognosis from TCGA database showed inconsistent results in which high expression of Drp1 was correlated with worse survival probability of all, male, female in lung adenocarcinoma (P < .05), but not in LUSC (P > .05). CONCLUSION: Drp1 was highly expressed in lung cancer based on bioinformatics analysis and tissue microarray, but there was a lot of inconsistency in prognosis depending on different levels of Drp1 from the bioinformatics analysis.

A case of herbicide-induced acute fibrinous and organizing pneumonia?

BACKGROUND: To improve the understanding of acute fibrinous and organizing pneumonia (AFOP), we present one case of AFOP proven by percutaneous lung biopsy along with clinical features, chest imaging and pathology. CASE PRESENTATION: A 50-year-old man was admitted to our department after he was given empiric therapy for community-acquired pneumonia (CAP). The clinical symptoms of the patient were dry cough, chills, night sweats and high fevers. Chest computed tomography (CT) scan showed a high-density shadow in the right lung lobe, similar to lobular pneumonia. The patient was preliminarily diagnosed with community-acquired pneumonia; however, antibacterial treatment was ineffective. To confirm the diagnosis, we performed bronchoscopy and percutaneous lung biopsy; pathology was consistent with AFOP. After he was treated with glucocorticoids, the patient's symptoms were relieved, and the shadow seen on imaging dissipated during the follow-up period. CONCLUSIONS: AFOP is a rare histopathological diagnosis that can be easily misdiagnosed. Clinicians need to consider the possibility of AFOP in the case of invalid antibacterial therapy.

Endobronchial hamartoma mimicking malignant lung tumor contralateral endobronchial metastasis: A case report.

RATIONALE: Endobronchial hamartoma, the most common benign lung tumor, is located in the bronchus, and it easily mimics lung cancer or bronchial metastasis. Endobronchial hamartoma can cause coughing, hemoptysis, and pulmonary infection; thus, it should be treated right away by surgery or fiberoptic bronchoscopy. PATIENT CONCERNS: We report a rare case of endobronchial hamartoma in which the clinical symptoms and imaging overlapped strongly with malignant lung tumor contralateral endobronchial metastasis. DIAGNOSES: Endobronchial hamartoma coexisting with a malignant lung tumor. INTERVENTIONS: Fiberoptic bronchoscopy was conducted, and the pathologic diagnosis was hamartoma. A second fiberoptic bronchoscopy was conducted, and fine-needle aspiration cytology of the enlarged lymph nodes indicated squamous cell carcinoma. OUTCOMES: The clinical symptoms were relieved, and the treatment options were docetaxel, cis-dichlorodiamineplatinum, and endostatin. LESSONS: Fiberoptic bronchoscopy needs to be guided by imaging and can be considered an effective method for the diagnosis of endobronchial hamartoma.

Reduced expression of miR­205­5p promotes apoptosis and inhibits proliferation and invasion in lung cancer A549 cells by upregulation of ZEB2 and downregulation of erbB3.

Previous studies have demonstrated that microRNA (miR)-205-5p expression is significantly increased in non­small cell lung cancer tissues and is associated with tumor differentiation grade. The aim of the present study was to explore the effects of miR­205­5p on viability, apoptosis and invasion of lung cancer A549 cells. The hsa­miR­205­5p small interfering RNA (siRNA) inhibitor was transfected into A549 cells and expression of miR­205­5p was detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). Cell viability, apoptosis and invasion were assayed by Cell Counting kit­8, Annexin V/propidium iodide double staining and Transwell assay, respectively. Target genes of miR­205­5p were predicted using bioinformatics analysis. Expression of mRNA and protein levels of candidate target genes following miR­205­5p inhibition were detected using RT­qPCR and western blot analysis respectively. The results demonstrated that relative survival rates of A549 cells were significantly inhibited in miR­205­5p siRNA­transfected cells at 24 and 48 h compared with control cells. Apoptosis was markedly increased in the miR­205­5p siRNA cells compared with control cells. The number of invaded cells following miR­205­5p siRNA silencing was significantly decreased compared with control cells. Bioinformatics analysis revealed that erb­B2 receptor kinase 3 (erbB3), zinc finger E­box binding homeobox 2 (ZEB2), clathrin heavy chain (CLTC) and mediator complex subunit 1 (MED1) may be potential target genes of miR­205­5p. Reduced expression of miR­205­5p significantly increased the expression of ZEB2 mRNA and protein, inhibited the expression of erbB3 protein, but had no significant effect on the expression levels of CLTC and MED1. In summary, reduced expression of miR­205­5p promoted apoptosis and inhibited proliferation and invasion in lung cancer A549 cells through upregulation of ZEB2 and downregulation of erbB3. The present results suggested that the increased miR­205­5p expression observed in non­small cell lung cancer tissues may contribute to increased proliferation and invasion of lung cancer cells and thus to cancer progression.

A randomized, double-blind, multicenter Phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia.

BACKGROUND/PURPOSE: To compare the clinical efficacy and safety of nemonoxacin with levofloxacin in treating community-acquired pneumonia (CAP) in a Phase II clinical trial. METHODS: One hundred ninety-two patients with CAP were randomized to receive oral nemonoxacin (500 mg or 750 mg) or levofloxacin (500 mg) once daily for 7-10 days. Clinical and bacteriological responses were determined at the test of cure (TOC) visit in the full analysis set (FAS). RESULTS: The clinical cure rate of nemonoxacin (500 mg), nemonoxacin (750 mg), and levofloxacin (500 mg) was 93.3%, 87.3%, and 88.5%, respectively, in the FAS (n = 168), and 93.0%, 93.9%, and 88.9%, respectively in the per protocol set (n = 152). At the TOC visit, nemonoxacin at 500 mg and 750 mg was proven to be noninferior to levofloxacin at 500 mg in the FAS in terms of clinical efficacy. The overall bacteriological success rate was 83.3% in both nemonoxacin groups and 80.0% in the levofloxacin 500 mg group in the bacteriological FAS. The comprehensive efficacy rate was comparable among the three groups (87.5% for the nemonoxacin 500 mg group, 93.8% for the nemonoxacin 750 mg group, and 81.3% for the levofloxacin 500 mg group). Most drug-related adverse events were mild and transient, mainly gastrointestinal symptoms such as nausea and vomiting, transient neutropenia, and elevated liver enzymes. No drug-related serious adverse events occurred. CONCLUSION: Either 500 mg or 750 mg of oral nemonoxacin taken once daily for 7-10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7-10 days is recommended for future Phase III clinical trials. ClinicalTrials.gov identifier: NCT01537250.

Genetic diversity of avian influenza A (H10N8) virus in live poultry markets and its association with human infections in China.

Following the first human infection with the influenza A (H10N8) virus in Nanchang, China in December 2013, we identified two additional patients on January 19 and February 9, 2014. The epidemiologic, clinical, and virological data from the patients and the environmental specimen collected from 23 local live poultry markets (LPMs) were analyzed. The three H10N8 cases had a history of poultry exposure and presented with high fever (>38°C), rapidly progressive pneumonia and lymphopenia. Substantial high levels of cytokines and chemokines were observed. The sequences from an isolate (A/Environment/Jiangxi/03489/2013 [H10N8]) in an epidemiologically linked LPM showed highly identity with human H10N8 virus, evidencing LPM as the source of human infection. The HA and NA of human and environmental H10N8 isolates showed high identity (99.1-99.9%) while six genotypes with internal genes derived from H9N2, H7N3 and H7N9 subtype viruses were detected in environmental H10N8 isolates. The genotype of the virus causing human infection, Jiangxi/346, possessed a whole internal gene set of the A/Environment/Jiangxi/10618/2014(H9N2)-like virus. Thus, our findings support the notion that LPMs can act as both a gene pool for the generation of novel reassortants and a source for human infection, and intensive surveillance and management should therefore be conducted.

Clinical characteristics of human infection with a novel avian-origin influenza A(H10N8) virus.

BACKGROUND: Novel influenza A viruses of avian-origin may be the precursors of pandemic strains. This descriptive study aims to introduce a novel avian-origin influenza A (H10N8) virus which can infect humans and cause severe diseases. METHODS: Collecting clinical data of three cases of human infection with a novel reassortment avian influenza A (H10N8) virus in Nanchang, Jiangxi Province, China. RESULTS: Three cases of human infection with a new reassortment avian influenza A(H10N8) virus were described, of which two were fatal cases, and one was severe case. These cases presented with severe pneumonia that progressed to acute respiratory distress syndrome (ARDS) and intractable respiratory failure. CONCLUSION: This novel reassortment avian influenza A (H10N8) virus in China resulted in fatal human infections, and should be added to concerns in clinical practice.

A randomized controlled clinical trial of levofloxacin 750 mg versus 500 mg intravenous infusion in the treatment of community-acquired pneumonia.

The objective of this study was to compare the efficacy and safety of levofloxacin 750 mg for 5 days versus 500 mg for 7-14 days intravenous (IV) in the treatment of community-acquired pneumonia (CAP). This clinical trial was the first of its kind conducted in Chinese people and also in Asian population. A total of 241 were enrolled and randomized to 750 mg group (n = 121) or 500 mg (n = 120) group from 10 study centers. The median treatment duration was 5.0 days in 750 mg and 9.0 days in 500 mg group. The median total dose was 3750 mg in 750 mg and 4500 mg in 500 mg group. The bacterial eradication rate was 100% in both groups. The overall efficacy rate in 750 mg group was 86.2% (94/109), and 84.7% (94/111), in 500 mg group of full analysis set visit 4, 95% confidence interval of 1.6% (-7.8-10.9%); the statistical results showed that 750 mg group was non-inferior to 500 mg group. The most common clinical adverse drug reactions were injection site adverse reactions in both 750 mg group and 500 mg group; the other common adverse drug reactions were insomnia, nausea, skin rash, etc. The most common drug-related laboratory abnormalities were neutrophil percentage decreased, decreased white blood cell count, alanine aminotransferase, and aspartate aminotransferase elevation in both 750 mg group and 500 mg group. Most of adverse drug reactions were mild in severity and well-tolerated. In summary, the regimen of levofloxacin 750 mg IV for 5 days was at least as effective and well tolerated as 500 mg IV for 7-14 days for the treatment of CAP.

Relative expressions of miR-205-5p, miR-205-3p, and miR-21 in tissues and serum of non-small cell lung cancer patients.

Objective was to assess and compare the relative expressions of miR-205-5p, miR-205-3p, and miR-21-3p in tissues and serum among non-small cell lung carcinoma (NSCLC) patients, benign pulmonary conditions patients, and healthy volunteers. Serum samples were obtained between October 2011 and September 2012 from 20 NSCLC patients undergoing surgical treatment, 20 patients diagnosed with a benign lung disease (pulmonary tuberculosis, pneumonia, chronic obstructive pulmonary disease, or interstitial pneumonia) (lesion group), and 20 healthy volunteers (control group). NSCLC patients provided cancer tissues and cancer-adjacent normal tissues during surgery (paired specimens). Quantitative RT-PCR was used to assess miR-205-5p, miR-205-3p, and miR-21-3p expressions in serum and tissue samples. The relative expressions of miR-205-5p and miR-205-3p were significantly higher in NSCLC tissues compared with cancer-adjacent paired specimens (both P < 0.001). In the serum, significantly higher miR-205-5p, miR-205-3p, and miR-21-3p relative expressions were observed in the NSCLC group compared with the two other groups (all P < 0.001). The relative expressions of miR-205-5p and miR-21-3p in NSCLC tissues and serum were significantly correlated (r = 0.553, P = 0.011; and r = -0.541, P = 0.014, respectively), while no significant correlation was observed for miR-205-3P (P = 0.120). Expressions of miR-205-5p and miR-205-3P in squamous cell carcinoma specimens were significantly higher than in lung adenocarcinoma specimens (both P = 0.001). Similarly, higher serum miR-205-5p and miR-205-3p levels were observed in squamous cell carcinoma patients (P = 0.033 and P = 0.002, respectively). In this preliminary and novel study, miR-205-5p was more useful as a marker for NSCLC than miR-205-3p or miR-21, indicating a potential for future applications in NSCLC diagnosis and prognosis.

Xiaoqinglong granules as add-on therapy for asthma: latent class analysis of symptom predictors of response.

Xiaoqinglong granules (XQLG) has been shown to be an effective therapy in asthma animal models. We reviewed the literature and conducted this study to assess the impact of XQLG as an add-on therapy to treatment with fluticasone/salmeterol (seretide) in adult patients with mild-to-moderate, persistent asthma. A total of 178 patients were randomly assigned to receive XQLG and seretide or seretide plus placebo for 90 days. Asthma control was assessed by asthma control test (ACT), symptoms scores, FEV(1), and PEF. Baseline patient-reported Chinese medicine (CM)-specific symptoms were analyzed to determine whether the symptoms may be possible indicators of treatment response by conducting latent class analysis (LCA). There was no statistically significant difference in ACT score between two groups. In the subset of 70 patients with symptoms defined by CM criteria, XQLG add-on therapy was found to significantly increase the levels of asthma control according to global initiative for asthma (GINA) guidelines (P = 0.0329). There was no significant difference in another subset of 100 patients with relatively low levels of the above-mentioned symptoms (P = 0.1291). Results of LCA suggest that patients with the six typical symptoms defined in CM may benefit from XQLG.

Greatest International ANtiinfective Trial (GIANT) with moxifloxacin in the treatment of acute exacerbation of chronic bronchitis: subanalysis of Chinese data of a global, multicenter, noninterventional study.

BACKGROUND AND OBJECTIVE: A single infective acute exacerbation of chronic bronchitis (AECB) has a sustained effect on health status. Although a number of clinical investigations have demonstrated the efficacy of antibiotics in AECB, increased bacterial resistance has caused concern about the efficacy of currently available antibiotic therapies. This subanalysis of a global noninterventional study aimed to evaluate the impact of AECB on the patient and the community and the effectiveness and safety of a treatment with moxifloxacin (MXF) tablets in daily life clinical practice in China. METHODS: This prospective, noninterventional, noncontrolled, multicenter observational study, which started in China in April 2004 and ended in February 2007, was part of the global GIANT study. Patients with a diagnosis of mild to severe AECB were treated with MXF tablets 400 mg for a period at the physician's discretion. The observation period for each patient covered a complete treatment period with MXF. For each patient, the physician documented data at an initial visit (baseline) and at least one follow-up visit. Data were collected on demography, diagnosis of infection, pretreatment, concomitant diseases and medications, MXF therapy, course of symptoms during investigations, and final assessment of therapy with respect to MXF. RESULTS: In the Chinese subset of the GIANT study, a total of 11,377 patients were included in the intention-to-treat/safety population. At the end of the initial treatment period, improvement and recovery from infection was observed for 98.6% (n = 11,217/11,377) and 92.6% (n = 10,540/11,377) of all patients. After 1 week of treatment, 76.3% (n = 8681/11,377) of patients had recovered. Median time until improvement and recovery was 3.0 and 6.0 days, respectively. Correspondingly, in 95.8% (n = 10,903/11,377) of all patients, overall effectiveness during the initial treatment period with MXF was assessed as "very good" or "good". Compared with the last AECB, the number of days with impact on daily-life activities and the number of nights with sleep disturbances decreased from 3.0 to 2.0 (median) and from 2.0 to 1.0 (median), respectively. In general, MXF treatment was very well tolerated, with physician's overall assessment of tolerability as "good" or "very good" in 95.2% (n = 10,834/11,377) of patients. The incidence rate of adverse events and adverse drug reactions was 0.82% (n = 93) and 0.67% (n = 76), respectively. The most frequent adverse events were gastrointestinal disorders such as nausea (0.31%, n = 35) and vomiting (0.19%, n = 22), which were mostly drug-related. One individual serious adverse event (dyspnea) occurred during the observation period, which was assessed as drug-related. CONCLUSION: MXF was effective and well tolerated in patients suffering from AECB. The fast speed of the drug's onset of action was associated with rapid improvement of clinical parameters.

Population pharmacokinetics of oral levofloxacin 500 mg once-daily dosage in community-acquired lower respiratory tract infections: results of a prospective multicenter study in China.

This study aimed to explore the pharmacokinetic features of levofloxacin (LVFX) in Chinese patients with infections and to confirm oral LVFX 500 mg once daily as an optimal treatment regimen based on pharmacokinetic-pharmacodynamic (PK-PD) analysis. A total of 1052 plasma samples from 164 Chinese adult patients with community acquired lower respiratory tract infections (CALRTIs) and 18 healthy volunteers were used for population PK analysis. LVFX 500-mg tablets were given once daily. A nonlinear mixed effects model (NONMEM) program was used for population PK model-building and a two-compartment model with first-order absorption process was established. Creatinine clearance (CL(cr)) and body weight were identified as intrinsic factors which significantly affected oral clearance (CL(t)/F) and the apparent volume of distribution of the central compartment (V1/F), respectively. The final model is described as follows: CL(t)/F (l/h) = (8.97 + 0.917 x (CL(cr) (ml/min)-100.92) x 60/1000) x exp (eta(CLt/F)). V1/F (l) = (85.3 + 1.22 x (weight (kg)-60.75)) x exp (eta(V1/F)). Q/F (l/h) = 0.351. V2/F (l) = 6.81. k(a) (h(-1)) = 1.44 x exp(eta(ka)). Based on the population PK model, mean C(max) and AUC(0-24h) in CALRTI patients were estimated as 5.13 microg/ml and 58.98 microg.h/ml, respectively. A subgroup analysis showed that patients with mild renal dysfunction (50 ml/min < or = CL(cr) < 80 ml/min) had 34% higher AUC(0-24h) values compared to patients with normal renal function (CL(cr) > or = 80 ml/min). Postmodeling simulation using final population PK estimates also showed that C(max) and AUC(0-24h) increased markedly in patients with severe renal dysfunction. The results indicate that LVFX dosage adjustment should be individualized on the basis of the CL(cr), especially in those with CL(cr) less than 50 ml/min. None of the PK parameters had any correlation with the occurrence of adverse events. PK-PD analysis indicated that, in patients treated with LVFX 500 mg once daily, the AUC(0-24h)/MIC ratio exceeded the target for those major CALRTI pathogens isolated. In addition, the C(max)/MIC ratio reached 5 for Streptococcus pneumoniae, indicating that the emergence of LVFX-resistant S. pneumoniae could be prevented during the therapy with this dosage regimen. These results demonstrate that oral LVFX 500 mg once daily has favorable PK parameters and PK-PD features in patients with CALRTIs, and the results strongly support this dosage regimen for the treatment of CALRTI.

Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China.

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.

[Clinical characteristic analysis of the first human case infected by influenza A (H5N1) in Jiangxi Province].

OBJECTIVE: To describe the clinical, laboratory and radiological presentation of a human case infected by influenza A (H5N1), and to understand its management and prognosis. METHODS: The clinical and autopsy data of the first human case infected by influenza A (H5N1) in Jiangxi Province were collected and analyzed. RESULTS: The first case infected by influenza A (H5N1) in Jiangxi Province was confirmed by laboratory findings with reverse transcription-polymerase chain reaction (RT-PCR) and influenza A (H5N1) isolation. The patient had been healthy in the past and exposed to the environment of bird flu before illness. The initial symptoms included high fever with influenza-like symptoms, and then cough and purulent sputum mixed with blood appeared. The clinical situation deteriorated progressively with occurrence of diarrhea and dyspnea. Laboratory abnormalities included decrease of peripheral white blood cells and lymphocytes, urine protein, dramatic increase of enzymes associated with hepatic injury and myocarditis and decrease of serum albumin. Six days later, penicillin-resistant streptococcus pneumoniae was isolated from multiple sputum cultures. With the deterioration of clinical situation, several other bacteria and fungi were found in sputum culture. Pulmonary infiltrates were evident in right middle and lower lobe at day 5 after illness, and rapidly progressed to involve bilateral lungs as acute respiratory distress syndrome (ARDS)-like changes. The patient was treated with antiviral, antibacterial, and antifungal reagents, and corticosteroids and invasive mechanical ventilation were also administered, but without any improvement. The patient died 27 days after the onset of symptoms and an autopsy was performed. Pathologically, the lungs exhibited diffuse alveolar damage. The lymphocytes in the spleen, the lymph nodes and the tonsils were depleted prominently with histiocytic hyperplasia and hemophagocytic phenomena. Edema and degeneration of myocytes in the heart and extensive acute tubular necrosis in the kidney were observed. CONCLUSION: The prognosis was very poor if influenza A (H5N1) infected human cases was developed as ARDS with multiple organ damage or failure.