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Objective To compare the efficacy and safety of levofloxacin 750 mg for 5 days versus 500 mg for 7‐14 days intravenous (IV ) infusion in the treatment of community‐acquired pneumonia (CAP ) . Methods This study was a multi‐center , randomized , open‐label , non‐inferiority , controlled clinical trial .The CAP patients were randomized to receive levofloxacin 750 mg IV daily for 5 days or levofloxacin 500 mg IV daily for 7‐14 days .The clinical symptoms , laboratory tests , imaging results and microbiology data were collected and compared between the two treatment groups in terms of efficacy and safety .Results A total of 241 patients were enrolled in this clinical trial from 10 study centers .Among these patients ,223 were eligible for full analysis set (FAS) analysis ,including 111 in 750 mg group and 112 in 500 mg group .Of the 223 patients in FAS ,211 were eligible for per‐protocol set (PPS) analysis ,including 107 in 750 mg group and 104 in 500 mg group .Two hundred and forty‐one patients were included in safety set (SS) ,including 121 patients in 750 mg group and 120 in 500 mg group .The median treatment duration was 5 .0 days in 750 mg and 9 .0 days in 500 mg group .The median total dose was 3 750 mg in 750 mg group and 4 500 mg in 500 mg group .The overall efficacy rate was 86 .2% in 750 mg group and 84 .7% in 500 mg group in terms of FAS at visit 4 ,which suggested that the efficacy of 750 mg group was non‐inferior to 500 mg group .Of the 111 FAS patients in 750 mg group ,40 were bacteriological evaluable ,and 41 strains of pathogens were isolated .Forty‐nine of the 112 FAS patients in 500 mg group were bacteriological evaluable ,and 51 bacterial strains were obtained .The bacterial eradication rate was 100% in both groups .The clinical treatment efficacy rate for atypical pathogens was 100% in both groups .In 750 mg group ,the most common clinical adverse drug reactions (ADRs) were injection site adverse reactions including injection site pruritus ,pain and hyperemia .The other common ADRs were insomnia ,nausea ,skin rash .The most common drug‐related laboratory abnormalities were neutrophil percentage decreased , decreased white blood cell (WBC ) count , alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation .Most of the ADRs were mild in severity and well‐tolerated .The safety profile of the two treatments was comparable in terms of the drug‐related treatment discontinuation and the incidence of ADRs .Conclusions The short‐course regimen of levofloxacin 750 mg IV for 5 days is at least as effective and well tolerated as the long‐course regimen of 500 mg IV for 7‐14 days in treatment of CAP .
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Objective To analyze the clinical characteristics of patients with L isteria septicemia for better clinical diagnosis and management of the disease .Methods A retrospective study was carried out in 13 patients with confirmed diagnosis of Listeria septicemia from July 2009 to November 2013 in West China Hospital of Sichuan University .The clinical features ,laboratory tests ,treatments and clinical outcomes were reviewed and analyzed . Results The vast majority of the 13 patients were immunocompromised or with critical organ dysfunction . The in vitro antimicrobial susceptibility testing indicated that penicillin ,ampicillin and levofloxacin were the most active agents against Listeria ,followed by imipenem ,erythromycin , ciprofloxacin and tetracycline .Only 33 .3% of the 13 Listeria isolates were sensitive to oxacillin .Eight patients were cured ,2 improved ,2 died after therapy .The remaining one patient gave up therapy .Conclusions The incidence of Listeria septicemia was associated with advanced age and presence of underlying diseases .Early etiology diagnosis and appropriate antibacterial therapy can improve the outcome of such patients .Actively treating underlying diseases helps reduce the mortality rate .
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ObjectiveTo investigate the inhibitory effect of bone morphogenetic protein 7 (BMP7) on proliferation of rat hepatic stellate cells (HSC).MethodsHSC-T6 cells were cultured in vitro,and divided into four groups:control group,transforming growth factor (TGF) β1 group,TGFβ1 + BMP7 group,and TGFβ1 + BMP7 + Noggin group. The mRNA expressions of smad1,α-smooth muscle actin (α-SMA),gremlin and fibronectin (FN) were determined by semi-quantitative reverse transcriptasepolymerasechainreaction(RT-PCR).Theproteinexpressionsof phosphorylated-smad1/5/8 (P-smad1/5/8),α-SMA and gremlin were detected by Western blot.The statistical analysis were done using one-factor analysis of variance,LSD-t test,Dunnett's T3 test and Pearson linear correlation analysis.ResultsPhosphorylated-smad1/5/8,α-SMA,gremlin and FN were expressed on HSC-T6 cells in control group,which were significantly up-regulated after TGFβ1 stimulation (P＜0.05).The expressions of α-SMA,gremlin and FN were significantly down-regulated in TGFβ1 + BMP7 group compared with TGFβ1group, while P-smad1/5/8 expression was upregulated (1.613±0.031 vs.2.503±0.014; t=34.89,P＜0.05).The expressions of α-SMA,gremlin and FN in TGFβ1 + BMP7 + Noggin group were up-regulated than those in TGFβ1 + BMP7 group,while P-smad1/5/8 was down-regulated (t=34.05,P＜0.05).There was no difference of total smad1 mRNA expression among each group.ConclusionThese results collectively suggest that BMP7 strongly inhibits the expressions of α-SMA,gremlin and FN.
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Objective To observe the expressions of small heterodimer partner (SHP) in rat model of hepatic fibrosis and its role in fibrosis.Methods A total of 30 healthy male SD rats were divided into two groups: 6 rats in control group and 24 rats in model group.The model group was further divided into four subgroups which were sacrificed at different time points,2,4,6 and 8 weeks after intraperitoneal injection of dimethylnitrosamine (DMN).After establishment of the rat model,blood samples and liver tissue specimens were collected at week 2,4,6 and 8 respectively.The sections of liver tissue were stained with HE and Masson and then were observed under optical microscope.The expressions of SHP mRNA and protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot,respectively.The comparison of means among the groups was performed by univariate ANOVA.Results The hepatic fibrosis was most obvious at 4 weeks and 6 weeks after the intraperitoneal injection.In model groups,alanine aminotransferase (ALT) and aspartateaminotransferase (AST) levels gradually increased and reached a peak at week 4,which were (169.2±16.2) and (193.3±31.1) U/L,respectively.Meanwhile,albumin level in the model group decreased gradually,reaching the nadir at week 6,and the differences were statistically significant at all selected time points between the model group and control group (FAST =83.10,FALT =104.63,FAlb =54.24; all P＜0.05).After modeling,the expression of SHP mRNA and protein in model group were significantly increased than those in control group,and reached a peak at week 4 (0.4494±0.0555 and 1.1155 ±0.1546,respectively),then both mRNA and protein levels decreased gradually at week 6 and 8 which obviously lower than the control group.Transforming growth factor (TGF)β1 mRNA expression level also increased gradually,reaching a peak at week 4 (0.9625±0.1196),and the differences between model subgroups and control group were statistically significant (F=25.740,171.383,118.393 and 94.343; all P＜0.05).Linear correlation analysis showed that SHP mRNA was positively correlated with TGFβ1 mRNA (r=0.593,P＜0.01).Conclusion During the progression of hepatic fibrosis,the SHP expression increases at the beginning and then turns to decrease,which suggests that SHP may play an important role in the development of hepatic fibrosis.
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Objective To improve the diagnosis and treatment based on the retrospective clinical analysis of 86 patients with leishmaniasis, an endemic disease caused by various species of Leishmania. Methods The data of 86 consecutive patients with visceral leishmaniasis and lymph node leishmaniasis were retrospectively reviewed, including epidemiological data, clinical manifestations, laboratory features, diagnosis, therapeutic procedures and prognosis. Results There were specific endemic zones of leishmaniasis in Sichuan province. The main clinical symptoms and signs in the initial evaluation were: fever (100%), splenomegaly (100%), enlarged lymph nodes with hepatosplenomegaly (58.1%). All patients were treated with sodium pentavalent antimony gluconate (SPAG). About 95.3% (82/86) of the patients were cured, 3.5% (3/86) improved, and 1.2% (1/86) relapsed. Splenotomy was carried out for 2.3% (2/86) of the patients. The misdiagnosis rate was 30.2%.Conclusions Visceral leishmaniasis has no specific manifestations and is easily misdiagnosed. If leishmaniasis is suspected, bone marrow biopsy and smear examination, lymph node biopsy, rk-39 strip test for visceral leishmaniasis pathogen should be done to improve the outcome. SPAG is the first choice for leishmaniasis chemotherapy.
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Objective To explore the effect of self-management health education on promoting the medical compliance of patients with metabolic syndrome. Methods Fifty-six patients with metabolic syn-drome were divided into the observation group and the control group at random, with 28 patients in each group. The self-management health education was only given to the observation group, the control group was given rou-tine instruction. After three months, the patients' medical compliance and the ecological parameters (fasting blood glucose, 2 hours' postprandial blood glucose, glycosylated hemoglobin, triglyceride) were tested, the re-suits went through χ2 test and t test. Results The observation group had a better medical compliance than that of the control group, and the biochemieal parameters were greatly alleviated. Conclusions Nursing inter-vention is an ef-feetive measure to improve the medical compliance of patients with metabolic syndrome.
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Objective To investigate the clinical characteristics and therapeutic methods of bac-terial colonization and infection of Acinetobacter baumannii on the wound of earthquake induced patients. Methods A retrospective study was done on 42 Wenehuan earthquake induced patients with positive wound germiculture of Acinetobacter baumannii. There were 24 males and 18 females, at mean age of 37 years (12-96 years). Open injury was located at the upper arm in one patient, at the forearm in four, at the thigh in 12, at the calf in 23 and at the trunk in two. The time between injury and treatment varied from 3 to 7 days. The clinical characteristics including the bacteria identification and drug sensitivity test were studied to compare drug resistance to 15 antibiotics. Results Bacterial colonization of Acineto-bacter baumannii was found in 31 patients (8.2%) and infection of Acinetobacter baumannii in 11 (2.9%). After debridement, pruphylactic antibiotics and nutrition support, 15 patients with bacterial colonization were managed with Ⅱ stage suture or skin grafting. The other 16 patients were transferred to hospitals of other provinces after germiculture turned negative. Through debridement and drainage, antibi-otic therapy and nutrition support, the infection was controlled and the wound eliminated in six patients through Ⅱ stage suture but four were concomitant with pulmonary infection and one with septicemia. Drug sensitivity test showed that sensitive rate to imipenem, amikacin, levofloxacin, ticarcillin-clavulanic acid, tobramycin were 59.5%, 21.4%, 21.4%, 19.5% and 19.0% respectively. Conclusions The risk factors of infection of Acinetobacter baumannii include severe tissue trauma, severe wound contamination, delayed treatment and weak body resistance. During treatment, the bacterial colonization and infection of Acinetobacter baumannii should be distinguished and treated respectively. Correct wound treatment, suit-able antibiotic therapy and increased body resistance are key to improvement of clinical curative effect.
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Objective To study the effects of efflux pump inhibitors(CCCP and PAβN)on carbapenems in Pseudomonas aernginosa(P.aeruginosa)clinical isolates and investigate the association between the resistance to imipenem or meropenem and expression levels of efflux pumps of P.aeruginosa.Methods MICs of imipenem or meropenem combined with efflux pump inhibitors including carbonyl cyanide m-chlorophenylhydrazone(CCCP,107 strains)and Phe-Arg-β-naphthylamide(PAβN,71 strains)against imipenem-resistant strains were determined by agar dilution method,and changes of MICs were observed.For 32 strains with different resistant phenotypes to imipenem and meropenem,the mRNA expression levels of three efflux pump genes(mexA,mexD and mexF)were quantified by real time fluorescent quantitative PCR.Results The resistance rate of imipenem and meropenem didn't prove any significant difference in the presence of efflux pump inhibitors.The X2 value of imipenem combined with CCCP and PAβN were 0.338 and 0.086,respectively(P＞0.05),while that of meropenem combined with CCCP and PAβN were 1.065 and 1.458(P＞0.05).No significant in MICs of carbapenems were seen in over half of P. aeruginesa isolates. MICs of carbapenems was significantly downregulated for 4-fold or above in eight isolates. Overexpression of efflux pumps genes were present in 24 of 27 carbapenem-resistant isolates(88. 9% ). Efflux pumps genes including MexAB-OprM, MexCD-OprJ and MexEF-OprN were all overexpressed in 13 isolates,constituting 54. 2% of all carbapenem-resistant isolates. There were 3 isolates in which beth MexAB-OprM and MexCD-OprJ showed overexpression,constituting 12. 5%. Also,MexAB-OprM and MexEF-OprN overexpressed in 3 isolates. There were 2 isolates (8.3%) showing MexEF-OprN overexpression and MexAB-OprM alone. MexCD-OprJ didn't showed overexpression alone. Furthermore,the expression levels of efflux pumps genes mexA,mexD and mexF in isolates susceptible to both in imipenem and meropenem were 0. 48±0. 48,0. 48±0. 53 and 0. 30±0. 41,respectively,which were much lower than that in carbapenem-resistant ones (P＜0. 05 ). MexA gene was expressed at a higher level in meropenemresistant isolates than meropenem-susceptible ones (P＜0. 05 ). Conclusions When the concentration of CCCP and PAβN were 5 μg/ml and 20 μg/ml respectively,the efforts on the carhapenems resistance of P.aeruginosa were small Overexpression of MexAB-OprM might play an important role in meropenemresistance in P. aerugines. Overexpression of MexCD-OprJ and MexEF-OprN was associated with imipenemresistance. However,the relationship between them and meropenem-resistance need to be explored in the future.
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<p><b>OBJECTIVE</b>To evaluate the role of outer membrane protein (Omp) F-deficiency and active efflux in the accumulation of hydrophilic fluoroquinolones ciprofloxacin (CPLX) and lomefloxacin (LMLX) in resistant E. coli strains.</p><p><b>METHODS</b>Fluoroquinolone accumulation in bacteria and the effect of active efflux were measured by a fluorescence method. The outer membrane proteins of the bacteria were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). E. coli strains in this study included control strains JF701 and JF703 that are OmpC- or OmpF-deficient mutants of E. coli K-12, respectively, and the fluoroquinolone susceptible strain the fluoroquinolone susceptible strain of Escherichia coli (Ecs) and its in vitroselected resistant strains R2 and R256, and the clinical resistant isolates R5 and R6.</p><p><b>RESULTS</b>The steady-state accumulation concentration of each drug in Ecs appeared to be the same as in JF701, while in the OmpF-deficient strain JF703, it was 1/5 CPLX or 1/2 LMLX lower than that in JF701, but JF703 was still susceptible to fluoroquinolones. On the other hand, compared with susceptible strains, a 2- to 10-fold decrease in the accumulation of each drug was found in the resistant strains except R2, in which the accumulation was slightly higher than in JF703. After the addition of 2,4-dinitrophenol (DNP), accumulation of each drug increased, especially in resistant strains, indicating that the function of the active efflux (pump) system in these bacteria had been enhanced dramatically. Furthermore, both OmpF and OmpC in Ecs, OmpF-deficiency in R2 and R256 and OmpC-deficiency in R5 and R6 were observed.</p><p><b>CONCLUSION</b>The decreased accumulation of hydrophilic fluoroquinolones in E. coli involved OmpF-deficiency and active efflux (pump), and the latter may be an important factor.</p>
Subject(s)
2,4-Dinitrophenol , Pharmacology , Anti-Infective Agents , Metabolism , Pharmacology , Ciprofloxacin , Metabolism , Pharmacology , Drug Resistance, Bacterial , Escherichia coli , Metabolism , Fluoroquinolones , Porins , Physiology , Quinolones , Metabolism , PharmacologyABSTRACT
Objective To investigate the drug-resistance and distribution of 142 strains acinetobacter baumannii.Methods Drug-resistance test of acinetobacter baumannii strains was observed in 13 kinds of antibiotics.The drug sensitivity tests was performed by the method of Kirby-Bauer paper-diffusion with the standard of NCCLS.AmpC enzyme was examined by cefoxitin three dimension test and PCR amplification of ampC structure gene were studied.Results The main sources of specimen were sputum,wound secretion,urine and blood.The respiratory tract was a major site to the development of acinetobacter baumannii.Acinetobacter baumannii strain emerged mostly in the intensive care unites.The drug resistance to cefotaxime,ceftriaxome and aztreonam were high.PCR amplification showed that of 142 acinetobacter baumannii strains,23 strains had ampC structure gene which accounted for 16 2% total strains.The drug resistance of acinetobacter baumannii producing AmpC enzyme were significantly higher than those of non-producing AmpC.The best choice of treatment was imipenem.Conclusions Acinetobacter baumannii have higher multiple-antibiotic resistance,the finding prompting us to project prospective control strategies.