Cloning and functional analysis of IPI gene from Fritillaria unibracteata Hsiao et K. C. Hsia / 药学学报

An open reading frame (ORF) of isopentenyl-diphosphate delta isomerase gene (FuIPI) was cloned from Fritillaria unibracteata Hsiao et K. C. Hsia. (F. unibracteata). Furthermore, the bioinformatics and functional analyses of FuIPI were performed in this study. The result showed that, the ORF of FuIPI gene was 825 bp, encoding a polypeptide of 274 amino acids in length, with a relative molecular mass of about 31 kD and a theoretical isoelectric point of 5.61. Sequence analysis showed that FuIPI contained conserved structural domains and key residues involved in the catalyzing process. The phylogenetic analysis exhibited that FuIPI was closely related to IPIs of Dendrobium officinale and Musa acuminate. Real-time PCR analysis showed that FuIPI was distributed in different tissues of F. unibracteata, but had the highest transcriptional level in leaves, followed by stems, bulbs, and flowers. Furthermore, the FuIPI protein was successfully expressed in Escherichia coli BL21(DE3). The purified FuIPI protein successfully catalyzed the conversion from isopentenyl diphosphate (IPP) to dimethylallyl pyrophosphate (DMAPP). The above results provided a theoretical basis for further investigation of the molecular role of FuIPI in the biosynthesis of alkaloids.

Evaluation of in-vitro susceptibility of ß-lactam-resistant Gram-negative bacilli to ceftazidime-avibactam and ceftolozane-tazobactam from clinical samples of a general hospital in southern Brazil

ABSTRACT Background: The spread of carbapenemase- and extended-spectrum β-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of β-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. Methods: Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The β-lactamase-encoding genes were investigated using polymerase chain reaction. Results: High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-β-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. Conclusions: C/A and C/T were active against microorganisms with β-lactam-resistant phenotypes, except when resistance was mediated by metallo-β-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more β-lactamase-encoding genes (62.5% and 77.4%, respectively).

Actividad in vitro de delafloxacina frente a microorganismos aislados de infecciones osteoarticulares y de piel y partes blandas en Buenos Aires, Argentina

Resumen Se estudió la actividad in vitro de delafloxacina, ciprofloxacina y levofloxacina por los métodos epsilométrico y de difusión por discos frente a 181 aislamientos clínicos de infecciones de piel y osteoarticulares. Se incluyeron 40 Staphylococcus aureus resistentes a meticilina (SARM), 44 S. aureus sensibles a meticilina (SASM), 46 estafilococos coagulasa negativos (ECN), 23 Klebsiella pneumoniae y 28 Pseudomonas aeruginosa. Las CIM50/CIM90 (mg/l) de delafloxacina, ciprofloxacina y levofloxacina respectivamente fueron 0,004/0,064, 0,25/16 y 0,125/4 frente a SARM; 0,002/0,004, 0,125/0,25 y 0,125/0,25 frente a SASM; 0,008/0,25, 0,125/>32 y 0,25/>32 frente a ECN; 4/>32,>32/>32 y 16/>32 frente a K. pneumoniae y 1/>32, 0,5/>32 y 4/>32 frente a P. aeruginosa. La proporción de aislamientos sensibles a delafloxacina, ciprofloxacina y levofloxacina fue la siguiente: SARM, 97,5%; 82,5% y 82,5%; SASM, 97,7%; 95,5% y 95,5%; ECN, 93,5%; 63,0% y 60,9%; K. pneumoniae, 21,7%; 26,1% y 43,5%; P. aeruginosa, 35,7%; 53,6% y 42,8%. La concordancia categórica del método de difusión por discos y el método epsilométrico para evaluar la actividad in vitro de la delafloxacina fue del 98,8% en S. aureus y del 91,3% en ECN.

Abstract In vitro activities of delafloxacin, ciprofloxacin and levofloxacin were evaluated by epsilometric and disk diffusion methods against 181 bacterial isolates recovered from bone and skin infections. Isolates included were 84 Staphylococcus aureus (40 MRSA and 44 MSSA), 46 coagulase-negative staphylococci (CNS), 23 Klebsiella pneumoniae and 28 Pseudomonas aeruginosa. The MIC50/MIC90 (mg/l) for delafloxacin, ciprofloxacin and levofloxacin, respectively, were: MRSA, 0.004/0.064, 0.25/16 and 0.125/4; MSSA, 0.002/0.004, 0.125/0.25 and 0.125/0.25; CNS, 0.008/0.25, 0.125/>32 and 0.25/>32; K. pneumoniae, 4/>32,>32/>32 and 16/>32; P. aeruginosa, 1/>32, 0,5/>32 and 4/>32. Susceptibilities for delafloxacin, ciprofloxacin and levofloxacin, respectively, were: MRSA, 97.5%, 82.5% and 82.5%; MSSA, 97.7%, 95.5% and 95.5%; CNS, 93.5%, 63.0% and 60.9%; K. pneumoniae, 21.7%, 26.1% and 43.5%; P aeruginosa, 35.7%, 53.6% and 42.8%. The disk diffusion and epsilometric methods were concordant for evaluating in vitro susceptibility in staphylococci (categorical concordance of 98.8% for S. aureus and 91.3% for CNS).

Evaluation of antimicrobial, hypotensive and diuretic effect of Eugenia uniflora extracts / Avaliação do efeito antimicrobiano, hipotensivo e diurético de extratos de Eugenia uniflora

The genus Eugenia sp. (Myrtaceae) comprises plants with reported antioxidant and antidiarrheal capability among other therapeutic potentials. The aim of this study was to evaluate the antimicrobial activity of essential oil; diuretic and hypotensive activities of aqueous extracts from leaves of Eugenia uniflora. The antimicrobial activity was evaluated . The diuretic and hypotensive activities were evaluated in normotensive Wistar rats by measuring blood pressure and urine flow after received four different concentrations of aqueous extracts (10%, 15%, 20% and 25%). Essential oil inhibited the growth of Candida parapsilosis and Candida albicans with MIC values lower than 14.41 mg/mL, equal to 57.75 mg/mL for Candida krusei. Among antibacterial effect, essential oil inhibited growth with a MIC equals to 153.93 mg/mL for all strains tested, except for Escherichia coli (MIC equals to 307.96 mg/mL. Aqueous extracts showed powerful reductions of the arterial pressure (34% and 31% lower than the control), after administration of 10% and 25% of aqueous extract, respectively. However, the animals that received the aqueous extract at the 15% and 20% concentrations presented a discrete hypotensive effect (20% and 21% lower than control group, respectively) concomitantly to powerful diuretic effect (280% and 91% higher than control group, respectively). These data confirmed the potential biological effect of this species, and represents an important step toward a depth study on the therapeutic properties of this species

O gênero Eugenia sp. (Myrtaceae) compreende plantas com capacidade antimicrobiana e antioxidante entre outros potenciais terapêuticos. O objetivo deste estudo foi avaliar a atividade antimicrobiana de óleo essencial; atividade diurética e hipotensora de extrato aquoso de folhas de Eugenia uniflora. A atividade antimicrobiana foi avaliada pela determinação da concentração inibitória mínima (MIC) e concentração mínima bactericida (MBC) de cepas bacterianas e concentração fungicida mínima (MFC) para fungos. A atividade diurética e hipotensora foi avaliada em ratos Wistar normotensos pela mensuração da pressão sanguínea e fluxo urinário após administração de quatro diferentes concentrações de extrato aquoso (10%, 15%, 20% e 25%). Óleo essencial inibiu o crescimento de Candida parapsilosis e Candida albicans com valores de MIC menores que 14,41 mg/mL, igual a 57,75 mg/mL para Candida krusei. A respeito do efeito antimicrobiano, o óleo essencial inibiu o crescimento de todas as cepas testadas, com MIC igual a 153,93 mg/mL, exceto para Escherichia coli (MIC igual a 307.96 mg/mL). O extrato aquoso mostrou redução importante da pressão arterial (34% e 31% quando comparado ao controle), após administração de 10% e 25% do extrato aquoso, respectivamente. Contudo, os animais que receberam o extrato aquoso na concentração de 15% e 20% apresentaram discreto efeito hipotensor (20% e 21% menor que o grupo controle, respectivamente) concomitantemente ao importante efeito diurético (280% e 91% maior quando comparado ao grupo controle, respectivamente). Esses achados confirmam o potencial efeito biológico dessa espécie, e representa um importante embasamento para estudos relacionados as propriedades terapêuticas da Eugenia uniflora

Validación del uso tradicional de especies de asclepias contra el veneno de bothrops diporus (yarará chica) en el nordeste de Argentina / Validation of the traditional use of asclepias species against bothrops diporus (yarará chica) venom in northeast of Argentina

La familia Asclepiadaceae posee tradición en etnomedicina. En el nordeste argentino, A.mellodora y A. curassavica se utilizan como cataplasmas en accidentes de ofidios. En este trabajo, los extractos acuosos, etanólicos y hexánicos de A. mellodora y A. curassavica se evaluaron por SDS-PAGE para determinar su actividad alexitérica. El estudio in vitro de la capacidad inhibitoria de las actividades proteolítica, hemolítica indirecta y coagulante permitieron determinar que ambas especies manifiestan actividad, siendo A. mellodora más activa. Estadísticamente los extractos de A. mellodora fueron igualmente activos contra el veneno de Bothrops diporus y no mostraron diferencias significativas respecto del órgano utilizado en la inhibición de la actividad coagulante. Este resultado está en consonancia con la forma tradicional de su uso como cataplasma. Sobre el extracto etanólico de las raíces de A. mellodora se realizó un fraccionamiento bioguiado que permitió identificar fracciones de compuestos responsables de la actividad.

The Aclepiadaceae family has been reported by its use in ethnomedicine. In the northeast of Argentina, A. mellodora and A. curassavica are traditionally used in ofidic accidents as poultices. In this work, aqueous, alcoholic and hexanoic extracts were analyzed by SDS-PAGE to determine their anti-snake activity. The in vitro study of the inhibitory ability of the following activities: proteolytic, indirect hemolytic activity and inhibition of the coagulant activity, allowed demonstrating that both species were active against venom, being A. mellodora the most active. Statistically, all extracts of A. mellodora were active against venom in the inhibition of the coagulant activity, without significant differences with respect to the organ used; which is consistent with the traditional use as external poultice. The alcoholic extract of A. mellodora roots was subjected to a bio-guided separation. The fractions obtained were enriched in compounds which could probably be responsible for the activity against venom.

In vitro activity of a novel cannabinoid receptor l selective antagonist LMJ07 / 国际药学研究杂志

Objective: LMJ07 is a novel cannabinoid receptorl (CB1R) selective antagonist discovered by our lab. In the present study, its affinity and antagonistic activity against CB1R were evaluated at the molecular and cellular levels by receptor binding experiment, CB1R internalization experiment and by monitoring the change in cytoskeletal and intracellular signal induced by CB1R activation. Methods: With the CB1R selective antagonist rimonabant (SR141716A) as control, the affinity and selectivity of LMJ07 to CB1R and CB2R were assayed by radioligand binding assays, and the G protein-independent antagonistic activity against cannabinoid receptor (CBR) was assayed by enhanced green fluorescein protein (EGFP)-CBR internalization with hierarchiae cluscer anclysis (HCA) analysis. At the same time, we evaluated the changes in cytoskeletal and the intracellular cAMP levels in response to LMJ07 treatment in CHO-CB1 cells by Cellkey label-free assays and homogeneous time-resolved fluorescence (HTRF). Additionally, we also confirmed the CB1R antagonistic efficacy of LMJ07 by detecting the content of Ca2+ in primary cultured hippocampal neuronal cells which could express CB1R with continuous fluorescence detection technology. Results: LMJ07 is a selective CB1R antagonist with high affinity, which can selectively antagonize receptor endocytosis induced by CB1RactivationIt’s affinity and antagonistic efficacy to CB1R were equal to those of rimonabant. In CHO-CB1 cells, LMJ07 (0.01-10μmol/L)could dose-dependently inverse the change in cytoskeletal as well as the increase in intracellular cAMP induced by CBR agonist Win55212-2. In the primary cultured hippocampal neuronal cells, LMJ07 (10 nmol/L-1 μmol/L) could block the increase in [Ca2+] induced by CB1R agonist Win55212-2. Conclusion: LMJ07 is a new selective CB1R antagonist, which shows equal affinity and antagonistic activity against CB1R as the widely accepted CB1R antagonist rimonabant. In addition, the combination of high content analysis (HCS) and Cellkey label-free assay provides a better research tool for rapid and high throughput screening of novel CB1R antagonists.

In vitro Antitheilerial Activity of Paluther (Artemether 80) Against Theileria lestoquardi.

Aim: The aim of this study was to screen Artemether 80 for activity against Theileria lestoquardi (Apicomplexa: Theileridae) using buparvaquone as a standard drug. Study Design: In vitro study under laboratories conditions. Place and Duration of Study: Veterinary Research Institute, between 2006 and 2008. Methodology: Artemether 80 was screened for the first time to investigate activity against T. lestoquardi at different concentrations. Blood was collected separately from normal sheep and sheep infected naturally with Theileria. Normal lymphocyte cells and lymphocyte cells infected with Theileria were isolated from heparinized blood with Ficoll-paque. Isolated cells were grown in Minimum Essential Medium (MEM), supplemented with 20% calf serum and sub cultured. The parasite was identified with indirect fluorescent antibody test (IFA). A volume of 2.7 ml of lymphoblast cell suspension at concentration of 5x104 cell/ ml was distributed in tissue culture plates, and then 0.3 ml of drug at concentrations of 0.1, 1.0, 10 and 100 mg/L was added separately. A volume of 0.3 ml MEM was added to infected untreated control. Results: The in vitro antitheilerial activity of Artemether 80 against T. lestoquardi 48 h after exposure was 0%, 14%, 30% and 45% at concentrations of 0.01, 0.1, 1.0 and 10 mg/L, respectively as compared with activity of buparvaquone at the same concentrations being 74%, 83%, 92% and 100%, respectively. Both Artemether 80 and buparvaquone caused in vitro partial cytotoxic effect at the highest concentrations. Activity and/ or partial cytotoxic effect of both drugs caused changes in the morphology of macroscizonts and host lymphoblast cells, decreased the number of macroschizonts/cell, mean number of dividing cells, increased the number of cells with extra cellular macroschizonts. Conclusion: It was concluded that Artemether 80 is slightly effective in vitro against T. lestoquardi.

Rapid Determination of CYP2 C9 Activity by UPLC-MS/MS / 中国药师

Objective:To establish an ultra performance liquid chromatography-tandem quadruple mass spectrometry ( UPLC-MS/MS) method to determine CYP2C9 activity in vitro. Methods:An ACQUITY UPLC? BEH C18 (100 mm × 2. 1 mm, 1. 7 μm) column was used as the stationary phase at 30℃. The mobile phase consisted of acetonitrile-water ( containing 0. 1% formic acid and 0. 5%ammonia water) (40∶60, v/v). The flow rate was 0. 2 ml·min-1. Chlorpropamide was used as the internal standard. The MS condi-tions were as follows:ESI with positive ion detection mode. Self-prepared CYP2C9?1, ?2, ?3 and ?13 protein were incubated with tolbutamide at 37℃ and 800μl ethyl acetate was added to stop the reaction. After centrifuged at 10 000g, the organic layer was then dried using nitrogen, the residue was re-dissolved in 200μl mobile phase and determined by UPLC-MS/MS. Results: The reten-tion time of 4-hydroxytolbutamide was 1. 21 min. An excellent linear calibration curve of 4-hydroxytolbutamide was obtained within the concentration range of 0. 05-5 ng·μl-1(r=0. 999 8). The lower limit of quantification of 4-hydroxytolbutamide was 0. 01 ng·μl-1 with the average recovery of 99. 3%-100. 3%. The intra- and inter-day RSDs were all less than 5%. There was no interference from the endogenous substances existing in the incubation system. The catalytic activity of the variants CYP2C9?2,?3 and?13 after tol-butamide was incubated with CYP2C9?1,?2,?3 and?13 was 47. 3%, 11% and 0. 3% of wild type CYP2C9?1. Conclusion:The method is simple and stable, and suitable for the fast evaluation of cytochrome CYP2C9 activity in vitro and relevant studies on the inhibitors.

In vitro activity of amphotericin B cochleates against Leishmania chagasi

Cochleate delivery vehicles are a novel lipid-based system with potential for delivery of amphotericin B (AmB). In this study, the efficacy of cochleates was evaluated by examining the in vitro activity of AmB cochleates (CAMB) against Leishmania chagasi in a macrophage model of infection. We demonstrate that CAMB is nontoxic to macrophages at concentrations as high as 2.5 μg/mL, whereas the conventional formulation, AmB deoxycholate, showed high toxicity at this concentration. The in vitro activity of CAMB against L. chagasi was found to be similar to that of the reference drug AmB deoxycholate, with ED50s of 0.017 μg/mL and 0.021 μg/mL, respectively. Considering that L. chagasi affects organs amenable to cochleate-mediated delivery of AmB, we hypothesize that CAMB will be an effective lipid system for the treatment of visceral leishmaniasis.

Actividad comparativa in vitro de doripenem y de otros carbapenemes frente a Pseudomonas aeruginosa / In vitro activity of doripenem and other carbapenems against Pseudomonas aeruginosa

Según estudios previos, el nuevo carbapeneme doripenem sería más activo frente a Pseudomonas aeruginosa en comparación con otros carbapenemes. En este estudio evaluamos la actividad in vitro del doripenem, el meropenem y el imipenem frente a 93 aislamientos de P. aeruginosa mediante los métodos de dilución en agar y de difusión con discos. Las CIM50 y CIM90 de los carbapenemes fueron (μg/ml): imipenem, 4 y 8; meropenem, 2 y 8; doripenem, 2 y 4, respectivamente. El doripenem fue 1 a 3 diluciones más activo que el imipenem para un 82% de los aislamientos. Comparado con el meropenem, el doripenem fue, 1-3 diluciones más activo frente a un 50% de los aislamientos, mientras que en el 49% la CIM fue la misma. Los porcentajes de resistencia según los métodos de dilución y de difusión fueron: imipenem = 7,5%/49,5% y meropenem = 3,2%/9,7%. Para el doripenem, estos valores variaron según los puntos de corte (PC) que se consideraron: 1,1%/2,2% usando el PC del CLSI para el imipenem y el meropenem, o 1,1%/17,2% según los PC sugeridos por Brown et al. El método de difusión presentó un elevado porcentaje de errores menores en la categorización de los aislamientos respecto de la dilución en agar, lo que sobrestimó la resistencia. El doripenem mostró muy buena actividad frente a P. aeruginosa, superior a la del imipenem y al menos equiparable a la del meropenem, por lo que puede considerarse una interesante opción para el tratamiento de infecciones por esta bacteria.

Doripenem, a new carbapenem, has shown to be more active against Pseudomonas aeruginosa than other carbapenems. The activity of doripenem, imipenem and meropenem was evaluated against 93 P. aeruginosa isolates, by agar dilution and disk diffusion methods. MIC50 and MIC90 were as follows (μg/ml): doripenem, 2 and 4; meropenem, 2 and 8; and imipenem, 4 and 8, respectively. Doripenem MICs were 1 to 3 dilutions lower (i.e. more active) than those for imipenem in 82% of the isolates. In comparison with meropenem, doripenem was 1 to 3 dilutions more active in 50% of the isolates. Forty-nine percent of isolates showed the same MIC for both antibiotics. Resistance percentages for both methods were (dilution/diffusion): imipenem = 7.5%/49.5% and meropenem = 3.2%/9.7%. As the CLSI has not established cut off values for doripenem yet, resistance rates for this antibiotic were estimated by considering (a) the same cut off values for imipenem/meropenem set up by the CLSI, and (b) those suggested by Brown et al. In case (a), resistance rates would be 1.1%/2.2% whereas in case (b) 1.1%/17.2% for agar dilution and disk diffusion, respectively. In scenarios where resistance to carbapenem is based on mechanisms other than carbapenemases, doripenem has a promising future for treating P. aeruginosa infections.

In vitro antibacterial activity in seed extracts of Manilkara zapota, Anona squamosa, and Tamarindus indica

Extracts prepared from seeds of Manilkara zapota, Anona squamosa, and Tamarindus indica were screened for their antibacterial activity by disc diffusion and broth dilution methods. Acetone and methanol extracts of T. indica seeds were found active against both gram-positive and gram-negative organisms. MIC values of potent extracts against susceptible organisms ranged from 53-380 μg/mL. Methanol extract of T. indica and acetone extract of M. zapota seeds were found to be bactericidal.

In vitro Activities of Mecillinam Against Clinical Isolates of Enterobacteriaceae

BACKGROUND: Mecillinam, an amidinopenicillin antibiotic, has been used to treat urinary tract infections and bacterial enteritis in many countries. In this study, we evaluated in vitro activity of mecillinam against Enterobacteriaceae isolates from urine, and Salmonella and Shigella isolates from patients with bacterial gastroenteritis. MATERIALS AND METHODS: A total of 308 clinical strains were collected and were comprised of Escherichia coli (n=109), Klebsiella pneumoniae (n=52), Enterobacter spp. (n=30), Serratia marcescens (n=30) and Proteus spp. (n=29) isolated from a university hospital in Korea in 2007, and of Salmonella spp. (n=28) and Shigella spp. (n=30) isolated from Korean diarrheal patients from 2001 to 2006. Antimicrobial susceptibility was tested by Clinical Laboratory Standard Institute (CLSI) agar dilution method. CLSI breakpoint of mecillinam for E. coli urinary tract isolates was applied to all other isolates. RESULTS: In E. coli, rate of susceptibility to ampicillin was 30%, but 99-100% to amikacin and cefotaxime. Most (96%) of E. coli isolates, including extended-spectrum beta-lactamase (ESBL) producers, were susceptible to mecillinam. All ESBL producers, except for one isolate, were inhibited by 128 microg/mL and most of them were resistant to mecillinam. All Salmonella isolates and 27 of 30 Shigella isolates were susceptible to mecillinam. CONCLUSION: Mecillinam was active in vitro against most Enterobacteriaceae, Salmonella, and Shigella isolates except for S. marcescens. Therefore, mecillinam can be a good alternative agent for treating urinary tract infection and bacterial gastroenteritis.

In vitro Activities of Mecillinam Against Clinical Isolates of Enterobacteriaceae

BACKGROUND: Mecillinam, an amidinopenicillin antibiotic, has been used to treat urinary tract infections and bacterial enteritis in many countries. In this study, we evaluated in vitro activity of mecillinam against Enterobacteriaceae isolates from urine, and Salmonella and Shigella isolates from patients with bacterial gastroenteritis. MATERIALS AND METHODS: A total of 308 clinical strains were collected and were comprised of Escherichia coli (n=109), Klebsiella pneumoniae (n=52), Enterobacter spp. (n=30), Serratia marcescens (n=30) and Proteus spp. (n=29) isolated from a university hospital in Korea in 2007, and of Salmonella spp. (n=28) and Shigella spp. (n=30) isolated from Korean diarrheal patients from 2001 to 2006. Antimicrobial susceptibility was tested by Clinical Laboratory Standard Institute (CLSI) agar dilution method. CLSI breakpoint of mecillinam for E. coli urinary tract isolates was applied to all other isolates. RESULTS: In E. coli, rate of susceptibility to ampicillin was 30%, but 99-100% to amikacin and cefotaxime. Most (96%) of E. coli isolates, including extended-spectrum beta-lactamase (ESBL) producers, were susceptible to mecillinam. All ESBL producers, except for one isolate, were inhibited by 128 microg/mL and most of them were resistant to mecillinam. All Salmonella isolates and 27 of 30 Shigella isolates were susceptible to mecillinam. CONCLUSION: Mecillinam was active in vitro against most Enterobacteriaceae, Salmonella, and Shigella isolates except for S. marcescens. Therefore, mecillinam can be a good alternative agent for treating urinary tract infection and bacterial gastroenteritis.

In vitro activity of ceftobiprole against hospital-acquired bacteria commonly causing infections in hospitalized patients at Siriraj Hospital.

Objective: To determine the in vitro activity of ceftobiprole against resistant bacteria commonly causing infections in hospitalized patients at Siriraj Hospital. Methods: The studied organisms were MRSA (32 isolates), Enterococcus sp. (30 isolates), ESBL-producing E.coli (20 isolates), ESBL-producing K.pneumoniae (20 isolates), MDR P.aeruginosa (30 isolates) and MDR A.baumannii (30 isolates). The susceptibility of ceftobiprole was determined by the disk diffusion test for all 162 isolates and the MIC was determined by the E-test method for 5 isolates of each organism. Results: All isolates of MRSA and 77% of Enterococcus sp. isolates were susceptible to ceftobiprole. All isolates of ESBL-producing E.coli and MDR A.baumannii were not susceptible to ceftobiprole. Only 10% to 20% of ESBL-producing K.pneumoniae and P.aeruginosa were susceptible to ceftobiprole. The MICs of ceftobiprole against all tested organisms were correlated with the inhibition zone diameters. Conclusion: Ceftobiprole is very active against MRSA and is moderately active against Enterococcus sp. Ceftobiprole is considered inactive or less active against ESBL-producing gram negatives, MDR P.aeruginosa and MDR A.baumannii.

In Vitro Activity of Arbekacin Against Clinical Isolates of Staphylococcus species and Gram-negative Bacilli / 대한진단검사의학회지

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and some gram-negative bacilli are very prevalent nosocomial pathogens, commonly causing mixed infections, and are often resistant to multiple drugs. Arbekacin is an aminoglycoside used for the treatment of MRSA infections, but is also active against some gram-negative bacilli. The aim of this study was to determine in vitro activity of arbekacin against recent clinical isolates of staphylococci and gram-negative bacilli. Materials and METHODS: The strains were isolated from clinical specimens of patients at Severance Hospital in 2003. Antimicrobial susceptibility was tested by the Clinical and Laboratory Standards Institute agar dilution method. The following arbekacin breakpoints were used: susceptible, or =16 microgram/mL . RESULTS: All isolates of staphylococci tested were inhibited by 32-fold and >32-128-fold lower than those of amikacin and gentamicin, respectively. The resistance rates of MRSA, methicillin-susceptible S. aureus, methicillin-resistant coagulase-negative staphylococci (CNS) and methicillin-susceptible CNS were 0% to arbekacin, 0-54% to amikacin, and 24-79% to gentamicin. The MIC90s of arbekacin for Escherichia coli and Citrobacter freundii, 1 microgram/mL and 16 microgram/mL, were 2-4-fold and 8-16-fold lower than those of amikacin and gentamicin, respectively. However, The MIC90s of arbekacin for other species of gram-negative bacilli, 64->128 microgram/mL, were similar to those of other aminoglycosides. CONCLUSIONS: Arbekacin may be a useful alternative to glycopeptides for the treatment of monomicrobial methicillin-resistant staphylococcal infections, as well as mixed infections with gram-negative bacilli, as most isolates of E. coli, C. freundii and some other gram-negative bacilli were also susceptible to arbekacin.

In Vitro Activity of Arbekacin Against Clinical Isolates of Staphylococcus species and Gram-negative Bacilli / 대한진단검사의학회지

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and some gram-negative bacilli are very prevalent nosocomial pathogens, commonly causing mixed infections, and are often resistant to multiple drugs. Arbekacin is an aminoglycoside used for the treatment of MRSA infections, but is also active against some gram-negative bacilli. The aim of this study was to determine in vitro activity of arbekacin against recent clinical isolates of staphylococci and gram-negative bacilli. Materials and METHODS: The strains were isolated from clinical specimens of patients at Severance Hospital in 2003. Antimicrobial susceptibility was tested by the Clinical and Laboratory Standards Institute agar dilution method. The following arbekacin breakpoints were used: susceptible, or =16 microgram/mL . RESULTS: All isolates of staphylococci tested were inhibited by 32-fold and >32-128-fold lower than those of amikacin and gentamicin, respectively. The resistance rates of MRSA, methicillin-susceptible S. aureus, methicillin-resistant coagulase-negative staphylococci (CNS) and methicillin-susceptible CNS were 0% to arbekacin, 0-54% to amikacin, and 24-79% to gentamicin. The MIC90s of arbekacin for Escherichia coli and Citrobacter freundii, 1 microgram/mL and 16 microgram/mL, were 2-4-fold and 8-16-fold lower than those of amikacin and gentamicin, respectively. However, The MIC90s of arbekacin for other species of gram-negative bacilli, 64->128 microgram/mL, were similar to those of other aminoglycosides. CONCLUSIONS: Arbekacin may be a useful alternative to glycopeptides for the treatment of monomicrobial methicillin-resistant staphylococcal infections, as well as mixed infections with gram-negative bacilli, as most isolates of E. coli, C. freundii and some other gram-negative bacilli were also susceptible to arbekacin.