Comparative In Vitro Activity of Quinupristin/Dalfopristin and Seven Other Antimicrobials Against Methicillin-Susceptible and Methicillin-Resistant Nosocomial Staphylococcus aureus Bloodstream Isolates

Abstract

Staphylococcus aureus strains resistant to a variety of antimicrobial agents are often found in the hospital environment and are responsible for many life-threatening infections. The activity of quinupristin/dalfopristin against 84 Staphylococcus aureus bloodstream isolates (both methicillin resistant and methicillin sensitive) was compared to the activity of vancomycin, teicoplanin, erythromycin, oxacillin, clindamycin, gentamicin, rifampicin. The Minimum Inhibitory Concentrations of these agents was evaluated with the Epsilometer Test. Quinupristin/dalfopristin inhibited all methicillin-sensitive strains at 1mg/L, and 75% of methicillin-resistant strains at 1,5mg/L. According to these results, quinupristin-dalfopristin shows promising in-vitro activity and may be a welcome alternative treatment for methicillin-resistant staphylococcal infections, resulting in reduced use of glycopeptides.     

In Vitro Antibacterial Activity of the New Quinolone Bay y3118 against Clinical Isolates

Summary

The in vitro antibacterial activity of the new fluoroquinolone Bay y3118 against 609 clinical isolates was evaluated. Bay y3118 exhibited activity against a broad spectrum of organisms, including Gram-negative bacilli, Gram-positive cocci, mycobacteria. The activity of Bay y3118 was often superior to that of other quinolones. Against Gram-negative bacilli its activity was similar to that of ceftriaxone, cefotaxime, ceftazidime and imipenem except for Serratia marcescens, Klebsiella pneumoniae, Enterobacter spp. and Xanthomonas maltophilia, where its activity was superior. Gentamicin and piperacillin sometimes were less active. Bay y3118 was active against a large number of Gram-positive cocci. The fluoroquinolones tested were active against all the strains of Mycobacterium tuberculosis, but only Bay y3118 was effective against Mycobacterium avium.     

In Vitro Activity of Ampicillin-Sulbactam Against Clinical Multiresistant Acinetobacter baumannii Isolates

Abstract

We evaluated the in vitroactivity of ampicillin-sul-bactam in comparison with that of broad-spectrum antimicrobial agents against Acinetobacter baumannii isolates. Two hundred and twelve clinical isolates collected between January 1993 and March 1995 from two tertiary hospitals located in São Paulo, Brazil were tested for susceptibility by the disk diffusion method against several broad-spectrum antimicrobial agents, including imipenem, ciprofloxacin, ceftazidime, aztreonam, amikacin, and polymyxin B. All strains were susceptible to polymyxin B. The second most active compound was the combination ampicillin-sulbactam (88% susceptibility). Only 79% of the isolates were susceptible to imipenem. Ciprofloxacin was active against 60 (28%) and amikacin against 34 (16%) isolates. Ceftazidime was the most active cephalosporin; however, only 9% of the isolates were susceptible to this compound. Both aztreonam and ampicillin alone showed very poor activity against this species (1% susceptibility). The prevalence of severe infections due to A. baumannii is increasing very rapidly in the tertiary hospitals of São Paulo and there are very few options for the treatment of these infections. Polymyxin B is invariably in vitro active against this species; however, this compound can cause severe side effects and is not commercially available for intravenous use in Brazil and in several other countries. Our results indicated that the combination ampicillin-sulbactam may be an alternative drug for the treatment of infections due to multiresistant A. baumannii; however, further studies are necessary to evaluate the clinical role of this compound for the treatment of severe infections.     

In Vitro Antifungal Activity of Sertaconazole Against 309 Dermatophyte Clinical Isolates

Abstract

Three hundred and nine strains belonging to 11 species of dermatophyte moulds were tested against sertaconazole following mainly the National Committee for Clinical Laboratory Standards (M38-P) for filamentous fungi. However, several important factors such as the temperature (28°C vs 35°C) and time of incubation (4-10 d vs 21-74 h), have been modified. Sertaconazole was active against all the clinically important dermatophyte moulds involved in human infections tested. Overall geometric mean MIC of sertaconazole was 0.21 μg/ml with a MIC range of 0.01-8 μg/ml. MIC₅₀ and MIC₉₀ were respectively of 0.25 and 1 μg/ml. Sertaconazole was very active against Epidermophyton floccosum, Trichophyton rubrum, Trichophyton tonsurans and Microsporum canis (geometric means 0.08, 0.13, 0.13 and 0.19 μg/ml respectively). Microsporum audouinii had the lowest susceptibility in the study (geometric mean 0.59 μg/ml). Considering MIC₅₀ and MIC₉₀ these differences were significantly in favor of the activity of sertaconazole against E. floccosum (0.06 and 0.5 μg/ml respectively).     

Comparative In- Vitro Activity of Fourteen Antibiotics Against Clinical Isolates of Enterococci

Summary

The in-vitto antibacterial activities of fourteen antimicrobial agents, including ampicillin, amikacin, Augmentin, ceftazidime, cefotaxime, ceftriaxone, ciprofloxacin, erythromycin, gentamicin, penicillin G, piperacillin, rifampicin, streptomycin and vancomycin, were compared against 195 enterococcal strains isolated from clinical specimens received at the King Abdulaziz University Hospital in Saudi Arabia. The antibacterial susceptibility was determined by the minimal inhibitory concentration (MIC) using an agar dilution method. Ampicillin, Augmentin and vancomycin exhibited the greatest activity, inhibiting 90% of the tested strains (MIC90) at 2 μg/ml, followed by penicillin G and piperacillin with MIC90 of 4 μg/ml. Erythromycin, third generation cephalosporins, aminoglycosides and rifampicin, on the other hand, had poor activity against enterococci with MIC90s well above the obtainable serum concentrations. The clinical implications of resistance to aminoglycosides and the alternative antimicrobial therapy in serious entrococcal infections are discussed in the text.     

In Vitro Antifungal Activity of Hamycin against Histoplasma Farciminosum

Die Behandlung der epizootischen Lymphangitis ist noch unbefriedigend. Das Schlachten der erkrankten Tiere führt kaum zur Ausrottung der Krankheit; von unbeachtet gebliebe-nen Fällen können immer wieder neue Epidemien ausgehen. Die Suche nach einer wirk-samen medikamentösen Behandlung ist deshalb notwendig.
Die erfolgreiche Behandlung zweier Pferde mit dem antibiotischen Antimykoticum Hamycin war Veranlassung, dieses Polyen in vitro zu testen. Stämme von Histoplasma farciminosum erwiesen sich als sehr empfindlich. Die minimale Hemmkonzentration betrug 0,005 bis 0,01 μg mikronisiertes Hamycin/ml mod. Czapek-Dox-Agar, bzw. Blutagar.
Aufgrund dieser Untersuchung ist für in vivo-Versuche eine Dosierung von 10mg/kg oder 20 mg/kg Körpergewicht angezeigt. Diese Dosis ergibt Hamycin-Blutspiegel, die hoher liegen als die minimale Hemmkonzentration. Nach Utz et al. ist Hamycin auch gegen Blastomyces dermatitidis wirksam.     

The In Vitro Activity of Trospectomycin against Anaerobic Bacteria

Abstract

The authors evaluated the activity of trospectomycin, a new aminocyclitol which is characterized by good antibacterial and broad spectrum activity, in comparison with clindamycin and ampicillin on a sample of recent isolates: Bacteroides fragilis (15 strains), Bacteroides urealyticus (5 strains), Bacteroides vulgatus (5 strains), Bacteroides spp. (15 strains), Prevotella melaninogenica (6 strains), Porphyromonas asaccha-rolytica (7 strains), Mobiluncus spp. (3 strains), Peptococcus niger (3 strains), Peptococcus variabilis (9 strains), Peptococcus spp (30 strains), Peptostreptococcus anaerobius (5 strains), Peptostreptococcus asaccharolyticus (3 strains), Peptostreptococcus spp. (25 strains) and Propioni-bacterium spp. (7 strains). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for all strains by microtiter serial dilutions in Wilkins-Chalgren broth in an anaerobic chamber in an atmosphere of 10% H₂, 10% CO₂, 80% N₂. All the drugs tested exert their activity against Gram-positive and Gram-negative anaerobic isolates. In particular, trospectomycin is quite active against Gram-positive cocci (MIC 90 = 4 - 8 mg/l), Gram-negative rods (MIC 90 = 8 - 16 mg/l), Gram-positive rods (MIC 90 = 4 mg/l) and Mobiluncus spp. (MIC 90 = 0.5 mg/l).     

In Vitro and In Vivo Anticancer Activity of Gimatecan against Hepatocellular Carcinoma

Objective: Gimatecan is a new camptothecin (CPT) analogue that inhibits tumor growth by targeting DNA topoisomerase I (TOP I) and introducing strong and persistent DNA cleavage. Anti-tumor activity has been demonstrated with a wide range of solid tumors in previous preclinical and clinical studies. Here, we investigated for the first time the effects of gimatecan on the proliferation of hepatocellular carcinoma (HCC) cells both in vitro and in vivo. Methods: Anticancer efficacy of gimatecan were evaluated in a panel of HCC cell lines and corresponding mouse xenograft models. Inhibition of cell proliferation was measured by CellTiter-Glo cell viability assay. In vivo, gimatecan and control preparations were orally administered every four days, for a total of four times. Tumor volume and body weights of the mice were measured twice weekly. Results: In vitro cytotoxicity evaluation showed that gimatecan inhibited the proliferation of a large panel of HCC cell lines in a dose dependent manner, with IC50 values ranging between 12.1~1085.0 nM. In vivo evaluation in mouse xenograft models showed significant antitumor effects of gimatecan at 0.8mg/kg and 0.4mg/kg as compared to the control group. Conclusion: This study suggested that gimatecan may have the potential to be used as a chemotherapeutic agent for the treatment of HCC.     

Comparative In Vitro Activity of Tigecycline Against Aerobic and Facultative Isolates Recovered from Hospitalized Patients: An Argentinean Multicenter Study

Abstract

Tigecycline, the 9-t-butylglycylamino derivative of minocycline is the first commercially available glycylcycline exhibiting an extended spectrum of antibacterial activity due to its capacity to evade the tetracycline ribosomal and efflux resistance mechanisms. We conducted a collaborative In Vitro study determining the activity of tigecycline compared to 14 antimicrobials against clinically relevant isolates obtained from adult patients hospitalized in 9 Argentinean institutions. Minimum inhibitory concentrations (MICs) were determined by the reference broth microdilution method. The number of isolates and MICs 50/90 (mg/L) for tigecycline were the following: Acinetobacter spp. 132 (0.5/1); Escherichia coli 220 (0.12/0.25); Klebsiella spp. 220 (0.5/1), Enterobacter spp. 205 (0.5/1); Serratia spp. 84 (0.5/2); Haemophilus influenzae 96 (0.25/0.5); Staphylococcus aureus 223 (0.12/0.25); Streptococcus pneumoniae 98 (≤0.25/1); S. agalactiae 51 (0.5/0.5); Enterococcus spp. 104 (0.06/0.12); Pseudomonas aeruginosa 169 (8/16). We conclude that tigecycline is a promising drug for the treatment of infections in hospitalized patients in Argentina.     

Comparative In Vitro Activity of Sparfloxacin (AT 4140, RP 64206 - SPFX) Against 275 Multiresistant Clinical Isolates

The in-vitto activity of sparfloxacin was compared with that of pefloxacin, ofloxacin, ciprofloxacin, imipenem, ceftazidime, gentamicin and amikacin against 275 multiresistant nosocomial clinical isolates. They consisted of Pseudomonas aetuginosa (37), Entetobacter cloacae (42), Acinetobactet anitratus (60), Klebsiella pneumoniae (37) and Staphylococcus sp (99). Minimum inhibitory concentrations (MIC₉₀) and geometric mean MICs for sparfloxacin were as follows (mg/1): P. aeruginosa 128 - 23.7, E. cloacae 1 - 0.13, A. anitratus 2 - 0.14, K. pneumoniae 1 - 0.08, MRSA 16 - 0.98, MSSA 0.12 - 0.03, MRSE 0.25 - 0.12 and MSSE 0.12 - 0.05. It is concluded that sparfloxacin was the most potent agent against staphylococci and A. anitratus including strains resistant to the other quinolones while ciprofloxacin was the most potent agent against P. aeruginosa, E. cloacae and K. pneumoniae.     

In- Vitro Activity of Ciprofloxacin and Sixteen Other Antimicrobial Agents against Blood Culture Isolates

Summary

The in-vitro antibacterial activities of seventeen antimicrobial agents including ampicillin, amikacin, Augmentin, aztreonam, cefazolin, cefuroxime, cefotaxime, ceftizoxime, ceftriaxone, ciprofloxacin, cloxacillin, erythromycin, gentamicin, penicillin G, piperacillin and vancomycin were compared against 100 Gram-negative and Gram-positive strains isolated from blood culture specimens received at the King Abdulaziz University Hospital (KAUH), in Jeddah, Saudi Arabia.

The antibacterial susceptibility was determined by the minimal inhibitory concentration (MIC), using an agar dilution method. Ciprofloxacin exhibited the greatest activity, inhibiting 90% of the tested strains (MIC₉₀) at a concentration ranging from < 0.015-0.5 mg/L. Against cloxacillin resistant or susceptible strains of Staphylococcus aureus and coagulase-negative staphylococci, ciprofloxacin had similar activity with MIC₉₀, of 0.2 mg/L. Salmonella typhi and salmonella species which were resistant to ampicillin and augmentin remained sensitive to ciprofloxacin (Mid₉₀ < 0.015-0.125) mg/L.). Against gentamicin sensitive and resistant Pseudomonas aeruginosa and Pseudomonas species, ciprofloxacin MIC₉₀ was 0.5 and 1 mg/L respectively. Aminoglycosides, third generation cephalosporins, aztreonam and antipseudomonal penicillins, on the other hand, showed high MIC₉₀ well above the obtainable serum concentrations against Enterobacteriaceae and Pseudomonas species.     

Comparative In- Vitro Activity of Piperacillin and Piperacillin Plus Tazobactam Towards Beta-Lactamase Producing Clinical Isolates

Summary

The authors evaluated the in-vitro antibacterial activity of piperacillin alone and of piperacillin combined with tazobactam, a new beta-lactamase inhibitor, on 398 clinical isolates, both Gram-positive and Gram-negative. The piperacillin/tazobactam combination was evaluated in the fixed ratio 8:1. The vast majority of the microorganisms tested had reduced susceptibility to piperacillin (minimum inhibitory concentration (MIC) range 0.12— > 256 mg/1) due to beta-lactamase production.

The following results were obtained: against Haemophilus influenzae, tazobactam was effective in reducing the MICs of piperacillin by 512 fold. The activity of piperacillin/tazobactam was lower against Pseudomonas sp., while some activity was demonstrated against some strains of Klebsiella. Good activity was seen not only against methicillin-susceptible (MS) staphylococci but also against some methicillin-resistant (MR) strains. In the latter, the combination of piperacillin/tazobactam was active only if the strains showed beta-lactamase production. These findings are interesting above all in regard to the synergistic effect demonstrated against MR beta-lactamase producing staphylococci and the Klebsiella-Enterobacter-Serratia (KES) group.     

In Vitro Activity of Meropenem against Ciprofloxacin-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

Abstract

The in-vitro susceptibilities of a total of 174 ciprofloxacin-resistant Enterobacteriaceae and Pseudomonas aeruginosa were determined. According to the BSAC and NCCLS breakpoints, meropenem, aztreonam, ceftibuten, ceftazidime, imipenem and cefotaxime were the most active (>90%) antimicrobial agents tested against Enterobacteriaceae. Susceptibility of these strains to piperacillin/tazobactam, cefpodoxime and cefixime (84.96%) was higher than that to tobramycin, gentamicin and fosfomycin (50-75%). More than 90% of P. aeruginosa were susceptible to meropenem when both interpretative susceptibility breakpoint criteria were used. Piperacillin, piperacillin/tazobactam and ceftazidime were active against 50-75% of the same strains. Meropenem was the most active antimicrobial tested against all ciprofloxacin-resistant clinical isolates assayed.     

In Vitro Activity of Thiamphenicol,Erythromycin and Fluoroquinolones against Legionella pneumophila

Abstract

The antistreptococcal activity of telithromycin and 11 different comparators was evaluated in 26 multi-drug resistant (MDR) Streptococcus pneumoniae strains collected during 2002-2003 as part of the ongoing PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) Italian Surveillance Program. The strains were characterized for their susceptibility to antibiotics both at the phenotypic and genotypic levels; furthermore, the association of erm(B), mef(A) class and tet(M) genes, as well as the mobile elements carrying them were determined. The strains in this study were resistant to penicillin (MIC ≥2 mg/l) in 23.1% of cases, resistant to tetracycline in 88.4%, to cotrimoxazole in 34.6% and cefuroxime in 26.9% while only telithromycin and levofloxacin retained 100% activity against all microorganisms. Co-existence of different resistance determinants was found in 19.2% of all isolates collected in our laboratory, coming from southern Italy. Twenty-three isolates showing the MLS_B phenotype of resistance possessing the erm(B) gene (88.5%), associated with tet(M), were carried on the same Tn1545-like element, while two isolates showing the M phenotype possessing the mef(A) gene alone, were carried on Tn1207.1. In only one strain were mef(E) and tet(M) together carried on Tn2009.     

In vitro Activity of Ertapenem against Common Clinical Isolates in Relation to Human Pharmacokinetics

Abstract

The In vitro activity of ertapenem against bacterial pathogens isolated from patients with moderate to severe complicated intra-abdominal, complicated skin/skin structure, acute pelvic, or complicated urinary tract infection or community acquired pneumonia was compared to ceftriaxone and piperacillintazobactam and related to known plasma concentrations of the three agents. Ertapenem was more potent against methicillin-susceptible Staphylococcus aureus (MSSA) than ceftriaxone and piperacillin-tazobactam and was more potent and more active than both of these agents against Enterobacteriaceae and anaerobes. Piperacillin-tazobactam was the most active agent against enterococci and Pseudomonas aeruginosa. All isolates of Enterobacteriaceae (n=1088), Streptococcus pyogenes (n=37), Streptococcus agalactiae (n=48), MSSA (n=187), Haemophilus influenzae (n=59), and Moraxella catarrhalis (n=9) were susceptible to ertapenem; <1% of 1284 anaerobes and only 1 of 113 Streptococcus pneumoniae (a penicillin-resistant isolate) were resistant to ertapenem. The MIC value at which 90% of all Enterobacteriaceae, streptococci, MSSA, H. influenzae, M. catarrhalis, and anaerobes were inhibited (MIC₉₀) was ≤μg/ml and below the mean plasma concentration of total ertapenem following a 1 g intravenous infusion for at least 24 hours, i.e., the entire recommended dosing interval, and below the free drug concentration for at least 8 h.     

体外培养DC-CIK细胞杀伤白血病细胞实验研究

目的:未缓解的急性白血病患者的外周血中存在一定比例的白血病细胞,能否诱导CIK细胞的增殖用于复发难治白血病的挽救治疗值得探讨。体外诱导培养缓解期及未缓解期急性白血病患者来源的DC-CIK细胞,比较其增殖能力,免疫表型及杀瘤活性的变化。方法:提取复发难治白血病患者和缓解期患者的研究对象的外周血单个核细胞,按常规方法诱导产生DC-CIK细胞,在培养过程中计算细胞增殖倍数,用流式细胞仪检测CD3CD8、CD3CD56双阳性率,并在细胞增殖期检测比较其对K562细胞及患者单个核细胞的杀伤活性。结果:缓解组和未缓解组来源的DC-CIK细胞均不断快速增殖,培养第15天时,缓解组CD3₊CD8₊和CD3₊CD56₊细胞分别占(87.5EeEe1.29)%,(63.8EeEe1.98)%,未缓解组分别占(88.6EeEe3.4)%,(66.8EeEe4.1)%,此时应用CCK-8法测得在效靶比为20:1时,缓解组对K562细胞的杀伤率为(42.64EeEe3.25)%,未缓解组为(57.49EeEe2.87)%;相同效靶比下,未缓解组对患者的单个核细胞的杀伤率为(67.29EeEe7.95)%。结论:应用未缓解患者的外周血单个核细胞,同样可以培养出DC-CIK细胞,具有与缓解组来源的DC-CIK细胞一致的高增殖活性和高CD3₊CD8₊、CD3₊CD56₊表达,一样对K562细胞杀伤活性较强,并对患者单个核细胞具有特异杀伤活性,未缓解患者来源的CIK细胞中未检测到白血病细胞残留,可以应用于难治白血病的挽救治疗。     

In Vitro Activity of Cefpirome (HR 810) against Enterococci and Staphylococci

Summary

The inhibitory activity of cefpirome (HR 810), a new cephalosporin derivative for parenteral use, was tested by agar dilution methods against Enterococcus faecatis (100 strains), Staphylococcus aureus (40 strains) and coagulase-negative staphylococcal species (60 strains) in comparison with other beta-lac ta m antibiotics.

For E. faecalls, the cefpirome minimum inhibitory concentration (MIC) range was 2-128 μg/ml, with an MIC,, of 8 μg/ml, and an MIC₉₀, of 64 μg/ml. The optimal bactericidal activity against strains with MICs of ≤ 8 μg/ml occurred at 2-4 times the MIC, and the reduction in the initial inoculum was 99.9-99.7% after 24 h incubation at these concentrations.

Mec gene-negative staphylococci (both S. aureus and coagulase- negative species) had cefpirome MICs of 0.25-2 μg/ml (MIC₅₀ 0.5 μg/ml, MIC₉₀ 1 μg/ml). Mec gene-positive strains had MICs of 0.5-128 μg/ml (MIC₅₀ 2 μg/ml, MIC₉₀ 32 μg/ml). Strains with borderline resistance to oxacillin which did not harbor the mec gene and which were susceptible to cefpirome maintained their susceptibility even when high-density inocula were used and after several passages in media containing the antibiotic.

These studies present some potential advantages of cefpirome over other cephalosporins in the inhibitory activity against Gram-positive cocci.