Activity of BAY y 3118, a Novel 4-Quinolone,against Brucella melitensis

Summary

We have tested the in-vitro activities of BAY y 3118, a new chlorofluoroquinolone, ciprofloxacin, sparfloxacin, streptomycin, tetracycline and rifampin against 59 strains of Brucella melhensis. BAY y 3118 (MIC₉₀, 0.12 mg/L) was twice as active as sparfloxacin and tetracycline (MIC₉₀ 0.25 mg/L). The activity of ciprofloxacin, rifampin and streptomycin (MIC₉₀, 0.5, 2, and 8 mg/L, respectively) was, respectively, four-, sixteen-, and more than sixty-fold lower than that of BAY y 3118.     

Influence of Human Ascitic Fluid on the In Vitro Antibacterial Activity of Moxifloxacin

Abstract

We investigated the in vitro influence of HAF on the antibacterial activity of moxifloxacin against Escherichia coli ATCC 10798, Escherichia coli K-12, Proteus rettgeri (Sanelli), Staphylococcus aureus ATCC 25923 Staphylococcus aureus NCTC 1808 and Staphylococcus epidermidis ATCC 12228. Human ascitic fluid was obtained from 6 cirrhotic patients by paracentesis. The interaction effect was evaluated by the checkerboard technique. Our results indicate the ability of human ascitic fluid to reduce minimum inhibitory concentrations of moxifloxacin against Gram-negative bacteria, but not against Gram-positives.     

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.     

Comparative Study of the In Vitro Antibacterial Activity of Ciprofloxacin and Thirteen other Antimicrobial Drugs with Respect to Recently Isolated Pathogens

Summary

The in vitro antibacterial activity of ciprofloxacin and 13 other antimicrobial drugs was evaluated with respect to 569 pathogens, mainly isolated from urine. Ciprofloxacin was found active in 96.1% of all of the Gram-positive and Gram-negative strains tested, amikacin in 90.6%, ceftazidime in 89.8%, ceftriaxone in 85.3%, piperacillin in 82.7%, tobramycin in 82.6%, gentamicin in 81.5%, aztreonam in 78.3%, nitrofurantoin in 72.6%, cotrimoxazole in 71.6%, cinoxacin in 71.0%, pipemidic acid in 70.6%, nalidixic acid in 66.7%, ampicillin in 50.1%. Ciprofloxacin was found to be the most active of the drugs studied against the bacterial strains which cause urinary, respiratory and other infections.     

In Vitro Activity of Lomefloxacin (SC-47111) Against Enterobacteriaceae,Enterococci and Staphylococci

Summary

The activity of lomefloxacin, a new difluorinated quinolone, was tested against 190 Enterobacteriaceae strains (belonging to 23 different species), 70 enterococci and 70 staphylococci. As regards Enterobacteriaceae, the activity of lomefloxacin was the same as that of norfloxacin in 9 out of the 23 species tested, and only slightly lower in further 8 species. Minimum inhibitory concentrations (MIC) values for 90% of strains were 0.5 μg/ml in 2 species, 0.25 μg/ml in 6, 0.125 μg/ml in 4, and lower than 0.125 μg/ml in 8. Slightly higher values were obtained for Serratia marcescens (2 μg/ml), whilst, as already reported for the other new quinolones, the susceptibility of the Providencia genus was very poor, with MIC values up to 128 μg/ml for the vast majority of strains. Lomefloxacin proved bactericidal at the MIC in all the Enterobacteriaceae strains tested but 20. In the latter strains, however, bactericidal activity could be appreciated at values slightly exceeding MIC. As regards enterococci, the MIC for 90% of strains was 32 μg/ml. Minimum bactericidal concentration (MBC) was the same as the MIC for 78% of the strains tested and was only twofold higher in all the others. The new drug was also active against staphylococci having an MIC50 and MIC₉₀ of 0.5 and 2 μg/ml, respectively. It was bactericidal at the MIC for 62% of the strains and at twofold the MIC for all the others.     

In Vitro Antibacterial Activity of DX-619, a Novel Des-F (6)-Quinolone Against Clinical Isolates in China

Abstract

The aim of the study was to investigate In Vitro antibacterial activity and bactericidal effect of DX-619 and other nine comparators against 1,101 recently collected clinical bacterial isolates in China. The minimum inhibitory concentrations (MICs) of antimicrobials were determined by a CLSI recommended standard agar dilution method and the minimum bactericidal concentrations (MBCs) were examined by the broth dilution method. Time-kill curves against representative isolates of Staphylococcus aureus, enterococci, and Klebsiellia pneumoniae were also conducted.

DX-619 exhibited excellent antibacterial activity against 1,101 clinical isolates, especially to multi-drug resistant Gram-positive cocci. The MIC₉₀s of DX-619 were ≤0.016 and 0.125 mg/L against methicillin-sensitive and -resistant S. aureus, 0.062 and 0.125 mg/L against methicillin-sensitive and -resistant S. epidermidis, respectively, which were 8-512 and 64-128 fold lower than those of comparative fluoroquinolones. The MIC₉₀s of DX-619 for penicillin-sensitive and -non-sensitive Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium were 0.016, 0.062, 0.25 and 0.5 mg/L, respectively. The MIC₉₀s of DX-619 against Enterobacteriaceae (except for Escherichia coli) and glucose-nonfermenting bacilli were ≤4 mg/L, which were comparable to other comparators. MBCs and time-kill curves showed that DX-619 was a potent bactericidal agent. There was no significant inoculum effect on MICs. But the activities of DX-619 against S. aureus, K. pneumoniae and Pseudomonas aeruginosa were decreased by acidic pH and human serum. DX-619 was a potent antibacterial compound against multi-drug resistant bacteria including Gram-positive cocci, such as S. aureus and enterococci, which may warrant further exploration.     

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.     

The Antitumor Activity of Meisoindigo against Human Colorectal Cancer HT-29 Cells In Vitro and In Vivo

Abstract

The study was conducted to examine the antitumor activity of meisoindigo on HT-29 cells In Vitro and In Vivo. The cytotoxicity of meisoindigo was evaluated by MTT assay. The related genes and proteins were inspected with RT-PCR and western blot assay respectively, and the effects of meisoindigo on the cell cycle were analyzed by flow cytometry. The efficacy of meisoindigo In Vivo was evaluated in an HT-29 cell xenograft nude mice model. The results show that meisoindigo effectively inhibits HT- 29 cell proliferation (IC₅₀ 4.3 mmol/L), arrests HT-29 cells in G2/ M phase and induces HT-29 cell apoptosis. The downstream genes and proteins of GSK-3β(ser⁹) expression level decrease. Meisoindigo significantly inhibits the HT-29 xenograft tumors growth at the dose of 100 mg/kg. The mechanism of meisoindigo activity against HT-29 cells may be related to its inhibition of glycogen synthase kinase-3β, GSK-3β(ser⁹) phosphorylation in Wnt signaling pathway. These findings indicate the potential value of meisoindigo for the treatment of colorectal cancer.     

Antibacterial Activity of the Dialysates and Sera during Treatment with Chemotherapeutic Combinations in Continuous Ambulatory Peritoneal Dialysis (CAPD)

Summary

In everyday clinical practice, different chemotherapeutics are mostly applied intraperitoneally in treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Antibacterial activity of the dialysates and sera were studied, according to their bacteriostatic effect after the intraperitoneal and/or peroral administration of chemotherapy. All samples were tested by the two-fold dilution method. We found that the best therapeutical effect is obtained by applying the combination of two compatible chemotherapeutics, in which the first acts in the peritoneal cavity, and the other represents the «pool» of chemotherapeutics forming a barrier to the spreading of bacteria into other distant parts of the body.     

In- Vitro Activity of Ampicillin/Sulbactam and Other Antibiotics against Clinical Isolates of Haemophilus sp. and Branhamella catarrhalis

Summary

The ampicillin/sulbactam combination is one of several such drug combinations of a beta-lactam and suicide inhibitor having a wide spectrum of activity.

These characteristics induced us to evaluate the in vitro activity of this combination towards 54 strains of Haemophilus sp. (38 beta-lactamase producers) and 20 strains of Branhamella catarrhalis (16 beta-lactamase producers).

All strains were isolated from sputum, sinusal aspiration and tympanocentesis.

In the case of Haemophilus sp beta-lactamase producers, minimal inhibitory concentrations of ampicillin were reduced 8 times by the use of the inhibitor; good results were also obtained for B. catarrhalis.

Haemophilus influenzae, B. catarrhalis together with Streptococcus pneumoniae are recognized as the major pathogens involved in upper respiratory tract infections. The increasing frequency of beta-lactamase producing strains has impaired the use of aminopenicillins.

The combination of an inhibitor and beta-lactam restore the activity of the latter, suggesting that this combination can serve as first choice in therapy.     

Parameters Characterizing the In Vitro Activity of Cefixime,a New Oral Broad Spectrum Cephalosporin,Against Respiratory and Urinary Pathogens

Summary

The wide and potent in vitro activity of cefixime, a new oral broad spectrum cephalosporin, has been confirmed on a collection of respiratory and urinary pathogens recently isolated in Italy. The new cephem emerged as the most bactericidal of all the comparators tested against several fast as well as slowly-growing gram-negative species including Enterobac-teria, Haemophilus and Moraxella, irrespective of their ability to synthetize β-lactamases. Among the gram-positive species Streptococcus pyogenes and 5. pneumoniae were effectively covered.

Cefixime activity was not adversely influenced by several important variables such as pH (over the range from 5 to 8), inoculum size (from 10⁵ to 10⁸ CFU per ml) and the presence of 50% human serum or urine. Time-kill tests confirmed a pronounced bactericidal potency of the drug especially towards common respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae and S. pyogenes). Killing of urinary strains was optimal at cefixime concentrations reached in urine since eradication, except for Proteus mirabilis, was enhanced with increasing levels of the drug. The absence of an untoward paradoxic effect on the rate of cefixime bactericidal action was confirmed by employing a dynamic bladder model simulating the pharmacokinetic parameters of the drug after a single 200 mg daily dosage. Interactions of cefixime with several other drugs that may be employed in combination therapy were generally prone to provide indifference and synergism while antagonism was never observed. Favorable interactions were also registered when cefixime acted with other antibiotics on partially resistant species such as Staphylococci and Pseudomonas. The new cephem seems to provide excellent opportunities for expanding oral cephalosporin therapy to a wide range of infections produced by susceptible pathogens in the adult and pediatric populations.     

In vitro-Untersuchungen zur proteolytischen und lipolytischen Aktivität hefeähnlicher Pilze sowie deren Vindenz gegenüber Mäusen/In vitro Investigations on the Proteolytic and Lipolytic Activity of Yeast-like Fungi and their Virulence against Mice

Zusammenfassung: Die Verfasser untersuchten die proteolytische und die lipolytische Aktivität von hefeähnlichen Pilzen, die von Patienten mit symptomatischer oder asymptomatischer Candidose des Urogenitaltraktes isoliert worden waren. An Mäusen wurden mit den gleichen Stämmen Virulenzteste durchgeführt. Bei den Untersuchungen ergab sich, daß aufgrund der festgestellten enzymatischen Aktivitäten nicht eindeutig auf die Virulenz der hefeähnlichen Pilze geschlossen werden kann.
Summary: The proteolytic and lipolytic activity of several yeast-like strains was investigated. The strains had been isolated from patients with symptomatic or asymptomatic candidosis of the urogenital tract. The virulence of these strains was tested in mice. The results show that it is not possible to draw conclusions on the virulence of yeast-like fungi form their proteolytic or lipolytic activity.