scholarly journals Efficacy of Cefepime and Imipenem in Experimental Murine Pneumonia Caused by Porin-Deficient Klebsiella pneumoniae Producing CMY-2 β-Lactamase

2005 ◽  
Vol 49 (8) ◽  
pp. 3311-3316 ◽  
Author(s):  
Cristina Pichardo ◽  
José Manuel Rodríguez-Martínez ◽  
María E. Pachón-Ibañez ◽  
Carmen Conejo ◽  
José Ibáñez-Martínez ◽  
...  
Keyword(s):  
Body Weight ◽  
Survival Rate ◽  
Klebsiella Pneumoniae ◽  
Untreated Control ◽  
In Vitro Activity ◽  
Postantibiotic Effect ◽  
Bacterial Concentration ◽  
Inoculum Effect

ABSTRACT Previous studies have shown decreased in vitro activity of zwitterionic cephalosporins and carbapenems against porin-deficient Klebsiella pneumoniae expressing a plasmid-mediated AmpC-type β-lactamase (PACBL). The in vitro and in vivo activities of cefepime and imipenem were evaluated against the porin-deficient strain K. pneumoniae C2 and its CMY-2-producing derivative [K. pneumoniae C2(pMG248)]. The MICs (in micrograms/milliliter) of cefepime and imipenem against K. pneumoniae C2 were 0.125 and 0.25, respectively, while the corresponding values against K. pneumoniae C2(pMG248) were 8 and 16. Cefepime showed a greater inoculum effect than imipenem against both strains. Imipenem showed a significant postantibiotic effect (>2 h) against K. pneumoniae C2(pMG248) at 1×, 2×, 4×, 6×, and 8× MIC. The maximum concentrations of drug in serum of cefepime and imipenem in a pneumonia model using mice were 124.1 and 16.9 μg/ml, respectively. ΔT/MIC for K. pneumoniae C2 and C2(pMG248) were 1.29 h and 0.34 h for imipenem and 2.96 h and 1.27 h for cefepime. Both imipenem (30 mg/kg of body weight every 3 h) and cefepime (60 mg/kg every 4 h), administered for 72 h, increased the survival rate (86.6% and 100%) compared with untreated control animals (26.6%, P < 0.003) infected with K. pneumoniae C2. For the CMY-2-producing strain, imipenem, but not cefepime, increased the survival rate compared to the controls (86.6% and 40% versus 40%, P < 0.01). Bacterial concentration of the lungs was significantly decreased by both antimicrobials. In conclusion, imipenem was more active in terms of survival than cefepime for the treatment of murine pneumonia caused by a porin-deficient K. pneumoniae expressing PACBL CMY-2.

scholarly journals Efficacy of Macrolides and Telithromycin against Leptospirosis in a Hamster Model

2006 ◽  
Vol 50 (6) ◽  
pp. 1989-1992 ◽  
Author(s):  
James E. Moon ◽  
Michael C. Ellis ◽  
Matthew E. Griffith ◽  
Joshua S. Hawley ◽  
Robert G. Rivard ◽  
...  
Keyword(s):  
Body Weight ◽  
Untreated Control ◽  
Antimicrobial Agents ◽  
Leptospira Interrogans ◽  
In Vitro Activity ◽  
Hamster Model ◽  
In Vivo Efficacy ◽  
Daily Dose

ABSTRACT Human studies support the use of β-lactams and tetracyclines in the treatment of leptospirosis. Additional agents from these and other classes of antimicrobials also have in vitro activity against Leptospira species, though corroborating in vivo data are limited or lacking. We evaluated the therapeutic efficacy of azithromycin, clarithromycin, and telithromycin in a lethal hamster model of leptospirosis using Leptospira interrogans serogroup Canicola serovar Portlandvere. A range of dosages for each antimicrobial was given to the infected animals on days 2 through 7 (5 days) of the 21-day survival model. All untreated control animals survived less than 10 days from infection. Ninety to 100% of doxycycline controls, treated for 5 days with 5 mg/kg of body weight of drug, survived to 21 days. Treatment with azithromycin (daily dose: 6.25, 12.5, 25, 50, 100, or 200 mg/kg) resulted in 100% survival at all evaluated doses. Animals receiving 20 mg/kg or more of clarithromycin (daily dose: 1, 5, 10, 15, 20, 40, 60, or 100 mg/kg) had improved survival. Ninety-eight percent of animals treated with telithromycin (daily dose: 1, 5, 10, 15, 20, or 40 mg/kg) survived. We conclude that all agents tested have demonstrated in vivo efficacy in treating acute leptospirosis. These results provide support for further evaluation of macrolide and ketolide antimicrobial agents in human trials.

scholarly journals In Vitro and In Vivo Activities of Amikacin, Cefepime, Amikacin plus Cefepime, and Imipenem against an SHV-5 Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Strain

2001 ◽  
Vol 45 (4) ◽  
pp. 1287-1291 ◽  
Author(s):  
Dóra Szabó ◽  
András Máthé ◽  
Zsolt Filetóth ◽  
Piroska Anderlik ◽  
László Rókusz ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Susceptibility Test ◽  
In Vitro Susceptibility ◽  
High Inoculum ◽  
Extended Spectrum ◽  
Inoculum Effect ◽  
Do So

ABSTRACT The in vitro and in vivo effectiveness of amikacin, cefepime, and imipenem was studied using a high inoculum of an extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain. An in vitro susceptibility test at the standard inoculum predicted the in vivo outcome of amikacin or imipenem while it did not do so for cefepime due to the inoculum effect.

scholarly journals Fluopsin C for Treating Multidrug-Resistant Infections: In vitro Activity Against Clinically Important Strains and in vivo Efficacy Against Carbapenemase-Producing Klebsiella pneumoniae

2019 ◽  
Vol 10 ◽  
Author(s):  
Miguel Octavio Pérez Navarro ◽  
Ane Stefano Simionato ◽  
Juan Carlos Bedoya Pérez ◽  
André Riedi Barazetti ◽  
Janaina Emiliano ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
In Vivo Efficacy

scholarly journals In Vitro Activity of Difloxacin against Canine Bacterial Isolates

2000 ◽  
Vol 12 (3) ◽  
pp. 218-223 ◽  
Author(s):  
R. van den Hoven ◽  
J. A. Wagenaar ◽  
R. D. Walker
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Proteus Mirabilis ◽  
In Vitro Activity ◽  
Bacterial Isolates ◽  
Postantibiotic Effect ◽  
Gram Negative ◽  
Neutral Ph ◽  
Staphylococcus Intermedius

The in vitro activity of difloxacin against canine bacterial isolates from clinical cases was studied in the United States and The Netherlands. Minimal inhibitory concentrations (MIC), the postantibiotic effect, the effect of pH on antimicrobial activity, and the bacterial killing rate tests were determined according to standard techniques. The MICs of American and Dutch isolates agreed in general. The MICs of the American gram-negative isolates ranged from 0.06 to 2.0 μg/ml, and the MICs of the Dutch gram-negative isolates ranged from 0.016 to 8.0 μg/ml. A few European strains of Proteus mirabilis and Klebsiella pneumoniae had relatively high MICs. Bordetella bronchiseptica also was less susceptible to difloxacin. The MICs of the American gram-positive cocci ranged from 0.125 to 4.0 μg/ml, and the MICs of Dutch isolates ranged from 0.125 to 2.0 μg/ml. Difloxacin induced a concentration-dependent postantibiotic effect that lasted 0.2–3 hours in cultures with Escherichia coli, Staphylococcus intermedius, Streptococcus canis, Proteus spp., and Klebsiella pneumoniae. There was no postantibiotic effect observed against canine Pseudomonas aeruginosa. Decreasing the pH of the medium increased the MIC of Proteus mirabilis for difloxacin. The MICs of Escherichia coli and Klebsiella pneumoniae were lowest at neutral pH and were slightly increased in acid or alkaline media. At a neutral pH, most tested bacterial species were killed at a difloxacin concentration of 4 times the MIC. Similar results were obtained when these same bacteria were tested against enrofloxacin. A Klebsiella pneumoniae strain in an acidic environment was readily killed at difloxacin or enrofloxacin MIC, but at neutral pH the drug concentration had to be raised to 4 times the MIC for a bactericidal effect. After 24 hours of incubation at pH 7.1, difloxacin and enrofloxacin had similar bactericidal activity for all bacteria tested except Staphylococcus intermedius. Against S. intermedius, difloxacin was more bactericidal than enrofloxacin.

scholarly journals Activity and Diffusion of Tigecycline (GAR-936) in Experimental Enterococcal Endocarditis

2003 ◽  
Vol 47 (1) ◽  
pp. 216-222 ◽  
Author(s):  
Agnès Lefort ◽  
Matthieu Lafaurie ◽  
Laurent Massias ◽  
Yolande Petegnief ◽  
Azzam Saleh-Mghir ◽  
...  
Keyword(s):  
Body Weight ◽  
Half Life ◽  
Type Strain ◽  
Postantibiotic Effect ◽  
Bacteriostatic Effect ◽  
Elimination Half ◽  
Resistant Mutants ◽  
And Diffusion

ABSTRACT The activity of tigecycline (GAR-936), a novel glycylcycline, was investigated in vitro and in experimental endocarditis due to the susceptible Enterococcus faecalis JH2-2 strain, its VanA type transconjugant BM4316, and a clinical VanA type strain, E. faecium HB217 resistant to tetracycline. MICs of GAR-936 were 0.06 μg/ml for the three strains. In vitro pharmacodynamic studies demonstrated a bacteriostatic effect of GAR-936 that was not enhanced by increasing concentrations to more than 1 μg/ml and a postantibiotic effect ranging from 1 to 4.5 h for concentrations of 1- to 20-fold the MIC. Intravenous injection of [14C]GAR-936 to five rabbits with enterococcal endocarditis sacrificed 30 min, 4 h, or 12 h after the end of the infusion evidenced a lower clearance of GAR-936 from aortic vegetations than from serum and a homogeneous diffusion of GAR-936 into the vegetations. In rabbits with endocarditis, GAR-936 (14 mg/kg of body weight twice a day [b.i.d.]) given intravenously for 5 days was bacteriostatic against both strains of E. faecalis. Against E. faecium HB217, bacterial counts in vegetations significantly decreased during therapy (P < 0.01), and the effect was similar with GAR-936 at 14 mg/kg b.i.d., 14 mg/kg once a day (o.d.), and 7 mg/kg o.d., which provided concentrations in serum constantly above the MIC. Mean serum elimination half-life ranged from 3.3 to 3.6 h. No GAR-936-resistant mutants were selected in vivo with any regimen. We concluded that the combination of prolonged half-life, significant postantibiotic effect, and good and homogeneous diffusion into the vegetations may account for the in vivo activity of GAR-936 against enterococci susceptible or resistant to glycopeptides and tetracyclines, even when using a o.d. regimen in rabbits.

scholarly journals Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial–mesenchymal transition inhibition in vitro and in vivo

2021 ◽  
Author(s):  
Lin Chen ◽  
Azeem Alam ◽  
Aurelie Pac-Soo ◽  
Qian Chen ◽  
You Shang ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Body Weight ◽  
Survival Rate ◽  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Tgf Β1 ◽  
E Cadherin

AbstractEpithelial–mesenchymal transition (EMT) plays a crucial role in the development of pulmonary fibrosis. This study aims to investigate the effects of valproic acid (VPA) on EMT in vitro and in vivo. In vitro, EMT was induced by the administration of transforming growth factor-β1 (TGF-β1) in a human alveolar epithelial cell line (A549). The dose effects of VPA (0.1–3 mM) on EMT were subsequently evaluated at different timepoints. VPA (1 mM) was applied prior to the administration of TGF-β1 and the expression of E-cadherin, vimentin, p-Smad2/3 and p-Akt was assessed. In addition, the effects of a TGF-β type I receptor inhibitor (A8301) and PI3K-Akt inhibitor (LY294002) on EMT were evaluated. In vivo, the effects of VPA on bleomycin-induced lung fibrosis were evaluated by assessing variables such as survival rate, body weight and histopathological changes, whilst the expression of E-cadherin and vimentin in lung tissue was also evaluated. A8301 and LY294002 were used to ascertain the cellular signaling pathways involved in this model. The administration of VPA prior to TGF-β1 in A549 cells prevented EMT in both a time- and concentration-dependent manner. Pretreatment with VPA downregulated the expression of both p-Smad2/3 and p-Akt. A8301 administration increased the expression of E-cadherin and reduced the expression of vimentin. LY294002 inhibited Akt phosphorylation induced by TGF-β1 but failed to prevent EMT. Pretreatment with VPA both increased the survival rate and prevented the loss of body weight in mice with pulmonary fibrosis. Interestingly, both VPA and A8301 prevented EMT and facilitated an improvement in lung structure. Overall, pretreatment with VPA attenuated the development of pulmonary fibrosis by inhibiting EMT in mice, which was associated with Smad2/3 deactivation but without Akt cellular signal involvement.

scholarly journals In Vitro Activities of Ceftazidime–Avibactam and Aztreonam–Avibactam at Different Inoculum Sizes of Extended-Spectrum β-Lactam-Resistant Enterobacterales Blood Isolates

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1492
Author(s):  
Moonsuk Bae ◽  
Taeeun Kim ◽  
Joung Ha Park ◽  
Seongman Bae ◽  
Heungsup Sung ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Extended Spectrum ◽  
Broth Microdilution Method ◽  
Tertiary Center ◽  
Inoculum Effect

β-lactam–avibactam combinations have been proposed as carbapenem-sparing therapies, but little data exist on their in vitro activities in infections with high bacterial inocula. We investigated the in vitro efficacies and the inoculum effects of ceftazidime–avibactam and aztreonam–avibactam against extended-spectrum β-lactam-resistant Enterobacterales blood isolates. A total of 228 non-repetitive extended-spectrum β-lactam-resistant Escherichia coli and Klebsiella pneumoniae blood isolates were prospectively collected in a tertiary center. In vitro susceptibilities to ceftazidime, aztreonam, meropenem, ceftazidime–avibactam, and aztreonam–avibactam were evaluated by broth microdilution method using standard and high inocula. An inoculum effect was defined as an eightfold or greater increase in MIC when tested with the high inoculum. Of the 228 isolates, 99% were susceptible to ceftazidime–avibactam and 99% had low aztreonam–avibactam MICs (≤8 mg/L). Ceftazidime–avibactam and aztreonam–avibactam exhibited good in vitro activities; MIC50/MIC90 values were 0.5/2 mg/L, 0.125/0.5 mg/L, and ≤0.03/0.25 mg/L, respectively, and aztreonam–avibactam was more active than ceftazidime–avibactam. The frequencies of the inoculum effect with ceftazidime–avibactam and aztreonam–avibactam were lower than with meropenem (14% vs. 38%, p < 0.001 and 30% vs. 38%, p = 0.03, respectively). The β-lactam-avibactam combinations could be useful as carbapenem-sparing strategies, and aztreonam–avibactam has the better in vitro activity but is more subject to the inoculum effect than ceftazidime–avibactam.

scholarly journals In Vitro and In Vivo Activities of CS-758 (R-120758), a New Triazole Antifungal Agent

2002 ◽  
Vol 46 (2) ◽  
pp. 367-370 ◽  
Author(s):  
Yasuki Kamai ◽  
Tamako Harasaki ◽  
Takashi Fukuoka ◽  
Satoshi Ohya ◽  
Katsuhisa Uchida ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Antifungal Agent ◽  
The Other ◽  
In Vitro Activity ◽  
Effective Doses ◽  
Low Levels ◽  
Systemic Infections

ABSTRACT The activity of CS-758 (R-120758), a new triazole antifungal agent, was evaluated and compared with those of fluconazole, itraconazole, and amphotericin B in vitro and with those of fluconazole and itraconazole in vivo. CS-758 exhibited potent in vitro activity against clinically important fungi. The activity of CS-758 against Candida spp. was superior to that of fluconazole and comparable or superior to those of itraconazole and amphotericin B. CS-758 retained potent activity against Candida albicans strains with low levels of susceptibility to fluconazole (fluconazole MIC, 4 to 32 μg/ml). Against Aspergillus spp. and Cryptococcus neoformans, the activity of CS-758 was at least fourfold superior to those of the other drugs tested. CS-758 also exhibited potent in vivo activity against murine systemic infections caused by C. albicans, C. neoformans, Aspergillus fumigatus, and Aspergillus flavus. The 50% effective doses against these infections were 0.41 to 5.0 mg/kg of body weight. These results suggest that CS-758 may be useful in the treatment of candidiasis, cryptococcosis, and aspergillosis.

Standard Biocompatibility Studies Do Not Predict All Effects of PVA/CMC Anti-Adhesive Gel in vivo

2016 ◽  
Vol 56 (3-4) ◽  
pp. 109-122 ◽  
Author(s):  
Christiane Freytag ◽  
Erich K. Odermatt
Keyword(s):  
Wound Healing ◽  
Body Weight ◽  
Abdominal Wall ◽  
Untreated Control ◽  
Wall Model ◽  
Adhesion Properties ◽  
Good Biocompatibility ◽  
End To End

Purpose: PVA/CMC (polyvinyl alcohol/carboxymethyl cellulose) hydrogel fulfills various physiochemical properties required for an adhesion barrier and has shown good anti-adhesion properties in previous in vivo studies. In this investigation, we assessed the in vitro and in vivo biocompatibility of PVA/CMC gel and compared this to the functionality and promotion of wound healing for two surgical indications. Methods: Standardized ISO10993 in vitro and in vivo biocompatibility studies, comprising cytotoxicity, genotoxicity, acute systemic toxicity, delayed contact and maximization sensitization test, intracutaneous reactivity and local muscle implantation, were performed on PVA/CMC gel. In the functional studies, PVA/CMC gel was applied - on the one hand - to a rabbit abdominal wall model enforced with a polypropylene mesh for testing the anti-adhesion properties and - on the other hand - to an end- to-end anastomosis model that was selected for surveying potential influences of different dosages of PVA/CMC gel on anastomotic wound healing. Results: The ISO10993 methods indicated generally good biocompatibility properties, such as the absence of cytotoxic and mutagenic effects as well as no signs of systemic toxicity and sensitization potentials. No irritation effects were observed after the intracutaneous injection of lipophilic PVA/CMC sesame oil extract. However, the injection of hydrophilic PVA/CMC physiologic saline extract induced slight irritation. Following rabbit muscle implantation of the PVA membrane for 2, 4, 12, 26 and 52 weeks, a slight irritant effect was observed at 12 weeks due to the peak of phagocytosis. In the functionality tests, PVA/CMC gel showed good anti-adhesive effects in the abdominal wall model enforced with the mesh, with significantly lower and less tense adhesions compared to the untreated control. However, moderate signs of inflammation, especially in the spleen were observed after the intra-abdominal implantation of 3.3 ml PVA/CMC gel per kg body weight. In the end-to-end anastomosis model, PVA/CMC gel had no influence on wound healing. For dosages of 1-6 ml gel per treatment, no signs of intestinal leaks were detected, and tensile strength was equal to that of the untreated control, but again more moderate signs of inflammation in the spleen were observed at a dosage >3 ml. Conclusion: Comparing the standardized ISO10993 methods, anti-adhesive PVA/CMC gel displays good biocompatibility. However, those methods do not seem to be sensitive enough because the rabbit abdominal wall and the end-to-end anastomosis models display more effects with respect to the dosage and routes of the intra-abdominal resorption of PVA/CMC gel - with the recommended <2 ml PVA/CMC gel per kg body weight as a secure dosage.

scholarly journals In Vitro and In Vivo Efficacies of T-3811ME (BMS-284756) against Mycoplasma pneumoniae

2001 ◽  
Vol 45 (1) ◽  
pp. 312-315 ◽  
Author(s):  
Masahiro Takahata ◽  
Masako Shimakura ◽  
Ritsuko Hori ◽  
Kazuo Kizawa ◽  
Yozo Todo ◽  
...  
Keyword(s):  
Body Weight ◽  
Mycoplasma Pneumoniae ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
In Vitro Activity ◽  
Free Base ◽  
Once Daily ◽  
Viable Cells

ABSTRACT T-3811, the free base of T-3811ME (BMS-284756), a new des-F(6)-quinolone, showed a potent in vitro activity (MIC at which 90% of the isolates tested are inhibited [MIC90], 0.0313 μg/ml) against Mycoplasma pneumoniae. The MIC90 of T-3811 was 4-fold higher than that of clarithromycin but was 4- to 8-fold lower than those of trovafloxacin, gatifloxacin, gemifloxacin, and moxifloxacin and was 16- to 32-fold lower than those of levofloxacin, ciprofloxacin, and minocycline. In an experimental M. pneumoniae pneumonia model in hamsters, after the administration of T-3811ME (20 mg/kg of body weight as T-3811, once daily, orally) for 5 days, the reduction of viable cells of M. pneumoniae in bronchoalveolar lavage fluid was greater than those of trovafloxacin, levofloxacin, and clarithromycin (20 and 40 mg/kg, orally) (P < 0.05).

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