scholarly journals In VitroActivity andIn VivoEfficacy of Posaconazole in Treatment of Murine Infections by Different Isolates of theAspergillus terreusComplex

2010 ◽  
Vol 55 (2) ◽  
pp. 676-679 ◽  
Author(s):  
Valentina Salas ◽  
F. Javier Pastor ◽  
M. M. Rodríguez ◽  
Enrique Calvo ◽  
Emilio Mayayo ◽  
...  
Keyword(s):  
Body Weight ◽  
Murine Model ◽  
Aspergillus Terreus ◽  
Broth Microdilution ◽  
Level Of Activity ◽  
Tissue Burden ◽  
Different Strains ◽  
High Level ◽  
Murine Infections

ABSTRACTPosaconazole (PSC) is an antifungal drug recommended as an alternative for the treatment of invasive aspergillosis in patients who are refractory or intolerant to primary antifungal therapy. We have evaluated thein vitroactivity of PSC against 21 strains of theAspergillus terreuscomplex using both broth microdilution and disk diffusion (Neo Sensitabs) methods. PSC showed the same high level of activity against all the strains with the twoin vitromethods used. We developed a murine model of disseminated infection to evaluate the efficacy of PSC at 5, 10, or 20 mg/kg of body weight twice a day by using 6 different strains chosen randomly. PSC showed good efficacy, especially at 20 mg/kg, as measured by prolonged survival, tissue burden reduction, histopathology, and lowered galactomannan levels. The PSC levels in serum on the fourth day of treatment were higher than the MICs for the strains tested.

scholarly journals MIC Values of Voriconazole Are Predictive of Treatment Results in Murine Infections by Aspergillus terreus Species Complex

2013 ◽  
Vol 57 (3) ◽  
pp. 1532-1534 ◽  
Author(s):  
Valentina Salas ◽  
F. Javier Pastor ◽  
Deanna A. Sutton ◽  
Enrique Calvo ◽  
Emilio Mayayo ◽  
...  
Keyword(s):  
Species Complex ◽  
Aspergillus Terreus ◽  
Serum Levels ◽  
Treatment Results ◽  
Cutoff Value ◽  
Content Type ◽  
Fungal Load ◽  
Tissue Burden ◽  
Murine Infections

ABSTRACTWe evaluated the efficacy of voriconazole against nine strains ofAspergillus terreuswith different MICs (0.12 to 4 μg/ml) by using a murine model. Markers of efficacy included survival, tissue burden, galactomannan antigenemia, and drug serum levels. Voriconazole was especially effective in prolonging survival and reducing the fungal load in infections by strains that showed MICs that were less than or equal to the epidemiological cutoff value (1 μg/ml).In vitrodata might be useful for predicting the outcome ofA. terreusinfections.

scholarly journals In VitroActivity andIn VivoEfficacy of Anidulafungin in Murine Infections byAspergillus flavus

2010 ◽  
Vol 55 (3) ◽  
pp. 1290-1292 ◽  
Author(s):  
Enrique Calvo ◽  
F. Javier Pastor ◽  
Emilio Mayayo ◽  
Valentina Salas ◽  
Josep Guarro
Keyword(s):  
High Activity ◽  
Aspergillus Flavus ◽  
Murine Model ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Broth Microdilution ◽  
Disseminated Infection ◽  
Tissue Burden ◽  
Murine Infections

ABSTRACTAnidulafungin (AFG) showed high activity against 27 strains ofAspergillus flavusby use of broth microdilution and disk diffusion methods. This drug was effectivein vivoin a murine model of disseminated infection with five isolates tested. AFG was able to prolong survival and reduce tissue burden of infected mice but not able to reduce galactomannan serum concentrations. The AFG serum levels were above the corresponding minimum effective concentrations (MEC) for all of the strains tested.

scholarly journals In Vitro Activities of RWJ-54428 (MC-02,479) against Multiresistant Gram-Positive Bacteria

2001 ◽  
Vol 45 (5) ◽  
pp. 1422-1430 ◽  
Author(s):  
Suzanne Chamberland ◽  
Johanne Blais ◽  
Monica Hoang ◽  
Cynthia Dinh ◽  
Dylan Cotter ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Penicillin G ◽  
Significant Activity ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Level Of Activity ◽  
Resistant Strains ◽  
High Level

ABSTRACT RWJ-54428 (MC-02,479) is a new cephalosporin with a high level of activity against gram-positive bacteria. In a broth microdilution susceptibility test against methicillin-resistant Staphylococcus aureus (MRSA), RWJ-54428 was as active as vancomycin, with an MIC at which 90% of isolates are inhibited (MIC90) of 2 μg/ml. For coagulase-negative staphylococci, RWJ-54428 was 32 times more active than imipenem, with an MIC90 of 2 μg/ml. RWJ-54428 was active against S. aureus, Staphylococcus epidermidis, and Staphylococcus haemolyticus isolates with reduced susceptibility to glycopeptides (RWJ-54428 MIC range, ≤0.0625 to 1 μg/ml). RWJ-54428 was eight times more potent than methicillin and cefotaxime against methicillin-susceptible S. aureus (MIC90, 0.5 μg/ml). For ampicillin-susceptible Enterococcus faecalis (including vancomycin-resistant and high-level aminoglycoside-resistant strains), RWJ-54428 had an MIC90 of 0.125 μg/ml. RWJ-54428 was also active against Enterococcus faecium, including vancomycin-, gentamicin-, and ciprofloxacin-resistant strains. The potency against enterococci correlated with ampicillin susceptibility; RWJ-54428 MICs ranged between ≤0.0625 and 1 μg/ml for ampicillin-susceptible strains and 0.125 and 8 μg/ml for ampicillin-resistant strains. RWJ-54428 was more active than penicillin G and cefotaxime against penicillin-resistant, -intermediate, and -susceptible strains ofStreptococcus pneumoniae (MIC90s, 0.25, 0.125, and ≤0.0625 μg/ml, respectively). RWJ-54428 was only marginally active against most gram-negative bacteria; however, significant activity was observed against Haemophilus influenzae andMoraxella catarrhalis (MIC90s, 0.25 and 0.5 μg/ml, respectively). This survey of the susceptibilities of more than 1,000 multidrug-resistant gram-positive isolates to RWJ-54428 indicates that this new cephalosporin has the potential to be useful in the treatment of infections due to gram-positive bacteria, including strains resistant to currently available antimicrobials.

scholarly journals In Vivo Activity of Posaconazole against Mucor spp. in an Immunosuppressed-Mouse Model

2002 ◽  
Vol 46 (7) ◽  
pp. 2310-2312 ◽  
Author(s):  
Qiu N. Sun ◽  
Laura K. Najvar ◽  
Rosie Bocanegra ◽  
David Loebenberg ◽  
John R. Graybill
Keyword(s):  
Body Weight ◽  
Mouse Model ◽  
Amphotericin B ◽  
Immunosuppressed Mouse ◽  
Tissue Burden

ABSTRACT The in vivo activities of posaconazole, itraconazole, and amphotericin B in neutropenic mice with zygomycosis were compared. The in vitro MICs of posaconazole and itraconazole for the strains of Mucor spp. used in this study ranged from 0.125 to 8 μg/ml and 0.25 to 8 μg/ml, respectively. The in vitro MIC range for amphotericin B is 0.125 to 0.25 μg/ml. At twice-daily doses of ≥15 mg/kg of body weight, posaconazole prolonged the survival of the mice and reduced tissue burden.

scholarly journals Antifungal Therapy in a Murine Model of Disseminated Infection by Cryptococcus gattii

2010 ◽  
Vol 54 (10) ◽  
pp. 4074-4077 ◽  
Author(s):  
Enrique Calvo ◽  
F. Javier Pastor ◽  
M. Mar Rodríguez ◽  
Isabel Pujol ◽  
Josep Guarro
Keyword(s):  
Body Weight ◽  
Brain Tissue ◽  
Amphotericin B ◽  
Murine Model ◽  
Systemic Infection ◽  
Cryptococcus Gattii ◽  
Pulmonary Cryptococcosis ◽  
Fungistatic Activity ◽  
Fungal Load ◽  
Tissue Burden

ABSTRACT We have evaluated the efficacy of posaconazole (PSC), voriconazole (VRC), and amphotericin B (AMB) in a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis.

scholarly journals EarlyIn VitroandIn VivoDevelopment of High-Level Daptomycin Resistance Is Common in Mitis Group Streptococci after Exposure to Daptomycin

2013 ◽  
Vol 57 (5) ◽  
pp. 2319-2325 ◽  
Author(s):  
Cristina García-de-la-Mària ◽  
Juan M. Pericas ◽  
Ana del Río ◽  
Ximena Castañeda ◽  
Xavier Vila-Farrés ◽  
...  
Keyword(s):  
Body Weight ◽  
Streptococcus Bovis ◽  
Streptococcus Mitis ◽  
Content Type ◽  
Group 4 ◽  
Viridans Group Streptococcus ◽  
High Level ◽  
Time Kill

ABSTRACTThe development of high-level daptomycin resistance (HLDR; MIC of ≥256 mg/liter) after exposure to daptomycin has recently been reported in viridans group streptococcus (VGS) isolates. Our study objectives were as follows: to know whetherin vitrodevelopment of HLDR after exposure to daptomycin was common among clinical isolates of VGS andStreptococcus bovis; to determine whether HLDR also developed during the administration of daptomycin to treat experimental endocarditis caused by the daptomycin-susceptible, penicillin-resistantStreptococcus mitisstrainS. mitis351; and to establish whether combination with gentamicin prevented the development of HLDRin vitroandin vivo. In vitrostudies were performed with 114 VGS strains (mitis group, 92; anginosus group, 10; mutans group, 8; and salivarius group, 4) and 54Streptococcus bovisstrains isolated from 168 consecutive patients with infective endocarditis diagnosed between 1995 and 2010. HLDR was only observed after 24 h of exposure to daptomycin in 27% of the mitis group, including 27% ofS. mitisisolates, 47% ofS. oralisisolates, and 13% ofS. sanguisisolates. In our experimental model, HLDR was detected in 7/11 (63%) and 8/12 (67%) isolates recovered from vegetations after 48 h of daptomycin administered at 6 mg/kg of body weight/24 h and 10 mg/kg/24 h, respectively.In vitro, time-kill experiments showed that daptomycin plus gentamicin was bactericidal againstS. mitis351 at tested concentrations of 0.5 and 1 times the MIC and prevented the development of HLDR.In vivo, the addition of gentamicin at 1 mg/kg/8 h to both daptomycin arms prevented HLDR in 21 out of 23 (91%) rabbits. Daptomycin plus gentamicin was at least as effective as vancomycin plus gentamicin. In conclusion, HLDR develops rapidly and frequentlyin vitroandin vivoamong mitis group streptococci. Combining daptomycin with gentamicin enhanced its activity and prevented the development of HLDR in most cases.

scholarly journals Posaconazole Combined with Amphotericin B, an Effective Therapy for a Murine Disseminated Infection Caused by Rhizopus oryzae

2008 ◽  
Vol 52 (10) ◽  
pp. 3786-3788 ◽  
Author(s):  
M. Mar Rodríguez ◽  
Carolina Serena ◽  
Marçal Mariné ◽  
F. Javier Pastor ◽  
Josep Guarro
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Murine Model ◽  
Rhizopus Oryzae ◽  
Effective Therapy ◽  
Prolonged Survival ◽  
Low Doses ◽  
Disseminated Infection ◽  
Tissue Burden

ABSTRACT In a murine model of disseminated zygomycosis, low doses of amphotericin B (0.3 mg/kg body weight/day) combined with posaconazole (40 mg/kg/day) prolonged survival and reduced tissue burden with respect to that of controls and that of both drugs administered alone. Results were similar to those obtained with amphotericin B given alone at 0.8 mg/kg/day.

scholarly journals Anidulafungin in Treatment of Experimental Invasive Infection by Candida parapsilosis:In VitroActivity, (1→3)-β-d-Glucan and Mannan Serum Levels, Histopathological Findings, andIn VivoEfficacy

2011 ◽  
Vol 55 (11) ◽  
pp. 4985-4989 ◽  
Author(s):  
Valentina Salas ◽  
F. Javier Pastor ◽  
Enrique Calvo ◽  
Emilio Mayayo ◽  
Guillermo Quindós ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Serum Levels ◽  
Sensu Stricto ◽  
Invasive Infection ◽  
Content Type ◽  
Level Of Activity ◽  
High Level ◽  
Different Doses

ABSTRACTWe have evaluated thein vitroactivity of anidulafungin (AFG) against 31 strains ofCandida parapsilosissensu stricto by using broth microdilution, disk diffusion, and minimal fungicidal concentration (MFC) determination procedures. The two first methods showed a high level of activity of the drug, while MFCs were 1 to 5 dilutions higher than their corresponding MICs. To assess if MICs were predictive ofin vivooutcomes, six strains representing different AFG MICs (0.12 to 2 μg/ml) were tested in a murine model of disseminated infection treated with different doses of the drug (1, 5, or 10 mg/kg of body weight). AFG was able to prolong the survival of mice infected with all the strains tested but was able to reduce the tissue burden of those mice infected only with the strains that showed the lowest MIC (0.12 μg/ml).

scholarly journals Efficacy of nikkomycin Z against experimental pulmonary blastomycosis.

1997 ◽  
Vol 41 (9) ◽  
pp. 2026-2028 ◽  
Author(s):  
K V Clemons ◽  
D A Stevens
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Murine Model ◽  
Prolonged Survival ◽  
Blastomyces Dermatitidis ◽  
Good Activity ◽  
Synthetase Inhibitor ◽  
Chitin Synthetase ◽  
Nikkomycin Z

Nikkomycin Z is a chitin synthetase inhibitor. In vitro, nikkomycin Z had good activity against Blastomyces dermatitidis, with an MIC of 0.78 microg/ml and a minimal fungicidal concentration of 3.1 microg/ml. The efficacies of various treatment durations (3, 5, or 10 days) and doses (200, 400, or 1,000 mg/kg of body weight) of nikkomycin Z given twice daily were compared with those of itraconazole at 200 mg/kg given twice daily and amphotericin B at 6.25 mg/kg in a murine model of pulmonary blastomycosis. All treatments prolonged survival compared with untreated controls (P < 0.05 to 0.01); 100% survival was achieved with 5 or 10 days of any nikkomycin Z dose or with amphotericin B. Amphotericin B and nikkomycin Z, but not itraconazole, reduced infection compared with controls. Amphotericin B and the 10-day regimens of all nikkomycin Z doses were equivalent and superior to itraconazole or nikkomycin Z for < or = 5 days at any dose (P < 0.05 to 0.01). Increased duration and/or dosage improved the efficacy of nikkomycin Z, with 10 days of each dose curing 50 to 90% of the animals. Only a 1,000-mg/kg/day dose of nikkomycin Z was curative when treatment lasted less than 10 days. In contrast, itraconazole cured no mice, while amphotericin B cured all mice. Based on the total amount of drug given, amphotericin B was estimated to be 32 times as active as nikkomycin Z and nikkomycin Z was estimated to be 3 times as active as itraconazole. Overall, nikkomycin Z given orally was well tolerated, had good activity against blastomycosis, and could result in biological cure, thus producing results equivalent to those of parenteral amphotericin B.

scholarly journals Efficacy of Daptomycin against Bacillus anthracis in a Murine Model of Anthrax Spore Inhalation

2010 ◽  
Vol 54 (10) ◽  
pp. 4471-4473 ◽  
Author(s):  
Henry S. Heine ◽  
Jennifer Bassett ◽  
Lynda Miller ◽  
Bret K. Purcell ◽  
W. Russell Byrne
Keyword(s):  
Body Weight ◽  
Bacillus Anthracis ◽  
Murine Model ◽  
Day Treatment ◽  
Survival Rates ◽  
Treatment Groups ◽  
Anthrax Spore ◽  
Phosphate Buffered Saline

ABSTRACT Daptomycin demonstrated in vitro (MIC90, 4 μg/ml) and in vivo activities against Bacillus anthracis. Twice-daily treatment with a dose of 50 mg/kg of body weight was begun 24 h after challenge and continued for 14 or 21 days; results were compared to those for controls treated with phosphate-buffered saline or ciprofloxacin. Day 43 survival rates were 6/10 mice for the 14-day and 9/10 mice for the 21-day treatment groups, compared to survival with ciprofloxacin: 8/10 and 9/10 mice, respectively. Culture results from tissues removed at the termination of the experiment were negative.

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