scholarly journals Comparison of the effects of aztreonam and tigemonam against Escherichia coli and Klebsiella pneumoniae in vitro and in vivo.

1991 ◽  
Vol 35 (3) ◽  
pp. 417-422 ◽  
Author(s):  
M L van Ogtrop ◽  
H Mattie ◽  
H F Guiot ◽  
E van Strijen ◽  
B R Sekh ◽  
...  
2007 ◽  
Vol 51 (4) ◽  
pp. 1481-1486 ◽  
Author(s):  
C. Andrew DeRyke ◽  
Mary Anne Banevicius ◽  
Hong Wei Fan ◽  
David P. Nicolau

ABSTRACT The purpose of this study was to examine the in vivo efficacies of meropenem and ertapenem against extended-spectrum-β-lactamase (ESBL)-producing isolates with a wide range of MICs. Human-simulated dosing regimens in mice were designed to approximate the free drug percent time above the MIC (fT>MIC) observed for humans following meropenem at 1 g every 8 h and ertapenem at 1 g every 24 h. An in vivo neutropenic mouse thigh infection model was used to examine the bactericidal effects against 31 clinical ESBL Escherichia coli and Klebsiella pneumoniae isolates and 2 non-ESBL isolates included for comparison at a standard 105 inoculum. Three isolates were examined at a high 107 inoculum as well. Meropenem displayed greater in vitro potency, with a median MIC (range) (μg/ml) of 0.125 (0.03 to 32), than did ertapenem, with 0.5 (0.012 to 128). Seven of the 31 ESBL isolates were removed from the efficacy analysis due to their inability to establish infection in the mouse model. When MICs were ≤1.5 μg/ml for ertapenem (≤0.5 μg/ml for meropenem), similar reductions in CFU (≈ 2-log kill) were observed for both ertapenem (fT>MIC ≥ 23%) and meropenem (fT>MIC ≥ 75%). Ertapenem showed bacterial regrowth for seven of eight isolates, with MICs of ≥2 μg/ml (fT>MIC ≤ 20%), while meropenem displayed antibacterial potency that varied from a static effect to a 1-log bacterial reduction in these isolates (fT>MIC = 30 to 65%). At a 107 inoculum, both agents eradicated bacteria due to adequate exposures (fT>MIC = 20 to 45%). Due to low MICs, no difference in bacterial kill was noted for the majority of ESBL isolates tested. However, for isolates with raised ertapenem MICs of ≥2 μg/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC.


2016 ◽  
Vol 60 (5) ◽  
pp. 3001-3006 ◽  
Author(s):  
Akihiro Morinaka ◽  
Yuko Tsutsumi ◽  
Keiko Yamada ◽  
Yoshihiro Takayama ◽  
Shiro Sakakibara ◽  
...  

ABSTRACTGram-negative bacteria are evolving to produce β-lactamases of increasing diversity that challenge antimicrobial chemotherapy. OP0595 is a new diazabicyclooctane serine β-lactamase inhibitor which acts also as an antibiotic and as a β-lactamase-independent β-lactam “enhancer” againstEnterobacteriaceae. Here we determined the optimal concentration of OP0595 in combination with piperacillin, cefepime, and meropenem, in addition to the antibacterial activity of OP0595 alone and in combination with cefepime, inin vitrotime-kill studies and anin vivoinfection model against five strains of CTX-M-15-positiveEscherichia coliand five strains of KPC-positiveKlebsiella pneumoniae. An OP0595 concentration of 4 μg/ml was found to be sufficient for an effective combination with all three β-lactam agents. In bothin vitrotime-kill studies and anin vivomodel of infection, cefepime-OP0595 showed stronger efficacy than cefepime alone against all β-lactamase-positive strains tested, whereas OP0595 alone showed weaker or no efficacy. Taken together, these data indicate that combinational use of OP0595 and a β-lactam agent is important to exert the antimicrobial functions of OP0595.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yishuai Lin ◽  
Ying Zhang ◽  
Shixing Liu ◽  
Dandan Ye ◽  
Liqiong Chen ◽  
...  

Colistin is being considered as “the last ditch” treatment in many infections caused by Gram-negative stains. However, colistin is becoming increasingly invalid in treating patients who are infected with colistin-resistant Escherichia coli (E. coli) and Klebsiella Pneumoniae (K. pneumoniae). To cope with the continuous emergence of colistin resistance, the development of new drugs and therapies is highly imminent. Herein, in this work, we surprisingly found that the combination of quercetin with colistin could efficiently and synergistically eradicate the colistin-resistant E. coli and K. pneumoniae, as confirmed by the synergy checkboard and time-kill assay. Mechanismly, the treatment of quercetin combined with colistin could significantly downregulate the expression of mcr-1 and mgrB that are responsible for colistin-resistance, synergistically enhancing the bacterial cell membrane damage efficacy of colistin. The colistin/quercetin combination was notably efficient in eradicating the colistin-resistant E. coli and K. pneumoniae both in vitro and in vivo. Therefore, our results may provide an efficient alternative pathway against colistin-resistant E. coli and K. pneumoniae infections.


2019 ◽  
Vol 31 (7) ◽  
pp. 1447-1453
Author(s):  
Nagarajan Padmini ◽  
Nagasundaram Rashiya ◽  
Natesan Sivakumar ◽  
Narayanan Dhiraviam Kannan ◽  
Ramamoorthy Manjuladevi ◽  
...  

2020 ◽  
Vol 148 ◽  
pp. 104446
Author(s):  
Nagarajan Padmini ◽  
Nagasundaram Rashiya ◽  
Natesan Sivakumar ◽  
Narayanan Dhiraviam Kannan ◽  
Ramamoorthy Manjuladevi ◽  
...  

mSphere ◽  
2021 ◽  
Author(s):  
Bosul Lee ◽  
Jun Yan ◽  
Amber Ulhaq ◽  
Sarah Miller ◽  
Wonjae Seo ◽  
...  

Rifabutin has been recently described as a potential adjunctive therapy for antibiotic-resistant A. baumannii infections due to hypersensitivity in iron-depleted media, which may more closely mimic an in vivo environment. Here, we report that this hyperactivity is specific for A. baumannii , rather than being a general effect for other pathogens.


2016 ◽  
Vol 97 (4) ◽  
pp. 572-578 ◽  
Author(s):  
A G Miroshnichenko ◽  
V M Brukhanov ◽  
I Ye Gossen ◽  
V Yu Perfilyev

Aim. To assess the antioxidants effectiveness (ascorbic acid, methylethylpiridinol, N-acetylcysteine) in reducing the gentamicin-induced nephrotoxicity in experimental infection caused by Escherichia coli or Klebsiella pneumoniae.Methods. The experiment was divided into two parts. In the first part, the effect of antioxidants on the sensitivity of bacteria to gentamicin in vitro according to changing the optical density of the bacterial suspension, in the second part - nephroprotective activity of antioxidants and their effects on antibiotic activity in experimental bacterial peritonitis were evaluated.Results. All antioxidants significantly reduce the sensitivity of E. coli to gentamicin in vitro, and the level of effect is directly proportional to the antioxidant concentration. Methylethylpiridinol has the most pronounced antagonistic action against gentamicin. It is found that methylethylpiridinol at a concentration of 4 mmol/l enhances development of Escherichia coli strain by 7 times by the 6th hour of incubation. Ascorbic acid and N-acetylcysteine have a similar probacterial activity profile. In the incubation mixtures containing a strain of Klebsiella pneumoniae, a similar pattern of increase in bacterial biomass optical density was observed with maximum values in the presence of the highest concentrations of antioxidants. In experimental infection, antioxidants reduce the activity of gentamicin against Escherichia coli and Klebsiella pneumoniae, without reducing the antibiotic nephrotoxicity.Conclusion. Ascorbic acid, methylethylpiridinol and N-acetylcysteine reduce the antibacterial activity of gentamicin against Escherichia coli and Klebsiella pneumoniae in vitro and in vivo, in a dose of 80 mg/kg they do not reduce gentamicin nephrotoxicity in bacterial peritonitis in rats; their use in the course of treatment with gentamicin is not only irrational, but also contraindicated.


Author(s):  
Ирина Владимировна Акулина ◽  
Светлана Ивановна Павлова ◽  
Ирина Семеновна Степаненко ◽  
Назира Сунагатовна Карамова ◽  
Александр Владиславович Сергеев ◽  
...  
Keyword(s):  

Проведено токсикологическое исследование соединений с антибактериальными свойствами из группы терпенов ментанового ряда в условиях in vitro и in vivo: лимонена (B34), его производного (+)-1,2-оксида лимонена (B60) и серосодержащего монотерпенового соединения 2-(1’-гидрокси-4’-изопренил-1’-метилциклогексил-2’-тио)метилэтаноата (B65). В условиях in vitro (культура опухолевых клеток HeLa) изучаемые монотерпены в диапазоне концентраций 2 – 200 мкг/мл обладали цитотоксичностью. Ингибирующая концентрация (ИК50) для B34 составила 231 (167 – 295) мкг/мл, для B60 – 181 (105 – 257) мкг/мл, ИК50 B65 – 229 (150 – 308) мкг/мл. Исследование генотоксичности показало, что B34 и B65 в диапазоне концентраций 50 – 1000 мкг/мл не индуцируют SOS мутагенез в клетках Escherichia coli PQ37, тогда как B60 в концентрациях 500 и 1000 мкг/мл проявляет генотоксичность. In vivo в остром эксперименте на беспородных мышах установлена низкая токсичность B34 и его производных при различных путях введения. Наименьший показатель острой токсичности имеет B65, в связи с чем дополнительно на крысах проведено изучение его хронической токсичности. Ежедневное внутрижелудочное введение B65 в разовых дозах, составляющих 1/10 и 1/20 ЛД50 (1000 мг/кг и 500 мг/кг), в течение 1 мес не вызывало гибели животных, значимых нарушений общего состояния, изменения динамики массы тела, морфопатологических изменений. Внутрижелудочное введение B65 крысам в высокой токсической дозе 2000 мг/кг (1/5 ЛД50) в течение месяца вызывает патоморфологические изменения структуры печени.


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