In vitro and in vivo activities of the diazabicyclooctane OP0595 against AmpC-derepressed Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a common cause for healthcare-associated infections, which have been historically treated by antipseudomonal β-lactam agents in the clinical setting. However, P. aeruginosa has evolved to overcome these β-lactam agents via multiple endogenous resistance mechanisms, including derepression of the chromosomal cephalosporinase (AmpC).

Investigations on yearly changes in tebipenem susceptibility of bacterial isolates from pediatric patients -A post-marketing surveillance of tebipenem pivoxil granules for pediatric.

We conducted the post-marketing surveillance of tebipenem pivoxil (Orapeneme fine granules 10% for pediatric), an oral carbapenem antibacterial agent, to investigate changes in bacterial susceptibility against tebipenem (TBPM). Bacterial strains used in this surveillance were methicillin-susceptible Staphylococcus aureus (MSSA: 303 strains), Streptococcus pneumoniae (554 strains), other Streptococcus spp. (242 strains: including Streptococcus pyogenes 133 strains), Moraxella catarrhalis (306 strains) and Haemophilus influenzae (506 strains) isolated from pediatric patients in 15 medical facilities in Japan between April 2010 and March 2015.

In Vitro and In Vivo Activities of OP0595, a New Diazabicyclooctane, against CTX-M-15-Positive Escherichia coli and KPC-Positive Klebsiella pneumoniae.

Gram-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" against Enterobacteriaceae 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, in in vitro time-kill studies and an in vivo infection model against five strains of CTX-M-15-positive Escherichia coli and five strains of KPC-positive Klebsiella pneumoniae An OP0595 concentration of 4 μg/ml was found to be sufficient for an effective combination with all three β-lactam agents. In both in vitro time-kill studies and an in vivo model 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.

[Effect of diet on the pharmacokinetics of tebipenem pivoxil fine granules in healthy male volunteers].

Tebipenem pivoxil (TBPM-PI), a novel oral carbapenem antibiotic, is a prodrug of tebipenem (TBPM). We assessed the pharmacokinetics of TBPM-PI fine granules at 250 mg as potency in healthy male volunteers in fasting and non-fasting states. Cmax of TBPM in the non-fasting state was lowered to approximately 60% of that in the fasting state, however AUC(0-infinity) and urinary excretion of TBPM in the non-fasting state were almost equivalent to those in the fasting state when TBPM-PI fine granules were administered.

Pharmacokinetic and pharmacodynamic properties of biapenem, a carbapenem antibiotic, in rat experimental model of severe acute pancreatitis.

Objectives: It is known that prophylaxis with imipenem reduces the risk of infection accompanying severe acute pancreatitis. In this study,we modified a rat experimental model of severe acute pancreatitis for antibiotic evaluation, and the effect of biapenem was compared with that of imipenem to determine the usefulness of biapenem.

Methods: Severe acute pancreatitis was induced by 5% sodium taurocholate.

CP5484, a novel quaternary carbapenem with potent anti-MRSA activity and reduced toxicity.

A new series of 1beta-methyl carbapenems possessing a 6,7-disubstituted imidazo[5,1-b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus was prepared, and the activities of these compounds against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. To study the effect of basic moieties on anti-MRSA activity, we introduced an amino, or imino, or amidino group at the 6-position of imidazo[5,1-b]thiazole in place of the carbamoylmethyl moiety of CP5068. Anti-MRSA activities of almost all basic group-substituted carbapenems were improved, though some of the compounds showed stronger acute toxicity in mice than IPM.

In vitro short-time killing activity of povidone-iodine (Isodine Gargle) in the presence of oral organic matter.

In order to estimate the clinical efficacy of a povidone-iodine oral antiseptic (PVP-I) on oral bacterial infectious diseases, we studied the effect of oral organic matter on the in vitro killing activity of PVP-I. In addition, we compared the in vitro short-time killing activity of PVP-I with those of other oral antiseptics using mouth-washing and gargling samples collected from healthy volunteers. When any of the mouth-washing and gargling samples was used, the standard (0.

[Antimicrobial activity of fosfomycin under various conditions against standard strains, beta-lactam resistant strains, and multidrug efflux system mutants].

The purpose of this study was to evaluate the possible benefit of fosfomycin (FOM) as prophylactic antibiotic in terms of antimicrobial activity and the potential of inducibility of beta-lactamase, compared with cefazolin, cefotiam, cefmetazole, and piperacillin that are commonly used as perioperative agents. The in vitro activity of FOM against aerobic Gram-negative bacteria using Mueller-Hinton agar or nutrient agar supplemented with glucose-6-phosphate (G6P) as tested medium increased within a range from 2 to 256 times the activity in the medium without G6P. However, the susceptibility of Gram-positive bacteria to FOM remained largely unchanged with or without G6P.

[Combined effects of arbekacin with biapenem against in vitro and in vivo model of a mixture of MRSA and Pseudomonas aeruginosa].

Combined effects of arbekacin (ABK) with biapenem (BIPM) were examined on both in vitro and in vivo model of a mixture of MRSA and Pseudomonas aeruginosa. As a result, significant effect in vitro was observed in combined use of ABK (1/2 MIC) with BIPM (1/4 and 1/2 MIC) against MRSA as compared with ABK or BIPM alone. Against P.

Optimization of dose and dose regimen of biapenem based on pharmacokinetic and pharmacodynamic analysis.

Pharmacokinetic and pharmacodynamic (PK/PD) parameters, which are important indices of the therapeutic efficacy of antimicrobials, and the minimum inhibitory concentration (MIC) predictive of clinical efficacy at common clinical doses, were examined for biapenem (BIPM; 300 mg b.i.d.

[Activity of fosfomycin against Escherichia coli O157:H7--morphological changes and production of Shiga toxins].

We examined the effects of fosfomycin (FOM), norfloxacin (NFLX), kanamycin (KM), chloramphenicol (CP), and ampicillin (ABPC) on the morphology of E. coli O157:H7, and the accumulation (cell fraction) and release (medium fraction) of Shiga toxins (Stxs: Stx1 and Stx2) in E. coli O157:H7 three hours after treatment with the antibiotics.

[Bactericidal activity of biapenem against various efflux system mutants of Pseudomonas aeruginosa].

The bactericidal activity of biapenem, a new carbapenem, against various efflux-mutants of Pseudomonas aeruginosa was compared with those of imipenem, panipenem, meropenem and ceftazidime. The bactericidal activity of biapenem against P. aeruginosa KG5001, a strain deficient in MexAB-OprM, MexCD-OprJ and MexXY-OprM, was very strong compared with those of imipenem and meropenem.