In Vivo Pharmacodynamics of β-Lactams/Nacubactam against Carbapenem-Resistant and/or Carbapenemase-Producing and in Murine Pneumonia Model.

Carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) have become global threats. CRE- and CPE- derived infections have been associated with high mortality due to limited treatment options. Nacubactam is a β-lactamase inhibitor and belongs to the new class of diazabicyclooctane.

Pharmacodynamic evaluation of meropenem, cefepime, or aztreonam combined with a novel β-lactamase inhibitor, nacubactam, against carbapenem-resistant and/or carbapenemase-producing Klebsiella pneumoniae and Escherichia coli using a murine thigh-infection model.

Background: Carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) are difficult to treat and are a serious public health threat. Nacubactam (NAC) is a novel non-β-lactam diazabicyclooctane β-lactamase inhibitor with in vitro activity against some Enterobacterales expressing classes of β-lactamases.

Methods: The antimicrobial efficacy of meropenem (MEM), cefepime (FEP), and aztreonam (ATM), each in combination with NAC, were assessed in vitro and in vivo against Klebsiella pneumoniae and Escherichia coli.

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.

Prediction of clinical bacteriological efficacy of oral antibiotics using a mechanism-based pharmacokinetic-pharmacodynamics modeling.

The objective of this study was to predict the clinical bacteriological efficacy of antibiotics and to examine the pharmacodynamics (PD) characteristics of antibiotics against bacterial strains using a mechanism-based pharmacokinetic-pharmacodynamics (PK-PD) modeling developed on the basis of interaction between drug concentrations and antibacterial activities. Dynamic PD parameters (epsilon, gamma, EC50) and growth rate of organisms (lambda) were obtained from in vitro time-kill profile data of oral antibiotics, tebipenem pivoxil (TBPM-PI) and cefditoren pivoxil (CDTR-PI) against Streptococcus pneumoniae or Haemophilus influenzae. PD characteristics of both drugs against S.

New concept and a theoretical consideration of the mechanism-based pharmacokinetics/ pharmacodynamics (PK/PD) modeling for antimicrobial agents.

Pharmacodynamic (PD) characterization (concentration-dependent, time-dependent, etc.) of antibiotics is determined by aspects of the pharmacodynamic interaction between antibiotics and microorganisms. There are three major aspects of the pharmacodynamic interaction between antibiotics and microorganisms; 1) the minimum drug concentration required for the exhibition of antibacterial activity (MIC: minimum inhibitory concentration, MBC: minimum bactericidal concentration, etc.

Therapeutic effect of ME1036 on endocarditis experimentally induced by methicillin-resistant Staphylococcus aureus.

The efficacy of ME1036, a novel parenteral carbapenem, was compared with that of vancomycin by using a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. Compared with vancomycin, ME1036 reduced the bacterial counts in the vegetations at a lower dosage or over a shorter period of administration when it was used for the treatment of MRSA endocarditis.