In vitro and in vivo antibacterial activities of OPC-20011, a novel parenteral broad-spectrum 2-oxaisocephem antibiotic.

Abstract

OPC-20011, a new parenteral 2-oxaisocephem antibiotic, has an oxygen atom at the 2- position of the cephalosporin frame. OPC-20011 had the best antibacterial activities against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae: MICs at which 90% of the isolates were inhibited were 6.25, 6.25, and 0.05 microg/ml, respectively. Its activity is due to a high affinity of the penicillin-binding protein 2' in MRSA, an affinity which was approximately 1,050 times as high as that for flomoxef. Against gram-negative bacteria, OPC-20011 also showed antibacterial activities similar to those of ceftazidime. The in vivo activities of OPC-20011 were comparable to or greater than those of reference compounds in murine models of systemic infection caused by gram-positive and -negative pathogens. OPC-20011 was up to 10 times as effective as vancomycin against MRSA infections in mice. This better in vivo efficacy is probably due to the bactericidal activity of OPC-20011, while vancomycin showed bacteriostatic activity against MRSA. OPC-20011 produced a significant decrease of viable counts in lung tissue at a dose of 2.5 mg/kg of body weight, an efficacy similar to that of ampicillin at a dose of 10 to 20 mg/kg on an experimental murine model of respiratory tract infection caused by non-ampicillin-susceptible S. pneumoniae T-0005. The better therapeutic efficacy of OPC-20011 was considered to be due to its potent antibacterial activity and low affinity for serum proteins of experimental animals (29% in mice and 6.4% in rats).

• Authors: M Matsumoto, H Tamaoka, H Ishikawa, M Kikuchi
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 42 Issue 11 Pg. 2943-9 (Nov 1998) ISSN: 0066-4804 [Print] United States
• PMID: 9797230 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Blood Proteins
• Carrier Proteins
• Lactams
• OPC 20011
• Penicillin-Binding Proteins
• Peptidyl Transferases
• Hexosyltransferases
• Muramoylpentapeptide Carboxypeptidase

Topics

• Animals
• Anti-Bacterial Agents (metabolism, pharmacology)
• Bacteria (drug effects)
• Bacterial Infections (drug therapy)
• Bacterial Proteins
• Blood Proteins (metabolism)
• Carrier Proteins (metabolism)
• Hexosyltransferases
• Lactams
• Male
• Mice
• Mice, Inbred ICR
• Microbial Sensitivity Tests
• Muramoylpentapeptide Carboxypeptidase (metabolism)
• Penicillin-Binding Proteins
• Peptidyl Transferases
• Rats
• Rats, Sprague-Dawley