hr-810 and Streptococcal-Infections

In this study, we evaluated the current effectiveness of 11 beta-lactam antibiotics for treatment of orofacial odontogenic infections by determining the antimicrobial susceptibility of the major pathogens. The antimicrobial susceptibilities of viridans streptococci (n = 47), Peptostreptococcus (n = 67), Porphyromonas (n = 18), Fusobacterium (n = 57), black-pigmented Prevotella (n = 59) and non-pigmented Prevotella (n = 47) isolated from pus specimens of 93 orofacial odontogenic infections to penicillin G, cefmetazole, flomoxef, cefoperazone, cefoperazone/sulbactam, ceftazidime, cefpirome, cefepime, cefoselis, imipenem and faropenem were determined using the agar dilution method. Penicillin G, most cephalosporins, imipenem and faropenem worked well against viridans streptococci, Peptostreptococcus, Porphyromonas and Fusobacterium. Penicillin G and most cephalosporins, including fourth-generation agents, were not effective against beta-lactamase-positive Prevotella, though they were effective against beta-lactamase-negative strains. Cefmetazole, cefoperazone/sulbactam, imipenem and faropenem expressed powerful antimicrobial activity against beta-lactamase-positive Prevotella. In conclusion, penicillins have the potential to be first-line agents in the treatment of orofacial odontogenic infections. Most of the other beta-lactam antibiotics, including fourth-generation cephalosporins, were not found to have greater effectiveness than penicillins. In contrast, cefmetazole, cefoperazone/sulbactam, imipenem and faropenem were found to have greater effectiveness than penicillins.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteroidaceae Infections; beta-Lactams; Cefepime; Cefmetazole; Cefoperazone; Cefpirome; Ceftazidime; Ceftizoxime; Cephalosporins; Drug Resistance, Bacterial; Drug Therapy, Combination; Fusobacterium; Fusobacterium Infections; Gram-Positive Bacterial Infections; Humans; Imipenem; Lactams; Microbial Sensitivity Tests; Mouth Diseases; Penicillin G; Penicillins; Peptostreptococcus; Porphyromonas gingivalis; Prevotella; Streptococcal Infections; Streptococcus; Sulbactam

Topics: Cefpirome; Cephalosporins; Drug Therapy, Combination; Enterococcus faecalis; Gentamicins; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Streptococcal Infections; Streptococcus

In systemic and local infections, the therapeutic efficacy of cefpirome was compared to that of imipenem and cefotaxime. Murine septicemia induced with methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains responded well to cefpirome and imipenem therapy, the ED50 values ranged from 0.8 to 28.40 mg/kg and 0.5 to 15.58 mg/kg, respectively. The carbapenem also displayed high efficacy against Enterococci and was more potent than cefpirome. Cefotaxime, however, exhibited lower activity or proved to be inactive against these strains. With ED50 values of 0.03 to 31.33 mg/kg, cefpirome was the most active of the three antibiotics in protecting mice challenged with Enterobacteriaceae. The corresponding ED50 values of imipenem and cefotaxime ranged from 0.72 to 70.95 mg/kg and 0.06 to 66.30 mg/kg, respectively. Despite distinctly lower in vitro activity against the infecting organism, cefpirome showed efficacy similar to imipenem in the treatment of subcutaneous S. aureus abscesses in mice. It was more effective than imipenem and cefotaxime against experimental Klebsiella pneumonia in mice and the Escherichia coli infected granuloma pouch in rats.

Topics: Abscess; Animals; Bacterial Infections; Cefotaxime; Cefpirome; Cephalosporins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Granuloma; Imipenem; Male; Mice; Mice, Hairless; Mice, Inbred C3H; Pneumonia; Rats; Rats, Inbred Strains; Sepsis; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections

With cefpirome (HR 810) the MICs for both methicillin-resistant Staphylococcus aureus (MRSA) and for Streptococcus faecalis were 8.0 mg/l. At 4 x MIC, cefpirome killed MRSA as rapidly as did vancomycin while for enterococci, cefpirome, vancomycin or ampicillin alone were not bactericidal. However, all agents were bactericidal when combined with 2 mg/l of gentamicin, although gentamicin combined with cefpirome showed a smaller decrease in cfu/ml than the combination with ampicillin or vancomycin. A mouse thigh infection model was developed in which the thigh muscle was infected with bacteria and either no therapy or concurrent antibiotic therapy was initiated. On the subsequent day, the entire thigh muscle was quantitatively cultured. In this model, the numbers of enterococci at the infection site at 24 h were reduced by 2.1 logs with no treatment, 2.6 with cefpirome (25 mg/kg/day), 2.8 with ampicillin (150 mg/kg/day), and 2.7 with vancomycin (25 mg/kg/day). For MRSA the reductions were 1.1 logs with no therapy, 2.8 with vancomycin, and 3.0 with cefpirome. The apparent enhanced in-vivo activity of cefpirome for MRSA argues for further evaluation of this antibiotic for treatment of MRSA and other Gram-positive cocci, including enterococci.

Topics: Aminoglycosides; Ampicillin; Animals; Anti-Bacterial Agents; Cefpirome; Cephalosporins; Enterococcus faecalis; Methicillin; Mice; Microbial Sensitivity Tests; Penicillin Resistance; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections

HR 810 or cefpirome is a new amino thiazole cephalosporin whose specific characteristic is a cyclopentenopyridinium group in position 3 of the cephem nucleus. This structure is responsible for a broad spectrum of activity, covering Enterobacteriaceae, including cephalosporinase-producing Enterobacter spp. and Citrobacter spp., Staphylococcus aureus, Pseudomonas aeruginosa and group D Streptococci.

Topics: Animals; Bacterial Infections; Cefpirome; Cephalosporins; Citrobacter; Enterobacter; Enterobacteriaceae; Enterococcus faecalis; Klebsiella Infections; Male; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Salmonella Infections, Animal; Salmonella typhimurium; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes