hr-810 and Staphylococcal-Infections

Vancomycin is always the drug of choice for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in spite of his bactericidal kinetic.. The aim of this study was to evaluate in vivo the improvement of bactericidal kinetic of vancomycin associated with cefpirome against MRSA infection in critically ill patients.. The prospective cross-over study was carried out in 20 patients with severe pneumonia or bacteremia. There were randomized to receive vancomycin 2 g per day (Group 1, n = 10) or vancomycin with cefpirome 2 g x 2 (Group 2, n = 10). Clinical recovery, bacteriologic parameters (bactericidal kinetic and bactericidal power in vivo at the peak and the valley), duration of ventilation and stay in ICU were comparatively explored in both groups.. Clinical outcome did not significantly differ between Group 1 and 2. Bactericidal kinetics were better in the Group 2 (40% vs 60% after 6 hours to the dilution for 1/8e) but the difference was not significant. However, bactericidal power in sera was also better in the Group 2 with more bactericidal dilution at 1/16e (68% vs 88.8%: NS) and overall at 1/32e (10.5% vs 50%: p < 0.05) and CRP, an inflammatory marker, was significantly lower in the Group 2 than in the Group 1 (119.5 +/- 24 mg/l vs 198.6 +/- 78 mg/l: p < 0.05) on the third day.

Topics: Adult; Aged; Bacteremia; Cefpirome; Cephalosporins; Critical Care; Drug Therapy, Combination; Female; Humans; Male; Methicillin Resistance; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

Antibiotics not only support to alleviate the infections but also facilitate to avert the multiplication of microbes. Due to the irrational use of antibiotics, the resistance of antibiotics has been augmented which results may increase in morbidity and mortality with the span of time. World renowned regulatory bodies like Food and Drug Administration (FDA), Center of Disease Control and Prevention (CDC), and World Health Organization (WHO) vigorously advocate the surveillance of the resistance of antibiotics. During the present study by Kirby-Bauer disk diffusion method 141 clinical isolates of Staphylococcus aureus (n=47, 33.34%), Escherichia coli (n=54, 38.3%), Proteus species (n=26, 18.4%), and Klebsiella pneumoniae (n=14, 9.92%) are evaluated against cefepime and cefpirome which comes of fourth generation cephalosporin. It has been found that cefpirome has better bactericidal activity than cefepime against E. coli and K. pneumoniae while cefepime has been possessed better antibacterial activity against S. aureus and Proteus species which were isolated from respiratory tract infections, blood stream infection, intra-abdominal and urinary tract infections, and skin and soft tissue infections. K. pneumoniae, E. coli, Proteus species, and S. aureus were 34.8%, 26.3%, 11.3%, and 37.7% resistance against cefepime respectively. S. aureus, E. coli, K. pneumoniae, Proteus species has shown 41.4%, 21.7%, 17.6%, and 8.9% resistance against cefpirome correspondingly.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cefpirome; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; In Vitro Techniques; Intraabdominal Infections; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pakistan; Proteus; Proteus Infections; Respiratory Tract Infections; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus; Urinary Tract Infections

Infections caused by coagulase-negative staphylococci are becoming increasingly important, particularly those of nosocomial origin, as the organisms are frequently multi-resistant. New antimicrobial strategies are needed. The bactericidal activity of a combination of cefpirome with either vancomycin or teicoplanin against 12 strains of methicillin-resistant staphylococci with a decreased susceptibility to teicoplanin was determined in vitro by a time killing method. Strains Mu3 and Mu50 of Staphylococcus aureus were also studied. Cefpirome (0.125-0.5 x MIC) combined with vancomycin (0.25-1 x MIC) or teicoplanin (0.125-1 x MIC) acted synergically against 12 isolates over 18 h in most cases. A synergistic killing effect was also observed with the Mu3 and Mu50 strains of glycopeptide-intermediate S. aureus but over a longer period.

Topics: Anti-Bacterial Agents; Cefpirome; Cephalosporins; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Glycopeptides; Humans; In Vitro Techniques; Oxacillin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus haemolyticus

Topics: Anti-Bacterial Agents; Cefpirome; Cephalosporins; Colony Count, Microbial; Drug Resistance, Microbial; Drug Therapy, Combination; Gentamicins; Humans; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

A patient with intracerebral hematoma suffered from postoperative bacterial meningitis. Staphylococcus aureus was found from CSF. The organism was multiple drug resistant and refractory to antibiotics including piperacillin (PIPC), cephalexin (CEX), cefotaxime (CTX), ceftazidime (CAZ) and latamoxef (LMOX). It was susceptible to cefpirome (CPR). Treatment with CPR resulted in clinical improvement associated with clearing of the organism from CSF. Serum level of CPR was high enough and CPR penetration into the CSF was satisfactory. The results suggest that CPR is an extremely effective antibiotic for meningitis caused by CPR-susceptible bacteria. Evaluation of the CPR penetration into the CSF of adult meningitis was rarely reported. The result we obtained was important in the treatment for the adult meningitis.

Topics: Adult; Cefpirome; Cephalosporins; Female; Humans; Meningitis, Bacterial; Staphylococcal Infections; Time Factors

Results of in vitro time-kill synergy studies using subinhibitory, inhibitory, or suprainhibitory concentrations of bactericidal agents were compared with treatment outcomes of experimental infective endocarditis due to a methicillin-susceptible strain of Staphylococcus aureus. For rifampin-cephalosporin combinations, in vitro synergy testing using recommended fractions of the MIC failed to predict antagonism in vivo while concentrations above the MIC corresponded with antagonism in vivo.

Topics: Animals; Cefazolin; Cefpirome; Cephalosporins; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Endocarditis, Bacterial; Gentamicins; Microbial Sensitivity Tests; Nafcillin; Predictive Value of Tests; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Time Factors

The transferability of cefpirome (HR810, CPR) to cerebrospinal fluid (CSF) was studied employing rabbits with experimental meningitis caused by Staphylococcus aureus. The mean serum concentration was 362 +/- 6.63 micrograms/ml at 15 minutes after intravenous administration of the drug at a dose level of 100 mg/kg. The mean concentration in CSF was maximum at 60 minutes after administration, and the mean maximum concentration was 14.6 +/- 2.85 micrograms/ml. Pharmacokinetic parameters calculated from these values were as follows, Cmax (CSF/serum): 4.04%; AUC (CSF/serum): 5.14% between 15 and 60 minutes, 8.12% between 15 and 120 minutes and 10.4% between 15 and 180 minutes; T 1/2 for CPR in CSF: 154 minutes; T 1/2 (CSF/serum): 3.96. In comparison to those of other beta-lactam antibiotics which were obtained in the same way, the transferability of CPR was intermediate, but the peak CSF level was high, and in consideration of the antimicrobial potency against the main pathogens of meningitis, it appears worthwhile of running clinical trials for this drug.

Topics: Animals; Cefpirome; Cephalosporins; Disease Models, Animal; Injections, Intravenous; Meningitis; Rabbits; Staphylococcal Infections

Pharmacokinetics and clinical effects of cefpirome (CPR, HR 810) in children were studied. When 20 mg/kg and 40 mg/kg doses of CPR were administered to 4 children through 30 minutes' drip infusion, half-lives were 1.23 +/- 0.23 (mean +/- S.D.) hours and 1.37 +/- 0.35 (mean +/- S.D.) hours, respectively for the 2 dose levels, and recovery rates in urine in the first 6 hours after administration were 74.8% and 56.1%, respectively. CPR was administered to 15 cases (3 tonsillitis, 3 bronchitis, 5 bronchopneumonia, 1 acute cystitis, 1 coxoiliatitis, 1 otitis media, 1 otitis externa). The efficacy rate was 86.7%. Seven strains of bacteria were isolated and identified 4 Haemophilus influenzae, 3 Staphylococcus aureus, 1 Pseudomonas sp. from these cases. These bacteria in children were followed after administration of CPR. Six strains were eradicated and one was reduced in number. No adverse effects of CPR were observed except in 2 cases, one of which showed transient eosinophilia and the other showed a transient increase of transaminase. These results suggest that CPR may be an effective and safe drug to use on children clinically.

Topics: Absorption; Adolescent; Bacterial Infections; Cefpirome; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Female; Haemophilus Infections; Haemophilus influenzae; Half-Life; Humans; Infant; Male; Respiratory Tract Infections; Staphylococcal Infections

Cefpirome (HR 810) is a new cephalosporin with a 2,3-cyclopentenopyridine group in the 3-position side chain. It was compared with other cephem antibiotics in protective and therapeutic effects on various experimental infections, systemic and local, in mice and rats. HR 810 had more potent protective effect than ceftazidime (CAZ), cefoperazone (CPZ), and cefotaxime (CTX) on systemic infections induced by Escherichia coli Ec-31, Staphylococcus aureus SMITH, and Serratia marcescens Sm-6 in mice. Against systemic infection with Pseudomonas aeruginosa HR 810 was as effective as CAZ. Mice with leukopenia induced by cyclophosphamide were systemically infected with methicillin-resistant S. aureus (MRSA), methicillin-susceptible S. aureus (MSSA), Enterobacter cloacae, Acinetobacter calcoaceticus, and Enterococcus faecalis. HR 810 was superior to cefuzonam (CZON) and cefmetazole against MRSA and MSSA and was much more active than any other antibiotics tested against E. cloacae and A. calcoaceticus. In the activity against E. faecalis, HR 810 was inferior to ampicillin but superior to CZON. In mice with pyelonephritis caused by E. coli Ec-7, the rank order of activities was HR 810 greater than CAZ greater than CTX greater than CPZ. HR 810 was more effective than latamoxef, CAZ, CTX, and CPZ in improving lung infections induced by Streptococcus pneumoniae HL 438 and Klebsiella pneumoniae Kp-51 in mice. HR 810 was superior to CTX and CPZ and comparable to cefazolin in therapeutic effects on intrauterine infections with E. coli Ec-89 and S. aureus SMITH in rats.

Topics: Animals; Cefpirome; Cephalosporins; Escherichia coli; Female; Klebsiella Infections; Klebsiella pneumoniae; Lung Diseases; Male; Methicillin; Mice; Penicillin Resistance; Pseudomonas Infections; Pyelonephritis; Rats; Staphylococcal Infections; Staphylococcus aureus; Uterine Diseases

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