hr-810 and Gram-Negative-Bacterial-Infections

Cefpirome is a fourth-generation cephalosporin with good activity against both gram-positive and gram-negative bacteria. A multicentre trial was performed to study the efficacy and safety of cefpirome 2 g twice daily in the treatment of sepsis. Sixty-three cases were recruited from 10 hospitals from April 1996 to January 1998. Fifty seven cases could be evaluated according to the protocol. The APACHE II score was used to measure severity of illness, with 46.9 per cent of patients having APACHE II score more than 10 and two patients more than 20; both were cured. The most common pathogens were gram-negative bacteria with E. coli predominating 16/40 (40.0%), followed by Klebsiella 8/40 (20.0%). The overall clinical success rates were 54 out of 57 patients (94.7%). In patients with positive blood culture, the clinical cures were achieved for 20/22 (90.9%). Cefpirome showed good efficacy and safety in the empirical treatment of suspected bacteremia or sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Cefpirome; Cephalosporins; Drug Administration Schedule; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Treatment Outcome

In an international, multicenter, open-label, randomized comparative study, adult patients in intensive care units were enrolled to receive cefpirome intravenously at 2 g twice daily or ceftazidime intravenously at 2 g three times daily for the empiric treatment of pneumonia. Randomization was performed after a double stratification according to the investigator's initial choice of monotherapy or combination therapy and then on the basis of the severity of disease. The primary endpoint was the clinical response at the end of treatment in the intent-to-treat population. Data for all patients were reviewed by a blinded observer. Of the 400 enrolled patients, 201 received cefpirome (monotherapy, 56%) and 199 received ceftazidime (monotherapy, 51%). Pneumonia was hospital acquired for 75% of the patients. Clinical failures rates were 34 versus 36% (odds ratio = 0.922; upper bound of 90% confidence interval = 1.301) in the intent-to-treat analysis for cefpirome and ceftazidime, respectively. For the cefpirome and ceftazidime groups, there were 35 versus 30% clinical failures among monotherapy-stratified patients, respectively, and 34 versus 42% clinical failures among combination therapy-stratified patients, respectively. The rates of clinical failures in the per-protocol analysis were 38 and 42%, respectively. In the population of patients evaluable for bacteriologic efficacy, eradication or presumed eradication was obtained for 71% (172 of 241) and 70% (162 of 230) of the pathogens isolated from the patients receiving cefpirome and ceftazidime, respectively. The mortality rates within 2 weeks after the end of treatment were similar (cefpirome group, 31%; ceftazidime group, 26%), as were the percentages of patients with at least one treatment-related adverse event (17 and 19%, respectively). An empiric treatment strategy with cefpirome at 2 g twice daily is equivalent in terms of efficacy and tolerance to ceftazidime at 2 g three times daily for the treatment of pneumonia in patients in intensive care units.

Topics: Adult; Cefpirome; Ceftazidime; Cephalosporins; Critical Care; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Drug Tolerance; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Pneumonia, Bacterial; Prospective Studies; Treatment Outcome

In an open, randomized multiclinic trial, hospitalized patients with upper or complicated lower urinary tract infections requiring treatment with a parenteral antibiotic were randomized to receive 1 g doses of cefpirome (594 patients) or ceftazidime (303 patients) 12 hourly for at least five days. Cefpirome was considerably more active in vitro than ceftazidime against Gram-positive pathogens isolated from the urine samples. At the early follow-up, 2-15 days after treatment, clinical cure was achieved in 86% and 82% of the patients in the cefpirome and ceftazidime groups respectively. Elimination of the causative pathogen without recurrence or early reinfection was achieved in 87% of the patients in both groups. Drug related adverse events occurred in 8.9% of cefpirome treated patients and in 4.6% of those receiving ceftazidime. No specific type of adverse reaction accounted for this difference. Treatment was discontinued because of adverse events in 2.5% and 1.7% of the patients respectively. Cefpirome was found to be safe and at least as effective as ceftazidime for the treatment of urinary tract infections in hospitalized patients.

Topics: Cefpirome; Ceftazidime; Cephalosporins; Drug Administration Schedule; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Urinary Tract Infections

To develop a population pharmacokinetics model for cefpirome in ICU patients, to assess pharmacokinetic-pharmacodynamic profiles vs. MIC distribution of likely ICU pathogens, and to assess their expected cumulative fraction of response (CFR).. Prospective observational study in a multidisciplinary ICU.. Twelve patients received 2g cefpirome intravenously over 12h. Thirteen blood samples were taken on two occasions. Demographic and creatinine clearance data were collected. Based on the final covariate model obtained using NONMEM, Monte Carlo simulations were undertaken to simulate free-drug concentrations for two administration methods: intermittent bolus administration (IBA) and continuous infusion (CI) with a loading dose of 0.5 g. Concentration-time profiles were evaluated by the probability of achieving free-drug concentrations above the MIC for more than 65% of dosing interval. Using MIC distributions from the EUCAST programme the CFR for each method was evaluated. A three-compartment model with zero-order input best described the concentration-time data. The CFR for Escherichia coli and Klebsiella spp. was greater than 97% in all IBA and CI doses but for Pseudomonas aeruginosa, and Acinetobacter spp. achieved target concentrations of 56% and 46%, respectively. High-dose CI cefpirome (6g/day) for P. aeruginosa and Acinetobacter spp. was required to achieve CFR of 89%.. Measured creatinine clearance appears to be a good marker of cefpirome clearance and potentially could be used to individualise cefpirome therapy. When given as IBA or CI for E. coli and Klebsiella spp., cefpirome should be successful. Cefpirome fails to achieve the bactericidal target even when administered at high-doses such as 6g/day for P. aeruginosa and Acinetobacter spp. Prospective clinical studies are needed to conclusively validate these findings.

Topics: Adult; Aged; Anti-Bacterial Agents; Cefpirome; Cephalosporins; Creatinine; Critical Illness; Dose-Response Relationship, Drug; Female; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Intensive Care Units; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Monte Carlo Method

The in vitro activities of new expanded spectrum of fourth-generation cephalosporins, cefepime and cefpirome, were compared with those of three third-generation cephalosporins, cefoperazone, ceftazidime, and ceftriaxone, that are commonly used in the treatment of serious infections caused by aerobic gram-negative bacteria. The agar dilution method described by the US National Committee for Clinical Laboratory Standards was used to determine the minimum inhibitory concentrations of antibiotics tested. 302 clinical isolates, representing a cross-section of Klebsiella and Enterobacter species and Pseudomonas aeruginosa were tested. Cefepime was considerably more active than other antibiotics tested, against Klebsiella species and Enterobacter species, and demonstrated activity similar to ceftazidime against Pseudomonas aeruginosa. Ceftazidime was active against Pseudomonas aeruginosa but was less potent against Enterobacter species. Cefoperazone and ceftriaxone were less active than ceftazidime against Pseudomonas aeruginosa. Cefepime had slightly greater activity than cefpirome against the gram-negative bacteria tested. However, cefepime and cefpirome were found to be highly active against many resistant organisms that traditionally have been difficult to treat.

Topics: Cefepime; Cefpirome; Cephalosporins; Cross Infection; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests

In vitro activities of cefepime and cefpirome against 96 isolates of Chryseobacterium indologenes and 21 of C. meningosepticum were determined by the agar dilution method. Overall, cefepime was more active than cefpirome against C. indologenes (MIC at which 50% of the isolates were inhibited [MIC50] and MIC90, 4 and 16 microg/ml, respectively, for cefepime and 8 and 128 microg/ml, respectively, for cefpirome). Both agents had poor potency against C. meningosepticum (MIC50 and MIC90, 64 and >256 microg/ml, respectively, for cefepime and 128 and >256 microg/ml, respectively, for cefpirome).

Topics: Cefepime; Cefpirome; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Flavobacterium; Gram-Negative Bacterial Infections; Humans; In Vitro Techniques; Microbial Sensitivity Tests

Topics: Adult; Ascitic Fluid; Cefpirome; Cephalosporins; Diffusion; Female; Gram-Negative Bacterial Infections; Humans; Injections, Intravenous; Liver Cirrhosis; Male; Middle Aged