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Cefoperazone was compared with clindamycin plus gentamicin for the treatment of pelvic infections. Of 102 women, 95 (93%) demonstrated a good clinical response (47 with cefoperazone and 48 with clindamycin plus gentamicin). Of the seven failures, four were secondary to side effects and three were clinical failures.
Certain beta-lactams have been shown to increase the clearance of tobramycin. We evaluated the pharmacokinetics of cefoperazone and tobramycin, alone and in combination, in healthy volunteers. No significant alteration in pharmacokinetic behavior was noted for cefoperazone or tobramycin alone or in combination.
Two groups of 10 healthy ambulatory subjects, i.e., a group of 10 persons less than or equal to 30 years of age (mean age, 27.6 years) and a group of 10 persons greater than or equal to 65 years of age (mean age, 70 years), were randomized in a single-trial crossover design to receive 1 and 2 g of cefoperazone with a 1-week washout between doses. The elderly subjects had both decreased estimated creatinine clearances and decreased albumin concentrations in serum. Cefoperazone concentrations in serum of elderly persons were significantly higher at each interval from 30 min to 6 h for the 2-g dose. Compared with that in younger persons, the total clearance in elderly subjects was significantly lower for both the 1- and 2-g doses, the renal clearance was significantly lower for the 2-g dose, and the area under the curve was significantly higher for the 2-g dose in the elderly persons. The half-life at beta phase was higher in the elderly persons at both the 1- and 2-g doses but not significantly so. Changes in total clearance and area under the curve and higher levels in serum in the elderly persons suggest a longer duration of antimicrobial activity in this age group.
The apparent diffusion coefficient of a bound drug, cefoperazone, was studied. The protein binding of cefoperazone was studied by voltammetry, a technique which permitted instant measurements. The apparent diffusion coefficients were similar in agar and fibrin and lower in rat brain tissue. The influence of protein on the value of the apparent diffusion coefficient was negligible. The hypothesis that only the free drug diffuses was supported. The percentage of binding determined by voltammetry corresponded to the true concentration of drug which diffuses and is much lower than the percentage of binding determined by the ultrafiltration centrifugation method. This discrepancy could be explained by the rate of dissociation of the protein-drug complex.
By the agar dilution checkerboard method, striking synergy between cefoperazone and imipenem was observed with 32 strains of methicillin-resistant Staphylococcus aureus (fractional inhibitory concentration indices, < or = 0.03 to 0.34; mean, 0.12 +/- 0.08). By the double-disk diffusion method, the synergy was confirmed, but about 60% of strains showed antagonism manifest by truncation of the zone of inhibition around cefoperazone. The mechanism may involve auxiliary factors distinct from those essential for the expression of methicillin resistance.
At sites of neutrophilic inflammation, tissue injury by neutrophil elastase is favored by phagocyte-induced hypochlorous acid-dependent inactivation of the natural elastase inhibitor alpha(1)-antitrypsin. In the present study, cefoperazone prevented alpha(1)-antitrypsin inactivation by neutrophils and reduced the recovery of hypochlorous acid from these cells. Moreover, the antibiotic reduced the free elastase activity in a neutrophil suspension supplemented with alpha(1)-antitrypsin without affecting the cells' ability to release elastase. These data suggest that the drug inactivates hypochlorous acid before its reaction with alpha(1)-antitrypsin, thereby permitting the antiprotease-mediated blockade of released elastase. In conclusion, cefoperazone appears to have the potential for limiting elastase-antielastase imbalances, attenuating the related tissue injury at sites of inflammation.
Cefoperazone disk diffusion test and minimum inhibitory concentration comparison studies were performed on 421 recent bacterial isolates, using 30- and 75-micrograms commercially prepared disks. Acceptable correlation coefficients (-0.82 to -0.86) and very major (false-susceptible) interpretive error rates (less than 1%) were obtained with both disk concentrations. The interpretive criteria for both disks were identical. Using the preferred 75-micrograms disk, the Thornsberry et al. criteria (J. Clin. Microbiol. 15:769-776, 1982) of greater than or equal to 18 mm = susceptible (less than or equal to 32 micrograms/ml) and less than or equal to 14 mm = resistant (greater than 64 micrograms/ml) resulted in only 5.5% of strains having indeterminate-range zone diameters; the 30-micrograms disk had 6.9% of strains with indeterminate zone diameters. The 75-micrograms disk, excluding the testing of enterococci, minimized the very major and other interpretive errors to less than 5%. Larger zone diameters will contribute few technical problems with either disk concentration. Data from 1,320 zone diameters submitted for each quality control strain indicated no significant (P greater than 0.05) difference between disks made by the three major manufacturers, and consistent results were obtained within each laboratory with numerous lots of Mueller-Hinton agar (except for one manufacturer). Individual daily test and accuracy quality control ranges were calculated from clinical investigator laboratory data at 16 hospitals based on mean zone sizes and from an additional 8 laboratories with both mean and median calculations. The quality control data were nearly identical, and ranges calculated by the two methods were very similar. Susceptibility tests of Pseudomonas aeruginosa indicate that the cefoperazone disk or minimum inhibitory concentration test would accurately predict P. aeruginosa susceptibility test results for other pseudomonas-active cephalosporins (cefsulodin and ceftazidime), thus producing no very major interpretive errors.
The optimum method for isolating Campylobacter upsaliensis from stools has not been clearly defined. In a preliminary study, cefoperazone amphotericin teicoplanin (CAT) selective medium isolated six C. upsaliensis strains which were not detected using modified cefoperazone charcoal deoxycholate (mCCDA). In order to identify the factors that underlie the superiority of CAT over mCCDA for isolating C. upsaliensis, we examined the effect of incubation time and antibiotic content of culture media on the growth of C. upsaliensis isolates using semiquantitative methods. The recovery of a subgroup of C. upsaliensis isolates from seeded stool specimens was also evaluated. Differences in growth of C. upsaliensis on CAT and mCCDA were modest and were not explained by the antibiotic profiles of the two media. Recovery of C. upsaliensis from spiked human feces on CAT was superior to that on mCCDA at lower concentrations of organisms (10(3) CFU/ml). We conclude that although CAT is more suitable than mCCDA for the isolation of C. upsaliensis from stools, the superiority of CAT for detecting this organism is not accounted for by the antibiotic composition of the medium.
A new selective medium, cefoperazone MacConkey agar (CMA), was developed for primary isolation of Laribacter hongkongensis from stool. Its performance in quantitative recovery and in a clinical evaluation of 4,741 human diarrheal stool specimens was superior to that of charcoal cefoperazone deoxycholate agar. In addition, with CMA, Arcobacter butzleri was unexpectedly isolated from the stools of six patients.
The recent emergence of spectinomycin resistant penicillinase producing Neisseria gonorrhoeae (PPNG) and the high prevalence of PPNG strains among the gonococcal isolates in Seoul represent a grave challenge to the programme for controlling sexually transmitted disease (STD). Fifty men with uncomplicated gonococcal urethritis caused by PPNG strains were treated with a single intramuscular injection of 1 g cefoperazone. Forty two patients were followed up. All patients recovered including three who became reinfected and required further treatment. Two patients (4.8%) developed postgonococcal urethritis (PGU). The MIC90 of cefoperazone measured by an agar dilution susceptibility test was 0.12 mg/l.
Forty patients with acute cholecystitis were divided into two randomized groups on the basis of the emergency antimicrobial therapy received, and were treated for a period of 5 days. The first group was given ceftriaxone (Rocephin), the second cefoperazone (Cefobis). This concomitant antimicrobial treatment of acute cholecystitis proved to be effective in 85% of the patients; 15% underwent 'à chaud' surgery on the 6th day because of a lack of response to the treatment. Ceftriaxone and cefoperazone proved to be equally effective. Use of ceftriaxone, however, was simpler (one injection a day) and the cost of treatment substantially lower.
Forty patients with leukemia or aplastic anemia were randomized to receive one of the following antibiotic regimens at the onset of fever during granulocytopenia: cefoperazone + amikacin (regimen A), cefoperazone + sisomicin (regimen B), cefotaxime + amikacin (regimen C), cefotaxime + sisomicin (regimen D). All patients were receiving gut decontamination at the time of randomization. Patients were monitored twice weekly with swabs and cultures for bacteria and fungi. Overall, there were 56 febrile episodes: 31 were proven bacterial, 3 were probable, and 16 were of unknown origin. Response rates were comparable in all 4 treatment regimens: 90%, 91%, 92% and 92%, respectively. Three patients died of bacterial infections (2 Gram+, 1 Gram-), one patient died with probable infection, 6 febrile episodes were related to fungal infection (Candida), and 2 patients died. The mortality rate was comparable in all groups. Two patients died of renal failure. Abnormalities in liver function tests were observed, but were without consequences. There were no statistical differences in renal-hepatic toxicity in the 4 arms.
A number of recent articles have reviewed the problem of hypoprothrombinemia and bleeding associated with antibiotic therapy. We report three cases in which bleeding is believed to be related to a prolonged prothrombin time secondary to cefoperazone therapy. Reports of coagulopathies such as these are increasing in number and call attention to the need to monitor the prothrombin time during cefoperazone therapy.
The stability and compatibility of clindamycin phosphate admixed with four beta-lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial-fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours.
The antibacterial activity of tazobactam-piperacillin was compared with that of sulbactam-ampicillin, clavulanic acid-ticarcillin, sulbactam-cefoperazone and piperacillin against beta-lactamase-producing bacteria isolated from patients with complicated urinary tract infections. Tazobactam-piperacillin showed a broad antibacterial spectrum against gram-negative and gram-positive bacteria. The minimum inhibitory concentrations (MIC90) of tazobactam-piperacillin were 6.25 micrograms/ml against Escherichia coli, 1.56 micrograms/ml against Proteus mirabilis, 3.13 micrograms/ml against Proteus vulgaris, 6.25 micrograms/ml against methicillin-susceptible Staphylococcus aureus, and 6.25 micrograms/ml coagulase-negative methicillin-susceptible staphylococci. Against all beta-lactamase-producing bacteria tested the antibacterial activity of tazobactam-piperacillin was at least 4- to 64-fold stronger than that of piperacillin, clavulanic acid-ticarcillin, and sulbactam-ampicillin, and similar to or greater than that of sulbactam-cefoperazone except for E. coli.
A total of 40 strains of the B. fragilis group was isolated from clinical specimens in two hospital centers in Fortaleza from 1993 to 1997. The most frequently isolated species was Bacteroides fragilis (19 strains) and most isolates came from intra-abdominal and wound infections. The susceptibility profile was traced for cefoxitin, cefoperazone and ticarcillin-clavulanate by using the agar dilution reference method. All isolates were susceptible to ticarcillin-clavulanate (128/2 microg/ml). Resistance rates of 15 and 70% were detected to cefoxitin (64 microg/ml) and cefoperazone (64 microg/ml), respectively. Such regional results permit a better orientation in choosing this group of antibiotics for prophylaxis and therapy especially in relation to cefoxitin, which is frequently used in the hospital centers studied.
Major pancreatic infection is responsible for more than 80% of deaths in patients with acute pancreatitis. Therefore, the role of antimicrobial drugs in the prevention and treatment of secondary parcreatic infection is very important. The choice of antimicrobial drugs must be based upon the ability of the drug to exceed the therapeutic concentration in pancreas for the common pathogens. The penetration of ciprofloxacin and cefoperazone into pancreas was investigated in ten patients who had undergone pancreatoduodenectomy. The pancreatic juice was temporarily diverted to the exterior via a panoreatic duct catheter. The pancreatic tissue was obtained intraoperatively and pancreatic juice was drained postoperatively. The antimicrobial drug concentrations were determined by high-performance liquid chromatography. The concentrations of ciprofloxacin and cefoperazone in pancreatic juice were 44% and 17%, respectively, of those in serum, and exceeded the in vitro concentration (MIC-90) for most bacteria associated with pancreatic infections. The result indicates that ciprofloxacin and cefoprazone appear to be appropriate for both prophylaxis and therapy of secondary pancreatic infections.
Escherichia coli HX88108, which is resistant to cefoperazone(CPZ), was isolated from a severely infected patient. We studied genetical basis of beta-lactamase produced in E. coli HX88108 by pFL25, one of the recombinant plasmid of pFC. Largescale pFL25 plasmid was extracted, purified, and cleaved with restriction endonuclease EcoR I, Sal I, Pvu I, then subcloned into vector pUC19 as 1.9 kb, 0.9 kb, 0.65 kb fragments respectively. Recomminant plasmids were selected by alpha-complementation and determined by restriction endonuclease analysis. DNA sequencing was performed by the dideoxy polymerase chain termination method. Partial nucleotide sequence(1-78 nucleotide position) of the gene was found to be highly homologous (97%) with the gene coding for TEM-52 extended spectrum beta-lactamase of K. pneumonise, suggesting that the beta-lactamase coded by the cefoperazone resistant gene might be derived from TEM-type beta-lactamase.