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PubMedDate not supplied

Cefoperazone for the treatment of infections in patients with cancer.

Cefoperazone was used for the treatment of 105 febrile episodes in 103 patients with cancer. A dose of 12 g/day was administered according to two different schedules, one for neutropenic patients (neutrophil count, less than 1,000/mm3), the other for nonneutropenic patients. The rate of response for 85 episodes of documented infection was 68%. The rates of response for patients with bacteremia and pneumonia were 72% and 41%, respectively; all patients with soft-tissue and urinary-tract infections responded. Fifty-five percent of patients infected with Pseudomonas aeruginosa, the most common gram-negative organism causing infection, responded to therapy. Among patients infected with Staphylococcus aureus, the most common gram-positive organism causing infection, 82% responded. As expected, the rate of response was higher for patients with adequate neutrophil counts. In neutropenic patients the overall response was good, particularly when the neutropenia resolved. However, the occasional occurrence of resistant strains of bacteria precludes the use of cefoperazone alone as initial therapy for neutropenic patients. Toxic adverse reactions, including drug-induced fever, diarrhea, and rash, occurred rarely and were transient. This study indicates that cefoperazone has low toxicity and is effective for the treatment of infections in patients with cancer.

Adult↗

PubMedDate not supplied

Treatment of typhoid fever and other systemic salmonelloses with cefotaxime, ceftriaxone, cefoperazone, and other newer cephalosporins.

Third-generation cephalosporins have been considered for the treatment of systemic salmonelloses because of emerging resistance among Salmonella species to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Twelve patients with typhoid/paratyphoid fever, nine with nontyphoid salmonella bacteremia, and two with Salmonella meningitis were treated with cefotaxime; one leukemic patient with Salmonella dublin bacteremia received ceftizoxime. All infections were cured except for one in a patient with sickle cell anemia; this patient's illness recurred but was cured with a second course of cefotaxime followed by ceftriaxone. A review of the literature documented cures with cefotaxime in 50 of 61 patients with typhoid/paratyphoid fever, all of four with salmonella osteomyelitis, 12 of 14 with salmonella meningitis, and 44 of 49 with non-typhoid salmonella bacteremia. Ceftriaxone and cefoperazone cured, respectively, 23 of 25 and 32 of 33 patients with typhoid/paratyphoid fever. The relapse rates of typhoid fever treated with cefotaxime, ceftriaxone, and cefoperazone were 6%, 4%, and 0%, respectively. Cefotaxime, ceftriaxone, and cefoperazone are acceptable alternative antibiotics for the treatment of salmonelloses caused by multiresistant organisms.

Adolescent↗

PubMed1986

In-vitro activity of cefoperazone-sulbactam against Bacteroides species.

The in-vitro activity of two combinations of sulbactam and cefoperazone against 187 strains of Bacteroides fragilis were evaluated; their activity was compared with that of the drugs alone, and correlated with the production of beta-lactamase by the bacterial strains. The results indicated that both combinations had a synergistic effect: the addition of 8 mg/l of sulbactam to the MIC of cefoperazone reduced the percentage of resistant strains from 58% to 0.5%; while the combination of two parts of cefoperazone to one pact of sulbactam lowered the resistance rate to 1%. Synergy was observed most frequently with beta-lactamase positive strains, but it also occurred among beta-lactamase negative strains.

Bacteria, Anaerobic↗

PubMed1989

The influence of cefoperazone, cefotaxime, ceftazidime and aztreonam on phagocytosis by human neutrophils in vitro.

The uptake and intracellular breakdown of Escherichia coli by human neutrophils was studied under the influence of cefoperazone, cefotaxime, ceftazidime and aztreonam. Non-opsonized as well as serum- and IgG-opsonized bacteria were used, and bacteria and neutrophils were exposed both separately before phagocytosis and together during uptake and in the postingestion phase. Preincubation of the neutrophils with the drugs stimulated their subsequent uptake of untreated serum-opsonized and non-opsonized E. coli in an antibiotic-free medium. With serum-opsonized bacteria this stimulating effect was reversed when the drugs were also present during phagocytosis. The uptake of IgG-opsonized bacteria was largely unaffected both after preincubation of the neutrophils and when the antibiotics were present during phagocytosis. With all four drugs, pre-exposure of bacteria before IgG-opsonization gave a much higher uptake than exposure after IgG-opsonization. Contrary to this, preincubation of the bacteria followed by serum-opsonization inhibited (cefotaxime, ceftazidime) or did not influence (cefoperazone, aztreonam) subsequent uptake in the absence of the drugs. The release of bacterial breakdown products from the cells in the postingestion phase was also inhibited by cefotaxime and ceftazidime after serum-opsonization. With non-opsonized and IgG-opsonized bacteria, however, a stimulation of intracellular breakdown was induced by the presence of these drugs during phagocytosis. Aztreonam and cefoperazone did not significantly influence this phase of phagocytosis. These observations suggest that the drugs bind to both neutrophils and bacteria in an individual manner and modify the binding and function of opsonins.

Anti-Bacterial Agents↗

PubMed1990

A randomized clinical study of cefoperazone and sulbactam versus gentamicin and clindamycin in the treatment of intra-abdominal infections.

This report summarizes the experience of investigators in four medical centres who compared the combination of cefoperazone/sulbactam against gentamicin/clindamycin in the treatment of intra-abdominal infections. One hundred and fifty-two patients were enrolled in the study and all were evaluable for safety and tolerance, 110 were evaluable for efficacy. Of the 76 patients (49 male, 27 female) treated with cefoperazone/sulbactam 66 (86.8%) were cured, five (6.6%) improved and five (6.6%) failed to respond to treatment. Of 34 patients treated with gentamicin/clindamycin, 21 (61.8%) were cured, four (11.8%) improved and nine (26.4%) failed. Cure rates for patients receiving cefoperazone/sulbactam were significantly higher than those of patients receiving gentamicin/clindamycin (P less than 0.006). Failures in both groups were attributable in part to pseudomonal and enterococcal infection and abscess formation. The addition of sulbactam to cefoperazone rendered cefoperazone-resistant organisms susceptible to cefoperazone in 11 of the 76 cases (14.4%) and thus permitted treatment with this agent. The present study confirms the safety and clinical efficacy of cefoperazone/sulbactam and suggests that this combination is a viable alternative to an aminoglycoside plus clindamycin for intra-abdominal infections.

Abdomen↗

PubMedDate not supplied

Factors affecting the analysis of cefoperazone in cerebral spinal fluid.

The measurement of cefoperazone concentrations in cerebral spinal fluid (CSF) is important to understanding the biodisposition and pharmacokinetic behavior of the drug. We have demonstrated that cefoperazone is unstable in methanol and at alkaline pH and these factors may affect the accurate quantitation of the drug in CSF. Buffering CSF samples with acetate is recommended to improve cefoperazone stability in CSF.

Cefoperazone↗

PubMed1985

Comparison of netilmicin with cefoperazone for the treatment of severe or complicated urinary tract infections.

A randomised trial was undertaken to compare the efficacy and safety of netilmicin and cefoperazone for the treatment of severe or complicated urinary tract infections. Thirty-two patients completed the study. Fifteen of 16 patients treated with netilmicin and nine of 16 treated with cefoperazone were cured. This difference was statistically significant (p = 0.037). No serious side effects or toxicity occurred with either drug, although five patients developed diarrhea after treatment with cefoperazone.

Acute Disease↗

PubMed1980

Comparative activities of the oxa-beta-lactam LY127935, cefotaxime, cefoperazone, cefamandole, and ticarcillin against multiply resistant gram-negative bacilli.

A total of 91 multiply resistant bacterial strains, including Klebsiella pneumoniae (32 strains), Pseudomonas aeruginosa (16 strains), and Serratia marcescens (43 strains), were collected during hospital epidemics of nosocomial infection from 1975 to 1979. These strains were resistant to gentamicin, tobramycin, cephalothin, chloramphenicol, and ampicillin. Their susceptibility to three new broad-spectrum beta-lactams, LY127935 (a 1-oxa-beta-lactam), cefotaxime (HR 756), and cefoperazone (T 1551), was compared with the susceptibility of random strains of nine species of aerobic gram-negative bacilli collected in the same hospital in 1979. Susceptibility to cefamandole and ticarcillin was also determined. Strains of staphylococci and streptococci from that hospital and two nearby city-county hospitals were also compared for the three new cephalosporins and other effective antibiotics. The agar dilution method was used to measure the minimum inhibitory concentration for each antibiotic. The multiply resistant strains (minimum inhibitory concentration for gentamicin >/= 8 mug/ml) usually were as susceptible to the three new broad-spectrum beta-lactams as were non-multiply resistant strains. Both Klebsiella pneumoniae and Serratia marcescens, including multiply resistant and non-multiply resistant strains, were most susceptible to the 1-oxa-beta-lactam LY127935 and cefotaxime. P. aeruginosa (both multiply resistant and non-multiply resistant strains) were most susceptible to cefoperazone. All three new beta-lactams were active against non-multiply resistant strains of Escherichia coli, Enterobacter spp., Proteus spp., and Citrobacter spp. Providencia stuartii were most susceptible to cefotaxime and the 1-oxa-beta-lactam LY127935. The three new beta-lactams were all less active against staphylococci (especially methicillin-resistant Staphylococcus aureus) than cephalothin. Streptococcus pyogenes and S. pneumoniae were very susceptible to cefotaxime and cefoperazone, though less susceptible to LY127935. None of the three new beta-lactams was active against S. faecalis. All were very active against both penicillinase-positive and -negative strains of Neisseria gonorrhoeae.

Bacteria↗

PubMed1980

In vitro antimicrobial activity of cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and other beta-lactam antibiotics against Neisseria gonorrhoeae and Haemophilus influenzae, including beta-lactamase-producing strains.

Minimum inhibitory concentrations and agar disk diffusion tests were determined on clinical isolates of beta-lactamase-positive and beta-lactamase-negative Neisseria gonorrhoeae and Haemophilus influenzae with the newer beta-lactam antibiotics, cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and piperacillin, and with seven older beta-lactam antibiotics. All the drugs were active against beta-lactamase-negative strains of N. gonorrhoeae and H. influenzae. The drug most active against beta-lactamase-positive N. gonorrhoeae was cefotaxime, followed closely by cefoperazone, moxalactam, piperacillin, and mezlocillin. The drugs most active against beta-lactamase-positive strains of H. influenzae were cefotaxime, moxalactam, cefoperazone, and cefamandole.

Azlocillin↗

PubMed1980

Susceptibilities of anaerobic bacteria to cefoperazone and other antibiotics.

Two hundred fifty clinical isolates of anaerobic bacteria were tested for suceptibility to cefoperazone, cefamandole, cefoxitin, carbenicillin, clindamycin, and chloramphenicol. Anaerobic gram-positive cocci were susceptible to all of the antibiotics tested. Clindamycin was the most active agent against Bacteroides species, followed by chloramphenicol and then cefoxitin. Cefoperazone was less active than cefoxitin and equal in activity to carbenicillin. Cefamandole was the least active antibiotic against Bacteroides. B. distasonis, B. vulgatus, B. thetaiotaomicron, and B. ovatus were more resistant to the antibiotics than B. melaninogenicus, B. oralis, or B. bivius. Clindamycin was the most active agent against Clostridium species, followed by chloramphenicol; the three cephalosporins and carbenicillin were about equal in activity. Clindamycin was the most active antibiotic against Fusobacterium species, followed by chloramphenicol, carbenicillin, and cefoperazone (which were about equally active) and then cefamandole.

Anti-Bacterial Agents↗

PubMed1980

In vitro activity of cefoperazone against nonfermenters and Aeromonas hydrophila.

The in vitro activity of cefoperazone against 380 strains (33 species and unnamed groups) of nonferenters and 20 strains of Aeromonas hydrophila was studied by a microdilution method of determining minimal inhibitory concentrations. For comparison, the activities of ampicillin, ticarcillin, and cefamandole were simultaneously studied. Cefoperazone was the most active drug against Pseudomonas sp., Achromobacter xylosoxidans, Flavobacterium meningosepticum. Flavobacterium sp. (group IIb), Group IVc biotype 2, Group Ve, and Aeromonas hydrophila. Against other organisms it was equivalent in activity to or less active than comparative antibiotics. The only organisms which were usually resistant to 128 microgram of cefoperazone per ml were strains of Flavobacterium odoratum and Group IIk biotype 1.

Aeromonas↗

PubMed1981

Pharmacokinetics of cefoperazone in normal volunteers and subjects with renal insufficiency.

We examined the pharmacokinetics of the new beta-lactam agent, cefoperazone, in normal and functionally anephric dialysis subjects with normal liver function. All subjects received 3 g of cefoperazone intravenously, and serial serum and urine samples were taken thereafter for up to 36 h. The serum levels, volume of distribution (0.22 liter/kg, normal; 0.19 liter/kg; dialysis), beta half-life (2.07 h, normal; 2.03 h, dialysis), and total body clearance (96.2 ml/min, normal; 92.9 ml/ min, dialysis) were all not significantly different between the two groups. Cefoperazone may be administered without adjustment of dose for any degree of renal dysfunction to patients with normal hepatic function.

Adult↗

PubMed1981

Bactericidal activity of cefoperazone with CP-45,899 against large inocula of beta-lactamase-producing Haemophilus influenzae.

Bactericidal activity of cefoperazone, alone and in combination with the beta-lactamase inhibitor CP-45,899, was tested against inocula of 10(7) colony-forming units of beta-lactamase-producing isolates of Haemophilus influenzae type b per ml. Of 19 strains tested, 10 required greater than or equal to 64 microgram of cefoperazone per ml for killing, whereas no strains were killed by less than 64 microgram of CP-45,899 per ml. Synergy occurred with the combination of 4 microgram of each agent per ml against 9 of the 10 cefoperazone-resistant strains.

Anti-Bacterial Agents↗

PubMed1982

Pharmacokinetics and bacteriological efficacy of cefoperazone, ceftriaxone, and moxalactam in experimental Streptococcus pneumoniae and Haemophilus influenzae meningitis.

The pharmacokinetics and bacteriological efficacy of cefoperazone, cefuroxime, ceftriaxone, and moxalactam were evaluated in the experimental rabbit meningitis model of Haemophilus influenzae type b or Streptococcus pneumoniae infection. The cerebrospinal fluid penetration of these beta-lactam antibiotics was from 3 to 14% and was greater in Haemophilus-infected that in pneumococcus-infected animals. With the exception of moxalactam, the antibacterial activity in cerebrospinal fluid and change in concentration of bacteria during therapy with the test drugs were comparable to those of penicillin G in pneumococcal infection. In animals infected with H. influenzae, cefoperazone, moxalactam, and ceftriaxone were as effective as chloramphenicol in reducing the bacterial counts in cerebrospinal fluid. Moxalactam and ceftriaxone produced the largest cerebrospinal fluid bactericidal titers against this beta-lactamase-producing strain of Haemophilus. On the basis of these data, it was concluded that ceftriaxone and cefoperazone were effective against both pathogens in this meningitis model, whereas moxalactam was effective against only Haemophilus, and cefuroxime was effective against only S. pneumoniae.

Animals↗

PubMed1982

Activity of cefoperazone against ampicillin-resistant bacteria in agar and broth dilution tests.

Examination of the activity of cefoperazone against ampicillin-resistant, gramnegative bacteria in agar dilution and simultaneously in broth dilution revealed that strains could be divided into three classes: class I strains were susceptible in agar (mean minimal inhibitory concentration [MIC], 0.5 mg/liter) as well as in broth dilution (mean MIC, 1.5 mg/liter), class II strains were susceptible in agar (MIC, 0.9 mg/liter), but resistant in broth dilution (MIC, 182 mg/liter); and class III strains were highly resistant in both test systems. Among 100 randomly selected ampicillin-resistant Escherichia coli cultures, 51 belonged to class I and 49 belonged to class II. Class III E. coli strains were much rarer. Similar results were obtained with cefamandole and cephalothin, but not with six other second-and third-generation cephalosporins. MICs of cefoperazone against cultures of all three classes were influenced by initial inoculum size. The inoculum effect was greatest with class II strains. Examination of bactericidal activity by cefoperazone showed killing of class I and class II E. coli strains and of class III strains of other genera during the first hours of incubation and regrowth after the drug was destroyed by the action of TEM beta-lactamase (penicillinase). Representative class I bacteria produced 10 to 100 times less TEM beta-lactamase than did class II strains. It appeared that the quantitative difference in TEM production was the reason for the different resistance phenotypes in class I and class II strains. Salmonella and Klebsiella strains of class III produced the same amounts of TEM beta-lactamase as did class II E. coli strains. Probably, some factors other than beta-lactamase contributed to the class III phenotype in these species.

Ampicillin↗

PubMed1982

Cefoperazone: regression analysis, disk content, and disk susceptibility testing considerations.

Cefoperazone agar dilution minimal inhibitory concentration (MIC) susceptibility results were compared with zones of inhibition produced by disk diffusion susceptibility testing. Disks containing 30, 50, 75, and 100 micrograms of cefoperazone were tested for purposes of regression line comparisons and error rate-bounded analysis. Results suggest that if the MIC equivalent of susceptibility is 32 micrograms/ml, either a 50-micrograms disk with zone sizes of susceptibility (S) greater than or equal to 15 mm and resistance (R) less than or equal to 12 mm or a 75-micrograms disk with zone sizes of S greater than or equal to 17 mm and R less than or equal to 14 mm may be appropriate. If the MIC equivalent of susceptibility is 64 micrograms/ml, this would dictate use of a 75-micrograms disk with zone sizes of S greater than or equal to 17 mm and R less than or equal to 12 mm. Disks containing either less than or equal to 30 or greater than or equal to 100 micrograms of cefoperazone did not adequately discriminate among susceptible and resistant bacterial strains at either the 32- or 64-micrograms/ml MIC equivalent.

Anti-Bacterial Agents↗

PubMed1983

Cefoperazone pharmacokinetics in preterm infants.

The elimination pharmacokinetics of cefoperazone, a new cephalosporin, were studied in 15 preterm infants ranging in gestational age from 32 to 36 weeks and in postnatal age from 1 to 6 days. The infants received a single dose of either 50 or 250 mg of cefoperazone per kg by intravenous infusion. Blood samples were collected at specified times after completion of the drug infusion and then assayed for cefoperazone. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for plasma half-life, elimination rate constant, apparent steady-state volume of distribution, and total body clearance were 5.53 h, 0.15 h-1, 124 ml/kg, and 36 ml/h per kg, respectively, for the group receiving a 50-mg/kg dose and 5.76 h, 0.14 h-1, 111 ml/kg, and 35 ml/h per kg, respectively, for the group receiving a 250-mg/kg dose. Positive correlations between gestational age and clearance and elimination rate were detected. A 50-mg/kg dose every 12 h ensured adequate serum levels for most of the common neonatal pathogens. Other than a transient rise in eosinophils in four subjects, no adverse effects were noted.

Anti-Bacterial Agents↗

PubMed1983

Pharmacokinetics of cefoperazone in full-term and premature neonates.

The pharmacokinetics of cefoperazone were evaluated in 28 newborn infants who were being treated for sepsis. A dose of 50 mg/kg was administered intravenously on days 0 to 2 in all, with a second dose administered on days 5 to 7 in 14 infants. Cerebrospinal fluid penetration was also studied in seven neonates. The mean peak concentration of cefoperazone in the serum of premature infants less than 33 weeks of gestational age, 159 (standard deviation, +/- 22) micrograms/ml, was higher than concentrations in premature infants 33 to 36 weeks of age and full-term infants (110 +/- 41 and 109 +/- 29 micrograms/ml, respectively). The mean concentrations 24 h after dosage were similar in all three groups, 13 to 17 micrograms/ml. The mean serum half-lives were similar in the three subgroups and ranged from 7 to 9 h. After the dose at 5 to 7 days, mean blood levels in the subgroups at 0.5 h were 149, 112, and 112 micrograms/ml; 24-h levels ranged from 9 to 12 micrograms/ml. The mean serum half-lives ranged from 5 to 7 h. Cerebrospinal fluid levels in patients with meningitis ranged from 2.8 to 9.5 micrograms/ml and in patients without meningitis from 1 to 7 micrograms/ml. Peak blood levels were 15 to 1,000 times higher than the 90% minimal inhibitory concentration of common pathogens found in newborns. These observations support the potential efficacy of cefoperazone in treatment of infections, including meningitis, in newborn infants.

Cefoperazone↗