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The plasma disposition of cefoperazone was investigated after intravenous (IV) and intramuscular (IM) administrations of 20 mg/kg as a single dose in six camels (Camelus dromedarius) in a crossover design. Blood plasma samples were analysed by high-performance liquid chromatography (HPLC). After IV administration, elimination half-life (t 1/2β ), volume of distribution at steady state (V dss ), total body clearance (Cl tot ) and mean residence time (MRT) of cefoperazone were 1.95 h, 0.38 L/kg, 0.17 L/h/kg and 2.16 h, respectively. After IM administration of cefoperazone, peak plasma concentration (C max ) was 21.95 μg/mL and it was obtained at (t max ) 1.23 h. Absorption half-life (t 1/2ab ), elimination half-life and mean absorption time were 0.45 h, 2.84 h and 2.07 h, respectively. The bioavailability of cefoperazone was 89.42%. The lack of local reaction or any other adverse effects and the very good bioavailability following IM administration indicate that cefoperazone might be a promising alternative treatment for a variety of infectious diseases in camels.

The aim of the research was an examination of potential impact of milk yield on the intercompartmental clearance - distribution clearance as well as determination of the variability of obtained pharmacokinetic parameters by the population approach using a two-compartmental structural model. Blood perfusion has a considerable impact on physiology of the udder and kinetics of drugs that are distributed in this organ. The research was performed on healthy Holstein- Friesian and Polish Black-White cows at the age of 4-10 years. Determination of antibiotics (ampicillin, amoxicillin, cefoperazone, penicillin G prokaine, cloxacillin, cefacetril) concentration was carried out after their every intramammary administration to one quarter of the udder. A population pharmacokinetic model was created to fit milk concentration data. General milk yield of a single cow was used as a variable. A population analysis was conducted using non-linear mixed-effect modeling. The impact of milk productivity was set solely by reference to intercompartmental clearance only in case of penicillin G, cloxacillin and ampicillin. It, has been found that milk yield, depending on a drug, influenced the distribution clearance of the drug to varying degrees. It means indirectly that increased perfusion of the udder has a different impact on drug distribution from the udder to the bloodstream., (Copyright© by the Polish Academy of Sciences.)

A rapid, accurate and specific high-performance liquid chromatography-tandem mass spectrometry method has been validated for the simultaneous determination of cefoperazone and sulbactam in a small volume sample for children. A Shim-pack XR-ODS C 18 column with gradient elution of water (0.1% formic acid) and acetonitrile (0.1% formic acid) solution was used for separation at a flow rate of 0.3 mL/min. The calibration curves of two analytes in serum showed excellent linearity over the concentration ranges of 0.03-10 μg/mL for cefoperazone, and 0.01-3 μg/mL for sulbactam, respectively. This method involves simple sample preparation steps and was validated according to standard US Food and Drug Administration and European Medicines Agency guidelines in terms of selectivity, linearity, detection limits, matrix effects, accuracy, precision, recovery and stability. This assay can be easily implemented in clinical practice to determine concentrations of cefoperazone and sulbactam in children., (Copyright © 2017 John Wiley & Sons, Ltd.)

The aim of the study was to carry out retrospective and prospective comparative analyses of the pharmacokinetics of CEF after single intramammary (IMM) administration in cows. The prospective study (study A) was conducted on 9 dairy cows of the Polish Black-White race with clinical mastitis during the lactation period. Milk samples were collected at 2, 4, 6, 8, 10, 24, 36, 48, 72 and 84 h after single IMM administration of 250 mg of CEF to one quarter. Drug concentrations in milk samples were determined by HPLC-MS/MS technique and the results of the pharmacokinetic analysis were compared to those obtained in previous studies based on the microbiological (study B) and HPLC-UV methods (study C and D). Pharmacokinetic parameters were calculated based on adapted two-compartment model of drug distribution. One of the findings of the comparison of the analysed investigations is that the CEF kinetics determined with the microbiological method is consistent with the results obtained by the authors of this paper. Both studies yielded similar results of the key pharmacokinetic parameters related to the level of the drug distribution to tissues and elimination half-life. In the pharmacodynamic analysis, the observations in all four studies were entirely consistent and have shown lower values of T>MIC90 in healthy animals and significantly higher values in infected dairy cows. The comparison of studies A, B, C, and D revealed that the time of complete CEF wash-out of 90.90% varied and amounted to 5.7, 8.0, 2.2, and 2.2 days after administration of the drug, respectively. It was confirmed that not only the type of the analytical method but also correct sampling have a significant impact on determination of the correct value of the drug half-life after IMM administration. The comparative analysis of studies in which the milk yield was high and low allows a conclusion that this parameter in the case of CEF has no significant effect on T>MIC90.

Purpose: Cefoperazone/sulbactam (CFP/SUL) is a β-lactam/β-lactamase inhibitor combination with little data available for the development of effective dosing guidelines during continuous renal replacement therapy. This study aimed to investigate the pharmacokinetics (PK) of cefoperazone/sulbactam in critically ill patients on continuous venovenous hemofiltration (CVVH)., Methods: A prospective, single-center, and open-label study was conducted. Critically ill patients receiving CVVH with 3 g cefoperazone/sulbactam (2.0/1.0 g) intravenously every 8 h were recruited. Serial blood and ultrafiltrate samples were paired collected for initial dose (occasion 1) and steady state (occasion 2). PK was assessed by non-compartmental analysis, and pharmacodynamics (PD) was evaluated by the percent of time for which drug concentrations exceed the minimum inhibitory concentration (%T >MIC)., Results: Total fourteen patients were enrolled. Volume of distribution at steady state (V ss) of cefoperazone and sulbactam for initial doses (20.8 ± and 28.4 L, respectively) increased significantly compared with those in healthy volunteers (P = 0.009 for CFP, P = 0.030 for SUL). Both cefoperazone and sulbactam showed significantly lower total clearance (CLt) (46.2 and 117.6 mL/min, respectively) compared with healthy volunteers (P = 0.000 for CFP, P = 0.017 for SUL). There is no significant difference in PK between occasion 1 and occasion 2 (P > 0.05). For occasion 1, mean CVVH clearance accounted for 34.3 and 33.9 % for CLt of cefoperazone and sulbactam, respectively. The minimum PD target of 60%T >MIC was achieved in seven of eight patients. For occasion 2, eight of nine patients achieved cefoperazone concentrations that were above the MIC for the entire dosing interval., Conclusions: PK of cefoperazone/sulbactam was altered in critically ill patients undergoing CVVH. Therapeutic drug monitoring would be recommended to individualize the dose regimen.

Objective: To study the concentrations and pharmacokinetics of 6 different kinds of antibiotics in rabbit bile, and evaluate their microbicidal potential., Methods: Thirty-six health rabbits were randomly divided into 6 groups, and each group was 6 rabbits. After anaesthesia, the common bile duct of rabbit was isolated and cumulated with a silicone tube. The rabbits were administered intravenously with the equal-effect dose of antibiotics. Bile (1.5 ml) was collected at different time points after administration, and the concentration of antibiotics of bile was assayed by high performance liquid chromatography. The bile drug concentration-time data were processed by software to figure out the pharmacokinetic parameters such as maximum concentration (C(max)), peak time (T(max)), half-life time (T(1/2)), clearance (CL) and apparent volume of distribution (VD). The bile antibiotics concentration contrasted to the minimum inhibitory concentration (MIC), and attained the bactericidal index (C(max)/MIC) and the time when the drug concentration exceeded the MIC (T(>MIC))., Results: The C(max) and T1/2 of each antibiotic were as the followings: piperacillin (7 950 ± 3 023) mg/L and (1.97 ± 1.23) h, ceftriaxone (1 104 ± 248) mg/L and (3.14 ± 0.57) h, cefoperazone (5 215 ± 2 225) mg/L and (0.89 ± 0.13) h, meropenem (31.97 ± 12.44) mg/L and (0.36 ± 0.11) h, levofloxacin (66.3 ± 36.9) mg/L and (3.32 ± 2.57) h, metronidazole (28.2 ± 10.2) mg/L and (0.81 ± 0.33) h, respectively. Piperacillin/tazobactam and cefoperazone/sulbactam had the largest bactericidal index and the longest T(>MIC), and their bactericidal indexes were (62.1 ± 23.6) - (993.8 ± 377.9) and (164.8 ± 69.0) - (659.3 ± 275.9), their T(>MIC) were (6.00 ± 2.53) - (8.00 ± 0.00) h and (6.33 ± 1.97) - (8.00 ± 0.00) h. The bactericidal index and T(>MIC) of levofloxacin were the smallest, which were (2.1 ± 1.2) - (8.3 ± 4.6) and (0.54 ± 0.25) - (2.67 ± 1.03) h . Ceftriaxone and meropenem were as the medium, and their bactericidal indexes and T(>MIC) were (4.3 ± 1.0) - (69.2 ± 15.5) , (1.42 ± 0.65) - (8.00 ± 0.00) h and (2.0 ± 0.8) - (1 031.3 ± 401.4) , (0.29 ± 0.10) - (1.83 ± 0.26) h. The bactericidal index of metronidazole to anaerobic ranged from 7.4 to 294.9, and the T(>MIC) ranged from 1.88 to 5.00 h., Conclusions: The bile concentrations of six antibiotics all exceed their effective bactericidal concentrations. The concentration-time curves of piperacillin, cefoperazone, meropenem and metronidazole conformed to one-compartment model, and ceftriaxone and levofloxacin are conformed to two-compartment model. Piperacillin/tazobactam and cefoperazone/sulbactam have the largest bactericidal index and the longest T(>MIC), so they can be chosen as the first choice for the therapy of hepatobiliary infection.For the anaerobic, the microbicidal potential of metronidazole is high.

A rapid and highly sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for simultaneous determination of cefoperazone sodium and sulbactam sodium in human plasma was developed. The analytes and internal standard (IS), cefuroxime sodium, were extracted from human plasma via liquid-liquid extraction with ethyl acetate and separated on a Waters Xterra C18 column within 3.5 min. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique, operating in selected reaction monitoring (SRM) and negative ion mode. The precursor to product ion transitions monitored for cefoperazone, sulbactam and IS were m/z 644.1→528.0, 232.1→140.0, and 423.0→362.0, respectively. The assay was validated in the linear range of 0.1-20 μg/mL for cefoperazone and 0.02-4 μg/mL for sulbactam. The intra- and inter-day precisions (CV%) were within 8.39% for each analyte. The recoveries were greater than 87.3% for cefoperazone and 87.2% for sulbactam. Each analyte was found to be stable during all sample storage, preparation and analytical procedures. The method was successfully applied in a pharmacokinetic study of Sulperazon injection in six hospital-acquired pneumonia (HAP) patients., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Selection of the antimicrobial agent and maintenance of adequate drug concentrations at the site of infection are the most relevant problems in mastitis antibiotic therapy. Intramammary drug efficacy can be maximized by keeping drug concentrations at the site of infection above the minimum inhibitory concentration (MIC) as long as possible; the most important pharmacokinetic and pharmacodynamic (PK/PD) measure for efficacy evaluation is time during which drug concentrations exceed the MIC (t>MIC). To evaluate this measure, the PK profile of cefoperazone (CFP) after single intramammary administration in healthy and subclinical infected Staphylococcus aureus cows and the MIC of Staph. aureus field strains were assessed. In addition, the degree of drug passage from udder to bloodstream was investigated by measuring systemic drug absorption in healthy and infected animals. Cefoperazone concentrations were quantified by HPLC in quarter milk samples and blood serum samples. Systemic drug absorption was negligible in healthy animals (0.020+/-0.006 microg/mL serum at 4 h), whereas it was higher in infected animals (0.102+/-0.079 microg/mL at 4h and 0.025 microg/mL at 24 h), probably due to the damage of epithelial cell junctions caused by subclinical infections. The MIC90 value for CFP in Staph. aureus field strains (n=24) was 0.64 microg/mL. The PK/PD evaluation, determined by t>MIC, showed a longer persistence of CFP in infected quarters than in healthy ones (mean residence time was 8.37+/-1.51 vs. 11.42+/-5.74 h in September and 2.07+/-0.43 vs. 3.31+/-0.91 h in October), with a t>MIC of 45+/-6 h for infected quarters versus 38+/-5 h for healthy quarters different only in October. This could mean a prolonged time in which microorganisms are exposed to drug activity and thus, a greater efficacy of the drug., (Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Wide-spectrum quinolones such as moxifloxacin and levofloxacin as well as high-order cephalosporins such as cefoperazone and cefepime have increased antimicrobial activity. However, little is known about their distribution in fetal blood. Therefore, the aim of this study was to measure and compare maternal and fetal blood levels of these agents. For the measurement of blood levels, 9 pregnant women received cefepime hydrochloride, 10 received cefoperazone, 10 received moxifloxacin and 12 received levofloxacin intravenously. Maternal and umbilical cord blood samples were drawn during delivery. Antibiotic levels were analysed by high-performance liquid chromatography. Mean transplacental passage rates of moxifloxacin, levofloxacin, cefepime and cefoperazone were 74.84%, 66.53%, 23.21% and 12.68%, respectively, and mean transfetal passage rates were 90.78%, 84.22%, 79.17% and 79.78%, respectively. The transplacental passage rate for either quinolone was significantly higher than that of either cephalosporin, and the transplacental passage rate of cefoperazone was lower than that of cefepime. In conclusion, both quinolones have high transplacental passage rates. Cefepime and cefoperazone have a lower transplacental passage rate and thus may be used as prophylaxis in situations where transplacental passage is undesirable., (Copyright (c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Objective: To perform a bioequivalence study of the two 1.5 g cefoperazone (1.0 g) and sulbactam (0.5 g) between Cefper and Sulperazon injections., Material and Method: The present study was performed in 24 Thai healthy male volunteers who were intramuscularly injected a single dose of 1.5 g cefoperazone and sulbactam. A single dose, two periods, two sequences, double blind randomized crossover with a one-week washout period was used. Blood samples were collected before and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after intramuscular injection and determined for cefoperazone and sulbactam plasma concentration by validated HPLC-UV methods. The pharmacokinetic parameters were analyzed by noncompartmental analysis and the ANOVA was carried out., Results: Tax of both cefoperazone and sulbactam for volunteers who were injected with either Cefper or Sulperazon injection were not significantly different (p > 0.05). The 90% confidence intervals of the log of ratio of either C(max) or AUC(last) or AUC(inf) of both cefoperazone and sulbactam between 1.5 g Cefper and Sulperazon injections were within the bioequivalence range of 0.80-1.25., Conclusion: The 1.5 g cefoperazone and sulbactam injection of Cefper and Sulperazone used in the present study are bioequivalent.

Sulbactam irreversibly inhibits the hydrolytic activity of beta-lactamases. This compound is commercially available in combination with either ampicillin or cefoperazone. In each instance, the activity of the partner antibiotic against beta-lactamase-producing bacteria is restored. One of the particular advantages of using sulbactam-containing combinations is that sulbactam itself has inherent activity against some Acinetobacter baumannii. Sulbactam combinations have not demonstrated strong selective pressures for extended-spectrum beta-lactamase-producing Enterobacteriaceae and vancomycin-resistant enterococci. In contrast to clavulanate, sulbactam does not induce class I (Ampc) chromosomal beta-lactamases in Enterobacteriaceae.

Cefoperazone is a third generation cephalosporin antibiotic with a broad spectrum against gram-positive and gram-negative bacteria. It is clinically effective in the treatment of the biliary tract infections. In the present study, we utilized microdialysis sampling technique with shunt linear probe for continuous monitoring levels of cefoperazone from rat biliary ducts. The effects of berberine (a potential P-glycoprotein enhancer) pretreatment were also evaluated. Analysis of cefoperazone in the dialysates was achieved using a reversed phase RP-18 column (250 mm x 4.6 mm i.d.; particle size 5 microm) maintained at ambient temperature. The mobile phase comprised 100 mM monosodium phosphate (pH 5.5)-methanol (70:30, v/v), and the flow rate of the mobile phase was 1 ml/min. The UV detector wavelength was set at 254 nm. The area under the concentration-time curve and elimination half-life of cefoperazone were about 242.3+/-13.4 min mg/ml and 64.1+/-28.2 min, respectively. No significant effect was showed on the pharmacokinetics of cefoperazone with berberine pretreatment. This study represents a successful application of biliary microdialysis sampling technique, which is feasible for pharmacokinetic and biliary drug excretion studies.

A fully validated simple, sensitive and selective square-wave stripping voltammetry procedure was described for the trace quantification of cefoperazone in bulk form, formulations and human serum/plasma. The procedure was based on reduction of the adsorbed drug onto a hanging mercury drop electrode. The procedural conditions were optimized as: frequency=60Hz, scan increment=8mV, pulse amplitude=25mV, preconcentration potential=-0.3V (versus Ag/Ag/KCl(s)), preconcentration duration=60-150s and an acetate buffer of pH 4.2 as a supporting electrolyte. A limit of detection of 4.5x10(-10)M and a limit of quantitation of 1.5x10(-9)M bulk cefoperazone were achieved following preconcentration of the drug onto the hanging mercury drop electrode for 150s. The proposed square-wave adsorptive cathodic stripping voltammetric procedure was successfully applied for trace quantification of cefoperazone in human serum and plasma. The achieved limits of detection and quantitation of the drug in human serum were 6x10(-10)M (0.375ngml(-1)) and 2x10(-9)M (1.250ngml(-1)), respectively. The pharmacokinetic parameters of cefoperazone in plasma of hospitalized volunteers were successfully estimated.

The pharmacokinetics and intramuscular (i.m.) bioavailability of cefoperazone and cefamandole (20mg/kg) were investigated in dogs and the findings related to minimal inhibitory concentrations (MICs) for 90 bacterial strains isolated clinically from dogs. The MICs of cefamandole for Staphylococcus intermedius (MIC(90) 0.125 microg/mL) were lower than those of cefoperazone (MIC(90) 0.5 micro/mL) although the latter was more effective against Escherichia coli strains (MIC(90) 2.0 microg/mL vs. 4.0 microg/mL). The pharmacokinetics of the drugs after intravenous administrations were similar: a rapid distribution phase was followed by a slower elimination phase (t((1/2)lambda2) 84.0+/-21.3 min for cefoperazone and 81.4+/-9.7 min for cefamandole). The apparent volume of distribution and body clearance were 0.233 L/kg and 1.96 mL/kg/min for cefoperazone, 0.190 L/kg and 1.76 mL/kg/min for cefamandole. After i.m. administration the bioavailability and peak serum concentration of cefamandole (85.1+/-13.5% and 35.9+/-5.4 microg/mL) were significantly higher than cefoperazone (41.4+/-7.1% and 24.5+/-3.0 micog/mL), but not the serum half-lives (t(1/2el) 134.3+/-12.6 min for cefoperazone and 145.4+/-12.3 min for cefamandole). The time above MIC(90) indicated that cefamandole can be administered once daily to dogs for the treatment of staphylococcal infections (T>MIC for S. intermedius 23.8+/-0.3 and for Staphylococcus aureus 21.6+/-0.6h).

In vitro and in situ intestinal transport of beta-lactam antibiotics in the presence of two novel pharmaceutical excipients, caprylocaproyl and lauroyl macrogolglycerides (Labrasol and Gelucire 44/14), is described. The objective was to compare the effects of both macrogolglycerides on the intestinal transport of cephalexin, a substrate of oligopeptide transporters, and cefoperazone, a non-substrate of them. The in vitro transport studies were performed using a sheet of rat jejunum mounted in Ussing-type diffusion chambers. The in situ studies used an isolated internal loop model in the rat. Labrasol and Gelucire 44/14 were used as the excipients at low concentrations (0.01-0.5%, w/v). The membrane permeability of both drugs was compared by apparent permeability coefficients (P(app)) determined from changes in the amount of permeation vs. time in in vitro studies and by apparent absorptive clearance (CL(app)) determined from changes in the steady state drug concentration of perfusate in in situ studies. The P(app) value of cephalexin increased with an increase in the concentration of Labrasol (0.05-0.5%) compared to the value without Labrasol. The enhancing effect of Labrasol on cephalexin transport was similarly observed in in situ studies, and when 0.5% Labrasol was used in the presence of glycyl-L-leucine or L-alanyl-L-alanine, 60 or 46% enhancement of the active transport of cephalexin by Labrasol was obtained. On the other hand, Gelucire 44/14 did not affect the P(app) and CL(app) of either drug. The different effects of the excipients on cephalexin transport were thought to be due to the influences of size parameters such as a polydispersity index and particle size, and the change in the short-circuit current of jejunum by the addition of the excipient.

The authors evaluated the pharmacokinetics of cefoperazone and sulbactam in 9 liver transplant patients. Cefoperazone and sulbactam were administered as an intravenous infusion over 30 minutes every 12 hours for six doses, and multiple blood samples were collected immediately after the first dose (administered during the surgery) and after the last dose. The concentrations of cefoperazone and sulbactam in serum and, when possible, in urine and bile collected over one dosing interval were measured by high-pressure liquid chromatography. The concentration of cefaperazone ranged from 436 to 4118 microg/ml, and sulbactam ranged from 3.3 to 8.7 microg/ml in the bile samples. The intraoperative clearance of cefoperazone (0.53+/-0.18 ml/min/kg) was significantly higher than the postoperative clearance (0.21+/-0.23 ml/min/kg). The half-life of cefaperazone, although not statistically significantly different, was prolonged in all patients during the postoperative period. The clearance of sulbactam (1.51+/-0.51 ml/min/kg) was lower than what is reported in patients with normal renal function but was comparable to what has been reported in patients with renal impairment and in critically ill patients. There were no significant differences in any of the pharmacokinetic parameters of sulbactam during and after surgery. The pharmacokinetic parameters of cefoperazone and sulbactam were significantly altered in liver transplant patients compared to what has been reported in normal subjects but were similar to what has been reported in patients with liver and renal impairment. There was a significant impairment in the biliary excretion of cefoperazone during the postoperative period in liver transplant patients. Although the percentage of the dose of cefoperazone excreted in the bile was drastically reduced, the biliary concentrations were generally high and above the MIC for most organisms. Given that both renal and hepatic elimination of cefoperazone is decreased, leading to a lower clearance and longer half-life in liver transplant patients, lower doses (1-2 g per day) of cefoperazone may be sufficient in liver transplant patients during the immediate postoperative period.

Provision and maintenance of adequate concentrations of antibiotics at infection sites is very important in treating highly resistant infections. For diseases like implant related osteomyelitis (IRO) it is best to provide this locally via implanted drug formulations, as systemic administration of the antibiotic may not be effective due to damaged vasculature. In this study, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) rods containing 7, 14 and 22% (mol) 3-hydroxyvalerate were loaded with sulbactam:cefoperazone or gentamicin, and their antibiotic release behaviours were studied under in vitro conditions in physiological phosphate buffer at room temperature. The release patterns were representative of release from monolithic devices where a rapid early release phase is followed by a slower and prolonged release. With PHBV 22 rods, the latter phase continued for approximately 2 months. This duration is critical because a proper antibiotic therapy of IRO requires the minimal effective concentration for at least 6 weeks. After in vitro release, voids with sharp edges were detected on the rods, indicating that the drug crystals dissolved but the polymer did not undergo erosion within this test period. Changing the polymer:drug ratio from 2:1 to 20:1 substantially decreased the drug release rate. A change of polymer type, however, did not lead to any detectable changes in the release patterns. Gentamicin release also followed a similar pattern, except that the concentration of the drug in the release medium exhibited a decrease after long release periods, indicating degradation (or decomposition) of the antibiotic in the release medium.

Six patients received 1 g and six other patients received 2 g of cefoperazone and sulbactam 15 minutes before lumbar disc surgery. Liquid chromatographic analysis of disc tissue revealed that only patients receiving the 2-g dose had mean tissue levels above the minimum inhibitory concentration for Staphylococcus aureus and epidermidis.

A sensitive microbore HPLC method was developed for the simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis. Two microdialysis probes were inserted into the jugular vein/right atrium and brain striatum of Sprague-Dawley rats. Cefoperazone (50 mgkg(-1), i.v.) was then administered via the femoral vein. Blood and brain dialysates were collected and eluted with a mobile phase containing methanol-100 mM monosodium phosphoric acid (30:70, v/v, pH 5.5). The wavelength of the UV detector was set at 254 nm. The detection limit of cefoperazone was 20 ng mL(-1). Isocratic separation of cefoperazone was achieved within 10 min. The intra- and inter-assay accuracy and precision of the analyses were < or =10% in the range of 0.05-10 microg mL(-1). The ratio of the area under the concentration curve of cefoperazone in rat brain and blood was estimated to be about 7-8%. It is concluded that cefoperazone is capable of penetrating the blood-brain barrier.

The effect of acute renal failure on the disposition of cefoperazone was investigated. Rats, 3 days after uranyl nitrate treatment, were used to model acute renal failure. Although plasma-protein binding of cefoperazone decreased significantly in acute renal failure compared with control rats, the plasma clearance of total (bound plus unbound) drug after intravenous administration (50 mg kg(-1)) did not differ significantly between the two groups (5.61+/-2.37 mL min(-1) for control and 4.75+/-2.82 mL min(-1) for acute renal failure). Consequently the plasma clearance of the unbound drug in acute renal failure (6.14+/-1.16 mL min(-1)) was significantly lower than in control rats (15.6+/-3.7 mL min(-1), P < 0.025). Plasma clearance of the drug (both total and unbound) was also dependent on bile flow, and clearance of the unbound drug in acute renal failure rats was lower than in control rats with identical bile flow rates. To examine the mechanism of reduced unbound cefoperazone clearance, an in-vitro experiment using a simultaneous perfusion system of rat liver and kidney was performed. By changing perfusate plasma protein from bovine serum albumin to human serum albumin, the plasma clearance of the total cefoperazone changed to one-sixth in proportion to the unbound cefoperazone in the perfusate plasma. On the other hand, the plasma clearance of the total and unbound drug in acute renal failure rats decreased significantly compared with controls. These results demonstrate that the plasma clearance of unbound cefoperazone, which is mainly eliminated by the liver, decreased in acute renal failure in rats, probably due to changes in hepatic transport.

Background: Penetration of antibiotics into the pancreas is considered to be an important criterion in determining the most appropriate antibiotic treatment during severe acute pancreatitis. Our study investigated pancreatic penetration of five antibiotics in rats with and without acute necrotizing pancreatitis (ANP) (non-pancreatitis rats (NR), pancreatitis rats (AP))., Methods: ANP was induced by intraductal bile acid injection, and 3 h later the antibiotic was administered. In both NR and AP the antibiotic concentrations were evaluated in blood and pancreatic tissue 90 min after antibiotic administration., Results: The tissue/serum (T/S) ratios for NR were 16% with amikacin, 24% with amoxycillin/clavulanic acid, 27% with piperacillin, 59% with ofloxacin, and 108% with cefoperazone. The ratios for AP were 7%, 23%, 26%, 52%, and 70%, respectively. T/S ratios were similar for NR and AP except for amikacin, for which the T/S ratio was lower in AP than in NR (P = 0.02). Pancreatic tissue concentrations of antibiotics with high penetration rates (cefoperazone and ofloxacin) were sufficient to inhibit most of the pathogens expected during acute pancreatitis. The concentrations of the other antibiotics were less than the minimal inhibitory concentrations (MIC) for common potential pathogens in pancreatic infection., Conclusions: Cefoperazone and ofloxacin showed the best pancreatic penetration of the five antibiotics tested. The high concentrations of these antibiotics in the pancreatic tissue would have enabled efficient antibacterial activity against most of the potential pathogens causing pancreatic infection. An early stage of acute necrotizing pancreatitis did not have a major effect on the pancreatic concentrations of the antibiotics.

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.

The pharmacokinetics and bioavailability of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase (t1/2 (alpha): 4.22 +/- 2.73 min) was followed by a slower elimination phase (t1/2(beta) 0.77 +/- 0.19 h). The apparent volume of distribution was 0.68 +/- 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 +/- 0.74 microgram/mliter. After IM administration a bioavailability of 42.00 +/- 5.33% was obtained. Half-life of absorption was 2.51 +/- 0.72 min and t1/2(beta) was 1.52 +/- 0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91 +/- 0.85 microgram/mliter and 5.56 +/- 0.70 microgram/mliter, respectively.

Klebsiella pneumoniae O3 lipopolysaccharide (LPS) has been found to dramatically modify the pharmacokinetics of the beta-lactam antibiotic cefazolin in rats. This study investigated the effect of LPS on the biliary excretion of the beta-lactam antibiotic cefoperazone (CPZ) in rats. CPZ is known to be actively secreted into the bile by a carrier-mediated transport system. LPS (250 micrograms/kg of body weight) was infused for 20 to 30 min 2 h before an intravenous administration of CPZ (20 mg/kg). The pharmacokinetic parameters of CPZ were estimated by a noncompartment model. LPS induced a significant decrease in the systemic clearance (by approximately 50%) and an increase in the mean residence time of CPZ. Significant decreases were also seen in the bile flow rate and in the biliary recovery of unchanged CPZ in the LPS-treated rats. LPS tended to increase the proportion of urinary excretion of CPZ. LPS significantly decreased the biliary clearance (by approximately 55%) and renal clearance (by approximately 35%) of CPZ. However, no changes in the volume of distribution at steady state for CPZ were observed between the treatment groups. Our findings suggest that LPS induces changes in the pharmacokinetics of CPZ as a result of changes occurring in the biliary secretory system.

1H NMR spectroscopy at 400 MHz has been applied to the analysis of whole bile samples produced by the isolated perfused rat liver. Using relatively simple NMR experiments biliary excretory products of cefoperazone and benzyl chloride were identified as cefoperazone itself and a benzyl-glutathione conjugate, respectively. Our use of 13C isotopic labelling demonstrates how 1H/13C heteronuclear NMR techniques can be used to produce uncrowded and informative spectra from whole bile. From the use of a HMQC-COSY experiment the structure of a benzyl-glutathione conjugate contained in whole bile was confirmed.

Unlabelled: In this study, the rabbits were categorized into three groups. The scald (III degrees TBS 10%-15%) was caused by exposing these area to hot water at 90 degrees C for 40 seconds. Every rabbit was injected CPZ (25 mg/kg) three times. The changes in the concentration of CPZ were measured by employing MBPD and HPLC methods and experimental data were analyzed by using pharmacokinetic computer program., Results: 1) The T1/2e of CPZ injection in subeschar region was longer and the Cmax was higher than that of intravenous route. 2) The concentration in blood was shown two times higher than after subeschar injection. 3) The levels of concentration were higher than MIC'S in an area of 6.5 cm diameter 24-36 hours after injection., Conclusion: CPZ injection in subeschar region was the best route of treatment and prevention of subeschar infection.

A novel, simple, clinically useful quantitative liver function test, called the galactose single point (GSP) method, was developed to assess residual liver function by measuring galactose blood concentration 1 hour after galactose was administered (0.5 g/kg). This method was applied to the study of cefoperazone kinetics in patients with hepatic cirrhosis. To study the influence of hepatic cirrhosis on the residual liver function and the correlation between the residual liver function and the pharmacokinetics of cefoperazone, a dose of 1 g of cefoperazone was administered to 11 healthy volunteers and 12 patients with liver cirrhosis. The GSP method, the galactose elimination capacity (GEC) test, and the modified galactose elimination capacity (MGEC) test were done for each volunteer and patient to measure residual liver function. The galactose concentrations were determined enzymatically. Cefoperazone was administered intravenously, and blood and urine samples were collected at appropriate intervals after drug administration. All blood and urine samples were stored at -30 degrees C until high-performance liquid chromatography analysis. Cefoperazone plasma concentrations were much higher in cirrhosis patients than in normal subjects at all times. The elimination half-life, hepatic clearance, mean residence time, and renal clearance of cirrhosis patients differed significantly from those of healthy volunteers. The plasma protein binding was unaltered in both groups. Urinary excretion of cefoperazone was significantly increased in cirrhosis patients (23.95 +/- 5.06% for normal men and 51.09 +/- 11.50% in cirrhosis patients). Hepatic clearance, fraction excreted in urine, and total clearance significantly correlated with GSP, GEC, and MGEC (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Cefoperazone is a semisynthetic cephalosporin antibiotic containing a piperazine side chain, which results in antipseudomonal activity. Unlike the other cephalosporins, it is mainly cleared by the liver (60-80%) and it may be more sensitive to changes in the liver function and/or plasma protein binding than other cephalosporins, which are not primarily cleared by the liver. In order to study the influence of chronic lobular hepatitis on the pharmacokinetics of cefoperazone, a dose of 1 g of cefoperazone was administered to 11 normal, healthy volunteers and 16 subjects with chronic lobular hepatitis. In each volunteer or patient, a novel galactose single-point (GSP) method, the galactose elimination capacity (GEC) test, and the modified galactose elimination capacity (MGEC) test were also performed as a measure of residual liver function. Cefoperazone was administered intravenously over a period of 3-5 min. Blood and urine samples were collected at appropriate intervals after drug administration and stored at -30 degrees C until high-pressure liquid chromatographic (HPLC) analysis. The cefoperazone hepatic clearance, mean residence time, and renal clearance in hepatitis patients were significantly different from those of normal healthy volunteers, whereas the plasma protein binding was unaltered between the two groups. Urinary excretion of cefoperazone showed a highly significant increase in patients, 23.95 +/- 5.06% and 37.54 +/- 13.61% for normal men and hepatitis patients respectively. Hepatic clearance and fraction excreted in urine significantly correlated with values of GSP and MGEC respectively (p < 0.05). These results suggest (i) cefoperazone kinetics was significantly altered in patients with chronic lobular hepatitis; (ii) GSP, a novel simple, clinically useful quantitative liver function test, can predict the cefoperazone hepatic clearance in patients with liver dysfunction.

This study compared the safety and efficacy of cefoperazone plus sulbactam with that of clindamycin plus gentamicin in the treatment of intra-abdominal infection. Seventy-six patients were included in the analysis of an open, randomized, comparative, single-site trial. Forty-seven patients received cefoperazone-sulbactam, and 29 patients received clindamycin plus gentamicin. Thirty-three patients (70%) who received cefoperazone-sulbactam and 15 patients (52%) who received clindamycin plus gentamicin were cured of infection, did not suffer a relapse within one month after the end of treatment, and did not receive any other antibiotics during the follow-up period (P = 0.17). In patients treated with cefoperazone-sulbactam there were four cases of superinfection, one patient had a prolonged prothrombin time, six patients had a poor response, two patients received antibiotics during follow-up, and one patient died during follow-up because of cancer. Treatment with clindamycin plus gentamicin was associated with five cases of superinfection, four patients had a poor response, four patients had a drug reaction, and one patient required antibiotics in the follow-up period. Serum levels of cefoperazone-sulbactam measured at one and three hours after dosing were consistent with earlier findings in normal volunteers. Two hundred and one pathogens were isolated, and 17 of 122 aerobic isolates (14%) were resistant to cefoperazone-sulbactam, and 17 of 122 (14%) were resistant to both clindamycin and gentamicin. Eleven of 79 (14%) anaerobic isolates were resistant to cefoperazone, none was resistant to cefoperazone-sulbactam, and 10 of 79 (13%) were resistant to clindamycin. The results of this study show that cefoperazone-sulbactam is an effective and safe alternative to clindamycin plus gentamicin in the treatment of intra-abdominal infections.

Objective: To determine the steady-state pharmacokinetics of intravenously administered cefoperazone and sulbactam when given in combination to patients with acute appendicitis., Methods: Six patients with normal renal and hepatic function received cefoperazone 2 g with sulbactam 1 g prior to appendectomy and then every 12 hours. Serial blood samples were collected after each patient received at least three doses of cefoperazone/sulbactam., Results: Cefoperazone and sulbactam could be best described by a two-compartment model. Mean +/- SD values for cefoperazone steady-state volume of distribution (Vssd), elimination half-life (t1/2 beta), clearance (Cl), and area under the curve (AUC0-t) were 19.8 +/- 8.0 L, 3.97 +/- 1.06 h, 62.6 +/- 16.3 mL/min, and 556.9 +/- 122.0 mg.h/L, respectively. Sulbactam Vssd, t1/2 beta, Cl, and AUC0-t were 34.7 +/- 13.9 L, 1.39 +/- 0.4 h, 288.6 +/- 68.2 mL/min, and 64.8 +/- 24.5 mg.h/L, respectively., Conclusions: Compared with data from healthy volunteers, cefoperazone exhibited a decreased Cl and increased Vssd and t1/2 beta in patients with acute appendicitis. An increased Vssd also was observed for sulbactam. The disposition of cefoperazone/sulbactam is altered in this group of patients; however, these changes are not likely to warrant a dosage reduction.

The therapeutic efficacy of liposomal cefoperazone against Pseudomonas aeruginosa was investigated in a granulocytopenic mouse model of acute lung infection. Granulocytopenia was induced in mice by intraperitoneal (i.p.) injection of 200 mg/kg cyclophosphamide. Mice were challenged by exposure to an aerosol containing P. aeruginosa and were treated i.p. with liposomal cefoperazone prepared by the dehydration-rehydration method. The half-life of free cefoperazone in the lungs following i.p. administration of the liposomal drug was significantly lengthened (13 min vs. 261 min), and the cefoperazone activity in the lungs remained above the MIC longer after administration of liposomal cefoperazone than after treatment with cefoperazone. Liposomal cefoperazone was more effective than cefoperazone alone in preventing death of granulocytopenic mice from lethal pulmonary challenge with P. aeruginosa (75% vs. 38% survival, p = 0.031). Finally, P. aeruginosa was cleared faster from the lungs of mice treated with liposomal cefoperazone when compared with those treated with cefoperazone. This study shows that incorporation of cefoperazone into liposomes enhances the activity of the antibiotic against P. aeruginosa in a granulocytopenic host.

The penetration of ceftriaxone and cefoperazone into bile and gallbladder tissue was prospectively studied in 21 adult patients undergoing early surgery for acute cholecystitis. Comparable tissue, bile, and serum concentrations of the drugs were demonstrable; however, significantly fewer preoperative doses of ceftriaxone were required for adequate perioperative treatment. In view of its higher serum half-life and superior antibacterial activity toward common biliary pathogens, ceftriaxone appears to be a useful drug for the perioperative management of acute cholecystitis.

Experimental diabetes mellitus was induced in adult male rats by injecting streptozotocin (STZ; 60 mg/kg iv) for the purpose of surveying changes in the pharmacokinetics of biliary excretion after the intravenous administration of 40 mg/kg of cefoperazone (CPZ) or cephradine (CED). CPZ, CED, and other organic anions share affinity for the organic anion transport system in the bile canalicular membrane. The STZ treatment had a marked influence on the distribution and elimination of both cephalosporins. The blood levels of both cephalosporins at each time point after administration differed significantly between the STZ-treated and control rats. The values of mean residence time (MRT) of CPZ and CED were significantly decreased in the STZ-treated rats. Basal bile flow rates were increased after the administration of CPZ in the control and STZ-treated rats. Biliary clearance (CLbile) of CPZ was more than 60% of the CLtot, whereas CLbile of CED was less than 20% of CLtot in both groups of rats. The mean CLbile value of CPZ in the STZ-treated rats was 1.0 ml/min higher than that of the control rats, whereas the mean CLbile value of CED was almost the same as that of the control rats. The increased CLbile of CPZ suggested that diabetes alters the biliary excretion of CPZ. The changes in MRT of CPZ in the STZ-treated and control rats are mainly caused by an increase in the biliary excretory rate and renal clearance. The changes in MRT of CED in the STZ-treated and control rats are caused by a decrease in the apparent volume of distribution and increased renal clearance.

The pharmacokinetics of cefoperazone 2 g combined with sulbactam 1 g after a single dose administered intravenously were evaluated in 24 subjects with normal and impaired renal function. Subjects were categorized into four groups based on endogenous creatinine clearance Clcr. Patients in groups 1, 2 and 3 had ClcrS of greater than 60, 31 to 60, and 10 to 30 mL/min/1.73 m2, respectively. Patients in group 4 required maintenance haemodialysis and were assumed to have Clcr less than 10 mL/min/1.73 m2. Pharmacokinetic parameters were determined by noncompartmental methods. No significant differences (P greater than 0.05) in mean peak serum cefoperazone-sulbactam concentrations for group 1 (208.4/29.0 mg/L), group 2 (199.0/34.1 mg/L), group 3 (163.2/35.0 mg/L), and group 4 (234.0/66.0 mg/L) were noted. Correlations between both total serum (r = 0.58) and renal (r = 0.35) clearance and creatinine clearances were negative for cefoperazone, although both were shown to decline with diminished renal function. Correlations between serum (r = 0.85) and renal (r = 0.72) clearances and creatinine clearance for sulbactam were, on the other hand, both positive and declined in a linear fashion. No significant differences in steady state volumes of distribution were noted for either cefoperazone (P = 0.53) or sulbactam (P = 0.85) amongst the four groups. After 24 h, urinary recovery was also comparable for both cefoperazone (P = 0.64) and sulbactam (P = 0.85) amongst the four groups. The concentrations of cefoperazone and sulbactam remained at or above the MICs (16/8 mg/L) for common bacterial pathogens for 2.5, 3, 7 and 14 h in groups 1, 2, 3 and 4, respectively.

Cefepime is a new broad-spectrum cephalosporin with excellent gram-positive and gram-negative activity including activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter cloacae. The pharmacokinetic disposition of cefepime is similar to that of ceftazidime. We compared the pharmacokinetic characteristics and the extent and duration of bactericidal activity in serum and suction-induced blister fluid after single 2-g intravenous doses of cefepime, ceftazidime, and cefoperazone given to healthy subjects. One clinical isolate each of E. cloacae, P. aeruginosa, and S. aureus was used to assess bactericidal activity. Results of the pharmacokinetic analysis were similar to previously reported data for these drugs. The high serum protein binding of cefoperazone (approximately 90%) contributed to poor blister fluid penetration. The other drugs penetrated well into this fluid compartment. Cefepime showed significantly greater bactericidal activity in serum and blister fluid against E. cloacae than the other study drugs, ceftazidime was significantly better in serum and blister fluid against P. aeruginosa, and cefoperazone was significantly better against S. aureus only in serum. None of the study drugs had significant bactericidal activity in blister fluid against S. aureus. Cefepime is a promising antimicrobial agent for the treatment of infections due to E. cloacae.

The peritoneal absorption of cefoperazone, administered by intraperitoneal (ip) perfusion in a large volume (100 mg/40 ml), was investigated in rats. Its pharmacokinetics was also studied after ip or intravenous (iv) injection of 100 mg/kg in two groups of rats. The peritoneal uptake after the two modes of ip administration was rapid, peaking in less than 20 minutes and the means of peak concentrations were similar. The peak remained high in the group perfused with a large volume for at least 4 hours, which was the end of sample collection. In addition, the absorption half-life and the fraction (F) reaching systemic circulation were calculated and found to be 10.0 +/- 2.5 min and 0.93, respectively. A brief distribution phase (t1/2 alpha 8.0 +/- 0.67 minutes) appeared only after the iv bolus. Otherwise the decline in serum concentration was monoexponential with half-lives of 39.0 +/- 4.0 and 63.6 +/- 7.5 min for the iv and ip injected groups, respectively. The stability of cefoperazone in plasma was also investigated in this study. It was found to be unstable at physiological pH even at -30 degrees C and the samples collected should be buffered in acidic media to optimize stability. The degradation process is likely to contribute to its elimination kinetics during in vivo administration.

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.

The cefoperazone and sulbactam concentrations in human prostatic fluid were measured following intravenous administration of sulbactam/cefoperazone (SBT/CPZ) and its clinical efficacy and safety in the treatment of 11 patients with acute or chronic bacterial prostatitis were evaluated. Cefoperazone concentrations in prostatic fluid (PF) one hour after an intravenous infusion of SBT/CPZ at a dose of 1 g and 2 g were 0.57 +/- 0.26 micrograms/ml and 1.37 +/- 0.86 micrograms/ml, respectively, both exceeding the MIC against most of the isolated strains from expressed prostatic secretion (EPS). The sulbactam levels in PF at doses of 1 g and 2 g of SBT/CPZ were 0.30 +/- 0.18 micrograms/ml and 0.38 +/- 0.13 micrograms/ml, respectively, both of which were high enough to potentiate antimicrobial activity of cefoperazone. The peak of MIC distribution of sulbactam/cefoperazone against E. coli (14 strains) and S. epidermidis (21 strains) isolated from EPS of patients with bacterial prostatitis was in a range of 0.1-0.2 micrograms/ml and 0.2-0.78 micrograms/ml as described for the cefoperazone concentration, respectively, which were superior to those of cefoperazone, ceftazidime and piperacillin, all compared as control, SBT/CPZ exhibited 8 fold or more potent antimicrobial activity than cefoperazone against beta-lactamase producing E. coli and CNS. Clinically, SBT/CPZ was given to 11 patients diagnosed as having bacterial prostatitis in a daily dose of 2-4 g for 5 to 8 days. The drug was found to be effective in all (100%) of 5 patients with acute prostatitis and in 3 (75.0%) of 4 patients who were judged to be assessable among 6 chronic patients. No side effects of any kind were observed in any of the patients treated. In laboratory tests, a transient thrombocytopenia was reported for one patient. SBT/CPZ is particularly useful in the treatment of acute bacterial prostatitis caused by GNR. This drug is useful for chronic prostatitis those, caused primarily by CNS which is susceptible to this agent. This drug is available as an injectable form, subjects for its appropriate usage will be those who show acute exacerbation of infection or who do not respond to oral therapy.

Hyperglycemia may modify pharmacokinetics of some antibiotics as shown in the literature. We studied the influence of glycaemic levels on pharmacokinetics properties of cefoperazone in 12 type 1 insulin dependent diabetic patients. Hyperglycaemia was obtained by a reduction of one quarter of their usual insulin dosage and normoglycaemia by an artificial pancreas (Biostator GCIIS). Cefoperazone had a high protein affinity and a high biliary elimination. Pharmacokinetic study was performed during a 8 hour period following one gram intravenous bolus. We did not found any influence of glycaemic level (normoglycaemia or hyperglycaemia) on the pharmacokinetic parameters of cefoperazone.

Three hundred and twenty patients were enrolled in a prospective randomized trial comparing cefoperazone, ceftizoxime and ceftriaxone for initial therapy of infectious episodes in cancer patients. Patients with neutropenia were excluded. In 286 evaluable episodes, the response rates associated with the three agents were 77% for cefoperazone, 70% for ceftizoxime and 72% for ceftriaxone, with no statistically significant differences between the three treatment groups. The overall response rate for all episodes of pneumonia (64%) was significantly lower than the response rate for all other infections (81%; p = 0.002), and the mortality associated with pneumonia (9%) was higher than that associated with all other episodes (2%; p = 0.01). Patients with infections due to gram-negative organisms responded well to all three agents, whereas patients with gram-positive infections responded more favorably to cefoperazone. Two different schedules of ceftriaxone were used. The clinical response did not differ significantly between patients receiving ceftriaxone once daily and those receiving it twice daily. The incidence of superinfection and relapse was extremely low and all three agents were well tolerated. It is concluded that extended spectrum cephalosporins are effective as single agents for the treatment of infections in cancer patients with adequate neutrophil counts.