Concentrations Of Cefoperazone Research Articles

Vibrational Analysis and Concentration Dependent SERS Study of Cefoperazone

Cefoperazone is a broad-spectrum antibiotic that is extremely efficient in the treatment of respiratory, abdominal, or genital infections. Vibrational spectroscopic techniques, FT-IR, Raman, and SERS, along with DFT calculations, were involved in investigating the normal modes of vibration and adsorption behavior of this antibiotic. Using both the experimental and theoretical data, the bands in the Raman and IR spectra were assigned to the normal vibrational modes. The SERS spectra were successively obtained by using silver and gold colloidal nanoparticles as a substrate. Their analysis revealed that the molecule is chemisorbed on the nanostructured surface through the as-denoted nitrogen ring. Changes observed in the SERS spectra recorded at different cefoperazone concentrations, i.e., modifications in the relative intensity of specific bands suggest the reorientation of adsorbed molecules towards the metal surface.

[Pharmacokinetics and pharmacodynamics of antibiotics in septic children treated with extracorporeal membrane oxygenation].

Objective: To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibacterial agents in children with sepsis treated by extracorporeal membrane oxygenation (ECMO). Methods: In this prospective cohort study, 20 children with sepsis (confirmed or suspected) who were treated with ECMO and antimicrobial in the Department of Critical Medicine of Hunan Children's Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through therapeutic drug monitoring (TDM), the PK-PD parameters of antibacterial agents were analyzed. Twenty five children with sepsis in the same department who were treated with vancomycin but no ECMO at the same time were enrolled as the control group. The individual PK parameters of vancomycin were calculated by Bayesian feedback method. The PK parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison. Results: Twenty patients in the ECMO group, included 6 males and 14 females, with an onset age of 47 (9, 76) months. In the ECMO group, 12 children (60%) were treated with vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases; AUC/minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11 children (55%) who were treated with β-lactam antibiotics, there were 10 cases with drug concentration at 50% dosing interval (CT50)>4 MIC and 9 cases with trough concentration>MIC, both CT50 and trough concentration of cefoperazone reached the target. Among the 25 cases of control group, 16 were males and 9 females, with an onset age of 12 (8, 32) months. There was a positive correlation between vancomycin trough concentration and AUC (r2=0.36, P<0.001). The half-life of vancomycin and the 24-hour AUC (AUC0-24 h) in the ECMO group were higher than those in the control group (5.3 (3.6, 6.8) vs. 1.9 (1.5, 2.9) h, and 685 (505, 1 227) vs. 261 (210, 355) mg·h/L, Z=2.99, 3.50, respectively; both P<0.05), and the elimination rate constant and clearance rate was lower than those in the control group (0.1 (0.1, 0.2) vs. 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) vs. 2.0 (1.1, 2.8) L/h, Z=2.99, 2.11, respectively; both P<0.05). Conclusion: The PK-PD parameters in septic children treated by ECMO varied with a longer half-life, higher AUC0-24 h, lower elimination rate constant and clearance rate.

Pharmacokinetics of cefoperazone/sulbactam in critically Ill thrombotic thrombocytopenic purpura patients undergoing therapeutic plasma exchange.

The aim of this study was to investigate the pharmacokinetics (PK) of cefoperazone (CFP) and sulbactam (SUL) in critically ill thrombotic thrombocytopenic purpura (TTP) patients undergoing therapeutic plasma exchange (TPE). Critically ill TTP patients receiving a dose of 3g CFP/SUL (2.0g/1.0g) intravenously every 8h were included in the study. TPE session began 10min after the end of CFP/SUL infusion. Serial blood samples were collected at 0, 1, 2, 3, 4, 6 and 8h at the fourth infusion with TPE and the sixth infusion without TPE. Effluent samples were collected at the effluent port of plasma eliminated at the end of TPE. Concentrations of CFP and SUL in plasma and effluent were measured using LC-MS/MS. PK parameters were calculated based on two-compartment open model. Five critically ill TTP patients receiving CFP/SUL monotherapy were enrolled. T1/2α of CFP and SUL with TPE was 0.62 and 1.30h, respectively. For CFP, T1/2β with TPE were significantly higher than those without TPE (5.85±3.16 vs. 4.41±2.74, p=0.016). Vss with TPE were significantly higher than those without TPE (7.23±0.89 vs. 5.24±0.80L, p=0.024). AUC0-8 with TPE were significantly lower compared with those without TPE (1380.98±411.99 vs. 1581.61±500.22mg*h/L, p=0.011). Relatively, CLt with TPE were significantly higher than those without TPE (1.56±0.46 vs. 1.37±0.44L/h, p=0.010). For SUL, Vss and CLt were higher significantly with TPE than those without TPE (28.11±8.42 vs. 18.87±6.45L, p=0.002; 10.74±2.01 vs. 8.60±2.10L/h, p=0.048). Mean QPE of CFP and SUL were 344.42±55.37 and 34.65±10.09mg, respectively. Mean fe% of CFP and SUL were 17.22±2.77% and 3.46±1.01%, respectively. TPE enhances the clearance of CFP and SUL in critically ill TTP patients. CFP is more likely to be removed than SUL due to its a low V and high Pb. TPE is suggested to begin 1-2 h after the end of CFP/SUL infusion. Plasma concentration monitoring is advised when CFP/SUL must be administered during TPE.

An adapted LC-MS/MS method for the determination of free plasma concentration of cefoperazone in children: Age-dependent protein binding

Antimicrobial activity of cefoperazone, a high protein bound cephalosporin, depends on its unbound concentration. However, the protein binding data of cefoperazone in children is limited, making it challenging to optimize antimicrobial therapy in pediatric clinical practice. Furthermore, a validated method to measure the free part in children is unavailable with the small volume of samples that can be obtained. Therefore, in the present study, we developed and validated an LC-MS/MS method for the determination of free cefoperazone in children. In this study, 70 μL of plasma was used to prepare the ultrafiltrate (only containing the free drug). Chromatographic separation of the analyte was achieved on a C18 column using gradient elution with a mobile phase of acetonitrile and water (0.1% formic acid). Negative electrospray ionisation in the multiple reaction monitoring mode was applied for the detection of cefoperazone and ceftiofur (internal standard). The calibration curve was prepared in the range of 5–5000 ng/mL with excellent linearity. For each level of quality control samples, the intra- and inter-day precision (CV) was below 9.0%, and the accuracy ranged from 91.5% to 105.0%. The matrix effect was less than 11.7%, and the recovery was between 92.9% and 95.9% of cefoperazone. The validated method has been successfully applied to the determination of free plasma concentration of cefoperazone in pediatric patients. The results of the unbound fraction showed considerable individual variability (range: 8.1–48.0%). The correlation analysis showed that age and albumin had significant effects on the protein binding of cefoperazone.

Determination of cefoperazone and sulbactam in serum by HPLC‐MS/MS: An adapted method for therapeutic drug monitoring in children

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 C18 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.

The impact of inoculum size on the activity of cefoperazone-sulbactam against multidrug resistant organisms.

This study aims to assess the invitro activity of cefoperazone alone and different cefoperazone-sulbactam ratios against different inoculum sizes of multidrug resistant organisms. Minimum inhibitory concentrations (MICs) of cefoperazone, cefoperazone-sulbactam at fixed ratio of 1:1 and 2:1 against a normal inoculum size of 5×105CFU/ml and a high inoculum size of 5×107CFU/ml were measured. Each 33 isolates of extended-spectrum β-lactamases (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae, carbapenem-resistant E. coli, and carbapenem-resistant Pseudomonas aeruginosa and a total of 122 isolates of carbapenem-resistant Acinetobacter baumannii were collected. After the addition of sulbactam at a 1:1 ratio, most MIC50 and MIC90 values decreased. Cefoperazone-sulbactam at a 1:1 ratio had a higher susceptibility rate against ESBL-producing E. coli, carbapenem-resistant E. coli, and carbapenem-resistant A. baumannii than cefoperazone-sulbactam at a 2:1 ratio (all P<0.05). For ESBL-producing E. coli, the susceptibility rate of cefoperazone-sulbactam at ratios of (1:1) and (2:1) decreased from 97.0 to 87.9% and 90.9 to 60.6%, for normal to high inoculum, respectively. For ESBL-producing K. pneumoniae, both susceptibility rate of cefoperazone-sulbactam at ratios of (1:1) and (2:1) decreased from 75.8%, and 63.6% at normal inoculum to 51.5% and 42.4% at high inoculum. Cefoperazone-sulbactam at a 1:1 ratio has greater invitro activity against most multidrug resistant organisms than cefoperazone-sulbactam at a 2:1 ratio. Such combinations were not influenced by the inoculum size of ESBL-producing E. coli and K. pneumoniae and could be a therapeutic option for treating severe infections.

Tracking Cefoperazone/Sulbactam Resistance Development In vivo in A. baumannii Isolated from a Patient with Hospital-Acquired Pneumonia by Whole-Genome Sequencing.

Cefoperazone/sulbactam has been shown to be efficacious for the treatment of infections caused by Acinetobacter baumannii; however, the mechanism underlying resistance to this synergistic combination is not well understood. In the present study, two A. baumannii isolates, AB1845 and AB2092, were isolated from a patient with hospital-acquired pneumonia before and after 20 days of cefoperazone/sulbactam therapy (2:1, 3 g every 8 h with a 1-h infusion). The minimum inhibitory concentration (MIC) of cefoperazone/sulbactam for AB1845 and AB2092 was 16/8 and 128/64 mg/L, respectively. Blood samples were collected on day 4 of the treatment to determine the concentration of cefoperazone and sulbactam. The pharmacokinetic/pharmacodynamic (PK/PD) indices (%T>MIC) were calculated to evaluate the dosage regimen and resistance development. The results showed that %T>MIC of cefoperazone and sulbactam was 100% and 34.5% for AB1845, and 0% and 0% for AB2092, respectively. Although there was no available PK/PD target for sulbactam, it was proposed that sulbactam should be administered at higher doses or for prolonged infusion times to achieve better efficacy. To investigate the mechanism of A. baumannii resistance to the cefoperazone/sulbactam combination in vivo, whole-genome sequencing of these two isolates was further performed. The sequencing results showed that 97.6% of the genome sequences were identical and 33 non-synonymous mutations were detected between AB1845 and AB2092. The only difference of these two isolates was showed in sequencing coverage comparison. There was a 6-kb amplified DNA fragment which was three times higher in AB2092, compared with AB1845. The amplified DNA fragment containing the blaOXA-23 gene on transposon Tn2009. Further quantitative real-time PCR results demonstrated that gene expression at the mRNA level of blaOXA-23 was >5 times higher in AB2092 than in AB1845. These results suggested that the blaOXA-23 gene had higher expression level in AB2092 via gene amplification and following transcription. Because gene amplification plays a critical role in antibiotic resistance in many bacteria, it is very likely that the blaOXA-23 amplification results in the development of cefoperazone/sulbactam resistance in vivo.

The fluorescence and resonance Rayleigh scattering spectral study and analytical application of cerium (IV) and cefoperazone system

In weak acidic medium of pH3.5–5.6, Ce(IV) can be reduced by cefoperazone (CPZ) to be Ce(III), which further combined with CPZ to form complex Ce(OH)3CPZ. This complex not only has higher fluorescence than Ce(III), but also results in significant increase of resonance Rayleigh scattering (RRS), second order scattering (SOS) and frequency doubling scattering (FDS). The wavelengths of maximum fluorescence exciting and emission are located at 356nm/349nm, while the maximum wavelengths of RRS, SOS and FDS are at 312nm, 550nm and 390nm, respectively. The intensity of fluorescence and scattering are all linear with the concentration of CPZ in certain conditions. The detection limit of most sensitive RRS method for CPZ is 2.1ngmL−1. The optimum conditions for detecting CPZ using RRS method are investigated. The effect of co-existing substances shows that the method has excellent selectivity, especially since other cephalosporins don't have similar reactions. Therefore, it can be achieved to determine CPZ in cephalosporins selectively. The paper also focuses on the reaction mechanism, the consistent and contracture of the resultant. The reasons for enhanced intensity are presumed in the meantime.

Proposal for agar disk diffusion interpretive criteria for susceptibility testing of bovine mastitis pathogens using cefoperazone 30 μg disks

Cefoperazone is a third generation cephalosporin which is commonly used for bovine mastitis therapy. Bacterial pathogens involved in bovine mastitis are frequently tested for their susceptibility to cefoperazone. So far, the cefoperazone susceptibility testing using 30μg disks has been hampered by the lack of quality control (QC) ranges as well as the lack of interpretive criteria. In 2014, QC ranges for 30 μg cefoperazone disks have been established for Staphylococcus aureus ATCC® 25923 and Escherichia coli ATCC® 25922. As a next step, interpretive criteria for the susceptibility testing of bovine mastitis pathogens should be developed. For this, 637 bovine mastitis pathogens (including 112 S. aureus, 121 coagulase-negative staphylococci (CoNS), 103 E. coli, 101 Streptococcus agalactiae, 100 Streptococcus dysgalactiae and 100 Streptococcus uberis) were investigated by agar disk diffusion according to the document Vet01-A4 of the Clinical and Laboratory Standards Institute (CLSI) using 30μg cefoperazone disks and the results were compared to the corresponding MIC values as determined by broth microdilution also according to the aforementioned CLSI document. Based on the results obtained and taking into account the achievable milk concentration of cefoperazone after regular dosing, the following interpretive criteria were proposed as a guidance for mastitis diagnostic laboratories: for staphylococci and E. coli ≥23mm (susceptible), 18–22mm (intermediate) and ≤17mm (resistant) and for streptococci ≥18mm (susceptible), and ≤17mm (non-susceptible). These proposed interpretive criteria shall contribute to a harmonization of cefoperazone susceptibility testing of bovine mastitis pathogens.

Comparative pharmacokinetics of cefoperazone following intravenous and intramuscular administration in goats

The pharmacokinetic profile of cefoperazone was studied in goats following intravenous and intramuscular administration of 20mg/kg body weight. Cefoperazone concentrations in serum were determined by microbiological assay technique using Escherichia coli (ATCC 10536) as test organism. Following i.v. administration, the cefoperazone serum concentration–time curve was best fitted in a two compartment open model. Cefoperazone has moderate distribution in the body of goats with Vdss of 0.44±0.03L/kg. The elimination half-life (T0.5(β)), area under curve (AUC) and total body clearance (Cltot) were 1.97±0.14h, 149.63±8.61μgml−1h−1, and 2.17ml/min/kg, respectively. Following i.m. administration, the drug was very rapidly absorbed, with an absorption half-life (T0.5(ab)) of 0.12±0.01h. The maximum serum concentration (Cmax) of 30.42±3.53μgml−1 was attained at (Tmax) 0.58±0.02h, with an elimination half-life (T0.5(el)) of 2.53±0.11h. The systemic bioavailability of cefoperazone in the goats after i.m. administration was 83.62% and in vitro protein binding was 20.34%. The serum concentrations of cefoperazone along 12h post i.m. injection in this study were exceeding the MIC of different susceptible micro-organisms responsible for serious disease problems. Consequently, a suitable intramuscular dosage regimen for cefoperazone was 20mg/kg repeated at 12h intervals in goats. The drug was detected in urine up to 12 and 18h following i.v. and i.m. administration, respectively.

Pharmacokinetic interaction of nitroxynil and cefoperazone in goats

The pharmacokinetic aspects of cefoperazone (CEFO) were investigated via intravenous (IV), and intramuscular (IM) injections in clinically healthy goats at a dose of 20 mg/kg b.wt. Goats were pre-treated with nitroxynil (25%) or nitroxynil (34%) subcutaneously in a dose 10 mg/kg b.wt, respectively. Cefoperazone was injected intramuscularly nine hours following anthelmintic administration, and blood samples were taken by jugular venipuncture at standardized intervals. Cefoperazone concentrations in serum were determined by microbiological assay technique. Goats pre-treated with nitroxynil (25%) or nitroxynil (34%) showed a significant decrease in serum cefoperazone level as compared to non-anthelmintic treated goats. The obtained data revealed that administration of nitroxynil in both concentrations negatively affected most of the cefoperazone parameters. In this respect, the elimination half-life T0.5(el), Cmax, AUC, and the systemic bioavailability (F %) were significantly decreased in both groups of nitroxynil-treated goats compared to non-anthelmintic treated goats. On the other hand, there were no significance differences between both nitroxynil (25% and 34%) treated goats. Concomitant administration of nitroxynil (25% and 34%) with cefoperazone resulted in significant alterations in the disposition kinetic of cefoperazone in goats. Consequently, the interaction between nitroxynil and cefoperazone could be of clinical significance and may require monitoring and adjustment of cefoperazone dosage.

Effects of ampicillin, cefazolin and cefoperazone treatments on GLT-1 expressions in the mesocorticolimbic system and ethanol intake in alcohol-preferring rats

Chronic ethanol consumption is known to downregulate expression of the major glutamate transporter 1 (GLT-1), which increases extracellular glutamate concentrations in subregions of the mesocorticolimbic reward pathway. While β-lactam antibiotics were initially identified as potent upregulators of GLT-1 expression, only ceftriaxone has been extensively studied in various drug addiction models. Therefore, in this study, adult male alcohol-preferring (P) rats exposed chronically to ethanol were treated with other β-lactam antibiotics, ampicillin, cefazolin or cefoperazone (100mg/kg) once daily for five consecutive days to assess their effects on ethanol consumption. The results demonstrated that each compound significantly reduced ethanol intake compared to the saline-treated control group. Importantly, each compound significantly upregulated both GLT-1 and pAKT expressions in the nucleus accumbens and prefrontal cortex compared to saline-treated control group. In addition, only cefoperazone significantly inhibited hepatic aldehyde dehydrogenase-2 enzyme activity. Moreover, these β-lactams exerted only a transient effect on sucrose drinking, suggesting specificity for chronically inhibiting ethanol reward in adult male P rats. Cerebrospinal fluid concentrations of ampicillin, cefazolin or cefoperazone have been confirmed using high-performance liquid chromatography. These findings demonstrate that multiple β-lactam antibiotics demonstrate efficacy in reducing alcohol consumption and appear to be potential therapeutic compounds for treating alcohol abuse and/or dependence. In addition, these results suggest that pAKT may be an important player in this effect, possibly through increased transcription of GLT-1.

Cefoperazone sodium preparation behavior after intramammary administration in healthy and infected cows

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 μg/mL serum at 4h), whereas it was higher in infected animals (0.102±0.079 μg/mL at 4h and 0.025 μg/mL at 24h), 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 μg/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±5.74h in September and 2.07±0.43 vs. 3.31±0.91h in October), with a t>MIC of 45±6h for infected quarters versus 38±5h 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.

A Fatal Case of Suspected Anaphylaxis with Cefoperazone and Sulbactam: LC‐MS Analysis

Cefoperazone and sulbactam are prescribed in combination and used in the treatment of moderate to severe bacterial infections. Serious anaphylaxis is a rare side effect. This report describes a fatal case of suspected anaphylaxis after intravenous administration of a combination of the two drugs. Heart blood was analyzed for cefoperazone by protein precipitation with acetonitrile and by liquid-liquid precipitation for sulbactam after protein precipitation with aqueous acetonitrile, followed by tandem mass spectrometry in the product ion scan mode for identification and by liquid chromatography mass spectrometry in the selected ion monitoring mode for quantitation. Calibration curves for cefoperazone and sulbactam were linear over the range 0.07 to 1.93 and 0.046 to 0.914 microg/ml respectively. The decedent's blood concentrations of cefoperazone and sulbactam were 0.368 and 0.143 microg/ml respectively. As these concentrations were below concentrations reported after single dosing studies and below those considered to be minimally inhibitory, death was presumed to have been caused by hypersensitivity and not an overdose. In conclusion, this procedure is useful for detecting and quantitating cefoperazone and sulbactam in postmortem blood and may be useful in the evaluation of anaphylaxis.

BmeRABC5 Is a Multidrug Efflux System That Can Confer Metronidazole Resistance inBacteroides fragilis

The RND-family efflux pump gene bmeB5 was previously shown to be overexpressed in metronidazole-resistant laboratory mutants of Bacteroides fragilis. In the present study, we characterized the bmeABC5 genes and an upstream putative TetR-family regulator gene (bmeR5). bmeR5 (645 bp) was located 51 bp upstream of bmeA5 and encoded a 24.9-kDa protein. Deletant strains lacking bmeB5 or bmeR5 were constructed from a wild-type B. fragilis strain ADB77. Strain antimicrobial susceptibility was determined and gene expression was quantified. bmeR5 was overexpressed in Escherichia coli using a 6x-His tag system; BmeR5-His6 was isolated from inclusion bodies and its binding to bmeABC5 promoter regions was determined. BmeR5-His6 bound specifically to the bmeR5-bmeC5 intergenic region (IT1). Deletion of bmeR5 (ADB77DeltabmeR5) resulted in a significant (p < 0.05) increase in expression of bmeA5, bmeB5, and bmeC5, and > two-fold increase in minimum inhibitory concentrations (MICs) of ampicillin, cefoxitin, cefoperazone, ciprofloxacin, imipenem, metronidazole, ethidium bromide, and sodium dodecyl sulfate (SDS). MICs were reduced by the efflux pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP). The MICs of ampicillin, cefoperazone, metronidazole, and SDS were reduced by approximately two-fold in ADB77DeltabmeB5. A multidrug (metronidazole)-resistant, nim-negative B. fragilis clinical isolate overexpressed bmeABC5 genes, had a G-->T point mutation in IT1, and significantly reduced binding to BmeR5-His6. These data demonstrate that BmeR5 is a local repressor of bmeABC5 expression and that mutations in IT1 can lead to a derepression and resistance to multiple antimicrobial agents, including metronidazole.

The peculiarities of Pseudomonas aeruginosa resistance to antibiotics and prevalence of serogroups

Pseudomonas aeruginosa is one of the most common nonfermenting aerobic gram-negative microorganisms identified in clinical specimens of hospitalized patients. The emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa strains is a growing concern in hospital-acquired infections. Typing of strains is important for identifying the sources of infection as well as prevention of cross-infections and monitoring of the efficacy of antimicrobial therapy. The aim of this study was to evaluate the antimicrobial resistance and prevalence of Pseudomonas aeruginosa serogroups isolated at Kaunas University of Medicine Hospital, Lithuania. Minimum inhibitory concentrations of piperacillin, cefoperazone, ceftazidime, cefotaxime, cefepime, imipenem, meropenem, gentamicin, amikacin, tobramycin, and ciprofloxacin for 609 Pseudomonas aeruginosa strains isolated from various clinical specimens between November 2001 and November 2002 were determined by the microdilution method in Mueller-Hinton agar using interpretative guidelines of National Committee for Clinical Laboratory Standards. Serogroups of Pseudomonas aeruginosa strains were identified using serums of Seiken Co. Ltd (Tokyo, Japan), containing antibodies against antigens of Pseudomonas aeruginosa O-group. Pseudomonas aeruginosa strains were the most sensitive to ceftazidime (78.9%), imipenem (73.6%), meropenem (70.9%) and the most resistant to gentamicin (54.1%) and ciprofloxacin (52.5%). Multidrug-resistant strains made up 9.85% of all Pseudomonas aeruginosa strains investigated. Multidrug-resistant Pseudomonas aeruginosa strains were 1.5-3.5 times more resistant to antibiotics compared to non-multidrug-resistant strains, except to amikacin: multidrug-resistant strains were more sensitive (81.7%) than non-multidrug-resistant Pseudomonas aeruginosa strains (61.0%). Pseudomonas aeruginosa serogroups O:E and O:B were the most common serogroups (34.7% and 29.0%, respectively) followed by serogroups O:I (11.4%) and O:A (10.1%). Pseudomonas aeruginosa serogroup O:E strains were the most prevalent among multidrug-resistant strains (48.3%). The results of our study show that serogroup O:E was the most prevalent serogroup of Pseudomonas aeruginosa in our hospital, and its resistance to antibiotics was the highest.

Pharmacokinetics of Cefoperazone and Sulbactam in Liver Transplant Patients

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.

Pharmacokinetics of cefoperazone in horses.

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.

First and second derivative spectrophotometric determination of cefoperazone and sulbactam in injections

A simple, spectrophotometric assay to measure the concentrations of cefoperazone and sulbactam in injectable formulations is described. Since zero-order spectra are subject to interference, derivative spectrophotometry was used to enhance the spectral details. A linear relationship between derivative amplitudes and the concentrations of the compounds was found. Beer's law is obeyed up to 75 and 80 μ ml −1 of cefoperazone in the first and second derivative modes, respectively, and up to 75 μ ml −1 of sulbactam in the second derivative mode. Detection limits were 0.64 and 0.88 μ ml −1, respectively for cefoperazone in the first and second derivative modes and 0.30 μ ml −1 for sulbactam in the second derivative mode. The method is rapid, simple, does not require a separation step and has successfully been applied to the assay of commercial injections containing cefoperazone and sulbactam.

Inhibitory effect of clindamycin on production of beta-lactamase in beta-lactam-resistant bacteria.

The inhibitory effect of clindamycin on beta-lactamase biosynthesis was investigated in beta-lactam resistant bacteria with inducible and/or constitutive production of the enzyme(s). Clinical isolates of Enterobacter cloacae (E. cloacae) and Pseudomonas aeruginosa (P. aeruginosa) were examined. Three strains of each, against which sulbactam at 8 micrograms/ml reduced the minimum inhibitory concentration (MIC) of cefoperazone (CPZ) at least 4 fold, were studied in greater detail. Although clindamycin had no appreciable effect on bacteria growth at concentrations up to 50 micrograms/ml, it suppressed inducible beta-lactamase biosynthesis almost completely at a concentration of 20 micrograms/ml. There was also a significant reduction of constitutive enzyme biosynthesis by clindamycin at 50 micrograms/ml. Thus, it was estimated that a high concentration of clindamycin was required to suppress beta-lactamase biosynthesis in beta-lactamase producing bacteria of the constitutive type.