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BACKGROUND Respiratory tract infections in the elderly are difficult to cure and can easily recur, thereby posing a great threat to patient prognosis and quality of life. AIM To investigate the therapeutic effects of different antibiotics in elderly patients with respiratory tract infection. METHODS Seventy-four elderly patients with respiratory tract infection were randomly allocated to a study (n = 37; treated with cefoperazone sodium/sulbactam sodium) or control (n = 37; treated with piperacillin sodium/tazobactam sodium on the basis of routine symptomatic support) group. Both groups were treated for 7 d. Time to symptom relief (leukocyte recovery; body temperature recovery; cough and sputum disappearance; and rale disappearance time), treatment effect, and laboratory indexes [procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (NE)] before and 7 d after treatment and the incidence of adverse reactions were assessed. RESULTS In the study group, the time to WBC normalization (6.79 ± 2.09 d), time to body temperature normalization (4.15 ± 1.08 d), time to disappearance of cough and sputum (6.19 ± 1.56 d), and time to disappearance of rales (6.68 ± 1.43 d) were shorter than those of the control group (8.89 ± 2.32 d, 5.81 ± 1.33 d, 8.77 ± 2.11 d, and 8.69 ± 2.12 d, respectively; P = 0.000). Total effective rate was higher in the study group (94.59% vs 75.68%, P = 0.022). Serum PCT (12.89 ± 3.96 μg/L), CRP (19.62 ± 6.44 mg/L), WBC (20.61 ± 6.38 × 109/L), and NE (86.14 ± 7.21%) levels of the study group before treatment were similar to those of the control group (14.05 ± 4.11 μg/L, 18.79 ± 5.96 mg/L, 21.21 ± 5.59 × 109/L, and 84.39 ± 6.95%, respectively) with no significant differences (P = 0.220, 0.567, 0.668, and 0.291, respectively). After 7 d of treatment, serum PCT, CRP, WBC, and NE levels in the two groups were lower than those before treatment. Serum PCT (2.01 ± 0.56 μg/L), CRP (3.11 ± 1.02 mg/L), WBC (5.10 ± 1.83 × 109/L), and NE (56.35 ± 7.17%) levels were lower in the study group than in the control group (3.29 ± 0.64 μg/L, 5.67 ± 1.23 mg/L, 8.13 ± 3.01 × 109/L, and 64.22 ± 8.08%, respectively; P = 0.000). There was no significant difference in the incidence of adverse reactions between the groups (7.50% vs 12.50%, P = 0.708). CONCLUSION Piperacillin sodium/tazobactam sodium is superior to cefoperazone sodium/ sulbactam sodium in the treatment of elderly patients with respiratory tract infection with a similar safety profile.

We report a case of rashes in a patient undergoing cesarean section. She was administered cefoperazone and sulbactam sodium + metronidazole sodium chloride combined with morphine hydrochloride perioperatively, which caused a rash as an adverse side effect. The patient, 35 years old, underwent lower uterine segment cesarean section under combined spinal-epidural anesthesia. She received intravenous infusion of cefoperazone sodium and sulbactam sodium + metronidazole sodium chloride for anti-infection therapy before operation and morphine hydrochloride for analgesia at the end of the operation. The patient later experienced skin itching and had rashes on the waist, abdomen, and back. According to the patient's physical signs, the correlation with drug injection time, and the adverse side effects reported in the drug instructions and related literature, the adverse side effect may have been caused by cefoperazone sodium and sulbactam sodium, metronidazole sodium chloride, and morphine hydrochloride. The drugs were suspended, and the patient was given anti-allergic treatment. After that, the above symptoms subsided. Therefore, we suspect that cefoperazone sodium and sulbactam sodium, metronidazole sodium chloride, or morphine hydrochloride injection, or a combination of two or more of these drugs, caused the adverse side effect of skin rash in the patient. This study reports a case of adverse side effects of skin itching and rash after the use of cefoperazone sodium and sulbactam sodium, metronidazole sodium chloride, and morphine hydrochloride in a pregnant woman undergoing cesarean section. The occurrence of adverse side effects in special populations should attract clinicians' attention. When giving such drugs, medical personnel should take a full history the patient's allergy and closely monitor the occurrence of adverse side effects in the early stages of medication.

The authors report a rare case of primary cutaneous mucormycosis caused by Mucor irregularis and cutaneous Klebsiella pneumoniae infections in a 67-year-old Chinese woman. After the administration of liposomal amphotericin B combined with cefoperazone/sulbactam sodium, the patient recovered. Invasive fungal infection combined with cutaneous bacterial infection should receive attention.

Green chemistry aims to develop earth-friendly chemical processes and products that will prevent or minimize pollution and hazardous substances. In this work, the green chemistry was applied for th...

Aim of the study was to develop an efficient alternative for bone infections obtained during or after reconstruction surgeries using third generation antibiotic [ceftriaxone and sulbactam sodium (CFS)] loaded mesoporous bioactive glass (MBG) nanopowders. MBG nanopowders were prepared using cationic surfactant CTAB by wet chemical process, which gave spherical morphology (

Background With essentially no drug available to control the infection caused by the extensively drug-resistant Acinetobacter baumannii (XDR-Ab) in infants and young children, this study explored the clinical outcomes of pediatric patients with drug-resistant XDR-Ab who were treated with rifampicin in combination with sulbactam sodium. Methods The data for clinical outcomes, microbiological responses, and side effects were collected and evaluated for 12 critically ill infants and young children diagnosed with ventilator-associated pneumonia caused by XDR-Ab following surgical treatment for congenital heart disease in a pediatric cardiac intensive care unit. This study was approved by local institutional review board (IRB). Results Two patients died from the complex underlining diseases. The other 10 patients were weaned off the mechanical ventilation successfully within 4-15 days after the start of treatment with rifampicin combined with sulbactam sodium and discharged home. Three cases experienced adverse side effects, including severe rash and elevated aminotransferase level. Conclusion The combination of rifampicin and sulbactam sodium appeared to be an effective and safe therapy for severe ventilator-associated pneumonia caused by XDR-Ab in infants and young children. Side effects such as skin rashes and elevated aminotransferase levels can be reversed once rifampicin is discontinued in time. (Funded by the Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Chang-sha, China; the Departments of Anesthesiology and Pain Medicine of University of California Davis Health; and the National Institutes of Health.).

The rapid detection of β-lactamases (Blas) and effective screening of Bla inhibitors are critically important and urgent for solving antibiotic resistance and improving precision medicine. Here a novel fluorescent probe CDC-559 was designed and synthesized, which can be used for the selective and direct detection of AmpC Blas. More importantly, it can realize screening the Bla inhibitors with sulbactam sodium and tazobactam as model compounds, and the half-maximal inhibitory concentration are 0.279 μM and 0.053 μM, respectively. CDC-559 can be applied not only to examine the resistance of the strains, but also to categorize its mode of action specifically, which is consistent with the essential result of the Blas. The research suggests that CDC-559 probe features its tremendous potential in the rapid detection of AmpC Blas as well as the strains with AmpC-encoded gene, which is instructive in promoting better antibiotic stewardship practices and developments.

Acute localized exanthematous pustulosis is a localized variant of acute generalized exanthematous pustulosis, which is characterized by the eruption of multiple scattered pustules following drug administration. A 72-year-old woman presented with multiple erythematous pustules on her face, which had appeared two days after using cefoperazone and sodium sulbactam. Histopathological findings showed subcorneal pustules and mixed inflammatory cell infiltration in the dermis. The pustules resolved within about two weeks after the patient discontinued the antibiotics. This report discusses the case of a woman with a cutaneous drug reaction consistent with acute localized exanthematous pustulosis that occurred after cefoperazone and sodium sulbactam were administered.

A reverse phase - liquid chromatographic method with UV detection is developed for simultaneous estimation of ceftriaxone sodium and sulbactam sodium in rat plasma. A simple protein precipitation technique was employed for the extraction of drugs from blank plasma. Chromatographic separation of the two drugs was achieved on C18 column (250 mm X 4.6 mm, i.d, 5 μm) using a mobile phase consisting of 10mM potassium dihydrogen orthophosphate buffer (pH - 5) and aceto nitrile (90:10 % v/v). The developed liquid chromatographic method eluted both the drugs with a reasonable retention time, acceptable symmetric peak shape and good resolution. The developed bio - analytical method was linear, accurate, and precise over the co ncentration range of 20 - 150 μg mL - 1 for ceftriaxone and 10 - 75 μg mL - 1 for sulbactam. The developed method was successfully applied to monitor ceftriaxone and sulbactam sodium concentrations in rat plasma.

There is an urgent need to discover new anti-microbial agents that can overcome the increasing antibiotic resistance posed by multidrug resistant, β-lactamase producing bacteria. β-Lactam antibiotics are structurally related through the presence of a core β-lactam ring. Resistant pathogens are able to produce β-lactamase enzymes that hydrolyze the β-lactam ring and inactivate the antibiotic. One approach to counteract this resistance is to develop β-lactamase inhibitors, which, on administration with β-lactams, restores the antibiotic activity for its continued clinical use. In the present study, a fungal Penicillium strain was isolated, identified and characterized for its antimicrobial and β-lactamase inhibition activities. The strain was identified as Penicillium piceum and was grown in suitable media under submerged cultivation. The antibacterial activity was observed against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Higher antimicrobial activity was observed against gram-positive bacteria as compared to gram-negative bacteria. A certain amount of antifungal activity was also observed against the fungal strains of Penicilium chrysogenum, Rhizopus stolonifer, Fusarium moniliforme, Aspergillus niger, Giberella fujikuroi and Saccharomyces cerevisiae. Iodometric and bioassay analyses confirmed that P. piceum produced β-lactamase inhibitors having activity against penicillinase (Bacillus cereus). Solvent-solvent extraction with butanol yielded a three-fold increase in β-lactamase inhibition activity. High-performance liquid chromatography analysis of the concentrated product proved it to be a single compound. The infrared (IR) spectrum of the compound was compared with the reference IR spectra of sulbactam sodium, tazobactam and potassium clavulanate. It was found to be different thereby inferring the need for extensive structural elucidation for future applications.

Meropenem and Sulbactam sodium as combination injection is used for the treatment of lower respiratory tract infection caused by gram negative bacteria in adults only. The aim of this research work to developed and validate simple, specific and sensitive RP-HPLC method for estimation of Meropenem and Sulbactam sodium in combined pharmaceutical dosage form. In RP-HPLC, method was carried out by isocratic technique on a reversed-phase. HyperSil C18 column kept at ambient temperature and UV detection at 225 nm with mobile phase containing a mixture of water with 0.2% triethylamine and Acetonitrile pH 6.0 adjusted with Ortho-phosphoric acid (80:20 v/v), at a flow rate of 1.0 ml/min. Calibration curves were linear in the concentration range of 8-18 μg/ml for MPM (r 2 = 0.9998) and SUL 4-9 μg/ml for SUL (r 2 = 0.9995).the method was validated in terms of accuracy, precision ,interday, intraday and robustness as per ICH guideline. Thus all three methods were found to be simple, sensitive, accurate, precise so these methods applicable for routine analysis.

Purpose To develop a novel complex antimicrobial agent and determine the optimal components of the composite antimicrobial agents and its antimicrobial activity in vitro. Methods According to antimicrobial mechanisms，antibacterial spectrums，physical and chemical properties and applicabilities of existing antimicrobial agents in clinical use, select out cefoperazone sodium, sulbactam sodium and cephradine as the basic components to make a novel complex antimicrobial agent. Utilize yeast, staphylococcus aureus and E. coli bacteria as test bacteria. Do the three factors four-level orthogonal experiments by the maximum amount, the middle amount, low amount and Minimum amount of the three-component agent to research the optimum ratio of the drug. Measure the titer of the compound antimicrobial agent by the way of tube-plate method (2 doses). With known contents of Penicillin Sodium for Injection as control, and determine its minimum inhibitory concentration against staphylococcus aureus, E. coli and yeast by using the agar doubling dilution method. The experimental results were analysized by statistical analysis software SPSS16.0. Results The results of the three factors four-level orthogonal experiments indicate the optimum ratios of Cefoperazone Sodium, Sulbactam Sodium and Cephradine against E. coli, yeast and staphylococcus aureus were 2:2:3, 1:2:2 and 2:6:5, their titers were 1353.9U/mg, 982.7U/mg and 1015.5U/mg. With the highest titer proportion 2:2:3 as the composition of the antimicrobial compound. This compound antimicrobial agent had a good antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria and Fungi, its minimal inhibitory concentration (MIC) against staphylococcus aureus, E. coli and yeast were 2.000μg/ml, 0.500μg/ml and 16.000μg/ml. Conclusion This research acquires a composite of antibiotics. This antimicrobial compound has a broader spectrum and higher antimicrobial activity in vitro comparing with traditional common single antibiotics, and it especially has a good antimicrobial activity against fungi. The results set a scientific foundation for enriching clinical medicines.

Background: A fixed dose combination of cefuroxime sodium (β lactam antibiotic) and sulbactam sodium (β Lactamase inhibitor) is used in ratio of 2:1 as powder for injection for the treatment of resistant lower respiratory tract and other infections. Aims: A simple, precise, and accurate ion-pair reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for determination of cefuroxime Na(CEF) and sulbactam Na(SUL) in injection. Materials and Methods: Isocratic RP-HPLC separation was achieved on an ACE C 18 column (150×4.6 mm id, 5 μm particle size) using the mobile phase 0.002 M tetrabutylammonium hydroxide sulfate (TBAH) in 10 mm potassium di-hydrogen phosphate buffer-acetonitrile (86:14 v/v, pH 3.7) at a flow rate of 1.0 ml/min. Results and Conclusion: The retention time of sulbactam Na and cefuroxime Na were 3.2 min and 10.2 min, respectively. The ion-pairing reagent improved the retention of highly polar sulbactam Na on reverse-phase column. The detection was performed at 210 nm. The method was validated for linearity, precision, accuracy, robustness, solution stability, and specificity. The method was validated for linearity, precision, accuracy, robustness, solution stability, and specificity. The method was linear in the concentration range of 10-100 μg/ml for cefuroxime Na and 5-50 μg/ml for sulbactam Na, with a correlation coefficient of 0.9999 and 0.9998 for the respective drugs. The intraday precision was 0.13-0.21% and 0.48-0.65%, and the interday precision was 0.32-0.81% and 0.60-0.83% for cefuroxime Na and sulbactam Na, respectively. The accuracy (recovery) was found to be in the range of 98.76-100.61% and 98.99-100.30% for cefuroxime Na and sulbactam Na, respectively. The drugs were found to degrade under hydrolytic and oxidative conditions. The drugs could be effectively separated from different degradation products, and hence the method can be used for stability analysis.

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.

Problem statement: To develop a sensitive method to determine simultaneously ceftizidime and sulbactam in spiked plasma and combined formulation. Approach: In this study an isocratic High performance liquid chromatographic method with UV detection at 230 nm was described for simultaneous determination of Ceftazidime and sulbactam sodium in plasma and combined dosage form. Chromatographic separation of two drugs was achieved on a Hypersil ODS C-18 column using a mobile phase consisting of a binary mixture of acetonitrile and tetrabutyl ammonium hydroxide adjusted to pH 5.0 with orthophosphoric acid in ratio 25:75. Results: The developed performance liquid chromatographic method offers symmetric peak shape, good resolution and reasonable retention time for both drugs. Linearity, accuracy and precision were found to be acceptable over the concentration range of 125-625 ppm for Ceftazidime and 62.5-312.5 ppm for sulbactam sodium. Conclusion: The results showed that this method could be well used for the simultaneous estimation of Ceftazidime and Sulbactam in plasma and combined formulation.

An isocratic liquid chromatographic method with UV detection at 220 nm is described for simultaneous determination of ceftriaxone sodium and sulbactam sodium in Sulbactomax. Chromatographic separation of two drugs was achieved on a Hypersil ODS C-18 column using a mobile phase consisting of a binary mixture of acetonitrile and tetrabutyl ammonium hydroxide adjusted to pH7.0 with orthophosphoric acid in ratio 70:30. The developed Liquid Chromatographic method offers symmetric peak shape, good resolution and reasonable retention time for both drugs. Linearity, accuracy and precision were found to be acceptable over the concentration range of 125-750 ppm for ceftriaxone sodium and 62.5-375 ppm for sulbactam sodium. The LC method can be used for the quality control of formulated products containing ceftriaxone and sulbactam.

A microcalorimetric technique based on the bacterial heat output was applied to evaluate the influence of antibiotics PIP (Piperacillin Sodium) and composite preparation of PIP and SBT (Sulbactam Sodium) on the growth of E. coli DH5α. The power–time curves of the growth metabolism of E. coli DH5α were studied using a TAM Air Isothermal Microcalorimeter at 37°C. By analyzing the power–time curves, the parameters such as growth rate constants (k), inhibitory ratio (I), the maximum heat power (Pm) and the time of the maximum heat power (tm) were obtained. The results show that different concentrations of antibiotics affect the growth metabolism of E. coli DH5α. The PIP in the concentration range of 0–0.05 µg mL–1 has a stimulatory effect on the E. coli DH5α growth, while the PIP of higher concentrations (0.05 –0.25 µg mL–1) can inhibit its growth. It seems that the composite preparation composed of PIP and SBT cannot improve the inhibitory effect on E. coli DH5α as compared with the PIP.

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination were studied in 6 sheep, after intravenous and intramuscular injection at a single dose rate of 20 mg/kg body weight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open 2-compartment model after intravenous administration and a onecompartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.32 ± 0.06 L/kg and 0.42 ± 0.04 L/kg, respectively and the total body clearances were 0.69 ± 0.07 and 0.38 ± 0.03 L/kg-h, respectively. The elimination halflives of ampicillin after intravenous and intramuscular administration were 0.32 ± 0.05 h and 0.75 ± 0.27 h, respectively, whereas for sulbactam the half-lives were 0.74 ± 0.10 h and 0.89 ± 0.16 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (72.76 ± 9.65 % for ampicillin and 85.50 ± 8.35% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.25 ± 0.10 h and 0.24 ± 0.08 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.01 + 7.36 mg/L of ampicillin and 10.39 3.95 mg/L of sulbactam). Both drugs had a similar pharmacokinetic behavior after intramuscular administration in sheep. Since the plasma concentrations of sulbactam where consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillinsulbactam combination in a higher than 2:1 ratio.

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination after intravenous (i.v.) and intramuscular (i.m.) injection at a single dose rate of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were studied in 10-day-old neonatal calves (n = 10). The plasma concentration-time data of both antibiotics were best fitted to an open two-compartment model after i.v. administration. After i.m. administration, an open two-compartment model demonstrated first order absorption. The apparent volumes of distribution of ampicillin and sulbactam, calculated by the area method, were 0.20+/-0.01 and 0.18+/-0.01 L/kg, respectively, and the total body clearances were 0.51+/-0.03 and 0.21+/-0.01 L/kg h. The elimination half-lives of ampicillin after i.v. and i.m. administration were 0.99+/-0.03 and 1.01+/-0.02 h, respectively, whereas for sulbactam the half-lives were 2.24+/-0.02 and 3.44+/-0.94 h. The bioavailability after i.m. injection was high and similar for both drugs (70.31+/-0.2% for ampicillin and 68.62+/-4.44% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.47+/-0.02 and 0.72+/-0.01 h, respectively) and peak concentrations were also similar but not proportional to the dose administered (17.88+/-0.91 mg/L of ampicillin and 12.92+/-0.79 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after i.m. administration. Since the plasma concentrations of sulbactam were consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a ratio higher than 2:1.

An isocratic liquid chromatographic method with UV detection at 210 nm is described for simultaneous determination of amoxicillin sodium and sulbactam sodium in a new combination formulation. Chromatographic separation of the two drugs was achieved on a Hypersil C 18 column using a mobile phase consisting of a binary mixture of methanol and 0.01 mol/l sodium acetate (5:95, v/v). The commonly used paired-ion aqueous mobile phase for the determination of penicillins was avoided in this study. The developed LC method offers symmetric peak shape, good resolution and reasonable retention time for both drugs. Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 155.3–1553.0 μg/ml for amoxicillin sodium and 45.0–450.0 μg/ml for sulbactam sodium. The proposed LC method can be used for the quality control of formulated products containing these two drugs.

Solution calorimetric technique has been used to determine the compatibility of binary and ternary systems of ampicillin trihydrate (AMP), sulbactam sodium (SS), amoxicillin trihydrate (AM), potassium clavulanate (PC) and ciprofloxacin hydrochloride (CP). The enthalpy of solution (Δ sol H ) were obtained over a wide range of composition in the pH range 2–9. For all the pure drugs the Δ sol H is endothermic in nature. The molar enthalpies of interaction of binary (Δ H bi. E ) and ternary (Δ H ter. E ) mixtures of the drugs in aqueous buffers have been determined. The Δ H bi. E for all binary systems is negative and pH dependent (maximum pH 6–8) indicating the interaction among charged species of the drugs. In case of binary systems with CP the magnitude of Δ H bi. E indicate strong interactions. The variation and magnitude of Δ H bi. E for the systems is discussed in terms of hydrogen bonding and van der Waal’s interaction in the solution. The interaction parameter for ternary systems ( A ) is positive indicating repulsive interaction among the drugs. The coefficients h i ’s calculated from Redlich–Kister equation for binary systems (Δ H bi. E ) and ternary interaction parameter ( A ) were used to predict the compatibility of the marketed formulations in pH range studied.

A rapid and accurate high performance liquid chromatography (HPLC) method is described for simultaneous determination of piperacillin sodium and sulbactam sodium in sterile powder for injection. Chromatographic separation of the two drugs was achieved on a Diamonsil C18 column (150 × 4.6 mm, 5 µm) using a mobile phase consisting of a mixture of methanol and 0.01 M tetrabutylammonium hydroxide (TBAH) (50:50, v/v). The flow rate was 1.0 mL/min and detection was made at 220 nm. Salicylic acid was used as internal standard. Separation was completed in less than 15 min. The method was validated for system suitability, linearity, accuracy, precision, limit of quantitation, and robustness. The linear range for piperacillin sodium and sulbactam sodium was 103.0–1030.0 µg/mL and 24.0–240.0 µg/mL, respectively. Limit of quantitation (LOQ) was 22.05 µg/mL for piperacillin sodium and 5.48 µg/mL for sulbactam sodium. Relative standard deviation (RSD), for piperacillin sodium and sulbactam sodium was less than...

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination in six rabbits, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were investigated by using a high performance liquid chromatographic method for determining plasma concentrations. The plasma concentration-time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The disposition curves for both drugs were best described by an open two-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method for ampicillin and sulbactam were 0.62 +/- 0.09 and 0.45 +/- 0.05 L/kg, respectively, and the total body clearances were 0.65 +/- 0.04 and 0.42 +/- 0.05 L/kg h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.64 +/- 0.11 and 0.63 +/- 0.16 h, respectively, whereas for sulbactam the half-lives were 0.74 +/- 0.12 and 0.77 +/- 0.17 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (73.34 +/- 10.08% for ampicillin and 83.20 +/- 7.41% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.20 +/- 0.09 and 0.34 +/- 0.15 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.07 +/- 3.64 mg/L of ampicillin and 8.42 +/- 1.74 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after intramuscular administration in rabbits.

A sensitive, simple and inexpensive chemiluminescence (CL) method using flow injection is described for the determination of two beta-lactamase inhibitors sulbactam sodium and clavulanic acid (potassium salt) in their pure form, in pharmaceutical preparations and added to blood serum. The method is based on the enhancing effect of these compounds on the CL generated by the oxidation of luminol with hydrogen peroxide in alkaline medium. The CL intensity is a linear function of sulbactam sodium concentration over the range 0.1‐150m gm l 1 with a detection limit (2noise) of 0.05m gm l 1 , and for clavulanic acid over the range 0.01‐12m gm l 1 with a detection limit of 0.01m gm l 1 . The method is applied successfully to the determination of the drugs in their dosage forms without interference from co-formulated drugs. The method is specific for the intact drugs in the presence of their degradation products. © 2000 Elsevier Science B.V. All rights reserved.

A simple spectrophotometric method is used for the resolution of the binary mixtures of ampicillin sodium and sulbactam sodium. In aqueous solution, zero-order spectra are subject to interference, so first-derivative spectrophotometry was used to enhance the spectral details allowing the determination of ampicillin sodium from the signal at the zero-crossing point for sulbactam sodium at 268 nm. In 0.1 N sodium hydroxide, sulbactam sodium was determined from the absorbance at 260 nm with negligible contribution from ampicillin sodium. Also, sulbactam sodium was determined without interference using first- and second-derivative spectra in 0.1 N sodium hydroxide at 276 nm (peak-height) and 262-284 nm (peak-to-peak), respectively. The method is rapid, simple, does not require a separation step and allows the determination of each drug without interference from the other. The proposed method has been applied successfully to the assay of these drugs in mixtures and in commercial injections.

A high incidence (39%) of positive direct antiglobulin tests (DATs) has been reported in patients taking Unasyn [ampicillin sodium plus sulbactam sodium (a beta-lactamase inhibitor)]. Three of four patients, with positive DATs, receiving Unasyn or Timentin [ticarcillin disodium plus clavulanate potassium (also a beta-lactamase inhibitor)] developed a haemolytic anaemia (HA) associated with a positive DAT, which resolved when drug therapy was stopped. The patients' sera did not react with red blood cells (RBCs) in the presence of Unasyn or Timentin, but when drug-treated RBCs were tested, patients' sera and normal sera reacted equally by indirect antiglobulin test. Following incubation in normal sera, RBCs treated with Unasyn, Timentin, Augmentin (amoxicillin + clavulanate), sulbactam and clavulanate reacted with anti-human globulin and anti-human albumin (an index of non-specific adsorption); RBCs treated with ampicillin and amoxicillin were nonreactive. The beta-lactamase inhibitors sulbactam and clavulanate seem to cause nonimmunologic adsorption of protein onto RBCs in vitro. This may explain the high incidence of positive DATs detected in patients taking Unasyn, which contains sulbactam. It was not possible to prove that there was a direct association between the nonspecific uptake of protein onto drug-treated RBCs in vitro with the positive DATs or the HA.

UV spectrophotometric and high performance liquid chromatography (HPLC) methods were developed for simultaneous determination of meropenem (MERM) and sulbactam sodium (SB) in injection. UV spectrophotometric methods were developed using 0.1N sodium hydroxide as solvent. The Beer's plot for dual wavelength method was linear in the range of 4-24 μg mL(-1) and 2-12 μg mL(-1) for MERM and SB, respectively. The percent recoveries were found to be 98.52±1.23% for MERM and 101.45±1.1% for SB. Chemometrics assisted UV spectrophotometry was performed using Partial Least Square (PLS) analysis model and Principal Component Regression (PCR) analysis model. The % recoveries of the MERM were found to be 100.61±0.06% and 101.31±0.12% using PLS and PCR, respectively. The % recoveries of the SB were found to be 98.29±0.09% and 97.61±0.13% using PLS and PCR, respectively. Chromatography was performed on Hypersil BDS C18 column using methanol:acetonitrile:water (10:20:70 v/v/v) as mobile phase. The retention times of MERM and SB were found to be 2.9 min and 2.25 min, respectively. Developed HPLC method was found to be linear in the range of 50-250 μg mL(-1) and 25-125 μg mL(-1) for MERM and SB, respectively. The % recoveries were found to be 98.85±0.25% and 98.63±0.34% for MERM and SB, respectively. The developed analytical methods did not show any interference of the excipients when applied to pharmaceutical dosage form.

A Simple High Performance Thin Layer Chromatography method for the simultaneous estimation of cefepime hydrochloride and sulbactam sodium was developed. The determination was carried on Silica Gel 60 GF254 HPTLC Plates using the mobile phase of chloroform:ethyl alcohol: Diethyl amine: water (12:7:1:0.4V/V). The absorbances of the spots were measured by densitometry at 254nm. The Retention Factor (Rf) was found to be 0.17 for cefepime hydrochloride and 0.76 for sulbactam sodium respectively. Cefepime hydrochloride and sulbactam sodium showed linear response at concentration range 4-20 μg/band and 2-10 μg/band repepectively. The Correlation co-efficient (r 2 ) for cefepime hydrochloride and sulbactam sodium was found to be 0.9997 and 0.9997 respectively. The percentage recoveries obtained for cefepime hydrochloride and sulbactam sodium in range form 99.87-100.12 and 98.91-100.50.

Beta-lactamase inhibitors enhance the activity of beta-lactam antibacterials against beta-lactamase-producing bacteria. These agents cause irreversible inhibition of many plasmid-mediated and some chromosomal beta-lactamases. They result in successful inhibition of beta-lactamases produced by gram-positive bacteria including Staphylococcus aureus, and gram-negative bacteria including H. influenzae, Neisseria gonorrhoeae, Moraxella catarrhalis, Bacteroides fragilis, and some Enterobacteriaceae. Because the beta-lactamase inhibitors are generally less effective against chromosomally mediated type 1 beta-lactamases, many Citrobacter, Enterobacter, Morganella, and Serratia spp., and Pseudomonas aeruginosa are resistant to them. Clavulanic acid, sulbactam, and tazobactam are beta-lactamase inhibitors. Whereas clavulanic acid is used in combination with amoxicillin and ticarcillin, sulbactam sodium is used in combination with ampicillin and cefoperazone, and tazobactam in combination with piperacillin …

Farmasötiklerin sterilizasyonu için gama ışınları gibi yüksek enerjili iyonize edici radyasyon kullanımı, diğer sterilizasyon yöntemleriyle karşılaştırıldığında yüksek giricilik gücü, paketlenmiş ve ısıya duyarlı ürünlerde uygulanabilirliği gibi avantajlarından dolayı tercih edilmektedir. Ancak gama ışınlarının farmasötiklerin kalitesini etkileyebilecek radyolitik ara ürünler oluşturması radyosterilizasyonun bir dezavantajı olarak ortaya çıkmaktadır. Bu çalışmada, sıkça kullanılan sefazolin sodyum (CS) ve sulbaktam sodyum (SS) antibiyotiklerinin radyasyonla sterilize edilip edilemeyeceği araştırıldı. Bu amaca yönelik olarak gama ışınlarına tutulmuş örneklerde oluşan kökçelerin türleri, yapıları ve kinetik özellikleri Elektron Spin Rezonans (ESR) spektroskopisi kullanılarak incelendi. Işınlanmış CS dublet görünümünde bir spektrum verirken SS'nin birçok rezonans tepesine sahip ESR spektrumu verdiği belirlendi. İncelenen örneklerin 0.5-20 mW mikrodalga gücü aralığında doyum davranışları araştırıldı. CS için yedi, SS için ise dört farklı sıcaklıkta yapılan tavlama deneylerinden hesaplanan sönüm parametreleri, spektruma katkı getiren kökçe türlerinin sönüm aktivasyon enerjilerinin hesaplanmasında kullanıldı. Örneklerin 33 gün boyunca düzenli aralıklarla spektrumları kaydedilmek suretiyle oda sıcaklığındaki kökçe sönüm özellikleri araştırıldı. CS örneğinin 90K-350 K SS'nin ise 100K-400 K sıcaklık aralığında deneysel spektrumlarında ortaya çıkan karakteristik rezonans tepeleri ile ilgili sinyal şiddetlerinin sıcaklıkla değişimleri incelendi. Oda sıcaklığı altında tersinir bir şiddet artışı gözlenirken yüksek sıcaklıklarda şiddetteki azalmanın tersinir olmadığı saptandı. Değişik doz değerlerinde ışınlanan örnekler için elde edilen doz-cevap bulgularını açıklamak için farklı fonksiyonlar denendi ve her iki örnek için de doğrusal fonksiyona kare terim eklenerek elde edilen fonksiyonun deneysel sonuçlara en iyi uyumu sağladığı yargısına varıldı. Işınlamadan hemen sonra doz-cevap eğrilerinin doğrusal kısmından yararlanarak radyasyon dozunun CS için %3, SS için ise %4 yanılgı payı ile belirlenebileceği sonucuna varıldı. Mikrodalga doyum, doz-cevap, oda ve yüksek sıcaklıktaki sönüm bulguları birlikte değerlendirilerek spektrum benzetişim hesapları yapıldı. Bu yolla hesaplanan spektral parametre değerlerinin kullanılmasıyla oluşturulan kuramsal ESR spektrumlarının deneysel spektrumlar ile iyi bir uyum içerisinde oldukları belirlendi. Işınlama ile her iki örnek içerisinde iki farklı türde kökçe oluştuğu ancak CS'nin ve SS'nin bu kökçelerle ilgili radyasyon verimlerinin oldukça düşük olduğu ve dolayısı ile bu antibiyotiklerin radyasyonla sterilizasyonlarının olanaklı olduğu sonucuna varıldı. Use of ionizing radiation for sterilization of pharmaceutics is preferred because of advantages like high penetrating power, applicability on the packed and heat sensitive products when it is compared with the other sterilization methods. However the formation of radiolytic products by irradiation which may affect the quality of pharmaceutics is one of the disadvantages of this method. In this work, possibility of radiosterilization of commonly used cefazolin sodium (CS) and sulbactam sodium (SS) antibiotics were investigated. For this purpose, characterization of radical species produced in the samples by gamma radiation were examined by using Electron Spin Resonance (ESR) technique. While irradiated CS represent dublet ESR signal, irradiated SS exhibited an ESR spectrum with many resonance peaks. Saturation behaviours of the samples at 0.5-20 mW microwave power range were also studied. Decay parameters calculated from annealing temperatures studies at seven different temperatures for CS and four different temperatures for SS were used to calculate the activation energies of the radicals contributing to ESR spectra. Decay features of radicals at room temperature were investigated over a storage period of 33 days by recording spectra in regular time intervals. Temperature variations of the signal intensities related to the characteristic resonance peaks of spectra were examined in the range of 90K-350 K for CS and 100K-400 K for SS. Although the increase in the signal intensities were reversible at low temperatures, at high temperatures decreases in the intensities were irreversible. Different functions were tried to elucidate experimental dose-response curves obtained for irradiated samples at different dose values and for both sample it was found that, quadratic function described best the experimental results. It was concluded that, irradiation dose can be determined from linear part of the dose-response curves with an accuracy 3% for CS and 4% for SS. Simulation calculations were performed by evaluating the results obtained from microwave power saturation, dose-response curves, decay rates at room and high temperatures for the samples. It was determined that theoretical ESR spectrums formed by using spectral parameters calculated in this way correlated well with experimental spectrums. It was concluded that radiation produced two different radical species in both samples and as the radiation yields of irradiated solid CS and SS were fount to be low and consequently these antibiotics can be sterilized safely.

Some pharmacokinetic parameters of an ampicillin/sulbactam (2:1) combination were studied in six goats, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open two-compartment model. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.34 +/- 0.04 l/kg and 0.45 +/- 0.15 l/kg, respectively, and the total body clearances were 0.72 +/- 0.11 and 0.38 +/- 0.07 l/kg.h. The half-lives of ampicillin after intravenous and intramuscular administration were 0.32 +/- 0.04 h and 0.71 +/- 0.14 h, respectively. For sulbactam the half-lives were 0.79 +/- 0.18 h and 1.13 +/- 0.21 h after administration by the same routes. The bioavailability after intramuscular injection was high and similar for both drugs (98.29% for ampicillin and 101.84% for sulbactam). The mean peak plasma levels of ampicillin (0.43 +/- 0.27 h) and sulbactam (0.34 +/- 0.14 h) were reached at a similar time, and peak concentrations were also similar and non-proportional to the dose of the products administered (11.02 +/- 3.11 mg/l of ampicillin and 9.5 +/- 0.98 mg/l of sulbactam).

The stability and compatibility of ciprofloxacin with selected drugs in intravenous admixtures were studied. Ciprofloxacin 2 mg/mL in 5% dextrose was combined with each of 22 other drugs at concentrations commonly used in clinical practice. Each combination was maintained at room temperature (approximately 22 degrees C) in constant fluorescent light. Immediately after preparation and at 6 and 24 hours, each admixture was examined visually in normal fluorescent room light and the pH value was determined. For samples lacking visible precipitates or having pH changes of not more than 1 unit, ciprofloxacin concentration was assayed by using high-performance liquid chromatography. When combined with ciprofloxacin, 14 of the study drugs did not alter the concentration of ciprofloxacin, including amikacin sulfate, atracurium besylate, aztreonam, cimetidine hydrochloride, dobutamine hydrochloride, fluconazole, gentamicin sulfate, metronidazole (intravenous, ready to use), midazolam hydrochloride, norepinephrine bitartrate, pancuronium bromide, potassium chloride, tobramycin sulfate, and vecuronium bromide. There were five drugs that were determined to be incompatible with ciprofloxacin because of precipitate formation (amphotericin B, ampicillin sodium/sulbactam sodium, cefuroxime sodium, piperacillin sodium, and sodium bicarbonate). Incompatibility with ciprofloxacin based on pH changes of more than 1 unit was found with four drugs: ampicillin sodium/sulbactam sodium, ceftazidime, metronidazole hydrochloride (powder only), and ticarcillin disodium/clavulanate potassium. Intravenous ciprofloxacin 2 mg/mL admixed in 5% dextrose was stable and compatible with 14 of the 22 test drugs for up to 24 hours at room temperature. The other eight drugs should not be combined with ciprofloxacin.

Little information exists regarding the comorbidity of postoperative nonwound infections (NWIs) in patients with head and neck cancer. Prospectively, 225 patients were randomized in a double-blind fashion to receive either clindamycin or ampicillin sodium/sulbactam sodium for prevention of postoperative wound infection. Of the 113 patients receiving clindamycin, 14 developed nonwound infections, compared with 10 of 112 patients receiving ampicillin/sulbactam. A single site of nonwound infection occurred in 21 patients, and 2 sites occurred in 3 patients. The majority of infections were pulmonary (22), followed by urinary tract (3), septic phlebitis (1), and acute sinusitis (1). Gram-negative organisms were isolated more frequently among patients on clindamycin (18) versus ampicillin/sulbactam (6) (P = .014). Risk factors for pulmonary nonwound infection included: longer surgery, a greater than 70 packs per year smoking history, blood transfusion, and hypoalbuminemia (P < .05). Nonwound infections produce significant postoperative morbidity and the predominance of gram-negative organisms isolated from these infections has therapeutic implications.

Alkaline degradation of sodium sulbactam in methanol and in an aqueous solution has been investigated. The degradation in alkaline methanol produced methyl 5-carboxy-6-methyl-6-sulfino-4-aza-2-heptenoate (II) which showed an ultraviolet (UV) absorption maximum at 279 nm. The UV absorption almost disappeared when the solution was acidified with methanolic HCl solution, and reappeared on subsequent realkalization, suggesting interconversion between II and its protonated form. The degradation in aqueous alkaline solutions yielded 5-carboxy-6-methyl-6-sulfino-4-aza-2-heptenoic acid (IV), which showed λmax at 267 nm. IV was further degraded to 2-amino-3-methyl-3-sulfinobutanoic acid and formylacetic acid. The UV absorption of II and IV almost disappeared in aqueous acidic conditions, and reappeared on subsequent realkalization. These changes could be due to the hydrolysis of enamines II and IV to yield methyl formylacetate and formylacetic acid, respectively, in acidic conditions, and to the generation of the corresponding enolate ions on realkalization.

The title compound has been prepared from sulbactam sodium salt by a six-step sequence.