The comparison of the quality of selected brands of antibiotics in Tanzania sourced from different geographical regions.

OBJECTIVES: The quality of amoxicillin capsules, ceftriaxone for injection, and ciprofloxacin tablets was evaluated to determine whether there is any difference in quality when comparing the country of origin. This was undertaken because it has been claimed that antibiotics manufactured in Europe are of superior quality to those originating from Africa or Asia. METHODS: Samples of amoxicillin capsules, ceftriaxone for injection, and ciprofloxacin tablets were collected from three randomly selected wholesale pharmacies in each city, namely Arusha, Dar es Salaam and Mwanza, Tanzania. The collected samples of collected brands were subjected to quality control testing as per their respective pharmacopoeial monographs. Amoxil 250 mg capsules (Glaxo Wellcome, Mayenne, France), Rocephin (Roche, Switzerland) and Cipro-Denk 500 (Allphamed Pharbil Arzneimittel GmbH, Gottingen, Germany) were used as reference brands for the other generic brands of amoxicillin, ceftriaxone and ciprofloxacin, respectively. RESULTS: A total of 31 brands (10 different brands of amoxicillin capsules, 9 of ceftriaxone sodium injections, and 12 of ciprofloxacin tablets) were collected from the targeted regions and subjected to quality control testing. All samples of collected brands complied with the requirements of their respective pharmacopoeial monographs. CONCLUSIONS: There was no significant difference in quality between brands of amoxicillin capsules, ceftriaxone for injection, and ciprofloxacin tablets manufactured in Africa and Asia against those manufactured in Europe in terms of compliance with the respective pharmacopoeial monographs.

Response surface modeling of ceftriaxone removal from hospital wastewater.

In recent decades, an emerging concern of widespread antimicrobial resistance has been raised due to the existence of pharmaceutical samples such as antibiotics in an aqueous medium. Herein, antibiotic ceftriaxone (CTX) removal from hospital wastewater employing a hybrid process of electrocoagulation (EC) and adsorption (AD) was investigated. The response surface methodology (RSM) was employed to study the influences of main operating variables, including initial CTX concentration, pH, current density, reaction time, and chitosan dosage, on the removal efficiency of the treatment process. Under the optimum condition of the employed EC/AD hybrid treatment process, where initial CTX concentration, pH solution, the current density, adsorbent dosage, and reaction time were set at 20.0 mg L-1, 7.5, 6.0 mA cm-2, 0.75 g L-1, and 12.5 min, respectively, the removal efficiency of 100% was achieved. Analysis of variance (ANOVA) confirmed that the developed quadratic treatment model is highly significant. The applied EC/AD hybrid treatment process revealed the electrical energy consumption of 0.84 kWh m-3 and 0.2168 kWh (g Al)-1 per cubic meter of hospital wastewater and gram of consumed aluminum electrode, respectively. The second-order kinetic model with R2 of 0.9514 and the Langmuir isotherm model with R2 of 0.973 best fit the developed EC/AD hybrid treatment process, and qm was found to be 111.1 mg g-1. The obtained experimental results confirmed that the CTX concentration of the hospital wastewater was reduced to zero after applying the EC/AD hybrid process.

Enhanced antimicrobial de-escalation for pneumonia in mechanically ventilated patients: a cross-over study.

BACKGROUND: Antibiotics are commonly administered to hospitalized patients with infiltrates for possible bacterial pneumonia, often leading to unnecessary treatment and increasing the risk for resistance emergence. Therefore, we performed a study to determine if an enhanced antibiotic de-escalation practice could improve antibiotic utilization in mechanically ventilated patients with suspected pneumonia cared for in an academic closed intensive care unit (ICU). METHODS: This was a prospective cross-over trial comparing routine antibiotic management (RAM) and enhanced antimicrobial de-escalation (EAD) performed within two medical ICUs (total 34 beds) at Barnes-Jewish Hospital, an academic referral center. Patients in the EAD group had their antibiotic orders and microbiology results reviewed daily by a dedicated team comprised of a second-year critical care fellow, an ICU attending physician and an ICU pharmacist. Antibiotic de-escalation recommendations were made when appropriate based on microbiologic test results and clinical response to therapy. RESULTS: There were 283 patients evaluable, with suspected pneumonia requiring mechanical ventilation: 139 (49.1%) patients in the RAM group and 144 (50.9%) in the EAD group. Early treatment failure based on clinical deterioration occurred in 33 (23.7%) and 40 (27.8%) patients, respectively (P = 0.438). In the remaining patients, antimicrobial de-escalation occurred in 70 (66.0%) and 70 (67.3%), respectively (P = 0.845). There was no difference between groups in total antibiotic days ((median (interquartile range)) 7.0 days (4.0, 9.0) versus 7.0 days (4.0, 8.8) (P = 0.616)); hospital mortality (25.2% versus 35.4% (P = 0.061)); or hospital duration (12.0 days (6.0, 20.0) versus 11.0 days (6.0, 22.0) (P = 0.918). CONCLUSIONS: The addition of an EAD program to a high-intensity daytime staffing model already practicing a high-level of antibiotic stewardship in an academic ICU was not associated with greater antibiotic de-escalation or a reduction in the overall duration of antibiotic therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02685930 . Registered on 26 January 2016.

Potassium permanganate-acridine yellow chemiluminescence system for the determination of fluvoxamine, isoniazid and ceftriaxone.

Based on the oxidation of acridine yellow by permanganate in basic medium, a new chemiluminescence system was developed for the sensitive determination of some important drugs. The remarkable inhibiting effect of fluvoxamine, ceftriaxone and isoniazid on this reaction was applied to their detection. A possible mechanism was proposed for this system based on chemiluminescence emission wavelengths and experimental observations. Under optimum conditions, calibration graphs were obtained for 1 × 10(-9) to 1 × 10(-6) mol/L of fluvoxamine; 2 × 10(-8) to 8 × 10(-6) mol/L of ceftriaxone and 5 × 10(-8) to 4 × 10(-5) mol/L of isoniazid. This proposed method was satisfactorily used in the determination of these drugs in pharmaceutical samples and human urine and serum.

Development and validation of a spectrofluorimetric method for the quantification of ceftriaxone in pharmaceutical formulations and plasma.

We describe the development and validation of a new, simple, sensitive and cost-effective method for the determination of ceftriaxone in commercial formulations and spiked human plasma. The method proposes the conversion of ceftriaxone into a fluorescent product by reacting with ortho-phthalaldehyde (OPA) in the presence of sulfite at room temperature. The reaction medium is buffered to pH 10 using borate buffer. The derivatized reaction product is highly fluorescent and exhibits maximum fluorescence intensity at λ(em) = 386 nm after excitation at λ(ex) = 324 nm. The experimental parameters affecting progress of the derivatization reaction were carefully studied and optimized. Under optimum experimental conditions, the method has an excellent correlation coefficient of 0.9984 with a broad linear range of 0.4-20 µg/mL. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 1.30 × 10(-3) and 3.90 × 10(-3) µg/mL, respectively. The interference effects of common excipients on the quantification of drug were investigated and no interference effect was observed. The proposed method has been successfully applied to the determination of ceftriaxone in pharmaceutical formulations and spiked human plasma samples. The method has been validated statistically through percent recovery studies using standard addition and by comparison with a reference HPLC method. The developed method exhibits excellent inter- and intraday precision.

Comparison between original and generic versions of ceftriaxone sodium preparation for injection: compatibility with calcium-containing product.

The purpose of this study was to compare the compatibility of ROCEPHINE® Intravenous, the original manufacturer's ceftriaxone sodium preparation for injection, and seven generic versions thereof, with various calcium chloride injection 2%. The influence of calcium ion concentration, storage time and shaking strength on the appearance and quantity of insoluble microparticles in mixed solutions was examined using a light obscuration particle counter. In all products, the observed number of insoluble microparticles was proportional to the calcium ion concentration, storage time and shaking strength after the addition of calcium chloride solution. In several of the generic products, the number of insoluble microparticles was significantly higher than those of the original product, while in others it was lower. We evaluated the quality of the original and 7 generic preparations, measured the content of impurity and pH of the various ceftriaxone solutions, as impurity content and pH of solution are possible factor affecting compatibility. Three impurities were found in all products. The impurity content of several generic products, as estimated from their peak area on high performance liquid chromatography (HPLC), was significantly lower than that of the original product. pH of solution was difference between products. Although it was difficult that impurity and pH of solution verify critical factor affecting compatibility. The results show that there are differences in the appearance of insoluble microparticles between the original product and seven generic products, when calcium chloride injection 2% solution is added to the product.

[Level of evidence for therapeutic drug monitoring of ceftriaxone]. / Niveau de preuve du suivi thérapeutique pharmacologique de la ceftriaxone.

Ceftriaxone is a third generation cephalosporin with an original pharmacokinetics based on a long elimination half-life among cephalosporins, a high protein binding and a dual renal and biliary elimination. Also the pharmacokinetic parameters of ceftriaxone are highly variable in clinical situations such as severe renal insufficiency, liver and renal insufficiency, the elderly, the neonates less than 1 week of age and critically ill patients. In these clinical situations associated or not with high minimal inhibitory concentration (MIC) level, the relationship concentration-clinical outcome based on the ratio between trough plasma concentration and MIC can allow a dose adjustment. Consequently, therapeutic drug monitoring (TDM) of ceftriaxone could be possibly useful in these situations, whereas the necessity of TDM has still to be demonstrated to monitor toxicity.

[Rapid determination of ceftriaxone in mixed saliva of practically healthy subjects and patients with infectious and somatic pathologies].

A method for spectroscopic determination of ceftriaxone in saliva of healthy subjects and patients with upper respiratory tract infections was developed. The concentration range is 1-50 mcg/ml. The method is express and simple, and can be used to determine ceftriaxone in clinical tests and pharmacokinetic studies. Possible determination of ceftriaxone in aqueous solutions was demonstrated which is useful in analysis of drugs.

Indirect spectrophotometric determination of sodium ceftriaxone with n-propyl alcohol-ammonium sulfate-water system by extraction flotation of copper(II).

BACKGROUND: Although the determination methods of sodium ceftriaxone has been increasingly reported, these methods have their inherent limits preventing them from being broadly applied in common laboratories. In order to circumvent this problem, a rapid and simple method for the indirect spectrophotometric determination of sodium ceftriaxone is reported. METHOD: Sodium ceftriaxone was degraded completely in the presence of 0.20 mol/l sodium hydroxide in boiling water bath for 20 min. The thiol group (-SH) of the degradation product (I) of sodium ceftriaxone could reduce cupric to cuprous ions, and the resulting which was precipitated with the thiol group (-SH) of the degradation product (II) at pH 4.0. By determining the residual amount of copper (II), the indirect determination of sodium ceftriaxone can be achieved. RESULT: Standard curve of sodium ceftriaxone versus the flotation yield of copper(II) showed that sodium ceftriaxone could be determined in low concentrations. The linear range of sodium ceftriaxone was 0.70-32 microg/ml and the detection limit evaluated by calibration curve (3sigma/k) was found to be 0.60 microg/ml. CONCLUSION: A simple and efficient method was developed and it has been successfully applied to the determination of sodium ceftriaxone in human serum and urine samples, respectively. It is expected that this method will find broad applications in the detection of cephalosporin derivatives with similar structure.

A Critical Review of Analytical Methods for Determination of Ceftriaxone Sodium.

Ceftriaxone sodium is a third-generation semi-synthetic antibiotic belonging to the class of cephalosporins. Is administered only by parenteral route and has the ability to cross the blood-brain barrier. It has bactericidal action; its main activity is related to the Gram-negative bacteria, being also able to act against Gram-negative bacilli resistant to the first- and second-generation cephalosporins. The present study presents a survey of the characteristics, properties and analytical methods used for the determination of ceftriaxone sodium, for the gathering of data searches were carried out in scientific articles in the world literature, as well as in the official compendia. It is necessary to create awareness about the importance of developing effective and reliable analytical methods for quality control and consequently for conducting pharmacokinetic, bioavailability, bioequivalence studies as well as for the therapeutic monitoring of this drug. Most of the methods found use high-performance liquid chromatography, but also methods that use absorption spectroscopy ultraviolet, infrared spectroscopy, spectrofluorimetry and microbiological methods have been presented. A discussion was presented highlighting the need to develop new ecological methods using less toxic solvents, rapid analysis and miniaturization of the samples.

Highly sensitive detection of Ceftriaxone in water, food, pharmaceutical and biological samples based on gold nanoparticles in aqueous and micellar media.

A colorimetric assay with excellent sensitivity is reported to detect Ceftriaxone in aqueous and micellar solutions. Ceftriaxone could induce the aggregation of gold nanoparticles through hydrogen-bonding interaction and electrostatic attraction. As a result of aggregation, the surface plasmon resonance band around 520 nm decreases and a new band appears at 620 nm. The effect of surfactants was investigated on the aggregation. The band around 620 nm is shifted to around 685 nm in Triton X-100 micellar media and that is seen color conversion from red to deep blue which is clearly detectable by the naked eye. The results were improved in Triton X-100 micellar media as compared to aqueous media so that the lowest measured concentration and detection limit in micellar media have decreased 10 and 8 times, respectively. Triton X-100 showed strong effect on the stabilization of the solutions. The method has been successfully applied for the analysis of various real samples.

Determination of ceftriaxone sodium in pharmaceutical formulations by flow injection analysis with acid potassium permanganate chemiluminescence detection.

Based on the chemiluminescence (CL) emission generated from the oxidation of ceftriaxone sodium alkali hydrolysate by potassium permanganate in polyphosphoric acid (PPA), a novel determination method for ceftriaxone sodium was developed by using a flow-injection technique. The calibration curve appears to be linear in the range between 0.05 and 100 microg mL(-1) with a detection limit (3sigma) of 25 ng mL(-1), and a relative standard deviation (RSD) of 0.6% for eleven replicate determinations of 5.0 microg mL(-1) ceftriaxone sodium. The proposed method has been successfully utilized for the determination of ceftriaxone sodium in pharmaceutical formulations, while the chemiluminescence reaction mechanisms were investigated.

An ultrasensitive and selective method for the determination of Ceftriaxone using cysteine capped cadmium sulfide fluorescence quenched quantum dots as fluorescence probes.

In this paper, l-cysteine (Cys) coated CdS quantum dots (QDs) have been prepared, which have excellent water-solubility and are highly stable in aqueous solution. These QDs is proposed as sensitizers for the determination of Ceftriaxone. The quantum dot nanoparticles were structurally and optically characterized by Ultra Violet-Visible absorption Spectroscopy (UV-vis absorption spectroscopy), Fourier transform infrared spectroscopy (FT-IR spectra) and photoluminescence (PL) emission spectroscopy. High resolution transmission electron microscopy (HRTEM) confirms that the Cys-CdS QDs have a spherical structure with good crystallinity. Therefore, a new simple and selective PL analysis system was developed for the determination of Ceftriaxone (CFX). Under the optimum conditions, The response of l-Cys capped CdS QDs as the probe was linearly proportional to the concentration of Ceftriaxone ions in the range of 1.6×10(-9)-1.1×10(-3)M with a correlation coefficient (R2) of 0.9902. The limit of detection of this system was found to be 1.3nM. This method is simple, sensitive and low cost.

Acidity constants of cefetamet, cefotaxime and ceftriaxone; the effect of the substituent at C3 position.

Ionization constants of three cephalosporin antibiotics, cefetamet (CEF), cefotaxime (CFX) and ceftriaxone (CFTR) are determined using pH-potentiometric titrations at I=0.1 M (NaCl) and t=25 degrees C. Cefetamet and cefotaxime have three ionization groups: carboxylic, amide and aminothiazole. Besides those three, ceftriaxone possesses an hydroxytriazinone group as new and additional ionization center. In acid medium two overlapping acid-base processes are occurring with acidity constants being: pK1 2.93 (COOH) and pK2 3.07 (aminothiazole) for cefetamet, and pK1 2.21 (COOH) and pK2 3.15 (aminothiazole) for cefotaxime. In the case of ceftriaxone the situation is even more complicated, three overlapping processes coexist with pK1 2.37 (COOH), pK2 3.03 (aminothiazole) and pK3 4.21 (hydroxytriazinone). Protolysis of amide group is happening in the alkaline medium as completely separated process from those in acid medium. The acidity constants which correspond to amide group are pK3 10.65 (CEF), pK3 10.87 (CFX) and pK4 10.74 (CFTR). The influence of the C3 substituent on the dissociation process of the neighboring ionization group, particularly carboxylic group, was considered. The differences in acidity of CEF, CFX and CFTR (pK1: 2.93, 2.21 and 2.37, respectively) are likely to be caused by the stereoelectronic properties of substituents in the beta-position to the carboxylic group due to the combined inductive, hyperconjugative and resonance effects.

Stability of ceftriaxone disodium in Biotrakson and Tartriakson.

The influence of temperature and relative air humidity on the stability of ceftriaxone disodium (CTN) in Biotrakson and Tartriakson was investigated. At RH = 0%, the degradation of ceftriaxone was the first-order reaction, while at RH from 50.9% to 76.4% it was an autocatalytic first-order reaction relative to the substrate concentration. The influence of temperature on the stability of CTN was described by the following equations in the case of Biotrakson: RH =0% ln k = (-23488 +/- 7320) x 1/T+ 45.1; RH = 76.4% ln k = (-9492 +/- 1128) x 1/F + 16.1, and for Tartriakson: RH = 0% ln k = (-23491 +/- 7370) x 1/T + 42.4; RH = 76.4% ln k = (-10397 +/- 3034) x 1/T + 18.8. The influence of humidity on the stability of Biotrakson was described by the following equation: ln k = (0.0823 +/- 0.0272) x RH% -17.0 and for Tartriakson ln k = (0.0895 +/- 0.0246) x RH% -17.6.

Identification of a new isomer from a reversible isomerization of ceftriaxone in aqueous solution.

A reversible isomerization of ceftriaxone in aqueous solution was observed, and the structure of the isomer was determined by mass spectrometry and various 1D and 2D NMR techniques. The mechanism of isomerization was also discussed. Finally, molecular docking simulations were performed and the antimicrobial activities of the isomers were measured. This showed that the biological activity of ceftriaxone was stronger than that of its isomer. The results reported in this article may be important to quality control requirements and to the stability of ceftriaxone products.

Differential pulse adsorptive stripping voltammetric determination of ceftriaxone at a static mercury dropping electrode.

Ceftriaxone is a member of the "third generation" of cephalosporin antibiotics which adsorbs strongly onto a mercury electrode. By using this phenomenon and by accumulating this compound at a static mercury dropping electrode prior to differential pulse voltammetric measurements, very high sensitivities can be readily achieved. The influence of several variables (including accumulation time, modulation amplitude, rest period, scan rate, and drop size) on the adsorptive stripping response has been evaluated. Peak currents were measured with a hanging mercury dropping electrode at -0.78 V versus an Ag/AgCl reference electrode in pH 3.0 Britton-Robinson buffer. The linear calibration range was 3.31 x 10(-11) to 2.17 x 10(-6) M.

Ion-paired reversed-phase high-performance liquid chromatography assay for determination of ceftriaxone in human plasma and urine.

A rapid, sensitive, and specific ion-paired reversed-phase HPLC assay for ceftriaxone in human plasma and urine is described. Small volumes (50 microL) of sample are deproteinized with acetonitrile and are directly injected on a C18 analytical column. The UV absorbance is monitored at 280 nm. The assay is linear between 1 and 125 micrograms/mL of ceftriaxone, with less than 10% coefficient of both intra- and interday variation. Chromatography was specific for ceftriaxone as endogenous compounds and 30 common drugs did not interfere. The assay was used in open heart surgery patients where potential interference from corticosteroids was overcome.

Stability of parenteral ceftriaxone disodium solutions in frozen and liquid states: effect of freezing and microwave thawing.

The stability of ceftriaxone disodium solutions stored in glass bottles was tested in two parenteral solvents (0.9% NaCl; 5% dextrose) at two concentration rates (10 and 50 mg/mL) and three temperatures (-22 degrees C, 5 degrees C, room temperature). The solutions, which had been initially frozen, were thawed at room temperature or by exposure to microwave radiations. The stability of each sample was determined by a quantitative bacteriological agar gel diffusion assay and by high-performance liquid chromatography. The results of this study indicate that admixtures of ceftriaxone disodium at the concentration rates tested can be frozen for six months without a significant loss in antibiotic activity. At room temperature, the stability is dependent on the concentration of ceftriaxone disodium. At 5 degrees C, the stability is related to the concentration of ceftriaxone and of the solvent. The results obtained by both analytical methods are very close. In order to perform routine assays, the high-performance liquid chromatography method was chosen on the basis of its rapidity and reproducibility.

Sensitive assay for the determination of cefazolin or ceftriaxone in plasma utilizing LC.

A rapid, specific and very sensitive liquid chromatographic assay using standard ultraviolet detection has been developed to measure cefazolin (CFZ) or ceftriaxone (CFX) in small samples (200 microl) of plasma using either drug as the internal standard for measurement of the other. A rapid extraction was performed using C18 bonded Sep Pak cartridges with high extraction efficiency for both drugs. The chromatographic system employed the use of a Nova-Pak C18 4-microm cartridge with a radial compression system preceded by a Guard-Pak with a C18 insert. The mobile phase consisted of an aqueous solution containing 10 mM of dibasic potassium phosphate and 10 mM cetyltrimethylammonium bromide (pH 6.5) with acetonitrile (73:27 v/v). The drug and internal standard (CFZ/CFX) were detected using a UV detector set at a wavelength of 274 nm. Assay results were linearly related to the concentration (r > 0.997) for the wide range which was examined (0.005-120 microg/ml) for either drug. We report the precision, accuracy, recovery, linearity, sensitivity and specificity of this assay. The intra-run and inter-run CV was less than 9.02%. This method is currently being used for clinical therapeutic monitoring and pharmacokinetic studies of CFZ and CFX in patients undergoing cesarean section.