Study of prescribing pattern of antimicrobials in a tertiary care hospital

Background: Antimicrobials are routinely prescribed in several disease conditions in which infections are established or suspected to be the reason for the illness. Excessive and irrational use of antimicrobials leads to development of drug resistance in microorganisms, besides increasing health-care expenditure. Antimicrobial resistance (AMR) leads to increase in morbidity and mortality. The rational use of antimicrobials is a major health need in all countries. Hence, assessment of prescribing pattern of antimicrobials is essential for clinical, educational, and economic purposes. Aims and Objectives: The objectives of the study were to evaluate and compare the prescribing pattern of antimicrobials by assessing – (i) commonly used antimicrobials; and (ii) disease conditions for which they were prescribed. Materials and Methods: It was a prospective observational study done for a period of 1 month. All the prescriptions in which antimicrobials were prescribed in the outpatient departments (OPD) and in-patient wards (IP) were included in the study. Prescriptions were analyzed for demographic and antibiotic data. Results: 1092 prescriptions were collected and analyzed. Among them, 690 prescriptions were from OPD and 382 prescriptions from in patient wards. Out patient data: Cefixime (21.30%) was commonly prescribed followed by fixed dose combination of Amoxicillin + Clavulanic acid (14.64%) and Ciprofloxacin (8.84%). Cefixime was commonly prescribed for URTI (13.43%). Oral route (82.17%) was the preferred route of administration. IP data: Cefotaxime (26.45%) was commonly prescribed followed by fixed dose combination of Piperacillin + Tazobactum (15.29%) and Ceftriaxone (14.46%). Cefotaxime was commonly prescribed preoperatively for most of the surgeries (76.56%). Intravenous route (46.86%) was the preferred route of administration. Single antimicrobial therapy (81.41%) was preferred followed by double (17.80%) and triple (0.79%) antimicrobial therapy. Conclusion: Cefixime and cefotaxime were commonly used in OPD and in patient wards, respectively. Oral route and intravenous route were the preferred route in OPD and IP wards, respectively. Single antimicrobial therapy was commonly preferred in both IP and out-patient wards. Although double and triple antimicrobial therapy was prescribed in small number of patients, it should be cautiously used to prevent AMR.

Solubility enhancementofcefixime trihydrate by solid dispersions using hydrotropic solubilization technique and their characterization

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.

Cefixime and ornidazole combination induced fixed drug eruption: a case report

Cefixime, a third generation cephalosporin and ornidazole, a nitroimidazole is used for a wide variety of conditions like urinary tract infections, otitis media, pharyngitis, uncomplicated gonorrhea and anaerobic infections. Fixed drug eruption (FDE) is commonly associated with anticonvulsants, antimicrobials and NSAIDs. Here we report a case of a rare cefixime and ornidazole combination induced fixed drug eruption. A 39 year old male developed hyper-pigmented patches over both forearms and left thigh after consuming fixed dose combination of cefixime and ornidazole tablet for the treatment of urinary tract infection.

Analysis of polymer impurities in cefixime raw materials and preparations / 药学学报

To establish a method for the determination of polymer impurities in cefixime raw materials and preparations, a cefixime degradation solution containing polymer impurities was prepared by forced polymerization. Polymer impurities in the degradation solution were separated and identified by high performance gel chromatography and the column switching-LC-MSn method. A new RP-HPLC method for cefixime polymer was established and validated with a Phenomenex Gemini-C18 column using a mobile phase gradient elution of 0.5% formic acid-water solution and 0.5% formic acid-acetonitrile solution. The results showed that when using this high performance gel chromatography method some small molecular weight impurities were co-eluted with the polymers, resulting in a poor specificity and poor quantitative accuracy. But when using the RP-HPLC method, three polymer impurities were detected with good specificity, sensitivity and robustness, including two cefixime dimers, and dehydrate dimer. Therefore, the described RP-HPLC method is suitable for the quality control of polymer impurities in cefixime, and cefixime degradation solution can be used as suitable solution for analysis of cefixime polymers.

Effectiveness and safety evaluation of oral cefixime and moxifloxacin fixed dose combination in lower respiratory tract infections

Background: Scientific literature advocates the need for combination therapies in combatting lower respiratory tract infection (LRTI). Cefixime (400 mg) and moxifloxacin (400 mg) fixed dose combination (FDC) is currently approved in India for the management of LRTI, but data related to its real world usage is lacking. The present study was designed to understand the real world use (effectiveness and safety) of this FDC in LRTI.Methods: This retrospective study was conducted at out-patient departments of 5 hospitals between August 2018 and January 2019. After ethics committee approval, data of adults LRTI patients who received FDC of cefixime (400 mg) and moxifloxacin (400 mg) for at least 72 hours was collected. Improvement in LRTI symptoms (cough, sputum volume and purulence, fever, dyspnea, pleuritic chest pain, sleep disturbance, fatigue) were scored at baseline and follow-up using a 5-point severity scale. White blood cell (WBC) counts at baseline and end-of-treatment were compared.Results: Data of 190 patients having mean age 42.33+16.15 years was evaluated. Majority were males (61.58%), with commonest LRTI infection being community acquired pneumonia (CAP) (84.21%). Commonest clinical symptom reported (97.37%) was cough. All patients showed improvement in symptoms and significant improvement in all mean symptom scores were noted (p<0.05). Of the 30 patients having WBC above normal range, 29 showed a decrease in count at end of treatment. No adverse events were reported.Conclusions: Oral FDC of cefixime (400 mg) and moxifloxacin (400 mg) was efficacious in improving all symptoms reported by LRTI patients without causing any adverse event.

A case series of cefixime induced Steven抯 Johnson Syndrome

Drug induced adverse reactions are a major health problem. Drug hyper sensitivity reactions manifest themselves in many diseases, of which some are very severe. The most common allergic reactions occur in the skin. Stevens-Johnson syndrome is mainly caused by drugs (antimicrobials e.g.: penicillin抯, sulphonamides and cephalosporin抯 e.g.: cefixime, antiepileptic抯, NSAIDS), infections and also by other risk factors not yet identified. The most common allergic reactions occur in the skin. These reactions ranging from simple pruritic eruptions to potentially life threatening events are a significant cause of iatrogenic morbidity and mortality. Identification of the cause, withdrawal of the trigger and supportive management is crucial to improve the patient state. Despite of all therapeutic efforts, mortality is high and increases with disease severity, patient抯 age and underlying medical conditions. Survivors may suffer from long-term squeal such as strictures of mucous membranes including severe eye problems.

Clinical effect of Cefixime on the treatment for patients with acute bacterial enteritis and the influence on serum inflammatory factors / 国际检验医学杂志

Objective To investigate the clinical effect of cefixime on the treatment for patients with acute bacterial enteritis and the influence on serum inflammatory factors .Methods A total of 92 cases with acute bacterial enteritis ,treated in our hospital from June 2015 to September 2016 ,were selected as the research object ,and randomly divided into cefixime group and cefaclor group , with 46 cases in each group .The cefixime group was given treatment of cefixime ,and cefaclor group was given treatment of cefa-clor ,for 5 to 7 consecutive days .Observation of clinical treatment effect was performed .Results On the first three days after treat-ment ,the number of diarrhea of cefixime group is lower than the one of cefaclor group ,and the difference was statistically significant (P<0 .05);after Day 3 of treatment ,the levels of CRP ,CER ,AAG ,IL-8 ,PCT ,TNF-alpha of cefixime group were lower than those of cefaclor group ,and the difference was statistically significant (P<0 .05);after Day 3 of treatment ,efficiency rate ,effective rate and invalid rate of cefixime group were 50 .0% ,47 .83% and 2 .17% ,respectively ;efficiency rate ,effective rate and invalid rate of cefaclor group were 32 .61% ,56 .52% and 10 .87% respectively ;the treatment effect of cefixime group is better than that of cefaclor group ,and the difference was statistically significant (P<0 .05) .Conclusion The clinical effects of cefixime on the treatment for patients with acute bacterial enteritis is better than that of cefaclor .

Development and evaluation of bilayer tablets of combination of antibiotics for the treatment of sexually transmitted disease

ABSTRACT The present research work was envisaged to develop bilayer tablets to improve therapeutic efficacy of antibiotic combination for the treatment of sexually transmitted diseases. The combination of two antibiotics i.e. cefixime trihydrate and ofloxacin were used for the preparation of bilayer tablets which act against genito-urinary infections. The formulations comprise of cefixime trihydrate as immediate release layer formulated using different superdisintegrants and ofloxacin as extended release layer containing HPMC K100M. Evaluation of bilayer tablets were performed for the immediate release cefixime layer and sustain release ofloxacin layer with optimization of excipients. The immediate release layer of cefixime showed complete release within 30 min and ofloxacin release was extended up to 24 hours. The similarity factor value of ofloxacin sustained release layer was found to be 87.01 for initial and 80.35 after 3 months stability when compared with marketed reference product. The present study revealed that cefixime trihydrate and ofloxacin bilayer tablets were successfully developed for the use against sexually transmitted infections.

Physicochemical characterization of spray dried cefixime polymeric nanoparticles using factorial design approach.

The objective of the present study was to improve the physicochemical properties of poorly water soluble cefixime by preparing its nanoparticles using a hydrophilic polymer polyvinylpyrrolidone K30 (PVP). The nanoparticles of cefixime were prepared by spray drying technique. A 32 factorial design approach was employed for the optimization of nanoparticle batches. The present model demonstrated significance of factors such as drug to polymer ratio (X1) and feed flow rate (X2) of spray dryer on the production yield (Y1), particle size (Y2) and % drug release at 15 min (Y3). The pure drug and prepared nanoparticles were characterized by Fourier transformation infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), X-ray powder diffraction (XPRD), Scanning electron microscopy (SEM), particle size, saturation solubility and in vitro drug release. The results of DSC and XPRD revealed transformation of the crystalline nature of cefixime into an amorphous form which was supported by SEM. A significant improvement in solubility and dissolution rate was noticed in case of prepared nanoparticles as compared to pure cefixime. These results suggested that preparation of polymeric nanoparticles by spray drying technique might be a promising approach for improving the physicochemical properties of cefixime.

Development and validation of a new and economical stability indicating RP-HPLC method for cefixime trihydrate

ABSTRACT The present work describes the development of a new high performance liquid chromatographic (HPLC) method for the determination of Cefixime trihydrate under different stress conditons as specified by ICH. For the analysis, a Phenomenex (250 x 4.6 mm, 5 µm particle size) ODS column and a SPD 20 A UV detector at 289 nm was used. The selected mobile phase was 10 mM disodium hydrogen phosphate (with 0.5% TEA, pH adjusted to 6.3 with OPA) and methanol in the ratio of 75:25 (v/v) in isocratic mode at a flow rate of 1 mL.min-1.The linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.9997 in the concentration range of 5-100 μg.mL-1. The stress degradation was performed using acid, alkali, water, hydrogen peroxide and uv light.

RESUMO O presente trabalho descreve o desenvolvimento de um novo alta performance cromatografia líquida (HPLC) método para a determinação de cefixima tri-estresse sob diferentes condições, conforme especificado pelo ICH. Para a análise, a Phenomenex (250 x 4,6 mm, 5 µm de granulometria) ODS coluna e a SPD 20 um detector de UV em 289 nm foi utilizado. A fase móvel selecionado foi de 10 mM hidrogenofosfato dissódico (com 0,5% TEA, o pH ajustado para 6,3 com OPA) e de metanol em razão de 75:25 (v/v) no modo isocrático com uma taxa de fluxo de 1 mL.min-1. A análise de regressão linear para dados da calibração parcelas apresentaram boa relação linear com r2 = 0,9997 no intervalo de concentração de cerca de 5 100 µg.mL-1. Degradação do estresse foi realizado utilizando um ácido, alcalino, a água, o peróxido de hidrogênio e luz uv.

Validated UV-Visible Spectrophotometric method for simultaneous estimation of Cefixime and Moxifloxacin in Pharmaceutical Dosage Form.

A simple, accurate, sensitive, economical and reliable first order derivative spectrophotometric method was developed and validated for the estimation of cefixime and moxifloxacin in pharmaceutical dosage form. The optimum conditions for the analysis of the drugs were established. First order derivative method was developed for quantification of cefixime and moxifloxacin. Spectrum was obtained by dissolving cefixime and moxifloxacin in methanol and water (60:40 v/v); wavelength selected was 260 nm for cefixime and 316 nm for moxifloxacin. The Beer’s law was obeyed in the concentration range of 2-12 μg/ml. Results of tablet analysis showed percent relative standard deviation (% RSD) in the range of 0.1576 to 0.2183 for cefixime and moxifloxacin which indicate repeatability of the method respectively. Recoveries do not differ significantly from 100% which show there was no interference from the common excipient used in tablet formulation indicating accuracy and reliability of the method. The method was validated as per ICH guideline and found to be accurate, precise and rugged. It was also validated in terms of linearity, accuracy, precision, and specificity, limit of detection and limit of quantitation.

Effect of Bifidobacterium tetravaccine tablets(live) combined with cefixime on C-reactive protein, ceruloplasmin, haptoglobin and α1-acid glycoprotein in patients with bacterial enteritis / 中国生化药物杂志

Objective To analysis effect of Bifidobacterium tetravaccine tablets ( live ) combined with cefixime on C-reactive protein, ceruloplasmin, haptoglobin and α1-acid glycoprotein in patients with Bacterial enteritis.Methods 58 patients who were diagnosed with Bacterial enteritis were collected.All patients were randomly divided into experimental group and control group, 29 cases in each group, On the basis of conventional treatment, the control group was treated with cefixime, and the experimental group was treated with Bifidobacterium tetravaccine tablets ( live) on the basis of control group.After treatment, the serum levels of CRP, CER, HPT, AAG and clinical curative effect were detected in all patients.Results After treatment, CRP, CER, HPT, AAG levels were lower than before treatment (P<0.05),compared with control group, CRP, CER, HPT, AAG levels were lower than in the experimental group( P<0.05);the total effective rate was higher in the experimental group (χ2 =4.35, P<0.05).Conclusion Bifidobacterium tetravaccine tablets(live) combined with cefixime can significantly reduce the serum CRP, CER, HPT, AAG levels in patients with bacteria enteritis, improve the clinical efficacy, have guidance significance for clinic.

Uncertainty of Measurement for Cefixime in Human Plasma by HPLC-MS/MS / 医药导报

Objective To develop a method on evaluating the uncertainty during the determination of cefixime in human plasma by high performance liquid chromatography-tandem mass spectrometry ( HPLC-MS/ MS). Methods We analyzed various factors that can cause the uncertainty in the whole process of determination, which includ repeatability, weighting,preparation of standard solutions, sample preparation, equipment error and calibration curve fitting. The expanded uncertainty was evaluated by calculating uncertainty of each component and combined. Results The expanded uncertainty for low ( 80 ng ? mL-1 ), medium ( 560 ng ? mL-1 ) and high ( 9 600 ng ? mL-1 ) level of cefixime was 14. 93, 23. 65, 137.95 ng?mL-1 ,respectively (P= 95%). Conclusion The uncertainty of determining cefixime in human plasma by HPLC-MS/ MS is mainly caused by the calibration curve fitting,repeatability and HPLC-MS/ MS error.

Open-label, randomized, crossover comparative bioavailability study of cefixime from two tablet formulations after single oral administration.

Background: Cefixime is an oral extended spectrum third generation cephalosporin, which has marked in vitro bactericidal activity against a wide variety of Gram-positive and Gram-negative organisms, effective in the treatment of community-acquired infections such as respiratory tract infection and urinary tract infection. The objective of this randomized, crossover study was to compare the bioequivalence (BE) of two tablets of test (Milixim® 200 mg, containing 200 mg of cefixime) with Reference formulation (Cefixime, 400 mg). Methods: A total of 12 healthy volunteers were randomly assigned to crossover, single-dose treatment regimens. Serial blood samples were collected, and plasma concentrations of cefixime were analyzed using the high-performance liquid chromatographic technique. Pharmacokinetic parameters and BE limits were calculated using non-compartmental methods. Results: The mean Cmax for the test and reference formulations were 4435.0298±149 and 4408.2150±1021 ng/mL, respectively. The mean area under the serum concentration curve (AUC)0-t were 38108.2614±8583.6535 and 38457.5791±8105.2529 ng/hr/mL The mean ratios (test: reference) for Cmax, AUC0-t, were 99.7% and 98.5%, respectively. There were no significant differences in pharmacokinetic parameters between groups. Overall, the 90% confi dence interval for the intra-individual ratios of the log-transformed Cmax and AUC values of the two formulations were within the BE interval of 80-125%. Conclusion: The study has demonstrated the BE of milixim and reference formulation of cefixime.

Comparative in vitro antibacterial analysis of different brands of cefixime against clinical isolates of Staphylococcus aureus and Escherichia coli.

The objective of this study was to compare the antibacterial activity of standard and different brands of Cefixime, against standard samples and clinical isolates of E. coli and S. aureus collected from different hospitals. Standard samples and isolates of E. coli and S. aureus were separately cultured in Mueller Hinton broth. After the bacterial incubation, 5 ml solution each of standard Cefixime and its different brands were added to the test tubes containing bacterial culture. Cefixime samples were added in the concentration of 0.0625, 0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 32, 64 and 128μg/ml to separate test tubes. The cultures were again incubated and then the culture samples were analyzed by UV-spectrophotometer, and minimum inhibitory concentrations of all samples were determined. The analysis and interpretation of results were done by single factor ANOVA. An MIC of 0.75μg/ml and 8μg/ml of standard Cefixime was found for standard E. coli and S. aureous respectively. Standard Cefixime and its six selected brands exhibited a higher MIC range for clinical isolates of S. aureus than the clinical isolates of E. coli. Higher MIC values of standard Cefixime and its brands were observed for clinical isolates of E. coli and S. aureus. Higher MIC values for the clinical isolates of E. coli and S. aureus indicated that both the organisms have developed resistance to Cefixime in comparison to standard microorganisms acquired from ATCC.

Antimicrobial effect of cefixime on 6 species of periodotopathogens / 대한치주과학회지

The aim of this study was to determine the minimal inhibitory concentration(MIC) of cefi- xime, which is a 3rd generation of cefalosporin, against 6 species of putative periodon- topathogens; Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Prevotella inter- media, Prevotella nigrescens, Tannerella forsythia and Porphyromonas gingivalis. The efficacy of cefixime was examined by comparing it with that of several antibiotics(amoxicillin, Aug- mentin(R) ciprofloxacin, metronidazole, and tetracycline), which were used as the control. The MIC was measured using a microdilution method. The MIC of cefixime against the putative periodotopathogens, as a single use regimen, was relatively lower than that of the other antibiotics. The MIC of cefixime/metronidazole against P. intermedia ChDC KB14, P. nigres- cens ChDC KB50, F. nucleatum ChDC PV-F37, F. nucleatum ChDC F130, and F. nucleatum ChDC F175, as a simultaneous regimen, was lower than that of the other antibiotics. The concentration of cefixime in the crevicular fluid of volunteers who received 250mg every 12 hours for 3 days was 9microgram/ml after 9 hours. In conclusion, cefixime showed good anti- microbial activity in a single treatment or as a combined therapy with amoxicillin, Aug- mentin(R) or metronidazole against 6 periodontopathogens.

Preparation Technology of Cefixime Suspension and the Influencing Factors of Its Sedimentation Volume Ratio / 中国药房

OBJECTIVE:To optimize the preparation technology of cefixime suspension and study its stability.METHODS:The effects of hydroxypropyl cellulose,xanthan gum and sodium lauryl sulfate in different proportions on the sedimentation volume ratios of the suspensions were investigated by orthogonal experiments to optimize the preparation technology.The stability of the preparation was studied by accelerated test.RESULTS:The optimum preparation technology for cefixime suspension was as follows:the proportions of sodium dodecylsulfate,xanthan gum,and hydroxy-propyl methyl cellulose(HPMC) were 10%,20%,and 15%,respectively.The prepared suspension had simple formula and good stability,with all indexes up to the quality specification for suspension.CONCLUSION:The suspension prepared in accordance with this formula was able to meet the requirements of Chinese Pharmacopoeia on dry suspension.

Determination of Cefixime in Human Plasma with HPLC / 中国药房

OBJECTIVE:To establish a HPLC method for determining cefixime in human plasma.METHODS:Analytical column was Discovery C 18 (4.6mm?250mm,5?m),the mobile phase consisted of methanol-acetate buffer-triethylaming(28∶72∶0.5V/V),the flow rate was1.0ml/min.The detection was performed at UV286nm.Plasma concentrations of cefixime and internal standard(Cephradine)were determined by HPLC.RESULTS:The calibration curve was linear in the concentrations ranging from0.1to5.0?g/ml(r=0.9995).The detection limit was0.1?g/ml.The recovery was(96.63?3.17)%.The within-day RSD was less than6.10%and between-day RSD was less than6.69%.CONCLUSION:The method is simple,sensitive,accurate and suitable for determination of cefixime in human plasma and pharmacokinetic study.

Tratamiento de la neumonía del lactante con ceifixima en dosis única diaria / Treatament of pneumonia in infants with daily single oral dose of cefixime

Para evaluar la eficacia clínica y la tolerancia a la Cefixima, se trató con ella un grupo de 25 niños y niñas lactantes de 2 a 23 meses de edad, que padecían neumonías bacterianas. Se usó una dosis de 8 mg/kg/día, por vía oral, durante catorce días y en una sola toma. Los signos clínicos evaluados, los hallazgos radiológicos y los de laboratorio mejoraron en el transcurso de la terapia. Se presentaron un caso (4 por ciento) de intolerancia gastrointestinal y doce (48por ciento) con aumento de las transaminasas. En el 24 por ciento se encontró el agente causal. No se detectó una diferencia significativa en el comportamiento clínico y paraclínico de los niños con neumonía de etiología conocida en comparación con aquéllos en que no se la definió. Se obtuvo un 96 por ciento de resultados muy buenos en la terapia. Se debe investigar más el efecto del medicamento sobre la función hepática

Treatment of pneumonia in infants with dail y single oral dose of cefixime Twenty five male and female Infants aged two to twenty-three months suffering from bacterial pneumonia were treated with cefixime in order to evaluate clinical efficiency and tolerance. A daily single oral dose of 8 mg kg was given for fourteen days. Clinical status and radiologic and laboratory findings improved during the course of therapy. A case of gastrointestinal intolerance (4%) and twelve (48%) of high levels of transaminases were observed. In 6 cases (24%) the ethiologic agent was found. No significant differences were detected in clinical or paraclinical behavior between the groups of known and unknown ethiology. Therapy was quite successful in 96% of the C8ses. Hepatic effects of cefixime ought to be further Investigated