[Modern pharmacotherapy of acute bacterial sinusitis: results of an open randomized clinical trial of the therapeutic equivalence of Cefixime EXPRESS and Suprax Solutab]. / Sovremennaya farmakoterapiya ostrogo bakterial'nogo sinusita: rezul'taty otkrytogo randomizirovannogo klinicheskogo issledovaniya terapevticheskoi ekvivalentnosti preparatov «Tsefiksim EKSPRESS¼ i «Supraks Solyutab¼.

BACKGROUND: Acute bacterial sinusitis is one of the most common causes of prescribing systemic antibacterial drugs in otorhinolaryngology. With bacterial etiology of the disease, beta-lactam antibiotics are prescribed, in particular cefixim. Cefixim in the form of dispersible tablets has high clinical and bacteriological efficiency, as well as good tolerability in patients with acute sinusitis. OBJECTIVE: To study the therapeutic equivalence of two drugs of cefixim (reproduced drug Cefixim Express and reference drug Suprax Solutab) in patients with acute bacterial sinusitis. MATERIAL AND METHODS: 60 adult patients with a diagnosis of acute bacterial sinusitis took part in a randomized open comparative clinical study. Patients of group 1 (n=30) received the drug Cefixim Express in the form of dispersible tablets 400 mg once a day. Group 2 (n=30) received Suprax Solutab in the form of dispersible tablets 400 mg once a day. The duration of treatment course was 7 days. All patients conducted general clinical and otorhinolaryngological examinations, assessment of symptoms of acute sinusitis, assessment of the general clinical impression of the therapy, tolerance of treatment, analysis of the frequency of unwanted phenomena before treatment, 3 days after the beginning of therapy and after the course completion (7 days). RESULTS: Recovery occurred in 63.3% of patients in group 1 according to the inspection on the 7th day of treatment and in 66.67% of patients in group 2. The rate of clinical symptoms regression by the end of therapy was comparable in the comparison groups. Hyperemia of the nasal mucosa, purulent nasal discharge and difficulty in nasal breathing (p<0.01) regressed by the 7th day in patients of both treatment groups. The incidence of adverse reactions on the 7th day of treatment in group 1 was 10%, in group 2 - 6.7% (p>0.05). CONCLUSION: The drug Cefixim Express has high therapeutic effectiveness in the treatment of acute bacterial sinusitis, comparable to Suprax Solutab. Cefixime EXPRESS has demonstrated a good tolerability and a favorable safety profile.

Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial.

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2-3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

Effects of Cefixime on Immune Functions and Inflammatory Factors in Children with Urinary Tract Infection and Targeted Nursing Strategies

Objective: This study aims to explore the effects of cefixime on immune functions and inflammatory factors in children with urinary tract infection and to investigate its nursing strategies. Methods: A total of 161 children with urinary tract infection who were diagnosed in our hospital from November 2019 to November 2021 were selected. All children were treated with cefixime and received targeted nursing strategies. The indices of immune functions and the levels of inflammatory factors were compared before and after the treatment. The satisfaction degree of children’s family members, recurrence rate and incidence of adverse reactions were measured. Results: The levels of CD3+, CD4+ and CD4+/CD8+ in children after the treatment were significantly higher but the CD8+ level was significantly lower than those before the treatment (p < 0.001). The levels of C-reactive protein, tumour necrosis factor-α and interleukin-6 after the treatment were lower than those before the treatment (p < 0.001). The average score of nursing satisfaction of children’s family members was (84.53 ± 13.65) points, with the total satisfaction degree of 90.68% (146/161). Within 6 months after the treatment, only six children had urinary tract infection again and the recurrence rate was 3.73% (6/161). During the treatment, seven children had adverse reactions to the drug, with an incidence rate of 4.35% (7/161). Conclusions: Cefixime can improve the immune function of children with urinary tract infection and reduce the levels of inflammatory factors. The implementation of targeted nursing strategies can improve clinical satisfaction and reduce the recurrence rate of the disease and thus can be helpful to establish a comprehensive and efficient clinical program for children with urinary tract infection (AU)

Comparative study of cefixime and tetracycline as an evaluation policy driven by the antibiotic resistance crisis in Indonesia.

Antibiotic resistance is a serious threat that occurs globally in the health sector due to increased consumption of inappropriate antibiotics. Guidelines for prescribing antibiotics for ARTIs have been issued in general practice to promote rational antibiotic prescribing. This study was conducted to compare the effectiveness of cefixime and tetracycline as a solution to improve monitoring of appropriate antibiotic use in the treatment of ARTIs. All stock isolates were rejuvenated first, and cultured on standard media and Kirby-Bauer disc diffusion method was used for susceptibility testing in accordance with the Clinical and Laboratory Standard Institute's (CLSI) recommendations. Identification of bacteria from a single isolate was carried out to determine which bacteria were resistant to cefixime and tetracycline. A total of 466 single isolates of bacteria were analyzed, which showed a percentage of resistance to cefixime 38.0%, and tetracycline 92.86%. Bacterial isolates were resistant to cefixime and tetracycilne was a genus of Haemophilus, Streptococcus, Corynebacterium, Staphylococcus, and bordetella. Cefixime compared to tetracycline was proven to be superior in terms of the effectiveness of ARIs treatment.

Relay oral therapy in febrile urinary tract infections caused by extended spectrum beta-lactamase-producing Enterobacteriaceae in children: A French multicenter study.

OBJECTIVES: We need studies assessing therapeutic options for oral relay in febrile urinary tract infection (FUTI) due to ESBL-producing Enterobacteriaceae (ESBL-E) in children. Amoxicillin-clavulanate/cefixime (AC-cefixime) combination seems to be a suitable option. We sought to describe the risk of recurrence at 1 month after the end of treatment for FUTI due to ESBL-E according to the oral relay therapy used. MATERIALS AND METHODS: We retrospectively identified children <18 years who were included in a previous prospective observational multicentric study on managing FUTI due to ESBL-E between 2014 and 2017 in France. We collected whether children who received cotrimoxazole, ciprofloxacin or the AC-cefixime combination as the oral relay therapy reported a recurrence within the first month after the end of treatment. Then, we analyzed the susceptibility drug-testing of the strains involved. RESULTS: We included 199 children who received an oral relay therapy with cotrimoxazole (n = 72, 36.2%), ciprofloxacin (n = 38, 19.1%) or the AC-cefixime combination (n = 89, 44.7%). Nine (4.5%) patients had a recurrence within the first month after the end of treatment, with no difference between the 3 groups of oral relay (p = 0.8): 4 (5.6%) cotrimoxazole, 2 (5.3%) ciprofloxacin and 3 (3.4%) AC-cefixime combination. Phenotype characterization of 249 strains responsible for FUTI due to ESBL-E showed that 97.6% were susceptible to the AC-cefixime combination. CONCLUSIONS: The AC-cefixime combination represents an interesting therapeutic option for oral relay treatment of FUTI due to ESBL-E as the recurrence rate at 1 month after the end of treatment was the same when compared to cotrimoxazole and ciprofloxacin.

Design and development of lipid modified chitosan containing muco-adhesive self-emulsifying drug delivery systems for cefixime oral delivery.

Current study was aimed to design and develop muco-adhesive self-nano emulsifying drug delivery system (SNEDDs) for improved pharmacokinetics of Cefixime (CFX) in rabbits. The components of SNEDDs formulation i.e., cinnamon oil, Tween® 80, and PEG 200 as oil, surfactant, and co-surfactant respectively were selected based on their high solubilizing capability of the drug. SNEDDs formulation was optimized using Design of experiments (D-optimal design) in terms of droplet size, poly dispersity index and zeta potential. The optimized SNEDDs formulation was studied for various parameters like droplet size, morphology, zeta potential, emulsification, optical clarity, thermodynamic stability, GIT stability, and robustness to dilution. CFX was loaded to optimized formulation to form CFX-SNEDDs. Furthermore, acyl-chitosan, a muco-adhesive agent, was added to CFX-SNEDDS to prepare CHT-CFX-SNEDDS. In vitro drug release showed the controlled release behavior reached a maximum value of 70 % at pH 6.8 within 24 h. The droplet size, atomic force microscopy, and optical clarity analysis revealed the formation of nanosized emulsion (156 ± 25 nm) with spherical morphology. Also in vivo pharmacokinetic studies on rabbits showed an increased drug plasma concentration for CHT-CFX-SNEDDs (15 ± 3 µg/mL) and CFX-SNEDDs (9 ± 2 µg/mL) in comparison with control CFX (4 ± 1 µg/mL). The results indicated that the developed CHT-CFX-SNEDDs with an increased degree of solubilization, permeation, and nanosized range emulsion enhance the oral performance of CFX.

Are oral cefuroxime axetil, cefixime and cefditoren pivoxil adequate to treat uncomplicated acute pyelonephritis after switching from intravenous therapy? A pharmacokinetic/pharmacodynamic perspective / Cefuroxima axetilo, cefixima y cefditoren pivoxil, ¿son adecuadas en la terapia secuencial de la pielonefritis aguda no complicada? Perspectiva farmacocinética y farmacodinámica

OBJECTIVES: The goal of this study is to assess, by means of pharmacokinetic/pharmacodynamic (PK/PD) analysis using the Monte Carlo simulation, the adequacy of oral cephalosporins cefuroxime axetil, cefixime and cefditoren at different dosing regimens as switch therapy after intravenous cephalosporin treatment in uncomplicated acute pyelonephritis. METHODS: The methodology included: (I) dosing regimen selection and acquisition of pharmacokinetic data; (II) microbiological data acquisition; and (III) Monte Carlo simulation to estimate the PTA (probability of PK/PD target attainment) and CFR (cumulative fraction of response), as indicators of treatment success. RESULTS: At the current susceptibility breakpoints defined by EUCAST and CLSI for either cefuroxime axetil or cefixime, the probability of bactericidal target attainment is zero for the dosage regimens simulated. Considering the bactericidal target %fT > MIC > 70%, the likelihood of the cefuroxime 500- mg q8 h regimen or the cefixime 200- mg q12h regimen producing this exposure or achieving this target is only above 90% for organisms yielding MICs ≤ 0.5 mg/l and MICs ≤ 0.25 mg/l, respectively. Cefditoren pivoxil 400 mg q12h provided probabilities of bactericidal target attainment of 80% or higher for MICs ≤ 0.03 mg/l, and ≤ 0.25 mg/l if considering total instead of free drug concentrations. CONCLUSIONS: The results of the PK/PD target attainment analysis reveal that the likelihood of treatment success based upon the current breakpoints proposed by either EUCAST or CLSI is low. Of the three cephalosporins, cefixime 400 mg q12 h prove to be the best option in oral APN treatment, although this regimen is currently off label

OBJETIVOS: El objetivo de este estudio es evaluar, mediante el análisis farmacocinético/farmacodinámico (PK/PD) empleando la simulación de Montecarlo, la idoneidad de las cefalosporinas orales cefuroxima axetilo, cefixima y cefditoren en diferentes regímenes de dosificación, como terapia secuencial tras el tratamiento intravenoso con cefalosporinas, en pielonefritis aguda no complicada. MÉTODOS: La metodología incluyó: 1) selección del régimen de dosificación y adquisición de datos farmacocinéticos; 2) adquisición de datos microbiológicos; y 3) simulación de Montecarlo para estimar la probabilidad de alcanzar el objetivo (PTA) PK/PD y la fracción de respuesta acumulada (CFR), como indicadores del éxito del tratamiento. RESULTADOS: Para los puntos de corte de sensibilidad actuales definidos por EUCAST y CLSI para cefuroxima axetilo o cefixima, la probabilidad de alcanzar el objetivo bactericida es cero para los regímenes de dosificación simulados. Teniendo en cuenta el objetivo bactericida %fT > MIC > 70%, la probabilidad de que el régimen de cefuroxima 500 mg/cada 8h o el régimen de cefixima 200 mg/cada 12 h produzca esta exposición o alcance este objetivo es solo superior al 90% para los organismos que producen MIC ≤ 0,5 mg/l y MIC ≤ 0,25 mg/l, respectivamente. Cefditoren pivoxil 400 mg/cada 12 h proporcionó probabilidades de alcanzar el objetivo bactericida del 80% o más para MIC ≤ 0,03 mg/l, y ≤ 0,25 mg/l si se considera el fármaco total en lugar de libre. CONCLUSIONES: Los resultados del análisis PK/PD revelan que la probabilidad de éxito del tratamiento basado en los puntos de corte actuales propuestos por EUCAST o CLSI es baja. De las 3 cefalosporinas, la cefixima 400mg/cada 12h resultó ser la mejor opción en el tratamiento oral de pielonefritis aguda, aunque este régimen está actualmente fuera de ficha técnica

A Case of Acute Generalized Exanthematous Pustulosis by Cefixime with Oral Mucosal Involvement.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction characterized by the development of numerous sterile and non-follicular pustules on an erythematous base with no or minimal mucous membrane involvement associated with fever and leucocytosis. Cefixime is a cephalosporin-type beta-lactam antibiotic commonly used for the management of several infections. The Cefixime-induced AGEP cases are known to be rare. Here, we present the case report of a 26-year old female who developed Cefixime-induced AGEP with mucosal membrane involvement. To the best of our knowledge, this is the first case to report the mucosal membrane involvement in Cefixime-induced AGEP. We are presenting this case report to draw the attention on the existence and plethora of symptoms of Cefixime-induced AGEP hoping that the clinicians will reckon these in their differential diagnosis and implement the appropriate management strategies for this rare adverse event in their clinical practice.

Are oral cefuroxime axetil, cefixime and cefditoren pivoxil adequate to treat uncomplicated acute pyelonephritis after switching from intravenous therapy? A pharmacokinetic/pharmacodynamic perspective.

OBJECTIVES: The goal of this study is to assess, by means of pharmacokinetic/pharmacodynamic (PK/PD) analysis using the Monte Carlo simulation, the adequacy of oral cephalosporins cefuroxime axetil, cefixime and cefditoren at different dosing regimens as switch therapy after intravenous cephalosporin treatment in uncomplicated acute pyelonephritis. METHODS: The methodology included: (i) dosing regimen selection and acquisition of pharmacokinetic data; (ii) microbiological data acquisition; and (iii) Monte Carlo simulation to estimate the PTA (probability of PK/PD target attainment) and CFR (cumulative fraction of response), as indicators of treatment success. RESULTS: At the current susceptibility breakpoints defined by EUCAST and CLSI for either cefuroxime axetil or cefixime, the probability of bactericidal target attainment is zero for the dosage regimens simulated. Considering the bactericidal target %fT>MIC>70%, the likelihood of the cefuroxime 500-mg q8h regimen or the cefixime 200-mg q12h regimen producing this exposure or achieving this target is only above 90% for organisms yielding MICs≤0.5mg/l and MICs≤0.25mg/l, respectively. Cefditoren pivoxil 400mg q12h provided probabilities of bactericidal target attainment of 80% or higher for MICs≤0.03mg/l, and ≤0.25mg/l if considering total instead of free drug concentrations. CONCLUSIONS: The results of the PK/PD target attainment analysis reveal that the likelihood of treatment success based upon the current breakpoints proposed by either EUCAST or CLSI is low. Of the three cephalosporins, cefixime 400mg q12h prove to be the best option in oral APN treatment, although this regimen is currently off label.

Association between treatment with oral third-generation cephalosporin antibiotics and mortality outcomes in Ebola virus disease: a multinational retrospective cohort study.

OBJECTIVE: To evaluate the association between oral third-generation cephalosporin antibiotic treatment and mortality in Ebola virus disease (EVD). METHODS: This retrospective cohort studied EVD-infected patients admitted to five Ebola Treatment Units in Sierra Leone and Liberia during 2014-15. Empiric treatment with cefixime 400 mg once daily for five days was the clinical protocol; however, due to resource variability, only a subset of patients received treatment. Data on sociodemographics, clinical characteristics, malaria status and Ebola viral loads were collected. The primary outcome was mortality compared between cases treated with cefixime within 48 h of admission to those not treated within 48 h. Propensity scores were derived using clinical covariates. Mortality between treated and untreated cases was compared using propensity-matched conditional logistic regression and bootstrapped log-linear regression analyses to calculate an odds ratio (OR) and relative risk (RR), respectively, with associated 95% confidence intervals (CI). RESULTS: Of 424 cases analysed, 360 (84.9%) met the cefixime treatment definition. The mean age was 30.5 years and 40.3% were male. Median cefixime treatment duration was 4 days (IQR: 3, 5). Among cefixime-treated patients, mortality was 54.7% (95% CI: 49.6-59.8%) vs. 73.4% (95% CI: 61.5-82.7%) in untreated patients. In conditional logistic regression, mortality likelihood was significantly lower among cases receiving cefixime (OR = 0.48, 95% CI: 0.32-0.71; P = 0.01). In the bootstrap analysis, a non-significant risk reduction was found with cefixime treatment (RR = 0.82, 95% CI: 0.64-1.16, P = 0.11). CONCLUSION: Early oral cefixime may be associated with reduced mortality in EVD and warrants further investigation.

OBJECTIF: Evaluer l'association entre le traitement antibiotique oral avec des céphalosporine de troisième génération et la mortalité dans la maladie au virus Ebola (MVE). MÉTHODES: Cette étude de cohorte rétrospective a été menée chez des patients infectés par la maladie au virus Ebola admis dans cinq unités de traitement Ebola en Sierra Leone et au Libéria en 2014-2015. Le traitement empirique avec Cefixime 400 mg une fois par jour pendant cinq jours était le protocole clinique. Cependant, en raison de la variabilité des ressources, seul un sous-ensemble de patients a reçu un traitement. Des données sur la sociodémographie, les caractéristiques cliniques, le statut du paludisme et les charges virales d'Ebola ont été collectées. Le critère principal était la mortalité comparée entre les cas traités au céfixime dans les 48 heures suivant l'admission et ceux non traités dans les 48 heures. Les scores de propension ont été dérivés à l'aide de covariables cliniques. La mortalité entre les cas traités et non traités a été comparée à l'aide d'analyses de régression logistique conditionnelle et de régression log-linéaire bootstrapées pour calculer respectivement un rapport de cotes (OR) et un risque relatif (RR), avec des intervalles de confiance (IC) à 95% associés. RÉSULTATS: Sur 424 cas analysés, 360 (84,9%) répondaient à la définition du traitement au céfixime. L'âge moyen était de 30,5 ans et 40,3% étaient des hommes. La durée médiane du traitement par le céfixime était de 4 jours (IQR: 3, 5). Parmi les patients traités au Cefixime, la mortalité était de 54,7% (IC95%: 49,6 à 59,8%) vs 73,4% (IC95%: 61,5 à 82,7%) chez les patients non traités. Dans la régression logistique conditionnelle, la probabilité de mortalité était significativement plus faible parmi les cas recevant du céfixime (OR = 0,48 ; IC95%: 0,32 à 0,71; P = 0,01). Dans l'analyse bootstrap, une réduction du risque non significative a été trouvée avec le traitement au céfixime (RR = 0,82, IC95%: 0,64 à 1,16 ; P = 0,11). CONCLUSION: Le céfixime par voie orale rapide peut être associé à une mortalité réduite dans la MVE et mérite une investigation plus approfondie.

Loading of Cefixime to pH sensitive chitosan based hydrogel and investigation of controlled release kinetics.

Chitosan (biopolymer) and polyvinyl pyrolidone (PVP) with aminopropyletriethoxy silane (cross linker) based hydrogels were prepared and tested for controlled drug release. The drug release and kinetics were studied as a function of pH. Formulations were characterized by Fourier Transform Infrared (FTIR) and Thermogravimetric (TGA) analysis and TAP 32 hydrogel formulation was the most stable and hydrogel samples showed promising antibacterial activity against E. coli strain. The maximum swelling (4386%) was observed for TAP 32 formulation in distilled water, which was decreased with the concentration of ions. The diffusion exponent (n) values of all hydrogel formulations were recorded to be <0.5, which is an indication of Quasi-Fickian diffusion. The maximum swelling was observed at pH 2 and decreased at higher pH. The pH sensitivity of hydrogels found to be promising for their use in drug delivery, which was tested for cefixime drug. Drug release of 81.6% was observed for the period of 12 h in a simulated gastric fluid (SGF). The values of R2 for zero order, first order, Higuchi, Hixson, Korsmeyer-Peppas and Baker-Lonsdale were 0.97, 0.9818, 0.99, 0.99, 0.88 and 0.80, respectively. The hydrogels based on chitosan and PVP revealed potential for controlled cefixime drug release in gastric pH medium.

Cephalosporin-induced linear IgA dermatosis in a child: Case report and literature review.

Linear IgA dermatosis (LAD) is a rare, subepidermal blistering disease with mucocutaneous involvement. It may be idiopathic or drug induced. We describe a 4-year-old girl who presented with a vesiculobullous eruption after she had been treated with cefixime for urinary tract infection. A diagnosis of drug-induced LAD was made based on clinical, histopathological, and immunofluorescence findings. Naranjo adverse drug reaction algorithm was used to assess imputability resulting with a "probable" association. In literature, cephalosporin antibiotics are rarely reported in association with LAD. To our knowledge, this is the first case of a cefixime-induced LAD among adults and children.

Effectiveness of audit and feedback in addressing over prescribing of antibiotics and injectable medicines in a middle-income country: an RCT.

Overprescribing of antibiotics and injectable medicines is common in ambulatory care in many low- and middleincome countries. We evaluated the effects of three different interventions in improving physician prescribing. We conducted a four-armed randomized controlled trial with one-month and three- months follow-up. General physicians, pediatricians, and infectious disease specialists were included in this study if they had an outpatient office in Tehran, Iran. The study involved two behaviorally guided interventions: "new-design audit and feedback (NA&F)"; "printed educational material (PEM)" and an existing intervention of "routinely conducted audit and feedback (RA&F)". The theoretical framework underpinning the intervention was the theory of planned behavior. Main outcome measures were the percentage change in the proportion of prescriptions containing injectable dexamethasone; oral amoxicillin and cefixime. NA&F reduced the proportion of prescriptions particularly those containing dexamethasone injectable and cefixime (1.64, 0.99 absolute percentage change, p = 0.006, p = 0.01 respectively). PEM reduced the proportion of prescriptions containing cefixime (0.93 absolute percentage change p = 0.04). Other primary outcomes had no significant differences. A secondary outcome measure showed overall prescribing of injectables also reduced (absolute risk reduction: 3%). Overally, the study provides strong evidence that using theoretical insights in the development of the intervention improved prescribing behavior that lasted at least three months after the intervention. The design, format, and presentation of messages in feedback forms significantly influence the impact of audit and feedback on physician prescribing. While the interventions were effective, the impacts on inappropriate prescribing were modest and limited. In settings with rampant problems of overprescribing, intensive interventions are required to substantially improve prescribing patterns. Graphical abstract Graphical abstract.

Cefixime-associated acute generalized exanthematous pustulosis: Rare cases in India.

BACKGROUND: Cefixime is a widely used third-generation cephalosporin schedule H1 drug, which is prescribed for the treatment of otitis media, respiratory tract infections, and uncomplicated urinary tract infections and is effective against infections caused by Enterobacteriaceae and Haemophilus influenzae species in India. The National Coordination Centre (NCC)-Pharmacovigilance Programme of India (PvPI), Indian Pharmacopoeia Commission (IPC), has received rare individual case safety reports (ICSRs) for acute generalized exanthematous pustulosis (AGEP) associated with the use of cefixime. MATERIALS AND METHODS: IPC, NCC-PvPI also acts as a national collaborating center for pharmacovigilance activities under the aegis of Ministry of Health and Family Welfare, Government of India; moreover, it is a member country in global pharmacovigilance system, World Health Organization-Uppsala Monitoring Centre, Sweden. There are more than 250 government/corporate medical colleges and hospitals acting as regional adverse drug reaction monitoring centers, actively functioning under PvPI. Furthermore, various stakeholders including consumers and pharmaceutical industries also play a significant contribution. NCC-PvPI receives spontaneous ICSRs from various stakeholders. RESULTS: NCC-PvPI, IPC has received a total of four spontaneous ICSRs for cefixime-induced AGEP. After clinical evaluation of reported ICSRs, a strong causal relationship was established between AGEP and cefixime and was supported by published literature and histopathological examination of skin. Based on the statistics with positive information component (IC025 Value: 0.17) and proportionality relative risk (PRR:3.4), PvPI considered cefixime-associated AGEP may be a potential signal. CONCLUSION: Hence, initially, AEGP is considered by PvPI as drug safety alert in July 2016. Therefore, to enhance the safety of population in rational usage of medication, as a result, there is a need for physicians and health-care professionals to sensitize about serious adverse reaction while prescribing the cefixime as signal in India.

Association of oral ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin with the risk of serious ventricular arrhythmia: a nationwide cohort study in Korea.

OBJECTIVE: To evaluate whether oral ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin increase the risk of ventricular arrhythmia in Korea's general population. DESIGN: Population-based cohort study using administrative claims data on a national scale in Korea. SETTING: All primary, secondary and tertiary care settings from 1 January 2015 to 31 December 2015. PARTICIPANTS: Patients who were prescribed the relevant study medications at outpatient visits. PRIMARY OUTCOME MEASURES: Each patient group that was prescribed ciprofloxacin, levofloxacin, ofloxacin or moxifloxacin was compared with the group that was prescribed cefixime to assess the risk of serious ventricular arrhythmia (ventricular tachycardia, fibrillation, flutter and cardiac arrest). Using logistic regression analysis with inverse probability of treatment weighting using the propensity score, OR and 95% CI for serious ventricular arrhythmia were calculated for days 1-7 and 8-14 after the patients commenced antibiotic use. RESULTS: During the study period, 4 888 890 patients were prescribed the study medications. They included 1 466 133 ciprofloxacin users, 1 141 961 levofloxacin users, 1 830 786 ofloxacin users, 47 080 moxifloxacin users and 402 930 cefixime users. Between 1 and 7 days after index date, there was no evidence of increased serious ventricular arrhythmia related to the prescription of ciprofloxacin (OR 0.72; 95% CI 0.49 to 1.06) and levofloxacin (OR 0.92; 95% CI 0.66 to 1.29). Ofloxacin had a 59% reduced risk of serious ventricular arrhythmia compared with cefixime during 1-7 days after prescription. Whereas the OR of serious ventricular arrhythmia after the prescription of moxifloxacin was 1.87 (95% CI 1.15 to 3.11) compared with cefixime during 1-7 days after prescription. CONCLUSIONS: During 1-7 days after prescription, ciprofloxacin and levofloxacin were not associated with increased risk and ofloxacin showed reduced risk of serious ventricular arrhythmia. Moxifloxacin increased the risk of serious ventricular arrhythmia.

Characterization and microbiological evaluation of chitosan-alginate microspheres for cefixime vaginal administration.

Chitosan-alginate microspheres (MS) were developed for cefixime vaginal administration, to overcome problems associated with its oral administration. The effect of increasing drug-loading amount, by keeping the chitosan-alginate content constant, was investigated. Mucoadhesion studies indicated that all formulations assured in situ permanence longer than 2 h. Entrapment efficiency increased with drug loading concentration in the starting solution, reaching a plateau at 30 mg/mL indicative of the achievement of an optimal drug-to-polymer ratio. MS swelling properties increased with the entrapped drug amount, and, interestingly, water-uptake reached its maximum value at the same drug loading concentration of 30 mg/mL. The relationship found between MS water-uptake and drug release rate confirmed MS prepared with 30 mg/mL cefixime as the best formulation. Microbiological studies showed a relation between cefixime release rate from MS and Escherichia coli viability reduction, definitely indicating the selected MS formulation as the best for an effective local treatment of urogenital infections.

A Phase 1 Pharmacokinetic and Safety Study of Extended-Duration, High-dose Cefixime for Cephalosporin-resistant Neisseria gonorrhoeae in the Pharynx.

BACKGROUND: There are no fully oral recommended treatment regimens for gonorrhea. Inadequately treated pharyngeal gonococcal infections are a likely reservoir for transmission and development of antimicrobial resistance. We sought to determine an oral cefixime dosing regimen that would theoretically treat pharyngeal infections by gonococci with minimum inhibitory concentrations 0.5 µg/mL. METHODS: We conducted an open-label, nonrandomized, phase I pharmacokinetic and safety study of cefixime in 25 healthy male and female volunteers divided into 4 dosing cohorts (cohort A, 400 mg; cohort B, 800 mg; cohort C, 1200 mg; and cohort D, 800 mg every 8 hours × 3 doses [total dose 2400 mg]) with a target serum concentration of at least 2.0 µg/mL for more than 20 hours. Cefixime concentrations from serum and pharyngeal fluid were determined with use of a validated liquid chromatography-tandem mass spectrometry assay. Safety measures included laboratories, physical examinations, and symptom diaries. RESULTS: None of the single-dose regimens attained the target concentration; however, 50% of subjects in cohort D attained the target concentration. Variation in absorption and protein binding contributed to differences in concentrations. Pharyngeal fluid concentrations were negligible. The single-dose regimens were well tolerated; the multidose regimen resulted in mild to moderate gastrointestinal symptoms in 43% of subjects. CONCLUSIONS: None of the dosing regimens achieved the target concentration. However, the proposed theoretical target was extrapolated from penicillin data; there are no empirically derived pharmacokinetic/pharmacodynamic criteria for pharyngeal gonorrhea. Under alternative cephalosporin-specific therapeutic goals, the multidose regimen may be effective, although the absence of cefixime in pharyngeal fluid is concerning. A clinical trial evaluating efficacy and defining pharmacokinetic/pharmacodynamic outcomes may be warranted.

Antibiotics for treating gonorrhoea in pregnancy.

BACKGROUND: Gonorrhoea is a sexually transmitted infection that is caused by Neisseria gonorrhoeae, and is a major public health challenge today. N gonorrhoeae can be transmitted from the mother's genital tract to the newborn during birth, and can cause gonococcal ophthalmia neonatorum as well as systemic neonatal infections. It can also cause endometritis and pelvic sepsis in the mother. This review updates and replaces an earlier Cochrane Review on antibiotics for treating this infectious condition. OBJECTIVES: To assess the clinical effectiveness and harms of antibiotics for treating gonorrhoea in pregnant women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2017), LILACS database (1982 to April 5, 2017), the WHO International Clinical Trials Registry Platform (ICTRP; April 5, 2017), ClinicalTrials.gov (April 5, 2017), the ISRCTN Registry (April 5, 2017), and Epistemonikos (April 5, 2017). We also searched reference lists of all retrieved articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the use of antibiotics for treating gonorrhoea in pregnancy. The antibiotics could have been used alone or in combination, were administered parenterally, orally, or both, and were compared with another antibiotic.We included RCTs regardless of their publication status (published, unpublished, published as an article, an abstract, or a letter), language, or country. We applied no limits on the length of follow-up.We excluded RCTs using a cluster- or cross-over design, or quasi-RCTs. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. MAIN RESULTS: We included two RCTs, that randomised 514 pregnant women (347 women analysed) at a mean gestational age of 22 weeks. Both trials were conducted in the outpatient department of the same two hospitals in the USA between 1993 and 2001, and had a follow-up of 14 days. One of the trials was sponsored by a drug company. We considered both trials to be at a high risk of bias.One trial compared ceftriaxone (125 mg, intramuscular) with cefixime (400 mg, oral); the other trial had three arms, and assessed ceftriaxone (250 mg, intramuscular) versus either amoxicillin (3 g, oral) plus probenecid (1 g, oral) or spectinomycin (2 g, intramuscular). We did not include the spectinomycin data because this medication is no longer produced. We were unable to conduct meta-analysis because the trials compared different medications.We found inconclusive evidence that there were clear differences in the cure of gonococcal infections (genital, extragenital, or both) between intramuscular ceftriaxone versus oral amoxicillin plus oral probenecid (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.98 to 1.16; one RCT; 168 women; very low-quality evidence) or intramuscular ceftriaxone versus oral cefixime (RR 0.99, 95% CI 0.91 to 1.08; one RCT; 95 women; very low-quality evidence).Neither of the trials reported on two of this review's primary maternal outcomes: incidence of obstetric complications (miscarriage, premature rupture of membranes, preterm delivery, or fetal death), or disseminated gonococcal infection, or on the incidence of neonatorum ophthalmia in the neonates.One trial reported one case of vomiting in the oral amoxacillin plus probenecid group. Trials reported pain at the injection sites, but did not quantify it. Hyperberbilurrubinemia was more frequent in neonates whose mothers were exposed to ceftriaxone. There were no clear differences between groups for neonatal malformation. AUTHORS' CONCLUSIONS: This Cochrane Review found high levels of cure of gonococcal infections in pregnancy with the given antibiotic regimens. However, the evidence in this review is inconclusive as it does not support one particular regimen over another. This conclusion was based on very low-quality evidence (downgraded for poor trial design, imprecision) from two trials (involving 514 women), which we assessed to be at a high risk of bias for a number of domains. The harm profiles of the antibiotic regimes featured in this review remain unknown.High-quality RCTs are needed, with sufficient power to assess the clinical effectiveness and potential harms of antibiotics in pregnant women with gonorrhoea. These should be planned according to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT),conducted following CONSORT recommendations, and based on Patient-Centered Outcomes Research Institute (PCORI) outcomes.