Evaluation of assay and in-vitro dissolution profile of certain fixed-dose combination using green analytical method.

OBJECTIVES: The pharmaceutical industry and the National Regulatory Authorities (NRAs) are now focusing on the dissolution of multi-component drugs for quality control testing and predicting in vivo results to further consolidation of the biowaiver concept. The mixed formulation of Ciprofloxacin hydrochloride (CIP) and Metronidazole (MET) have been used as a model for simultaneous determination and obtaining in vitro dissolution profiles by using green analysis method namely (UV-CWT(Db4, a=490)). MATERIAL AND METHODS: The proposed method (UV-CWT(Db4, a=490)) includes UV detection combined with Continuous Wavelet Transform (CWT) with Daubechies family and the order of fourth at the scaling factor (a=490) has been used and validated for analyzing and obtaining the dissolution profiles of the fixed-dose combination (CIP-MET). RESULTS: The proposed method (UV-CWT(Db4, a=490)) has been validated effectively in accordance with ICH rules, regarding linearity, specificity, rigor, and preciseness of the working range (3.0-16.0µg/mL) for both (CIP) and (MET), respectively. As well as figures of merit were concluded. The dissolution profiles of CIP-MET tablets were acquired by the proposed (UV-CWT (Db4, a=490)) and HPLC reported methods were conveniently compared using the indicators f1 and f2 ("difference" and "similarity") the results ensured that there were no statistically differences between the methods. In addition, the green assessment tool, namely analytical eco-scale, evaluated and compared the greenness of the suggested method (UV-CWT(Db4, a=490)) and HPLC reported one. CONCLUSION: The suggested process (UV-CWT(Db4, a=490)) was considered as an excellent green, rapid, accurate, economical and minimum-steps method for simultaneously resolve and construct the dissolution curves of a fixed-dose combination drug (CIP-MET) in a short time and without the use of organic solvents, enabling significant labor and resource savings.

Development of a new liquid chromatographic method for the simultaneous separation of ciprofloxacin degradation products with 5-hydroxymethyl-furfural, impurity of D-glucose, in an intravenous solution for perfusion.

The place occupied by fluoroquinolones is very important clinically. Ciprofloxacin has been the most widely prescribed one which exhibits good activity against Pseudomonas aeruginosa and Acinetobacter. D-glucose is frequently used as an excipient in most formulations for perfusion solutions. Since there is much interest in pharmaceutical quality control of such formulations, separation of impurities from the main drug substances and accurate assay quantification, and since there is no reference or monograph until nowadays that has been reported for the simultaneous separation of ciprofloxacin degradation products along with 5-hydroxymethyl-furfural (5-HMF), impurity of D-glucose, classified as a high toxic substance, thus our aim of this work is to develop a new simple, sensitive and stability indicating method allowing this separation by high-performance liquid chromatography. We have started from the chromatographic conditions recommended by the British Pharmacopoeia, and by optimizing the nature of the stationary phase, the composition of the mobile phase and the injection volume. After optimisation, the retained chromatographic conditions have enabled the separation of all impurities with good resolution factor greater than 1.5 for each pair of peaks and with good symmetry peak shape. The developed method was validated according to the International Conference of Harmonisation (ICH) guidelines for specificity, detection and quantification limits, and then it was applied to stability study of the formulation subjected to different ICH prescribed stress conditions. The 5-HMF was checked to be the impurity issued from D-glucose hydrolysis by high temperature mainly after autoclaving of pharmaceuticals. The developed method was proved to be simple, specific with very low limit of quantification. Hence, it can be considered as a method for stability indicating and routine quality control analysis in pharmaceutical industries.

Ciprofloxacin-resistant Neisseria meningitidis in Canada: likely imported strains.

The prevalence of ciprofloxacin-resistant Neisseria meningitidis in Canada was studied by testing 346 isolates received at the National Microbiology Laboratory during the calendar years 2013 to 2015. Of the 277 individual invasive and 69 noninvasive isolates tested, only 2 serogroup C (MenC) isolates were found to be resistant to ciprofloxacin. Both MenC were typed as sequence type (ST)-4821, a unique clone found mainly in China, thus suggesting both isolates might be from travel-related or imported cases. This prompted us to also examine 6 serogroup A (MenA) isolates in our collection, since MenA is not currently endemic in Canada. Three MenA from 2006 were resistant to ciprofloxacin and they were typed as ST-4789. A ciprofloxacin-resistant MenA strain of ST-4789 was responsible for a meningococcal disease outbreak in Delhi, India, in 2005 to 2006. The 2 MenC and 3 MenA ciprofloxacin-resistant N. meningitidis were from patients residing in British Columbia.

Six cases during 2012-2015 and literature review of Chryseobacterium indologenes infections in pediatric patients.

Chryseobacterium indologenes is a widespread bacteria in the environment, especially hospitals, and a rarely reported human pathogen. The lowest frequency has been reported in children under 5 years of age. Clinical manifestations of C. indologenes include nosocomial pneumoniae, biliary tract infection, peritonitis, surgical wound infection, intravascular catheter-related bacteremia, cellulitis, and primary bacteremia. There is a knowledge gap in the management of C. indologenes infections, especially pertaining children, because of multiple antibiotic resistance and limited data in the literature concerning effective empirical treatment. In the published literature, a total of 16 cases of C. indologenes infections were reported in the pediatric age group. Herein, we present our experience in 6 children with C. indologenes infections. Early and prompt management of C. indologenes infections, particularly in children with mechanic ventilation, with polymicrobial infections, and under the age of 2 years, is of major importance because these factors seem to have a negative effect on the prognosis of infections caused by C. indologenes. Ciprofloxacin and TPM-SMX may be the best therapeutic choices for a combined initial empirical treatment of the patients.

[Should fluoroquinolones be feared during pregnancy and breastfeeding?] / Faut-il craindre les fluoroquinolones chez une femme enceinte ou qui allaite ?

Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin) are antibiotics which pharmacological and therapeutic advantages resulted in a large use, now restricted because of resistances emergence and adverse effect risk. For pregnant or breastfeeding women they still are a cause of concern, based on the joint toxicity described in children directly treated, thus limiting their use in these populations. However, the data about exposed pregnancies published over time have not so far confirm these fears and allow, when a fluoroquinolone is clearly indicated, not to deprive pregnant patients of the therapeutic benefit of these important antibiotics and to envisage their use whatever the term of the pregnancy, within the current scope of their prescription. During breastfeeding the use of some of them can be considered.

Evolution of Bacterial Persistence to Antibiotics during a 50,000-Generation Experiment in an Antibiotic-Free Environment.

Failure of antibiotic therapies causes > 700,000 deaths yearly and involves both bacterial resistance and persistence. Persistence results in the relapse of infections by producing a tiny fraction of pathogen survivors that stay dormant during antibiotic exposure. From an evolutionary perspective, persistence is either a 'bet-hedging strategy' that helps to cope with stochastically changing environments or an unavoidable minimal rate of 'cellular errors' that lock the cells in a low activity state. Here, we analyzed the evolution of persistence over 50,000 bacterial generations in a stable environment by improving a published method that estimates the number of persister cells based on the growth of the reviving population. Our results challenged our understanding of the factors underlying persistence evolution. In one case, we observed a substantial decrease in persistence proportion, suggesting that the naturally observed persistence level is not an unavoidable minimal rate of 'cellular errors'. However, although there was no obvious environmental stochasticity, in 11 of the 12 investigated populations, the persistence level was maintained during 50,000 bacterial generations.

[DRESS syndrome induced by ciprofloxacine]. / DRESS syndrome à la ciprofloxacine.

The Drug rash with hypereosinophilia and systemic symptoms (DRESS) syndrome, or hypersensitivity syndrome, is a severe drug-induced hypersensitivity syndrome. It has been exceptionally described with ciprofloxacin. We report a 47-year-old-woman who developed DRESS syndrome, 2 days after taking ciprofloxacin for a urinary infection. She had a generalized maculopapular rash, severe rhabdomyolysis, liver involvement, renal failure and hypereosinophilia. Clinical symptoms had completely resolved after ciprofloxacin withdrawal. Renal failure has decrease after short corticosteroid treatment.

Comparación entre ciprofloxacina y antibióticos de otros grupos farmacológicos para el tratamiento de infecciones del tracto urinario / Comparison between ciprofloxacine and antibiotics of other pharmacological groups for urinary tract infection treatment / Comparação entre a ciprofloxacina e outros antibióticos grupos farmacológicos para o tratamento de infecções do tracto urinário

ResumenIntroducción. Las infecciones de tracto urinario son un tema común en los servicios de consulta externa y emergencias de los centros de salud. El uso inadecuado e irracional de antibióticos puede favorecer la aparición de cepas resistentes y limitar la capacidad de respuesta de estos fármacos. Este artículo busca revisar el uso de quinolonas (específicamente ciprofloxacina) con antibióticos de otros grupos farmacológicos y comparar efectividad y resistencia bacteriana.Método. A partir de la metodología que señala la práctica clínica basada en la evidencia para las revisiones rápidas, se estableció una pregunta clínica a la que se le procuró responder mediante la búsqueda de investigaciones primarias en bases de datos electrónicas como MEDLINE, PubMed, Cochrane Library Plus y el Journal of Infection.Resultado. Según el tipo de bacteria y cepa analizada, hay presencia de resistencia a diversos antibióticos. Las infecciones de origen comunitario han sido tratadas con betalactámicos, nitrofurantoína, trimetoprimsulfametoxasol y fluoroquinolonas (especialmente ciprofloxacina).Conclusión. No se determinó si las quinolonas son más efectivas que los antibióticos que pertenecen a otros grupos farmacológicos

AbstractIntroduction. Urinary tract infections are a common reason of consultation in medical practical in ambulatory and emergency rooms in centers of health. The inadequate and irrational use of antibiotics can favor the appearance of resistant bacterial strain and limit the capacity of response of these medicines. This article seeks to review the use of quinolones (specifically ciprofloxacine) with antibiotics of other pharmacological groups and to compare efficiency and bacterial resistance.Method.From the methodology that indicates the clinical practice based on the evidence for the rapid reviews, there was established a clinical question to which response was tried to give by means of the search of primary investigations in electronic databases like MEDLINE, PubMed, Cochrane Library Plus and the Journal of Infection.Result. According to the type of bacterium and analyzed bacterial strain there is presence of resistance to diverse antibiotics. The infections of community origin have been treated by beta-lactamics, nitrofurantoine, trimetoprimsulfametoxasol and fluoroquinolones (specially ciprofloxacine).Conclusion. It was not possible to determine if the quinolonas are more effective than the antibiotics that belong to other pharmacological groups.

ResumoIntrodução. As infecções do trato urinário são um tema comum nos serviços de consulta externa e emergências dos centros de saúde. O uso inadequado e irracional de antibióticos pode favorecer o aparecimento de cepas resistentes e limitar a capacidade de resposta destes medicamentos. Este artigo busca revisar o uso de quinolonas (especificamente ciprofloxacina) com antibióticos de outros grupos farmacológicos e comparar efetividade e resistência bacteriana.Método. A partir da metodologia que aponta a prática clínica baseada na evidência para as revisões rápidas, se estabeleceu uma pergunta clínica que se procurou responder mediante pesquisas primárias em bases de dados eletrônicas como MEDLINE, PubMed, Cochrane Library Plus e o Journal of Infection.Resultado. Segundo o tipo de bactéria e cepa analisada, há presença de resistência a diversos antibióticos. As infecções de origem comunitária tem sido tratadas com betalactâmicos, nitrofurantoína, trimetoprimsulfametoxasol e fluoroquinolonas (especialmente ciprofloxacina).Conclusão. Não se determinou se as quinolonas são mais eficazes que os antibióticos que pertencem a outros grupos farmacológicos

Desensibilización con ciprofloxacina en una paciente con infección urinaria parcialmente tratada / Desensitization with ciprofloxacin in a patient with partially treated urinary tract infection

Por más de 30 años se han usado ampliamente las fluoroquinolonas a las cuales ha habidobuena tolerancia; son de amplio espectro contra gérmenes grampositivos y gramnegativos,aunque la actividad de la norfloxacina, la ciprofloxacina y la ofloxacina contra estreptococos yalgunos anaerobios es limitada; tienen, además, buena biodisponibilidad oral y adecuadapenetración en los tejidos. Se presentan reacciones características de hipersensibilidadaproximadamente en 1 por cada 50.000. tratamientos. Se describe un caso de desensibilizaciónoral exitosa con ciprofloxacina en una paciente con infección urinaria crónica parcialmentetratada. Esta es la primera desensibilización con quinolonas reportada en Colombia.

Desensitization with ciprofloxacin in a patient with partially treated urinary tract infectionFluoroquinolones have been widely used for over 30 years and tolerance to them has beengood. They are of broad spectrum against both gram positive and gram negative bacteria, althoughthe activity of norfloxacin, ciprofloxacin and ofloxacin against streptococci and some anaerobicbacteria is rather limited. Their oral bioavailability is good and tissue penetration is adequate.68IATREIA / VOL 23/No. 1/ MARZO/ 2010Hipersensitivity reactions occur in about 1 per 50.000treatments. We report a case of successful oraldesensitization with ciprofloxacin in a patient withchronic partially treated urinary tract infection. This isthe first desensitization with quinolones reported inColombia.