RESUMO
Abstract The quality, efficacy, and safety of medicines are usually verified by analytical results. Measurement uncertainty is a critical aspect for the reliability of these analytical results. The pharmacopeial compendia usually adopt a simple acceptance rule that does not consider information from measurement uncertainty. In this work, we compared decision-making using simple acceptance and decision rules with the use of guard-band for multiparameter evaluation of ofloxacin ophthalmic solution and acyclovir topical cream. Ciprofloxacin ophthalmic solution and acyclovir topical cream samples were subject to pharmacopeial tests and assays. Multivariate guard-band widths were calculated by multiplying the standard uncertainty (u) by an appropriate multivariate coverage factor (k'). The multivariate coverage factor (k') was obtained by the Monte Carlo method. According to the simple acceptance rule, all the results obtained for ciprofloxacin ophthalmic solution and acyclovir topical cream are within the specification limits. However, the risk of false conformity decisions increases for ciprofloxacin tests. Decisions made using the simple acceptance rule and decision rules with the use of guard-band may differ. The simple acceptance rule may increase the risk of false conformity decisions when the measured value is close to the regulatory specification limits and/or when the measurement uncertainty value is inappropriately high. Nevertheless, the guard-band decision rule will always reduce the risk of false conformity decisions. Therefore, using information on measurement uncertainty in conformity assessment is highly recommended to ensure the proper efficacy, safety, and quality of medicines.
Assuntos
Preparações Farmacêuticas/análise , Análise Multivariada , Medição de Risco/tendências , Incerteza , Aciclovir/efeitos adversos , Ciprofloxacina/efeitos adversosRESUMO
The high load of agrochemicals and antibiotics present in agricultural aquatic environments represents a risk for wildlife. Since enteric bacteria, which play a key role in the physiological functioning of their hosts, are sensitive to a wide variety of pollutants, their study allows to evaluate the health of organisms. This study aimed to evaluate the effects of commercial formulations of a glyphosate-based herbicide (GBH) and the antibiotic ciprofloxacin (CIP), individually and in mixture, on the bacterial diversity of the intestinal content of common toad (Rhinella arenarum) tadpoles. The diversity of cultivable fast-growing bacteria with low nutritional requirements was evaluated using classic microbiological tests and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry identification. Bacterial diversity varied among treatments. Taxa diversity increased in the GBH-treated group but decreased in the CIP-treated group. Remarkably, Yersinia spp. and Proteus spp. were only found in the GBH-treated group. The prevalence of Klebsiella spp. and Pseudomonas spp. decreased in the intestinal microbiota of the GBH-CIP-treated group. To our knowledge, this is the first report on the alteration of cultivable enteric bacteria of autochthonous tadpoles due to two pollutants of emerging concern. Our results demonstrate that R. arenarum tadpoles can be used as non-conventional model organisms for environmental pollution monitoring. Our preliminary findings would contribute to understanding how the presence of GBH and CIP in freshwaters may represent a threat to wildlife and human health by causing enteric dysbiosis of part of the bacterial community.
Assuntos
Microbioma Gastrointestinal , Herbicidas , Animais , Humanos , Larva , Ciprofloxacina/efeitos adversos , Herbicidas/farmacologia , Enterobacteriaceae , Antibacterianos/efeitos adversos , GlifosatoRESUMO
Kounis syndrome (KS) is a rare syndrome characterized by the co-occurrence of acute coronary syndromes in the setting of mast cell and platelet activation in response to hypersensitivity reactions. It can be manifested as coronary vasospasms, acute myocardial infarction, or stent thrombosis triggered by drugs, vaccines, foods, coronary stents, and insect bites. It is a life-threatening condition that needs to be adequately recognized for early diagnosis and appropriate treatment. In this case report, we present a 71-year-old patient with a history of arterial hypertension and non-ST elevation myocardial infarction six months earlier that was treated percutaneously with angioplasty plus stent implantation in the circumflex artery, who subsequently presented to the emergency department due to generalized itching associated with tongue swelling, dyspnea, and chest pain after ingestion of ciprofloxacin for the treatment of a urogenital infection. An electrocardiogram showed ST elevation in II, III, and aVF leads, and positive troponin; thus, a coronary arteriography was performed that showed complete thrombotic stent occlusion in the circumflex artery. Consequently, diagnosis of type 4b inferolateral acute myocardial infarction secondary to ciprofloxacin-triggered type III Kounis syndrome was made. The aim of this report is to understand the relationship between the allergic reaction to ciprofloxacin and the acute coronary syndrome, and to create awareness of the importance of early diagnosis and treatment of this potentially fatal syndrome.
Assuntos
Síndrome Coronariana Aguda , Hipersensibilidade , Síndrome de Kounis , Infarto do Miocárdio , Trombose , Síndrome Coronariana Aguda/induzido quimicamente , Síndrome Coronariana Aguda/complicações , Idoso , Ciprofloxacina/efeitos adversos , Humanos , Hipersensibilidade/complicações , Síndrome de Kounis/diagnóstico , Síndrome de Kounis/etiologiaAssuntos
Pustulose Exantematosa Aguda Generalizada , Ciprofloxacina/efeitos adversos , Glucocorticoides/administração & dosagem , Mupirocina/administração & dosagem , Soluções Oftálmicas , Pele/patologia , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/fisiopatologia , Pustulose Exantematosa Aguda Generalizada/terapia , Administração Tópica , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Biópsia/métodos , Ciprofloxacina/administração & dosagem , Conjuntivite Bacteriana/tratamento farmacológico , Diagnóstico Diferencial , Substituição de Medicamentos , Emolientes/administração & dosagem , Humanos , Masculino , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/efeitos adversos , Resultado do Tratamento , Suspensão de TratamentoRESUMO
BACKGROUND: Many gaps in the burden of resistant pathogens exist in endemic areas of low- and middle-income economies, especially those endemic for carbapenem resistance. The aim of this study is to evaluate risk factors for carbapenem-resistance, to estimate the association between carbapenem-resistance and all-cause 30-day mortality and to examine whether mortality is mediated by inappropriate therapy. METHODS: A case-control and a cohort study were conducted in one tertiary-care hospital in Medellín, Colombia from 2014 to 2015. Phenotypic and genotypic characterization of isolates was performed. In the case-control study, cases were defined as patients infected with carbapenem-resistant K. pneumoniae (CRKP) and controls as patients infected with carbapenem-susceptible K. pneumoniae (CSKP). A risk factor analysis was conducted using logistic regression models. In the cohort study, the exposed group was defined as patients infected with CRKP and the non-exposed group as patients infected with CSKP. A survival analysis using an accelerated failure time model with a lognormal distribution was performed to estimate the association between carbapenem resistance and all-cause 30-day-mortality and to examine whether mortality is mediated by inappropriate therapy. RESULTS: A total of 338 patients were enrolled; 49 were infected with CRKP and 289 with CSKP. Among CRKP isolates CG258 (n = 29), ST25 (n = 5) and ST307 (n = 4) were detected. Of importance, every day of meropenem (OR 1.18, 95%CI 1.10-1.28) and cefepime (OR 1.22, 95%CI 1.03-1.49) use increase the risk of carbapenem resistance. Additional risk factors were previous use of ciprofloxacin (OR 2.37, 95%CI 1.00-5.35) and urinary catheter (OR 2.60, 95%CI 1.25-5.37). Furthermore, a significant lower survival time was estimated for patients infected with CRKP compared to CSKP (Relative Times 0.44, 95%CI 0.24-0.82). The strength of association was reduced when appropriate therapy was included in the model (RT = 0.81 95%CI 0.48-1.37). CONCLUSION: Short antibiotic courses had the potential to reduce the selection and transmission of CRKP. A high burden in mortality occurred in patients infected with CRKP in a KPC endemic setting and CRKP leads to increased mortality via inappropriate antibiotic treatment. Furthermore, dissemination of recognized hypervirulent clones could add to the list of challenges for antibiotic resistance control.
Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos , Doenças Endêmicas , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/genética , Meropeném/uso terapêutico , Idoso , Antibacterianos/efeitos adversos , Estudos de Casos e Controles , Cefepima/efeitos adversos , Cefepima/uso terapêutico , Ciprofloxacina/efeitos adversos , Ciprofloxacina/uso terapêutico , Colômbia , Farmacorresistência Bacteriana Múltipla , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Klebsiella pneumoniae/isolamento & purificação , Modelos Logísticos , Masculino , Meropeném/efeitos adversos , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Cateteres Urinários/efeitos adversosAssuntos
Anafilaxia/imunologia , Ciprofloxacina/efeitos adversos , Hipersensibilidade a Drogas/imunologia , Imunoglobulina E/imunologia , Mastócitos/imunologia , beta-Arrestina 2/imunologia , Anafilaxia/induzido quimicamente , Anafilaxia/patologia , Animais , Ciprofloxacina/farmacologia , Hipersensibilidade a Drogas/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Mastócitos/patologia , Camundongos , Camundongos KnockoutRESUMO
The occurrence of damage on bacterial DNA (mediated by antibiotics, for example) is intimately associated with the activation of the SOS system. This pathway is related to the development of mutations that might result in the acquisition and spread of resistance and virulence factors. The inhibition of the SOS response has been highlighted as an emerging resource, in order to reduce the emergence of drug resistance and tolerance. Herein, we evaluated the ability of betulinic acid (BA), a plant-derived triterpenoid, to reduce the activation of the SOS response and its associated phenotypic alterations, induced by ciprofloxacin in Staphylococcus aureus. BA did not show antimicrobial activity against S. aureus (MIC > 5000 µg/mL), however, it (at 100 and 200 µg/mL) was able to reduce the expression of recA induced by ciprofloxacin. This effect was accompanied by an enhancement of the ciprofloxacin antimicrobial action and reduction of S. aureus cell volume (as seen by flow cytometry and fluorescence microscopy). BA could also increase the hyperpolarization of the S. aureus membrane, related to the ciprofloxacin action. Furthermore, BA inhibited the progress of tolerance and the mutagenesis induced by this drug. Taken together, these findings indicate that the betulinic acid is a promising lead molecule in the development helper drugs. These compounds may be able to reduce the S. aureus mutagenicity associated with antibiotic therapies.
Assuntos
Farmacorresistência Bacteriana/efeitos dos fármacos , Recombinases Rec A/genética , Staphylococcus aureus/genética , Triterpenos/farmacologia , Ciprofloxacina/efeitos adversos , Ciprofloxacina/farmacologia , DNA Bacteriano/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Mutagênese/efeitos dos fármacos , Mutagênese/genética , Triterpenos Pentacíclicos , Resposta SOS em Genética/efeitos dos fármacos , Resposta SOS em Genética/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Fatores de Virulência/genética , Ácido BetulínicoRESUMO
Introdução: canais radiculares necrosados e não tratados se caracterizam pela presença de uma microbiota mista e polimicrobiana.O E. faecalis demonstra alta resistência a medicamentos usados durante o tratamento endodôntico, sendo um dos poucos microrganismos que tem demonstrado in vitro resistir ao efeito antibacteriano do hidróxido de cálcio. Além disso, é a espécie bacteriana mais frequentemente isolada, com prevalência variando entre 29% e 77% nos canais radiculares de dentes com insucesso endodôntico. Objetivo: avaliar a atividade antibacteriana dos cimentos endodônticos MTA Fillapex, Sealapex, Sealer 26 e Endofill puros e acrescidos de amoxicilina e ciprofloxacina frente a duas linhagens ATCC de Enterococcus faecalis (ATCC 29212 e ATCC 4083). Método: os testes foram realizados pela técnica de difusão radial dos cimentos aplicados diretamente no ágar, impregnados em discos de papel aplicados sobre o ágar e pelo teste de contato direto. Para a análise estatística utilizaram-se os testes de ANOVA e Tukey com nível de significância de 5%. Resultados e Discussão: os resultados mostraram que pela técnica da difusão radial, considerando os cimentos puros, o Sealapex foi o único que apresentou halo de inibição frente às duas linhagens. Já, quando da associação da amoxicilina e ciprofloxacina o MTA Fillapex demonstrou os melhores halos de inibição para as duas linhagens. Todos os cimentos tiveram a ação potencializada pela adição dos antibióticos (p<0,05). Pela técnica de difusão dos cimentos impregnados em discos de papel, o cimento Sealapex puro fresco revelou atividade antimicrobiana e também em todas as variáveis de tempo. Quando acrescidos os antibióticos, todos os cimentos tiveram a ação antimicrobiana potencializada pelas drogas, em todas as variáveis de tempo. Este mesmo resultado foi observado na técnica do contato direto dos cimentos com ambas as linhagens. Conclusão: a atividade antibacteriana, frente ao E. faecalis, dos cimentos MTA Fillapex, Endofill, Sealer e Sealapex acrescidos os antibióticos amoxicilina e ciprofloxacina, é potencializada mesmo após um longo período da presa dos cimentos.
Introduction: necrotic root canals and untreated are characterized by the presence of a mixed and polymicrobial flora. E. faecalis show high resistance to drugs used during endodontic treatment, one of the few microorganisms which have shown in vitro to resist the antibacterial effect of calcium hydroxide. Furthermore, it is the bacterial species most often isolated, with a prevalence ranging between 29% and 77%, in root canals of teeth with endodontic failure. Objective: the aim of this study was to evaluate the antibacterial activity of the sealers MTA Fillapex, Sealapex, Sealer 26 and Endofill, pure and loaded with amoxicillin and ciprofloxacin against two ATCC strains of Enterococcus faecalis (ATCC 29212 and ATCC 4083). Method: the tests were conducted by means of radial diffusion technique of the cement applied in to the agar, impregnated paper discs applied on the agar and by the direct contact test. For the statistical analysis, the ANOVA and the Tukey?s test were used at a 5% significance level. Results and Discussion: results showed that, through the technique of radial diffusion, regarding the pure cements, the Sealapex was the only one that showed inhibition halo for the two strains. However, considering the association of amoxicillin and ciprofloxacin Fillapex, the MTA showed better inhibition zones for the two strains. All cements had their actions enhanced by with addition of antibiotics (p <0.05). Through the technique of diffusion of cements impregnated in paper discs, the Sealapex pure fresh cement revealed an antimicrobial activity and also in all the variables of time. When loaded with antibiotics, all cements had the antimicrobial action potentiated by drugs in all variables of time. The same result was observed in the technique of direct contact of cement with both strains. Conclusionn: the antibacterial activity against the E. faecalis, of the cements MTA Fillapex, Endofill, Sealer and Sealapex loaded with the antibiotics amoxicillin and ciprofloxacin, is enhanced even after a long period of use of cements.
Assuntos
Enterococcus faecalis/efeitos dos fármacos , Cimentos Dentários/análise , Antibacterianos/uso terapêutico , Técnicas In Vitro , Teste de Materiais , Ciprofloxacina/efeitos adversos , Infecções por Bactérias Gram-Positivas , Amoxicilina/efeitos adversosRESUMO
OBJECTIVES AND DESIGN: A systematic review with meta-analysis of randomized controlled trials (RGT) on the efficacy and safety of ciprofloxacin in the treatment of acute or complicated urinary tract infections in adults. Primary outcomes were bacteriological eradication, clinical cure, bacterial resistance, and adverse event rates. RESULTS: Initially, 111 RGTs were identified. We excluded 81 studies due to low quality methodology. An analysis of the remaining RGTs identified therapeutic equivalence of ciprofloxacin against other antimicrobials in terms of bacterial eradication and clinical cure at the end of treatment and in subsequent stages. The percentage of bacterial resistance was similar in both groups, while the percentage of related adverse events was significantly lower in the groups treated with ciprofloxacin. CONCLUSIONS: We conclude that ciprofloxacin is a safe and effective therapeutic alternative for the treatment of acute or complicated urinary tract infections in adults.