Tobramycin promotes fracture healing by upregulating expressions of ALP and RUNX2 proteins through activating Wnt/β-catenin pathway / 中国骨伤

OBJECTIVE@#To explore effect of tobramycin (TOB) on healing of femoral fractures in rats.@*METHODS@#Totally 32 male sprague-dawley (SD) rats were selected and randomly divided into sham group (group A), fracture group (group B), fracture with TOB group (group C) and fracture + TOB + IWR-1 group (group D), 8 rats in each group. Close femoral fracture model in rats were established in group B, C and D, group A was sham operation without otherwise process. Group D was intraperitoneal injected 100 μl (8 μM) of Wnt pathway inhibitor IWR-1-endo (IWR-1) before molding at 1 day. At 1 day after molding, 100 μl (100 μM) of TOB was intraperitoneally injected into group C and D at once a day for 7 days. At 7 weeks after modling, fracture healing of group B, C and D were observed by X-ray, Western blotting was appilied to detect alkaline phosphatase(ALP) and Runt related transcription factor 2 (RUNX2) and β-catenin of Wnt passway.@*RESULTS@#X-ray results showed fracture line disappeared, callus formation and fracture healing well in group C compared with begning of molding; while a little fracture line, callus formation and fracture malunion in group B and d could be seen. Western blotting results showed ALP, RUNX2 and expression of β-catenin in group B, C and D were higher than that of group A (@*CONCLUSION@#Tobramycin could promote osteoblast differentiation and fracture healing by stimulating Wnt / β-catenin signaling pathway, up regulating expression of ALP and RUNX2.

Resistência aos antimicrobianos e diversidade genética de variantes fenotípicas de Pseudomonas aeruginosa não sensíveis aos carbapenêmicos recuperadas de pacientes com fibrose cística com infecção pulmonar crônica: uma análise temporal / Antimicrobial resistance and genetic diversity of phenotypic variants of carbapenem non susceptible Pseudomonas aeruginosa recovered from patients with cystic fibrosis with chronic lung infection: a temporal analysis

Pseudomonas aeruginosa, bactéria ubíqua e versátil, pode se comportar como um patógeno oportunista, com ampla capacidade adaptativa, por múltiplos fatores de virulência e resistência. Como agente patogênico nas infecções pulmonares em pacientes com fibrose cística (FC), é motivo de prognóstico ruim, aumento de hospitalizações e altas taxas de morbimortalidade, sendo quase impossível a sua erradicação, ao evoluírem para a cronicidade. Globalmente, é notável o aumento nos índices de amostras não sensíveis aos carbapenêmicos e a múltiplos antimicrobianos, essenciais à terapêutica. Assim, avaliamos temporalmente a susceptibilidade aos antimicrobianos e a presença de amostras hipermutáveis (HPM) em P. aeruginosa de diferentes morfotipos, não sensíveis aos carbapenêmicos (PANSC), obtidas de pacientes FC com infecção pulmonar crônica, acompanhados em dois centros de referência no Rio de Janeiro. De 2007 a 2016, a análise retrospectiva, através dos resultados obtidos no teste de disco-difusão (TDD), permitiu selecionar amostras de PANSC incluídas neste trabalho. Usando os resultados obtidos no TDD, foi definida a susceptibilidade a outros antimicrobianos, bem como os fenótipos de resistência, multi-(MDR), extensivo-(XDR) e pandroga resistentes (PDR). Adicionalmente, determinou-se a concentração inibitória mínima (CIM) para imipenem (IPM), meropenem (MEM), doripenem (DOR) e polimixina (POL). Através de teste fenotípico, foi calculada a frequência de mutação espontânea e as amostras hipermutáveis foram caracterizadas. O sequenciamento de genoma total (SGT) foi realizado em seis amostras de diferentes morfotipos, incluindo uma variante fenotípica rara, a small colony variant (SCV). Essas amostras foram recuperadas em dois episódios de exacerbação do paciente. Foram investigadas a clonalidade, resistência a antimicrobianos e virulência. Das 143 amostras, de 18 pacientes (9 pediátricos e 9 adultos), os resultados do TDD apontaram taxas de não susceptibilidade superiores a 44% para gentamicina, amicacina, tobramicina e ciprofloxacina, e maiores de 30 % para POL. Pela determinação da CIM, quase a totalidade (96%) das amostras foram não sensíveis a IMP, seguidos de 56% para MEM e 44% para DOR. Analisando-se a distribuição dos valores da CIM50 e CIM90 nos dois grupos de pacientes, os valores para IMP foram maiores entre as amostras dos pacientes pediátricos, equivalendo a 32 µg/mL e 64 µg/mL, respectivamente. Cerca de 25%, 37% e 6% eram MDR, XDR e PDR, respectivamente. Aproximadamente 12% eram HPM, e mais da metade destas foram XDR. Após o SGT, as seis amostras, recuperadas do caso clínico foram classificadas em um novo sequence type (ST2744), com a presença de genes de resistência adquiridos blaPAO, blaOXA-50, aph(3')-Iib, fosA, catB7 e crpP, apresentando mutações em genes codificadores de porinas e bombas de efluxo. Entretanto, não foram observados marcadores genéticos clássicos exclusivos para os fenótipos SCV e HPM. Este é o primeiro relato de P. aeruginosa SCV na FC, no Brasil. A vigilância epidemiológica de P. aeruginosa é crucial para a conduta terapêutica, bem como para o sucesso da resposta do paciente e erradicação da infecção pulmonar, justificando o uso de técnicas fenotípicas e moleculares na detecção dos mecanismos de resistência e virulência desse microrganismo na FC.

Pseudomonas aeruginosa, a ubiquitous and versatile bacterium, can behave as an opportunistic pathogen, with strong adaptive capacity, due to multiple virulence and resistance factors. As a pulmonary infection pathogen in patients with cystic fibrosis (CF), it is related with poor prognosis, increased hospitalizations and high rates of morbidity and mortality, and the eradication is almost impossible, especially after chronicity. The increase rates of isolates non-susceptible to carbapenem and multiple antimicrobials, essentials to therapy, have been observed worldwide. Therefore, we assessed the antimicrobial susceptibility and the presence of hypermutability (HPM) in non-susceptible to carbapenem P. aeruginosa (PANSC) isolates from different morphotypes, obtained from CF patients with chronic pulmonary infection, followed at two reference centers in Rio de Janeiro. Using the results obtained by disk-diffusion test (DDT) between 2007 to 2016, we select 143 PANSC and susceptibility to other antimicrobials was defined, as well as the resistance phenotypes, multi- (MDR), extensive- (XDR) and pandrug resistant (PDR). Additionally, the minimum inhibitory concentration (MIC) for imipenem (IPM), meropenem (MEM), doripenem (DOR) and polymyxin (POL) was determined. Hypermutable isolates were characterized by determination of mutation frequency. Whole genome sequencing (WGS) was performed in six morphotypes isolates, including the small colony variant (SCV), a rare variant phenotype. These isolates were recovered in two exacerbation episodes. Clonality, antimicrobial resistance and virulence were investigated. Of the total (143 isolates) isolated from 18 patients (9 pediatric and 9 adults), non-susceptibility rates above than 44% for gentamicin, amikacin, tobramycin and ciprofloxacin, and more than 30% for POL were observed. Almost all (96%) of the isolates were non-susceptible to IPM by MIC determination, followed by 56% for MEM and 44% for DOR. MIC50 (32 µg/mL) and MIC90 (64 µg/mL) rates for IPM were higher among pediatric patient isolates and 25%, 37% and 6% were MDR, XDR and PDR, respectively. 12% of all isolates were classified as HPM and more than half were categorized as XDR. Using WGS, the six isolates recovered from the clinical case, were identified as a new sequence type (ST2744). Acquired resistance genes blaPAO, blaOXA-50, aph (3')-Iib, fosA, catB7 and crpP and mutations in encoding genes for porins and efflux pumps, was annotated. None exclusive classic genetic markers related to SCV and HPM phenotypes were not observed. This is the first Brazilian report of P. aeruginosa SCV in CF. Our results highlight the importance of epidemiological surveillance in P. aeruginosa. The application of phenotypic and molecular techniques to investigate resistance and virulence mechanisms, can contribute to therapeutic success in CF.

Radial Keratoneuritis in Aeromonas Keratitis

PURPOSE: We report a case of Aeromonas keratitis presenting as radial keratoneuritis. CASE SUMMARY: A 33-year-old woman with a history of cleaning her contact lenses with tap water presented with decreased visual acuity for 1 day in the left eye. The patient showed diffuse corneal edema, stromal infiltration, and radial keratoneuritis, which were thought to be pathognomonic for Aeromonas keratitis. Based on the patient's clinical findings and past history, a diagnosis of Aeromonas keratitis was made and she was prescribed topical fortified cefazolin (50 mg/mL, 5%), tobramycin (3 mg/mL), and 0.02% chlorhexidine per hour. Culture results from the contact lens and contact lens solution confirmed infection by Aeromonas hydrophilia. Polymerase chain reaction results for Aeromonas were negative. After 8 days of treatment, the uncorrected visual acuity was 0.7/0.3 with improvement in her corneal findings. CONCLUSIONS: Radial keratoneuritis is not always pathognomic for Aeromonas keratitis and can be present in Aeromonas keratitis. Therefore, ophthalmologists should be cautious when interpreting this clinical sign.

Eficacia de la azitromicina versus tobramicina. Uso tópico en niños con conjuntivitis bacteriana. Revisión sistemática y meta-análisis / Efficacy of azithromycin versus tobramycin in topical formulation in children with bacterial conjunctivitis. A systematic review and meta-analysis

Introducción. La conjuntivitis bacteriana aguda (CBA) es una patología frecuente en niños. El uso de antibióticos tópicos acelera la recuperación, reduce recidivas y previene complicaciones. Un tratamiento abreviado, con menor número de aplicaciones diarias podría mejorar la adherencia al mismo. Actualmente, se proponen intervenciones con esquemas terapéuticos con estas características. Objetivo. Evaluar la eficacia del uso de azitromicina en esquemas breves, comparada con tobramicina para el tratamiento de CBA en niños. Materiales y métodos. Se realizó la búsqueda bibliográfica en MEDLINE, Cochrane Library y LILACS, considerando la evidencia disponible hasta mayo de 2019. Se incluyeron ensayos clínicos controlados aleatorizados (ECCAs) y ensayos clínicos controlados (ECCs). Resultados. Incluimos 3 ECCAs con 557 participantes. La mayoría de los dominios investigados fueron de bajo e incierto riesgo de sesgo. Comparado con el tratamiento estándar ­tobramicina­, la azitromicina podría incrementar la cura clínica al tercer día (3 estudios, 557 participantes: RR 1.36 IC95% 0.92 a 2.01; I2 54%; con baja certeza de evidencia) y al finalizar el tratamiento (3 estudios, 557 participantes: RR 1.03 IC95% 0.91 a 1.17; I2 50%; con baja certeza de evidencia). En ambos tratamientos los IC incluyen beneficio, pero también cierto grado de daño. La azitromicina podría reducir levemente la cura bacteriológica al finalizar el tratamiento (3 estudios, 556 participantes: RR 0.97 IC95% 0.91 a 1.03; I2 14%; moderada certeza de evidencia) comparado con la tobramicina. El IC es impreciso, debido a a que cruza la línea de nulidad. Conclusión de los autores. Basados fundamentalmente en resultados con baja a moderada calidad de evidencia, la azitromicina podría incrementar la cura clínica y reducir la cura bacteriológica en niños con CBA comparada con la tobramicina; sin embargo, los IC 95% indican también ausencia de beneficio. No se describen eventos adversos. Serán necesarios nuevos ECCAs para reducir la imprecisión observada en los resultados, y acceder al efecto de la azitromicina

Introduction. Acute bacterial conjunctivitis is a frequent pathology in children. The use of topical antibiotics accelerates recovery, reduces recurrences and prevents complications. A short treatment course with less instillation could improve treatment compliance. Nowadays, short term treatments are proposed. Objective. To assess the efficacy of topical azithromycin in short term regimen, compared with topical tobramycin in children with CBA. Materials and methods. A literature search was performed in MEDLINE, Cochrane and LILACs, including literature published until May 2019. Controlled and randomized clinical trials (RCTs) were included. Results. We included three RCTs with 557 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to the standard treatment (tobramycin), azithromycin may increase the clinical cure on third day (3 studies, 557 participants: RR 1.36 95% CI 0.92 to 2.01; I2 54%; low certainty of evidence) and at the end of treatment (3 studies, 557 participants: RR 1.03 95% CI 0.91 to 1.17; I2 50%; low certainty of evidence). However, in both results the CIs included benefit and harm. Azithromycin probably slightly reduce the bacteriological cure at the end of treatment (3 studies, 556 participants: RR 0.97 95% CI 0.91 to 1.03; I2 14%; moderate certainty of evidence). Conclusion. Based mainly on low quality of evidence identified, azithromycin treatment may increase the clinical cure, and probably reduce the bacteriological cure; however, the 95% CIs indicates lack of benefit too. None of the papers analyzed reported serious adverse effects in the participants. Given these results and considering that the regimen of azithromycin could have other benefits such as better adherence to treatment, we consider that azithromycin should be included as the antibiotic of choice for the treatment of acute bacterial conjunctivitis. Further adequate-powered RCTs are needed to reduce the imprecision of the results and allowing us to access the true effect of short treatment of azithromycin

Utilização de lente de contato escleral na abordagem terapêutica da úlcera neurotrófica corneana / Use of scleral contact lens in the therapeutic approach of corneal neurotrophic ulcer

Resumo Neste artigo descrevemos como conduzimos com sucesso um caso de úlcera neurotrófica não responsivo à terapia convencional com o uso de lente de contato escleral e as vantagens desta terapêutica.

Abstract In this paper we describe how we successfully conducted a case of neurotrophic ulcer not responsive to conventional therapy using scleral contact lens and the advantages of this therapy.

Mild encephalopathy with a reversible splenial lesion in a girl with acute pyelonephritis / 소아과

We report the case of a 12-year-old girl who had mild encephalopathy with a reversible splenial lesion (MERS) associated with acutepyelonephritis caused by Escherichia coli. The patient was admitted with a high fever, and she was diagnosed with acute pyelonephritis based on pyuria and the results of urine culture, which detected cefotaxime-sensitive E. coli. Although intravenous cefotaxime and tobramycin were administered, her fever persisted and her C-reactive protein level increased to 307 mg/L. On day 3 of admission, she demonstrated abnormal neuropsychiatric symptoms, such as delirium, ataxia, and word salad. Magnetic resonance imaging (MRI) of the brain performed on day 4 showed marked hyperintensities in the bilateral corpus callosum and deep white matter on diffusion-weighted images, with corresponding diffusion restriction on apparent diffusion coefficient mapping. No abnormalities or pathogens were detected in the cerebrospinal fluid; however, lipopolysaccharides (LPS, endotoxin) were detected in plasma (41.6 pg/mL), associated with acute neurological deterioration. Her clinical condition gradually improved, and no neurological abnormalities were observed on day 6. Follow-up brain MRI performed 2 weeks later showed near-disappearance of the previously noted hyperintense lesions. In this patient, we first proved endotoxemia in a setting of MERS. The release of LPS following antibiotic administration might be related to the development of MERS in this patient. The possibility of MERS should be considered in patients who present with acute pyelonephritis and demonstrate delirious behavior.

Cryotherapy on Refractory Fungal Corneal Ulcer: A Case Report

PURPOSE: We report a case of cryotherapy for fungal corneal ulcers that did not respond to antifungal agents. CASE SUMMARY: A 58-year-old man was transferred to our hospital with a left eye corneal ulcer due to pain and visual impairment in his left eye for two weeks, and he was suspected to have a history of fungal infection. At the time of admission, corneal opacity and progressive ulcerative lesions were observed at 5 o'clock in the left eye and visual acuity was 0.025, uncorrected. The corneal ulcer marginal resection, bacterial culture, and potassium hydroxide preparation (KOH) test were performed on lesion sites. Cultures of Candida albicans were reported to grow, topical antibiotics (Fortified tobramycin, Fortified cefazolin, moxifloxacin), and anti-fungal agents (fortified amphotericin B, 0.5%, Natamycin) were administered, but no improvement was observed for 2 weeks. On the 14th day after admission, Cryotherapy was performed. After surgery, eye drops were equally applied, and there was no other discomfort other than pain for 3 days after the operation. He discharged 10 days after surgery, the corneal lesion was healed and the visual acuity was improved to 0.32, uncorrected. CONCLUSIONS: We report a case of cryotherapy for fungal corneal ulcers that did not react with topical antifungal drugs and improved visual acuity and symptom improvement.

Antibiótico inalatório (tobramicina) para colonização das vias aéreas em pacientes com fibrose cística / Inhaled antibiotic (tobramycin) for colonization of the airways in patients with cystic fibrosis

Contexto: Os pacientes com fibrose cística apresentam infecções respiratórias recorrentes, também chamadas de exacerbações, causadas por bactérias, em especial a Pseudomonas aeruginosa. As infecções geram piora da função pulmonar e reduzem sua qualidade de vida. A proposta avaliada é o uso da tobramicina em nebulização para reduzir as exacerbações respiratórias. Pergunta: Nos pacientes com fibrose cística o uso de tobramicina inalatória reduz infecções respiratórias ou impacta em outros desfechos importantes para o paciente? Evidências científicas: Foi realizado monitoramento do horizonte tecnológico na base Cortellis e revisão da literatura priorizando revisões sistemáticas nas bases PubMed e biblioteca Cochrane. Não foram localizadas evidências de impacto em desfechos importantes para o paciente. O uso inalatório do antibiótico pode induzir broncoespasmos. Decisão: Incorporar a tobramicina inalatória para o tratamento da infecção crônica por Pseudomonas aeruginosa das vias aéreas em pacientes com fibrose cística, conforme Protocolo do Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS, dada pela Portaria SCTIE-MS nº 36 publicada no Diário Oficial da União (DOU) nº 207, de 27 de outubro de 2016.

Seguridad de tobramicina en polvo seco para inhalacion en pacientes con bronquiectasias no asociadas a fibrosis quistica colonizadas por pseudomona aeruginosa / Safety of tobramycin dry powder for inhalation in patients with bronchiectasis not associated with cystic fibrosis colonized by pseudomona aeruginosa

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación ha recibido la solicitud de evaluar la eficacia y seguridad de tobramicina en polvo seco para inhalación en pacientes con bronquiectasias no asociadas a fibrosis quística colonizada por Pseudomona Aeruginosa dentro del sistema de EsSalud, indicación actualmente no contemplada en el Petitorio Farmacológico de ESSALUD. Esta acción sigue lo estipulado en la Directiva N° 003-IETSI-ESSALUD-2016 y el objetivo final es determinar el estado del arte sobre la eficacia y seguridad de tobramicina en polvo seco para inhalación en el escenario específico descrito a continuación. Aspectos Generales: La bronquiectasia es una alteración anatómica acompañada de cambios histológicos. con dilataciones anormales e irreversibles de los bronquios. No es considerada como una enfermedad en sí misma. sino que es el resultado final de enfermedades o agresiones diferentes. Por lo general, surge como complicación de una patología de fondo, ya sea inflamatoria crónica o infecciosa. Existen reportes que evidencian un aumento en la prevalencia de las bronquiectasias. Así, Seitz et al. encontró que entre el 2000 al 2007 el número de los diagnósticos de bronquiectasias en Estados Unidos tuvo un aumento porcentual anual de 8,74%, con una prevalencia de periodo de 1,106 casos por 100,000. Además las bronquiectasias generan una importante carga para el sistema de salud. ya que se requieren largas estancias hospitalarias, consultas ambulatorias frecuentes y terapia médica extensa, solo en Estados unidos se encontró que significan $ 630 millones al año de gasto en salud. Tecnología Sanitaria de Interés: La Tobramicina es un antibacteriano aminoglucósido que actúa inhibiendo la síntesis proteica de las bacterias por unión a la unidad ribosomal 30S. Es bactericida a concentraciones iguales o ligeramente superiores a las concentraciones inhibitorias. Actualmente presenta dos presentaciones para inhalación, una solución para nebulización de 300 mg/ 5 ml y la tobramicina en polvo seco en capsulas de 28mg. La tobramicina en polvo para inhalación, está aprobada por la Agencia europea de medicamentos y por la FDA para el tratamiento supresor de las infecciones pulmonares crónicas debidas a Pseudomonas Aeruginosa en pacientes adultos y niños con fibrosis quística a partir de 6 años de edad. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de tobramicina en polvo seco para inhalación para pacientes con bronquiectasis no asociadas a FQ colonizadas por PA en las bases de datos de MEDLINE, EMBASE, CENTRAL, DARE y TRIPDATABASE. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales agencias de tecnologías sanitarias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de evidencia científica que sustente el uso de Tobramicina polvo inhalatorio en el tratamiento de bronquiectasias no asociadas a fibrosis quística según la pregunta PICO establecida. Para el presente documento se seleccionó el siguiente cuerpo de evidencia que es resumido a continuación: Guías Clínicas: Se identificó una única guía consensuada de recomendaciones en el manejo de las bronquiectasias no asociadas a FQ colonizadas por PA, esta fue elaborada por la sociedad de tórax de Reino Unido. Evaluaciones de tecnología sanitaria: Se identificó una evaluación de la tecnología que puede ser considerada como evidencia indirecta ya que es realizada en población con FQ y es presentada como un reporte para la FDA por un comité revisor, esta fue descrita en detalle en la sección de tecnología sanitaria. Revisiones sistemáticas: No se encontraron revisiones sistemáticas. Ensayos clínicos: Un ensayo de fase uno es considerada la única evidencia directa para nuestra población y la tecnología de interés. CONCLUSIONES: El tratamiento antibiótico inhalatorio por periodos largos en pacientes con colonización por PA y sin FQ no está sólidamente respaldado y se requiere de maycr evidencia para recomendarlo. La Tobramicina en polvo seco es una opción terapéutica que en pacientes con FQ ha demostrado tener mayores riesgos que beneficios usado como tratamiento antibiótico de largo plazo en pacientes con FQ y no se tiene la suficiente evidencia para incluirlo como terapia inhalatoria en pacientes sin FQ con colonización por PA. El Instituto de Evaluación de Tecnologías en Salud e Investigación (JETS') no aprueba el uso de tobramicina inhalatoria en polvo según el esquema planteado en la pregunta PICO para pacientes adultos con diagnóstico de bronquiectasias colonizadas por PA en pacientes con bronquiectasias no asociadas a FQ. Dado que la evidencia que respalda el uso de antibióticos inhalatorios en pacientes con bronquiectasias no asociadas a FQ colonizadas por PA, es de muy baja calidad, se requiere estudios que evalúen de forma directa la eficacia y seguridad de los antibióticos inhalatorios en este grupo de pacientes.

A 5-year Surveillance Study on Antimicrobial Resistance of Acinetobacter baumannii Clinical Isolates from a Tertiary Greek Hospital / 감염과화학요법

BACKGROUND: Acinetobacter baumannii has emerged as a major cause of nosocomial outbreaks. It is particularly associated with nosocomial pneumonia and bloodstream infections in immunocompromised and debilitated patients with serious underlying pathologies. Over the last two decades, a remarkable rise in the rates of multidrug resistance to most antimicrobial agents that are active against A. baumannii has been noted worldwide. We evaluated the rates of antimicrobial resistance and changes in resistance over a 5-year period (2010–2014) in A. baumannii strains isolated from hospitalized patients in a tertiary Greek hospital. MATERIALS AND METHODS: Identification of A. baumannii was performed by standard biochemical methods and the Vitek 2 automated system, which was also used for susceptibility testing against 18 antibiotics: ampicillin/sulbactam, ticarcillin, ticarcillin/clavulanic acid, piperacillin, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, meropenem, gentamicin, amikacin, tobramycin, ciprofloxacin, tetracycline, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Interpretation of susceptibility results was based on the Clinical and Laboratory Standards Institute criteria, except for tigecycline, for which the Food and Drug Administration breakpoints were applied. Multidrug resistance was defined as resistance to ≥3 classes of antimicrobial agents. RESULTS: Overall 914 clinical isolates of A. baumannii were recovered from the intensive care unit (ICU) (n = 493), and medical (n = 252) and surgical (n = 169) wards. Only 4.9% of these isolates were fully susceptible to the antimicrobials tested, while 92.89% of them were multidrug resistant (MDR), i.e., resistant to ≥3 classes of antibiotics. ICU isolates were the most resistant followed by isolates from surgical and medical wards. The most effective antimicrobial agents were, in descending order: colistin, amikacin, trimethoprim/sulfamethoxazole, tigecycline, and tobramycin. Nevertheless, with the exception of colistin, no antibiotic was associated with a susceptibility rate >40% for the entire study period. The most common phenotype showed resistance against ampicillin/sulbactam, cephalosporins, carbapenems, aminoglycosides, ciprofloxacin, and tigecycline. An extremely concerning increase in colistin-resistant isolates (7.9%) was noted in 2014, the most recent study year. CONCLUSION: The vast majority of A. baumannii clinical isolates in our hospital are MDR. The remaining therapeutic options for critically ill patients who suffer from MDR A. baumannii infections are severely limited, with A. baumannii beginning to develop resistance even against colistin. Scrupulous application of infection control practices should be implemented in every hospital unit. Lastly, given the lack of available therapeutic options for MDR A. baumannii infections, well-controlled clinical trials of combinations of existing antibiotics are clearly needed.

Green Nail Syndrome Treated with the Application of Tobramycin Eye Drop

Green nail syndrome (chromonychia) is a nail disorder characterized by onycholysis and green-black discoloration of the nail bed. This condition is often associated with chronic paronychia. Pseudomonas aeruginosa is the most commonly identified organism in cultures from the affected area. Despite the various treatment options available, removal of the nail is still necessary in many cases. A 35-year-old man presented with dark-greenish discoloration of the nail plate and onycholysis on the left thumbnail. He had been treated with oral antifungal and antibiotic agents for several months; however, the lesion showed no improvement. The diagnosis of green nail syndrome was established after a positive bacterial culture, and on the basis of the antibiotic sensitivity test result, tobramycin eye drop (Tobrex(R)) was then prescribed. Three weeks later, the nail discoloration almost vanished but the onycholysis remained. Herein, we recommend the application of tobramycin eye drop as an easy and safe treatment option for green nail syndrome.

Antibiotics Susceptibility in Bacterial Keratitis and Proper Initial Treatment

PURPOSE: The present study aims to determine the common pathogens involved in the etiology of bacterial keratitis and to analyze not only the antibiotic susceptibility of bacterial isolates from patients with bacterial keratitis but also the propriety of initial treatment. METHODS: A retrospective study of 161 eyes in 161 patients with bacterial keratitis, who were diagnosed by cultures from 2000 to 2011, was performed. Causative bacteria and antibiotic susceptibility were evaluated in consecutive 6-year periods. RESULTS: The most common bacteria was the pseudomonas species in the 2 time periods tested and cefazolin with tobramycin was the most commonly used antibiotic (125 cases, 77.6%) for initial treatment of bacterial keratitis. In vitro testing showed gram-negative susceptibility to tobramycin and ciprofloxacin was over 70%, gram-positive susceptibility to cephalothin and vancomycin was 100% and there was no significant difference between the 2 time periods tested. Eight cases had resistance to the initial treatment, but only 1 case showed treatment failure. CONCLUSIONS: Antibiotics used for initial treatment of bacterial keratitis were able to obtain a proper effect but several cases showed bacterial resistance to antibiotics. Thus, continued testing is essential to monitor for antibiotic resistance.

Outcomes of Peritonitis in Children on Peritoneal Dialysis: A 25-Year Experience at Severance Hospital

PURPOSE: Relatively little is known on the microbiology, risk factors and outcomes of peritoneal dialysis (PD)-associated peritonitis in Korean children. We performed this study in order to evaluate the incidence, treatment and clinical outcomes of peritonitis in pediatric PD patients at Severance Hospital. MATERIALS AND METHODS: We analyzed data from 57 PD patients younger than 18 years during the period between June 1, 1986 and December 31, 2011. The collected data included gender, age at commencement of PD, age at peritonitis, incidence of peritonitis, underlying causes of end stage renal disease, microbiology of peritonitis episodes, antibiotics sensitivity, modality and outcomes of PD. RESULTS: We found 56 episodes of peritonitis in 23 of the 57 PD patients (0.43 episodes/patient-year). Gram-positive bacteria were the most commonly isolated organisms (40 episodes, 71.4%). Peritonitis developed in 17 patients during the first 6 months following initiation of PD (73.9%). Peritonitis episodes rarely resulted in relapse or the need for permanent hemodialysis and no patient deaths were directly attributable to peritonitis. Antibiotic regimens included cefazolin+tobramycin from the years of 1986 to 2000 and cefazolin+ceftazidime from the years of 2001 to 2011. While antibiotic therapy was successful in 48 episodes (85.7%), the treatment was ineffective in 8 episodes (14.3%). The rate of continuous ambulatory PD (CAPD) peritonitis was statistically higher than that of automated PD (APD) (p=0.025). CONCLUSION: Peritonitis was an important complication of PD therapy and we observed a higher incidence of PD peritonitis in patients with CAPD when compared to APD.

A Case of Endophthalmitis Caused by Shewanella algae after Trauma

PURPOSE: To report a rare case of endophthalmitis caused by Shewanella algae after trauma. CASE SUMMARY: A 27-year-old man was referred for trauma caused by a fishing sinker in his right eye. On initial examination at another hospital, his visual acuity was light perception, and intraocular pressure was 50 mm Hg. On slit lamp examination, corneal edema and severe anterior chamber inflammation were observed. Consequently, the next day total pars plana vitrectomy, lensectomy, intravitreal silicone oil injection, and antibiotics injection were performed. After the operation, intraocular pressure was 15 mm Hg and the patient's pain was temporarily decreased. The presence of Shewanella algae in the vitreous culture was determined but antibiotic sensitivity was not proven. The patient received postoperative topical fortified vancomycin, ceftazidime, and tobramycin hourly and underwent intravenous antibiotic therapy. On postoperative day 25, the patient transferred to our hospital and ocular pain presented continuously. Intraocular inflammation was not severe but visual acuity was light perception because of retinal necrosis in the posterior pole. Therefore, the patient received topical fortified antibiotics and intravenous antibiotics therapy. On postoperative month 2, visual acuity was light perception and the patient's right eye progressed to pthisis bulbi. CONCLUSIONS: Here in the first case reported in Korea or other conturies of primary endophthalmitis by Shewanella algae after traumas. Shewanella algae endophthalmitis has a rapid progression and poor visual prognosis in spite of aggressive therapy.

Achromobacter xylosoxidans Keratitis after Contact Lens Usage

To report on Achromobacter xylosoxidans keratitis in two healthy patients who had worn contact lenses foran extended period of time. A 36-year-old female and a 21-year-old female visited our hospital with ocular pain and blurred vision. Both patients had a history of wearing soft contact lenses for over fve years with occasional overnight wear. At the initial presentation, a slit lamp examination revealed corneal stromal infiltrations and epithelial defects with peripheral neovascularization in both patients. Microbiological examinations were performed from samples of corneal scrapings, contact lenses, contact lens cases, and solution. The culture resulting from the samples taken from the contact lenses, contact lens cases, and solution were all positive for Achromobacter xylosoxidans. Confrming that the direct cause of the keratitis was the contact lenses, the frst patient was prescribed ceftazidime and amikacin drops sensitive to Achromobacter xylosoxidans. The second patient was treated with 0.3% gatifoxacin and fortifed tobramycin drops. After treatment, the corneal epithelial defects were completely healed, and subepithelial corneal opacity was observed. Two cases of Achromobacter xylosoxidans keratitis were reported in healthy young females who wore soft contact lenses. Achromobacter xylosoxidans should be considered a rare but potentially harmful pathogen for lens-induced keratitis in healthy hosts.

A Case of Peritonitis caused by Chryseobacterium meningosepticum in a Patient Treated with Peritoneal Dialysis / 대한신장학회지

Chryseobacterium meningosepticum is rarely encountered as a pathogen causing peritonitis in peritoneal dialysis (PD) patients. We report a case of peritonitis due to Chryseobacterium meningosepticum, which was treated successfully with intraperitoneal (IP) vancomycin and ciprofloxacin, and without PD catheter removal. Peritonitis was developed in a 53-year-old PD patient on the third hospital day. Although empirical IP treatment with cefazolin and tobramycin was initiated and maintained for 3 days, the fever and signs of peritonitis persisted. Antibiotics were changed to cefoperazone/sulbactam, amikacin, and vancomycin due to clinical deterioration. After 3 days of vancomycin use, leukocyte count in PD fluid was less than 100/mm3 and the patient became asymptomatic. On seventh day after the onset of peritonitis, Chryseobacterium meningosepticum was isolated from initial dialysate sample, and this strain was susceptible to ciprofloxacin, piperacillin, and piperacillin/tazobactam. Accordingly, we changed the antibiotics to ciprofloxacin and vancomycin, which were given for the total of 14 days. Even though Chryseobacterium meningosepticum is an uncommon causative organism of peritonitis in PD patients, this report suggests that vancomycin and ciprofloxacin are effective as empiric therapy, and early suspicion and appropriate antimicrobial therapy are crucial to the successful treatment of peritonitis due to Chryseobacterium meningosepticum without catheter removal.

Comparative nephrotoxic effects of gentamycin and tobramycin

To compare the nephrotoxic effects of two aminoglycosides namely, gentamycin and tobramycin on rabbits. Comparative study. Allama Iqbal Medical College Lahore, from January 2010 to December 2010. The serum levels of creatinine and electrolytes [sodium and potassium] were measured in different groups of rabbits [control group-A, gentamycin group B and tobramycin-group C]. Rabbits in group B and C received laboratory diet and 32 mg/kg/day of gentamycin and tobramycin were given through intramuscular [IM] route twice daily for 7 days. Blood samples were collected on day 1, 10, 16, and 22 of drug administration. Each rabbit of all groups was sacrificed on 22[nd] day of experiment. Kidneys were removed and histological examination of the 4 components of the renal tissue [glomeruli, tubules, blood vessels and interstitial tissue] was carried out. Level of serum creatinine was significantly increased in both experimental groups [B and C] as compared to the control group A. On the other hand, level of serum sodium was insignificantly increased in groups B and C, whereas level of serum potassium was significantly decreased in groups of rabbits receiving gentamycin and tobramycin as compared to control group. There was no significant difference in nephrotoxicity between gentamycin and tobramycin

Scrofuloderma and bilateral anterior staphyloma of eye: an unusual association

We report a patient with bilaterally symmetrical perforated corneal ulcers with formation of anterior staphyloma associated with scrofuloderma. A 22-year-old female in her third month postpartum presented with multiple perforated corneal ulcers bilaterally. There was a presence of a skin lesion that was consistent with scrofuloderma. Fine needle aspiration cytology of preauricular lymph nodes showed evidence of granulomatous inflammation consistent with tuberculosis. Corneal scraping revealed the presence of coagulase-negative Staphylococcus. She was treated with topical fortified combination antibiotics [cefazolin and tobramycin]. The corneal ulcer resolved with formation of anterior staphyloma in both eyes. The patient underwent anterior staphylectomy and tectonic keratoplasty in both eyes. Eight weeks postoperatively, her visual acuity improved to 20/200 in both eyes with clear grafts. Scrofuloderma may be associated with recurrent phlyctenulosis. Multiple corneal ulcerations coupled with use of topical steroids may result in corneal perforation and formation of anterior staphyloma

Utilidad de los antibióticos inhalados: más allá de la fibrosis quística / Inhaled antibiotic utility: more than cystic fibrosis

Inhalatory therapy is the preferred way for drugs targeting the lung, which permits to avoid adverse events associated to systemic use. Cystic fibrosis (CF) is the disease with the highest use of inhaled antibiotics, which has provided information extrapoled to other pathologies such as non-CF bronchiectasis and pneumonia associated to mechanical ventilation. The most studied antibiotics currently available in the market are tobramycin and colystin, both inhaled. This article analyzes the updated evidence and recommendations published regarding the use of inhaled antibiotics.

La terapia inhalatoria es la vía de elección para la administración de fármacos cuyo órgano diana es el pulmón, pues evita los efectos adversos asociados a su uso sistémico. La fibrosis quística (FQ) es la enfermedad en que se ha centrado la mayor utilización de antibióticos inhalados, aportando información que se ha extrapolado a otras patologías como las bronquiectasias no FQ y la neumonía asociada a ventilación mecánica. Los antibióticos más estudiados y actualmente disponibles en el mercado son la tobramicina y colistín inhalados. Este artículo revisa la evidencia actualizada y las recomendaciones publicadas en torno al uso de antibióticos por vía inhalatoria.

In-Vitro Efficacy of Synergistic Antibiotic Combinations in Multidrug Resistant Pseudomonas Aeruginosa Strains

PURPOSE: Combination antibiotic treatment is preferred in nosocomial infections caused by Pseudomonas aeruginosa (P. aeruginosa). In vitro synergism tests were used to choose the combinations which might be used in clinic. The aim of this study was to investigate the synergistic efficacy of synergistic antibiotic combinations in multidrug resistant P. aeruginosa strains. MATERIALS AND METHODS: Synergistic efficacies of ceftazidime-tobramycin, piperacillin/tazobactam-tobramycin, imipenem-tobramycin, imipenem-isepamycin, imipenem-ciprofloxacin and ciprofloxacin-tobramycin combinations were investigated by checkerboard technique in 12 multiple-resistant and 13 susceptible P. aeruginosa strains. RESULTS: The ratios of synergy were observed in ceftazidime-tobramycin and piperacillin/tazobactam-tobramycin combinations as 67%, and 50%, respectively, in resistant strains, whereas synergy was not detected in other combinations. The ratios of synergy were observed in ceftazidime-tobramycin, piperacillin/tazobactam-tobramycin, imipenem-tobramycin, imipenem-ciprofloxacin and imipenem-isepamycin combinations as 31%, 46%, 15%, 8%, 8%, and respectively, in susceptible strains, whereas synergy was not detected in ciprofloxacin-tobramycin combination. Antagonism was not observed in any of the combinations. CONCLUSION: Although the synergistic ratios were high in combinations with ceftazidime or piperacillin/tazobactam and tobramycin, the concentrations in these combinations could not usually reach clinically available levels. Thus, the solution of the problems caused by multiple resistant P. aeruginosa should be based on the prevention of the development of resistance and spread of the causative agent between patients.