Sensibilidad in vitro de Escherichia coli a la fosfomicina en urocultivos en un Servicio Asistencial Privado de Asunción / In vitro sensitivity of Escherichia coli to fosfomycin in urine cultures in a private healthcare service in Asunción

La fosfomicina es un antibiótico natural, que actúa sobre la síntesis de la pared celular, con actividad bactericida y de amplio espectro. En este trabajo se evaluó la sensibilidad in vitro de aislados de Escherichia coli (E. coli), incluidos aquellos que producen Beta Lactamasa de Espectro Extendido (BLEE) obtenidos a partir de urocultivos, tomados en diferentes lapsos de colección de datos, en personas de ambos sexos. Fueron incluidos 260 muestras de orina con desarrollo de E. coli provenientes de pacientes que concurrieron al Laboratorio San Roque. El aislamiento e identificación bacteriana se realizó según métodos convencionales y la sensibilidad a los antimicrobianos por el método de difusión de disco. Para la detección de la sensibilidad frente a fosfomicina fueron utilizados discos de 200 µg con el agregado de 50 µg de glucosa 6-fosfato. Se observó frente a los antibióticos evaluados mayor sensibilidad a fosfomicina (98,5%) y nitrofurantoína (97,7%). Ciprofloxacina, trimetoprima y la combinación sulfametoxazol/trimetoprima exhibieron frente a los mismos aislados sensibilidad menor y muy similar entre ellos, con 64,2%, 61,2% y 61,2% respectivamente. En 44 (16,9%) de los aislados de E. coli se detectó la presencia de BLEE y es destacable la alta sensibilidad que mostraron fosfomicina y nitrofurantoína, aún frente a los aislados BLEE positivos, con frecuencias de 90,9% y 93,2%, respectivamente. En resumen, la alta sensibilidad demostrada en el presente estudio por E. coli ante la fosfomicina, abre la posibilidad de considerar a este antibiótico de primera elección en las infecciones urinarias bajas, aún en los casos de gérmenes productores de BLEE, en la población de nuestro país.

Fosfomycin is a natural antibiotic, which acts on the synthesis of the cell wall, with broad spectrum bactericidal activity. In this study, the in vitro sensitivity of Escherichia coli (E. coli) isolates was evaluated, including those that produce Extended Spectrum Beta Lactamase (ESBL) obtained from urine cultures taken at different data collection times, in people of both sexes. Were included 260 urine samples with development of E. coli from patients who attended the San Roque laboratory. Bacterian isolation and identification was carried out according to conventional methods and antimicrobial sensitivity by the disk diffusion method. For detection of sensitivity to fosfomycin, 200 µg discs were used with the addition of 50 µg of glucose 6-phosphate. A greater sensitivity for fosfomycin (98.5%) and nitrofurantoin (97.7%) was observed against the evaluated antibiotics. Ciprofloxacin, trimethoprim and the sulfamethoxazole / trimethoprim combination exhibited in front of the same isolated lower sensitivity and very similar among them, with 64.2%, 61.2% and 61.2% respectively. In 44 (16.9%) of the E. coli isolates the presence of ESBL was detected and the high sensitivity shown by fosfomycin and nitrofurantoin is noteworthy, even compared to the positive ESBL isolates, with frequencies of 90.9% and 93,2%, respectively. In summary, the high sensitivity demonstrated in the present study by E. coli to fosfomycin opens the possibility of considering this first-choice antibiotic in lower urinary infections, even in ESBL-producing germs, in the population of our country.

Hipertensión intracraneal idiopática asociada a nitrofurantoína. Caso clínico / Idiopathic intracranial hypertension associated with nitrofurantoin. Case report

Resumen Introducción: La Hipertensión Intracraneal Idiopática (HICI) es un síndrome neurológico caracterizado por un aumento de la presión intracraneal en ausencia de lesión estructural o hidrocefalia. Los síntomas incluyen cefalea, tinnitus pulsátil, oscurecimientos visuales transitorios y pérdida visual. Dentro de los signos destacan diplopía por parálisis del VI par, edema de papila y disminución de la agudeza visual. Los pacientes no tienen compromiso de conciencia ni signos neurológicos focales. La principal complicación es la pérdida visual que puede ser irreversible. La asociación entre HICI y nitrofurantoína (NTF) se reportó en 1974. Caso clínico: Mujer de 42 años, con sobrepeso, que desarrolló una HICI aproximadamente 18 meses posterior al inicio de nitrofurantoína profiláctica. Consultó por cefalea frontal, opresiva que aumentaba con la maniobra de Valsalva, asociada a disminución fluctuante de la agudeza visual y episodios de oscurecimiento. Al examen destacó edema de papila bilateral, sin déficit neurológico focal. La presión del líquido cefalorraquídeo (LCR) fue de 25,5 cm de agua. La resonancia magnética mostró signos de aumento de la presión del LCR, sin lesiones estructurales ni hidrocefalia. El cuadro se recuperó concomitantemente a la suspensión de la NTF y el uso de topiramato. No se constató daño visual permanente. Conclusiones: Se debe sospechar la HICI en mujeres en edad fértil con sobrepeso. Dentro de los gatillantes del síndrome destacan varios fármacos, entre ellos la NTF. El principal objetivo del tratamiento de la HICI es preservar la función visual.

Abstract Introduction: Idiopathic intracranial hypertension (IIH) is a syndrome characterized by increased intracranial pressure without a space occupying lesion or hydrocephalus. The symptoms are headache, pulsatile tinnitus, transient visual obscurations, and visual loss. Signs are diplopia caused by sixth cranial nerve paresis and papilledema with its associated loss of sensory visual function. The patient maintains an alert and oriented mental state, but has no localizing neurologic findings. The only major morbidity with IIH is visual loss. The association between IIH and nitrofurantoin was reported in 1974. Case: A 42 years old female, overweighed, who developed IIH 18 months after the start of prophylactic nitrofurantoin. She had frontal oppressive headache that increased with the Valsalva maneuver, fluctuant visual loss and transient visual obscurations. She had bilateral papilledema without localizing neurologic findings. The cerebrospinal fluid (CSF) pressure was 25.5 cm H2O. Magnetic resonance imaging showed signs of increased CSF pressure without structural lesions or hydrocephalus. IIH recovered with the withdrawal of nitrofurantoin and the use of topiramate. There was not permanent visual loss. Conclusions: It is recommendable to suspect IIH in obese women in the childbearing years. There are several drugs associated with IIH including nitrofurantoin. The main objective of treatment is to prevent visual loss.

Resistencia a nitrofuranos en Salmonella enterica aisladas de carne para consumo humano / Nitrofuran resistance in Salmonella enterica isolated from meat for human consumption

RESUMEN En el presente estudio, se analizaron los mecanismos de resistencia a nitrofuranos en 18 muestras cár nicas con Salmonella enterica (15 de pollo, 2 de ternera y 1 de cerdo) de mercados de Lima (Perú). Determinaron los serotipos de los aislamientos y la sensibilidad a furazolidona y nitrofurantoina (con y sin el inhibidor de bombas de expulsión Phenyl-Arginine-β-Naphthylamide [PAβN]), las mutaciones en los genes snrA y cnr por PCR y la transferabilidad de la resistencia por conjugación. Se identificaron 15 muestras con S. infantis (13 muestras de pollo), 2 con S. enteritidis y 1 con S. anatum. Todos los aisla mientos, excepto S. anatum, fueron resistentes a ambos nitrofuranos (concentración mínima inhibidora [CMI] a furazolidona: 32-64 µg/mL, CMI a nitrofurantoina: 128-256 µg/mL), sin diferencias al adicio narse PAβN. Todos los aislamientos resistentes a nitrofuranos presentaron sustituciones en snrA y cnr (S. infantis: snrA STOP-151; cnr STOP-137; S. enteritidis: snrA STOP-180; cnr STOP-179). No se detectaron mecanismos transferibles de resistencia a nitrofuranos.

ABSTRACT The mechanisms of resistance to nitrofurans from 18 meat samples with Salmonella enterica (chicken: 15; beef: 2; pork: 1) collected in Lima (Peru) were analyzed. The isolates were serotyped and the susceptibility levels to furazolidone and nitrofurantoin [with and without the efflux pump inhibitor Phenyl-Arginine- β-naphthylamide (PAβN)], the presence of mutations in the snrA and cnr genes and the transferability of resistance by conjugation were established. Fifteen samples with S. infantis (13 from chicken samples), 2 with S. enteritidis and 1 with S. anatum were identified. All isolates except the S. anatum were resistant to both nitrofurans showing MICs (minimum inhibitory concentration) of furazolidone and nitrofurantoin of 32-64 μg/mL and 128-256 μg/mL, respectively. The addition of PAßN had no effect on the MIC levels. All nitrofuran-resistant isolates showed amino acid codon alterations at both snrA and cnr (S. infantis: snrA STOP-151; cnr STOP-137; S. enteritidis: snrA STOP-180; cnr STOP-179). No transferable mecha nisms of nitrofuran resistance were detected.

Multirresistencia de Escherichia coli y Klebsiella pneumoniae provenientes de pacientes con infección del tracto urinario adquirida en la comunidad / Escherichia coli and Klebsiellap neumoniae multiresistance from patients with urinary tract infection acquired in the community

Introducción: El incremento de la multirresistencia bacteriana constituye un problema de salud pública a nivel internacional. Objetivos: Determinar la susceptibilidad antimicrobiana y los patrones de multirresistencia en cepas de Escherichia coli y Klebsiella pneumoniae aisladas de urocultivos. Métodos: Se realizó un estudio descriptivo retrospectivo en el Centro Municipal de Higiene, Epidemiología y Microbiología, municipio Güines, provincia Mayabeque, Cuba, en el periodo comprendido de enero a diciembre de 2017. El estudio incluyó 250 cepas de Escherichia coli y 62 de Klebsiella pneumoniae aisladas e identificadas de muestras de orina de pacientes con infección del tracto urinario adquirida en la comunidad. La susceptibilidad antimicrobiana fue evaluada con el método de difusión en agar empleado la técnica de Kirby Bauer. Resultados: En Escherichia coli se observó niveles de resistencia superiores al 60 por ciento a los antimicrobianos ácido nalidíxico, cefotaxima, trimetoprim - sulfametoxazol y ceftazidima. La nitrofurantoína y la amikacina presentaron 88,8 por ciento y 83,8 por ciento de efectividad, respectivamente. Se apreció en Klebsiella pneumoniae altos valores de resistencia a ceftazidima, trimetoprim - sulfametoxazol y ácido nalidíxico. Amikacina, presentó niveles de sensibilidad de un 71 por ciento. La resistencia a las cefalosporinas de tercera generación se detectó en 78 (31,2 por ciento) de Escherichia coli y 26 (41,9 por ciento) de Klebsiella pneumoniae. De los aislados de Escherichia coli 143 (57,2 por ciento) y Klebsiella pneumoniae 35 (56,4 por ciento) presentaron multidrogoresistencia. Conclusiones: Existe la circulación de cepas resistentes a cefalosporinas de tercera generación y multidrogorresistentes causantes de infecciones de las vías urinarias adquiridas en la comunidad y se informa sobre los antibióticos (nitrofurantoína y amikacina) que podrían ser utilizados para combatirlas de forma empírica en esta área geográfica(AU)

Introduction: The increase of bacterial multiresistance constitutes a public health problem at the international level. Objectives: To determine antimicrobial sensitivity and multiresistance patterns in strains of Escherichia coli and Klebsiellapneumoniae isolated from urine cultures. Methods: A retrospective, descriptive study was conducted at the Municipal Center for Hygiene, Epidemiology and Microbiology, Güines municipality, Mayabeque Province, Cuba, in the period from January to December, 2017. The study included 250 Escherichia coli and 62 Klebsiellapneumoniae strains isolated and identified from urine samples from patients with urinary tract infection acquired in the community. Antimicrobial sensitivity was evaluated with the method of diffusion in agar using Kirby Bauer´s technique. Results: In Escherichia coli, resistance levels higher than the 60% were observed in antimicrobial nalidixic acid, cefotaxime, trimethoprim-sulfamethoxazole and ceftazidime. Nitrofurantoin and amikacin presented 88.8 percent and 83.8 percent of effectiveness, respectively. High values of resistance to ceftazidime, trimethoprim-sulfamethoxazole and nalidixic acid were present in Klebsiellapneumoniae. Amikacin presented sensitivity levels of 71 percent. Resistance to third-generation cephalosporins was detected in 78 (31.2 percent) of Escherichia coli and 26 (41.9 percent) Klebsiellapneumoniae. From the Escherichia coli and Klebsiellapneumoniae isolates, 143 (57.2 percent) and 35 (56.4 percent),respectively, presented multidrug resistance. Conclusions: There is circulation of strains which are resistant to third generation cephalosporins and multidrug resistants that cause urinary tract infections acquired in the community and there are reports on antibiotics (nitrofurantoin and amikacin) that might be used to combat them empirically in this geographical area(AU)

Patrón sensibilidad/resistencia en los urocultivos de pacientes con I.T.U. que consultan a urgencias de adultos, Hospital de San José entre enero de 2014 y diciembre de 2014 / Pattern Sensitivity/Resistance in the Urocultives of Patients with U.T.I. who Consult Adult Urgencies, San Jose Hospital between January 2014 and December 2014

Introducción: La infección del tracto urinario (ITU) es un motivo de consulta frecuente en urgencias, siendo necesario el tratamiento antibiótico empírico antes de obtener un urocultivo. Objetivo Determinar el patrón de sensibilidad/resistencia de los gérmenes aislados en los urocultivos de pacientes que ingresan por urgencias de adultos con sintomatología sugestiva de ITU. Métodos Se realizó un estudio observacional, descriptivo de corte transversal, recolectando los datos de los urocultivos de pacientes con diagnóstico de ITU que asistieron por urgencias adultos, y cumplieron los criterios de inclusión en el año 2014. Resultados Se analizaron 133 pacientes (133 urocultivos), 50,4% mujeres, edad promedio de 64,1 años (DE 19,1). Se encontró una frecuencia mayor de ITU alta (54,9%), e ITU no complicada (54,1%), la mayoría de origen en la comunidad (95,5%). El germen más frecuentemente aislado fue E. coli (56,4%), seguido por Klebsiella oxytoca (7,1%). La resistencia de E. coli fue del 55,7% para ampicilina sulbactam, 58,2% para nitrofurantoina, 40% para quinolonas y 32% para cefazolina. En pacientes con factores de riesgo urológico se encontró una resistencia entre el 40% al 50%. Se evidenció patrón BLEA (12,9%), AMPc (20%) y KPC (1,4%). Conclusión Los uropatógenos han aumentado de forma significativa su resistencia a las diferentes familias de antibióticos, entre ellas las cefalosporinas y las quinolonas, confirmando que medicamentos como ampicilina sulbactam, nitrofurantoina, y ciprofloxacina no están indicados en el manejo empírico de ITU en nuestra institución, especialmente al presentar factores de riesgo urológicos.

Introduction Urinary tract infection (UTI) is a frequent cause for assistance to the emergency services, in most cases is necessary initiate empirical antimicrobial management while obtaining the result of the uroculture. Therefore, it is vital to know the pattern of sensitivity/resistance of the most frequent uropathogens and thus offer the best initial treatment. Objective To determine the pattern of sensitivity / resistance of isolated germs in the urine cultures of adults patients admitted to the emergency room with UTI suggestive symptoms. Methods An observational, descriptive, cross-sectional study was conducted, collecting urine culture data from patients diagnosed with UTI who were attended in adult emergencies in 2014. Results A total of 133 patients were analyzed (133 urine cultures), 50.4% were women, with average age of 64.1 years (SD 19.1). Higher frequency of high urinary tract infection was found (54.9%), and uncomplicated UTI (54.1%), most UTI originated in the community (95.5%). The most frequently isolated germ was E. coli (56.4%), followed by Klebsiella oxytoca (7.1%). The resistance of E. coli was 55.7% for ampicillin sulbactam, 58.2% for nitrofurantoin, 40% for quinolones and 32% for cefazolin. In patients with urological risk factors, resistance was found between 40% and 50%. BLEA pattern (12.9%), cAMP (20%) and KPC (1.4%) were evidenced. Conclusion Uropathogens have significantly increased their resistance to different families of antibiotics, including cephalosporins and quinolones, confirming that drugs such as ampicillin sulbactam, nitrofurantoin, and ciprofloxacin are not indicated in the empirical management of UTI in our institution, especially with the presence of urological risk factors.

Sensibilidad a nitrofurantoína en el uropatógeno intrahospitalario E. Coli procedente de pacientes gerontes hospitalizados / Snsitivity to nitrofurantoin of urocultures from hospitalized gerontes with E. Coli from urinary tract infections

En la presente investigación se determinó la sensibilidad a nitrofurantoína (NTF) mediante un análisis observacional retrospectivo de informes de antibiogramas, por disco de difusión, de urocultivos provenientes de gerontes hospitalizados. En la serie observada (N=90) el desarrollo más frecuente fue E. Coli que presentó una sensibilidad a NTF de 100%. Al considerar la sensibilidad total (es decir de todos las bacterias uropatógenas Gram negativas, (BGN) la resistencia para NTF fue de 26%. Se debate además sus limitaciones médicas y algunos de los potenciales usos de NTF en pacientes hospitalizados

In the present investigation, sensitivity to nitrofurantoin (NTF) was determined through a retrospective observations analysis of reports of antibiograms, by diffusion disc, of urocultures from hospitalized gerontes. In the series observed (N=90), the most frequent development was E. coli, which showed a sensitivity to NTF of 100%. When considering the total sensitivity (ie of all Gram-negative uropathogenic bacteria, BGN) the resistance for NTF was 26%. It also discusses its medical limitations and some of the potential uses of NTF in hospitalized patients

Susceptibilidad in vitro a los antibióticos de bacterias productoras de infecciones urinarias en la mujer: evaluación retrospectiva de 5 años / In vitro susceptibility testing to antimicrobial agents of urinary tract infection bacteria in women: a 5-year retrospective study

INTRODUCCIÓN: Las crecientes tasas de resistencia que muestran los patógenos urinarios representan un grave problema. El objetivo de este estudio ha sido realizar un seguimiento de la etiología de las infecciones urinarias, de adquisición comunitaria, de la resistencia a los antimicrobianos de primera línea y la presencia de Betalactamasas de Espectro Extendido en bacilos gram negativos (BLEE). MATERIAL Y MÉTODOS: El estudio fue realizado entre enero de 2011 y diciembre de 2015 con datos del Laboratorio Microbiología del Hospital de Clínicas de la Universidad Nacional de Asunción. RESULTADOS: Se obtuvieron 1957 uropatógenos en mujeres. Escherichia coli fue el gérmen más frecuentemente aislado (57%), seguido de Klebsiella pneumoniae (11%) y Streptococcus agalactiae, Staphylococcus saprophyticus y Proteus mirabilis (2%). El promedio de resistencia de Escherichia coli fue para trimetoprim-sulfametoxazol 43 %, ciprofloxacina 32%, ampicilina-sulbactam 32%, cefotaxima 13%, piperacilina tazobactam 8%, nitrofurantoína 2% y meropenem no presentaba resistencia alguna en este lapso. El 11% de las cepas de Escherichia coli y el 30 % de Klebsiella pneumoniae produjo betalactamasas de espectro extendido. CONCLUSIONES: Las tasas de resistencia y de resistencias cruzadas que se evidencian en este estudio representan un grave problema que obliga a evaluar permanentemente el tratamiento empírico de las infecciones urinarias en nuestro hospital

INTRODUCTION: The growing resistance rates of urinary pathogens represent a serious problem. The aim of this study was to analyze the etiology of community-acquired urinary tract infections, their first-line antimicrobial resistance and the presence of extended-spectrum beta-lactamases (ESBL) in gram negative bacilli. METHODS: The study was conducted between January 2011 and December 2015 using data from the Microbiology Laboratory at the teaching hospital Hospital de Clínicas, which belongs to the National University of Asunción. RESULTS: A total of 1957 urinary pathogens were found in women. Escherichia coli was the most commonly isolated bacterium (57%), followed by Klebsiella pneumoniae (11%) and Streptococcus agalactiae (2%), Staphylococcus saprophyticus (2%) and Proteus mirabilis (2%). The resistance rates of Escherichia coliwere the following: to trimetoprim-sulfametoxazol, 43%; to ciprofloxacin, 32%; to ampicilin/sulbactam, 32%; to cefotaxime, 13 %; to piperacillin/tazobactam, 8%; nitrofurantoin, 2%, whereas it did not show resistance to meropenem during this period. Extended-spectrum beta-lactamases were produced by 11% of the E. coliisolates and 30% of the Klebsiella pneumoniae isolates. CONCLUSIONS: The resistance and cross-resistance rates found in this study pose a serious problem which compels the continuous assessment of the empirical therapy for urinary tract infections at this hospital

Herbal extracts differentially inhibit oxidative effects caused by the biotransformation of nifurtimox, nitrofurantoin and acetaminophen on rat liver microsomes / Extractos herbales inhiben diferencialmente los efectos oxidativos causados por la biotransformación de nifurtimox, nitrofurantoína y acetaminofeno en microsomas hepáticos de rata]

Inflammation is a cellular defensive mechanism associated to oxidative stress. The administration of nitrofurantoin, nifurtimox and acetaminophen generates oxidative stress by their biotransformation through CYP450 system. The main adverse effect described for the first two drugs is gastrointestinal inflammation and that of the last, hepatitis. Therefore, standardised dry extracts from Rosmarinus officinalis, Buddleja globosa Hope, Cynara scolymus L., Echinacea purpurea and Hedera helix were tested to evaluate their capacity to decrease drug-induced oxidative stress. For that, rat liver microsomes were incubated with drugs in the presence of NADPH (specific CYP450 system cofactor) to test oxidative damage on microsomal lipids, thiols, and GST activity. All drugs tested induced oxidation of microsomal lipids and thiols, and inhibition of GST activity. Herbal extracts prevented these phenomena in different extension. These results show that antioxidant phytodrugs previously evaluated could alleviate drugs adverse effects associated to oxidative stress.

Inflamación es un mecanismo de defensa el cual está asociado a estrés oxidativo. La administración de nitrofurantoína, nifurtimox y paracetamol genera estrés oxidativo al metabolizarse a través del sistema CYP450. El principal efecto adverso de los dos primeros fármacos es inflamación gastrointestinal y del tercero, hepatitis. Por lo tanto, utilizamos diversos extractos herbales para disminuir el estrés oxidativo inducido por estos fármacos. Para esto se incubaron microsomas hepáticos de rata con dichos fármacos en presencia de NADPH (cofactor específico del sistema CYP450) y se evaluó el daño oxidativo generado sobre los lípidos, los tioles y la actividad GST microsómica. Todos los fármacos indujeron oxidación de los lípidos y los tioles microsómicos e inhibieron la actividad GST. Los extractos herbales previnieron estos fenómenos oxidativos en diferente extensión. Estos resultados indican que fitofármacos antioxidantes previamente evaluados, podrían aliviar los efectos adversos asociados a estrés oxidativo de los fármacos.

In Vitro and in Vivo Effects of Nitrofurantoin on Experimental Toxoplasmosis

Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti-T. gondii candidate for clinical application.

The efficacy of immediate versus delayed antibiotic administration on bacterial growth and biofilm production of selected strains of uropathogenic Escherichia coli and Pseudomonas aeruginosa

Purpose The treatment of urinary tract infections (UTI) with antibiotics is commonly used, but recurrence and antibiotic resistance have been growing and concerning clinicians. We studied whether the rapid onset of a protective biofilm may be responsible for the lack of effectiveness of antibiotics against selected bacteria. Materials and Methods Two established uropathogenic Escherichia coli strains, UTI89 and CFT073, and two Pseudomonas aeruginosa strains, PA01 and Boston-41501, were studied to establish a reliable biofilm formation process. Bacterial growth (BG) was determined by optical density at 600 nm (OD 600) using a spectrophotometer, while biofilm formation (BF) using crystal violet staining was measured at OD 550. Next, these bacterial strains were treated with clinically relevant antibiotics, ciprofloxacin HCl (200 ng/mL and 2 μg/mL), nitrofurantoin (20 μg/mL and 40 μg/mL) and ampicillin (50 μg/mL) at time points of 0 (T0) or after 6 hours of culture (T6). All measurements, including controls (bacteria -1% DMSO), were done in triplicates and repeated three times for consistency. Results The tested antibiotics effectively inhibited both BG and BF when administered at T0 for UPEC strains, but not when the antibiotic administration started 6 hours later. For Pseudomonas strains, only Ciprofloxacin was able to significantly inhibit bacterial growth at T0 but only at the higher concentration of 2 μg/mL for T6. Conclusion When established UPEC and Pseudomonas bacteria were allowed to culture for 6 hours before initialization of treatment, the therapeutic effect of selected antibiotics was greatly suppressed when compared to immediate treatment, probably as a result of the protective nature of the biofilm. .

Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Susceptibility of Escherichia coli from Community-Acquired Urinary Tract Infection to Fosfomycin, Nitrofurantoin, and Temocillin in Korea

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Antimicrobial Resistance Pattern in Enterococcus faecalis Strains Isolated From Expressed Prostatic Secretions of Patients With Chronic Bacterial Prostatitis

PURPOSE: Enterococcus faecalis is one of the most common pathogens linked to chronic bacterial prostatitis (CBP). Owing to a limited number of previous studies addressing this topic, we aimed to determine the drug resistance patterns of E. faecalis strains isolated from CBP patients. MATERIALS AND METHODS: One thousand twenty-one patients visited a single hospital owing to chronic prostatitis for 5 years. Culture specimens were obtained by use of a modified Meares-Stamey method. The minimal inhibitory concentrations of the antimicrobials were assessed by use of the Vitek II microbial identification system as suggested by the Clinical and Laboratory Standards Institute. RESULTS: Forty-one samples from 41 patients who had significant E. faecalis loads for defining CBP were included in this study. The E. faecalis strains in our study were resistant to penicillin (9.7%), ampicillin (0%), ampicillin/sulbactam (0%), nitrofurantoin (0%), imipenem (0%), vancomycin (0%), teicoplanin (0%), quinupristin/dalfopristin (100%), ciprofloxacin (9.7%), levofloxacin (4.8%), norfloxacin (26.8%), erythromycin (95%), gentamicin (46.3%), tetracycline (97.5%), and trimethoprim/sulfamethoxazole (31.5%), respectively. CONCLUSIONS: Fluoroquinolones have been the preferred antibiotics for treating CBP. Because of their low rate of drug resistance, fluoroquinolones are suitable therapeutic agents for E. faecalis strains causing CBP in Korea. Even though tetracycline, erythromycin, and trimethoprim/sulfamethoxazole have been prescribed as an empirical antimicrobial therapy for chronic prostatitis, we cannot recommend these drugs for treatment of E. faecalis isolates because of the high rates of drug resistance.

Fusão renal completa em criança com infecção recorrente do trato urinário / Complete renal fusion in a child with recurrent urinary tract infection

O rim em bolo é uma rara anormalidade do trato urinário que pode ser diagnosticada em qualquer faixa etária. Durante investigação de infecção urinária recorrente em criança de 12 anos, foi revelada em tomografia computadorizada contrastada a presença de rim direito ectópico, com fusão renal, drenado por dois ureteres. Foi iniciado tratamento profilático com nitrofurantoína e o paciente se encontra assintomático.

Cake kidney, a rare anomaly of the urinary tract, may be diagnosed at any age range. During the investigation of recurrent urinary tract infection in a 12-year-old child, contrast-enhanced computed tomography demonstrated the presence of a right-sided ectopic kidney, with renal fusion, drained by two ureters. Prophylactic treatment with nitrofurantoin was instituted, and the patient currently remains asymptomatic.

Increasing antibiotic resistance among uropathogens isolated during years 2006-2009: impact on the empirical management

Urinary tract infections (UTI) are one of the most common infections with an increasing resistance to antimicrobial agents. PURPOSE: Empirical initial antibiotic treatment of UTI must rely on susceptible data from local studies. MATERIALS AND METHODS: Retrospective analysis of isolated bacteria from children with UTIs was performed at the university hospital during years 2006-2009. The findings were compared with data collected in a similar study carried out in 2002- 2003. RESULTS: A total of 1439 uropathogens were isolated. Escherichia coli (E.coli) was the leading cause, followed by Enterobacter, and other gram negative bacilli. It was observed resistance of E.coli to ceftriaxone, cefexime, amikacin, gentamycin, and nalidixic acid; Enterobacter to cefexime; and the resistance of gram negative bacilli to gentamicin and cefexime increased significantly. The highest effective antibiotic was Imipenem, ciprofloxacin, and amikacin with 96.7%, 95% and 91% sensitivity rates , respectively, followed by ceftriaxone 77.2%, gentamicin 77%, nitrofurantoin 76.4%, nalidixic acid 74.3% and cefexime with 70%. CONCLUSION: The use of nitrofurantoin or nalidixic acid as initial empirical antibacterial therapy for cystitis seems appropriate. For cases of simple febrile UTI, the use of initial parenteral therapies with amikacin or ceftriaxone followed by an oral third generation cephalosporin also seemed appropriated, and in cases of severely ill patients or complicated UTI, imipenem as monotherapy or, a combination of Ceftriaxone with an aminoglycoside, are recommended.

Espectro clínico de la hepatotoxicidad por nitrofurantoína en serie clínica de 12 pacientes / Clinical spectrum of nitrofurantoin hepatotoxicity in a series of 12 patients

Nitrofurantoin, commonly used for prolonged periods, can produce different patterns of liver damage. Patients: 12 women, mean age 55 years (range 17-72), with recurrent urinary infections, treated with nitrofurantoin for long periods of time (2 months to 15 years), who presented with secondary liver disease. Results: 7 had acute hepatitis (3 fulminant), 3 chronic hepatitis, and 2 cirrhosis. All acute cases had consistent liver biopsies, and 2 were treated with steroids and azathioprine for 2 and 7 months, with liver tests normalization. Two fulminant cases were transplanted (submassive hepatic necrosis on explanted livers) and 1 was successfully treated with steroids and mycofenolate. The 3 cases of chronic hepatitis also had confirmatory biopsies and 1 received steroids and azathioprine, with full recovery. The other 2 responded to the drug withdrawal and the 2 cirrhotic patients had only symptomatic treatment. All patients were negative for hepatitis virus, 7 (58 percent had positive anti-nuclear and/or anti-smooth muscle antibodies and 4 (33 percent) had elevated IgG levels. Conclusions: Nitrofurantoin may cause severe acute liver disease, even requiring liver transplantation. Nitrofurantoin can also cause chronic liver disease, have markers of autoimmunity and respond to immunosuppressive therapy. These data confirmed that nitrofurantoin can induce liver diseases, probably due to immunological mechanisms.

La nitrofurantoína, comúnmente utilizada por períodos prolongados, puede producir daño hepático, con diferentes formas de presentación y evolución. Pacientes: 12 mujeres, edad promedio 55 años (rango 17 a 72), con infecciones urinarias recurrentes, usuarias de nitrofurantoína por períodos prolongados (2 meses a 15 años), que presentaron daño hepático asociado a la droga. Resultados: 7 casos de hepatitis aguda (3 fulminantes), 3 casos de hepatitis crónica y 2 casos de cirrosis. Todos los casos de hepatitis agudas tenían biopsia hepática compatible y 2 fueron tratadas con corticoides y azatioprina por 2 y 7 meses, con normalización de los exámenes. De las 3 pacientes con hepatitis fulminante, 2 fueron trasplantadas (necrosis submasiva en el hígado explantado) y 1 fue tratada con corticoides y micofenolato, con buena respuesta. Los 3 casos de hepatitis crónica tenían confirmación histológica y 1 se trató con corticoides y azatioprina, con excelente evolución. Las otras pacientes respondieron favorablemente sólo a la suspensión del fármaco. Los 2 casos con cirrosis han recibido tratamiento sintomático. Todas las pacientes fueron negativas para los virus hepatitis, 7/12 (58 por ciento) tenían anticuerpos antinucleares y/o antimúsculo liso positivos y 4/12 (33 por ciento) IgG elevada. Conclusión: La nitrofurantoína puede provocar una severa enfermedad hepática aguda, requiriendo incluso trasplante hepático. Además, puede producir hepatitis crónica y cirrosis, tener marcadores de autoinmunidad y buena respuesta a la terapia inmunosupresora habitual. Lo anterior confirma su capacidad de inducir un daño hepático, probablemente por mecanismos inmunológicos.

Monitoring of antibiotic resistance in bacteria isolated from laboratory animals / 한국실험동물학회지

The drug resistance of microorganisms isolated from laboratory animals never treated with antibiotics is being reported consistently, while the number of laboratory animals used in medicine, pharmacy, veterinary medicine, agriculture, nutrition, and environmental and health science has increased rapidly in Korea. Therefore, this study examined the development of antimicrobial resistance in bacteria isolated from laboratory animals bred in Korea. A total of 443 isolates (7 species) containing 5 Sphingomonas paucimobilis, 206 Escherichia coli, 60 Staphylococcus aureus, 15 Staphylococcus epidermidis, 77 Enterococcus faecalis, 27 Citrobacter freundii, 35 Acinetobacter baumannii were collected from the nose, intestine, bronchus and reproductive organs of ICR mice and SD rats. Of these species, Acinetobacter baumannii and Enterococcus faecalis showed significant antimicrobial resistance according to the minimum inhibition concentration (MIC) in E-test. In case of Acinetobacter baumannii, several isolates showed MIC values 16-128 microg/mL for cefazolin and cefoxitin, and higher resistance (128-512 microg/mL) to nitrofurantoin than that of standard type. Resistance to cefazolin, cefoxitin and nitrofurantoin was detected in 17.14, 20.00, and 8.57% of the Acinetobacter baumannii isolates, respectively. In addition, 44.1% of the Enterococcus faecalis isolates collected from the laboratory animals were resistant to oxacillin concentration of 16-32 microg/mL range, while MIC value of standard type was below oxacillin concentration of 6 microg/mL. These results suggest that in rodent species of laboratory animals, Acinetobacter baumannii are resistance to cefazolin, cefoxitin and nitrofurantoin, whereas those of Enterococcus faecalis were resistance to oxacillin.

Mitigación de efectos adversos de nitrofurantoína administrada por vía oral utilizando un extracto seco estandarizado de Buddleja globosa Hope (matico) / Mitigation of adverse effects of nitrofurantoin administered orally using a standardized dry extract of Buddleja globosa Hope (matico)

La nitrofurantoína es un antibiótico derivado del nitrofurano utilizado como fármaco de primera elección para el tratamiento de infecciones del tracto urinario. Sin embargo, este fármaco produce serios efectos adversos principalmente de origen gastrointestinal. Se postula que las reacciones adversas se deberían al estrés oxidativo provocado por la nitroreducción de la nitrofurantoína que genera especies reactivas del oxígeno. Por lo tanto, BG126®, preparado herbal a base de hojas de Buddleja globosa Hope, podría mitigar los efectos adversos de nitrofurantoína; este fitofármaco se ha caracterizado por su alta actividad antioxidante (datos aún no publicados). Los resultados de este estudio clínico doble ciego y randomizado, mostraron que el tratamiento asociado de nitrofurantoína (200mg/día) y BG126® (2 cápsulas/día), efectivamente disminuyó los efectos adversos gastrointestinales de pacientes mujeres con infección bacteriana del tracto urinario (ITU). Entre estas reacciones adversas se cuantificó nausea, dolor abdominal y diarrea. Más aún, este tratamiento conjunto potenció la actividad antibacteriana de la nitrofurantoína; al final del tratamiento, todos los pacientes que recibieron nitrofurantoína y BG126® presentaron urocultivos negativos, mientras que el 19% de los pacientes que recibieron sólo nitrofurantoína mostraron urocultivos positivos, lo cual indica la presencia de cepas bacterianas resistentes a nitrofurantoína. Cabe destacar que a capacidad antioxidante plasmática de ambos grupos de pacientes no fue significativamente diferente. Así, no se observaron diferencias significativas en la capacidad reductora de hierro, ni en los niveles de MDA de ambos grupos de pacientes, el que recibió sólo nitrofurantoína y aquel que recibió en forma conjunta nitrofurantoína y BG126®. Estos resultados parecen indicar que la absorción de BG126® es baja y por tanto, el efecto observado es mayoritario a nivel de la pared gastrointestinal. El aumento de la resistencia a antibióticos de las diferentes cepas bacterianas que infectan al hombre, es un problema de salud pública a nivel mundial. Si sumamos a lo anterior, las reacciones adversas de los fármacos antibacterianos, como son los derivados de nitrofuranos, las estrategias terapéuticas contra las diversas infecciones bacterianas se ven muy limitadas. Interesantemente, BG126® no sólo disminuyó la severidad de las reacciones adversas provocadas por la nitrofurantoína, sino que al parecer potenció su efecto antibacteriano. Nuevos experimentos están en proceso con el objeto de dilucidar los mecanismos que permitan explicar el comportamiento antibacteriano de nitrofurantoína comparada con la mezcla nitrofurantoína-BG126®

Asymptomatic bacteriuria in antenatal patients in Ilorin, Nigeria

To determine the prevalence of asymptomatic bacteriuria, bacteriology and sensitivity pattern in Ilorin using the gold standard of urine culture. A prospective study was carried out from 1st July to 31st October 2007, at the University of Ilorin Teaching Hospital [UITH] on 125 consenting asymptomatic pregnant women, A structured proforma was used to collect information from the women and a midstream urine specimen collected for bacteriological culture, Of the 125 pregnant women, 50 had bacteriuria on urine culture giving a prevalence of 40%. The mean age of the women was 28.5 years with a standard deviation of 4.95. The age ranged between 14 and 40 years. Staphylococcus aureus was the commonest pathogen isolated [72%], followed by Proteus spp [14%]. Most of the organisms showed good sensitivity to Nitrofurantoin and gentamicin. The prevalence of asymptomatic bacteriuria in Ilorin is high and routine urine culture is advocated for all pregnant women at booking

Infecciones urinarias adquiridas en la comunidad: epidemiología a los antimicrobianos y opciones terapéuticas / Urinary infections acquired in community: epidemiology resistance to antibiotics and therapeutic options

Las infecciones del tracto urinario (ITU) constituyen uno de los principales motivos de consulta en el ámbito de atención primaria. En los últimos años se han producido cambios sustanciales en los patrones de sensibilidad de los principales patógenos urinarios, lo que ha condicionado cambios en el tratamiento empírico de éstas. El objetivo de este trabajo fue caracterizar las ITU en pacientes de la comunidad. La muestra estuvo conformada por 71 pacientes de ambos sexos mayores de 18 años. El género más afectado fue el femenino (80,28%). Los signos y síntomas más frecuentes fueron dolor lumbar, disuria y dolor abdominal. La presencia de cálculos renales fue el más importante factor predisponente (39,43%), seguido de la menopausia (23,94%). El 63,38% de los pacientes presentaron ITU previas. Escherichia coli fue el agente causal más frecuente (63,89%), seguido de Proteus mirabilis (6,94%). Las enterobacterias aisladas presentaron elevados niveles de resistencia a ampicilina, cefalotina y norfloxacina. El 51,52% de las enterobacterias presentaron resistencia a las fluoroquinolonas y en el 16,67% se demostró la producción de ß-lactamasas de espectro expandido (BLEE). La mayoría de los agentes causales fueron sensibles a la nitrofurantoína independientemente de la presencia de mecanismos de resistencia que afectan a otros grupos de antimicrobianos

Urinary tract infections (UTI) are one of the main reasons for consultation in primary care. In recent years, there have been substantial changes in susceptibility patterns for major urinary tract pathogens, which have conditioned changes in their empirical treatment. The aim of this study was to characterize UTI in patients from the community. The sample consisted of 71 patients of both sexes over 18 years of age. The most affected sex was the female (80.28%). The signs and symptoms were lumbar pain, dysuria and abdominal pain. The presence of kidney stones was the most important predisposing factor (39.43%), followed by menopause (23.94%); 63.38% of the patients had a previous UTI. Escherichia coli was the most common agent (63.89%), followed by Proteus mirabilis (6.94%). Isolates showed high levels of resistance to ampicillin, cephalothin and norfloxacin. 51.52% of the Enterobacteriaceae were resistant to fluoroquinolones and 16.67% showed production of extended spectrum ß-lactamases (ESBL). Most of the agents were susceptible to nitrofurantoin, regardless of the presence of resistance mechanisms affecting other antibiotic groups