Fosfomycin and nitrofurantoin: classic antibiotics and perspectives.

Antibiotics are essential molecules for the treatment and prophylaxis of many infectious diseases. However, drugs that combat microbial infections can become a human health threat due to their high and often indiscriminate consumption, considered one of the factors of antimicrobial resistance (AMR) emergence. The AMR crisis, the decrease in new drug development by the pharmaceutical industry, and reduced economic incentives for research have all reduced the options for treating infections, and new strategies are necessary, including the return of some traditional but "forgotten" antibiotics. However, prescriptions for these older drugs including nitrofurantoin and oral fosfomycin, have been based on the results of pioneer studies, and the limited knowledge generated 50-70 years ago may not be enough. To avoid harming patients and further increasing multidrug resistance, systematic evaluation is required, mainly for the drugs prescribed for community-acquired infections, such as urinary tract infections (UTI). Therefore, this review has the objective of reporting the use of two classic drugs from the nitrofuran and phosphonic acid classes for UTI control nowadays. Furthermore, we also explore new approaches used for these antibiotics, including new combination regimes for spectral amplification, and the prospects for reducing bacterial resistance in the fight against bacteria responsible for UTI.

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.

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. .

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA).

It is important to determine the toxicity of compounds and co-solvents that are used in cell monolayer permeability studies to increase confidence in the results obtained from these in vitro experiments. This study was designed to evaluate the cytotoxicity of new nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA) in Caco-2 cells to select analogues for further in vitro permeability analyses. In this study, nitrofurantoin and nifuroxazide, in addition to 6 furanic and 6 thiophenic nifuroxazide derivatives were tested at 2, 4, 6, 8 and 10 µg/mL. In vitro cytotoxicity assays were performed according to the MTT (methyl tetrazolium) assay protocol described in ISO 10993-5. The viability of treated Caco-2 cells was greater than 83% for all tested nitrofurantoin concentrations, while those treated with nifuroxazide at 2, 4 and 6 µg/mL had viabilities greater than 70%. Treatment with the nifuroxazide analogues resulted in viability values greater than 70% at 2 and 4 µg/mL with the exception of the thiophenic methyl-substituted derivative, which resulted in cell viabilities below 70% at all tested concentrations. Caco-2 cells demonstrated reasonable viability for all nifuroxazide derivatives, except the thiophenic methyl-substituted compound. The former were selected for further permeability studies using Caco-2 cells.

Nitrofurantoin-induced lung- and hepatotoxicity.

We present the case of a patient referred to the gastroenterology service for investigation of abnormal liver function tests. She had been taking nitrofurantoin for 16 months as prophylaxis against urinary tract infections. CT scan showed evidence of lung pneumonitis and low attenuation in the liver parenchyma. Nitrofurantoin-induced pneumonitis and hepatotoxicity was diagnosed. The patient responded both clinically and biochemically to withdrawal of nitrofurantoin. This combination of adverse reaction to nitrofurantoin is rare.

Eficacia de nitrofurantoina y amoxicilina en el tratamiento de bacteriuria asitomática en mujeres embarazadas en la sala de alto riesgo obstétrico en el Hospital Escuela Oscar Danilo Rosales Arguello en el período comprendido de julio a diciembre 2005 / Nitrofurantoina effectiveness and amoxicilina in the treatment of bacteriuria asitomática in women embarrassed in the room of high obstetric risk in the Hospital School Oscar Danilo Rosales Arguello in the understood period of July to December 2005

En la relación del presente estudio se incluyeron a 98 pacientes que cumplan con los criterios de inclusión, de cuyos resultados se pude inferir que: en relación a la edad gestacional el 63.3 porciento de las pacientes cursaban tercer trimestre de embarazo, seguido de 17.3 porciento que cursaba su segundo trimestre y solamente 16.6 porciento se encontraba en la etapa inicial de su gestación. Respecto a las alteraciones del examen de orina se observó que 80.7 porciento presento bacteriuría y solamente 12.2 porciento se evidencio la presencia de leucocitos y en 7.1 porciento de nitritos. Correlacionando examen general de orina y urocultivo se encontró que de las 98 pacientes en las que se encontró alteración del EGO 37 tuvieron cultivo negativo lo que representa 37.8 porciento y un 62.2 porciento correspondiente a 61 pacientes se evidencio la presencia de germen patógeno. De las 61 pacientes con crecimiento en el urocultivo se encontró la presencia de E coli en 29 pacientes para 47.5 porciento, seguido de enterobacter con 19.9 porciento en 12 pacientes y el tercer lugar correspondio a Klesiella con 16.3 porciento en 10 pacientes. Respecto a la sensibilidad bacteriana para E coli el germen más frecuente fue de 89.6 porciento para Nitrofurantoina en comparación con 82.7 porciento para amoxicilina, no siendo a´si con enterobacter cuya sensibilidad para amoxicilina fue de 100 porciento en contra de 75 porciento para Nitrofurantoina, en relación a Klebsiella predomino su sensibilidad a Nitrofurantoina con 80 porciento. En relación a la eficacia de ambos fármacos estudiados se encontró que de las 34 pacientes que recibieron esquema de Nitrofuranotina 30 presentaron curación para 88.2 porciento y solamente en 4 pacientes persistió el germen para 11.8 porciento. Las que recibieron esquema 2 con amoxicilina fueron 27 pacientes se observó su curación en 16 pacientes para 59.2 porciento y fracaso en 11 con 40.8 porciento...

Estudio comparativo prospectivo aleatorio de antibióticos en resección transuretral de próstata / Comparative prospective randomized study of antibiotics in transurethral resection of the prostate

Comparar las complicaciones infecciosas con el uso de 2 esquemas antibióticos en resección transuretral de próstata (RTU-P) de pacientes con bajo riesgo, de modo de reducir el uso de antibióticos en este tipo de pacientes. Secundariamente, intentar ponderar la influencia de los antecedentes clínicos, hallazgos y complicaciones intraoperatorias y evolución postoperatoria en el desarrollo de dichas complicaciones. Se diseñó un estudio comparativo, prospectivo, aleatorio, abierto de 95 pacientes con orina estéril, no usuarios de sonda uretrovesical, sometidos a RTU-P en el plazo de 1 año. El grupo 1 recibió una modificación del esquema antibiótico mayormente utilizado hasta la fecha, consistente en cefazolina 1 gr IV preoperatorio y cada 8 h durante el primer día (3 dosis), seguido de ciprofloxacino 250 mg VO, cada 12 h, hasta el retiro de la sonda uretrovesical (dosis terapéutica). El grupo 2 recibió cefazolina 1 g IV preoperatorio y a las 8 h postoperatorias (2 dosis), seguido de nitrofurantoína, 100 mg VO en la noche, hasta el retiro de la sonda uretrovesical (dosis profiláctica). Se excluyeron 5 pacientes del análisis después de la distribución aleatoria (5,3'porciento) y no hubo pérdidas en el seguimiento. Se analizan 90 pacientes, 45 en cada grupo, los cuales fueron comparables en sus características clínicas, parámetros quirúrgicos, parámetros postoperatorios y complicaciones. Se presentó fiebre (temperatura axilar igual o mayor a 37,5 °C) en el 2 porciento del grupo 1 y en el 11 porciento del grupo 2 (p=0,091). Se presentó bacteriuria postoperatoria (recuento > 100.000 UFC por mL) precoz o tardía en el 2 porciento del grupo 1 y en el 13 porciento del grupo 2 (p=0,049). Esto, posiblemente, se debió al espectro de acción y dosis de los antimicrobianos utilizados. La fiebre estuvo relacionada estadísticamente con la infección urinaria postoperatoria.

Electrovaporización prostática transuretral, una alternativa en el tratamiento de la hiperplasia prostática benigna. Experiencia en el hospital Central Militar / Quantitative determination of tissue androgenic receptors as a prognostic factor in patients who have prostatic carcinoma

La hiperplasia prostática benigna es la etiología más común de síntomas obstructivos urinarios bajos en hombres de 40 años de edad. Se han postulado alternativa de tratamiento como la resección transuretral de próstata. Se estudiaron 20 pacientes de marzo de 1996 a mayo de 1997 sometidos a electrovaporización prostática transuretral, teniendo como resultado mejoría de los síntomas obstructivos y disminución en el volumen de la glándula prostática; demostrando que este procedimiento es una alternativa para el tratamiento de la hiperplasia prostática benigna

[Acute cystourethritis during pregnancy]. / Cistouretritis aguda durante la gestación.

A prospective study was carried out in 103/863 obstetric patients with cystitis characterized by urinary urgency and frequency, dysuria, pyuria and suprapubic discomfort in the absence of systemic symptoms such as fever and costovertebral angle tenderness. The association of symptomatic lower urinary tract infection with low-count bacteriuria (10(2)-10(5) UFC/mL of urine) was present in all the patients. The incidence of cystourethritis was about 12%, most of the infections occurred at the first trimester. To learn whether a multiple-dose of nitrofurantoin or ampicillin is safe and effective therapy for acute uncomplicated urinary tract infections, 103 symptomatic pregnant women were randomly grouped to receive oral nitrofurantoin (100 mg t.i.d.) or ampicillin (500 mg t.i.d.) for five days. Seventeen patient were excluded since they did not return for follow-up. Escherichia coli was isolated in 67% of infections. Overall cure varied from 87% to 89%, without any great differences between the regimens. Nine patients had asymptomatic bacteriuria in the course of pregnancy, four developed acute pyelonephritis and one of them had abnormal intravenous pyelogram.

Estudio comparativo del sulfamoxol trimetoprin y la hidroximetil nitrofurantoina en infeccion urinaria

Se realizo un estudio doble ciego en 60 pacientes utilizando el sulfamoxol trimetoprim y la hidroximetil-nitrofurantoina en el tratamiento de la infeccion urinaria. Habiendose encontrado una buena respuesta terapeutica con ambas drogas aunque algo mayor en el grupo que recibio sulfamoxol trimetoprin; asi mismo en este grupo no se informaron efectos colaterales que se hicieron evidentes con la nitrofurantoina. El germen mas frecuente fue la Ecoli en ambos grupos. Los parametros de eficacia laboratorial se hicieron evidentes al cabo del tercer dia de iniciado el tratamiento.

Three-day therapy of lower urinary tract infections with nitrofurantoin macrocrystals: a randomized clinical trial.

Forty-nine girls between the ages of 2 and 18 years with a symptomatic urinary tract infection documented by two clean-catch urine cultures completed a double-blind study comparing the effectiveness of three days versus ten days of nitrofurantoin macrocrystal therapy. Localization of the infection to the lower urinary tract was presumed on the basis of clinical presentation. All patients had sterile urine on day two or three of therapy. In the ten-day group, two of 23 patients (8.7%) experienced a single relapse, and seven patients (30%) had 12 episodes of reinfection during a six-month follow-up. In the three-day group, two of 26 patients (7.7%) had a single relapse, and six patients (23%) had 12 episodes of reinfection. The rates of relapse and reinfection in the compared groups were not statistically significantly different (P greater than 0.05). Three days of treatment with nitrofurantoin macrocrystals is an effective regimen for symptomatic girls presumed to have uncomplicated lower urinary tract infections.