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BACKGROUND: Prostate cancer is the most common malignant solid tumour in men aged >70 years and is the second most common cause of death from oncological circumstances. AIM: To evaluate the effect of different short-term prophylactic antibiotic regimens in transrectal prostate biopsy (PB) on the incidence of infectious complications. METHODS: Patients who underwent transrectal ultrasound-guided PB between January 2021 and December 2022 were included in the prospective randomized study. According to the regimen of prophylaxis, patients were randomized into three groups: (1) fosfomycin trometamol 3 g, 3 h before the procedure + ciprofloxacin 500 mg, 2 h before the procedure; (2) fosfomycin trometamol 3 g, 3 h before and 24 h after the procedure; (3) ciprofloxacin 500 mg 12, 2 h before the procedure, and 12 h after the procedure. A rectal swab was performed 1-2 weeks before PB to evaluate the culture findings. Complications were evaluated during follow-up visits within one month after PB. FINDINGS: In the monitored period, 605 PBs were performed, and 544 patients met the inclusion criteria (184, 161, and 199 in groups 1, 2, and 3). Infectious complications occurred in 10 cases (1.83%), namely 3, 4, and 3 according to patient groups. There was no statistically significant difference between the individual groups. None of the patients required hospitalization and all were free of symptoms of sepsis. CONCLUSION: Short-term antibiotic prophylaxis in PB using fosfomycin trometamol, ciprofloxacin, or their combination appears to be effective. Fosfomycin trometamol is a suitable alternative to fluoroquinolone antibiotics.
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Fosfomicina , Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/patología , Profilaxis Antibiótica/métodos , Fosfomicina/uso terapéutico , Estudios Prospectivos , Trometamina , Recto , Biopsia/efectos adversos , Biopsia/métodos , Ciprofloxacina/uso terapéutico , Antibacterianos/uso terapéuticoRESUMEN
Objective To investigate the clinical efficacy and safety of long-term intermittent oral ad-ministration of fosfomycin trometamol(FMT)in the control of urinary tract infection and the reduction of stone recurrence rate after removal of upper urinary infection stones.Methods A total of 171 patients who met the inclusion criteria were enrolled and divided into the FMT group(using FMT),cephalosporin group(using cefixime),and blank group(not using antibiotics)according to the random number method,with 57 cases in each group.Finally,55 cases in the FMT group,47 cases in the cephalosporin group and 48 cases in the blank group were included in the statistical analysis,and the urinary tract infection and stone recurrence of the three groups were followed up regularly after the stone removal operation.Results There was no statisti-cal significance in the baseline data of the three groups(P>0.05).There were significant differences in the recurrence rate of urinary tract infection at the 3rd and 6th month among the 3 groups(P=0.010,P<0.001).Further pair-wise comparison showed that the recurrence rate of urinary tract infection at the 3rd month in the FMT group was lower than that in the blank group(P<0.05),but there was no statistical difference compared with the cephalosporin group(P>0.05).The recurrence rate of urinary tract infection at the 6th month in the FMT group was lower than that in the cephalosporin group and blank group(P<0.05).The recurrence rate of stones in the 1st and 3rd year of the three groups were statistically different(P= 0.028,0.015).Further pair-wise comparison showed that the 1st year stone recurrence rate of the FMT group was lower than that of the cephalosporin group and blank group(P<0.05).The 3rd year stone recurrence rate of the FMT group was lower than that of the blank group(P<0.05),but there was no statistical difference compared with the cephalosporin group(P>0.05).There was no significant difference in the total incidence of adverse drug re-action between the FMT group and cephalosporin group(P=0.131).Conclusion FMT is superior to cephalospo-rin in the control of urinary tract infection after lithotripsy for upper urinary tract infection.
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The worldwide prevalence of uncomplicated lower urinary tract infections (uUTIs) caused by multidrug-resistant Escherichia coli is increasing. To address this emergency, international guidelines recommend reducing administration of fluoroquinolones, in the context of growing resistance and the long-lasting and potentially disabling side effects of these drugs. The favoured drug to replace fluoroquinolones is fosfomycin trometamol (FT), a well-known derivate of phosphonic acid with broad-spectrum activity against Gram-negative and Gram-positive bacteria, including multidrug-resistant (MDR) strains. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recently reduced the susceptibility breakpoint for E. coli from 32 mg/L to 8 mg/L regarding FT used for uUTIs. This might lead to increased appropriate use of oral fosfomycin target therapy against E. coli and other microorganisms, and may be associated with a high likelihood of success. For species such as Klebsiella spp, particularly MDR strains, the absence of clinical breakpoints might lead to reduced use of oral fosfomycin, particularly if minimum inhibitory concentration is not available. To address this issue, this review presents an overview of the preclinical evidence on the activity of FT, and a systematic review of the clinical activity of FT in uUTIs in women, and in the prevention of infectious complications after prostate biopsy. The findings indicate that the safety and microbiological and clinical effectiveness of a single oral dose of FT are similar to that for comparator regimens with longer treatment schedules in women with uUTI, and FT can be considered a viable alternative to fluoroquinolones for antimicrobial prophylaxis in prostate biopsy. These observations and a broad clinical experience support the empirical use of FT for treating uUTI and indicate that FT is a promising candidate to effectively counteract antibiotic-resistant uUTIs throughout Europe.
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Antiinfecciosos , Fosfomicina , Infecciones Urinarias , Masculino , Femenino , Humanos , Fosfomicina/farmacología , Fosfomicina/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Trometamina/farmacología , Trometamina/uso terapéutico , Escherichia coli , Testimonio de Experto , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Antiinfecciosos/farmacología , Fluoroquinolonas/uso terapéuticoRESUMEN
The present Phase I study investigated, for the first time, fosfomycin pharmacokinetics in humans after two 3 g doses of fosfomycin trometamol administered 27 h apart, according to the dose regimen recommended for the prophylactic indication for transrectal prostate biopsy in adult men. Plasma, urine and seminal plasma concentrations were measured after one and two consecutive doses in 24 healthy men, representative of the target population of the prophylactic indication. Prostate and seminal vesicle concentrations were estimated based on seminal plasma concentrations using a one-step regression method. The exposure to fosfomycin was very similar in rate (Cmax, tmax) after one and two doses. The AUC showed a minimal increment. On average, the apparent volume of distribution was high (>100 L), and the mean clearance had an intermediate value. The total amount and dose fraction of fosfomycin excreted in urine showed a small increment after two doses. The renal clearance was about 5 L/h. The fosfomycin concentration in the prostate and seminal vesicles showed that the antibiotic increased on average after two consecutive doses. This result confirmed the ability of fosfomycin to distribute into the prostate and into seminal vesicles after one single dose and that a two consecutive dose regimen increases the antibiotic availability inside these peripheral tissues.
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Fosfomycin (FOF) is the first antimicrobial of the epoxide class. It is commercially available in oral and parenteral formulations. Oral FOF is widely used to treat uncomplicated cystitis in women, while parenteral FOF is extensively utilized for upper urinary tract infections. FOF has a broad-spectrum bactericidal activity with a low risk of cross-resistance to other antimicrobial classes. Therefore, parenteral FOF is increasingly prescribed adjunctive therapy to treat extra-urinary tract infections caused by multidrug-resistant, Gram-negative bacteria.
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Fosfomicina , Infecciones Urinarias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias , Farmacorresistencia Bacteriana Múltiple , Femenino , Fosfomicina/farmacología , Fosfomicina/uso terapéutico , Humanos , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
Urinary tract infections (UTIs) are prevalent worldwide, particularly among women. Their incidence increases with age, and treatment is increasingly challenging owing to antibiotic resistance and the lack of new agents. We investigated the susceptibility of current urinary isolates to fosfomycin and other antibiotics across Europe. This cross-sectional study collected consecutive urinary isolates from non-hospitalised women at 20 centres in Belgium, the UK, Italy, Spain and Russia. Bacteria were tested by disk diffusion with relevant antibiotics. As a quality control, a central laboratory re-tested, by agar dilution, (i) isolates found resistant to fosfomycin and (ii) every tenth isolate; all non-Russian sites were included. A total of 2848 isolates were analysed, principally Escherichia coli (2064; 72.5%), Klebsiella spp. (275; 9.7%) and Proteus spp. (103; 3.6%). For E. coli, agents active against >90% of isolates were nitrofurantoin (98.5%), fosfomycin (96.4%) and mecillinam (91.8%). Fosfomycin and nitrofurantoin remained active against >90% of cephalosporin-resistant E. coli. Among 143 E. coli recorded as susceptible locally by disk tests, 138 (96.5%) were confirmed susceptible by minimum inhibitory concentration (MIC) tests, however resistance was only confirmed in 29/58 (50.0%) of those reported resistant by local disk tests. Escherichia coli was found to be the most common uropathogen isolated and was highly susceptible to fosfomycin, nitrofurantoin and mecillinam, all used effectively for more than 30 years. Guidelines advocating fosfomycin for uncomplicated UTIs in women remain microbiologically valid.
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Infecciones por Escherichia coli , Fosfomicina , Infecciones Urinarias , Amdinocilina/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Estudios Transversales , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Femenino , Fosfomicina/farmacología , Fosfomicina/uso terapéutico , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Nitrofurantoína/farmacología , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiologíaRESUMEN
CONTEXT: Transrectal ultrasound-guided prostate biopsy (TRPB) has been a standard of care for diagnosing prostate cancer but is associated with a high incidence of infectious complications. OBJECTIVE: To achieve an expert consensus on whether fosfomycin trometamol provides adequate prophylaxis in TRPB and discuss its role as prophylaxis in transperineal prostate biopsy (TPPB). EVIDENCE ACQUISITION: An international multidisciplinary group of experts convened remotely to discuss how to best use fosfomycin in various clinical settings and patient situations. Six statements related to prostate biopsy and the role of fosfomycin were developed, based on literature searches and relevant clinical experience. EVIDENCE SYNTHESIS: Consensus was reached for all six statements. The group of experts was unanimous regarding fosfomycin as a preferred candidate for antimicrobial prophylaxis in TRPB. Fosfomycin potentially also meets the requirements for empiric prophylaxis in TPPB, although further clinical studies are needed to confirm or refute its utility in this setting. There is a risk of bias due to sponsorship by a pharmaceutical company. CONCLUSIONS: Antimicrobial prophylaxis is mandatory in TRPB, and fosfomycin trometamol is an appropriate candidate due to low rates of resistance, a good safety profile, sufficient prostate concentrations, and demonstrated efficacy in reducing the risk of infectious complications following TRPB. PATIENT SUMMARY: Patients undergoing transrectal ultrasound-guided prostate biopsy (TRPB) have a high risk of infectious complications, and antimicrobial prophylaxis is mandatory. However, increasing antimicrobial resistance, as well as safety concerns with fluoroquinolones, has restricted the number of antimicrobial options. Fosfomycin trometamol meets the requirements for a preferred antimicrobial in the prophylaxis of TRPB.
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Fosfomicina , Masculino , Humanos , Fosfomicina/uso terapéutico , Próstata/patología , Trometamina , Profilaxis Antibiótica , Biopsia/efectos adversos , Antibacterianos/uso terapéuticoRESUMEN
Fosfomycin trometamol (FT) has shown promising in vitro activity against multidrug-resistant (MDR) uropathogens; however, clinical data are limited in pediatric patients. We conducted a retrospective study to describe the clinical and microbiological outcomes of uncomplicated lower urinary tract infections (LUTIs) due to MDR Escherichia coli treated with oral FT in female adolescents. A total of 70 outpatients, with a median age of 13 years (range 12-16 years), were included. FT was initiated as definitive treatment of UTIs in all patients due to documented resistance against alternative oral agents. All patients received a single dose of 3 g oral FT. The post-treatment clinical and microbiological cure rates were 97% (68/70) and 94% (66/70), respectively. Only two (3%) patients reported mild, self-limited diarrhea. UTI relapse occurred in two (3%) patients. Our results suggest that oral FT might be an alternative option for outpatient treatment of uncomplicated LUTIs due to MDR E. coli in female adolescents.
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Infecciones por Escherichia coli , Fosfomicina , Infecciones Urinarias , Adolescente , Antibacterianos , Niño , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Femenino , Humanos , Estudios Retrospectivos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiologíaRESUMEN
BACKGROUND: Bacterial prostatitis can be difficult to treat as more and more bacteria are resistant to fluoroquinolone and/or Sulfamethoxazole-Trimethoprim which are the antibiotics of choice. Fosfomycin-Trometamol which is registered for uncomplicated urinary tract infections can be an option when other treatments can't be used. OBJECTIVE: To describe a case of prostatitis cured using a prolonged course of Fosfomycin-Trometamol. Patient: A 67 years-old man with a chronic bacterial prostatitis, with recurrences for more than 3 years, due to E. coli was treated with Fosfomycin-Trometamol 3g once a day for a week followed by 3 months of the same dose every two days. Prostatitis was clinically and bacteriologically cured and no relapse occurred after 6 months of follow-up. CONCLUSION: Fosfomycin-Trometamol can be a good option for the treatment of bacterial prostatitis when other antibiotics can't be used either for resistance or allergy.
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Fosfomicina , Prostatitis , Infecciones Urinarias , Anciano , Antibacterianos/uso terapéutico , Escherichia coli , Fosfomicina/uso terapéutico , Humanos , Masculino , Prostatitis/tratamiento farmacológico , Trometamina , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
PURPOSE: To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture. METHODS: Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB. PRIMARY OUTCOME: early-PJI after HHA. RESULTS: Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33-3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15-7.10]). CONCLUSIONS: Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Bacteriuria/microbiología , Artropatías/microbiología , Infecciones Relacionadas con Prótesis/microbiología , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Infecciones Asintomáticas/terapia , Bacteriuria/tratamiento farmacológico , Bacteriuria/etiología , Femenino , Fosfomicina/uso terapéutico , Humanos , Artropatías/tratamiento farmacológico , Artropatías/etiología , Masculino , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/etiología , Trometamina/uso terapéuticoRESUMEN
AIM: To evaluate the efficacy and safety of the antibacterial drug fosfomycin trometamol (Fosfomycin Esparma) in women of reproductive age with acute uncomplicated cystitis. MATERIALS AND METHODS: In order to assess the efficacy and safety of using fosfomycin trometamol (Fosfomycin Esparma), a prospective, non-randomized, uncontrolled study involving 32 women with acute uncomplicated cystitis was carried out. The average patients age was 27.3+/-3.1 years. Before the study, all women underwent a general clinical, bacteriological, and ultrasound examination. Inclusion criteria was the presence of pathognomonic symptoms of acute uncomplicated cystitis. Exclusion criteria were as following: complicated urinary tract infection, anatomical and functional disorders of the urinary tract, comorbidities. All patients were prescribed a study drug at a dose of 3 g, once. The efficiency of therapy was evaluated on days 3 and 14 after administration of Fosfomycin Esparma based on clinical and microbiological cure and safety. RESULTS: The only bacterial pathogen isolated from the urine was E. coli. In 4 cases (12.5%) strains produced extended-spectrum -lactamase. The sensitivity of E. coli to fosfomycin, piperacillin/tazobactam, amikacin and meropenem was 100%. A resistance to ampicillin was 15.6%, compared to 9.4% for levofloxacin and norfloxacin and 12% for cefotaxime, ceftazidime, cefpoxin. By the 3rd day after receiving fosfomycin, the symptoms of cystitis were resolved in all patients. On day 14, according to the results of the urine culture, there was no growth of bacteria. During the follow-up period, no significant side effects was detected. CONCLUSION: Our study showed that antibacterial drug Fosfomycin Esparma in women of reproductive age with acute uncomplicated cystitis is effective and safe. Maintaining a high sensitivity to fosfomycin allows us to recommend this drug as an empirical antibiotic therapy in this cohort of patients.
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Antibacterianos/uso terapéutico , Cistitis/tratamiento farmacológico , Fosfomicina/uso terapéutico , Infecciones Urinarias , Escherichia coli , Femenino , Humanos , Estudios ProspectivosRESUMEN
There are challenges regarding increased global rates of microbial resistance and the emergence of new mechanisms that result in microorganisms becoming resistant to antimicrobial drugs. Fosfomycin is a broad-spectrum bactericidal antibiotic effective against Gram-negative and certain Gram-positive bacteria, such as Staphylococci, that interfere with cell wall synthesis. During the last 40 years, fosfomycin has been evaluated in a wide range of applications and fields. Although numerous studies have been done in this area, there remains limited information regarding the prevalence of resistance. Therefore, in this review, we focus on the available data concerning the mechanisms and increasing resistance regarding fosfomycin.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Fosfomicina/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/microbiología , Bacterias Grampositivas/efectos de los fármacos , Infecciones por Bacterias Grampositivas/microbiología , Geografía , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Grampositivas/epidemiología , Humanos , PrevalenciaRESUMEN
BACKGROUND: Febrile Urinary Tract Infection (FUTI) is frequently treated initially with intravenous antibiotics, followed by oral antibiotics guided by clinical response and bacterial susceptibility patterns. Due to increasing infection rates with multiresistant Enterobacteriaceae, antibiotic options for stepdown treatment decline and patients more frequently require continued intravenous antibiotic treatment for FUTI. Fosfomycin is an antibiotic with high bactericidal activity against Escherichia coli and current resistance rates are low in most countries. Oral Fosfomycin-Trometamol 3000 mg (FT) reaches appropriate antibiotic concentrations in urine and blood and is considered safe. As such, it is a potential alternative for stepdown treatment. METHODS: The FORECAST study (Fosfomycin Randomized controlled trial for E.coli urinary tract infections as Alternative Stepdown Treatment) is a randomized, double-blind, double-dummy, non-inferiority trial in which 240 patients will be randomly allocated to a stepdown treatment with FT or ciprofloxacin (standard of care) for FUTI, caused by Escherichia coli with in vitro susceptibility to both antibiotics. The study population consists of consenting female patients (≥18 years) with community acquired E. coli FUTI. After intravenous antibiotic treatment during at least 48 (but less than 120) hours, and if eligibility criteria for iv-oral switch are met, patients receive either FT (3 g every 24 h) or ciprofloxacin (500 mg every 12 h) for a total antibiotic duration of 10 days. The primary endpoint is clinical cure (resolution of symptoms) 6-10 days post-treatment. Secondary endpoints are microbiological cure 6-10 days post-treatment, clinical cure, mortality, ICU admittance, relapse, reinfection, readmission, additional antibiotic use for UTI, early study discontinuation, adverse events, days of hospitalization and days of absenteeism within 30-35 days post-treatment. The sample size is based on achieving non-inferiority on the primary endpoint, applying a non-inferiority margin of 10%, a two-sided p-value of < 0.05 and a power of 80%. DISCUSSION: The study aims to demonstrate non-inferiority of oral fosfomycin, compared to oral ciprofloxacin, in the stepdown treatment of E. coli FUTI. TRIAL REGISTRATION: Registered at the Nederlands trial register (Dutch trial register) on 4-10-2017. TRIAL REGISTRATION NUMBER: NTR6449 . Secondary ID (national authority): NL60186.041.17.
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Ciprofloxacina/administración & dosificación , Infecciones por Escherichia coli/tratamiento farmacológico , Fiebre/tratamiento farmacológico , Fosfomicina/administración & dosificación , Infecciones Urinarias/tratamiento farmacológico , Administración Intravenosa , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Ciprofloxacina/efectos adversos , Método Doble Ciego , Estudios de Equivalencia como Asunto , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/complicaciones , Femenino , Fiebre/complicaciones , Fosfomicina/efectos adversos , Humanos , Persona de Mediana Edad , Placebos , Infecciones Urinarias/complicaciones , Adulto JovenRESUMEN
Empirical antibiotic treatment of urinary tract infections: from everyday clinical practice to EAU guidelines 2017 Recent epidemiological data confirm the increasing problem of antimicrobial resistance not only for hospitalized, healthcare-associated patients but also for outpatients. In particular, the progressive increase in resistance to broad-spectrum antibiotics, such as third-generation cephalosporins, fluoroquinolones, or carbapenems in Enterobacteriaceae, is an alarming situation for all urologists and general practitioners. The management of uncomplicated urinary tract infections are an important step in antibiotic stewardship achievement: a new approach is urgently required. All international Guidelines on urological infections suggest to take into account the following parameters for choosing antimicrobial therapy: spectrum and susceptibility patterns of the aetiological pathogens; efficacy for the particular indication in clinical studies; tolerability and adverse reactions; adverse ecological effects; costs and availability. In other words, an accurate evaluation of all patients and bacteria-related factors should be performed, along with the consideration of local data of bacterial resistance rate. According to these principles and the available susceptibility patterns in Italy, fosfomycin trometamol 3 g single dose and nitrofurantoin, are considered as drugs of first choice.
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Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Farmacorresistencia Bacteriana , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
RELEVANCE: Acute uncomplicated lower urinary tract infections (AULUTI) are one of the most common diseases in urological practice. The management of cystitis is commonly based on antibacterial therapy. Despite the high efficiency, inadequate prescription of antibiotics leads to an increase in microorganisms resistance. In light of these matters, the selection of antibacterial agents to which the sensitivity of bacteria is the highest is becoming increasingly challenging. AIM: To estimate the spectrum and local sensitivity of E. coli in patients with AULUTI. MATERIALS AND METHODS: The present study analyzed the results of bacterial culture sampled from 45 patients with AULUTI. The mean age of the patients was 44+/-17 years. All bacterial cultures were obtained in out-patient settings in the framework of a multicenter initiative study on the prevention of recurrent AULUTI with d-mannose. RESULTS: Microbiological studies of the urine of patients with AULUTI revealed the growth of E. coli in concentrations ranging from 104 to 107 CFU/ml. Assessment of sensitivity demonstrated 100% sensitivity of Escherichia coli to fosfomycin trometamol. CONCLUSION: According to the findings of microbiological studies, the patients with the AULUTI retain the highest sensitivity level of E.coli to phosphomycin trometamol, which allows it to be used as a first-line drug.
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Antibacterianos/uso terapéutico , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli/efectos de los fármacos , Trometamina/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Enfermedad Aguda , Adulto , Antibacterianos/administración & dosificación , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/microbiología , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Resultado del Tratamiento , Trometamina/administración & dosificación , Infecciones Urinarias/microbiologíaRESUMEN
We present the results of a multicenter retrospective study of 35 difficult-to-treat patients with urinary tract infections associated with indwelling urinary catheters (CAUTIs). All patients received oral administration of 3 g fosfomycin trometamol once a day for two days and then with a dose of 3 g every 48 h for two weeks. The most commonly isolated strains were: Escherichia coli (65.7%) and Enterococcus spp. (25.7%); prevalence of Extended-Spectrum Beta-Lactamase strains was 48.5%. Six patients (17.1%) had a clinical response after a single dose of fosfomycin trometamol, 12 (34.2%) after two doses and 13 (37.1%) patients had a clinical response after three or more doses. Four patients (11.6%) failed prolonged antibiotic treatment with fosfomycin trometamol. During the follow-up period, 30 out of 35 (85.7%) patients were without symptomatic infections. No significant side effects were reported. In conclusion, fosfomycin trometamol seems to be a valid treatment option in patients with CAUTIs.
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Antibacterianos/administración & dosificación , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Fosfomicina/administración & dosificación , Trometamina/administración & dosificación , Infecciones Urinarias/tratamiento farmacológico , Administración Oral , Anciano , Antibacterianos/efectos adversos , Esquema de Medicación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Enterococcus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Femenino , Fosfomicina/efectos adversos , Humanos , Masculino , Estudios Retrospectivos , Trometamina/efectos adversos , Infecciones Urinarias/microbiologíaRESUMEN
OBJECTIVES: Fosfomycin is increasingly being prescribed for treatment of uncomplicated urinary tract infections in an era of emerging drug resistance. Surprisingly, little is known of the urinary concentrations of fosfomycin and its interindividual variation after the standard single 3-g oral dose. We aimed to gain more insight into urinary fosfomycin pharmacokinetics to evaluate its effectiveness. METHODS: Three grams of fosfomycin trometamol was administered to 40 healthy female volunteers with an estimated mean glomerular filtration rate of >90 mL/min/1.73m2. Urine samples were collected from every urination during 48 hours, and then twice daily for up to 7 days. Time, volume, and pH were recorded. Concentrations were quantified with UPLC-MS/MS. Effectiveness was evaluated based on urinary concentrations and the target MIC of E. coli, the most common uropathogen. RESULTS: A high interindividual variability was found. Peak concentration was 1982.0 ± 1257.4 mg/L, urinary half-life 12.4 ± 5.7 hours, and excretion rate over 48 hours 29.9 ± 7.1 mg/h. Recovery was 44.5 ± 12.6% after 48 hours and 47.0 ± 10.4% after 7 days. Concentrations remained above the EUCAST breakpoint of 32 mg/L in 100% of the volunteers over the first 24 hours, 67.5% for 48 hours, and 30% for 72 hours. A high urinary output was associated with low urinary concentrations and consequently reduced time > MIC, AUC0-7days/MIC, and Cmax/MIC values. CONCLUSIONS: Considerable interindividual variability observed in the pharmacokinetics of fosfomycin signifies a risk for inadequate drug exposure in a significant proportion of the population. The current dosing regimen should therefore be reevaluated.
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Antibacterianos/farmacocinética , Fosfomicina/farmacocinética , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/orina , Administración Oral , Adolescente , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Cromatografía Líquida de Alta Presión , Femenino , Fosfomicina/administración & dosificación , Fosfomicina/uso terapéutico , Tasa de Filtración Glomerular , Voluntarios Sanos , Servicios de Atención de Salud a Domicilio , Humanos , Pruebas de Función Renal , Pruebas de Sensibilidad Microbiana , Espectrometría de Masas en Tándem , Urinálisis , Infecciones Urinarias/microbiología , Adulto JovenRESUMEN
Antibiotic resistance represents a real health emergency worldwide, mostly due to the lack of new antibiotics active against multidrug-resistant Enterobacteriaceae. Considering the global epidemiological situation in several infections, including urinary tract infections (UTIs), some antibiotics, such as fluoroquinolones and trimethoprim/sulphamethoxazole, can no longer be used for empiric treatment due to high resistance rates. However, some old antibiotics maintain high microbiological activity against UTI pathogens: according to many recent guidelines, fosfomycin trometamol, nitrofurantoin and pivmecillinam are recommended for the first-line treatment of uncomplicated UTIs. This article provides an overview of the therapeutic management of UTIs, especially uncomplicated and recurrent cystitis, as well as complicated UTIs such as catheter-related UTIs, and UTIs in males, post-menopausal women and diabetic patients, based on the main international guidelines.
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Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , Salud Global , Guías de Práctica Clínica como Asunto , Infecciones Urinarias/tratamiento farmacológico , Antibacterianos/efectos adversos , Quimioterapia Combinada/efectos adversos , Enterobacteriaceae/crecimiento & desarrollo , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/microbiología , Transición de la Salud , Humanos , Incidencia , Prevalencia , Factores de Riesgo , Infecciones Urinarias/epidemiología , Infecciones Urinarias/microbiologíaRESUMEN
The therapeutic management of uncomplicated bacterial urinary tract infections (UTIs) is based on short-term courses of oral antibiotics. The preferred drugs are nitrofurantoin trimethoprim-sulfamethoxazole, fosfomycin trometamol, fluoroquinolones and ß-lactam agents. The choice of agent for treating uncomplicated UTIs should be based on the pharmacokinetic characteristics of the molecule so that clinical benefit is optimized and the risk of antibacterial resistance is minimized. This article discusses the general pharmacokinetic-pharmacodynamic (PK/PD) aspects of antimicrobial chemotherapy, the PK/PD characteristics of oral antimicrobial agents for the treatment of uncomplicated UTIs and the pharmacological and therapeutic strategies for limiting or preventing bacterial resistance.
Asunto(s)
Antibacterianos/uso terapéutico , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Bacterias Grampositivas/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Administración Oral , Animales , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Disponibilidad Biológica , Farmacorresistencia Bacteriana , Quimioterapia Combinada/efectos adversos , Bacterias Gramnegativas/crecimiento & desarrollo , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/sangre , Infecciones por Bacterias Gramnegativas/microbiología , Bacterias Grampositivas/crecimiento & desarrollo , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/sangre , Infecciones por Bacterias Grampositivas/microbiología , Semivida , Humanos , Tasa de Depuración Metabólica , Guías de Práctica Clínica como Asunto , Infecciones Urinarias/sangre , Infecciones Urinarias/microbiologíaRESUMEN
Clinical midstream and urinary catheter isolates (n = 106) of extended-spectrum ß-lactamase (ESBL)-positive Escherichia coli, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae, Proteus mirabilis and meticillin-resistant Staphylococcus saprophyticus were tested against fosfomycin using the agar dilution method, the broth microdilution method and the gradient test described by the Clinical and Laboratory Standards Institute. Nitrofurantoin, co-trimoxazole, amoxicillin/clavulanic acid, cefuroxime, levofloxacin and ciprofloxacin were tested using the gradient test alone. Breakpoints from the European Committee on Antimicrobial Susceptibility Testing 2015 guidelines were used. Fosfomycin inhibited all of the ESBL-positive E. coli, P. mirabilis and meticillin-resistant S. saprophyticus strains isolated from urine, as well as 82% of KPC-producing K. pneumoniae isolates. Substantial agreement for fosfomycin activity was found for the three test methods, particularly for Enterobacteriaceae. This study confirmed that fosfomycin has good in vitro activity against more common multidrug-resistant uropathogens. Fosfomycin could be a reliable empirical therapeutic option for uncomplicated urinary tract infections caused by these organisms, and a valid option for sparing parenteral antibiotics, such as carbapenems.