RESUMEN
Ceftriaxone is a third-generation cephalosporin, worldwide use as a first-line treatment for several infections, including life-threatening infections as meningitis or endocarditis. Nowadays, ceftriaxone use is changing, embracing high-dose schemes, new populations treated and requirement of dose individualization and optimization. These reasons warranted the development of new sensitive assays. This study aimed to develop and validate a fast and handy bioanalytical method for the quantification of ceftriaxone in human plasma covering a broad range of concentrations. The analysis was performed using high-performance liquid chromatography coupled to tandem mass spectrometry. Sample preparation was based on protein precipitation with acetonitrile followed by centrifugation. Chromatography separation was performed on Phenomenex Luna C18 column (5 µm, 150 × 2.0 mm) and a mobile phase consisting of 70 % of mobile phase A (10 mM of ammonium acetate and 1% formic acid in purified water) and 30 % mobile phase B (0.1 % formic acid in acetonitrile) at a flow rate of 500 µl/min on an isocratic program. Both the analyte and the internal standard were quantified using the positive electrospray ionization (ESI) mode within a single runtime of 5.00 min. The method was validated following the U.S. Food and Drug Administration guidelines over the concentration range of 3-1000 µg/mL. The within-run and between-run precision and accuracy were <15 %, and therefore met the standard regulatory acceptance criterion. In conclusion, a sensitive and robust LC-MS/MS method was developed for a fast quantitation of ceftriaxone concentrations in plasma samples with multiples applications in research and clinical therapeutic drug monitoring.
Asunto(s)
Ceftriaxona , Espectrometría de Masas en Tándem , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Humanos , Reproducibilidad de los ResultadosRESUMEN
The inclusion of ampicillin-containing regimens in outpatient parenteral antimicrobial therapy programs (OPAT) depends upon solution stability under conditions similar to those experienced in these programs. Lack of this information could hinder the inclusion in OPAT of patients suffering from Enterococcus faecalis infective endocarditis treated with ampicillin plus ceftriaxone. The purpose of this study is to determine the stability of ampicillin and ampicillin plus ceftriaxone solutions in a simulated outpatient setting conditions. Solutions of ampicillin 24 g/liter and ampicillin 24 g/liter combined with ceftriaxone 8 g/liter were stored at 25°C ± 2°C, 30°C ± 2°C and 37°C ± 2°C for 48 h. Chemical and physical stability were evaluated at 20, 24, 30, and 48 h after manufacturing. The solutions were considered stable if the percentage of intact drug was ≥90% and color and clearness remained unchanged. After 24 h of storage at a controlled temperature, ampicillin solution in 0.9% sodium chloride was found to be stable for 30 h at 25 and 30°C and for 24 h at 37°C. In the ampicillin plus ceftriaxone combined solution, both antibiotics were found to be stable after 30 h of storage at 25 and 30°C, but at 37°C, the stability criterion was not met at any time point. Our study offers solid evidence demonstrating that the concentrations of both drugs at two of the tested temperatures (25°C and 30°C) were stable for up to 30 h. Therefore, both ampicillin alone and ampicillin plus ceftriaxone solutions would be appropriate candidates for inclusion in OPAT programs.
Asunto(s)
Ceftriaxona , Pacientes Ambulatorios , Ampicilina , Antibacterianos/uso terapéutico , Quimioterapia Combinada , Enterococcus faecalis , Humanos , TemperaturaRESUMEN
OBJECTIVES: Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are essential for improving antibiotic use in hospitals. However, their impact on entire healthcare systems has not been thoroughly assessed. Our objective was to provide the results of an institutionally supported ASP involving 31 public hospitals in Andalusia, Spain. METHODS: We designed an ecologic time-series study from 1 January 2014 to 31 December 2017. Quarterly, data on indicators were collected prospectively, and feedback reports were provided. PIRASOA is an ongoing clinically based quality-improvement programme whose key intervention is the educational interview, regular peer-to-peer interventions between advisors and prescribers to reinforce the appropriate use of antibiotics. Seventy-two indicators were monitored to measure prescribing quality (inappropriate treatments), antimicrobial consumption (defined daily doses per 1000 occupied bed-days), incidence density of MDR per 1000 occupied bed-days and crude mortality rate associated with bloodstream infections. We used Joinpoint regression software to analyse the trends. RESULTS: The quality of antimicrobial prescribing improved markedly, and the inappropriate treatment rate was significantly lower, with quarterly percentage change (QPC) = -3.0%, p < 0.001. Total antimicrobial consumption decreased (QPC = -0.9%, p < 0.001), specifically carbapenems, amoxicillin/clavulanic acid, quinolones and antifungal agents, whereas antipseudomonal cephalosporin use increased. While the incidence of MDR showed a sustained decreasing trend (QPC = -1.8%; p 0.002), the mortality of patients with bloodstream infections remained stable (QPC = -0.2%, p 0.605). CONCLUSIONS: To date, the PIRASOA programme has succeeded in optimizing the use of antimicrobial agents and has had a positive ecologic result on bacterial resistance at level of an entire healthcare system.
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Programas de Optimización del Uso de los Antimicrobianos , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Antiinfecciosos/uso terapéutico , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Prescripciones de Medicamentos/normas , Prescripciones de Medicamentos/estadística & datos numéricos , Farmacorresistencia Bacteriana Múltiple , Hospitales , Humanos , Incidencia , Pautas de la Práctica en Medicina/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Vigilancia en Salud Pública , España/epidemiologíaRESUMEN
Background: Acinetobacter baumannii causes frequently nosocomial infections worldwide. Its ability to survive on dry surfaces facilitates its spread and the persistence of endemic situations, especially in the intensive care units (ICUs).The objective of this paper is to describe a multicomponent intervention program designed to control a hyperendemic persistence of multidrug-resistant A. baumannii (MDR-Ab) and to characterize its impact. Methods: Design: Quasi-experimental intervention study based on open cohorts.Setting: Public tertiary referral centre. Period: January 2009-August 2017.Intervention: multifaceted program based on environmental decontamination, hand hygiene, antimicrobial stewardship, contact precautions, active surveillance, weekly reports and regular meetings.Analysis: joinpoint regression and interrupted time-series analysis. Results: The intervention was successfully implemented. Through the study period, the compliance with contact precautions changed from 0 to 100% and with hand hygiene, from 41.8 to 82.3%. Between 2012 and 2016, the antibiotic consumption decreased from 165.35 in to 150.44 daily-defined doses/1000 patients-days in the ICU. The incidence density of MDR-Ab in the ICU was 10.9 cases/1000 patients-days at the beginning of the intervention. After this moment, the evolution of the incidence density of MDR-Ab was: between months 0 and 6°, it remained stable; between months 7° and 10°: there was an intense decrease, with an average monthly percentage change (AMPC) = - 30.05%; from 11° month until the end, the decrease was lighter but continuous (AMPC:-2.77%), achieving an incidence density of 0 cases/1000 patients-days on the 18° month, without any new case for 12 months. From the 30° month until the end of the study period, several little outbreaks of MDR-Ab were detected, all of them rapidly controlled. The strains of MDR-Ab isolated during these outbreaks were not clonally related with the previously endemic one, which supports its eradication from the environmental reservoirs. Conclusion: The multicomponent intervention performed by a multidisciplinary team was effective to eradicate the endemic MDR-Ab.
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Infecciones por Acinetobacter/prevención & control , Infección Hospitalaria/prevención & control , Enfermedades Endémicas/prevención & control , Control de Infecciones/métodos , Centros de Atención Terciaria , Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/efectos de los fármacos , Adulto , Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos , Infección Hospitalaria/microbiología , Descontaminación , Manejo de la Enfermedad , Farmacorresistencia Bacteriana Múltiple , Higiene de las Manos , Implementación de Plan de Salud/métodos , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Estudios Longitudinales , Ensayos Clínicos Controlados no Aleatorios como Asunto , EspañaAsunto(s)
Antibacterianos/administración & dosificación , Monitoreo de Drogas/métodos , Oxigenación por Membrana Extracorpórea/métodos , Vancomicina/administración & dosificación , Adulto , Antibacterianos/farmacocinética , Humanos , Unidades de Cuidados Intensivos , Masculino , Vancomicina/farmacocinéticaRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Enterococcus faecalis is the third most common causal agent of infective endocarditis. Currently, the treatment recommended is a combination of ampicillin (2 g/4 h) plus ceftriaxone (2 g/12 h), so patients must remain hospitalized for almost 6 weeks to receive the treatment. They are not generally included in outpatient parenteral antimicrobial therapy programs because 2 different electronic pumps are required to administer these 2 antibiotics. To enable the treatment of patients with E. faecalis IE at home, we designed a continuation combination regimen of ceftriaxone 4 g once daily in a short infusion plus ampicillin 2 g/4 h using a programmable pump. METHODS: We analyzed a cohort of patients attended in an outpatient parenteral antimicrobial therapy program that has been working since 2012 in 2 tertiary hospitals. We selected patients attended in this program for E. faecalis IE treated with a continuation regimen of ampicillin 12 g daily (2 g/4 h) and ceftriaxone 4 g every 24 hours between July 2012 and March 2017. RESULTS AND DISCUSSION: Of the 720 patients included in the outpatient parenteral antimicrobial therapy program, 42 had infective endocarditis, and 4 (9.52%) were treated using the combination regimen described above. All patients were men, and all had left-sided native-valve infective endocarditis. All 4 patients received ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours in hospital, for a median duration of 25 days (IQR 15-32). Thereafter, in the program, they received the following regimen: a 30-minute infusion of ceftriaxone 4 g in 250 mL of saline solution, followed by ampicillin 12 g daily in 500 mL of saline solution delivered by a pump programmed to administer 2 g every 4 hours. Patients received this treatment at home for a median of 22.5 days (IQR 13-32). All patients achieved clinical and microbiological cure with no recurrences or complications after a lengthy follow-up period (median 365 days, IQR 221-406). No drug-related adverse events or problems with the pump system were reported. WHAT IS NEW AND CONCLUSIONS: Use of ceftriaxone 4 g in a single dose yields a mean plasma concentration of 30 µg/mL. Ceftriaxone also has a high plasma protein binding capability, and once this binding is saturated, there is no reason to administer higher doses. Therefore, it seems reasonable to use a dose of 4 g of ceftriaxone once daily to have a synergist effect with ampicillin within the vegetation, and enable the treatment of patients with E. faecalis infective endocarditis at home. In conclusion, the administration of ampicillin (2 g/4 h) plus ceftriaxone (4 g/24 h) as a continuation regimen in an outpatient parenteral antimicrobial therapy program may be as effective and safe as the usual lengthy in-hospital regimen (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) in patients with E. faecalis infective endocarditis.
Asunto(s)
Antibacterianos/administración & dosificación , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis/tratamiento farmacológico , Enterococcus faecalis/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Ampicilina/administración & dosificación , Ceftriaxona/administración & dosificación , Estudios de Cohortes , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Gentamicinas/administración & dosificación , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Pacientes AmbulatoriosRESUMEN
BACKGROUND: Evidence for the effectiveness of linezolid in neurosurgical infections (NSIs) is growing. The comfortable oral dosage and tolerance of linezolid opens the possibility for sequential antimicrobial treatment (SAT) in stable patients after a period of intravenous treatment. METHODS: To evaluate the efficacy and safety of SAT with oral linezolid in patients with NSI and to analyse the cost implications, an observational, non-comparative, prospective cohort study was conducted on clinically stable consecutive adult patients at the Neurosurgical Service. Following intravenous treatment, patients were discharged with SAT with oral linezolid. RESULTS: A total of 77 patients were included. The most common NSIs were: 41 surgical wound infections, 20 subdural empyemas, 18 epidural abscesses, and 16 brain abscesses. Forty-four percent of patients presented two or more concomitant NSIs. Aetiological agents commonly isolated were: Propionibacterium acnes (36 %), Staphylococcus aureus (23 %), Staphylococcus epidermidis (21 %) and Streptococcus spp. (13 %). The median duration of the SAT was 15 days (range, 3-42). The SAT was interrupted in five cases due to adverse events. The remainder of the patients were cured at the end of the SAT. A total of 1,163 days of hospitalisation were saved. An overall cost reduction of 516,188 was attributed to the SAT. Eight patients with device infections did not require removal of the device, with an additional cost reduction of 190,595. The mean cost saving per patient was 9,179. CONCLUSIONS: SAT with linezolid was safe and effective for the treatment of NSI. SAT reduces hospitalisation times, which means significant savings of health and economic resources.
Asunto(s)
Antibacterianos/efectos adversos , Costos y Análisis de Costo , Linezolid/efectos adversos , Procedimientos Neuroquirúrgicos/efectos adversos , Infecciones Estafilocócicas/prevención & control , Infección de la Herida Quirúrgica/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/economía , Femenino , Humanos , Linezolid/administración & dosificación , Linezolid/economía , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/etiología , Infección de la Herida Quirúrgica/tratamiento farmacológicoRESUMEN
OBJECTIVE: To proactively identify risks in the preparation of intravenous cytostatic drugs, and to prioritise and establish measures to improve safety procedures. MATERIAL AND METHODS: Failure Mode Effect Analysis methodology was used. A multidisciplinary team identified potential failure modes of the procedure through a brainstorming session. The impact associated with each failure mode was assessed with the Risk Priority Number (RPN), which involves three variables: occurrence, severity, and detectability. Improvement measures were established for all identified failure modes, with those with RPN>100 considered critical. The final RPN (theoretical) that would result from the proposed measures was also calculated and the process was redesigned. RESULTS: A total of 34 failure modes were identified. The initial accumulated RPN was 3022 (range: 3-252), and after recommended actions the final RPN was 1292 (range: 3-189). RPN scores >100 were obtained in 13 failure modes; only the dispensing sub-process was free of critical points (RPN>100). A final reduction of RPN>50% was achieved in 9 failure modes. CONCLUSIONS: This prospective risk analysis methodology allows the weaknesses of the procedure to be prioritised, optimize use of resources, and a substantial improvement in the safety of the preparation of cytostatic drugs through the introduction of double checking and intermediate product labelling.
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Citostáticos , Medición de Riesgo , Humanos , Estudios Prospectivos , SeguridadRESUMEN
The misuse of antibiotics has been related to increased morbidity, mortality and bacterial resistance. The development of antimicrobial stewardship programmes (ASPs) has been encouraged by scientific societies as an essential measure. An educational, institutionally supported ASP was developed in our tertiary-care centre. Local guidelines on the management of infectious syndromes were created. Antimicrobial prescriptions were chosen arbitrarily weekly and counselling interviews by expert clinicians were carried out, using a paedagogic, non-restrictive methodology. Satisfaction with the interview was assessed using anonymous questionnaires. The appropriateness of antimicrobial prescriptions as well as consumption was assessed prospectively throughout the year. Feedback regarding the correct use of treatments was communicated to each participating department periodically. The improvement in antimicrobial prescription was included among the annual objectives linked to economic incentives in every department. A total of 1206 counselling interviews were carried out during the first year. Fifty-three per cent of antimicrobial prescriptions (176/332) were inappropriate when the programme started. The rate of inappropriate prescriptions continuously declined to 26.4% (107/405) in the fourth trimester (p <0.001; RR = 0.38; 95% CI, 0.23-0.43). Antimicrobial consumption decreased from 1150 defined daily doses (DDDs) per 1000 occupied bed-days in the first trimester to 852 DDDs in the fourth, reflecting a reduction in antimicrobial expenditures of 42%. A total of 352 satisfaction questionnaires were received and 98% described the advice as positive. In conclusion, the implementation of an education-based ASP achieved a significant improvement in all antimicrobial prescriptions in the centre and a reduction in antimicrobial consumption, even when no restrictive measures were implemented. The programme was highly accepted by all prescribers.
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Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Utilización de Medicamentos , Encuestas y Cuestionarios , Centros de Atención Terciaria , Antibacterianos/economía , Prescripciones de Medicamentos , Humanos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/economía , Estudios ProspectivosRESUMEN
We performed a retrospective and observational study of 51 patients treated with tigecycline, as the treatment for nosocomial infections due to multidrug-resistant microorganisms, to evaluate the superinfection rate and their etiologies. Superinfections were diagnosed in 12 (23.5%) patients (seven due to Pseudomonas aeruginosa, 13.7%) and one patient had P. aeruginosa colonization. Five patients with superinfection died (41.6%), three due to superinfections and two to underlying diseases. The superinfection rate observed during tigecycline treatment is higher than that previously reported. Pseudomonas aeruginosa is the most frequent agent, being the cause of 58.5% of all superinfections.
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Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infección Hospitalaria/tratamiento farmacológico , Minociclina/análogos & derivados , Sobreinfección/epidemiología , Adulto , Anciano , Bacterias/clasificación , Bacterias/aislamiento & purificación , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/mortalidad , Infección Hospitalaria/microbiología , Infección Hospitalaria/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Minociclina/uso terapéutico , Prevalencia , Estudios Retrospectivos , Sobreinfección/microbiología , Sobreinfección/mortalidad , TigeciclinaRESUMEN
OBJECTIVE: To determine the prevalence of relevant drug-drug interactions (DDIs) and associated predictor factors in a sample of patients with multiple complex chronic diseases (polypathological patients) receiving multiple drug therapy. Our secondary objective was to determine the acceptance of a drug interaction reporting program with recommendations addressed to the prescribing physicians. SUBJECTS AND METHODS: A cross-sectional study performed in three primary care centres assigned to a teaching hospital. All patients with 2 or more chronic diseases and treated simultaneously with 5 or more drugs were recruited in the study. DDIs were detected by using Drug-Reax System((R)) (Micromedex) program, the Drug Data Base (Bot) Spanish General Council of Official Colleges of Pharmacists or literature search when needed. Those DDIs which, according to the opinion of the pharmacist investigators, required any intervention were considered relevant. Acceptance of the reported DDI recommendations was evaluated by means of a survey addressed by primary care physicians ("acceptable," pertinent recommendation to modify treatment). RESULTS: A total of 283 polypathological polymedicated patients were included. Mean age was 74.5 years (range 43-100 years). Mean number of diseases per patient was 2.5 and prescriptions 9.7). Out of a total of 2748 drug prescriptions, 1053 DDIs in 250 patients (96.5%) were identified. Of these, 45% were filtered as relevant DDIs. The presence of ischemic heart disease, two or more hospital admissions and having received 7 or more prescriptions were associated with the presence of DDIs. 177 informs containing 473 recommendations about DDIs were sent to primary care physicians from our Pharmacy Department. 339 recommendations were answered by primary care physicians, and 84% were favourably accepted. CONCLUSIONS: Almost every polypathological polymedicated patient is exposed to at least one DDI and about a 60% would require any intervention. Appropriate filtering and personalising recommendations in a collaborative way may represent an adequate manner to improve the risk-benefit ratio of the drug prescriptions.
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Enfermedad Crónica/tratamiento farmacológico , Interacciones Farmacológicas , Polifarmacia , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Servicios de Información sobre Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como AsuntoRESUMEN
OBJECTIVE: To determine the effectiveness of the intervention of a multidiscipline antimicrobial control group in the correct prescription of Ertapenem. METHOD: A four-month long, prospective study into prescriptions for Ertapenem was carried out in a third-level hospital. Assessment into the degree of suitability of each prescription according to the infections commission usage criteria. In the situation where prescriptions were not suitable, recommendations were given and acceptance of this was recorded. The effectiveness of the antimicrobial treatment used was assessed and treatment was considered effective when there was remission of the signs and symptoms of the infection when the treatment was completed. The treatment was considered to have failed when the signs and symptoms of infection persisted or progressed, requiring the addition of another antimicrobial agent, changing antibiotics or the prolongation of the treatment for longer than 2 weeks. Lastly, the differences in the average length of stay and the duration of the antibiotic treatment between groups were analysed. RESULTS: Forty-eight prescriptions were assessed. The usage criterion was adequate in 48 % of cases, with 78 % effectiveness in this group. In the cases where the prescription was not adequate, but a change in prescription was accepted, the effectiveness was 92 %, with 55.5 % of those cases not accepting recommendation for change. The average stay was higher in this last group (p = 0.07). The duration of the antibiotic treatment in the patients who accepted the change in prescription was significantly less than in those who did not accept it (2 vs 7.4 days, p < 0.0001). CONCLUSIONS: The control of Ertapenem prescriptions by a multidisciplinary team was effective.
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Antibacterianos/uso terapéutico , Grupo de Atención al Paciente , beta-Lactamas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Prescripciones de Medicamentos/normas , Ertapenem , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: To define the role of those drugs available for hepatitis B treatment and analyse current treatment guides prepared by the leading scientific societies in the field. METHODS: Bibliographic searches were carried out in the databases PubMed and EMBASE, using the search word <
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Antivirales/uso terapéutico , Hepatitis B/tratamiento farmacológico , Adenina/análogos & derivados , Adenina/uso terapéutico , Guanina/análogos & derivados , Guanina/uso terapéutico , Humanos , Lamivudine/uso terapéutico , Organofosfonatos/uso terapéutico , Guías de Práctica Clínica como Asunto , TenofovirRESUMEN
OBJECTIVE: To determine the frequency and causes for discontinuing treatment with tenofovir and analyse possible predictive factors for changing this therapy in pretreated HIV patients. METHOD: A multi-centre, observational and retrospective study of all HIV patients undergoing treatment with tenofovir between July 2002 and December 2005. Data were obtained from databases for outpatients attending the three pharmacy departments participating in the study, and by reviewing clinical histories. The main sociodemographic, clinical and analytical variables at the start of treatment with tenofovir were collected. The causes for discontinuing treatment were classified as follows: adverse effects, virological failure, death and "other causes". A survival analysis was performed using the Kaplan-Meier method to analyse the possible predictive factors for discontinuing treatment. RESULTS: A total of 733 patients were included in the study and the median treatment period was 34.7 months. A total of 23.8% of patients discontinued treatment for the following reasons: adverse effects (43.2%), death (17.7%), virological failure (14.8%) and "other causes" (24.4%). There were 99 cases of lost to follow-up. In the survival analysis an association was found between normal serum creatinine values (p = 0.0042) at the start of treatment and the statistically significant probability of discontinuing treatment. CONCLUSIONS: Almost a quarter of the patients discontinued treatment with tenofovir during the study. The main cause for this was adverse effects. No association was found between any abnormal basal analytical parameter and a greater probability of discontinuing treatment.