Non-Adherence in Adult Male Patients with Community-Acquired Pneumonia: Relative Forgiveness of Amoxicillin versus Respiratory Fluoroquinolones.

The consequences of non-adherence to treatment (NAT) on antimicrobial efficacy may depend on drug forgiveness-a property that should account for pharmacokinetics (PK) and pharmacodynamics (PD) as well as interindividual variability. In this simulation study, relative forgiveness (RF) in NAT, defined as the probability of a successful PK/PD target (PTA) attained under perfect adherence compared to imperfect adherence, was evaluated for amoxicillin (AMOX) (oral 1000 mg/8 h) and two respiratory fluoroquinolones-levofloxacin (LFX) (oral 750 mg/24 h) and moxifloxacin (MOX) (oral 400 mg/24 h)-in virtual outpatients with community-acquired pneumonia for S. pneumoniae. Several NAT scenarios (delay in dose intake and a missed dose) were considered. PK characteristics of virtual patients, including variability in creatinine clearance (70-131 mL/min) and S. pneumoniae susceptibility variability associated with geographical location, were simulated in NAT. In this regard, in regions of low MIC delays from 1 h to 7 h or omission of dose ingestion would not have negative consequences on the efficacy of AMOX because of its good RF associated with the AMOX PK and PD properties; RF of LFX 750 mg or MOX 400 mg/24 h regimen vs. AMOX 1000 mg/8 h is one. However, in regions of elevated MIC for S. pneumoniae AMOX loses its RF, LFX and MOX vs. AMOX, showing higher RF (>1) depending on the CLCR of patients. These results illustrate the importance of considering the RF of antimicrobial drugs in NAT and provide a framework for further studying its implications for clinical success rates.

Key Factors in Effective Patient-Tailored Dosing of Fluoroquinolones in Urological Infections: Interindividual Pharmacokinetic and Pharmacodynamic Variability.

Fluoroquinolones (FQs) are a critical group of antimicrobials prescribed in urological infections as they have a broad antimicrobial spectrum of activity and a favorable tissue penetration at the site of infection. However, their clinical practice is not problem-free of treatment failure, risk of emergence of resistance, and rare but important adverse effects. Due to their critical role in clinical improvement, understanding the dose-response relation is necessary to optimize the effectiveness of FQs therapy, as it is essential to select the right antibiotic at the right dose for the right duration in urological infections. The aim of this study was to review the published literature about inter-individual variability in pharmacological processes that can be responsible for the clinical response after empiric dose for the most commonly prescribed urological FQs: ciprofloxacin, levofloxacin, and moxifloxacin. Interindividual pharmacokinetic (PK) variability, particularly in elimination, may contribute to treatment failure. Clearance related to creatinine clearance should be specifically considered for ciprofloxacin and levofloxacin. Likewise, today, undesired interregional variability in FQs antimicrobial activity against certain microorganisms exists. FQs pharmacology, patient-specific characteristics, and the identity of the local infecting organism are key factors in determining clinical outcomes in FQs use.

[De Novo renal mass on kidney grafts.] / Tumores de novo en trasplante renal.

OBJECTIVE: Cancer is the 3rd cause of death in the Spanish kidney transplant population. The risk of developing a tumour is multifactorial. Improvements in follow-up and increased graft survival have led to an increase in the incidence of de novo tumours in these patients. MATERIAL AND METHODS: We have conducted a systematic review of articles published in online medical databases related to de novo tumours in kidney transplant recipients. We have evaluated the incidence of de novo neoplasms in patients who under went a kidney transplant at the Hospital Universitario de Cruces from January 2011 to December 2018. RESULTS AND DISCUSSION: Different characteristics have been described within the transplanted population that could promote the development of tumours. The alteration of the antitumor response, the altered ability to respond to infections, drug´s carcinogenic effect, and agreater susceptibility ultraviolet rays damage are some of the most repeated. As a consequence, overall risk of cancer increases two to three times in the transplanted population. Overall, in our analysis, the neoplasms that showed the highest incidence were urological (21.98%), followed by haematological (16.63%) and digestive tract (14.58%). CONCLUSION: There is a higher incidence and risk of de novo tumour development in the kidney transplant population, which probably requires optimizing patient follow-up and developing more precise screening strategies that can be modified depending on geographic and individual variations, to reduce the impact on survival that it may have on our patients.

OBJETIVO: Las neoplasias son la 3ª causa de muerte en la población trasplantada renal en España. El riesgo de desarrollar una neoplasia es multifactorial. Con las mejoras en el seguimiento y el aumento de la supervivencia del injerto, se está produciendo un incremento en la incidencia de neoplasias de novo en estos pacientes.MATERIAL Y MÉTODOS: Análisis bibliográfico de las neoplasias de novo en pacientes trasplantados renales mediante la revisión sistemática de artículos publicados en bases de datos médicas online. Recogida y evaluación de la incidencia de neoplasias de novo en pacientesa los que se les realizó un trasplante de riñón en el Hospital Universitario de Cruces desde enero de 2011 hasta diciembre 2018.RESULTADOS Y DISCUSIÓN: Dentro de la población trasplantada se han descrito diferentes vías que podrían promover la aparición de neoplasias. Unas de las hipótesis más repetidas son la alteración de la respuesta antitumoral, la capacidad alterada para contrarrestar infecciones, características cancerígenas de los medicamentos en sí y una mayor susceptibilidad a los efectos dañinos de los rayos ultravioleta. La influencia de todos estos factores se traduce en un incremento de dos a tres veces en la incidencia de neoplasias en esta población. De forma global, en todos los estudios analizados, las neoplasias que mostraron mayor incidencia fueron las urológicas (21,98%), seguidas de las hematológicas (16,63%) y del tracto digestivo (14,58%).CONCLUSIÓN: Se evidencia una mayor incidencia de tumores de novo en la población trasplantada renal, que probablemente requiera una optimización en el seguimiento de los pacientes, desarrollando estrategias de screening más precisas que puedan modificarse en función de las variaciones geográficas e individuales, para disminuir el impacto en la supervivencia que puedan tener estas neoplasias de novo.

Tumores de novo en trasplante renal / New tumors in kidney transplantation

Objetivo: Las neoplasias son la 3ª causade muerte en la población trasplantada renal en España. El riesgo de desarrollar una neoplasia es multifactorial. Con las mejoras en el seguimiento y el aumentode la supervivencia del injerto, se está produciendo unincremento en la incidencia de neoplasias de novo enestos pacientes. Material y métodos: Análisis bibliográfico de lasneoplasias de novo en pacientes trasplantados renalesmediante la revisión sistemática de artículos publicadosen bases de datos médicas online. Recogida y evaluación de la incidencia de neoplasias de novo en pacientes a los que se les realizó un trasplante de riñón en elHospital Universitario de Cruces desde enero de 2011hasta diciembre 2018.Resultados y discusión: Dentro de la poblacióntrasplantada se han descrito diferentes vías que podríanpromover la aparición de neoplasias. Unas de las hipótesis más repetidas son la alteración de la respuesta antitumoral, la capacidad alterada para contrarrestarinfecciones, características cancerígenas de los medicamentos en sí y una mayor susceptibilidad a los efectosdañinos de los rayos ultravioleta. La influencia de todosestos factores se traduce en un incremento de dos a tresveces en la incidencia de neoplasias en esta población.De forma global, en todos los estudios analizados, lasneoplasias que mostraron mayor incidencia fueron lasurológicas (21,98%), seguidas de las hematológicas(16,63%) y del tracto digestivo (14,58%). COonclusión: Se evidencia una mayor incidencia detumores de novo en la población trasplantada renal,que probablemente requiera una optimización en elseguimiento de los pacientes, desarrollando estrategiasde screening más precisas que puedan modificarse enfunción de las variaciones geográficas e individuales,para disminuir el impacto en la supervivencia que puedan tener estas neoplasias de novo.(AU)

Objetive: Cancer is the 3rd cause ofdeath in the Spanish kidney transplant population. Therisk of developing a tumour is multifactorial. Improvements in follow-up and increased graft survival have ledto an increase in the incidence of de novo tumours inthese patients.Material and methods: We have conducted a systematic review of articles published in online medicaldatabases related to de novo tumours in kidney transplant recipients. We have evaluated the incidence ofde novo neoplasms in patients who underwent a kidneytransplant at the Hospital Universitario de Cruces fromJanuary 2011 to December 2018. Results and discussion: Different characteristicshave been described within the transplanted populationthat could promote the development of tumours. The alteration of the antitumor response, the altered ability torespond to infections, drug ́s carcinogenic effect, and agreater susceptibility ultraviolet rays damage are someof the most repeated. As a consequence, overall riskof cancer increases two to three times in the transplanted population. Overall, in our analysis, the neoplasmsthat showed the highest incidence were urological(21.98%), followed by haematological (16.63%) anddigestive tract (14.58%).Conclusion: There is a higher incidence and riskof de novo tumour development in the kidney transplantpopulation, which probably requires optimizing patientfollow-up and developing more precise screening strategies that can be modified depending on geographicand individual variations, to reduce the impact on survival that it may have on our patients.(AU)