Evaluating the optimal time for amikacin administration with respect to haemodialysis using an in vitro pharmacodynamic simulation against epidemic nosocomial OXA-48 producing Klebsiella pneumoniae ST405 strains.

OBJECTIVES: Bacterial viability and enrichment of resistance resulting from three different amikacin administration schedules with respect to haemodialysis (HD) were assessed against three OXA-48-producing Klebsiella pneumoniae isolated during an outbreak in a Spanish hospital. METHODS: A previously described two-compartment dynamic system was used. Three possible amikacin administration schedules were simulated: (i) haemodialysis immediately after amikacin infusion (pre-HD); (ii) infusion immediately after haemodialysis (post-HD); and (iii) infusion at 50% interdialytic period. Amikacin standard dose (SD) and double dose (DD) were simulated for each schedule. Values of Cmax/MIC, Cmax/MPC (mutant prevention concentration), AUC0-48h/MIC, AUC0-48h/MPC and %TMSW (percentage of time that the concentration was inside the mutant selection window) were determined with experimental data and were correlated with the area under the bacterial killing curve of the total population and the resistant subpopulation. RESULTS: Both with SD and DD, the pre-HD schedule resulted in increases at 48h in bacterial counts of the total population at the expense of enrichment of pre-existing resistant subpopulations from 12h onwards for all strains. The estimated %TMSW that prevented enrichment of resistant mutants was <61.5%. The AUC0-48h/MPC (with values of ≈40 being associated with countering of increases in resistant subpopulations) was better than the %TMSW as a predictive parameter. CONCLUSION: This study showed that the longest times concentrations were above the MPC (i.e. highest AUC0-48h/MPC, lowest %TMSW), the lowest enrichment of resistant subpopulations. This implies use of the highest possible amikacin dose (limited by toxicity) and post-HD as the best administration schedule.

Reacciones de hipersensibilidad a membranas sintéticas de hemodiálisis / Hypersensitivity reactions to synthetic haemodialysis membranes

La realización de una sesión de hemodiálisis (HD) supone un cierto riesgo de aparición de reacciones adversas de hipersensibilidad, al estar en contacto abundantes cantidades de sangre con diferentes materiales de origen sintético. En HD han sido descritas reacciones de hipersensibilidad al óxido de etileno y a membranas no biocompatibles como el cuproamonio. También se han comunicado casos de hipersensibilidad con membranas biocompatibles como la polisulfona, e incluso con polisulfona asociada a polivinilpirrolidona. En este artículo queremos describir seis casos acontecidos en nuestro servicio de reacciones de hipersensibilidad mayoritariamente temprana a la sesión de HD, caracterizados por mal estado general, desaturación, broncoespasmo e hipotensión arterial, con buena respuesta a la suspensión temporal de la sesión y con reaparición en sesiones posteriores siempre que se utilizase un dializador sintético. Todas tienen en común no haberse dado de nuevo en sucesivas observaciones cuando las sesiones fueron realizadas con una membrana de celulosa (AU)

Undergoing a haemodialysis (HD) session poses a certain risk of hypersensitivity adverse reactions as large quantities of blood are in contact with various synthetic materials. Hypersensitivity reactions to ethylene oxide and non-biocompatible membranes, such as cuprophane, have been described in HD. Cases of hypersensitivity with biocompatible membranes, such as polysulfone, and even polysulfone-polyvinylpyrrolidone, have also been reported. In this article we describe six cases of mostly early-stage hypersensitivity reactions to HD occurring in our department, characterised by malaise, desaturation, bronchospasm and arterial hypotension, with good response to the session's temporary suspension and with reappearance in subsequent sessions that used a synthetic dialyser. No hypersensitivity reactions reappeared in successive observations when the sessions were carried out using a cellulose membrane (AU)

Hypersensitivity reactions to synthetic haemodialysis membranes.

Undergoing a haemodialysis (HD) session poses a certain risk of hypersensitivity adverse reactions as large quantities of blood are in contact with various synthetic materials. Hypersensitivity reactions to ethylene oxide and non-biocompatible membranes, such as cuprophane, have been described in HD. Cases of hypersensitivity with biocompatible membranes, such as polysulfone, and even polysulfone-polyvinylpyrrolidone, have also been reported. In this article we describe six cases of mostly early-stage hypersensitivity reactions to HD occurring in our department, characterised by malaise, desaturation, bronchospasm and arterial hypotension, with good response to the session’s temporary suspension and with reappearance in subsequent sessions that used a synthetic dialyser. No hypersensitivity reactions reappeared in successive observations when the sessions were carried out using a cellulose membrane.

Procinéticos como causantes de nefritis intersticial granulomatosa / Prokinetic agents as a cause of granulomatous interstitial nephritis

Las nefritis intersticiales granulomatosas son entidades con escasa incidencia en la clínica habitual; suelen asociarse con cuadros infecciosos, como la tuberculosis, trastornos inmunológicos, como la sarcoidosis, el lupus eritematoso sistémico o la crioglobulinemia y, más frecuentemente, con el uso de fármacos, sobre todo los antibióticos, los inhibidores de la bomba de protones o los antiinflamatorios no esteroideos; no se ha descrito su asociación con el uso de agentes procinéticos. Presentamos el caso de una paciente de 64 años de edad que desarrolla este cuadro tras la toma de cinitaprida, un estimulador de la motilidad intestinal que ingería sin conocimiento de su médico

Granulomatous interstitial nephritides are uncommon entities in routine clinical practice. These entities are usually associated with infectious diseases such as tuberculosis, or immune diseases, such as sarcoidosis, systemic lupus erythematosus or cryoglobulinemia. However, these diseases are most frequently associated with drug intake, especially antibiotics, proton pump inhibitors and nonsteroidal anti inflammatory drugs. An association with prokinetic agents has not previously been reported. We report the case of a 64-year-old woman who developed acute renal failure with this histological pattern after taking the motility promoter cinitapride without her physician's knowledge

[Prokinetic agents as a cause of granulomatous interstitial nephritis]. / Procinéticos como causantes de nefritis intersticial granulomatosa.

Granulomatous interstitial nephritides are uncommon entities in routine clinical practice. These entities are usually associated with infectious diseases such as tuberculosis, or immune diseases, such as sarcoidosis, systemic lupus erythematosus or cryoglobulinemia. However, these diseases are most frequently associated with drug intake, especially antibiotics, proton pump inhibitors and nonsteroidal anti inflammatory drugs. An association with prokinetic agents has not previously been reported. We report the case of a 64-year-old woman who developed acute renal failure with this histological pattern after taking the motility promoter cinitapride without her physician's knowledge.