Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis.

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.

A multimodal intervention program to control a long-term Acinetobacter baumannii endemic in a tertiary care hospital.

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.

Estudio comparativo de la técnica del ganglio centinela entre los casos de carcinoma de mama multifocal y unifocal / Comparative study of sentinel node biopsy in patients with multifocal breast carcinoma versus in those with unifocal breast carcinoma

Objetivo valorar los resultados de la biopsia del ganglio centinela (BGC) en pacientes con cáncer de mama multifocal (CMMF) en comparación con el unifocal (CMUF). Pacientes y métodos se han realizado e incluido en una base de datos de manera prospectiva 1.535 BGC a pacientes de 9 centros hospitalarios. De ellos 174 presentaban CMMF. Para la BGC se utilizaron coloides de Tc-99m y la vía de administración fue mayoritariamente la profunda, repartiendo el trazador en los diferentes focos. Resultados el índice de detección global fue del 93,8%, sin encontrar diferencias entre ambos grupos (el 94,8% en CMMF frente al 93,4%). La media de GC detectados fue de 1,46, siendo mayor en el grupo CMMF (1,58 frente a 1,45; p=0,036). La localización fue extraaxilar en el 19,6%, más frecuente en el grupo CMMF (el 23,4 frente al 18,9%, no significativo) y más en el territorio de la cadena mamaria interna y en el nivel III axilar. La incidencia de metástasis en los GC biopsiados fue del 27,3%, mayor en el grupo CMMF (el 29,1 frente al 26,7%, no significativo), con una media de GC afectados mayor (0,42 frente a 0,32, no significativo). En la linfadenectomía axilar se identificó afectación de ganglios adicionales en una proporción igual en ambos grupos (29,7%). Conclusionesla BGC parece tener un rendimiento similar en tumores unifocales y multifocales. En tumores multifocales, parece haber un patrón de drenaje linfático específico, con mayor número de GC detectados y probablemente con mayor número de localizaciones de GC extraaxilares (AU)

Objective To evaluate the results for sentinel node biopsy (SNB) in patients with multifocal breast cancer (MBC) in comparison to in those with unifocal breast cancer (UBC). Patients and methods A total of 1535 prospective SNB (174 on patients with MBC) were performed at 9 hospitals. In most patients, Tc-99m album in colloids were injected intraparenchymally into each tumoral focus for SNB. Results The overall identification rate was 93.8%; no differences between groups were observed (94.8% in MBC vs 93.4% in UBC). The mean number of sentinel nodes detected was 1.46, being higher in the MBC group than in the UBC group (1.58 vs 1.45; p=0.036). Extra-axillary sentinel nodes were found in 19.6%; extra-axillary sentinel nodes were more common in the MBC group (23.4% vs 18.9%, ns) and in the internal mammary chain and in level III axillary lymph nodes. The incidence of sentinel node metastasis was 27.3% (29.1% MBC vs 26.7% UBC, ns), and the mean number of positive sentinel nodes was 0.42 in the MBC group vs 0.32 in the UBC group (p=ns). Axillary dissection identified the same rate of positive additional nodes (29.7%) in both groups. Conclusions The diagnostic yield of SNB seems similar in MBC and UBC. In MBC, there appears to be a specific pattern of lymphatic drainage, with a higher number of sentinel nodes detected and probably a higher number of extra-axillary sentinel nodes (AU)

[Comparative study of sentinel node biopsy in patients with multifocal breast carcinoma versus in those with unifocal breast carcinoma.]. / Estudio comparativo de la técnica del ganglio centinela entre los casos de carcinoma de mama multifocal y unifocal.

OBJECTIVE: To evaluate the results for sentinel node biopsy (SNB) in patients with multifocal breast cancer (MBC) in comparison to in those with unifocal breast cancer (UBC). PATIENTS AND METHODS: A total of 1535 prospective SNB (174 on patients with MBC) were performed at 9 hospitals. In most patients, Tc-99m albumin colloids were injected intraparenchymally into each tumoral focus for SNB. RESULTS: The overall identification rate was 93.8%; no differences between groups were observed (94.8% in MBC vs 93.4% in UBC). The mean number of sentinel nodes detected was 1.46, being higher in the MBC group than in the UBC group (1.58 vs 1.45; p=0.036). Extra-axillary sentinel nodes were found in 19.6%; extra-axillary sentinel nodes were more common in the MBC group (23.4% vs 18.9%, ns) and in the internal mammary chain and in level III axillary lymph nodes. The incidence of sentinel node metastasis was 27.3% (29.1% MBC vs 26.7% UBC, ns), and the mean number of positive sentinel nodes was 0.42 in the MBC group vs 0.32 in the UBC group (p=ns). Axillary dissection identified the same rate of positive additional nodes (29.7%) in both groups. CONCLUSIONS: The diagnostic yield of SNB seems similar in MBC and UBC. In MBC, there appears to be a specific pattern of lymphatic drainage, with a higher number of sentinel nodes detected and probably a higher number of extra-axillary sentinel nodes.

Egg handling and storage.

The temperature and relative humidity of storage, as well as the gaseous environment, interact with the fertile egg over time during storage in such a way as to affect the success of incubation either negatively or positively. This interaction occurs both above and below the "physiological zero", at which embryonic metabolism is minimal. This interaction below physiological zero implies that certain physical aspects of the egg must be affected by the environmental conditions. As the eggshell is a relatively fixed component, changes in albumen, shell membranes, cuticle, yolk, or embryo proper must account for these time- and environment-related effects. It is concluded that the major contributor is the albumen, as it is obviously the most dynamic component below physiological zero and is strategically positioned.

Hepatic transport of organic anions in taurolithocholate-induced cholestasis in rats.

The hepatic transport of organic anions was evaluated in taurolithocholate-induced cholestasis in rats. Taurolithocholate (3 mumol per 100 g body wt., i.v.) diminished bile flow by 61%, whereas biliary excretion of bile salts was normalized after 80 min. Tm studies of sulfobromophthalein revealed reduced biliary excretion (-58%) and increased hepatic content of the dye (+75%). Conjugation pattern in bile showed that free sulfobromophthalein was increased by 57%, suggesting that hepatic conjugation was also impaired. This finding, however, could not fully explain the reduced sulfobromophthalein excretion since Tm of its non-metabolizable analog phenol-3,6-dibromophthalein was also decreased (-41%). Compartmental analysis of plasma decay of both dyes revealed that, whereas hepatic uptake was unaltered, canalicular excretion was reduced and reflux from the liver into plasma was increased by the cholestatic agent. Studies on transport of phenol-3,6-dibromophthalein by isolated hepatocytes showed that while uptake was unaffected, the treatment reduced (-36%) the release from hepatocytes preloaded with the dye. Neither glutathione S-transferase activity nor binding of sulfobromophthalein to cytosolic proteins was altered when evaluated in vitro, suggesting that reduced conjugation and enhanced sinusoidal reflux were not due to an irreversible effect of taurolithocholate on this enzyme. In conclusion, taurolithocholate impairs the hepatic transport of organic anions by impairing canalicular excretion and intrahepatic conjugation, as well as by increasing transfer from the liver into the plasma.

Effect of lysosomotropic agents on the taurocholate-stimulated biliary excretion of horseradish peroxidase.

The effects of the lysosomotropic agents chloroquine and leupeptin on the taurocholate-stimulated biliary excretion of horseradish peroxidase (HRP) was studied in bile fistula rats. HRP (0.5 mg/100 g body wt) was injected into the portal vein during taurocholate (0.4 mumol/min/100 g body wt) or saline infusion. HRP appeared in bile showing both an early (approx. 5 min) and a late (approx. 25 min) excretion peak. The late peak, which represented about 95% of the total HRP excreted, is due to transcellular vesicular transport. The early peak is mainly due to paracellular leakage although a rapid vesicular transport also contributes. Taurocholate infusion significantly increased the biliary output of HRP (both peaks) and of the endogenous lysosomal enzyme acid phosphatase. Pretreatment with chloroquine or leupeptin inhibited the taurocholate-stimulated late excretion of HRP into bile, without affecting its early excretion. The lysosomotropic agents did not affect the biliary excretion of bile salts but significantly inhibited the taurocholate-stimulated biliary excretion of acid phosphatase. The results are consistent with a role of lysosomes in the taurocholate-stimulated major transcellular vesicular transport of HRP into bile.