Whole-genome analysis and description of an outbreak due to carbapenem-resistant Ochrobactrum anthropi causing pseudo-bacteraemias.

Ochrobactrum anthropi, a rare human pathogen, has been isolated predominantly from patients with catheter-related bacteraemia and rarely from other infections. In 2016, six cases of pseudo-bacteraemia caused by carbapenem-resistant O. anthropi isolates were recovered from an Argentinian hospital. The resistant phenotype exposed by the isolates caught our attention and led to an extensive epidemiologic investigation. Here we describe the characterization of a carbapenem-resistant O. anthropi outbreak whose probable cause was by contaminated collection tubes. The genome analysis of one strain revealed the presence of various resistant determinants. Among them, a metal-dependent hydrolase of the ß-lactamase superfamily I, phnP, was found. Lately the recovery of unusual multidrug-resistant pathogens in the clinical setting has increased, thus emphasizing the need to implement standardized infection control practice and epidemiologic investigation to identify the real cause of hospital outbreaks.

Molecular characterization of KPC-2-positive Klebsiella pneumoniae isolates from a neurosurgical centre in Argentina.

Carbapenem-resistant Enterobacteriaceae is a growing concern worldwide. Klebsiella pneumoniae is an important nosocomial pathogen with a high capacity for nosocomial spread. We described the occurrence of plasmid-encoded KPC-2-harbouring K. pneumoniae isolates recovered from a neurosurgical centre in Argentina. The blaKPC-2 gene was surrounded by ISkpn6 and ISkpn7.

First case of bacteraemia due to Acinetobacter schindleri harbouring blaNDM-1 in an immunocompromised patient.

Clinically significant NDM-1-producing Acinetobacter schindleri has not yet been described in the literature. We report the first case of bacteraemia due to an A. schindleri strain harbouring blaNDM-1 recovered from an immunocompromised patient. Our report reinforces the fact that NDM-1 can easily be acquired by Acinetobacter species.

Widespread dispersion of the resistance element tet(B)::ISCR2 in XDR Acinetobacter baumannii isolates.

Acinetobacter baumannii is a significant nosocomial pathogen often associated with extreme drug resistance (XDR). In Argentina, isolates of A. baumannii resistant to tetracyclines have accounted for more than 40% of drug-resistant isolates in some hospitals. We have previously reported the dispersion of the tet(B) resistance element associated with the ISCR2 transposase in epidemiologically unrelated A. baumannii isolates recovered from 1983 to 2011. This study extends this surveillance to 77 recent (2009-2013) XDR A. baumannii isolates with different levels of minocycline susceptibility. Isolates were examined by a pan-PCR assay, which showed six different amplification patterns, and specific PCRs were used for the confirmation of the the ΔISCR2-tet(B)-tet(R)-ISCR2 element. The tet(B) gene was present in 66 isolates and the ISCR2 element in 68 isolates; the tet(B) gene was associated with ISCR2 in all tet(B)-positive isolates. We conclude that this element is widespread in XDR A. baumannii isolates from Argentina and could be responsible for the emergence of tetracycline resistance in recent years.

Genetic Variability of AdeRS Two-Component System Associated with Tigecycline Resistance in XDR-Acinetobacter baumannii Isolates.

The emergence of tigecycline resistance has increased in the last years. Although tigecycline-resistant Acinetobacter baumannii isolates were described all over the world, few reports regarding the molecular basis of this resistance are available. It has been recognized that the overexpression of AdeABC efflux pump is related to the tigecycline-resistant phenotype. In 37 clinical A. baumannii isolates we first determined the tigecycline-resistant phenotype and then, within a selected group, we analyzed the sequence of the adeRS operon, which is involved in the expression of the AdeABC efflux pump. Nucleotide sequence analysis of adeR and adeS showed the presence of 5 and 16 alleles, respectively. These results expose a high genetic variability in both genes, the adeS gene being more susceptible to genetic variation. The presence of 2 AdeR and 2 AdeS new variants were reported. Two of the new AdeRS variants were present in the intermediate and the resistant tigecycline A. baumannii isolates, suggesting a putative role in the development of the observed phenotype. More studies need to be addressed to determine the role of the genetic variability observed in the adeRS operon.

Preferential carriage of class 2 integrons in Acinetobacter baumannii CC113 and novel singletons.

Our understanding of the distribution of integrons associated with multidrug resistance in Acinetobacter baumannii isolates around the world remains incomplete. The association between the class 1 and 2 integron A. baumannii-positive isolates (n = 60), recovered since 1982 from 11 Argentinean hospitals, and the circulating lineages, was investigated. While class 2 integrons were highly significantly associated with clonal lineage CC113B/CC79P (P = 0·009) and novel singletons (P = 0·001), class 1 integrons were found not to be associated with CC109B/CC1P or other lineages. The study reveals a differential distribution of class 2 integrons in lineages, and suggests that the prevalence of intI2 in Argentina is related to the emergence of novel singletons in recent years and to the abundance of CC113B/CC79P, which has been the local dominant lineage for several decades.

[Assessing quality in the process of using hazardous drugs-prescription and preparation]. / Evaluación de la calidad en el proceso de utilización de fármacos peligrosos: prescripción y preparación.

OBJECTIVE: To evaluate the quality of cytotoxic drug prescription based on the results of an interventional pharmaceutical program and the quality of the final product based on quality-control prior to preparation. STUDY PERIOD: July 2002-March 2003. Hazardous drug prescription was evaluated through an analysis of pharmaceutical interventions during therapeutical monitoring. Depending on repercussion in patients, they were classified in three categories (treatment optimization, resource optimization or criteria unification). Data obtained from manual quality control programs prior to hazardous drug preparation were evaluated. RESULTS: Sixty-four interventions were made (9 interventions per 100 prescriptions): 55% were classified as treatment optimization, 28% as resource optimization and 17% as criteria unification. A total of 66% of the interventions focused on treatment optimization were caused by prescription errors. Ninety-seven per cent were accepted. Out of 2,074 preparations, 1,951 were evaluated (94.9%). A 5.1% of non-evaluated preparations were due to a lack of registration and 0.8% to violations in the established protocol. CONCLUSIONS: Results of the interventional Pharmaceutical program show that an assisted prescription system is necessary, not only to detect prescription errors but also to prevent them. Manual controls in different stages of the process are useful and they should be complementary to other more reliable dosification controls.

Evaluación de la calidad en el proceso de utilización de fármacos peligrosos: prescripción y preparación / Assesing quality in the process of using hazarous drugs-prescription and preparation

Objetivo: Evaluar la calidad de la prescripción de citostáticos a partir de los resultados obtenidos en el programa de intervenciones farmacéuticas y la calidad de la preparación mediante un control de calidad realizado de forma previa a la elaboración. Métodos: Periodo de estudio: julio 2002-marzo 2003. Prescripción: se evaluó mediante el análisis de las intervenciones farmacéuticas realizadas durante la monitorización terapéutica de los tratamientos con fármacos peligrosos. Para su evaluación se clasificaron en 3 categorías según la repercusión en el paciente (optimización del tratamiento, optimización de recursos, unificación de criterios). Preparación: se evaluaron los registros obtenidos en el programa de control de calidad manual, previo a la elaboración de las preparaciones de fármacos peligrosos. Resultados: Se realizaron 64 intervenciones (9 intervenciones por cada 100 prescripciones): 55% fueron para optimizar el tratamiento, 28% para optimizar recursos, 17% para unificar criterios. De las intervenciones enfocadas a optimizar el tratamiento, un 66% fueron por errores de prescripción. El 97% de las intervenciones fueron aceptadas. De las 2.074 preparaciones realizadas se evaluaron 1.951 (94,9%). De las preparaciones no evaluadas, un 5,1% fue por falta de registro y un 0,8% por falta de cumplimiento del protocolo establecido. Conclusiones: Los resultados obtenidos en el programa de intervenciones farmacéuticas evidencian la necesidad de implantar un sistema de prescripción asistida, que nos permitirá actuar no sólo en la detección de errores de prescripción, sino en su prevención. La realización de controles manuales en diferentes puntos del proceso de elaboración resulta útil y debería ser una medida complementaria a otros controles más fiables de dosificación

Objective: To evaluate the quality of cytotoxic drug prescription based on the results of an interventional pharmaceutical program and the quality of the final product based on quality-control prior to preparation. Methods: Study period: July 2002-March 2003. Hazardous drug prescription was evaluated through an analysis of pharmaceutical interventions during therapeutical monitoring. Depending on repercussion in patients, they were classified in three categories (treatment optimization, resource optimization or criteria unification). Data obtained from manual quality-control programs prior to hazardous drug preparation were evaluated. Results: Sixty-four interventions were made (9 interventions per 100 prescriptions): 55% were classified as treatment optimization, 28% as resource optimization and 17% as criteria unification. A total of 66% of the interventions focused on treatment optimization were caused by prescription errors. Ninety-seven per cent were accepted. Out of 2,074 preparations, 1,951 were evaluated (94.9%). A 5.1% of non-evaluated preparations were due to a lack of registration and 0.8% to violations in the established protocol. Conclusions: Results of the interventional pharmaceutical program show that an assisted prescription system is necessary, not only to detect prescription errors but also to prevent them. Manual controls in different stages of the process are useful and they should be complementary to other more reliable dosification controls

Experiencia y valoración de la rotación de un farmacéutico residente por el servicio de pediatría / Experience in and assessment of the rotation of a pharmacy resident by the Pediatric Service

Introducción. La incorporación de un farmacéutico al equipo pediátrico de un hospital puede ayudar a la toma de decisiones en la terapéutica del niño. El objetivo de este estudio fue la valoración del resultado de la rotación de un farmacéutico residente por el Servicio de Pediatría; esta valoración se realizó mediante el registro y clasificación del tipo de intervenciones farmacéuticas efectuadas. Material y método. Se llevó a cabo un estudio prospectivo y descriptivo. Las actividades del farmacéutico en el Servicio de Pediatría derivadas de su incorporación al pase de visita con los médicos fueron: ayudar a la valoración del tratamiento adecuado para cada paciente, realizar hojas de seguimiento farmacoterapéutico para cada niño, revisar las prescripciones médicas así como sus transcripciones a la hoja de enfermería, asegurando la correcta administración de los tratamientos. También se efectuaron notas informativas y se creó un sistema de recogida de datos para la correcta clasificación y valoración de las intervenciones farmacéuticas llevadas a cabo. Resultados. Durante el periodo de estudio, (agosto-octubre de 2003) se realizaron 90 intervenciones farmacéuticas, distribuidas en un 53 por ciento como consultas farmacoterapéuticas, en un 12 por ciento como recomendaciones farmacéuticas, y en un 35 por ciento como detección de errores de medicación. Conclusiones. La incorporación de un farmacéutico al equipo médico que atiende al paciente pediátrico puede ayudar a mejorar su calidad asistencial, así como contribuir a un uso adecuado y racional de su terapéutica mientras dura el ingreso e, incluso, en el tratamiento durante el alta, complementando la información a los padres si es necesario (AU)

[Detection and classification of medication errors at Joan XXIII University Hospital]. / Detección y clasificación de errores de medicación en el Hospital Universitari Joan XXIII.

INTRODUCTION: Medication errors are multifactorial and multidisciplinary, and may originate in processes such as drug prescription, transcription, dispensation, preparation and administration. The goal of this work was to measure the incidence of detectable medication errors that arise within a unit dose drug distribution and control system, from drug prescription to drug administration, by means of an observational method confined to the Pharmacy Department, as well as a voluntary, anonymous report system. The acceptance of this voluntary report system's implementation was also assessed. MATERIAL AND METHODS: A prospective descriptive study was conducted. Data collection was performed at the Pharmacy Department from a review of prescribed medical orders, a review of pharmaceutical transcriptions, a review of dispensed medication and a review of medication returned in unit dose medication carts. A voluntary, anonymous report system centralized in the Pharmacy Department was also set up to detect medication errors. RESULTS: Prescription errors were the most frequent (1.12%), closely followed by dispensation errors (1.04%). Transcription errors (0.42%) and administration errors (0.69%) had the lowest overall incidence. Voluntary report involved only 4.25% of all detected errors, whereas unit dose medication cart review contributed the most to error detection. CONCLUSIONS: Recognizing the incidence and types of medication errors that occur in a health-care setting allows us to analyze their causes and effect changes in different stages of the process in order to ensure maximal patient safety.

Measurement of matrix metalloproteinases and tissue inhibitors of metalloproteinases in blood and tissues. Clinical and experimental applications.

The balance between production and activation of MMPs and their inhibition by TIMPs is a crucial aspect of cancer invasion and metastasis. On the basis of the concept that MMPs synthesized in tissues seep into the bloodstream, we have examined MMP levels in the plasma of patients with cancer. In colorectal, breast, prostate, and bladder cancer, most patients with aggressive disease have increased plasma levels of gelatinase B. In patients with advanced colorectal cancer, high levels of either gelatinase B or TIMP complex were associated with shortened survival. We propose that these assays may be clinically useful in characterizing metastatic potential in selected kinds of cancer. In rheumatoid arthritis and systemic lupus erythematosus (SLE), serum and plasma levels of stromelysin-1 were approximately 3-5-fold increased. Fluctuating serum stromelysin-1 levels in SLE did not correspond with change in disease activity. In SLE, stromelysin-1 may be a component of the chronic tissue repair process rather than being responsible for inciting tissue damage. On the basis of these observations, we conclude that measurement of plasma/serum MMP and TIMP levels may provide important data for selecting and following patients considered for treatment with drugs that interfere with MMP activity.