Full characterization of plasmids from Achromobacter ruhlandii isolates recovered from a single patient with cystic fibrosis (CF) / Caracterización completa de plásmidos provenientes de aislamientos de Achromobacter ruhlandii recuperados de un único paciente con fibrosis quística

Abstract In the last decade Achromobacter spp. has been associated with chronic colonizationin patients with cystic fibrosis (CF). Although Achromobacter xylosoxidans is the most frequentspecies recovered within this genus, other species such as A. ruhlandii have also been reportedin these patients. Descriptions of mobile elements are scarce in Achromobacter and none ofthem have been originated in A. ruhlandii. The aim of this study was to report the full char-acterization of a plasmid which was maintained in four clonally related A. ruhlandii isolates.Between 2013 and 2015, nine A. ruhlandii isolates were recovered from a pediatric patientwith CF at a hospital in Buenos Aires. Four selected clonally related isolates were sequencedby Illumina MiSeq, annotated using RAST and manually curated. The presence of a unique plas-mid of 34096-bp and 50 CDS was observed in the four isolates, displaying only 1 nucleotidesubstitution translated into one amino acid change among them. These plasmids have a class 1integron containing the aac-(6)-Ib gene, a mercury resistance operon region and the relE/stbEtoxin/antitoxin system. Plasmids showed 79% similarity and 99% identity with pmatvim-7 fromPseudomonas aeruginosa. This is the first full description and characterization of a plasmid fromA. ruhlandii which was maintained over time.

Resumen Durante la última década, Achromobacter spp. han sido asociadas con la colonización crónica en pacientes con fibrosis quística. Si bien Achromobacter xylosoxidans es la especie más frecuentemente recuperada, otras especies como Achromobacter ruhlandii también fueron reportadas en nuestra región. Sin embargo, pocos reportes se han centrado en la descripción de elementos móviles, y ninguno de ellos los documenta en A. ruhlandii. El objetivo de este estudio fue reportar la caracterización completa de un plásmido conservado en 4 aislamientos clonalmente relacionados de A. ruhlandii. Se recuperaron 9 aislamientos de A. ruhlandii entre 2013 y 2015 de un único paciente con fibrosis quística proveniente de un hospital pediátrico de Buenos Aires, Argentina. Se realizó la secuenciación completa del genoma de los 4 aislamientos seleccionados según el perfil de resistencia antibiótica en un equipo Illumina MiSeq. Estos fueron anotados mediante RAST y curados manualmente. Se detectó la presencia de un solo plásmido de 34.096 pb y 50CDS en los 4 aislamientos, observándose únicamente un cambio nucleotídico traducido en un cambio aminoacídico en un aislamiento. Los plásmidos ensamblados se caracterizaron por presentar un integrón de clase 1 que contenía el gen aac-(6')-Ib, un operón de resistencia a mercurio y el sistema de toxina-antitoxina relE/stbE. Cabe destacar que estos plásmidos poseen un 79% de similitud y un 99% de identidad con el plásmido pmatvim-7 de Pseudomonas aeruginosa. Esta es la primera descripción y caracterización completa de un plásmido proveniente de A. ruhlandii.

Full characterization of plasmids from Achromobacter ruhlandii isolates recovered from a single patient with cystic fibrosis (CF).

In the last decade Achromobacter spp. has been associated with chronic colonization in patients with cystic fibrosis (CF). Although Achromobacter xylosoxidans is the most frequent species recovered within this genus, other species such as A. ruhlandii have also been reported in these patients. Descriptions of mobile elements are scarce in Achromobacter and none of them have been originated in A. ruhlandii. The aim of this study was to report the full characterization of a plasmid which was maintained in four clonally related A. ruhlandii isolates. Between 2013 and 2015, nine A. ruhlandii isolates were recovered from a pediatric patient with CF at a hospital in Buenos Aires. Four selected clonally related isolates were sequenced by Illumina MiSeq, annotated using RAST and manually curated. The presence of a unique plasmid of 34096-bp and 50 CDS was observed in the four isolates, displaying only 1 nucleotide substitution translated into one amino acid change among them. These plasmids have a class 1 integron containing the aac-(6')-Ib gene, a mercury resistance operon region and the relE/stbE toxin/antitoxin system. Plasmids showed 79% similarity and 99% identity with pmatvim-7 from Pseudomonas aeruginosa. This is the first full description and characterization of a plasmid from A. ruhlandii which was maintained over time.

Comparative genomics of ST5 and ST30 methicillin-resistant Staphylococcus aureus sequential isolates recovered from paediatric patients with cystic fibrosis.

Staphylococcus aureus chronic airway infection in patients with cystic fibrosis (CF) allows this pathogen to adapt over time in response to different selection pressures. We have previously shown that the main sequence types related to community-acquired methicillin-resistant S. aureus (MRSA) infections in Argentina - ST5 and ST30 - are also frequently isolated from the sputum of patients with CF, but in these patients they usually display multi-drug antimicrobial resistance. In this study, we sequenced the genomes of MRSA from four paediatric CF patients with the goal of identifying mutations among sequential isolates, especially those possibly related to antimicrobial resistance and virulence, which might contribute to the adaptation of the pathogen in the airways of patients with CF. Our results revealed genetic differences in sequential MRSA strains isolated from patients with CF in both their core and accessory genomes. Although the genetic adaptation of S. aureus was distinct in different hosts, we detected independent mutations in thyA, htrA, rpsJ and gyrA - which are known to have crucial roles in S. aureus virulence and antimicrobial resistance - in isolates recovered from multiple patients. Moreover, we identified allelic variants that were detected in all of the isolates recovered after a certain time point; these non-synonymous mutations were in genes associated with antimicrobial resistance, virulence, iron scavenging and oxidative stress resistance. In conclusion, our results provide evidence of genetic variability among sequential MRSA isolates that could be implicated in the adaptation of these strains during chronic CF airway infection.

Diversity of Achromobacter species recovered from patients with cystic fibrosis, in Argentina / Diversidad de las especies de Achromobacter recuperadas de pacientes con fibrosis quística en Argentina

Abstract Different phenotype-based techniques and molecular tools were used to describe the distribution of different Achromobacter species in patients with cystic fibrosis (CF) in Argentina, and to evaluate their antibiotic resistance profile. Phenotypic identification was performed by conventional biochemical tests, commercial galleries and MALDI-TOF MS. Genetic approaches included the detection of A. xylosoxidans specific marker blaoxa-114, the amplificaron and sequencing of the 16S rRNA gene, nrdA and blaOXA complete sequence, and MLST analysis. Phenotypic approaches, even MALDI-TOF, rendered inconclusive or misleading results. On the contrary, concordant results were achieved with the nrdA sequencing or sequence type (ST) analysis, and the complete blaOXA sequencing, allowing a reliable discrimination of different Achromobacter species. A. xylosoxidans accounted for 63% of Achromobacter infections and A. ruhlandii accounted for 17%. The remaining species corresponded to A. insuavis, A. dolens, A. marplatensis and A. pulmonis. Antimicrobial susceptibilities were determined by the agar dilution method according to CLSI guidelines. Piperacillin, piperacillin/tazobactam and car-bapenems were the most active antibiotics. However, the emergence of carbapenem-resistant isolates was detected. In conclusion, prompt and accurate identification tools were necessary to determine that different Achromobacter species may colonize/infect the airways of patients with CF. Moreover, antimicrobial therapy should be administered based on the susceptibility profile of individual Achromobacter sp. isolates. © 2019 Asociación Argentina de Microbiología. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Resumen Se emplearon diversas técnicas fenotípicas y moleculares para describir la distribución de diferentes especies del género Achromobacter en pacientes con fibrosis quística (FQ) en Argentina, y se evaluó el perfil de resistencia a los antibióticos. Se realizó la identificación fenotípica por pruebas bioquímicas convencionales, galerías comerciales y MALDI-TOF MS. El enfoque genético incluyó la detección del marcador especie-específico de A. xylosoxidans bla[PRESERVECIRC]tu, la amplificación y la secuenciación de los genes ARNr 16S, nrdA y secuencia completa de blaOXA, y el análisis por MLST. Los enfoques fenotípicos, incluso la técnica de MALDI-TOF, proporcionaron resultados no concluyentes o erróneos. Por el contrario, se obtuvieron resultados concordantes entre la secuenciación del gen nrdA o el análisis de secuenciotipos (ST) y la secuenciación completa de blaOXA, lo que permitió una discriminación confiable de las diferentes especies de Achromobacter. A. xylosoxidans representó el 63% de las infecciones por Achromobacter y A. ruhlandii representó el 17%. Las especies restantes correspondieron a A. insuavis, A. dolens, A. marplatensis y A. pulmonis. Se determinó la sensibilidad a antimicrobianos por el método de dilución en agar de acuerdo al CLSI. Los antibióticos más activos fueron piperacilina, piperacilina/tazobactam y carbapenemes. Sin embargo, se detectó la emergencia de aislamientos resistentes a carbapenemes. En conclusión, resultaron necesarias herramientas de identificación rápida y precisas para determinar las diferentes especies del género Achro-mobacter capaces de colonizar/infectar las vías respiratorias de los pacientes con FQ. Asimismo, la terapia antimicrobiana debería llevarse a cabo en función del perfil de sensibilidad de los aislamientos individuales de Achromobacter spp. © 2019 Asociacion Argentina de Microbiología. Publicado por Elsevier Espana, S.L.U. Este es un artículo Open Access bajo la licencia CC BY-NC-ND (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Diversity of Achromobacter species recovered from patients with cystic fibrosis, in Argentina.

Different phenotype-based techniques and molecular tools were used to describe the distribution of different Achromobacter species in patients with cystic fibrosis (CF) in Argentina, and to evaluate their antibiotic resistance profile. Phenotypic identification was performed by conventional biochemical tests, commercial galleries and MALDI-TOF MS. Genetic approaches included the detection of A. xylosoxidans specific marker blaoxa-114, the amplification and sequencing of the 16S rRNA gene, nrdA and blaOXA complete sequence, and MLST analysis. Phenotypic approaches, even MALDI-TOF, rendered inconclusive or misleading results. On the contrary, concordant results were achieved with the nrdA sequencing or sequence type (ST) analysis, and the complete blaOXA sequencing, allowing a reliable discrimination of different Achromobacter species. A. xylosoxidans accounted for 63% of Achromobacter infections and A. ruhlandii accounted for 17%. The remaining species corresponded to A. insuavis, A. dolens, A. marplatensis and A. pulmonis. Antimicrobial susceptibilities were determined by the agar dilution method according to CLSI guidelines. Piperacillin, piperacillin/tazobactam and carbapenems were the most active antibiotics. However, the emergence of carbapenem-resistant isolates was detected. In conclusion, prompt and accurate identification tools were necessary to determine that different Achromobacter species may colonize/infect the airways of patients with CF. Moreover, antimicrobial therapy should be administered based on the susceptibility profile of individual Achromobacter sp. isolates.

Factores de riesgo asociados a exacerbaciones respiratorias en pacientes pediátricos con fibrosis quística / Risk factors associated with pulmonary exacerbations in pediatric patients with cystic fibrosis

Introducción. Los pacientes con fibrosis quística presentan exacerbaciones respiratorias (ER) que requieren tratamiento endovenoso. El objetivo fue determinar los factores de riesgo asociados a ER y obtener porcentaje de pacientes que no recuperaban su función pulmonar previa. Población y métodos. Observacional, de cohorte, retrospectivo. Se revisaron las historias clínicas de los pacientes con fibrosis quística atendidos en el Hospital de Niños Ricardo Gutiérrez durante 2013. Se dividieron en: grupo 1, con ER (criterios de Fuchs), y grupo 2, sin ER. Se registró edad, género, mutación p.F508del, porcentaje del volumen espiratorio forzado en el primer segundo basal, puntaje Z de índice de masa corporal basal, colonización crónica (criterios de Leeds) por Pseudomonas aeruginosa, Staphylococcus aureus meticilino resistente y complejo Burkholderia cepacia, porcentaje de diabetes relacionada con fibrosis quística y recuperación del volumen espiratorio forzado en el primer segundo basal. Resultados. Se incluyeron 117 pacientes. Grupo 1: 50; y grupo 2: 67 pacientes. Se asociaron a las ER: el menor puntaje Z de IMC (RR: 1,45; p=0,002), p.F508del (RR: 3,23; p=0,05) y colonización crónica por el complejo Burkholderia cepacia (RR: 3,69; p = 0,002), Pseudomonas aeruginosa (RR: 1,89; p = 0,01) y Staphylococcus aureus meticilino resistente (RR: 2,32; p = 0,002). El 24 % no recuperó su función pulmonar. Conclusiones. p.F508del, el bajo estado nutricional y la colonización crónica fueron factores de riesgo para exacerbación. Una cuarta parte de los pacientes no recuperó su función pulmonar previa.

Introduction. Cystic fibrosis patients develop pulmonary exacerbations (PEs) that require intravenous treatment. The objective of this study was to determine the risk factors associated with PEs and establish the percentage of patients who failed to recover their lung function. Population and methods. Observational, retrospective, cohort study. The medical records of cystic fibrosis patients seen at Hospital de Niños Ricardo Gutiérrez in 2013 were reviewed. Patients were divided into group 1, with PE (Fuchs criteria), and group 2, without PE. Age, sex, p.F508del mutation, percentage of baseline forced expiratory volume in the first second, baseline body mass index Z-score, chronic Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex colonization (Leeds criteria), percentage of cystic fibrosis-related diabetes, and recovery of baseline forced expiratory volume in the first second were recorded. Results. A total of 117 patients were included. Group 1: 50, group 2: 67 patients. PEs were associated with a lower body mass index Z-score (RR: 1.45; p = 0.002), p.F508del mutation (RR: 3.23; p = 0.05), and chronic Burkholderia cepacia complex (RR: 3.69; p = 0.002), Pseudomonas aeruginosa (RR: 1.89; p = 0.01) and methicillin-resistant Staphylococcus aureus colonization (RR: 2.32; p = 0.002). Twenty-four percent of patients failed to recover their lung function. Conclusions. The presence of the p.F508del mutation, a poor nutritional status, and chronic colonization were the risk factors for exacerbation. A fourth of patients failed to recover their lung function.

Risk factors associated with pulmonary exacerbations in pediatric patients with cystic fibrosis. / Factores de riesgo asociados a exacerbaciones respiratorias en pacientes pediátricos con fibrosis quística.

INTRODUCTION: Cystic fibrosis patients develop pulmonary exacerbations (PEs) that require intravenous treatment. The objective of this study was to determine the risk factors associated with PEs and establish the percentage of patients who failed to recover their lung function. POPULATION AND METHODS: Observational, retrospective, cohort study. The medical records of cystic fibrosis patients seen at Hospital de Niños Ricardo Gutiérrez in 2013 were reviewed. Patients were divided into group 1, with PE (Fuchs criteria), and group 2, without PE. Age, sex, p.F508del mutation, percentage of baseline forced expiratory volume in the first second, baseline body mass index Z-score, chronic Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex colonization (Leeds criteria), percentage of cystic fibrosis-related diabetes, and recovery of baseline forced expiratory volume in the first second were recorded. RESULTS: A total of 117 patients were included. Group 1: 50, group 2: 67 patients. PEs were associated with a lower body mass index Z-score (RR: 1.45; p = 0.002), p.F508del mutation (RR: 3.23; p = 0.05), and chronic Burkholderia cepacia complex (RR: 3.69; p = 0.002), Pseudomonas aeruginosa (RR: 1.89; p = 0.01) and methicillinresistant Staphylococcus aureus colonization (RR: 2.32; p = 0.002). Twenty-four percent of patients failed to recover their lung function. CONCLUSIONS: The presence of the p.F508del mutation, a poor nutritional status, and chronic colonization were the risk factors for exacerbation. A fourth of patients failed to recover their lung function.

Introducción. Los pacientes con fibrosis quística presentan exacerbaciones respiratorias (ER) que requieren tratamiento endovenoso. El objetivo fue determinar los factores de riesgo asociados a ER y obtener porcentaje de pacientes que no recuperaban su función pulmonar previa. Población y métodos. Observacional, de cohorte, retrospectivo. Se revisaron las historias clínicas de los pacientes con fibrosis quística atendidos en el Hospital de Niños Ricardo Gutiérrez durante 2013. Se dividieron en: grupo 1, con ER (criterios de Fuchs), y grupo 2, sin ER. Se registró edad, género, mutación p.F508del, porcentaje del volumen espiratorio forzado en el primer segundo basal, puntaje Z de índice de masa corporal basal, colonización crónica (criterios de Leeds) por Pseudomonas aeruginosa, Staphylococcus aureus meticilino resistente y complejo Burkholderia cepacia, porcentaje de diabetes relacionada con fibrosis quística y recuperación del volumen espiratorio forzado en el primer segundo basal. Resultados. Se incluyeron 117 pacientes. Grupo 1: 50; y grupo 2: 67 pacientes. Se asociaron a las ER: el menor puntaje Z de IMC (RR: 1,45; p = 0,002), p.F508del (RR: 3,23; p = 0,05) y colonización crónica por el complejo Burkholderia cepacia (RR: 3,69; p = 0,002), Pseudomonas aeruginosa (RR: 1,89; p = 0,01) y Staphylococcus aureus meticilino resistente (RR: 2,32; p = 0,002). El 24 % no recuperó su función pulmonar. Conclusiones. p.F508del, el bajo estado nutricional y la colonización crónica fueron factores de riesgo para exacerbación. Una cuarta parte de los pacientes no recuperó su función pulmonar previa.

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in Cystic Fibrosis Patients from Argentina.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization in cystic fibrosis (CF) patients is an increasing problem in many countries. In our Respiratory Center at the Hospital de Niños "Dr. Ricardo Gutiérrez", Buenos Aires, Argentina, the prevalence has climbed from 23% in 1995 up to 32% in 2011. Our objective was to analyze the diversity of MRSA isolates recovered from respiratory samples of CF patients attending our center, characterizing their phenotypes and clonal distribution. Therefore, a prospective study was conducted on all CF patients attending the pediatric Respiratory Center between June 2012 and May 2013 to collect MRSA isolates. Antibiotic susceptibility testing, multilocus sequence typing, pulsed-field gel electrophoresis, spa typing, and agr genotyping were performed on collected isolates. The prevalence of MRSA during this period was 34.2%, and 71.9% of the patients were infected with isolates that carried SCCmec IV. High resistance rates were detected for gentamicin, erythromycin, clindamycin, ciprofloxacin, and rifampicin. Strains related to the community-associated MRSA clones, ST5-IV and ST30-IV, were the most frequently recovered. Remarkably, even though most of the isolates were related to these clones, the rate of multi-resistance shown in CF patients was higher than that reported for the same lineages recovered from other infections in our country.

Draft Genome Sequences of Burkholderia contaminans, a Burkholderia cepacia Complex Species That Is Increasingly Recovered from Cystic Fibrosis Patients.

Burkholderia contaminans belongs to the Burkholderia cepacia complex (BCC), a group of bacteria that are ubiquitous in the environment and capable of infecting the immunocompromised and people with cystic fibrosis. We report here draft genome sequences for the B. contaminans type strain LMG 23361 and an Argentinian cystic fibrosis sputum isolate.

Distribution of allelic variants of the chromosomal gene bla OXA-114-like in Achromobacter xylosoxidans clinical isolates.

Achromobacter xylosoxidans is increasingly being documented in cystic fibrosis patients. The bla(OXA-114) gene has been recognized as a naturally occurring chromosomal gene, exhibiting different allelic variants. In the population under study, the bla(OXA-114)-like gene was found in 19/19 non-epidemiological-related clinical isolates of A. xylosoxidans with ten different alleles including 1 novel OXA-114 variant.

OXA-258 from Achromobacter ruhlandii: a species-specific marker.

A new blaOXA-258 gene is described as a species-specific taxonomic marker for Achromobacter ruhlandii isolates (all recovered from cystic fibrosis patients). Even though OXA-258 differs from OXA-114 variants, isolates could be misidentified as A. xiloxosidans by the amplification of an inner fragment from the OXA-coding gene. A robust identification of A. ruhlandii can be achieved by sequencing this single OXA gene, as well as by a more laborious recently proposed multilocus sequence-typing (MLST) scheme.

Achromobacter xylosoxidans: an emerging pathogen carrying different elements involved in horizontal genetic transfer.

In the last few years, numerous cases of multidrug-resistant Achromobacter xylosoxidans infections have been documented in immunocompromised and cystic fibrosis patients. To gain insights into the molecular mechanisms and mobile elements related to multidrug resistance in this bacterium, we studied 24 non-epidemiological A. xylosoxidans clinical isolates from Argentina. Specific primers for plasmids, transposons, insertion sequences, bla(ampC), intI1, and intI2 genes were used in PCR reactions. The obtained results showed the presence of wide host range IncP plasmids in ten isolates and a high dispersion of class 1 integrons (n = 10) and class 2 integrons (n = 3). Four arrays in the variable region (vr) of class 1 integrons were identified carrying different gene cassettes as the aminoglycoside resistance aac(6')-Ib and aadA1, the trimethoprim resistance dfrA1 and dfrA16, and the ß-lactamase bla(OXA-2). In only one of the class 2 integrons, a vr was amplified that includes sat2-aadA1. The bla(ampC) gene was found in all isolates, confirming its ubiquitous nature. Our results show that A. xylosoxidans clinical isolates contain a rich variety of genetic elements commonly associated with resistance genes and their dissemination. This supports the hypothesis that A. xylosoxidans is becoming a reservoir of horizontal genetic transfer elements commonly involved in spreading antibiotic resistance.

In vitro susceptibility of Achromobacter spp. isolates: comparison of disk diffusion, Etest and agar dilution methods.

In this study, we analysed the antimicrobial susceptibility of 92 strains of Achromobacter spp. isolated from clinical samples to 18 antimicrobial agents. The disk diffusion method and Etest were compared with the agar dilution method, and the breakpoints of susceptibility and resistance for the disk diffusion method for the antimicrobials tested were determined. The most active antibiotics were piperacillin, piperacillin/tazobactam and the carbapenems. By applying the linear least-squares regression method, breakpoints could be established for antibiotics active against this genus such as imipenem, meropenem, ertapenem and trimethoprim/sulfamethoxazole (SXT). Other active antibiotics, such as piperacillin and minocycline, could be tested by the Etest method. The less active antibiotics such as gentamicin, doxycycline and tetracycline could be tested by the disk diffusion method. For the rest of the antimicrobial agents tested, breakpoints could not be established owing to the high percentage of errors and/or the poor linear regression coefficient obtained. Therefore, these antimicrobial agents should be tested by minimal inhibitory concentration determination. In summary, we recommend the following zone diameter breakpoints for resistant and susceptible, respectively: < or = 11 mm and > or = 22 mm for imipenem; < or = 13 mm and > or = 24 mm for meropenem; < or = 17 mm and > or = 24 mm for ertapenem; < or = 15 mm and > or = 21 mm for gentamicin; < or = 27 mm and > or = 28 mm for SXT; < or = 20 mm and > or = 29 mm for tetracycline; and < or = 20 mm and > or = 24 mm for doxycycline.

Nasal immunization with Burkholderia multivorans outer membrane proteins and the mucosal adjuvant adamantylamide dipeptide confers efficient protection against experimental lung infections with B. multivorans and B. cenocepacia.

Chronic lung infection by opportunistic pathogens, such as Pseudomonas aeruginosa and members of the Burkholderia cepacia complex, is a major cause of morbidity and mortality in patients with cystic fibrosis. Outer membrane proteins (OMPs) of gram-negative bacteria are promising vaccine antigen candidates. In this study, we evaluated the immunogenicity, protection, and cross-protection conferred by intranasal vaccination of mice with OMPs from B. multivorans plus the mucosal adjuvant adamantylamide dipeptide (AdDP). Robust mucosal and systemic immune responses were stimulated by vaccination of naive animals with OMPs from B. multivorans and B. cenocepacia plus AdDP. Using a mouse model of chronic pulmonary infection, we observed enhanced clearance of B. multivorans from the lungs of vaccinated animals, which correlated with OMP-specific secretory immunoglobulin A responses. Furthermore, OMP-immunized mice showed rapid resolution of the pulmonary infection with virtually no lung pathology after bacterial challenge with B. multivorans. In addition, we demonstrated that administration of B. multivorans OMP vaccine conferred protection against B. cenocepacia challenge in this mouse infection model, suggesting that OMPs provide cross-protection against the B. cepacia complex. Therefore, we concluded that mucosal immunity to B. multivorans elicited by intranasal vaccination with OMPs plus AdDP could prevent early steps of colonization and infection with B. multivorans and also ameliorate lung tissue damage, while eliciting cross-protection against B. cenocepacia. These results support the notion that therapies leading to increased mucosal immunity in the airways may help patients with cystic fibrosis.

Conservación de catéteres a 4 °C. Influencia sobre los cultivos cuantitativos / Catheter storage at 4 ºC. Influence on quantitative cultures

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Veintiun años de seguimiento clínico-epidemiológico en niños con fibrosis quística en un hospital de pediatría / Twenty one years of clinical-epidemiological following in childrens with cystic fibrosis in a pediatric hospital

Se presenta la experiencia del Centro Respiratorio del Hosp. de Niños R. Gutierrez de Bs. As. en niños con Fibrosis Quística. Los objetivos fueron determinar un patrón epidemiológico y describir las características clínicas, de laboratorio y bacteriológicas en esta población pediátrica. Se siguieron desde 1968 a 1988 [21 años] 414 pacientes con FQ diagnosticados con Test del Sudor positivo. Todos los pacientes presentaron bronquitis crónica, insuficiencia pancreática y/o antecedentes hereditarios positivos. La media del Test de Sudor fue de 72.3479ñ68.26, sin relación directa con el grado de malabsorción con la edad al diagnóstico. Se utilizó para la recolección de los datos una historia clínica computarizable y los datos se analizaron mediante programas estadísticos. La media de edad al diagnóstico fue 3.28 añosñ4.2 años, la edad al ingreso 3.76 añosñ4.55 y la media de edad al fallecimiento 8.55 añosñ7.06. El análisis de la gravedad al ingreso mostró un predominio de las formas graves, que presentaron alteraciones del peso y la talla y estuvieron relacionadas en forma inversa con la supervivencia de los pacientes. El sistema de evaluación de los pacientes al ingreso se realizó mediante el puntaje de Shwachman y mejoró a lo largo del tiempo [sólo 10.9 p.cto. de los niños no evaluados en el período 1982-1988]. No hubo diferencias en la evolución según sexo. En las familias con un sólo niño afectado la mortalidad fue más alta, 57.5 p.cto. y tan sólo se siguen en la actualidad 19.8 p.cto. de los pacientes; los grupos familiares más numerosos presentaron una mejor supervivencia. La tasa de mortalidad ponderada global fue de 8.1 p.cto. con diferencias estadísticamente significativas entre los períodos estudiados, 10.2 p.cto., 9.5 p.cto., 6.0 p.cto. [p<0.05]. El análisis de la supervivencia mostró que el 50 p.cto. de los niños seguían vivos entre 6 y 7 años después de su ingreso, el 33 p.cto. a los 10 años y sólo el 15 p.cto. a los 15 años. La supervivencia mejoró en los niños que ingresaron en los últimos años [1982-1988] se pudo -si bien los porcentajes son variables- afirmar que los niños más pequeños al ingreso [menores de 1 año] tuvieron menores tasas de supervivencia... (TRUNCADO)

Veintiun años de seguimiento clínico-epidemiológico en niños con fibrosis quística en un hospital de pediatría / Twenty one years of clinical-epidemiological following in childrens with cystic fibrosis in a pediatric hospital

Se presenta la experiencia del Centro Respiratorio del Hosp. de Niños R. Gutierrez de Bs. As. en niños con Fibrosis Quística. Los objetivos fueron determinar un patrón epidemiológico y describir las características clínicas, de laboratorio y bacteriológicas en esta población pediátrica. Se siguieron desde 1968 a 1988 [21 años] 414 pacientes con FQ diagnosticados con Test del Sudor positivo. Todos los pacientes presentaron bronquitis crónica, insuficiencia pancreática y/o antecedentes hereditarios positivos. La media del Test de Sudor fue de 72.3479ñ68.26, sin relación directa con el grado de malabsorción con la edad al diagnóstico. Se utilizó para la recolección de los datos una historia clínica computarizable y los datos se analizaron mediante programas estadísticos. La media de edad al diagnóstico fue 3.28 añosñ4.2 años, la edad al ingreso 3.76 añosñ4.55 y la media de edad al fallecimiento 8.55 añosñ7.06. El análisis de la gravedad al ingreso mostró un predominio de las formas graves, que presentaron alteraciones del peso y la talla y estuvieron relacionadas en forma inversa con la supervivencia de los pacientes. El sistema de evaluación de los pacientes al ingreso se realizó mediante el puntaje de Shwachman y mejoró a lo largo del tiempo [sólo 10.9 p.cto. de los niños no evaluados en el período 1982-1988]. No hubo diferencias en la evolución según sexo. En las familias con un sólo niño afectado la mortalidad fue más alta, 57.5 p.cto. y tan sólo se siguen en la actualidad 19.8 p.cto. de los pacientes; los grupos familiares más numerosos presentaron una mejor supervivencia. La tasa de mortalidad ponderada global fue de 8.1 p.cto. con diferencias estadísticamente significativas entre los períodos estudiados, 10.2 p.cto., 9.5 p.cto., 6.0 p.cto. [p<0.05]. El análisis de la supervivencia mostró que el 50 p.cto. de los niños seguían vivos entre 6 y 7 años después de su ingreso, el 33 p.cto. a los 10 años y sólo el 15 p.cto. a los 15 años. La supervivencia mejoró en los niños que ingresaron en los últimos años [1982-1988] se pudo -si bien los porcentajes son variables- afirmar que los niños más pequeños al ingreso [menores de 1 año] tuvieron menores tasas de supervivencia... (TRUNCADO)(AU)