Mycoplasma-induced minimally conscious state

Mycoplasma pneumoniae (M. pneumoniae) frequently causes community-acquired respiratory tract infection and often presents as atypical pneumonia. Following airborne infection and a long incubation period, affected patients mostly suffer from mild or even asymptomatic and self-limiting disease. In particular in school-aged children, M. pneumoniae is associated with a wide range of extrapulmonary manifestations including central nervous system (CNS) disease. In contrast to children, severe CNS manifestations are rarely observed in adults. We report a case of a 37 year-old previously healthy immunocompetent adult with fulminant M. pneumoniae-induced progressive encephalomyelitis who was initially able to walk to the emergency department. A few hours later, she required controlled mechanical ventilation for ascending transverse spinal cord syndrome, including complete lower extremity paraplegia. Severe M. pneumoniae-induced encephalomyelitis was postulated, and antimicrobial, anti-inflammatory and immunosuppressive therapy was applied on the intensive care unit. Despite early and targeted therapy using four different immunosuppressive strategies, clinical success was limited. In our patient, locked-in syndrome developed followed by persistent minimally conscious state. The neurological status was unchanged until day 230 of follow-up. Our case underlines that severe M. pneumoniae- related encephalomyelitis must not only be considered in children, but also in adults. Moreover, it can be fulminant and fatal in adults. Our case enhances the debate for an optimal antimicrobial agent with activity beyond the blood-brain barrier. Furthermore, it may underline the difficulty in clinical decision making regarding early antimicrobial treatment in M. pneumoniae disease, which is commonly self-limited.

Sickle cell disease: Its signs, symptoms and varied manifestations

Seventy-five sickle cell patients, age 3-36 years from Houston, Texas, participated in the research study to investigate sickle cell manifestations, conducted between November 1989 and August 1990. All the participants were blacks. There were 35 females and 39 males among the participants in this research study. One of the participants did not document the gender.^ The sickle cell history questionnaire was administered to the participants. Data collected from this study were statistically analyzed using frequencies, percentages, crosstabulations and chi-squares.^ Regular source of health care influences the time of diagnosis of sickle cell disease. Early diagnosis of sickle cell disease with proper care and management will reduce the morbidity and mortality rate of the disease.^ Fevers, bacterial infection, pneumoniae, anemiae, pains, ulcers and cardiovascular problems are common causes of hospitalizations. The average length of stay in the hospital on admission were higher among the sickle cell patients than their family members who themselves did not have sickle cell disease. ^

Burden of invasive pneumococcal disease in Harris County, Texas (2003--2010) and the implication for enhanced public health surveillance of isolates

Invasive pneumococcal disease (IPD) causes significant health burden in the US, is responsible for the majority of bacterial meningitis, and causes more deaths than any other vaccine preventable bacterial disease in the US. The estimated National IPD rate is 14.3 cases per 100,000 population with a case-fatality rate of 1.5 cases per 100,000 population. Although cases of IPD are routinely reported to the local health department in Harris County Texas, the incidence (IR) and case-fatality (CFR) rates have not been reported. Additionally, it is important to know which serotypes of S. pneumoniae are circulating in Harris County Texas and to determine if ‘replacement disease’ is occurring. ^ This study reported incidence and case-fatality rates from 2003 to 2009, and described the trends in IPD, including the IPD serotypes circulating in Harris County Texas during the study period, particularly in 2008 and 2010. Annual incidence rates were calculated and reported for 2003 to 2009, using complete surveillance-year data. ^ Geographic information system (GIS) software was used to create a series of maps of the data reported during the study period. Cluster and outlier analysis and hot spot analysis were conducted using both case counts by census tract and disease rate by census tract. ^ IPD age- and race-adjusted IR for Harris County Texas and their 95% confidence intervals (CIs) were 1.40 (95% CI 1.0, 1.8), 1.71 (95% CI 1.24, 2.17), 3.13 (95% CI 2.48, 3.78), 3.08 (95% CI 2.43, 3.74), 5.61 (95% CI 4.79, 6.43), 8.11 (95% CI 7.11, 9.1), and 7.65 (95% CI 6.69, 8.61) for the years 2003 to 2009, respectively (rates were age- and race-adjusted to each year's midyear US population estimates). A Poisson regression model demonstrated a statistically significant increasing trend of about 32 percent per year in the IPD rates over the course of the study period. IPD age- and race-adjusted case-fatality rates (CFR) for Harris County Texas were also calculated and reported. A Poisson regression model demonstrated a statistically significant increasing trend of about 26 percent per year in the IPD case-fatality rates from 2003 through 2009. A logistic regression model associated the risk of dying from IPD to alcohol abuse (OR 4.69, 95% CI 2.57, 8.56) and to meningitis (OR 2.42, 95% CI 1.46, 4.03). ^ The prevalence of non-vaccine serotypes (NVT) among IPD cases with serotyped isolates was 98.2 percent. In 2008, the year with the sample more geographically representative of all areas of Harris County Texas, the prevalence was 96 percent. Given these findings, it is reasonable to conclude that ‘replacement disease’ is occurring in Harris County Texas, meaning that, the majority of IPD is caused by serotypes not included in the PCV7 vaccine. Also in conclusion, IPD rates increased during the study period in Harris County Texas.^

Pathogenesis of antibiotic-associated diarrhea (AAD)---a systematic review

A common complication of antibiotic use is the development of diarrheal illness. The pathogenesis of antibiotic associated diarrhea (AAD) may be mediated through alteration of intestinal microbiota, overgrowth of opportunistic pathogens, and direct drug toxicity on the gut. Alterations in the intestinal microbiota result in metabolic imbalances, loss of colonization resistance and in turn allow proliferation of opportunistic pathogens. Currently less than 33% of AAD cases can be attributable to Clostridium difficile leaving a large number of cases undiagnosed and poorly treated. Although the pathogenesis of Clostridium difficile infection (CDI) has been well documented, the role of other putative microbial etiologies (Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida species) and their pathogenic mechanisms in AAD has been unclear. This review provides a comprehensive and systematic approach to the existing data on AAD and includes concise descriptions of the pathogenesis of CDI and non-CDI AAD in the form of figures.^

Significado de la Leucopenia en pacientes con bacteriemia

Objetivo: Evaluar parámetros clínicos, bacteriológicos y morbimortalidad de las bacteriemias en pacientes con leucopenia (<4.000 leucocitos/mm 3) y compararlas con bacteriemias con leucocitosis (>12.000/mm3). Material y métodos: Estudio protocolizado, descriptivo y observacional en pacientes con 2 o más hemocultivos positivos para el mismo germen hospitalizados en un servicio de clínica médica desde Marzo de 1989 a Agosto de 2007. Resultados: Se identificaron 728 bacteriemias, 94 (12,91%) con leucopenia (Grupo A) y 407 (55,90%) con leucocitosis (Grupo B). La edad media fue de 55,57 años (DS±16,93) en A y de 58,40 años (DS±17,34) en B. No hubo diferencias en la permanencia media: 19,59 días (DS±18,67) en A vs 21,21 (DS±19,53) en B ni en el sexo masculino (65,96 vs 57,25%)(pNS). La adquisición nosocomial (57,44 vs 40,29%) y el foco desconocido (25,53 vs 9,33%) y abdominal (17,14 vs 9,21%) fueron más frecuentes en A (p<0.01). La comorbilidad mayor (82,98 vs 41,24%), neoplasias (45,74 vs 12,84%) y la inmunosupresión (31,91 vs 6,17%) fueron significativas en A (p<0.01). La anemia (86,17 vs 62,40%) y la trombocitopenia (84,04 vs 25,06%) predominaron en A (p<0.01). Los Bacilos Gram Negativos predominaron en A (61,71 vs 37,83%)(p<0.01) [Klebsiella (17,02 vs 9,82%) y Pseudomonas (10,64 vs 1,47%) las más frecuentes (p<0.05)] y en B fue más frecuente S. aureus (31,69 vs 11,70%)(p<0.01). La mortalidad fue de 39,36% en A y 25,30% en B (p=0.006) y se asoció en el grupo A a mayor mortalidad en las primeras 24 horas (32,43 vs 16,50%), inmunosupresión (27,02 vs 7,76%), neumococcemias (52,94 vs 23,07%), sepsis (100 vs 88,35%) y trombocitopenia (75,67 vs 30,09%)(p<0,01).- Conclusiones: Las bacteriemias en pacientes leucopénicos comparadas con aquellas con leucocitosis se asociaron significativamente a adquisición nosocomial, foco desconocido y abdominal, presencia de comorbilidad mayor, neoplasias e inmunosupresión, a bacteriemias por Klebsiella y Pseudomonas y a significativa mayor mortalidad. Palabras claves: leucopenia, bacteriemias

Bacteriemias en Mayores de 65 años : resultados de un análisis comparativo

Objetivos: Evaluar parámetros clínicos, bacteriológicos y morbimortalidad en pacientes mayores de 65 años con bacteriemia (Grupo A) y compararlos con aquellas ocurridas en menores de 65 años (grupo B) hospitalizados en un servicio de clínica médica. Material y métodos: Estudio protocolizado, descriptivo y observacional, desde 1989-2006. Criterios de inclusión: dos o más hemocultivos positivos. Análisis estadístico con Epi Info 6.4 . Resultados: Se identificaron 668 bacteriemias: 258 (38,6%) en A y 410 (61,4%) en B. La edad media fue de 74,2 años (DS±7.01) y de 47,2 años (DS±13.7) respectivamente. No hubo diferencias en la permanencia media: 19,1 días (DS±17.07) en A y 19,9 (DS±18,1) en B, ni en el origen nosocomial (40,7 vs 44%). Los focos pulmonar (31 vs 21,2%)(p<0,008) y urinario (27 vs 18,8%)(p=0.017) fue más frecuentes en A. La fiebre >de 38 ºC fue menos frecuente en A (83,8 vs 90,9%)(p=0.0068), mientras que la hipotensión arterial (40,8 vs 32,2%)(p=0.03), oliguria (41,7 vs 30,9%)(p=0.005) y encefalopatía (54,5 vs 39,4%)(p=0.00014) fueron mas comunes en A. Los bacilos gram negativos predominaron en A (46 vs 37%)(p<0.01) con diferencias entre A.baumani (9,16 vs 4,6%) y E.coli (54,1 vs 42,7%)(p<0.05) y en B fueron más frecuentes por S.aureus MS (34.39 vs 24,63)(p=0.01). El shock séptico (33,9 vs 22,4%) y nuevas insuficiencias de órganos (31,1 vs 20,1%) prevalecieron en A (p<0,001). La mortalidad fue de 34,49% para A y de 23,41% para B (p=0,018) Conclusiones: Las bacteriemias en pacientes internados mayores de 65 años comparadas con las ocurridas en pacientes. de menor edad, se caracterizaron significativamente por tener predominio del foco pulmonar y urinario, de hipotensión arterial, oliguria y encefalopatía, de bacteriemia por BGN, principalmente A. baumanii y E. coli; mayor desarrollo de shock séptico, menor frecuencia de fiebre >38°C y de bacteriemia por MSS A, y significativa mayor mortalidad.

Cetoacidosis inducida por corticoides y gatifloxacina en una mujer joven no diabética

Objetivo: Comunicar un caso de cetoacidosis inducida por corticoides y gatifloxacina y discutir los mecanismos de esta inusual y seria complicación. Caso clínico: Mujer de 32 años, ingresa por neumonía adquirida en la comunidad de 5 días de evolución. Antecedentes: AR probable diagnosticada 4 meses antes tratada con metotrexate y corticoides intermitente. Examen físico: regular estado general, IMC 21, Tº 38ºC, FR 32/min, derrame pleural derecho, FC 96/min, PA 110/70, artralgias sin artritis. Exámenes complementarios: Hto 23%, GB 16300/mm3, VSG 96mm/1ºh, glucemia 0.90mg/dl, función hepática y amilasa normales, uremia 1.19g/l, creatinina 19mg/l. Hemocultivos (2) y esputo positivos para Neumococo penicilina-sensible. La neumonía responde a gatifloxacina. Deteriora la función renal hasta la anuria con acidosis metabólica. Se interpreta como glomerulonefritis lúpica rápidamente progresiva por proteinuria de 2g/24hs, FR (+) 1/1280, FAN (+) 1/320 homogéneo, Anti ADN (+) , complemento bajo: C3 29.4mg/dl y C4 10mg/dl, Ac anti Ro, La, Scl70, RNP y anticardiolipinas positivos. Se indica metilprednisolona EV (3 bolos 1g), complicándose con hiperglucemias de >6 g/l y cetoacidosis con cetonuria (+); Ac anti ICA y antiGAD negativos con HbA1C 5.2%. Es tratada en UTI (insulina y hemodiálisis). La paciente mejora, se desciende la dosis de corticoides, con normalización de la glucemia sin tratamiento hipoglucemiante. Comentarios 1) La presencia de HbA1C nomal, Ac anti ICA y GAD negativos permite descartar con razonable grado de certeza una diabetes tipo1 asociada al lupus. 2) El desarrollo de la cetoacidosis durante el tratamiento con corticoides y gatifloxacina y su resolución posterior avalan el rol etiológico de los mismos. 3) La cetoacidosis puede explicarse por estimulación de la gluconeogénesis y la insulinoresistencia a nivel de receptor y post-receptor generada por los fármacos potenciado por el estado inflamatorio relacionado con el lupus y la sepsis.

Bacteriemias por Pseudomonas Aeruginosa : análisis comparativo

Objetivos: Analizar características clínicas y morbimortalidad de las bacteriemias por Pseudomonas aeruginosa comparadas con Klebsiella spp en pacientes hospitalizados en un Servicio de Clínica Médica de adultos. Material y métodos: Estudio protocolizado, descriptivo, observacional de 15 años de duración. Criterio de inclusión: 2 o más hemocultivos positivos para el germen. Los datos fueron procesados en EPI Info 6.04. El criterio de significación se estableció para un error alfa menor del 5%. Resultados: Se detectaron en el período de estudio 282 bacteriemias por bacilos gram negativos de las cuales 19 fueron por Pseudomonas aeruginosa (6.7%) y 76 por Klebsiella (26.9%). No se encontraron diferencias significativas entre ambas en cuanto a edad media [53.9 años (DS±17.9 ) vs 58.7 años (DS±15.2)], sexo (femenino: 26.3 vs 38.2%) ni complicaciones (77.8 vs 77.3%). La presencia de neutropenia (52.6 vs 9.2%)(p<0.0001), comorbilidad mayor (94.7 vs 68.4%)(p<0.05), neoplasias (47.4 vs 22.4%)(p<0.05), uso de corticoides (21.1 vs 3.9%)(p<0.05), e inmunosupresores (31.6 vs 7.9%)(p<0.01), trombocitopenia (77.7 vs 49.3%) (p<0.05) y leucopenia (52.6 vs 21.3%)(p<0.01) fueron más frecuentes en las bacteriemias por P. aeruginosa. Resultó más frecuente la hipoalbuminemia (88.5 vs 37.5%)(p<0.001) en las bacteriemias por Klebsiella spp. No se encontraron diferencias significativas en cuanto a puerta de entrada conocida (78.9 vs 77.6%), anemia (84.2 vs 71.2%), complicaciones infecciosas (84.2 vs 73.7%), descompensación de comórbidas (55.6 vs 51.3%) y encefalopatía (36.8 vs 57.9%)(pNS). La mortalidad precoz (dentro de los 7 días) fue significativamente mayor en el grupo de las bacteriemias por P.aeruginosa (57.1 vs 12%) (p<0.01), sin diferencias en la mortalidad global (36.8 vs 32.9%) (pNS). Conclusiones: Las bacteriemias por P.aeruginosa comparadas con las producidas por Klebsiella spp. se asociaron significativamente a mayor frecuencia de neoplasias, leucopenia, trombocitopenia y neutropenia, comorbilidad mayor, uso de corticoides e inmunosupresores, y a mortalidad precoz.

Specific cleavage of chromosomal and plasmid DNA strands in gram-positive and gram-negative bacteria can be detected with nucleotide resolution

A sensitive and precise in vitro technique for detecting DNA strand discontinuities produced in vivo has been developed. The procedure, a form of runoff DNA synthesis on molecules released from lysed bacterial cells, mapped precisely the position of cleavage of the plasmid pMV158 leading strand origin in Streptococcus pneumoniae and the site of strand scission, nic, at the transfer origins of F and the F-like plasmid R1 in Escherichia coli. When high frequency of recombination strains of E. coli were examined, DNA strand discontinuities at the nic positions of the chromosomally integrated fertility factors were also observed. Detection of DNA strand scission at the nic position of F DNA in the high frequency of recombination strains, as well as in the episomal factors, was dependent on sexual expression from the transmissable element, but was independent of mating. These results imply that not only the transfer origins of extrachromosomal F and F-like fertility factors, but also the origins of stably integrated copies of these plasmids, are subject to an equilibrium of cleavage and ligation in vivo in the absence of DNA transfer.

Identification of a structural determinant for resistance to β-lactam antibiotics in Gram-positive bacteria

Streptococcus pneumoniae is the main causal agent of pathologies that are increasingly resistant to antibiotic treatment. Clinical resistance of S. pneumoniae to β-lactam antibiotics is linked to multiple mutations of high molecular mass penicillin-binding proteins (H-PBPs), essential enzymes involved in the final steps of bacterial cell wall synthesis. H-PBPs from resistant bacteria have a reduced affinity for β-lactam and a decreased hydrolytic activity on substrate analogues. In S. pneumoniae, the gene coding for one of these H-PBPs, PBP2x, is located in the cell division cluster (DCW). We present here structural evidence linking multiple β-lactam resistance to amino acid substitutions in PBP2x within a buried cavity near the catalytic site that contains a structural water molecule. Site-directed mutation of amino acids in contact with this water molecule in the “sensitive” form of PBP2x produces mutants similar, in terms of β-lactam affinity and substrate hydrolysis, to altered PBP2x produced in resistant clinical isolates. A reverse mutation in a PBP2x variant from a clinically important resistant clone increases the acylation efficiency for β-lactams and substrate analogues. Furthermore, amino acid residues in contact with the structural water molecule are conserved in the equivalent H-PBPs of pathogenic Gram-positive cocci. We suggest that, probably via a local structural modification, the partial or complete loss of this water molecule reduces the acylation efficiency of PBP2x substrates to a point at which cell wall synthesis still occurs, but the sensitivity to therapeutic concentrations of β-lactam antibiotics is lost.

Peptide methionine sulfoxide reductase contributes to the maintenance of adhesins in three major pathogens.

Pathogenic bacteria rely on adhesins to bind to host tissues. Therefore, the maintenance of the functional properties of these extracellular macromolecules is essential for the pathogenicity of these microorganisms. We report that peptide methionine sulfoxide reductase (MsrA), a repair enzyme, contributes to the maintenance of adhesins in Streptococcus pneumoniae, Neisseria gonorrhoeae, and Escherichia coli. A screen of a library of pneumococcal mutants for loss of adherence uncovered a MsrA mutant with 75% reduced binding to GalNAcbeta1-4Gal containing eukaryotic cell receptors that are present on type II lung cells and vascular endothelial cells. Subsequently, it was shown that an E. coli msrA mutant displayed decreased type I fimbriae-mediated, mannose-dependent, agglutination of erythrocytes. Previous work [Taha, M. K., So, M., Seifert, H. S., Billyard, E. & Marchal, C. (1988) EMBO J. 7, 4367-4378] has shown that mutants with defects in the pilA-pilB locus from N. gonorrhoeae were altered in their production of type IV pili. We show that pneumococcal MsrA and gonococcal PilB expressed in E. coli have MsrA activity. Together these data suggest that MsrA is required for the proper expression or maintenance of functional adhesins on the surfaces of these three major pathogenic bacteria.

New multivalent calixarene-based ligands for protein recognition and inhibition

One of the challenges that concerns chemistry is the design of molecules able to modulate protein-protein and protein-ligand interactions, since these are involved in many physiological and pathological processes. The interactions occurring between proteins and their natural counterparts can take place through reciprocal recognition of rather large surface areas, through recognition of single contact points and single residues, through inclusion of the substrates in specific, more or less deep binding sites. In many cases, the design of synthetic molecules able to interfere with the processes involving proteins can benefit from the possibility of exploiting the multivalent effect. Multivalency, widely spread in Nature, consists in the simultaneous formation between two entities (cell-cell, cell-protein, protein-protein) of multiple equivalent ligand-recognition site complexes. In this way the whole interaction results particularly strong and specific. Calixarenes furnish a very interesting scaffold for the preparation of multivalent ligands and in the last years calixarene-based ligands demonstrated their remarkable capability to recognize and inhibit or restore the activity of different proteins, with a high efficiency and selectivity in several recognition phenomena. The relevance and versatility of these ligands is due to the different exposition geometries of the binding units that can be explored exploiting the conformational properties of these macrocycles, the wide variety of functionalities that can be linked to their structure at different distances from the aromatic units and to their intrinsic multivalent nature. With the aim of creating new multivalent systems for protein targeting, the work reported in this thesis regards the synthesis and properties of glycocalix[n]arenes and guanidino calix[4]arenes for different purposes. Firstly, a new bolaamphiphile glycocalix[4]arene in 1,3-alternate geometry, bearing cellobiose, was synthesized for the preparation of targeted drug delivery systems based on liposomes. The formed stable mixed liposomes obtained by mixing the macrocycle with DOPC were shown to be able of exploiting the sugar units emerging from the lipid bilayer to agglutinate Concanavalin A, a lectin specific for glucose. Moreover, always thanks to the presence of the glycocalixarene in the layer, the same liposomes demonstrated through preliminary experiments to be uptaken by cancer cells overexpressing glucose receptors on their exterior surface more efficiently respect to simple DOPC liposomes lacking glucose units in their structure. Then a small library of glycocalix[n]arenes having different valency and geometry was prepared, for the creation of potentially active immunostimulants against Streptococcus pneumoniae, particularly the 19F serotype, one of the most virulent. These synthesized glycocalixarenes bearing β-N-acetylmannosamine as antigenic unit were compared with the natural polysaccharide on the binding to the specific anti-19F human polyclonal antibody, to verify their inhibition potency. Among all, the glycocalixarene based on the conformationally mobile calix[4]arene resulted the more efficient ligand, probably due its major possibility to explore the antibody surface and dispose the antigenic units in a proper arrangement for the interaction process. These results pointed out the importance of how the different multivalent presentation in space of the glycosyl units can influence the recognition phenomena. At last, NMR studies, using particularly 1H-15N HSQC experiments, were performed on selected glycocalix[6]arenes and guanidino calix[4]arenes blocked in the cone geometry, in order to better understand protein-ligand interactions. The glycosylated compounds were studied with Ralstonia solanacearum lectin, in order to better understand the nature of the carbohydrate‐lectin interactions in solution. The series of cationic calixarene was employed with three different acidic proteins: GB1, Fld and alpha synuclein. Particularly GB1 and Fld were observed to interact with all five cationic calix[4]arenes but showing different behaviours and affinities.

Banho de clorexidina para prevenção de colonização e infecção por micro-organismos multirresistentes na unidade de transplante de células tronco e hematopoiéticas

Introdução: Infecções relacionadas à assistência de saúde (IRAS) representam hoje um dos principais desafios da qualidade do cuidado do paciente, principalmente em pacientes submetido a transplante de células tronco e hematopoiéticas (TCTH) O banho diário com a clorexidina (CHG) degermante a 2% tem sido proposto principalmente em unidades de terapia intensivas (UTIs) para diminuir a colonização bacteriana do paciente e assim diminuir IRAS. O objetivo deste estudo foi avaliar o impacto do banho com CHG degermante a 2% em unidade de internação de TCTH na incidência de infecção e colonização por patógenos multirresistentes e ainda avaliar seu impacto na sensibilidade das bactérias ao antisséptico. Métodos: Foi realizado um estudo quasi-experimental, com duração de 9 anos, com início em janeiro/2005 até dezembro/2013. A intervenção foi iniciada em agosto de 2009, sendo que os períodos pré e pós-intervenção tiveram duração de 4,5 anos. As taxas de IRAS, infecção por gram-negativos multirresistentes e infecção e colonização por enterococo resistente a vancomicina (VRE) foram avaliadas através de série temporal, para estudar o impacto da intervenção. As concentrações inibitórias mínimas (CIM) das bactérias para a CHG com e sem o inibidor de bomba de efluxo (CCCP) foram avaliadas nos dois períodos. Os genes de resistência a CHG foram estudados por meio da PCR e a clonalidade dos isolados por eletroforese em campo pulsátil. Resultados: Foi observada redução significativa na incidência de infecção e colonização de VRE na unidade no período pós-intervenção (p: 0,001). Essa taxa permaneceu estável em outras UTIs clínicas do hospital. Contudo as taxas de infecção por Gram negativos multirresistentes aumentou nos últimos anos na unidade. Não ocorreu diminuição na taxa de IRAS na unidade. As CIMs testadas de CHG aumentaram nas amostras de VRE e K. pneumoniae após o período de exposição ao antisséptico, com queda importante da CIM após o uso do CCCP, revelando ser a bomba de efluxo, um importante mecanismo de resistência à CHG. As amostras de A. baumannii e P. aeruginosa não apresentaram aumento da CIM após período de exposição à clorexidina. As bombas de efluxo Ade A, B e C estiveram presentes na maioria dos A. baumannii do grupo controle (66%). A bomba cepA foi encontrada em 67% de todas as K. pneumoniae testadas e em 44,5% das P. aeruginosas do grupo pré intervenção. Observamos uma relação positiva entre a presença da CepA nas amostras de K. pneumoniae e a resposta ao CCCP: de todas as 49 amostras CepA positivas 67,3% obtiveram redução do seu MIC em 4 diluições após adição do CCCP. A avaliação de clonalidade demonstrou padrão policlonal das amostras de VRE, K. pneumoniae e A. baumannii avaliadas. Em relação às amostras de P. aeruginosa foi observado que no período pós-intervenção ocorreu predominância de um clone com > 80% semelhança em 10 das 22 amostras avaliadas pelo dendrograma. Conclusões: O banho de clorexidina teve impacto na redução da incidência de infecção e colonização por VRE na unidade de TCTH, e não teve o mesmo impacto nas bactérias gram-negativas. Os mecanismos moleculares de resistência à clorexidina estão intimamente ligados à presença de bomba de efluxo, sendo provavelmente o principal mecanismo de resistência e tolerância das bactérias ao antisséptico

Transferência transplacentária de anticorpos em gestações gemelares

Há poucos dados na literatura sobre o transporte transplacentário de imunoglobulinas em gestações múltiplas. O objetivo deste estudo foi observar fatores que influenciam a concentração de imunoglobulina G (IgG) no cordão umbilical dos neonatos e a transferência transplacentária de IgG total e de IgG contra o Streptococcus grupo B (EGB), e lipopolissacarídeos (LPS) de Klebsiella spp. e Pseudomonas spp.. Métodos: estudo prospectivo realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo no período de 2012 a 2013. Foram coletadas amostras de sangue materno e de cordão umbilical no momento do parto. Os critérios de inclusão foram gestações gemelares com ausência de sinais de infecção por HIV, citomegalovírus, Hepatites B e C, toxoplasmose e rubéola e ausência de doenças autoimunes, malformação fetal e síndromes genéticas. A análise multivariada foi realizada para avaliar a associação entre os níveis de IgG em cordão umbilical e as taxas de transferência de anticorpos com a concentração materna de IgG, a corionicidade da gestação, a presença de insuficiência placentária, a restrição de crescimento intrauterino, a idade gestacional de nascimento, o peso de nascimento, o tabagismo, a doença materna e a via de parto. Resultados: a concentração de IgG total em cordão umbilical apresentou correlação positiva com os níveis maternos séricos de IgG total e a idade gestacional do parto. Os níveis de IgG total em cordão umbilical foram significativamente menores em gestações monocoriônicas quando comparadas às dicoriônicas. A taxa de transferência de IgG total apresentou correlação positiva com a idade gestacional do parto, mas negativa com as concentrações maternas de IgG total. As concentrações de IgG contra EGB e LPS de Klebsiella spp. e Pseudomonas spp. apresentaram associação com os níveis maternos de IgG específicos contra esses antígenos e com o diabetes. Os níveis de IgG contra LPS de Klebsiella spp. também foram associados com o peso de nascimento e com hipertensão materna. As taxas de transferência de IgG contra EGB e LPS de Pseudomonas spp. apresentaram correlação com os níveis maternos de IgG específicos contra os antígenos referidos. A taxa de transferência de IgG contra EGB também esteve associada com a idade gestacional do parto, enquanto a taxa de transferência de IgG contra LPS de Pseudomonas spp. apresentou correlação com diabetes. Não houve correlação entre a taxa de transferência de IgG contra a LPS de Klebsiella spp. com nenhum fator analisado. Conclusão: em gestações gemelares, a concentração total de IgG em cordão umbilical foi influenciada pela concentração materna de IgG total, pela idade gestacional do parto e pela corionicidade placentária. As concentrações de IgG total foram significativamente menores em gestações monocoriônicas que em dicoriônicas. As concentrações séricas de IgG contra EGB e LPS de Klebsiella spp. e Pseudomonas spp. em cordão umbilical apresentaram associação com os níveis maternos de IgG específicos contra esses antígenos e com a presença de diabetes. Todos os outros parâmetros estudados apresentaram diferentes associações com as concentrações de IgG e com as taxas de transferências de IgG específicas contra cada antígeno investigado

Enterobacterias productoras de carbapenemasas: tipos, epidemiología molecular y alternativas terapéuticas

Los carbapenémicos son los antibióticos β-lactámicos de más amplio espectro activos frente a microorganismos grampositivos, gramnegativos y anaerobios. Estos agentes mantienen su actividad frente a enterobacterias productoras de β-lactamasas de espectro extendido (BLEE) o de cefalosporinasas AmpC. Dentro de las enterobacterias, la resistencia a los carbapenémicos está mediada principalmente por la producción de diferentes tipos de carbapenemasas, aunque esta resistencia también puede ser debida a una combinación pérdida de porinas más enzimas BLEE o una hiperexpresión de AmpC. Las carbapenemasas representan la familia de β-lactamasas más versátil, con un amplio espectro. La mayoría de estas enzimas reconocen e hidrolizan a casi todos los β- lactámicos y son resistentes a la acción de los inhibidores de los β-lactámicos. Dentro de las enterobacterias, las carbapenemasas se aíslan principalmente en K. pneumoniae y en menor medida en E. coli y otras especies, con una prevalencia más alta en el sur de Europa y Asia que en otras partes del mundo. Las carbapenemasas de la clase A, que pertenecen al grupo 2f de Bush-Jacoby, se pueden dividir en 5 grupos en base a su filogenética: GES, KPC, SME, IMI y NMCA. Las enzimas SME, NMC e IMI están codificadas en cromosómas mientras que las enzimas GES y KPC se encuentran codificadas en plásmidos. El gen blaKPC está asociado el transposón Tn4401. Clínicamente, el grupo que más interés tiene es el de las enzimas KPC. Existen 11 tipos descritos...