¿Deben implantarse programas de cribado de cepas productoras de carbapenemasas en pacientes que ingresan en la UCI? / Should screening programs for carbapenemase-producing strains be implemented in ICU patients?

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Risk factors for colonization by carbapenemase-producing enterobacteria at admission to a Surgical ICU: A retrospective study / Factores de riesgo para la colonización por enterobacterias productoras de carbapenemasas en el momento de admisión en una UCI quirúrgica: estudio retrospectivo

Introduction: In 2011, a hospital-wide outbreak of OXA-48 producing Klebsiella pneumoniae occurred in our hospital, an epidemiological setting of high ESBL-producing K. pneumoniae rates. This study identifies risk factors for colonization with carbapenemase-producing enterobacteria (CPE) at Surgical Intensive Care Unit (SICU) admission. Methods: A 2-year retrospective study was performed in all patients admitted to the SICU that following routine had a rectal swab collected upon admission. Results: Of 254 patients admitted, 41 (16.1%) harbored CPE (five showing two carbapenemase-producing isolates). Most frequent carbapenemase-producing isolates and carbapenemases were K. pneumoniae (39/46, 84.8%) and OXA-48 (31/46; 76.1%), respectively. Carriers significantly had higher rates of chronic renal disease, previous digestive/biliary endoscopy, hospitalization, ICU/SICU admission, intraabdominal surgery, and antibiotic intake, as well as higher median values of clinical scores (SOFA, SAPS II and APACHE II). In the multivariate analysis (R2 = 0.309, p < 0.001), CPE carriage was associated with prior administration of 3rd-4th generation cephalosporins (OR = 27.96, 95%CI = 6.88, 113.58, p < 0.001), β -lactam/ β -lactamase inhibitor (OR = 11.71, 95%CI = 4.51, 30.43, p < 0.001), abdominal surgery (OR = 6.33, 95%CI = 2.12, 18.89, p = 0.001), and prior digestive/biliary endoscopy (OR = 3.88, 95%CI = 1.56, 9.67, p = 0.004). Conclusions: A strong association between production of ESBLs and carriage of CPE (mainly OXA-48 producing K. pneumoniae) was found. According to the model, the co-selection of β-lactamases by previous exposure to broad-spectrum cephalosporins and β-lactam/ β -lactamase inhibitors (with lower relative risk), abdominal surgery and prior digestive/biliary endoscopy were factors associated with CPE carriage (AU)

Introducción: En 2011 se produjo un brote epidémico de Klebsiella pneumoniae productor de OXA-48 en nuestro hospital, un entorno epidemiológico de altas tasas de K. pneumoniae productor de BLEE. Este estudio identifica factores de riesgo de colonización por enterobacterias productoras de carbapenemasas (EPC) en el momento del ingreso en la unidad de cuidados críticos quirúrgicos (UCCQ). Métodos: Se realizó un estudio retrospectivo durante 2 años en todos los pacientes ingresados en la UCCQ a los que, siguiendo la rutina habitual, se les tomaba un hisopo rectal en el momento de ingreso. Resultados: De los 254 pacientes ingresados, 41 (16,1%) portaban EPC (5 con 2 aislados productores de carbapenemasas). Los aislados productores de carbapenemasas y las carbapenemasas más frecuentes fueron K. pneumoniae (39/46, 84,8%) y OXA-48 (31/46; 76,1%), respectivamente. Los portadores presentaban de forma significativa mayor frecuencia de insuficiencia renal crónica, historia previa de endoscopia digestiva/biliar, hospitalización, ingreso previo en UCI/UCCQ, cirugía intraabdominal y exposición a antibióticos, así como valores más altos (mediana) de SOFA, SAPS II y APACHE II. En el análisis multivariado (R2 = 0,309; p < 0,001), el estado de portador de EPC se asoció con la administración previa de cefalosporinas de amplio espectro (OR = 27,96; IC 95%: 6,88-113,58; p < 0,001), β-lactámicos/inhibidores de β -lactamasas (OR = 11,71; IC 95%: 4,51-30,43; p < 0,001), cirugía abdominal (OR = 6,33; IC 95%: 2,12- 18,89; p = 0,001) y endoscopia digestiva/biliar previa (OR = 3,88; IC 95%: 1,56-9,67; p = 0,004). Conclusiones: Se encontró una fuerte asociación entre la producción de BLEE y la portación de EPC (fundamentalmente K. pneumoniae productora de OXA-48). De acuerdo con el modelo, la co-selección de β-lactamasas tras exposición previa a cefalosporinas de amplio espectro y en menor medida a β-lactámicos/inhibidores de β-lactamasas, la cirugía abdominal y la endoscopia digestiva/biliar previa fueron factores asociados a la portación de EPC (AU)

Emergencia de Providencia rettgeri NDM-1 en dos departamentos de Colombia, 2012-2013 / Emergence of Providencia rettgeri NDM-1 in two departments of Colombia, 2012-2013

Introducción: En Colombia, entre 2012 y 2013 se identificaron 19 aislamientos con NDM, de los cuales 14 correspondían a Providencia rettgeri. Métodos: Los aislamientos se identificaron con Vitek-2, y la sensibilidad antimicrobiana se evaluó por microdilución en caldo. Las carbapenemasas se determinaron fenotípicamente con test de Hodge modificado y pruebas de sinergia con EDTA/SMA y APB, genotípicamente por PCR usando iniciadores específicos para KPC, GES, IMP, VIM, OXA-48 y NDM, y las relaciones genéticas se establecieron con Diversilab. Resultados: Los aislamientos fueron resistentes a carbapenémicos, cefalosporinas de tercera generación, piperacilina-tazobactam, amicacina, gentamicina y tigeciclina, excepto a aztreonam. Todos los aislamientos fueron positivos para EDTA/SMA y NDM-1 y negativos para APB y otras carbapenemasas. Se definieron 2 grupos genéticos: grupo 1 (n = 9 aislamientos), grupo 2 (n = 4 aislamientos), y un aislamiento no relacionado genéticamente. Conclusión: Este trabajo describe la circulación de grupos de P. rettgeri productores de NDM-1 en Colombia (AU)

Introduction: In Colombia, between 2012 and 2013, 19 isolates with NDM were identified, of which 14 corresponded to Providencia rettgeri. Methods: The isolates were identified by Vitek-2, and antimicrobial susceptibility was evaluated by broth microdilution. The carbapenemase phenotypes were determined with Modified Hodge Test and synergy tests with EDTA/SMA and APB, the genotypes by PCR using specific primers for KPC, GES, IMP, VIM, OXA-48 and NDM, and genetic relationships were established with DiversiLab. Results: The isolates were resistant to carbapenems, third-generation cephalosporins, piperacillintazobactam, amikacin, gentamicin and tigecycline, except aztreonam. All isolates were positive for EDTA/SMA and NDM-1, and negative for APB and other carbapenemases. Two genetic groups, group 1 (n = 9 isolates), group 2 (n = 4 isolates) and an isolate defined as not genetically related. Conclusion: This work describes the circulating of NDM-1-producing P. rettgeri in Colombia (AU)

Detección de enterobacterias productoras de carbapenemasas en la rutina del laboratorio / Laboratory detection of carbapenemase-producing Enterobacteriaceae

La detección de enterobacterias productoras de carbapenemasas en el laboratorio requiere un análisis pormenorizado del antibiograma y de la sensibilidad a todos los beta-lactámicos, la implementación con métodos fenotípicos de cribado y la confirmación mediante detección de la hidrólisis del carbapenem, inhibición de la actividad de la enzima con inhibidores específicos y mediante métodos moleculares (AU)

Detection of carbapenemase-producing Enterobacteriaceae in the laboratory requires an exhaustive analysis of the antibio gram and susceptibility to all beta-lactams, the implementation with phenotypic methods of screening as well as confirmatory procedures including the detection of the carbapenem hydrolysis, the inhibition of the enzyme activity with several specific inhibitor compounds and by molecular methods (AU)

Silica-based 2-(N,N-dimethylamino)-1,3-propanediol hydrophilic interaction liquid chromatography stationary phase for separating cephalosporins and carbapenems.

A silica-based stationary phase bearing both hydrophilic hydroxyl and amino groups was developed by covalently bonding a small molecular N,N-dimethylamino 1,3-propanediol moiety onto silica beads via copper(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (CuAAC). This new stationary phase showed good HILIC characteristics and high column efficiency (the theoretical plate number is up to 37000 plates m(-1) in the case of inosine) in the separation of polar compounds, such as nucleosides and bases, organic acids, cephalosporins, and carbapenems.

Click N-benzyl iminodiacetic acid: novel silica-based tridentate zwitterionic stationary phase for hydrophilic interaction liquid chromatography.

Iminodiacetic acid (IDA) is dicarboxylic acid amine, which may produce stronger interaction with polar or charged compounds than bidentate α,ß-amino acid. In this article, a novel type of tridentate zwitterionic HILIC stationary phase was prepared by covalently bonding N-benzyl IDA on silica gel via copper(I) catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (CuAAC). The structure of this stationary phase and all related intermediates was confirmed by NMR, FT-IR, MS spectrum and elemental analysis. The new stationary phase showed good HILIC characteristics and high column efficiency (the theoretical plate number is up to 44000 plates m(-1) in the case of guanosine) in the application of separation of polar compounds, including organic acids, organic bases, as well as highly polar and hydrophilic compounds, such as cephalosporins and carbapenems. Most of them displayed good peak shape and selectivity.

Determination of biapenem in a medicinal product by micellar electrokinetic chromatography with sweeping in an enhanced electric field.

The elaborated method of micellar electrokinetic chromatography (MEKC) used to separate biapenem from its related substances was successfully implemented using sweeping under an enhanced electric field, followed by UV absorption detection at 200nm. The best results were obtained with formic buffer (22.5mM) pH 4.3 and sodium dodecyl sulfate (150mM) added to the electrolyte as the sweeping agent. Neutral capillary (60/50cm; 50µm ID) with reverse polarity and voltage values of 22kV, were used throughout the investigation. The optimized method of biapenem determination, validated in terms of linearity, accuracy and precision, provides a detection limit of 0.5µg/mL at S/N=3 for biapenem. The repeatability of the CE system, expressed by relative standard deviations (RSD) in the migration times, for biapenem and its degradation products varied from 0.14 to 1.48%, whereas for the corrected peak areas RSD were about 0.68-8.43%. Satisfactory separation was achieved within 20min of electrophoresis; moreover all carbapenems (imipenem, meropenem, ertapenem, doripenem and biapenem) were separated from each other during analysis. The evaluated MEKC method was applied to the analysis of a medicinal product containing biapenem - Omegacin(®) 0.3g for intravenous drip infusion.

Isolation of the first IMP-4 metallo beta lactamase producing Klebsiella pneumoniae in Tianjin, China

This study shows for the first time the mechanism of carbapenem resistance of a Klebsiella pneumoniae clinical isolate TJ8 recovered from Tianjin medical university general hospital ,China. The modified Hodge test and EDTA synergy test were performed for the screening of carbapenemases and metallo-β-lactamases (MBLs), respectively. Polymerase chain reactions and DNA sequencing confirmed that the strain carried IMP-4 metallo-β-lactamase (MBL) , SHV-11 and TEM-1 β-lactamase. ClassⅠintegron was positive and gave a 3.0-kb PCR amplicon .IMP-4 was located in ClassⅠintegron 5'CS. The gene determinants were organized in the order of blaIMP-4-orfII-orfIII.In all, the results show that IMP-4 MBL production caused the TJ8 resistance to carbapenems.

Chromatographic separation studies of penicillins, cephalosporins and carbapenems on transition-metal silicate modified silica layers.

The chromatographic behavior of penicillins, cephalosporins and carbapenems has been studied on the thin layers of transition-metal ion (viz. Ni(2+)/Zn(2+)/Cu(2+)/Co(2+)) silicate modified silica. Transition-metal silicate (3.92%) and silica (96.08%) were found to be optimum and resulted in spherical-compact spots and improved resolution of the analytes. The effect of various mobile phases was also investigated. The chromatograms were visualized as yellow spots by placing in an I(2)-chamber. The method has been found to be reproducible and convenient for routine analysis.

Beta-lactams in the new millennium. Part-I: monobactams and carbapenems.

Beta-lactam ring-containing compounds such as penicillins, ampicillin, amoxicillin, cephalosporins and carbapenem are among the most famous antibiotics. This article reviews the recent developments in the study of such compounds. The introductory paragraph, which highlights the significance of the subject and cites most of the leading references of the previous century, is followed by an overview of beta-lactams and some novel methodologies for the synthesis of bi-, tri- and polycyclic derivatives. The rest of the sections deal with design, synthesis and biological activity of monobactams and carbapenems. Many of them have potential antibacterial activity, even against some resistant strains, and enzyme inhibitory activity.