fThe ability of Pseudomonas aeruginosa to develop resistance to most antimicrobials represents an important clinical threat worldwide. We report the dissemination in several Colombian hospitals of two predominant lineages of extensively drug-resistant (XDR) carbapenemase-producing P. aeruginosa strains. These lineages belong to the high-risk clones sequence type 111 (ST111) and ST235 and harbor bla VIM-2 on a class 1 integron and bla KPC-2 on a Tn4401 transposon, respectively. Additionally, P. aeruginosa ST1492, a novel single-locus variant of ST111, was identified. Clonal dissemination and the presence of mobile genetic elements likely explain the successful spread of XDR P. aeruginosa strains in Colombia.

Polymyxins are last-resort antimicrobial agents used to treat infections caused by carbapenem-resistant Due to the worldwide dissemination of polymyxin resistance in animal and human isolates, we aimed to characterize polymyxin resistance associated with the presence of in and nonfermenter Gram-negative bacilli, using isolates collected retrospectively in Colombia from 2002 to 2016. A total of 5,887 Gram-negative clinical isolates were studied, and 513 were found to be resistant to the polymyxins. Susceptibility to colistin was confirmed by broth microdilution for all-positive isolates, and these were further subjected to whole-genome sequencing (WGS). The localization of was confirmed by S1 pulsed-field gel electrophoresis (S1-PFGE) and CeuI-PFGE hybridization. Transferability was evaluated by mating assays. A total of 12 colistin-resistant isolates recovered after 2013 harbored, including 8 , 3 serovar Typhimurium, and 1 isolate isolates were unrelated by PFGE and belonged to 7 different sequence types (STs) and phylogroups. Typhimurium and isolates belonged to ST34 and ST307, respectively. The gene was plasmid borne in all isolates but two isolates which harbored it on the chromosome. Conjugation of was successful in 8 of 10 isolates (8.2 × 10 to 2.07 × 10 cell per recipient). Plasmid sequences showed that the plasmids belonged to four different Inc groups (a new IncP-1 variant and the IncFII, IncHI1, and IncH families). Our results indicate that is circulating in clinical isolates of colistin-resistant in Colombia and is mainly harbored in transferable plasmids.

RESUMEN Introducción Las infecciones del tracto urinario (ITU) son frecuentes en la comunidad. Sin embargo, la información de aislamientos resistentes en este contexto es limitada en Latinoamérica. Este estudio tiene como objetivo determinar la prevalencia y los factores de riesgo asociados con ITU de inicio en la comunidad (ITU-IC) causadas por Escherichia coli productor de betalactamasas de espectro extendido (BLEE) en Colombia. Materiales y métodos Entre agosto y diciembre de 2011 se realizó un estudio de casos y controles en 3 instituciones de salud de tercer nivel en Colombia. Se invitó a participar a todos los pacientes admitidos a urgencias con diagnóstico probable de ITU-IC, y se les pidió una muestra de orina. En los aislamien-tos de E. coli se realizaron pruebas confirmatorias para BLEE, susceptibilidad antibiótica, caracterización molecular (PCR en tiempo real para genes bla, repetitive element palindromic PCR [rep-PCR], multilocus sequence typing [MLST] y factores de virulencia por PCR). Se obtuvo información clínica y epidemiológica, y posteriormente se realizó el análisis estadístico. Resultados De los 2.124 pacientes seleccionados, 629 tuvieron un urocultivo positivo, en 431 de estos se aisló E. coli, 54 fueron positivos para BLEE y 29 correspondieron a CTX-M-15. La mayoría de los aislamientos de E. coli productor de BLEE fueron sensibles a ertapenem, fosfomicina y amikacina. La ITU complicada se asoció fuertemente con infecciones por E. coli productor de BLEE (OR = 3,89; IC 95%: 1,10–13,89; p = 0,03). E. coli productor de CTX-M-15 mostró 10 electroferotipos diferentes; de estos, el 65% correspondieron al ST131. La mayoría de estos aislamientos tuvieron 8 de los 9 factores de virulencia analizados. Discusión E. coli portador del gen blaCTX-M-15 asociado al ST131 sigue siendo frecuente en Colombia. La presencia de ITU-IC complicada aumenta el riesgo de tener E. coli productor de BLEE, lo cual debe tenerse en cuenta para ofrecer una terapia empírica adecuada.

el Grupo de Resistencia Bacteriana Nosocomial en Colombia: análisis e interpretación de la epidemiología molecular de los aislamientos. María Virginia Villegas: dirección científica, interpretación de los datos. Todos los autores participaron en la escritura y aprobación final del manuscrito. ARTÍCULO ORIGINAL Biomédica 2014;34(Supl. Conclusiones. Se observó un incremento en la tendencia de los microorganismos hacia la multirresistencia y una amplia distribución de las carbapenemasas. La articulación de la biología molecular con los sistemas de vigilancia permitió integrar el análisis del fenotipo con los mecanismos de resistencia involucrados en las bacterias estudiadas. Este análisis permitirá la elaboración de guías para el uso adecuado de antimicrobianos y contribuirá a la contención de estas bacterias multirresistentes en Colombia.Palabras clave: bacterias Gram negativas, farmacorresistencia bacteriana, vigilancia epidemiológica, Colombia.

The global success of multidrug-resistant Acinetobacter baumannii has been associated with the dissemination of a high-risk clone designated clonal complex (CC) 92 (Bartual scheme)/CC2 (Pasteur scheme), which is the most frequent genetic lineage in European, Asian, and North American carbapenem-resistant Acinetobacter isolates. In these isolates, carbapenem resistance is mainly mediated by β-lactamases encoded by bla, bla, bla, and/or bla genes. In this study, we characterized the population genetics of 121 carbapenem-resistant A. baumannii complex isolates recovered from 14 hospitals in seven cities in Colombia (2008-2010). Multiplex PCR was used to detect bla, bla, bla, and bla genes. Molecular typing was performed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). PCR showed that 118 (97.5%) of the isolates were positive for both bla and bla genes, and three other isolates were only positive for bla. PFGE identified 18 different pulsotypes, while MLST identified 11 different sequence types (STs), seven of which had not been previously described in Acinetobacter. None of the STs found in this study was associated with CC92/CC2. The most widespread STs in our isolates belonged to ST636 and their single-locus variants ST121/ST124/ST634 (CC636) followed by STs belonging to CC110. Our observations suggest a wide distribution of diverse A. baumannii complex clones containing bla in Colombian hospitals (especially CC636 and CC110) that differ from the high-risk clones commonly found in other regions of the world, indicating a distinct molecular epidemiology of carbapenem-resistant Acinetobacter spp. in Colombia.

BackgroundCarbapenemase-producing Enterobacteriaceae (CPE) currently pose a significant global public health threat. KPC carbapenemases are highly endemic in Colombia mostly among Enterobacteriaceae. In Klebsiella pneumoniae (Kpn), horizontal transfer of genes encoding KPC and expansion of isolates belonging to clonal group (CG) 258 resulted in epidemic levels of carbapenemase-producing Kpn. We aimed to understand the dynamics of transmission of KPC-genes among CPE infecting and colonizing patients in an endemic area of Colombia.MethodsWe conducted a surveillance study in 3 hospitals around Medellin, Antioquia (November 2013 to October 2015) that included patients colonized and infected (by physician criteria) with CPE. The isolates were collected, identified and typed initially using rep-PCR. A subset of isolates were chosen for Whole Genome Sequencing on the Illumina platform based on initial molecular characterization. De-novo assembly and maximum likelihood phylogenetic analyses were performed in all sequenced isolates.ResultsA total of 131 KPC-producing Enterobacteriaceae isolates were recovered from 77 colonized and 29 infected patients. A total of 76 selected isolates were sequenced. In Kpn, compartmentalization of KPC-3 within CG258 was observed, whereas KPC-2 was identified in different genetic backgrounds but not in CG258. In E. coli, blaKPC-2 was found in two clusters belonging to ST131 and ST349. In one hospital both Kpn (ST36,15,101,140, 502) and E. coli shared a 56 Kb plasmid harboring blaKPC-2 with high degree of identity to the conjugative IncN plasmid N3. The blaKPC-2 gene was found within a variation of Tn4401b harboring ISKpn6 and carrying both a Tn3-transposase and a resolvase. E. cloacae, C. freundii and S. marcescens only harbored KPC-2 (and not KPC-3) within the same Tn4401b structure.ConclusionThe KPC epidemic in an area of high endemicity in Colombia is driven by horizontal transfer of plasmids harboring blaKPC-2 among members of the Enterobacteriaceae family. These findings are consistent with a KPC-plasmid epidemic rather than clonal expansion of a successful genetic lineage. Controlling the KPC epidemic in Colombia would be challenging and is likely influenced by antibiotic consumption rather than patient to patient transmission.Disclosures A. M. Rada, COLCIENCIAS: Student, Research grant and Research support; N. Orozco, COLCIENCIAS: Research Contractor, Salary; C. Hernández-Gómez, Merck Sharp and Dohme, Pfizer: Consultant, Consulting fee; C. Pallares, Merck Sharp & Dohme, Pfizer: Consultant, Consulting fee; M. V. Villegas, Merck Sharp & Dohme, Pfizer: Consultant, Consulting fee and Research support; E. Restrepo, COLCIENCIAS: Investigator, Research support

BackgroundMultidrug-resistant Enterobacteriaceae (Ent) and Pseudomonas aeruginosa (Pae) are involved in a considerable number of healthcare-associated infections, thus representing a therapeutic challenge. Ceftolozane–tazobactam (C/T) is a combination of a novel cephalosporin with a known β-lactamase inhibitor. Ceftolozane has high affinity for penicillin-binding proteins, improved outer membrane permeability, increased stability against efflux and enhanced stability against chromosomal AmpC β-lactamases compared with other β-lactam antibiotics. This agent is not active against carbapenemases. We evaluated the in vitro activity of C/T against clinical isolates of Ent and Pae collected from 2016- 2017 and compared it to the activity of broad-spectrum antimicrobial agents.Methods1.644 Ent and Pae non-duplicate clinical isolates were collected in 13 medical centers located in 12 Colombian cities. Minimum inhibitory concentrations (MIC) were performed by broth microdilution and interpreted according to current CLSI guidelines. Isolates tested included 813 Escherichia coli (Eco), 441 Klebsiella pneumoniae (Kpn), 82 Enterobacter spp., (Enb); 60 Serratia marcescens (Sma) and 248 Pae. Comparator agents were ceftriaxone (CRO), cefotaxime (CTX), ceftazidime (CAZ), cefepime (FEP), piperacillin/tazobactam (TZP), ertapenem (ETP), imipenem (IMI), meropenem (MEM).ResultsSusceptibilities to C/T and comparators of 4 Ent species and Pae are shown in Table 1. Compared with other β-lactams such as CRO, CAZ, TZP, and FEP, C/T had considerably higher susceptibility rates against ESBL, non-carbapenem-resistant (CR) Eco and Kpn isolates. C/T MIC50/90 were: Eco (≤1/≤1); Kpn (≤1/128); Enb (≤1/64); Sma (≤1/≥256); Pae (≤1/≥256). In the case of P.aeruginosa despite the high resistance rates observed in the study, C/T had the best susceptibility, even higher than the carbapenems.ConclusionOverall, C/T demonstrated higher in vitro activity than currently available cephalosporins and TZP when tested against Ent and Pae. C/T provides an important treatment option against infections caused by non-carbapenemase producing Gram-negative pathogens. Further studies are warranted to identify an emerging mechanism of resistance in Colombia. Disclosures All authors: No reported disclosures.

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