WGS characterization of MDR Enterobacterales with different ceftolozane/tazobactam susceptibility profiles during the SUPERIOR surveillance study in Spain

Abstract

Objectives To analyse by WGS the ceftolozane/tazobactam (C/T) resistance mechanisms in Escherichia coli and Klebsiella spp. isolates recovered from complicated intra-abdominal and urinary tract infections in patients from Spanish ICUs (SUPERIOR surveillance study, 2016–17). Methods The clonal relatedness, the resistome and the virulome of 45 E. coli and 43 Klebsiella spp. isolates with different C/T susceptibility profiles were characterized. Results In E. coli, two (C/T susceptible) carbapenemase producers (VIM-2-CC23, OXA-48-ST38) were detected. The most relevant clone was ST131-B2-O25:H4-H30 (17/45), particularly the CTX-M-15-ST131-H30-Rx sublineage (15/17). ST131 strains were mainly C/T susceptible (15/17) and showed an extensive virulome. In non-ST131 strains (28/45), CTX-M enzymes [CTX-M-14 (8/24); CTX-M-15 (6/24); CTX-M-1 (3/24); CTX-M-32 (2/24)] were found in different clones. C/T resistance was detected in non-clonal E. coli isolates (13%, 6/45) with ESBL (4/6) and non-ESBL (2/6) genotypes. Among Klebsiella spp., Klebsiella pneumoniae (42/43) and Klebsiella michiganensis (1/43) species were identified; 42% (18/43) were carbapenemase producers and 58% showed a C/T resistance phenotype (25/43). OXA-48-ST11 (12/18), OXA-48-ST392 (2/18), OXA-48-ST15 (2/18), NDM-1-ST101 (1/18) and OXA-48+VIM-2-ST15 (1/18) isolates were found, all C/T resistant. Correlation between carbapenemase detection and resistance to C/T was demonstrated (P < 0.001). In non-carbapenemase-producing K. pneumoniae (25/43), C/T resistance (28%, 7/25) was detected in ESBL (3/7) and AmpC (2/7) producers. Overall, an extensive virulome was found and was correlated with carbapenemase carriage (P < 0.001) and C/T resistance (P < 0.05), particularly in OXA-48-ST11 strains (P < 0.05). Conclusions Prediction of antimicrobial susceptibility profiles using WGS is challenging. Carbapenemase-encoding genes are associated with C/T resistance in K. pneumoniae, but other resistance mechanisms might be additionally involved.

Antimicrobial activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa recovered during the Study for Monitoring Antimicrobial Resistance Trends (SMART) program in Spain (2016-2018)

“…In our study, the reduction of ceftolozane-tazobactam susceptibility was small in ESBL-producing E. coli isolates (95.3% susceptible) but was higher in ESBL-producing K. pneumoniae (43.1% susceptible) (Figures S1, S2 and 1). This fact in the latter species might be related to the coproduction of carbapenemases in ESBL producers, a frequent situation in molecularly characterized isolates with ceftolozane-tazobactam MICs >2/4 mg/L (74.2%, 92/124 isolates) and it was also reflected in the SUPERIOR study [ 32 ]. Coproduction of both type of enzymes was less prevalent in E. coli (23.5%, 4/17 isolates).…”

Presence of Chromosomal crpP-like Genes Is Not Always Associated with Ciprofloxacin Resistance in Pseudomonas aeruginosa Clinical Isolates Recovered in ICU Patients from Portugal and Spain

“…Ceftolozane-tazobactam is a new cephalosporin-β-lactamase inhibitor combination with a wide antimicrobial spectrum and high activity against MDR Gram-negative bacteria, with the exception of carbapenemase producers [23]. However, ceftolozane-tazobactam resistance has been recently described in ESBL-producing Enterobacterales populations, including those recovered during the STEP and SUPERIOR surveillance studies [24,25]. The selection pressure in the intestinal microbiota caused by the extensive use of antibiotics during decades has led to the emergence of MDR/XDR pathogens carrying multiple antibiotic resistance determinants, including mechanisms involved in quinolone resistance but also β-lactamases genes such as ESBL and carbapenemases.…”

June

“…We confirm in the present analysis an increase in the prevalence of ESBLs in Spain in K. pneumoniae and maintenance in E. coli when compared with previous and 1). This fact in the latter species might be related to the coproduction of carbapenemases in ESBL producers, a frequent situation in molecularly characterized isolates with ceftolozane-tazobactam MICs >2/4 mg/L (74.2%, 92/124 isolates) and it was also reflected in the SUPERIOR study [32]. Coproduction of both type of enzymes was less prevalent in E. coli (23.5%, 4/17 isolates).…”

“…Del mismo modo que S. pyogenes, todas las cepas de estreptococo β-hemolítico del grupo B estudiadas hasta el momento han mostrado completa tiempo-dependientes, o con efecto post-antibiótico. Además, traduce la importancia de considerar la condición de ayuno de los pacientes en estudios farmacodinámicos [25,32], así como la importancia de las consideraciones farmacocinéticas/farmacodinámicas (PK/PD) en la erradicación microbiana.…”

“…bovis. Un único caso documentado en humanos se comunicó en 1979 [32] en una mujer que previamente había estado en contacto con un fertilizante elaborado con estiércol de vaca. No obstante, esta tenía títulos altos de anticuerpos para M. pneumoniae, que acabaron bajando, sugiriendo que M. bovis no causó realmente la infección, sino que la colonizó de forma oportunista; una característica típica de su patogenicidad ya descrita anteriormente en ganado bovino [33].…”