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Background. Polymyxins including colistin are an important \"last-line\" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide. Methods. A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014. Reference colistin resistance determination as performed by broth macrodilution was compared to results from clinical microbiology laboratories (Etest) and to polymyxin resistance testing. Each patient was included once, at the time of their first colistin-tested CRKp positive culture. Time to 30-day in-hospital all-cause mortality was evaluated by Kaplan-Meier curves and Cox proportional hazard modeling. Results. In 246 patients with CRKp, 13% possessed ColR CRKp. ColR was underestimated by Etest (very major error rate = 35%, major error rate = 0.4%). A variety of rep-PCR strain types were encountered in both the ColS and the ColR groups. Carbapenem resistance was mediated primarily by blaKPC-2 (46%) and blaKPC-3 (50%). ColR was associated with increased hazard for in-hospital mortality (aHR 3.48; 95% confidence interval, 1.73–6.57; P < .001). The plasmid-associated ColR genes, mcr-1 and mcr-2 were not detected in any of the ColR CRKp. Conclusions. In this cohort, 13% of patients with CRKp presented with ColR CRKp. The apparent polyclonal nature of the isolates suggests de novo emergence of ColR in this cohort as the primary factor driving ColR. Importantly, mortality was increased in patients with ColR isolates.

Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with Cystic Fibrosis (CF). Herein, we describe a longitudinal analysis of a series of multidrug resistant (MDR) P. aeruginosa isolates recovered in a 17-month period, from a young female CF patient who underwent double lung transplantation. Our goal was to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence evolution over time. Twenty-two sequential P. aeruginosa isolates were obtained within a 17-month period, before and after a double-lung transplant. At the end of the study period, antimicrobial susceptibility testing, whole genome sequencing (WGS), phylogenetic analyses and RNAseq were performed in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time. The majority of isolates were resistant to almost all tested antibiotics. A phylogenetic reconstruction revealed 3 major clades representing a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggested that a group of closely related strains was present in the patient prior to transplantation and continued to change throughout the course of treatment. A trend toward accumulation of mutations over time was observed. Different mutations in the DNA mismatch repair gene mutL consistent with a hypermutator phenotype were observed in two clades. RNAseq performed on 12 representative isolates revealed substantial differences in the expression of genes associated with antibiotic resistance and virulence traits. The overwhelming current practice in the clinical laboratories setting relies on obtaining a pure culture and reporting the antibiogram from a few isolated colonies to inform therapy decisions. Our analyses revealed significant underlying genomic heterogeneity and unpredictable evolutionary patterns that were independent of prior antibiotic treatment, highlighting the need for comprehensive sampling and population-level analysis when gathering microbiological data in the context of CF P. aeruginosa chronic infection. Our findings challenge the applicability of antimicrobial stewardship programs based on single-isolate resistance profiles for the selection of antibiotic regimens in chronic infections such as CF.

Abstract Background Carbapenem resistance is a critical healthcare challenge worldwide. Particularly concerning is the widespread dissemination of Klebsiella pneumoniae carbapenemase (KPC). Klebsiella pneumoniae harboring blaKPC (KPC-Kpn) is endemic in many areas including the United States, where the epidemic was primarily mediated by the clonal dissemination of Kpn ST258. We postulated that the spread of blaKPC in other regions occurs by different and more complex mechanisms. To test this, we investigated the evolution and dynamics of spread of KPC-Kpn in Colombia, where KPC became rapidly endemic after emerging in 2005. Methods We sequenced the genomes of 133 clinical isolates recovered from 24 tertiary care hospitals located in 10 cities throughout Colombia, between 2002 (before the emergence of KPC-Kpn) and 2014. Phylogenetic reconstructions and evolutionary mapping were performed to determine temporal and genetic associations between the isolates. Results Our results indicate that the start of the epidemic was driven by horizontal dissemination of mobile genetic elements carrying blaKPC-2, followed by the introduction and subsequent spread of clonal group 258 (CG258) isolates containing blaKPC-3. Conclusions The combination of 2 evolutionary mechanisms of KPC-Kpn within a challenged health system of a developing country created the “perfect storm” for sustained endemicity of these multidrug-resistant organisms in Colombia.

We report the presence of the mcr-1 gene among 880 Escherichia coli clinical isolates collected in 13 hospitals from 12 Colombian cities between 2016 and 2019. Seven (0.8%) isolates were colistin resistant (MIC ≥ 4 µg/mL). These colistin-resistant isolates were screened for the presence of the mcr-1 gene; five carried the gene. These five isolates were subjected to whole genome sequencing (WGS) to identify additional resistomes and their ST. In addition, antimicrobial susceptibility testing revealed that all E. coli isolates carrying mcr-1 were susceptible to third generation-cephalosporin and carbapenems, except one, which carried an extended-spectrum β-lactamase (CTX-M-55), along with the fosfomycin resistance encoding gene, fosA. WGS indicated that these isolates belonged to four distinct sequence types (ST58, ST46, ST393, and a newly described ST14315) and to phylogroups B1, A, and D. In this geographic region, the spread of mcr-1 in E. coli is low and has not been inserted into high-risk clones such as ST131, which has been present in the country longer.

Polymyxin resistance in Klebsiella pneumoniae has been attributed to mutations in mgrB, phoPQ, pmrAB, and crrAB and to the presence of mcr plasmid-mediated genes. Herein, we describe the molecular characteristics of 24 polymyxin- and carbapenem-resistant K. pneumoniae isolates recovered from six Colombian cities between 2009 and 2019. Minimum inhibitory concentrations (MICs) to polymyxin were confirmed by broth microdilution, and whole-genome sequencing was performed to determine sequence type, resistome, and mutations in the genes related to polymyxin resistance, as well the presence of mcr. The results showed high-level resistance to polymyxin (MICs ≥ 4 μg/mL). blaKPC-3 was present in the majority of isolates (17/24; 71%), followed by blaKPC-2 (6/24; 25%) and blaNDM-1 (1/24; 4%). Most isolates belonged to the CG258 (17/24; 71%) and presented amino acid substitutions in PmrB (22/24; 92%) and CrrB (15/24; 63%); mutations in mgrB occurred in only five isolates (21%). Additional mutations in pmrA, crrA, and phoPQ nor any of the mcr resistance genes were identified. In conclusion, we found clonal dissemination of polymyxin and carbapenem-resistant K. pneumoniae isolates in Colombia, mainly associated with CG258 and blaKPC-3. Surveillance of this multidrug-resistant clone is warranted due to the limited therapeutic options for the treatment of carbapenem-resistant K. pneumoniae infections.

Report from the 28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2018), Madrid, Spain, 21-24 April 2018 Gram-negative bacteria such as and cause some of the most serious infections and are increasingly resistant to multiple drugs and in some cases, to all available antibiotics. Management of infections caused by these organisms is a global challenge that has serious implications for every hospital and department and therefore every delegate attending ECCMID 2018.

Abstract Background The ongoing conflict in Ukraine has exacerbated the risk of MDR bacterial infections in war-injured patients. Methods We present the case of a Ukrainian soldier who sustained a traumatic explosive injury to the bilateral lower extremities, underwent surgery and subsequently experienced an infection with a carbapenem-resistant Klebsiella pneumoniae. The isolate was subject to genomic WGS. Results This case study describes the successful management of a traumatic injury in a Ukrainian soldier infected with a carbapenem-resistant K. pneumoniae isolated from surgical wounds. WGS revealed a hypervirulent ST147 strain carrying multiple resistance and virulence factors, including blaNDM-1. Treatment with ceftazidime/avibactam and aztreonam was effective. Conclusions Ceftazidime/avibactam and aztreonam is highlighted as a promising regimen for MDR infections in conflict zones.

OBJECTIVE To determine whether antimicrobial-impregnated textiles decrease the acquisition of pathogens by healthcare provider (HCP) clothing. DESIGN We completed a 3-arm randomized controlled trial to test the efficacy of 2 types of antimicrobial-impregnated clothing compared to standard HCP clothing. Cultures were obtained from each nurse participant, the healthcare environment, and patients during each shift. The primary outcome was the change in total contamination on nurse scrubs, measured as the sum of colony-forming units (CFU) of bacteria. PARTICIPANTS AND SETTING Nurses working in medical and surgical ICUs in a 936-bed tertiary-care hospital. INTERVENTION Nurse subjects wore standard cotton-polyester surgical scrubs (control), scrubs that contained a complex element compound with a silver-alloy embedded in its fibers (Scrub 1), or scrubs impregnated with an organosilane-based quaternary ammonium and a hydrophobic fluoroacrylate copolymer emulsion (Scrub 2). Nurse participants were blinded to scrub type and randomly participated in all 3 arms during 3 consecutive 12-hour shifts in the intensive care unit. RESULTS In total, 40 nurses were enrolled and completed 3 shifts. Analyses of 2,919 cultures from the environment and 2,185 from HCP clothing showed that scrub type was not associated with a change in HCP clothing contamination (P=.70). Mean difference estimates were 0.118 for the Scrub 1 arm (95% confidence interval [CI], -0.206 to 0.441; P=.48) and 0.009 for the Scrub 2 rm (95% CI, -0.323 to 0.342; P=.96) compared to the control. HCP became newly contaminated with important pathogens during 19 of the 120 shifts (16%). CONCLUSIONS Antimicrobial-impregnated scrubs were not effective at reducing HCP contamination. However, the environment is an important source of HCP clothing contamination. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT 02645214 Infect Control Hosp Epidemiol 2017;38:1147-1154.

Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli i solates contained mcr-1 . Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.