scholarly journals 485. Clinical and Molecular Epidemiology of Carbapenem Non-susceptible Citrobacter sp.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S237-S238
Author(s):  
Ahmed Babiker ◽  
Daniel R Evans ◽  
Marrisa P Griffifth ◽  
Roberta T Mettus ◽  
Christi L McElheny ◽  
...  

Abstract Background Carbapenem non-susceptible Citrobacter sp. (CNSC) are becoming increasingly recognized as healthcare-associated (HA) pathogens, but data on clinical and molecular epidemiology, species diversity and mechanisms of carbapenem resistance are lacking. Methods We reviewed patients at University of Pittsburgh Medical Center with CNSC positive cultures from 2000 to 2018. The diversity of CNSC species among a subset of isolates from all UPMC sites was confirmed by 16S rRNA typing, and the presence of carbapenemase enzymes in the same isolates was determined by PCR amplificon. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Significance of epidemiological trends over time was determined by linear regression, and correlation with antibiotic consumption was determined by cross-correlation using STATA v15. Results Between 2000 and 2018, 3% (78/2817) of all Citrobacter sp. were CNS. CNSC rates increased from 4% in 2000 to 10% in 2018 (R2 = 0.206, P = 0.05), as did carbapenem consumption (6.5–34.5 DDDs/1000, R2 = 0.831, P < 0.001) (Figure 1). Twenty-one isolates from 19 patients were available for additional analysis. Patients had multiple comorbidities (84%), frequently acquired CNSC in the healthcare setting (84%), were colonized with other organisms (68%), and had high rates of in-hospital mortality/discharge to hospice (47%) (Table 1). C. freundii was the dominant species identified (16/21), followed by C. farmeri (2/21), C. koseri (2/21), and C. werkmanii (1/21). Carbapenemases were identified in 14 isolates, including KPC (n = 12), NDM (n = 2), and OXA-48 (n = 1) (Table 2). Isolates were frequently susceptible to ceftazidime–avibactam (MIC median [IQR]: 2[0.5,8]) 81%) and meropenem-vaborbactam (86%) (MIC median [IQR] 0.12[0.3,0.5]) (Table 2). Conclusion CNSC species are diverse, have emerged as an HA pathogen at our center, and cause high rates of mortality. Further studies, including ongoing genome sequencing and analysis, are required to better elucidate CNSC diversity and resistance mechanisms. Disclosures All authors: No reported disclosures.

2020 ◽  
Author(s):  
Ahmed Babiker ◽  
Daniel R. Evans ◽  
Marissa P. Griffith ◽  
Christi L. McElheny ◽  
Mohamed Hassan ◽  
...  

AbstractCarbapenem-non-susceptible Citrobacter spp. (CNSC) are increasingly recognized as healthcare-associated pathogens. Information regarding their clinical epidemiology, genetic diversity, and mechanisms of carbapenem resistance is lacking. We examined microbiology records of adult patients at the University of Pittsburgh Medical Center (UMPC) Presbyterian Hospital (PUH) from 2000-2018 for CNSC, as defined by ertapenem non-susceptibility. Over this timeframe, the proportion of CNSC increased from 4% to 10% (P=0.03), as did carbapenem daily defined doses/1000 patient days (6.52 to 34.5, R2=0.831, P<0.001), which correlated with the observed increase in CNSC (lag=0 years, R2=0.660). Twenty CNSC isolates from 19 patients at PUH and other UPMC hospitals were available for further analysis, including whole-genome short-read sequencing and additional antimicrobial susceptibility testing. Of the 19 patients, nearly all acquired CNSC in the healthcare setting and over half had polymicrobial cultures containing at least one other organism. Among the 20 CNSC isolates, C. freundii was the predominant species identified (60%). CNSC genomes were compared with genomes of carbapenem-susceptible Citrobacter spp. from UPMC, and with other publicly available CNSC genomes. Isolates encoding carbapenemases (blaKPC-2, blaKPC-3, and blaNDM-1) were also long-read sequenced, and their carbapenemase-encoding plasmid sequences were compared with one another and with publicly available sequences. Phylogenetic analysis of 102 UPMC Citrobacter spp. genomes showed that CNSC from our setting did not cluster together. Similarly, a global phylogeny of 64 CNSC genomes showed a diverse population structure. Our findings suggest that both local and global CNSC populations are genetically diverse, and that CNSC harbor carbapenemase-encoding plasmids found in other Enterobacterales.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Leena Al-Hassan ◽  
Mai M. Zafer ◽  
Hadir El-Mahallawy

Abstract Background Acinetobacter baumannii is an increasingly worrying organism in the healthcare setting, due to its multidrug resistance and persistence. Prolonged hospitalisation, immunocompromised patients and excessive antibiotic exposure all contribute to increasing the risk of A. baumannii infections, which makes cancer patients a significant risk group. This study aims to investigate the dissemination of A. baumannii at the National Cancer Institute (NCI) in Cairo – Egypt. Methods All bacterial isolates were typed using Multi-locus Sequence Typing (MLST) to characterise the epidemiology of isolates. The intrinsic OXA-51-like, and the acquired carbapanemases OXA-23, − 24/40, − 58, NDM, IMP, and VIM were also amplified and sequenced to genetically identify mechanisms of carbapenem resistance. Results MLST results show a high degree of multi-clonal dissemination, with 18 different Sequence Types (STs) identified, including 5 novel. The majority of isolates belonged to International Clone (IC) 2, and carbapenem resistance was detected in 93% of isolates and mediated by blaOXA-23, blaOXA-58, blaNDM-1 and blaVIM-1. We also report the presence of a resistant ST732 (OXA-378) which has been previously identified in migratory birds. Conclusions Multiple highly resistant clones were identified in a Cancer hospital in Cairo. It is vital that clinicians and healthcare workers are aware of the population of A. baumannii present in order to have appropriate treatment and infection control practices.


2009 ◽  
Vol 53 (11) ◽  
pp. 4783-4788 ◽  
Author(s):  
José-Manuel Rodríguez-Martínez ◽  
Laurent Poirel ◽  
Patrice Nordmann

ABSTRACT The contributions of different mechanisms of resistance to carbapenems among a collection of imipenem- and meropenem-nonsusceptible Pseudomonas aeruginosa isolates were investigated. This screening included the recently reported extended-spectrum cephalosporinases (ESACs) weakly hydrolyzing carbapenems. Eighty-seven percent of the studied isolates were resistant to imipenem. Genes encoding metallo-β-lactamases or carbapenem-hydrolyzing oxacillinases were not identified. The main mechanism associated with imipenem resistance was the loss of outer membrane protein OprD. Identification of overexpressed ESACs and loss of OprD were observed for 65% of the isolates, all being fully resistant to imipenem. Resistance to meropenem was observed in 78% of the isolates, with all but one also being resistant to imipenem. Overexpression of the MexAB-OprM, MexXY-OprM, or MexCD-OprJ efflux systems was observed in 60% of the isolates, suggesting the contribution of efflux mechanisms in resistance to meropenem. The loss of porin OprD and the overproduction of ESACs were observed in 100% and 92% of the meropenem-resistant isolates, respectively. P. aeruginosa can very often accumulate different resistance mechanisms, including ESAC production, leading to carbapenem resistance.


2020 ◽  
Vol 221 (Supplement_2) ◽  
pp. S156-S163 ◽  
Author(s):  
Jiao Liu ◽  
Lidi Zhang ◽  
Jingye Pan ◽  
Man Huang ◽  
Yingchuan Li ◽  
...  

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with poor patient outcomes. Data on risk factors and molecular epidemiology of CRE in complicated intra-abdominal infections (cIAI) in China are limited. This study examined the risk factors of cIAI with CRE and the associated mortality based on carbapenem resistance mechanisms. Methods In this retrospective analysis, we identified 1024 cIAI patients hospitalized from January 1, 2013 to October 31, 2018 in 14 intensive care units in China. Thirty CRE isolates were genotyped to identify β-lactamase-encoding genes. Results Escherichia coli (34.5%) and Klebsiella pneumoniae (21.2%) were the leading pathogens. Patients with hospital-acquired cIAI had a lower rate of E coli (26.0% vs 49.1%; P &lt; .001) and higher rate of carbapenem-resistant Gram-negative bacteria (31.7% vs 18.8%; P = .002) than those with community-acquired cIAI. Of the isolates, 16.0% and 23.4% of Enterobacteriaceae and K pneumoniae, respectively, were resistant to carbapenem. Most carbapenemase-producing (CP)-CRE isolates carried blaKPC (80.9%), followed by blaNMD (19.1%). The 28-day mortality was 31.1% and 9.0% in patients with CRE vs non-CRE (P &lt; .001). In-hospital mortality was 4.7-fold higher for CP-CRE vs non-CP-CRE infection (P = .049). Carbapenem-containing combinations did not significantly influence in-hospital mortality of CP and non-CP-CRE. The risk factors for 28-day mortality in CRE-cIAI included septic shock, antibiotic exposure during the preceding 30 days, and comorbidities. Conclusions Klebsiella pneumoniae had the highest prevalence in CRE. Infection with CRE, especially CP-CRE, was associated with increased mortality in cIAI.


2019 ◽  
Vol 74 (5) ◽  
pp. 1244-1252 ◽  
Author(s):  
Astrid Pérez ◽  
Eva Gato ◽  
José Pérez-Llarena ◽  
Felipe Fernández-Cuenca ◽  
María José Gude ◽  
...  

Abstract Objectives To characterize the antimicrobial susceptibility, molecular epidemiology and carbapenem resistance mechanisms in Pseudomonas aeruginosa isolates recovered from respiratory tract samples from patients with ventilator-associated pneumonia enrolled in the MagicBullet clinical trial. Methods Isolates were collected from 53 patients from 12 hospitals in Spain, Italy and Greece. Susceptibility was determined using broth microdilution and Etest. MALDI-TOF MS was used to detect carbapenemase activity and carbapenemases were identified by PCR and sequencing. Molecular epidemiology was investigated using PFGE and MLST. Results Of the 53 isolates, 2 (3.8%) were considered pandrug resistant (PDR), 19 (35.8%) were XDR and 16 (30.2%) were MDR. Most (88.9%) of the isolates from Greece were MDR, XDR or PDR, whereas fewer of the isolates from Spain (33.3%) and Italy (43.5%) showed antibiotic resistance. Three Greek isolates were resistant to colistin. Overall, the rates of resistance of P. aeruginosa isolates to imipenem, ciprofloxacin, ceftolozane/tazobactam and ceftazidime/avibactam were 64.1%, 54.7%, 22.6% and 24.5%, respectively. All isolates resistant to ceftolozane/tazobactam and ceftazidime/avibactam (Greece, n = 10; and Italy, n = 2) carried blaVIM-2. Spanish isolates were susceptible to the new drug combinations. Forty-eight restriction patterns and 27 STs were documented. Sixty percent of isolates belonged to six STs, including the high-risk clones ST-111, ST-175 and ST-235. Conclusions MDR/XDR isolates were highly prevalent, particularly in Greece. The most effective antibiotic against P. aeruginosa was colistin, followed by ceftolozane/tazobactam and ceftazidime/avibactam. blaVIM-2 is associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam, and related to highly resistant phenotypes. ST-111 was the most frequent and disseminated clone and the clonal diversity was lower in XDR and PDR strains.


2019 ◽  
Vol 6 (8) ◽  
Author(s):  
Pranita D Tamma ◽  
Sima L Sharara ◽  
Zoi D Pana ◽  
Joe Amoah ◽  
Stephanie L Fisher ◽  
...  

Abstract Background Knowledge of whether Enterobacterales are not susceptible to ceftriaxone without understanding the underlying resistance mechanisms may not be sufficient to direct appropriate treatment decisions. As an example, extended-spectrum β-lactamase (ESBL)–producing organisms almost uniformly display nonsusceptibility to ceftriaxone. Regardless of susceptibility to piperacillin-tazobactam or cefepime, carbapenem antibiotics are the treatment of choice for invasive infections. No such guidance exists for ceftriaxone-nonsusceptible organisms with mechanisms other than ESBL production. We sought to investigate the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales. Methods All consecutive Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis clinical isolates with ceftriaxone minimum inhibitory concentrations (MICs) of ≥2 mcg/mL from unique patients at a United States hospital over an 8-month period were evaluated for β-lactamase genes using a DNA microarray–based assay. Results Of 1929 isolates, 482 (25%) had ceftriaxone MICs of ≥2 mcg/mL and were not resistant to any carbapenem antibiotics. Of the 482 isolates, ESBL (blaCTX-M, blaSHV, blaTEM) and/or plasmid-mediated ampC (p-ampC) genes were identified in 376 (78%). ESBL genes were identified in 310 (82.4%), p-ampC genes in 2 (0.5%), and both ESBL and p-ampC genes in 64 (17.0%) of the 376 organisms. There were 211 (56%), 120 (32%), 41 (11%), and 4 (1%) isolates with 1, 2, 3, or ≥4 ESBL or p-ampC genes. The most common ESBL genes were of the blaCTX-M-1 group (includes blaCTX-M-15), and the most common p-ampC gene was blaCMY-2. Conclusions There is considerable diversity in the molecular epidemiology of ceftriaxone-nonsusceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making.


2014 ◽  
Vol 63 (12) ◽  
pp. 1654-1662 ◽  
Author(s):  
Julianna Mózes ◽  
Fatemeh Ebrahimi ◽  
Orsolya Gorácz ◽  
Cecília Miszti ◽  
Gábor Kardos

This study investigated the molecular epidemiology of Acinetobacter baumannii in the University of Debrecen in relation to antibiotic consumption. Overall and ward-specific antibiotic consumption was measured by the number of defined daily doses (DDD) per 100 bed-days between 2002 and 2012. Consumption was analysed against the number of A. baumannii positive patients per 100 bed-days, number of isolates per positive sample, and proportion of carbapenem resistant A. baumannii, using time-series analysis. Altogether 160 A. baumannii isolates from different wards were collected and analysed. Carbapenemase genes blaOXA-23-like , blaOXA-24-like , blaOXA-48-like , blaOXA-51-like , blaOXA-58-like and integrons were sought by PCR. Relatedness of isolates was assessed by PFGE. Prevalence and carbapenem resistance of A. baumannii were statistically associated with carbapenem consumption. Prevalence data followed carbapenem usage with three quarterly lags (r = 0.51–0.53, P<0.001), and meropenem and ertapenem, but not imipenem usage, affected prevalence. Colistin usage, in turn, lagged behind prevalence with one lag (r = 0.68–0.70, P<0.001). Six clusters were identified; the neurology ward with the lowest carbapenem consumption was associated with the carbapenem-susceptible cluster, as well as with the carbapenem-susceptible isolates in the cluster with variable susceptibility. Wards with high carbapenem usage almost exclusively harboured isolates from carbapenem-resistant clusters. All clusters were dominated by isolates of one or two wards, but most wards were represented in multiple clusters. Increases in prevalence and carbapenem resistance of A. baumannii were associated with usage of meropenem and ertapenem but not of imipenem, which led to the spread of multiple clones in the University.


2020 ◽  
Vol 41 (S1) ◽  
pp. s439-s439
Author(s):  
Valerie Beck

Background: It is well known that contaminated surfaces contribute to the transmission of pathogens in healthcare settings, necessitating the need for antimicrobial strategies beyond routine cleaning with momentary disinfectants. A recent publication demonstrated that application of a novel, continuously active antimicrobial surface coating in ICUs resulted in the reduction of healthcare-associated infections. Objective: We determined the general microbial bioburden and incidence of relevant pathogens present in patient rooms at 2 metropolitan hospitals before and after application of a continuously active antimicrobial surface coating. Methods: A continuously active antimicrobial surface coating was applied to patient rooms in intensive care units (ICUs) twice over an 18-month period and in non-ICUs twice over a 6-month study period. The environmental bioburden was assessed 8–16 weeks after each treatment. A 100-cm2 area was swabbed from frequently touched areas in patient rooms: patient chair arm rest, bed rail, TV remote, and backsplash behind the sink. The total aerobic bacteria count was determined for each location by enumeration on tryptic soy agar (TSA); the geometric mean was used to compare bioburden before and after treatment. Each sample was also plated on selective agar for carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and Clostridioides difficile to determine whether pathogens were present. Pathogen incidence was calculated as the percentage of total sites positive for at least 1 of the 4 target organisms. Results: Before application of the antimicrobial coating, total aerobic bacteria counts in ICUs were >1,500 CFU/100 cm2, and at least 30% of the sites were positive for a target pathogen (ie, CRE, VRE, MRSA or C. difficile). In non-ICUs, the bioburden before treatment was at least 500 CFU/100 cm2, with >50% of sites being contaminated with a pathogen. After successive applications of the surface coating, total aerobic bacteria were reduced by >80% in the ICUs and >40% in the non-ICUs. Similarly, the incidence of pathogen-positive sites was reduced by at least 50% in both ICUs and non-ICUs. Conclusions: The use of a continuously active antimicrobial surface coating provides a significant (P < .01) and sustained reduction in aerobic bacteria while also reducing the occurrence of epidemiologically important pathogens on frequently touched surfaces in patient rooms. These findings support the use of novel antimicrobial technologies as an additional layer of protection against the transmission of potentially harmful bacteria from contaminated surfaces to patients.Funding: Allied BioScience provided Funding: for this study.Disclosures: Valerie Beck reports salary from Allied BioScience.


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