Intestinal loads of extended-spectrum beta-lactamase and Carbapenemase genes in critically ill pediatric patients (original) (raw)
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Panacea Journal of Medical Sciences, 2023
Abstract Introduction: Intestinal carriage of carbapenem-resistant and (CREK) plays an important role in the epidemiology of carbapenemase producers. Less is known about the carriage of CREK among the outpatients when compared to carriage among patients in Intensive Care Units. (ICU) Therefore the present study was performed to detect colonization of CREK among ICU patients and outpatients of our tertiary care hospital. Materials and Methods: Rectal swabs from ICU patients and stool specimens from outpatients were collected. Identification and antimicrobial susceptibility were performed using Vitek 2 compact system. Screening for CREK was done by two methods and confirmed for carbapenemase production by mCIM. Carbapenemase genes were detected by multiplex polymerase chain reaction. Results: Overall 460 patients were analyzed for the intestinal carriage of CREK, 230 patients each from ICU and outpatients. 10.4% of outpatients and 26% of ICU patients found positive for CREK carriage. The target genes for carbapenemase production found in 78/86 CREK isolates. The majority of isolates 50/78 (64%) harbored beta-lactamase (bla) NDM gene followed by blaOXA-48 like in 18/78 (23%) isolates and 10/78(12%) isolates had both the genes. Conclusion: Detection of carbapenem-resistant genes in commensal flora of the gut is worrisome. Building proper awareness about the use of antimicrobials in the community and strict surveillance systems to monitor these resistant bacteria in humans, food-producing animals, and the environment could all help to reduce the colonization of CREK among healthy individuals. Implementation of strict infection control measures and prudent use of carbapenems can help to limit the spread of these superbugs in the hospital. Keywords: Carbapenemase, beta lactamase NDM1, Gastrointestinal carriage, Outpatients, Intensive Care Units, India
European Journal of Clinical Microbiology & Infectious Diseases, 2017
Gastrointestinal colonization of carbapenemresistant Enterobacteriaceae (CRE) could serve as a reservoir for the transmission of these pathogens in the clinical setting. The aim of this study was to investigate the intestinal carriage of CRE and to analyze risk factors for CRE carriage. Rectal swabs were collected from 95 patients at two Iranian university hospitals. CRE screening was performed using selective media (CHROMagar and MacConkey agar). Polymerase chain reaction (PCR) was used to detect carbapenemaseencoding genes. Clonal relatedness was investigated by pulsed-field gel electrophoresis (PFGE). The rate of carriage of CRE in hospitalized patients was 37.9%. Overall, 54 CRE isolates were identified, of which 47 were carbapenemaseproducers. All of the 54 CRE were detected using CHROMagar compared with 52 CRE detected using MacConkey agar. Fifteen patients were colonized by multiple CRE isolates. Three significant risk factors for CRE carriage were detected: intensive care unit (ICU) hospitalization, antibiotic exposure, and mechanical ventilation. bla OXA-48 was the most frequent carbapenemase detected, followed by bla NDM-1 and bla NDM-7. Eleven carbapenemase-producing Enterobacteriaceae (CPE) isolates co-harbored bla NDM-1 and bla OXA-48. Also, six CPE isolates co-harbored bla NDM-7 and bla OXA-48. We did not detect bla KPC , bla GES , bla IMP , or bla VIM. PFGE analysis showed that Escherichia coli clones were diverse, while Klebsiella pneumoniae isolates were divided into four clusters. Cluster I was the major clone carrying bla OXA-48 and bla CTX-M-15 genes. In our study, the carriage rate of CRE was high and the emergence of CPE isolates among patients is alarming. The implementation of adequate preventive measures such as active surveillance is urgently needed to control the spread of CPE in the healthcare setting.
Molecular diversity in mechanisms of carbapenem resistance in paediatric Enterobacteriaceae
International Journal of Antimicrobial Agents, 2012
The objective of this study was to investigate the trends and patterns of resistance in -lactamase-producing members of the family Enterobacteriaceae in a children's hospital over a 9-year period (1999 to 2007). Clinically significant isolates of the Enterobacteriaceae were screened for patterns of broad-spectrum resistance to -lactams. The strains likely to be resistant were subsequently confirmed by an inhibitor-based disc test. The plasmid-mediated resistance determinants in these isolates were identified by PCR and by in vitro transformation, which successfully reproduced the AmpC phenotype unrestricted by the species of the host organisms. Among 8,048 Enterobacteriaceae isolates belonging to the four chromosomal ampC-negative or -nonfunctional genera, 86 (1.07%) isolates (56 Escherichia coli isolates, 22 Klebsiella species isolates, 1 Proteus mirabilis isolate, and 7 Salmonella species isolates) exhibited broad-spectrum -lactam resistance patterns. These organisms collectively produced three classes of -lactamases, including class A extended-spectrum -lactamases (n ؍ 47), class C or AmpC -lactamases (n ؍ 36, including 4 isolates that produced both class A and class C enzymes), and class A or B carbapenem-hydrolyzing -lactamases (n ؍ 3). The proportion increased from 0.46% during the first 3 years to 1.84% during the last 3 years (relative risk [RR], 4.04; 95% confidence interval [CI], 2.28 to 7.42; P < 0.001). The increase was mainly due to the emergence of a plasmid-mediated bla CMY-2 -lactamase, the incidence of which increased from 0.11% during the first 3 years to 0.96% during the last 3 years (RR, 9.11; 95% CI, 2.76 to 30.1; P ؍ 0.001). Class A-type resistance increased slightly during the study period, from 0.35% during the first 3 years to 0.85% during the last 3 years (RR, 2.42; 95% CI, 1.15 to 5.07; P ؍ 0.02). A Proteus mirabilis strain was documented to possess a novel bla DHA determinant. Of special concern, three carbapenemase-producing isolates were identified between 2003 and 2006. The infections caused by resistant isolates of the Enterobacteriaceae mainly affected hospitalized patients with underlying conditions; however, 19 (22%) episodes were of community onset in otherwise well children. The rate of resistance to broad-spectrum -lactams among isolates of the Enterobacteriaceae is increasing in children in both hospitaland community-acquired settings, and the resistance is driven largely by plasmid-mediated AmpC -lactamases. These data have important implications for empirical antimicrobial strategies targeting serious pediatric infections. Further study of this problem is warranted.
International Journal of Antimicrobial Agents, 2021
Ceftolozane-tazobactam (C/T) is frequently used for infections caused by multidrug-resistant (MDR)-Enterobacterales isolates. Whole-genome sequencing (WGS, Illumina-Hiseq 40 0 0/NovaSeq 60 0 0, OGC, UK) was used to study the population structure, the resistome and the virulome of C/T-susceptible andresistant MDR Escherichia spp. (n = 30) and Klebsiella spp. (n = 78) isolates, recovered from lower respiratory, intra-abdominal and urinary tract infections of ICU patients from 11 Portuguese Hospitals (STEP study, 2017-2018). Minimum inhibitory concentrations (MICs) were determined (ISO-broth microdilution, breakpoints EUCAST-2020). In Escherichia spp. , a weak concordance between the phenotypic and the WGS method (P = 0.051) was observed in the carbapenemase detection (3/30) [ bla VIM-2 (2/3), bla KPC-3 (1/3)]; VIM-2-Escherichia coli isolates were C/T-susceptible and only the KPC-3-Escherichia marmotae producer showed C/T-resistance. Overall, CTX-M-15-E. coli-ST131-O25:H4-H30-Rx (11/30) was the most frequent subclone, followed by CTX-M-27-E. coli-ST131-O25:H4-H30 (4/4). Moreover, a wide resistome and virulome were detected in all E. coli isolates. Among Klebsiella spp. isolates [ K. pneumoniae (67/78), K. aerogenes (7/78), K. oxytoca (2/78), K. variicola (2/78)], concordance (P < 0.001) was observed between the phenotypic and the genomic carbapenemase detection (21/78) [ bla KPC-3 (14/21), bla OXA-48 (3/21), bla OXA-181 (3/21)]. A high correlation between C/T-resistance and carbapenemase detection was established (P < 0.05). Overall, a high clonal diversity was observed, mainly in KPC-3-producing K. pneumoniae isolates. An extensive resistome was detected in Klebsiella spp. isolates, whereas virulence determinants were mostly identified in carbapenemase producers (P < 0.001). WGS is a powerful tool for typing characterization and microbiological study of MDR-Enterobacterales pathogens. Furthermore, carbapenemase genes are associated with C/T-resistance in Klebsiella spp., but other mechanisms might also be involved.
Antibiotic Susceptibility Patterns for Carbapenem-Resistant Enterobacteriaceae
International Journal of Microbiology
Carbapenem is a broad-spectrum beta-lactam antibiotic considered the last choice for the treatment of antibiotic-resistant Gram-negative bacteria. Thus, the increasing rate of carbapenem resistance (CR) in Enterobacteriaceae is an urgent public health threat. This study aimed to evaluate the antibiotic susceptibility pattern of carbapenem-resistant Enterobacteriaceae (CRE) to new and old antibiotics. In this study, Klebsiella pneumoniae, E. coli, and Enterobacter spp. were collected from 10 hospitals in Iran for one year. CRE is recognized by resistance to meropenem and/or imipenem disk after identification of the collected bacteria. Antibiotic susceptibility of CRE against fosfomycin, rifampin, metronidazole, tigecycline, and aztreonam was detected by disk diffusion method and colistin by MIC. In this study, 1222 E. coli, 696 K. pneumoniae, and 621 Enterobacter spp. were collected from 10 hospitals in Iran in one year. Fifty-four E. coli (4.4%), 84 K. pneumoniae (12%), and 51 Enter...
Antimicrobial Resistance & Infection Control
Background: Antibiotic-resistant Enterobacteriaceae in the gastrointestinal flora can lead to infections with limited therapeutic options. Also, the resistant bacteria can be transferred from colonized persons to others. The present study was conducted to search the fecal carriage rates of (i) Enterobacteriaceae that produce extended-spectrum β-lactamase (ESBL-E) and/or (ii) plasmid-mediated AmpC β-lactamase (pAmpC-E), (iii) ciprofloxacin-resistant Enterobacteriaceae (CIP-RE), and (iv) carbapenem-intermediate or-resistant Enterobacteriaceae (CIRE) in Northern Cyprus. Methods: A total of 500 community-dwellers were recruited from consecutive admissions to the clinical laboratories of four hospitals. One rectal swab or stool sample was collected from each participant. A questionnaire was applied to evaluate possible risk factors associated with intestinal colonization of resistant bacteria. The samples were cultured on antibiotic containing media to screen for resistant bacteria colonization. The bacterial colonies that grew on the plates were subjected to further phenotypic tests to confirm the resistance. Results: Of 500 volunteers, ESBL-E, pAmpC-E, CIP-RE and CIRE carriage were detected in 107 (21.4%), 15 (3.0%), 51 (10.2%) and six (1.2%) participants, respectively. Escherichia coli was the most commonly recovered species among Enterobacteriaceae isolates. A significant proportion of ESBL-producing E. coli isolates (n = 22/107; 20.6%) was found to be co-resistant to CIP (p = 0.000, OR 3.21, 95% CI 1.76-5.87). In this study, higher socioeconomic status (CIP-RE: p = 0.024, OR 1.96, 95% CI 1.09-3.53), presence of gastrointestinal symptoms (CIRE: p = 0.033; OR 6.79, 95% CI 1.34-34.39), antibiotic use (ESBL-E: p = 0.031; OR 1.67, 95% CI 1.04-2.67; and CIRE: p = 0.033; OR 6.40, 95% CI 1.16-35.39), and travelling abroad (pAmpC-E: p = 0.010; OR 4.12, 95% CI 1.45-11.66) were indentified as risk factors.
Molecular characterization of clinical carbapenem-resistant Enterobacterales from Qatar
European Journal of Clinical Microbiology & Infectious Diseases
One hundred forty-nine carbapenem-resistant Enterobacterales from clinical samples obtained between April 2014 and November 2017 were subjected to whole genome sequencing and multi-locus sequence typing. Klebsiella pneumoniae (81, 54.4%) and Escherichia coli (38, 25.5%) were the most common species. Genes encoding metallo-β-lactamases were detected in 68 (45.8%) isolates, and OXA-48-like enzymes in 60 (40.3%). blaNDM-1 (45; 30.2%) and blaOXA-48 (29; 19.5%) were the most frequent. KPC-encoding genes were identified in 5 (3.6%) isolates. Most common sequence types were E. coli ST410 (8; 21.1%) and ST38 (7; 18.4%), and K. pneumoniae ST147 (13; 16%) and ST231 (7; 8.6%).
Antimicrobial Agents and Chemotherapy, 2007
To determine the epidemiology and risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR-PA) digestive tract colonization, weekly rectal and pharyngeal swabs were obtained in two serial incidence surveys (266 patients). Forty-two (16%) patients were CR-PA colonized (12 [29%] on admission and 30 [71%] in intensive care units). Pulsed-field gel electrophoresis showed extensive clonal diversity, although one specific clone (type B) was isolated from 11 patients. The presence of similar genotypes of CR-PA colonizing 30% of the CR-PA-colonized patients suggests the occurrence of cross-colonization; in addition, 10 pairs of carbapenem-susceptible P. aeruginosa (CS-PA) and subsequent CR-PA strains isolated from the same patients were found to be clonally identical and were considered to have been endogenously acquired (33%). All endogenously acquired CR-PA strains were isolated after exposure to a carbapenem, and 80% showed a phenotype of imipenem resistance (IR pattern) alone, while 67% of the CR-PA strains acquired by cross-transmission exhibited a multiresistant (MR) phenotype, with previous carbapenem exposure in 44%. Logistic regression analysis identified severity of acute illness (odds ratio [OR], 1.0; 95% confidence interval [CI], 1.0 to 1.1), prior carbapenem use (OR, 7.8; 95% CI, 1.7 to 35.3), and prior use of fluoroquinolones (OR, 11.0; 95% CI, 1.7 to 67.9) as independent risk factors for CR-PA digestive tract colonization. Overall, the local epidemiology of CR-PA digestive tract colonization was characterized by polyclonal endemicity with phenotype patterns of IR and MR divided evenly between patients. Restricting the use of particular agents, such as carbapenems and fluoroquinolones, should be considered advisable to minimize the problem of this antibiotic resistance. However, the possible risk for development of collateral unexpected bacterial resistance patterns should be accurately monitored.
The Lancet Infectious Diseases, 2020
Background Carbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA. Methods CRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Clinical data and bacteria were collected, and whole genome sequencing was done. This trial is registered with ClinicalTrials. gov, number NCT03646227. Findings 1040 patients with unique isolates were included, 449 (43%) with infection and 591 (57%) with colonisation. The CDC-defined CRE admission rate was 57 per 100 000 admissions (95% CI 45-71). Three subsets of CDC-defined CRE were identified: carbapenemase-producing Enterobacterales (618 [59%] of 1040), non-carbapenemase-producing Enterobacterales (194 [19%]), and unconfirmed CRE (228 [22%]; initially reported as CRE, but susceptible to carbapenems in two central laboratories). Klebsiella pneumoniae carbapenemase-producing clonal group 258 K pneumoniae was the most common carbapenemase-producing Enterobacterales. In 449 patients with CDC-defined CRE infections, DOOR outcomes were not significantly different in patients with carbapenemase-producing Enterobacterales, non-carbapenemase-producing Enterobacterales, and unconfirmed CRE. At 30 days 107 (24%, 95% CI 20-28) of these patients had died. Interpretation Among patients with CDC-defined CRE, similar outcomes were observed among three subgroups, including the novel unconfirmed CRE group. CDC-defined CRE represent diverse bacteria, whose spread might not respond to interventions directed to carbapenemase-producing Enterobacterales.