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Keywords = Enterobacter cloacae complex

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20 pages, 1699 KB  
Article
Whole-Genome Sequencing Reveals Heterogeneous Resistance Profiles and Selected Mobile Genetic Elements in Ecuadorian Clinical Enterobacter hormaechei subsp. xiangfangensis and subsp. hoffmannii
by Laura Bejarano, Miroslava Anna Šefcová, Karen Muñoz-Mawyin, Isaías Mejía Limones, César Marcelo Larrea-Álvarez, Gabriela Irene Andrade Mena, Erick Saráuz, Pedro Barba and Marco Larrea-Álvarez
Antibiotics 2026, 15(4), 387; https://doi.org/10.3390/antibiotics15040387 - 10 Apr 2026
Viewed by 833
Abstract
Background: Enterobacter hormaechei, a member of the Enterobacter cloacae complex (ECC), is increasingly recognized as a multidrug-resistant (MDR) nosocomial pathogen. However, subspecies-level genomic data from Ecuador remain limited. Methods: Four clinical E. hormaechei isolates from a hospital in northern Ecuador were [...] Read more.
Background: Enterobacter hormaechei, a member of the Enterobacter cloacae complex (ECC), is increasingly recognized as a multidrug-resistant (MDR) nosocomial pathogen. However, subspecies-level genomic data from Ecuador remain limited. Methods: Four clinical E. hormaechei isolates from a hospital in northern Ecuador were analyzed using antimicrobial susceptibility testing and whole-genome sequencing (WGS). Genomic characterization included multilocus sequence typing (MLST), resistome profiling, plasmid replicon detection, integron screening, genomic island analysis, and phylogenetic comparison with publicly available Ecuadorian genomes. Results: WGS identified three isolates as subsp. xiangfangensis (ST136 and ST337) and one as subsp. hoffmannii (ST145). Two ST136 isolates exhibited extensive MDR phenotypes associated with blaCTX-M-15, blaOXA-1, blaACT-16, and additional aminoglycoside and fluoroquinolone resistance genes. ST145 showed moderate resistance, whereas ST337 remained largely susceptible despite harboring blaACT-16. Multiple genomic islands and plasmid replicons (IncF/IncR or IncHI2) were detected. Phylogenetic analysis demonstrated clustering with previously reported Ecuadorian lineages. Conclusions: This study provides subspecies-level genomic characterization of clinical E. hormaechei in Ecuador and describes heterogeneous resistance profiles and associated mobile genetic elements, contributing baseline data for regional surveillance. Full article
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17 pages, 325 KB  
Article
Prevalence and Antimicrobial Resistance Profiles of E. coli, P. mirabilis, and E. cloacae Complex Isolated from Dogs with Otitis Externa
by Ionela Popa, Ionica Iancu, Alexandru Gligor, Kalman Imre, Emil Tîrziu, Timea Bochiș, Călin Pop, Janos Degi, Andrei Ivan, Michael Dahma, Ana-Maria Plotuna, Sebastian Alexandru Popa, Marius Pentea, Viorel Herman and Ileana Nichita
Antibiotics 2026, 15(4), 343; https://doi.org/10.3390/antibiotics15040343 - 27 Mar 2026
Cited by 1 | Viewed by 935
Abstract
Background/Objectives: Antimicrobial resistance (AMR) in companion animals is an emerging public health threat due to zoonotic potential and limited therapeutic options. Dogs with otitis externa may harbor multidrug-resistant (MDR) bacteria, including Escherichia coli (E. coli), Proteus mirabilis (P. mirabilis), [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) in companion animals is an emerging public health threat due to zoonotic potential and limited therapeutic options. Dogs with otitis externa may harbor multidrug-resistant (MDR) bacteria, including Escherichia coli (E. coli), Proteus mirabilis (P. mirabilis), and Enterobacter cloacae complex (E. cloacae complex), some producing extended-spectrum beta-lactamase (ESBL) or AmpC β-lactamases. This study aimed to assess the prevalence, AMR patterns, MDR occurrence, β-lactamase production, and co-infection profiles of these pathogens in canine otitis externa. Methods: Ear canal samples were collected from 592 dogs presenting clinical signs of otitis externa, with one sample per dog included in the analysis. Samples were collected from veterinary clinics in Timiș County, Romania, from 2022 to 2025. Samples were cultured on blood agar and MacConkey agar, followed by biochemical testing and MALDI-TOF mass spectrometry for bacterial identification. Antimicrobial susceptibility testing against 15 agents across six classes was performed using the VITEK® 2 system. MDR and β-lactamase production (ESBL, AmpC) were determined according to CLSI 2018 veterinary guidelines. Co-isolation with bacterial and fungal species were recorded. Results: E. coli, P. mirabilis, and E. cloacae complex were isolated in 9.12%, 6.25%, and 1.2% of cases, respectively. E. coli exhibited the highest resistance to aminoglycosides (tobramycin 72.2%, gentamicin 61.1%) and full susceptibility to carbapenems. P. mirabilis showed the highest resistance to ampicillin (54%) and trimethoprim + sulfamethoxazole (46%), with complete susceptibility to carbapenems and fluoroquinolones. E. cloacae complex displayed universal resistance to cephalosporins but remained susceptible to non-cephalosporin β-lactams (piperacillin–tazobactam), carbapenems and aminoglycosides. MDR prevalence was 35.2% for E. coli, 18.9% for P. mirabilis, and 14.3% for the E. cloacae complex. ESBL production was detected in 13% of E. coli and 8.1% of P. mirabilis isolates, while all E. cloacae complex isolates were AmpC-positive. Co-isolations were common, primarily involving Staphylococcus pseudintermedius (S. pseudintermedius) and Malassezia pachydermatis (M. pachydermatis). Conclusions: MDR and β-lactamase-producing bacteria were identified in dogs with otitis externa, emphasizing the importance of routine antimicrobial susceptibility testing, targeted therapy based on local resistance profiles, and continuous AMR surveillance to prevent treatment failure and mitigate zoonotic risk. Full article
14 pages, 797 KB  
Review
A New Challenge of Antibiotic-Resistant Bacteria: Carbapenem-Resistant Enterobacter cloacae Complex in a One Health Perspective
by Huina Wang, Jingyi Han, Yuhui Li, Dong Ding and Xuewen Li
Microorganisms 2026, 14(3), 594; https://doi.org/10.3390/microorganisms14030594 - 6 Mar 2026
Viewed by 1303
Abstract
Carbapenem-resistant Enterobacter cloacae Complex (CRECC) has emerged as an important multidrug-resistant pathogen in healthcare settings, although it has historically received less attention than carbapenem-resistant Klebsiella pneumoniae and other major carbapenem-resistant Enterobacterales (CRE). Recent epidemiological reports from several regions indicate increasing detection rates of [...] Read more.
Carbapenem-resistant Enterobacter cloacae Complex (CRECC) has emerged as an important multidrug-resistant pathogen in healthcare settings, although it has historically received less attention than carbapenem-resistant Klebsiella pneumoniae and other major carbapenem-resistant Enterobacterales (CRE). Recent epidemiological reports from several regions indicate increasing detection rates of CRECC in tertiary hospitals, where it is associated with bloodstream infections, pneumonia, urinary tract infections, and prolonged hospitalization. The dissemination of carbapenemase genes, particularly blaNDM, blaKPC, and blaOXA-48-like, carried predominantly on conjugative plasmids (e.g., IncFII, IncX3, IncL), represents the primary resistance mechanism, often accompanied by porin loss and efflux pump overexpression. High-risk clones such as ST171 and ST78 contribute to nosocomial persistence and outbreak potential. Beyond clinical settings, CRECC and related resistance determinants have been reported in companion animals, livestock, food products, wastewater systems, and natural aquatic environments. Although most available studies examine these sectors separately, the recurring detection of genetically related resistance genes and plasmid types suggests potential epidemiological links that warrant integrated surveillance. Environmental reservoirs, particularly hospital effluents and wastewater treatment systems, may facilitate the maintenance and dissemination of resistance genes. This review synthesizes current evidence on the epidemiology, resistance mechanisms, and evolutionary dynamics of CRECC in human, animal, and environmental contexts under a One Health framework. A better understanding of its ecological distribution and genetic plasticity is essential to inform coordinated surveillance strategies and mitigate the public health risks associated with the continued spread of carbapenem resistance. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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7 pages, 215 KB  
Case Report
Catheter-Related Bloodstream Infection with Leclercia adecarboxylata and Enterobacter cloacae Complex Co-Infection: A Case Report and Literature Review
by Po-Hsiu Huang, Po-Yu Liu and Hsien-Po Huang
Microorganisms 2026, 14(2), 402; https://doi.org/10.3390/microorganisms14020402 - 8 Feb 2026
Viewed by 792
Abstract
Catheter-related bloodstream infections (CRBSIs) caused by Leclercia adecarboxylata are uncommon, and polymicrobial cases are even rarer. We report the first documented case caused by co-infection with Leclercia adecarboxylata and Enterobacter cloacae complex (ECC) in a woman with breast cancer undergoing chemotherapy through an [...] Read more.
Catheter-related bloodstream infections (CRBSIs) caused by Leclercia adecarboxylata are uncommon, and polymicrobial cases are even rarer. We report the first documented case caused by co-infection with Leclercia adecarboxylata and Enterobacter cloacae complex (ECC) in a woman with breast cancer undergoing chemotherapy through an indwelling chemoport. Antimicrobial susceptibility testing revealed that both isolates were susceptible to β-lactams, quinolones, and aminoglycosides. The patient achieved complete clinical recovery following intravenous ciprofloxacin therapy and prompt removal of the chemoport. This case highlights the emerging clinical relevance of Leclercia adecarboxylata and Enterobacter cloacae complex as potential pathogens capable of causing polymicrobial bloodstream infections in immunocompromised hosts and underscores the importance of considering rare environmental Gram-negative organisms as potential causes of catheter-related infections, particularly in patients with malignancy or long-term vascular access. Full article
(This article belongs to the Section Medical Microbiology)
13 pages, 1484 KB  
Article
Clinical and Genetic Characteristics of Enterobacter cloacae and Klebsiella aerogenes in Children
by Ki Wook Yun, Ye Eun Kim, Dayun Kang and Hye Jeong Moon
Microorganisms 2026, 14(2), 292; https://doi.org/10.3390/microorganisms14020292 - 27 Jan 2026
Viewed by 1652
Abstract
This study investigated the clinical and genomic characteristics of Enterobacter cloacae complex (ECC) and Klebsiella aerogenes bloodstream infections (BSIs) in pediatric patients. A total of 115 BSI episodes (ECC: 86, K. aerogenes: 29) from 110 children hospitalized between 2011 and 2024 were [...] Read more.
This study investigated the clinical and genomic characteristics of Enterobacter cloacae complex (ECC) and Klebsiella aerogenes bloodstream infections (BSIs) in pediatric patients. A total of 115 BSI episodes (ECC: 86, K. aerogenes: 29) from 110 children hospitalized between 2011 and 2024 were retrospectively analyzed. Whole-genome sequencing was performed on available isolates to determine species, sequence types, and antimicrobial resistance (AMR) genes. Clinical characteristics, antibiotic usage, and outcomes were compared between groups. Patients with K. aerogenes BSI were younger and more likely to be preterm or diagnosed with urosepsis, while ECC infections were more frequently associated with hematologic malignancies. According to a multivariable analysis of the entire cohort (n = 115), K. aerogenes infection (OR [6.26], 95% CI [1.36–28.78]) and gentamicin resistance (OR [10.06], 95% CI [1.88–53.87]) were independently associated with 30-day mortality. Enterobacter hormaechei was the most common ECC species (68.4%) and exhibited the highest prevalence of AMR genes, particularly those conferring resistance to aminoglycosides, β-lactams, and trimethoprim–sulfamethoxazole. In contrast, K. aerogenes harbored few resistance genes. Multi-locus sequence typing analysis revealed high genetic diversity in both ECC and K. aerogenes, without evidence of dominant clonal expansion. Despite similarities in clinical presentation, ECC and K. aerogenes exhibit distinct age distributions, resistance profiles, and genetic diversity in pediatric BSIs. These findings underscore the importance of species-level identification and continued genomic surveillance to inform empirical antibiotic strategies and prevent the spread of resistant strains. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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16 pages, 500 KB  
Article
Faster Diagnosis of Suspected Lower Respiratory Tract Infections: Single-Center Evidence from BIOFIRE FilmArray® Pneumonia Panel Results vs. Conventional Culture Method
by Beatrice Silvia Orena, Lisa Cariani, Elena Tomassini, Filippo Girardi, Monica D’Accico, Alessia Pirrone, Caterina Biassoni, Daniela Girelli, Antonio Teri, Marco Tonelli, Claudia Alteri and Annapaola Callegaro
Diagnostics 2026, 16(2), 342; https://doi.org/10.3390/diagnostics16020342 - 21 Jan 2026
Cited by 1 | Viewed by 842
Abstract
Background/Objectives: Syndromic multiplex PCR assays such as BIOFIRE FilmArray® Pneumonia (PN) panel enable rapid and simultaneous detection of bacterial and viral pathogens in respiratory specimens, improving diagnostic accuracy and patient management in lower respiratory tract infections (LRTIs). Methods: In this [...] Read more.
Background/Objectives: Syndromic multiplex PCR assays such as BIOFIRE FilmArray® Pneumonia (PN) panel enable rapid and simultaneous detection of bacterial and viral pathogens in respiratory specimens, improving diagnostic accuracy and patient management in lower respiratory tract infections (LRTIs). Methods: In this retrospective observational study, PN panel results in 410 bronchoalveolar lavage (BAL) samples from hospitalized patients with suspected pneumonia were analyzed and compared with those obtained using the conventional culture (CC) method. Results: The PN panel showed an overall positivity rate of 54%, detecting bacteria in 39.0% of samples, viruses in 7.1%, and atypical bacteria in 2.2%. Using the conventional culture (CC) method, 33.9% of samples tested positive. Overall, 83 (20.2%) samples that were positive by the PN panel were negative by CC, whereas only 14 specimens (3.4%) were positive by CC and negative by PN panel. The most frequently detected pathogen by both the PN panel and CC was Staphylococcus aureus (n = 67, 16.34% for PN; n = 40, 9.76% for CC). Regarding diagnostic performance, the PN panel demonstrated a sensitivity of 89.02%, a specificity of 97.86%, and an overall accuracy of 97.63%. Lower sensitivity values were observed only for the Enterobacter cloacae complex (57.14%) and the Klebsiella pneumoniae group (75%). Specificity exceeded 92% for all bacterial targets. Conclusions: The PN panel confirms enhanced pathogen detection and a shortened time-to-result. It serves as a valuable adjunct for the timely diagnosis of LRTIs, supporting antimicrobial stewardship through more precise and appropriate antibiotic selection. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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9 pages, 216 KB  
Case Report
Use of Aztreonam–Avibactam with Rapid Eravacycline Step-Down Therapy for a Tibial Septic Non-Union by NDM-Producing Enterobacter cloacae
by Jacob M. Keck, Ryan K. Dare, Michael Saccente, Keyur S. Vyas and Rebekah N. Thompson
Antibiotics 2025, 14(11), 1109; https://doi.org/10.3390/antibiotics14111109 - 4 Nov 2025
Cited by 2 | Viewed by 1832
Abstract
New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales represent a major therapeutic challenge due to their resistance to nearly all β-lactams and frequent co-resistance to other antibiotic classes, leaving clinicians with few effective options. These challenges are amplified in orthopedic infections with hardware involvement, where biofilm [...] Read more.
New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales represent a major therapeutic challenge due to their resistance to nearly all β-lactams and frequent co-resistance to other antibiotic classes, leaving clinicians with few effective options. These challenges are amplified in orthopedic infections with hardware involvement, where biofilm formation and the need for prolonged antimicrobial therapy limit success. We describe a 55-year-old female with a history of right type 3 open pilon fracture complicated by hardware failure and revision, who presented with septic tibial nonunion and chronic drainage. During this admission, she underwent irrigation and debridement with hardware removal and intramedullary nail placement. Cultures grew Enterobacter cloacae complex resistant to meropenem, ceftazidime–avibactam, meropenem–vaborbactam, and cefiderocol, as well as Candida parapsilosis. Molecular testing confirmed NDM production, while reference testing showed susceptibility to aztreonam–avibactam (ATM-AVI). The patient was treated with ATM-AVI plus micafungin, achieving clinical stability within three days. Due to outpatient administration barriers with ATM-AVI, the patient was transitioned to eravacycline and micafungin. At eight-week follow-up, the patient remained clinically improved without relapse or adverse effects. This case highlights ATM-AVI as a critical therapy for NDM-producing orthopedic infections involving hardware and supports eravacycline as a feasible step-down option in outpatient management. Full article
20 pages, 2552 KB  
Article
Environmental Dispersion of Multiresistant Enterobacteriaceae in Aquatic Ecosystems in an Area of Spain with a High Density of Pig Farming
by Javier Díez de los Ríos, Noemí Párraga-Niño, María Navarro, Judit Serra-Pladevall, Anna Vilamala, Elisenda Arqué, María Baldà, Tamar Nerea Blanco, Luisa Pedro-Botet, Óscar Mascaró and Esteban Reynaga
Antibiotics 2025, 14(8), 753; https://doi.org/10.3390/antibiotics14080753 - 25 Jul 2025
Cited by 1 | Viewed by 1388
Abstract
Background: This study aimed to (a) assess the prevalence of multidrug-resistant (MDR) Enterobacteriaceae in the waters of two rivers and wastewater treatment plants (WWTPs) in a region of Catalonia, Spain; (b) genetically characterize the MDR strains; and (c) compare extended-spectrum β-lactamase (ESBL)-producing [...] Read more.
Background: This study aimed to (a) assess the prevalence of multidrug-resistant (MDR) Enterobacteriaceae in the waters of two rivers and wastewater treatment plants (WWTPs) in a region of Catalonia, Spain; (b) genetically characterize the MDR strains; and (c) compare extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolates from environmental and human sources. Methods: A total of 62 samples were collected from the influent and effluent of 31 WWTPs and 29 river water samples from 11 sites. Simultaneously, 382 hospitalized patients were screened for MDR Enterobacteriaceae using rectal swabs. All isolates underwent antibiotic susceptibility testing and whole-genome sequencing. Results: MDR Enterobacteriaceae were detected in 48.4% of WWTP samples, with 18.5% ESBL-producing E. coli and 1.5% (one sample) OXA-48-producing K. pneumoniae in influents, and 12.8% ESBL-producing E. coli in effluents. In river waters, 5.6% of samples contained ESBL-producing E. coli and 1.4% (1 sample) contained VIM-producing Enterobacter cloacae complex strains. Among patients, 10.2% (39/382) carried MDR Gram-negative bacilli, of which 66.7% were ESBL-producing E. coli. In aquatic ecosystems E. coli ST131 (13.3%) and ST162 (13.3%) were the most common strains, while in humans the common were E. coli ST131 (33.3%), ST69 (11.1%) and ST410 (7.4%) in humans. The most frequent environmental antibiotic resistance genes (ARG) were blaCTX-M-15 (24%) and blaTEM-1B (20%), while the most common ARGs were blaTEM-1B (20.4%), blaCTX-M15 (18.4%) and blaCTX-M-27 (14.3%). IncF plasmids were predominant in environmental and human strains. Conclusions: ESBL-producing E. coli and carbapenemase-producing Enterobacteriaceae are present in aquatic environments in the region. Phylogenetic similarities between environmental and clinical strains suggest a possible similar origin. Further studies are necessary to clarify transmission routes and environmental impact. Full article
(This article belongs to the Special Issue A One Health Approach to Antimicrobial Resistance, 2nd Edition)
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18 pages, 1178 KB  
Article
Prevalence and Antimicrobial Resistance of Gram-Negative ESKAPE Pathogens Isolated from Tertiary Care Hospital in Eastern India
by Paramjyoti Rana, Sweta Padma Routray, Surajit De Mandal, Rajashree Panigrahy, Anjan Kumar Sahoo and Enketeswara Subudhi
Appl. Sci. 2025, 15(15), 8171; https://doi.org/10.3390/app15158171 - 23 Jul 2025
Cited by 3 | Viewed by 5859
Abstract
Gram-negative ESKAPE pathogens pose major challenges to global public health due to their multidrug resistance and virulence. The present study aimed to study the prevalence and resistance of Gram-negative ESKAPE pathogens at a tertiary care hospital in Eastern India. A retrospective analysis was [...] Read more.
Gram-negative ESKAPE pathogens pose major challenges to global public health due to their multidrug resistance and virulence. The present study aimed to study the prevalence and resistance of Gram-negative ESKAPE pathogens at a tertiary care hospital in Eastern India. A retrospective analysis was conducted on 7343 non-duplicate isolates collected between January 2023 and December 2024. The bacterial isolates and their antibiotic susceptibility testing were identified using Kirby–Bauer disk diffusion techniques and the VITEK 2 Compact system, adhering to CLSI 2025 and EUCAST 2024 guidelines. Our findings indicate that Klebsiella pneumoniae was the most common isolate, followed by Pseudomonas aeruginosa, Acinetobacter baumannii complex, and Enterobacter cloacae complex, predominantly affecting male patients aged 18–64 years. Importantly, most of these isolates exhibit increased multidrug resistance (MDR) to several key antibiotics, including β-lactams and carbapenems, which further complicates the treatment process. The analysis of seasonal dynamics revealed an increased abundance of infections in monsoon and post-monsoon periods. These findings will be useful in understanding AMR in hospital environments and in developing strategies to prevent the occurrence and spread of antimicrobial resistance among pathogens. Full article
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26 pages, 477 KB  
Review
Global Epidemiology and Antimicrobial Resistance of Klebsiella Pneumoniae Carbapenemase (KPC)-Producing Gram-Negative Clinical Isolates: A Review
by Matthew E. Falagas, Christina-Maria Asimotou, Maria Zidrou, Dimitrios S. Kontogiannis and Charalampos Filippou
Microorganisms 2025, 13(7), 1697; https://doi.org/10.3390/microorganisms13071697 - 19 Jul 2025
Cited by 25 | Viewed by 7830
Abstract
Klebsiella pneumoniae carbapenemases (KPCs) are a group of class A β-lactamases of Gram-negative bacteria leading to difficult-to-treat infections. We evaluated the global epidemiology of KPC-producing Gram-negative clinical isolates. A systematic search of six databases (Cochrane Library, Embase, Google Scholar, PubMed, Scopus, and Web [...] Read more.
Klebsiella pneumoniae carbapenemases (KPCs) are a group of class A β-lactamases of Gram-negative bacteria leading to difficult-to-treat infections. We evaluated the global epidemiology of KPC-producing Gram-negative clinical isolates. A systematic search of six databases (Cochrane Library, Embase, Google Scholar, PubMed, Scopus, and Web of Science) was conducted. Extracted data were tabulated and evaluated. After screening 1993 articles, 119 were included in the study. The included studies originated from Asia (n = 49), Europe (n = 29), North America (n = 14), South America (n = 11), and Africa (n = 3); 13 studies were multicontinental. The most commonly reported KPC-producing species were Klebsiella pneumoniae (96 studies) and Escherichia coli (52 studies), followed by Enterobacter cloacae (31), Citrobacter spp. (24), Klebsiella oxytoca (23), Serratia spp. (15), Enterobacter spp. (15), Acinetobacter baumannii complex (13), Providencia spp. (11), Morganella spp. (11), Klebsiella aerogenes (9), Pseudomonas aeruginosa (8), Raoultella spp. (8), Proteus spp. (8), and Enterobacter aerogenes (6). Among the studies with specific blaKPC gene detection, 52/57 (91%) reported the isolation of blaKPC-2 and 26/57 (46%) reported blaKPC-3. The antimicrobial resistance of the studied KPC-producing isolates was the lowest for ceftazidime–avibactam (0–4%). Resistance to polymyxins, tigecycline, and trimethoprim–sulfamethoxazole in the evaluated studies was 4–80%, 0–73%, and 5.6–100%, respectively. Conclusions: The findings presented in this work indicate that KPC-producing Gram-negative bacteria have spread globally across all continents. Implementing proper infection control measures, antimicrobial stewardship programs, and enhanced surveillance is crucial. Full article
(This article belongs to the Special Issue ß-Lactamases, 3rd Edition)
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9 pages, 457 KB  
Communication
Antimicrobial Susceptibility Testing of the Combination of Aztreonam and Avibactam in NDM-Producing Enterobacterales: A Comparative Evaluation Using the CLSI and EUCAST Methods
by Linda Mei-Wah Chan, Doris Yui Ling Lok, River Chun Wai Wong, Alfred Lok-Hang Lee, Ingrid Yu-Ying Cheung, Christopher Koon-Chi Lai and Viola C. Y. Chow
Antibiotics 2025, 14(7), 675; https://doi.org/10.3390/antibiotics14070675 - 3 Jul 2025
Cited by 1 | Viewed by 4352
Abstract
Background: The combination of aztreonam (ATM) and avibactam (AVI) presents an important therapeutic option for carbapenem-resistant Enterobacterales, particularly the NDM-producing Enterobacterales. In 2024, both the CLSI and EUCAST published their methods in antimicrobial susceptibility testing for this combination of agents. [...] Read more.
Background: The combination of aztreonam (ATM) and avibactam (AVI) presents an important therapeutic option for carbapenem-resistant Enterobacterales, particularly the NDM-producing Enterobacterales. In 2024, both the CLSI and EUCAST published their methods in antimicrobial susceptibility testing for this combination of agents. Materials and Methods: Forty carbapenem-resistant Enterobacterales isolates, including Escherichia coli (n = 35), Enterobacter cloacae complex (n = 2), Klebsiella pneumoniae complex (n = 2), and Citrobacter freundii complex (n = 1) were included in this study. All isolates harbored the NDM carbapenemase except one, which had no known detected carbapenemases. Four antimicrobial susceptibility testing methods of the combination of ATM and AVI were evaluated on these isolates, including the CLSI broth disk elution (BDE) method, the disk diffusion (DD) method of aztreonam–avibactam (AZA) following the EUCAST breakpoints, the MIC test strip (MTS) method of AZA following the EUCAST breakpoints, and the gradient strip stacking (SS) method. BDE was used as the standard of comparison. Results: Using BDE as the standard of comparison, the AZA DD, AZA MTS, and SS methods had 100% categorical agreement (CA), 0% very major error (VME), and 0% major error (ME). The essential agreement (EA) between the AZA MTS and SS method was 57.5%. Conclusions: The AZA DD, AZA MTS, and the SS methods showed complete concordance with the BDE method. However, the MICs obtained from the AZA MTS and SS were not comparable. Full article
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14 pages, 1541 KB  
Article
First Report in the Americas of S. enterica Var. Enteritidis Carrying blaNDM-1 in a Putatively New Sub-Lineage of IncC2 Plasmids
by Nicolás F. Cordeiro, Romina Papa-Ezdra, Germán Traglia, Inés Bado, Virginia García-Fulgueiras, María N. Cortinas, Leticia Caiata, Mariana López-Vega, Ana Otero, Martín López, Patricia Hitateguy, Cristina Mogdasy and Rafael Vignoli
Antibiotics 2025, 14(6), 620; https://doi.org/10.3390/antibiotics14060620 - 18 Jun 2025
Cited by 2 | Viewed by 1715
Abstract
Background: Infections caused by carbapenem-resistant Enterobacterales have steadily multiplied over time, becoming a major threat to healthcare systems due to limited therapeutic options and high case-fatality rates. Case report: We studied a patient who, after being discharged from an ICU, developed salmonellosis caused [...] Read more.
Background: Infections caused by carbapenem-resistant Enterobacterales have steadily multiplied over time, becoming a major threat to healthcare systems due to limited therapeutic options and high case-fatality rates. Case report: We studied a patient who, after being discharged from an ICU, developed salmonellosis caused by an antibiotic-susceptible S. enteritidis. After undergoing treatment with ciprofloxacin, the patient presented an episode of asymptomatic bacteriuria originated by a carbapenem and ciprofloxacin-resistant S. enteritidis. Results: Whole genome sequencing analysis revealed that both Salmonella isolates belonged to the same strain, and that isolate SEn_T2 acquired a plasmid carrying both blaNDM-1 and qnrA1 genes (pIncCSEn) which was previously present in the patient’s gut in at least one Enterobacter cloacae isolate. Additionally, pIncCSEN was identified as a putatively new sub-lineage of IncC2 plasmids which lacked the first copy of the methyltransferase gene dcm and the rhs gene. The resistance genes blaNDM-1 and qnrA1 were incorporated into a Tn21-derived transposon that included a complex class 1 integron whose genetic arrangement was: intI1- dfrA12- orfF- aadA2- qacEΔ1-sul1-ISCR1- trpF- ble- blaNDM-1 (in reverse direction)- ISAba125-ISCR1- qnrA- cmlA1- qacEΔ1-sul1. Conclusions: Antimicrobial persistence and co-selection of antibiotic resistance play an important role in the dissemination of antimicrobial resistance genes; in this regard, a joint effort involving the infection control team, effective antibiotic stewardship, and genomic surveillance could help mitigate the spread of these multidrug resistant microorganisms. Full article
(This article belongs to the Special Issue Multidrug-Resistance Patterns in Infectious Pathogens)
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12 pages, 604 KB  
Article
Characterization of Enterobacter cloacae and Citrobacter freundii Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam–Avibactam and Comparator Agents (2019–2023)
by Helio S. Sader, Timothy B. Doyle, John H. Kimbrough, Rodrigo E. Mendes and Mariana Castanheira
Antibiotics 2025, 14(4), 382; https://doi.org/10.3390/antibiotics14040382 - 5 Apr 2025
Cited by 1 | Viewed by 2662
Abstract
Background: Citrobacter freundii (CFC) and Enterobacter cloacae (ECLC) species complexes represent important causes of hospital-associated infections, frequently are related to outbreaks, and have a great ability to develop antimicrobial resistance. We evaluated a large collection of CFC and ECLC isolates with decreased susceptibility [...] Read more.
Background: Citrobacter freundii (CFC) and Enterobacter cloacae (ECLC) species complexes represent important causes of hospital-associated infections, frequently are related to outbreaks, and have a great ability to develop antimicrobial resistance. We evaluated a large collection of CFC and ECLC isolates with decreased susceptibility to broad-spectrum cephalosporins (Ceph-DS) from United States (US) hospitals. Methods: A total of 43,325 Enterobacterales (1/patient) were collected in 2019–2023 and susceptibility tested by broth microdilution; among those, 5106 (11.8%) were CFC (n = 1374) or ECLC (n = 3732). Ceph-DS CFC (n = 379) and ECLC isolates (n = 1065), defined as isolates with ceftazidime MICs ≥ 16 mg/L and/or cefepime MICs ≥ 2 mg/L, were screened for β-lactamase genes by whole genome sequencing. Results: The most common ESBLs were CTX-M type (n = 98; 47.6% of ESBL producers), SHV type (n = 94; 45.6%), and OXA type (n = 78; 37.9%); ≥2 ESBLs were identified in 65 isolates (31.6%), mainly OXA-1/30 plus a CTX-M. A carbapenemase was identified in 55 of 64 (85.9%) carbapenem-resistant (CB-R) isolates, including KPC type (40 isolates; 62.5% of CB-R) and NDM-1 (16; 23.4% of CB-R). Aztreonam–avibactam was active against 99.6% of Ceph-DS and 100.0% of ESBL producers and CB-R isolates, including NDM producers. Ceftazidime–avibactam and meropenem–vaborbactam were active against 100.0% of ESBL producers (excluding carbapenemase co-producers) and 70.3–71.9% of CB-R isolates. Cefiderocol was active against 82.8% of CB-R isolates but only 46.7% of MBL producers. Conclusions: Aztreonam–avibactam was highly active against cephalosporin-nonsusceptible ECLC and CFC, including MBL producers. The activities of ceftazidime–avibactam, meropenem–vaborbactam, and cefiderocol were compromised against CB-R isolates due to the high frequency of NDM producers. Full article
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13 pages, 578 KB  
Review
Plasmid Dissemination in Multispecies Carbapenemase-Producing Enterobacterales Outbreaks Involving Clinical and Environmental Strains: A Narrative Review
by Louis Alglave, Karine Faure and Catherine Mullié
Microorganisms 2025, 13(4), 810; https://doi.org/10.3390/microorganisms13040810 - 2 Apr 2025
Cited by 10 | Viewed by 1889
Abstract
Outbreaks involving carbapenemase-producing enterobacteria (CPE) have become a common occurrence in healthcare settings. While clonal dissemination is firmly established as a cause for these outbreaks, horizontal gene transfers (HGTs) between different species of Enterobacterales found in clinical and environmental isolates are less so. [...] Read more.
Outbreaks involving carbapenemase-producing enterobacteria (CPE) have become a common occurrence in healthcare settings. While clonal dissemination is firmly established as a cause for these outbreaks, horizontal gene transfers (HGTs) between different species of Enterobacterales found in clinical and environmental isolates are less so. To gather evidence backing up this hypothesis, a review covering the 2013–2024 period was performed. HGTs between different species of clinical and environmental Enterobacterales were identified in thirteen papers, half of those published within the last three years. A combination of short- and long-read whole genome sequencing (WGS) was predominantly used to identify mobile genetic elements and plasmids. The more frequently reported carbapenemases were KPCs, followed by NDMs and IMPs. Predictably, broad-host-range plasmids were responsible for over 50% of HGTs, with the IncA/C group being in the lead. Klebsiella pneumoniae and Enterobacter cloacae complexes were the most frequent species identified in clinical samples, while Citrobacter freundii dominated environmental ones. Drains and pipework frequently constituted CPE reservoirs in protracted outbreaks, alternating epidemic outbursts with silent phases. Including WGS in a systematic environmental surveillance would help in swiftly identifying those CPE reservoirs and possibly help better control plasmid outbursts by allowing the implementation of adequate infection prevention and control measures. Full article
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20 pages, 8288 KB  
Article
Molecular Characterization of Gram-Negative Bacilli Isolated from a Neonatal Intensive Care Unit and Phenotypic and Molecular Detection of ESBL and Carbapenemase
by Thaís Alves Barbosa, Maria Regina Bentlin, Lígia Maria Suppo de Souza Rugolo, João César Lyra, Adriano Martison Ferreira, Ana Cláudia Moro Lima dos Santos, Nathalia Bibiana Teixeira, Letícia Calixto Medeiros Romero, Carlos Magno Castelo Branco Fortaleza and Maria de Lourdes Ribeiro de Souza da Cunha
Antibiotics 2025, 14(4), 342; https://doi.org/10.3390/antibiotics14040342 - 27 Mar 2025
Cited by 2 | Viewed by 2339
Abstract
Introduction: The increase in the rates of multidrug-resistant bacteria in healthcare environments has been recognized as a global public health problem. In view of the scarcity of data on the neonatal population, this study aimed to provide information on the genotypic and epidemiological [...] Read more.
Introduction: The increase in the rates of multidrug-resistant bacteria in healthcare environments has been recognized as a global public health problem. In view of the scarcity of data on the neonatal population, this study aimed to provide information on the genotypic and epidemiological characteristics of Gram-negative microorganisms isolated from colonization and infection sites in neonates admitted to a tertiary university center of high complexity. Methods: Enterobacterales and non-fermenting Gram-negative bacilli previously collected in a prospective cohort study were submitted to genotypic identification, detection of extended-spectrum β-lactamases (ESBL), carbapenemases and biofilm production, detection of specific virulence markers in Pseudomonas aeruginosa, and typing by pulsed-field gel electrophoresis. Results: The data found here revealed higher rates of infection by Klebsiella spp. and Serratia marcescens that caused bloodstream infection and pneumonia, respectively. In this study, high biofilm production was observed, with 95.0% of Enterobacterales and 100% of non-fermenting Gram-negative bacilli being producers. Most of the P. aeruginosa isolates carried pathogenicity factors such as alginate, hemolytic phospholipase C, exotoxin A, and rhamnolipids. The phenotypic analysis of ESBL revealed that 16 (5.3%) isolates produced these enzymes. Four of these isolates (66.7%) carried the CTX-M-9 gene, three (50%) carried the TEM gene, and one (16.7%) was positive for the SHV and CMY-2 genes. Univariate and multivariate Cox regression analyses were used to identify risk factors for colonization and infection by Gram-negative microorganisms. The results of multivariate analysis revealed that biofilm production by these microorganisms was associated with the persistence of colonization by the same pathogen in the newborn and increased by 75% the daily probability of the newborn developing infection. The production of ESBL also increased the daily probability of infection by 46.8 times. Conclusions: Enterobacterales showed average biofilm production, while the majority of non-fermenting Gram-negative bacilli were strong producers. The present data increase our knowledge of the molecular epidemiology of important Enterobacterales species, with emphasis on ESBL-producing Enterobacter cloacae and Klebsiella pneumoniae with emerging epidemiological potential in the neonatal intensive care unit of a tertiary university hospital. Furthermore, the results highlight the need for the monitoring and implementation of control measures and for restricting the use of broad-spectrum antibiotics. Full article
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