Epidemiology and control measures of an OXA-48-producing <i>Enterobacteriaceae</i> hospital-wide oligoclonal outbreak

Pérez-Blanco, Verónica; Bravo, Laura; Ruiz‐Carrascoso, Guillermo; Paño‐Pardo, José Ramón; Gómez-Gil, Rosa; Robustillo-Rodela, A.; García-Rodríguez, Julio; Mingorance, Jesús; Herruzo, Rafael

doi:10.1017/s0950268818000249

Cited by 19 publications

(17 citation statements)

References 19 publications

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“…OXA-48-producing K. pneumoniae were first detected in our hospital in December 2010 and have spread through several hospital units since then (Paño-Pardo et al, 2013;Pérez-Blanco et al, 2018). Two major and several minor sporadic clones have been identified.…”

Section: Introductionmentioning

confidence: 90%

Meropenem heteroresistance in clinical isolates of OXA-48–producing Klebsiella pneumoniae

López-Camacho

Paño‐Pardo

Sotillo

et al. 2019

Diagnostic Microbiology and Infectious Disease

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OXA-48-producing Klebsiella pneumoniae isolates often show growth of colonies within inhibition zones in carbapenem diffusion assays. The nature of these colonies was investigated in a series of clinical isolates of OXA-48producing K. pneumoniae obtained in the context of a hospital outbreak, and they were found to be persistent colonies that reproduced again the same phenotype when they were collected and tested in diffusion assays again. The frequency of mutations conferring resistance to meropenem (8 μg/mL) was determined for the same isolates. The average mutation frequency was 5.47·10 −6 (range: 2.59·10 −8 -5.87·10 −5 ), and the analysis of several resistant mutants showed that all of them had mutations in the ompK36 porin gene. Heteroresistance was investigated using population analysis profiling. The profiles were compatible with mutation frequency assays, and all the colonies analyzed were resistant mutants. In OXA-48-producing K. pneumoniae, the growth of persisters seems to be specific of diffusion assays.

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Section: Introductionmentioning

confidence: 90%

Meropenem heteroresistance in clinical isolates of OXA-48–producing Klebsiella pneumoniae

López-Camacho

Paño‐Pardo

Sotillo

et al. 2019

Diagnostic Microbiology and Infectious Disease

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“…The bla OXA-48 gene is often found in Tn1999 composite transposons that harbor copies of IS1999 flanking both sides of this ␤-lactamase gene (240). Isolates that express OXA-48 may be susceptible to cephalosporins and have only modestly elevated carbapenem MIC values, with many imipenem MICs of Յ2 g/ml (241,242). High-level resistance to carbapenems is usually due to a secondary nonenzymatic resistance mechanism in these isolates (239).…”

Section: Carbapenemase-producing Bacteriamentioning

confidence: 99%

Epidemiology of β-Lactamase-Producing Pathogens

Bush

Bradford²

2020

Clin Microbiol Rev

579

440

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SUMMARY β-Lactam antibiotics have been widely used as therapeutic agents for the past 70 years, resulting in emergence of an abundance of β-lactam-inactivating β-lactamases. Although penicillinases in Staphylococcus aureus challenged the initial uses of penicillin, β-lactamases are most important in Gram-negative bacteria, particularly in enteric and nonfermentative pathogens, where collectively they confer resistance to all β-lactam-containing antibiotics. Critical β-lactamases are those enzymes whose genes are encoded on mobile elements that are transferable among species. Major β-lactamase families include plasmid-mediated extended-spectrum β-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases now appearing globally, with geographic preferences for specific variants. CTX-M enzymes include the most common ESBLs that are prevalent in all areas of the world. In contrast, KPC serine carbapenemases are present more frequently in the Americas, the Mediterranean countries, and China, whereas NDM metallo-β-lactamases are more prevalent in the Indian subcontinent and Eastern Europe. As selective pressure from β-lactam use continues, multiple β-lactamases per organism are increasingly common, including pathogens carrying three different carbapenemase genes. These organisms may be spread throughout health care facilities as well as in the community, warranting close attention to increased infection control measures and stewardship of the β-lactam-containing drugs in an effort to control selection of even more deleterious pathogens.

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“…The most common STs identified in nationwide surveillances were ST101 in the United Kingdom (30) and ST395 in Poland (95). Regional nosocomial outbreaks of different K. pneumoniae STs have been reported from various countries, including the following: ST11, ST101, and ST405 in Spain (84), ST147 in Germany (131) and Slovenia (99), and ST11 in Croatia (98) and Spain (133). The analysis of the K. pneumoniae ST147 outbreak in Germany showed that bla OXA-48 was harbored on pOXA-48a-like IncL plasmids, while bla CTX-M-15 and other antimicrobial resistance genes were situated within IncR and IncC plasmids (131).…”

Section: Genetic Environments Surrounding Bla Oxa-48mentioning

confidence: 99%

The Global Ascendency of OXA-48-Type Carbapenemases

et al. 2019

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SUMMARY Surveillance studies have shown that OXA-48-like carbapenemases are the most common carbapenemases in Enterobacterales in certain regions of the world and are being introduced on a regular basis into regions of nonendemicity, where they are responsible for nosocomial outbreaks. OXA-48, OXA-181, OXA-232, OXA-204, OXA-162, and OXA-244, in that order, are the most common enzymes identified among the OXA-48-like carbapenemase group. OXA-48 is associated with different Tn1999 variants on IncL plasmids and is endemic in North Africa and the Middle East. OXA-162 and OXA-244 are derivatives of OXA-48 and are present in Europe. OXA-181 and OXA-232 are associated with ISEcp1, Tn2013 on ColE2, and IncX3 types of plasmids and are endemic in the Indian subcontinent (e.g., India, Bangladesh, Pakistan, and Sri Lanka) and certain sub-Saharan African countries. Overall, clonal dissemination plays a minor role in the spread of OXA-48-like carbapenemases, but certain high-risk clones (e.g., Klebsiella pneumoniae sequence type 147 [ST147], ST307, ST15, and ST14 and Escherichia coli ST38 and ST410) have been associated with the global dispersion of OXA-48, OXA-181, OXA-232, and OXA-204. Chromosomal integration of blaOXA-48 within Tn6237 occurred among E. coli ST38 isolates, especially in the United Kingdom. The detection of Enterobacterales with OXA-48-like enzymes using phenotypic methods has improved recently but remains challenging for clinical laboratories in regions of nonendemicity. Identification of the specific type of OXA-48-like enzyme requires sequencing of the corresponding genes. Bacteria (especially K. pneumoniae and E. coli) with blaOXA-48, blaOXA-181, and blaOXA-232 are emerging in different parts of the world and are most likely underreported due to problems with the laboratory detection of these enzymes. The medical community should be aware of the looming threat that is posed by bacteria with OXA-48-like carbapenemases.

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Epidemiology and control measures of an OXA-48-producing Enterobacteriaceae hospital-wide oligoclonal outbreak

Cited by 19 publications

References 19 publications

Meropenem heteroresistance in clinical isolates of OXA-48–producing Klebsiella pneumoniae

Meropenem heteroresistance in clinical isolates of OXA-48–producing Klebsiella pneumoniae

Epidemiology of β-Lactamase-Producing Pathogens

The Global Ascendency of OXA-48-Type Carbapenemases

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