scholarly journals Molecular surveillance reveals widespread colonisation by carbapenemase and extended spectrum beta-lactamase producing organisms in neonatal units in Kenya and Nigeria

2022 ◽  
Author(s):  
Thomas Edwards ◽  
Christopher T Williams ◽  
Macrine Olwala ◽  
Pauline Andang'o ◽  
Walter Otenio ◽  
...  
Keyword(s):  
Rectal Swab ◽  
Blood Stream Infection ◽  
Sub Saharan Africa ◽  
Antibiotic Prescribing ◽  
Beta Lactamase ◽  
High Resolution Melt ◽  
College Hospital ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Extremely Preterm

Objectives Neonatal sepsis, a major cause of death amongst infants in sub-Saharan Africa, is often gut derived. Impairments in immunity and the gut barrier in sick neonates allow colonisation by opportunistic pathogens such as Enterobacteriaceae to progress to blood stream infection. Colonisation by Enterobacteriaceae producing extended spectrum beta-lactamase (ESBL) or carbapenemase enzymes is particularly problematic and can lead to antimicrobial-resistant (AMR) or untreatable infections. We sought to explore the rates of colonisation by ESBL or carbapenemase producers and their genotypes in two neonatal units (NNUs) in West and East Africa. Methods Stool and rectal swab samples were taken at multiple timepoints from newborns admitted to the NNUs at the University College Hospital, Ibadan, Nigeria and the Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu, western Kenya. Samples were tested for ESBL and carbapenemase genes using a previously validated qPCR assay with high resolution melt analysis. Kaplan-Meier survival analysis was used to examine colonisation rates at both sites. Results A total of 119 stool and rectal swab samples were taken from 42 infants admitted to the two NNUs. Six (14.3%) infants were extremely preterm (gestation <28 weeks), 19 (45.2%) were born by Caesarean section and 3 (8.6%) mothers were HIV positive. Median (IQR) duration of admission was 12.5 (5-26) days and 12 (28.6%) infants died. Overall, colonisation with ESBL (37 infants, 89%) was more common than with carbapenemase producers (26, 62.4%; P = 0.093). Median survival time before colonisation with ESBL organisms was 7 days and with carbapenemase producers 16 days (P=0.035). The majority of ESBL genes detected belonged to the CTX-M-1 (36/38; 95%), and CTX-M-9 (2/36; 5%) groups. The most prevalent carbapenemase was blaNDM (27/29, 93%). Single blaVIM (1/32, 3%) and blaOXA-48 genes (1/32, 3%) were also detected. Conclusions Gut colonisation of neonates by AMR organisms was common and occurred rapidly in NNUs in Kenya and Nigeria. Active surveillance of colonisation will improve the understanding of AMR in these settings and guide infection control and antibiotic prescribing practice to improve clinical outcomes.

scholarly journals Colonisation with extended spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales in children admitted to a paediatric referral hospital in South Africa

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241776
Author(s):  
Babatunde O. Ogunbosi ◽  
Clinton Moodley ◽  
Preneshni Naicker ◽  
James Nuttall ◽  
Colleen Bamford ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Sub Saharan Africa ◽  
Infection Prevention And Control ◽  
Invasive Infection ◽  
Beta Lactamase ◽  
Cross Sectional ◽  
Extended Spectrum Beta Lactamase ◽  
Carbapenem Resistant ◽  
Extended Spectrum

Introduction There are few studies describing colonisation with extended spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenem-resistant Enterobacterales (CRE) among children in sub-Saharan Africa. Colonisation often precedes infection and multi-drug-resistant Enterobacterales are important causes of invasive infection. Methods In this prospective cross-sectional study, conducted between April and June 2017, 200 children in a tertiary academic hospital were screened by rectal swab for EBSL-PE and CRE. The resistance-conferring genes were identified using polymerase chain reaction technology. Risk factors for colonisation were also evaluated. Results Overall, 48% (96/200) of the children were colonised with at least one ESBL-PE, 8.3% (8/96) of these with 2 ESBL-PE, and one other child was colonised with a CRE (0.5% (1/200)). Common colonising ESBL-PE were Klebsiella pneumoniae (62.5%, 65/104) and Escherichia coli (34.6%, 36/104). The most frequent ESBL-conferring gene was blaCTX-M in 95% (76/80) of the isolates. No resistance- conferring gene was identified in the CRE isolate (Enterobacter cloacae). Most of the Klebsiella pneumoniae isolates were susceptible to piperacillin/tazobactam (86.2%) and amikacin (63.9%). Similarly, 94.4% and 97.2% of the Escherichia coli isolates were susceptible to piperacillin/tazobactam and amikacin, respectively. Hospitalisation for more than 7 days before study enrolment was associated with ESBL-PE colonisation. Conclusion Approximately half of the hospitalised children in this study were colonised with ESBL-PE. This highlights the need for improved infection prevention and control practices to limit the dissemination of these microorganisms.

scholarly journals A NOVEL AIR-DRIED MULTIPLEX HIGH RESOLUTION MELT ASSAY FOR THE DETECTION OF EXTENDED SPECTRUM BETA-LACTAMASE AND CARBAPENEMASE GENES

2021 ◽  
Author(s):  
Ana I. Cubas-Atienzar ◽  
Christopher T. Williams ◽  
Abhilasha Karkey ◽  
Sabina Dongol ◽  
Manandhar Sulochana ◽  
...  
Keyword(s):  
High Resolution ◽  
Antimicrobial Resistance ◽  
Room Temperature ◽  
Beta Lactamase ◽  
Bacterial Isolates ◽  
Pcr Assay ◽  
High Resolution Melt ◽  
Extended Spectrum Beta Lactamase ◽  
Time Points ◽  
Extended Spectrum

ABSTRACTHere we describe the development and evaluation of a novel an air-dried high-resolution melt (HRM) assay to detect eight major extended spectrum beta-Lactamase (ESBL) (SHV and CTXM groups 1 and 9) and Carbapenemase (NDM, IMP, KPC, VIM and OXA-48) genes that cause antimicrobial resistance. The assay was evaluated using 440 DNA samples extracted from bacterial isolates from Nepal, Malawi and UK and 390 clinical Enterobacteriaceae isolates with known resistance phenotypes from Nepal. The sensitivity and specificity for detecting the ESBL and Carbapenemase genes in comparison to the reference gel-base PCR and sequencing was 94.7% (95%CI: 92.5%-96.5%) and 99.2% (95%CI: 98.8%-99.5%) and 98.5% (95%CI: 97.0%-99.4%) and 98.5% (95%CI: 98.0%-98.9%) when compared to the original wet format. The overall phenotypic agreement was 91.1% (95%CI: 90.0%-92.9%) on predicting resistance to cefotaxime and carbapenems. We observed good inter-machine reproducibility of the air-dried HRM assay using the Rotor-Gene Q, QuantStudio™ 5, CFX96, LightCycler® 480 and MIC. Assay stability upon storage in the fridge (6.2°C ± 0.9), room temperature (20.35°C ± 0.7) and oven (29.7°C ± 1.4) were assessed at six time points for eight months and no loss of sensitivity occurred under all conditions. We present here a ready-to-use air-dried HRM-PCR assay that offers an easy, thermostable, fast and accurate tool for the detection of ESBL and Carbapenamase genes to improve AMR diagnosis and treatment.

scholarly journals The Relative Impact of Community and Hospital Antibiotic Use on the Selection of Extended-spectrum Beta-lactamase–producing Escherichia coli

2018 ◽  
Vol 69 (1) ◽  
pp. 182-188 ◽  
Author(s):  
Derek R MacFadden ◽  
David N Fisman ◽  
William P Hanage ◽  
Marc Lipsitch
Keyword(s):  
Escherichia Coli ◽  
Deterministic Model ◽  
National Level ◽  
Antibiotic Use ◽  
Antibiotic Prescribing ◽  
Beta Lactamase ◽  
Prevalence Data ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Relative Change

Abstract Antibiotic stewardship programs have traditionally focused on reducing hospital antibiotic use. However, reducing community antibiotic prescribing could have substantial impacts in both hospital and community settings. We developed a deterministic model of transmission of extended-spectrum beta-lactamase–producing Escherichia coli in both the community and hospitals. We fit the model to existing, national-level antibiotic use and resistance prevalence data from Sweden. Across a range of conditions, a given relative change in antibiotic use in the community had a greater impact on resistance prevalence in both the community and hospitals than an equivalent relative change in hospital use. However, on a per prescription basis, changes in antibiotic use in hospitals had the greatest impact. The magnitude of changes in prevalence were modest, even with large changes in antimicrobial use. These data support the expansion of stewardship programs/interventions beyond the walls of hospitals, but also suggest that such efforts would benefit hospitals themselves.

scholarly journals Genomic analysis of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli colonising adults in Blantyre, Malawi reveals previously undescribed diversity.

2021 ◽  
Author(s):  
Joseph M Lewis ◽  
Madalitso Mphasa ◽  
Rachel Banda ◽  
Mathew A Beale ◽  
Jane Mallewa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Species ◽  
Core Gene ◽  
Sub Saharan Africa ◽  
Beta Lactamase ◽  
Gene Phylogeny ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Local Selection

Escherichia coli is a ubiquitous bacterial species, associated with drug resistant infections; hundreds of thousands of genomes are now available, but are biased towards high-income countries and clinical isolates. Data from sub-Saharan Africa (sSA) are underrepresented in global sequencing efforts and may represent a major source of genetic diversity with respect to transmissible antimicrobial resistance (AMR). We carried out a genomic investigation of extended-spectrum beta-lactamase (ESBL)-producing E. coli colonising adults in Blantyre, Malawi to assess the diversity and AMR determinants and to place these isolates in the context of globally available genomes. We carried out short-read whole-genome sequencing of 473 colonising ESBL E. coli isolated from stool and placed them in the context of a previous curated species wide collection of 10,146 isolates using the popPUNK clustering algorithm and by constructing a core gene phylogeny. The most frequently identified STs in Malawian isolates were the globally successful ST131 and ST410, and blaCTX-M were the dominant ESBL genes, mirroring global trends. However, 37% of Malawian isolates did not cluster with any isolates in the global collection, and the core gene phylogeny was consistent with local subclades including in ST410 and several phylogroup A lineages. Apparent undescribed diversity in Malawian E. coli could be due to local selection pressures or sampling biases in global E. coli collections. Taking a one health approach to further sampling of E. coli from Malawi and sSA, and principled incorporation into unbiased global collections is necessary to understand local, regional and global transmission of both E. coli and priority AMR genes.

scholarly journals Local prevalence of extended-spectrum beta-lactamase (ESBL) producingEnterobacteriaceaeintestinal carriers at admission and co-expression of ESBL and OXA-48 carbapenemase inKlebsiella pneumoniae: a prevalence survey in a Spanish University Hospital

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e024879 ◽  
Author(s):  
Cristina Díaz-Agero Pérez ◽  
Nieves López-Fresneña ◽  
Angela L Rincon Carlavilla ◽  
Marta Hernandez Garcia ◽  
Patricia Ruiz-Garbajosa ◽  
...  
Keyword(s):  
Rectal Swab ◽  
Tertiary Hospital ◽  
University Hospital ◽  
Secondary Outcome ◽  
Beta Lactamase ◽  
Prevalence Survey ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
High Prevalence

ObjectiveTo assess the prevalence of extended-spectrum beta-lactamase (ESBL)-producingEnterobacteriaceae(ESBL-E) faecal carriers at admission in a University Hospital in Spain.DesignPrevalence survey.SettingPneumology, gastroenterology, urology and neurosurgery units at a university tertiary hospital in Madrid (Spain).ParticipantsA total of 10 643 patients aged 18 and older admitted from March 2014 to April 2016 with a rectal swab taken at admission or as soon as possible within the first 48 hours.Primary and secondary outcome measuresPrevalence of ESBL-E faecal carriers and prevalence of ESBL-E infections at admission.ResultsThe prevalance of ESBL-E carriers at admission was 7.69% (CI 95% 7.18 to 8.19). Most of the isolates wereEscherichia coli(77.51%), followed byKlebsiella pneumoniae(20.71%). Eighty-eight (10.41%) of ESBL-E were simultaneous ESBL and carbapenemase (CP) producers, 1.83% in the case ofE. coliand 42.86% amongK. pneumoniaeisolates. Of the ESBL typed, 52.15% belonged to the cefotaximases (CTX-M-15) type and 91.38% of the CP were oxacillinase (OXA-48) type. Only 0.43% patients presented an active infection by ESBL-E at admission.ConclusionsThe prevalence found in our study is very similar to that found in literature. However, we found a high percentage of simultaneous ESBL and CP producers, particularly inK. pneumoniae. Despite the high prevalence of colonised patients, the ESBL-infection rate at admission was very low.

scholarly journals Gut mucosal colonisation with extended-spectrum beta-lactamase producing Enterobacteriaceae in sub-Saharan Africa: a systematic review and meta-analysis

2019 ◽  
Vol 4 ◽  
pp. 160
Author(s):  
Joseph M. Lewis ◽  
Rebecca Lester ◽  
Paul Garner ◽  
Nicholas A. Feasey
Keyword(s):  
Risk Factors ◽  
Meta Analysis ◽  
Sub Saharan Africa ◽  
Beta Lactamase ◽  
Community Studies ◽  
Cross Sectional ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Increased Risk ◽  
Sub Saharan

Background: Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) threaten human health; and, in areas of sub-Saharan Africa (sSA) where carbapenems are not available, may render ESBL-E infections untreatable. Gut mucosal colonisation probably occurs before infection, making prevention of colonisation an attractive target for intervention, but the epidemiology of ESBL-E in sSA is poorly described. Objectives: Describe ESBL-E colonisation prevalence in sSA and risk factors associated with colonisation. Methods: Studies included were prospective cross-sectional or cohort studies reporting gut mucosal ESBL-E colonisation in any population in sSA. We searched PubMed and Scopus on 18 December 2018. We summarise the range of prevalence across sites and tabulated risk factors for colonisation. The protocol was registered (Prospero ID CRD42019123559). Results: From 2975 abstracts we identified 32 studies including a total of 8619 participants from a range of countries and settings. Six studies were longitudinal; no longitudinal studies followed patients beyond hospital discharge.  Prevalence varied between 5 and 84% with a median of 31%, with a relationship to setting: pooled ESBL-E colonisation in community studies was 18% (95% CI 12 to 28, 12 studies); in studies recruiting people at admission to hospital colonisation was 32% (95% CI 24 to 41% 8 studies); and for inpatients, colonisation was 55% (95% CI 49 to 60%, 7 studies). Antimicrobial use was associated with increased risk of ESBL-E colonisation, and protected water sources or water treatment by boiling may reduce risk. Conclusions: ESBL-E colonisation is common in sSA, but how people become carriers and why is not well understood. To inform the design of interventions to interrupt transmission in this setting requires longitudinal, community studies.

scholarly journals Circulation of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli of Pandemic Sequence Types 131, 648, and 410 Among Hospitalized Patients, Caregivers, and the Community in Rwanda

2021 ◽  
Vol 12 ◽  
Author(s):  
Elias Eger ◽  
Stefan E. Heiden ◽  
Katja Korolew ◽  
Claude Bayingana ◽  
Jules M. Ndoli ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Sub Saharan Africa ◽  
Type I ◽  
Beta Lactamase ◽  
Community Members ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Sequence Types

Multi-drug resistant (MDR), gram-negative Enterobacteriaceae, such as Escherichia coli (E. coli) limit therapeutic options and increase morbidity, mortality, and treatment costs worldwide. They pose a serious burden on healthcare systems, especially in developing countries like Rwanda. Several studies have shown the effects caused by the global spread of extended-spectrum beta-lactamase (ESBL)-producing E. coli. However, limited data is available on transmission dynamics of these pathogens and the mobile elements they carry in the context of clinical and community locations in Sub-Saharan Africa. Here, we examined 120 ESBL-producing E. coli strains from patients hospitalized in the University Teaching Hospital of Butare (Rwanda), their attending caregivers as well as associated community members and livestock. Based on whole-genome analysis, the genetic diversification and phylogenetics were assessed. Moreover, the content of carried plasmids was characterized and investigated for putative transmission among strains, and for their potential role as drivers for the spread of antibiotic resistance. We show that among the 30 different sequence types (ST) detected were the pandemic clonal lineages ST131, ST648 and ST410, which combine high-level antimicrobial resistance with virulence. In addition to the frequently found resistance genes blaCTX–M–15, tet(34), and aph(6)-Id, we identified csg genes, which are required for curli fiber synthesis and thus biofilm formation. Numerous strains harbored multiple virulence-associated genes (VAGs) including pap (P fimbriae adhesion cluster), fim (type I fimbriae) and chu (Chu heme uptake system). Furthermore, we found phylogenetic relationships among strains from patients and their caregivers or related community members and animals, which indicates transmission of pathogens. Also, we demonstrated the presence and potential transfer of identical/similar ESBL-plasmids in different strains from the Rwandan setting and when compared to an external plasmid. This study highlights the circulation of clinically relevant, pathogenic ESBL-producing E. coli among patients, caregivers and the community in Rwanda. Combining antimicrobial resistance with virulence in addition to the putative exchange of mobile genetic elements among bacterial pathogens poses a significant risk around the world.

scholarly journals Gut mucosal colonisation with extended-spectrum beta-lactamase producing Enterobacteriaceae in sub-Saharan Africa: a systematic review and meta-analysis

2020 ◽  
Vol 4 ◽  
pp. 160
Author(s):  
Joseph M. Lewis ◽  
Rebecca Lester ◽  
Paul Garner ◽  
Nicholas A. Feasey
Keyword(s):  
Risk Factors ◽  
Meta Analysis ◽  
Sub Saharan Africa ◽  
Beta Lactamase ◽  
Community Studies ◽  
Cross Sectional ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Increased Risk ◽  
Sub Saharan

Background: Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) threaten human health; and, in areas of sub-Saharan Africa (sSA) where carbapenems are not available, may render ESBL-E infections untreatable. Gut mucosal colonisation probably occurs before infection, making prevention of colonisation an attractive target for intervention, but the epidemiology of ESBL-E in sSA is poorly described. Objectives: Describe ESBL-E colonisation prevalence in sSA and risk factors associated with colonisation. Methods: Studies included were prospective cross-sectional or cohort studies reporting gut mucosal ESBL-E colonisation in any population in sSA. We searched PubMed and Scopus on 18 December 2018. We summarise the range of prevalence across sites and tabulated risk factors for colonisation. The protocol was registered (Prospero ID CRD42019123559). Results: From 2975 abstracts we identified 32 studies including a total of 8619 participants from a range of countries and settings. Six studies were longitudinal; no longitudinal studies followed patients beyond hospital discharge.  Prevalence varied between 5 and 84% with a median of 31%, with a relationship to setting: pooled ESBL-E colonisation in community studies was 18% (95% CI 12 to 28, 12 studies); in studies recruiting people at admission to hospital colonisation was 32% (95% CI 24 to 41% 8 studies); and for inpatients, colonisation was 55% (95% CI 49 to 60%, 7 studies). Antimicrobial use was associated with increased risk of ESBL-E colonisation, and protected water sources or water treatment by boiling may reduce risk. Conclusions: ESBL-E colonisation is common in sSA, but how people become carriers and why is not well understood. To inform the design of interventions to interrupt transmission in this setting requires longitudinal, community studies.

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