scholarly journals Quantifying antibiotic impact on within-host dynamics of extended-spectrum beta-lactamase resistance in hospitalized patients

2019 ◽  
Author(s):  
Rene Niehus ◽  
Esther van Kleef ◽  
Mo Yin ◽  
Agata Turlej-Rogacka ◽  
Christine Lammens ◽  
...  
Keyword(s):  
Drug Resistance ◽  
16S Rrna ◽  
Gene Family ◽  
Antibiotic Use ◽  
Beta Lactamase ◽  
Prospective Longitudinal Study ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Variable Nature ◽  
Prospective Longitudinal

AbstractAntibiotic exposure can perturb the human gut microbiome and cause changes in the within-host abundance of the genetic determinants of drug-resistance in bacteria. Such within-host dynamics are expected to play an important role in mediating the relationship between antibiotic use and persistence of drug-resistance within a host and its prevalence within a population. Developing a quantitative representation of these within-host dynamics is an important step towards a detailed mechanistic understanding of the population-level processes by which antibiotics select for resistance. Here we study extended-spectrum beta-lactamase (ESBL) producing organisms of the Enterobacteriaceae bacterial family. These have been identified as a global public health priority and are resistant to most first-line antibiotics for treatment of Enterobacteriaceae infections.We analyse data from 833 rectal swabs from a prospective longitudinal study in three European countries including 133 ESBL-positive hospitalised patients. Quantitative polymerase chain reaction was used to quantify the abundance of the CTX-M gene family – the most wide-spread ESBL gene family – and the 16S rRNA gene as a proxy for bacterial load. We find strong dynamic heterogeneity in CTX-M abundance that is largely explained by the variable nature of the swab sampling. Using information on time-varying antibiotic treatments, we develop a dynamic Bayesian model to decompose the serial data into observational variation and ecological signal and to quantify the potentially causal antibiotic effects.We find an association of treatment with cefuroxime or ceftriaxone with increased CTX-M abundance (approximately 21% and 10% daily increase, respectively), while treatment with meropenem or piperacillin-tazobactam is associated with decreased CTX-M (approximately 8% daily decrease for both). Despite a potential risk for indirect selection, oral ciprofloxacin is also associated with decreasing CTX-M (approximately 8% decrease per day). Using our dynamic model to make forward stochastic simulations of CTX-M dynamics, we generate testable predictions about antibiotic impacts on duration of carriage. We find that a typical course of cefuroxime or ceftriaxone is expected to more than double a patient’s carriage duration of CTX-M. A typical course of piperacillin-tazobactam or of meropenem – both options to treat hospital acquired infections (HAI) like pneumonia – would reduce CTX-M carriage time relative to ceftriaxone plus amikacin (also an option to treat HAIs) by about 70%. While most antibiotics showed little association with changes in total bacterial abundance, meropenem and piperacillin-tazobactam were associated with decrease in 16S rRNA abundance (3% and 4% daily decrease, respectively).Our study quantifies antibiotic impacts on within-host resistance abundance and resistance carriage, and informs our understanding of how changes in patterns of antibiotic use will affect the prevalence of resistance. This work also provides an analytical framework that can be used more generally to quantify the antibiotic treatment effects on within-host dynamics of determinants of antibiotic resistance using clinical data.

scholarly journals Extended-Spectrum Beta-Lactamase Gene Sequences in Gram-Negative Saprophytes on Retail Organic and Nonorganic Spinach

2011 ◽  
Vol 77 (5) ◽  
pp. 1601-1607 ◽  
Author(s):  
Eva Raphael ◽  
Lisa K. Wong ◽  
Lee W. Riley
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
16S Rrna Gene Sequencing ◽  
Drug Susceptibility Testing ◽  
Rrna Gene ◽  
Beta Lactamase ◽  
Human Pathogens ◽  
Gram Negative ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum

ABSTRACTA substantial proportion of infections caused by drug-resistant Gram-negative bacteria (GNB) in community and health care settings are recognized to be caused by evolutionarily related GNB strains. Their global spread has been suggested to occur due to human activities, such as food trade and travel. These multidrug-resistant GNB pathogens often harbor mobile drug resistance genes that are highly conserved in their sequences. Because they appear across different GNB species, these genes may have origins other than human pathogens. We hypothesized that saprophytes in common human food products may serve as a reservoir for such genes. Between July 2007 and April 2008, we examined 25 batches of prepackaged retail spinach for cultivatable GNB population structure by 16S rRNA gene sequencing and for antimicrobial drug susceptibility testing and the presence of extended-spectrum beta-lactamase (ESBL) genes. We found 20 recognized GNB species among 165 (71%) of 231 randomly selected colonies cultured from spinach. Twelve strains suspected to express ESBLs based on resistance to cefotaxime and ceftazidime were further examined forblaCTX-MandblaTEMgenes. We found a 712-bp sequence inPseudomonas teessideathat was 100% identical to positions 10 to 722 of an 876-bpblaCTX-M-15gene of anE. colistrain. Additionally, we identified newly recognized ESBLblaRAHN-2sequences fromRahnella aquatilis. These observations demonstrate that saprophytes in common fresh produce can harbor drug resistance genes that are also found in internationally circulating strains of GNB pathogens; such a source may thus serve as a reservoir for drug resistance genes that ultimately enter pathogens to affect human health.

scholarly journals The Effect of Infection Precautions on Colonization of Nursing Staff with Extended Spectrum Beta-Lactamase Producing Enterobacteriaceae in Three Beirut Hospitals

2020 ◽  
Author(s):  
Nicholas Haddad ◽  
Joanna Abi Ghosn
Keyword(s):  
Nursing Staff ◽  
Work Experience ◽  
Randomized Study ◽  
Antibiotic Use ◽  
Contact Precaution ◽  
Beta Lactamase ◽  
Cross Sectional ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
The Impact

Abstract Background: ESBL-PE are emerging worldwide. This study assesses the effect of contact precaution (CP) on ESBL-PE-colonization rates among nurses in 3 hospitals in Beirut, where ESBL is endemic, to define risk factors for colonization, and evaluate the ongoing use of CP to prevent ESBL-PE transmission to healthy nurses. Methods: Cross-sectional, non-randomized study completed in three hospitals. Hospital 1 required CP, Hospital 2 recently stopped CP, and Hospital 3 had stopped it 3 years previously. Questionnaires and stool-collection containers were distributed to all patient care nurses in those 3 hospitals. Returned samples were tested using agar dilution technique. Results: 269 of 733 nurses volunteered; 140 met inclusion criteria (no recent hospitalization, antibiotic use, known ESBL-PE colonization). 15% were ESBL-positive. Compared to nurses from Hospital 3, nurses from Hospital 1 were 59% less likely to be colonized, while nurses from Hospital 2 were 62% more likely to be colonized. Discussion: In hospitals where CP is ongoing for ESBL-positive patients, transmission to nursing staff was reduced. Additionally, a work experience of 2-4 years increased the odds of ESBL-PE colonization in comparison with longer nursing experience. HIGHLIGHTS : • We examined the impact of contact precautions (CP) for Extended spectrum beta-lactamase- producing Enterobacteriaceae (ESBL-PE) colonized patients on rates of ESBL-PE colonization in nursing staff. • We found significantly decreased rates of colonization in nurses from a hospital utilizing CP, and significantly increased rates of colonization among nurses from a hospital that recently • discontinued CP, compared with nurses from a hospital that had discontinued CP 3 years previously. • Findings suggest that contact precaution may be required to prevent ESBL-PE transmission from patients to nursing staff.

scholarly journals Relating knowledge, attitude and practice of antibiotic use to extended-spectrum beta-lactamase-producing Enterobacteriaceae carriage: results of a cross-sectional community survey

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e023859 ◽  
Author(s):  
Yin Mo ◽  
Ivan Seah ◽  
Pei Shi Priscillia Lye ◽  
Xiang Lee Jamie Kee ◽  
Kien Yee Michael Wong ◽  
...  
Keyword(s):  
Antibiotic Use ◽  
Community Dwelling ◽  
Molecular Characteristics ◽  
Beta Lactamase ◽  
Cross Sectional ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Modifiable Factors ◽  
Rectal Swabs ◽  
Stool Samples

ObjectivesTo study the correlation between knowledge, attitude and practices (KAP) of antibiotic consumption with epidemiology and molecular characteristics of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) carriage, in order to identify modifiable factors and public health interventions to reduce prevalence of multidrug-resistant organism colonisation in the community.DesignCross-sectional questionnaire of KAP towards antibiotic use and collection of stool samples or rectal swabs. ESBL-PE isolates obtained underwent whole genome sequencing to identify resistance genes.SettingA densely populated community in Singapore.ParticipantsThere were 693 healthy community-dwelling questionnaire respondents. Out of which, 305 provided stool samples or rectal swabs.ResultsThe overall knowledge of antibiotic use was poor (mean score 4.6/10, IQR 3.0–6.0). 80 participants (80/305, 26.2%) carried at least one ESBL-PE isolate. The most common ESBL-PE was Escherichia coli sequence type 131 carrying CTX-M type beta-lactamases (11/71, 15.5%). Living overseas for >1 year (OR 3.3, 95% CI 1.6 to 6.9) but not short-term travel, recent hospitalisation or antibiotic intake was associated with ESBL-PE carriage. Interestingly, higher knowledge scores (OR 2.0, 95% CI 1.03 to 3.9) and having no leftover antibiotics (OR 2.4, 95% CI 1.2 to 4.9) were independent factors associated with ESBL-PE carriage in the multivariate logistic regression model.ConclusionsWhile the role of trans-border transmission of antimicrobial resistance is well known, we may have to examine the current recommendation that all antibiotics courses have to be completed. Clinical trials to determine the optimum duration of treatment for common infections are critically important.

Antibiotic Use Is Not a Risk Factor of Infection by Extended-Spectrum Beta-Lactamase Producing Bacteria in Dr. Soetomo Hospital Surabaya

2015 ◽  
Vol 9 (4) ◽  
pp. 150-156
Author(s):  
NADHYA NUR FITRI ◽  
◽  
MUSOFA RUSLI ◽  
MANIK RETNO WAHYUNITISARI ◽  
◽  
...  
Keyword(s):  
Risk Factor ◽  
Antibiotic Use ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum

scholarly journals Quantifying antibiotic impact on within-patient dynamics of extended-spectrum beta-lactamase resistance

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Rene Niehus ◽  
Esther van Kleef ◽  
Yin Mo ◽  
Agata Turlej-Rogacka ◽  
Christine Lammens ◽  
...  
Keyword(s):  
Bacterial Load ◽  
Antibiotic Use ◽  
Beta Lactamase ◽  
Long Term Effects ◽  
Human Gut ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Oral Ciprofloxacin ◽  
The Relationship

Antibiotic-induced perturbation of the human gut flora is expected to play an important role in mediating the relationship between antibiotic use and the population prevalence of antibiotic resistance in bacteria, but little is known about how antibiotics affect within-host resistance dynamics. Here we develop a data-driven model of the within-host dynamics of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. We use blaCTX-M (the most widespread ESBL gene family) and 16S rRNA (a proxy for bacterial load) abundance data from 833 rectal swabs from 133 ESBL-positive patients followed up in a prospective cohort study in three European hospitals. We find that cefuroxime and ceftriaxone are associated with increased blaCTX-M abundance during treatment (21% and 10% daily increase, respectively), while treatment with meropenem, piperacillin-tazobactam, and oral ciprofloxacin is associated with decreased blaCTX-M (8% daily decrease for all). The model predicts that typical antibiotic exposures can have substantial long-term effects on blaCTX-M carriage duration.

scholarly journals Peningkatan Mutu Penggunaan Antibiotik Bijak Melalui Kesesuaian Temuan Hasil Kultur Dengan Kajian Risiko Pasien Menurut Model Regulasi Antimikroba Sistem Prospektif (Raspro)

2021 ◽  
Vol 3 (2) ◽  
pp. 114-118
Author(s):  
Ronald Irwanto Natadidjaja ◽  
Hadianti Adlani ◽  
Hadi Sumarsono
Keyword(s):  
Drug Resistance ◽  
Multi Drug Resistance ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
Diabetes Melitus

Masalah Mutu: Standar 4 Kajian SNARS 2018 menyatakan bahwa rumah sakit wajib memiliki surveilens kepekaan kuman terhadap antibiotik. Hal ini harus menjadi dasar pertimbangan pembuatan Panduan Penggunaan Antibiotik (PPAB). Di sisi lain, timbulnya kuman Multi Drug Resistance (MDR) juga dipengaruhi oleh berbagai faktor. Pemberian antibiotik empirik, selain berdasar pada pola kuman, juga sebaiknya mempertimbangkan berbagai faktor risiko timbulnya kuman MDR. Pilihan Solusi: Regulasi Antimikroba Sistem Prospektif (RASPRO) adalah sebuah model tataguna antimikroba yang disintesis dari berbagai kepustakaan dengan mempertimbangkan berbagai faktor yang dapat menyebabkan timbulnya kuman-kuman MDR pada surveilans kepekaan kuman, sehingga dapat mengarahkan klinisi pada peresepan antibiotik bijak. Implementasi: Kajian risiko yang dibuat dalam RASPRO menentukan bahwa immunocompromised dan/ atau dengan komorbid Diabetes Melitus yang tidak terkontrol atau dengan riwayat konsumsi antibiotik kurang dari 90 hari, dan/ atau riwayat perawatan di rumah sakit lebih dari 48 jam dalam waktu kurang dari 90 hari, dan/ atau riwayat penggunaan instrumen medis kurang dari 90 hari masuk dalam risiko MDR. Pasien-pasien yang tidak termasuk dalam kategori di atas akan masuk ke dalam prediksi infeksi oleh kuman multisensitif. Evaluasi dan Pembelajaran: Pada surveilans kepekaan kuman dengan data sekunder diambil dari sebuah rumah sakit swasta tipe B di Jakarta antara tahun 2016-2018, dengan rumus sampel tunggal, didapatkan 106 sampel kultur dari 86 pasien. Terdapat kesesuaian pada 54 dari 57 hasil kultur yang diambil dari pasien dengan kajian risiko infeksi kuman multisensitif (94,74%). Kesesuaian antara temuan hasil kultur MDR dengan kajian risiko model RASPRO terdapat pada 44 dari 49 kultur (89,80%), dengan 9 kultur menunjukkan Extended Spectrum Beta-Lactamase (ESBL). Total kesesuaian hasil kultur dengan kajian risiko empirik model RASPRO mencapai 92,45%. Tingginya persentase kesesuaian temuan kultur kuman penyebab infeksi dengan kajian faktor risiko model RASPRO sepertinya dapat menjadi pertimbangan dalam mengarahkan klinisi dalam pemberian antibiotik empirik spektrum sempit dan luas pada praktek klinis sehari-hari di rumah sakit. Dengan praktik seperti ini kualitas penggunaan antibiotik diharapkan dapat meningkat.

scholarly journals The Clinical and Molecular Epidemiology of CTX-M-9 Group Producing Enterobacteriaceae infections in children

2018 ◽  
Author(s):  
Latania K. Logan ◽  
Rachel L. Medernach ◽  
T. Nicholas Domitrovic ◽  
Jared R. Rispens ◽  
Andrea M. Hujer ◽  
...  
Keyword(s):  
Dna Analysis ◽  
Multivariable Analysis ◽  
Antibiotic Use ◽  
Resistant Bacteria ◽  
Unexpected Finding ◽  
Control Analysis ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum

AbstractBackgroundThe pandemic of extended-spectrum-beta-lactamase (ESBL)-producing-Enterobacteriaceae (Ent) is strongly linked to the dissemination of CTX-M-type-ESBL-Ent. We sought to define the epidemiology of infections in children due to an emerging resistance type, CTX-M-9-group-producing-Ent (CTX-M-9-grp-Ent).MethodsA multi-centered case-control analysis of Chicago children with CTX-M-9-grp-Ent infections was performed. Cases were defined as children possessing extended-spectrum-cephalosporin-resistant (ESC-R) infections. PCR and DNA analysis assessed beta-lactamase (bla) genes, multi-locus sequence types (MLST) and phylogenetic grouping of E. coli. Controls were children with ESC-susceptible (ESC-S)-Ent infections matched 3:1 by age, source, and hospital. The clinical-epidemiologic predictors of CTX-M-9-grp-Ent infection were assessed.ResultsOf 356 ESC-R-Ent isolates from children (median age 4.1 years), CTX-M-9-group was the solely detected bla gene in 44(12.4%). The predominant species was E. coli (91%) of virulent phylogroups D(60%) and B2(40%). MLST revealed multiple strain types. On multivariable analysis, CTX-M-9-grp-Ent occurred more often in E. coli (OR 7.0), children of non-black-white-Hispanic race (OR 6.5), and outpatients (OR 4.5) which was a very unexpected finding for infections due to antibiotic-resistant bacteria. Residents of South Chicago were 6.7 times more likely to have CTX-M-9-grp-Ent infections than those in the reference region (West), while residence in Northwestern Chicago was associated with an 81% decreased risk. Other demographic, comorbidity, invasive-device, and antibiotic use differences were not found.ConclusionsCTX-M-9-grp-Ent infection is strikingly associated with patient residence and is occurring in children without traditional in-patient exposure risk factors. This suggests that among children, the community environment may be a key contributor in the spread of these resistant pathogens.

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