#Genome #investigations show host #adaptation and #transmission of LA- #MRSA CC398 from #pigs into #Danish #healthcare #institutions (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Genome investigations show host adaptation and transmission of LA-MRSA CC398 from pigs into Danish healthcare institutions

Raphael Niklaus Sieber, Anders Rhod Larsen, Tinna Ravnholt Urth, Søren Iversen, Camilla Holten Møller, Robert Leo Skov, Jesper Larsen & Marc Stegger

Scientific Reports, volume 9, Article number: 18655 (2019)

 

Abstract

Over the last decade, an increasing number of infections with livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (LA-MRSA CC398) in persons without contact to livestock has been registered in Denmark. These infections have been suggested to be the result of repeated spillover of random isolates from livestock into the community. However, other studies also found emerging sub-lineages spreading among humans. Based on genome-wide SNPs and genome-wide association studies (GWAS), we assessed the population structure and genomic content of Danish LA-MRSA CC398 isolates from healthcare-associated infections from 2014 to 2016 (n = 73) and compared these to isolates from pigs in Denmark from 2014 (n = 183). Phylogenetic analyses showed that most human isolates were closely related to and scattered among pig isolates showing that the majority of healthcare-associated infections are the result of repeated spillover from pig farms, even though cases of human-to-human transmission also were identified. GWAS revealed frequent loss of antimicrobial resistance genes and acquisition of human-specific virulence genes in the human isolates showing adaptation in response to changes in selective pressures in different host environments, which over time could lead to the emergence of LA-MRSA CC398 lineages more adapted to human colonization and transmission.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA; Pigs; Human; Nosocomial outbreaks; Denmark.

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Molecular Characterization of #MRSA in a Tertiary Care #hospital in #Kuwait (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2019 Dec 6;9(1):18527. doi: 10.1038/s41598-019-54794-8.

Molecular Characterization of Methicillin- Resistant Staphylococcus aureus in a Tertiary Care hospital in Kuwait.

Alfouzan W1,2, Udo EE3, Modhaffer A1, Alosaimi A1.

Author information: 1 Microbiology Unit, Department of Laboratory Medicine, Farwaniya hospital, Ministry of Health, Sabah Al Nasser, Kuwait. 2 Department of Microbiology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait. 3 Department of Microbiology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait. EDET@hsc.edu.kw.

 

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) are a major cause of healthcare and community- associated infections due to their ability to express a variety of virulence factors. We investigated 209 MRSA isolates obtained from 1 January to 31 December 2016 using a combination of phenotypic and genotypic methods to understand the genetic backgrounds of MRSA strains obtained in a General hospital in Kuwait. Antibiotics susceptibility was performed with disk diffusion, and MIC was measured with Etest strips. Molecular typing was performed using SCCmec typing, spa typing, and DNA microarray for antibiotic resistance and virulence genes. The isolates were susceptible to vancomycin, teicoplanin, rifampicin, ceftaroline, and linezolid but were resistant to gentamicin, tetracycline, erythromycin, fusidic acid, chloramphenicol and ciprofloxacin. Molecular typing revealed six SCCmec types, 56 spa types and 16 clonal complexes (CC). The common SCCmec types were type IV (39.5%), type III (34.4%), type V (25.8%) and type VI (3.8%). The dominant spa types were t860 (23.9%), t945 (8.6%), t127 (6.7%), t688 (6.7%), t304 (6.2) and t044 (5.7%). The other spa types occurred sporadically. Genes for PVL was detected in 59 (28.2%) of the isolates. CC8-ST239-MRSA-III + SCCmer (23.3%) was the most prevalent clone, followed by CC6-MRSA-IV (8.3%), CC80-MRSA-IV [PVL+] (5.8%), CC5-MRSA-VI + SCCfus (5.0%), CC30-MRSA-IV[PVL+] (4.1%), CC1-MRSA-V + SCCfus [PVL+] (4.1%), CC5-MRSA-V + SCCfus (4.1%) and CC22-MRSA-IV[PVL+] (4.1%). The study revealed that despite the emergence of MRSA with diverse genetic backgrounds over the years, ST239-MRSA-III remained the dominant clone in the hospital. This warrants reassessment of infection prevention and control procedures at this hospital.

PMID: 31811246 DOI: 10.1038/s41598-019-54794-8

Keywords: Antibiotics; Drugs Resistance; MRSA; Staphylcoccus aureus; Nosocomial outbreaks; Kuwait.

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#Monoclonal #antibody anti-PBP2a protects mice against #MRSA (methicillin-resistant #Staphylococcus aureus) infections (PLOS One, abstract)

[Source: PLOS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Monoclonal antibody anti-PBP2a protects mice against MRSA (methicillin-resistant Staphylococcus aureus) infections

Felipe Betoni Saraiva, Ana Caroline Cavalcante de Araújo, Anna Érika Vieira de Araújo, José Procópio Moreno Senna

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Published: November 27, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225752

 

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterium responsible for serious nosocomial and community-acquired infections worldwide. Since few antibiotics are effective for treating MRSA infections, the development of new therapies is of great importance. Previous studies demonstrated that PBP2a is a target that generates protective antibodies against MRSA. A murine monoclonal antibody (MAb) that recognizes PBP2a from MRSA strains was previously isolated and characterized. In this report, we evaluated the biodistribution of this MAb in blood and tissues, as well as the extent of protection conferred using prophylactic and therapeutic assays compared to vancomycin treatment. Biodistribution was evaluated 12–96 h after MAb administration. It predominantly remained in the serum, but it was also detectable in the kidneys, lungs, and spleen at low concentrations (about 4.5% in the kidneys, 1.9% in the lungs, and 0.7% the spleen) at all observed timepoints. Prophylactic studies in a murine model demonstrated a significant bacterial load reduction in the kidneys of the groups treated with either with IgG (greater than 3 logs) or F(ab’)2 (98%) when compared to that of the control groups (untreated). Mice were challenged with a lethal dose, and the survival rate was higher in the treated mice. Treatment with the MAb resulted in a bacterial load reduction in the kidneys similar to that of mice treated with vancomycin, and a MAb/vancomycin combination therapy was also effective. These results demonstrate that an anti-PBP2a MAb may be a promising therapeutic for treating MRSA infections.

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Citation: Saraiva FB, de Araújo ACC, de Araújo AÉV, Senna JPM (2019) Monoclonal antibody anti-PBP2a protects mice against MRSA (methicillin-resistant Staphylococcus aureus) infections. PLoS ONE 14(11): e0225752. https://doi.org/10.1371/journal.pone.0225752

Editor: Paulo Lee Ho, Instituto Butantan, BRAZIL

Received: April 30, 2019; Accepted: October 29, 2019; Published: November 27, 2019

Copyright: © 2019 Saraiva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was supported by Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos (Fiocruz).

Competing interests: The authors have declared that no competing interests exist.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA; Monoclonal antibodies.

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#Evolution and #Global #Transmission of a #MDR, CA #MRSA #Lineage from the #Indian Subcontinent (MBio, abstract)

[Source: MBio, full page: (LINK). Abstract, edited.]

Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent

Eike J. Steinig, Sebastian Duchene, D. Ashley Robinson, Stefan Monecke, Maho Yokoyama, Maisem Laabei, Peter Slickers, Patiyan Andersson, Deborah Williamson, Angela Kearns, Richard V. Goering, Elizabeth Dickson, Ralf Ehricht, Margaret Ip, Matthew V. N. O’Sullivan, Geoffrey W. Coombs, Andreas Petersen, Grainne Brennan, Anna C. Shore, David C. Coleman, Annalisa Pantosti, Herminia de Lencastre, Henrik Westh, Nobumichi Kobayashi, Helen Heffernan, Birgit Strommenger, Franziska Layer, Stefan Weber, Hege Vangstein Aamot, Leila Skakni, Sharon J. Peacock, Derek Sarovich, Simon Harris, Julian Parkhill, Ruth C. Massey, Mathew T. G. Holden, Stephen D. Bentley, Steven Y. C. Tong

Paul J. Planet, Invited Editor, Victor J. Torres, Editor

DOI: 10.1128/mBio.01105-19

 

ABSTRACT

The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.

 

IMPORTANCE

The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA; CA-MRSA; India; Bangladesh.

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Longitudinal, strain-specific #Staphylococcus aureus #introduction & #transmission events in #households of #children with CA #MRSA #skin & soft tissue infection… (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Longitudinal, strain-specific Staphylococcus aureus introduction and transmission events in households of children with community-associated meticillin-resistant S aureus skin and soft tissue infection: a prospective cohort study

Ryan L Mork, PhD, Patrick G Hogan, MPH, Carol E Muenks, BA, Mary G Boyle, MSN, Ryley M Thompson, Melanie L Sullivan, BS, John J Morelli, BS, Jennifer Seigel, MSN, Rachel C Orscheln, MD, Juliane Bubeck Wardenburg, MD, Sarah J Gehlert, PhD, Carey-Ann D Burnham, PhD, Andrey Rzhetsky, PhD, Stephanie A Fritz, MD

Published: November 26, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30570-5

 

Summary

Background

Devising effective, targeted approaches to prevent recurrent meticillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infection requires an understanding of factors driving MRSA acquisition. We comprehensively defined household longitudinal, strain-level S aureus transmission dynamics in households of children with community-associated MRSA skin and soft tissue infection.

Methods

From 2012–15, otherwise healthy paediatric patients with culture-confirmed, community-onset MRSA infections were recruited for the Household Observation of MRSA in the Environment (HOME) prospective cohort study from hospitals and community practices in metropolitan St Louis (MO, USA). Children with health-care-related risk factors were excluded, as determined by evidence of recent hospital admission, an invasive medical device, or residence in a long-term care facility. Household contacts (individuals sleeping in the home ≥four nights per week) and indoor dogs and cats were also enrolled. A baseline visit took place at the index patient’s primary home, followed by four quarterly visits over 12 months. At each visit, interviews were done and serial cultures were collected, to detect S aureus from three anatomic sites of household members, two anatomic sites on dogs and cats, and 21 environmental surfaces. Molecular typing was done by repetitive-sequence PCR to define distinct S aureus strains within each household. Longitudinal, multivariable generalised mixed-effects logistic regression models identified factors associated with S aureus acquisition.

Findings

Across household members, pets, and environmental surfaces, 1267 strain acquisition events were observed. Acquisitions were driven equally by 510 introductions of novel strains into households and 602 transmissions within households, each associated with distinct factors. Frequent handwashing decreased the likelihood of novel strain introduction into the household (odds ratio [OR] 0·86, credible interval [CrI] 0·74–1·01). Transmission recipients were less likely to own their homes (OR 0·77, CrI 0·63–0·94) and were more likely to share bedrooms with strain-colonised individuals (OR 1·33, CrI 1·12–1·58), live in homes with higher environmental S aureus contamination burden (OR 3·97, CrI 1·96–8·20), and report interval skin and soft tissue infection (OR 1·32, CrI 1·07–1·64). Transmission sources were more likely to share bath towels (OR 1·25, CrI 1·01–1·57). Pets were often transmission recipients, but rarely the sole transmission source.

Interpretation

The household environment plays a key role in transmission, a factor associated with skin and soft tissue infection. Future interventions should inclusively target household members and the environment, focusing on straightforward changes in hand hygiene and household sharing behaviours.

Funding

National Institutes of Health, Agency for Healthcare Research and Quality, Children’s Discovery Institute, Burroughs Wellcome Foundation, Defense Advanced Research Projects Agency.

Keywords: Staphylococcus aureus; MRSA; CA-MRSA; Pediatrics.

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#Epidemiology and #antimicrobial #resistance of #MRSA isolates colonizing #pigs with different exposure to #antibiotics (PLOS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Epidemiology and antimicrobial resistance of methicillin-resistant Staphylococcus aureus isolates colonizing pigs with different exposure to antibiotics

Elizeth Lopes, Teresa Conceição, Laurent Poirel, Hermínia de Lencastre, Marta Aires-de-Sousa

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Published: November 20, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225497

 

Abstract

Background

In 2016, very high rates of methicillin-resistant Staphylococcus aureus (MRSA)-ST398 (99%) were found in Portuguese pig farms that used colistin, amoxicillin, and zinc oxide as feed additives. Since then, farms A and B banned the use of colistin, and farm C banned the use of both antibiotics.

Objective

The aim of the present study was to evaluate the impact of the ban of colistin and amoxicillin on pig MRSA carriage rates, clonal types and antimicrobial resistance, compared to the results obtained in 2016.

Methods

In 2018, 103 pigs (52 from farm B using amoxicillin only as a feed additive and 51 from farm C where no antibiotics were included in the feed regimen) were nasally swabbed for MRSA colonization. Isolates were tested for antimicrobial susceptibility, and characterised by spa typing, SCCmec typing and MLST. Whole genome sequencing (WGS) was performed for representative isolates.

Results

Overall, 96% of the pigs swabbed in 2018 carried MRSA, mostly ST398-SCCmec V-spa types t011/t108. MRSA from pigs not receiving antibiotics in the feed regimen showed susceptibility to a higher number of antibiotics, namely erythromycin, ciprofloxacin, gentamicin, and chloramphenicol. Notably, most of these isolates (n = 52) presented an unusual erythromycin-susceptibility/clindamycin-resistance phenotype. WGS showed that these isolates lacked the erm and the lnu genes encoding resistance to macrolides and lincosamides, respectively, but carried the vgaALC gene encoding resistance to lincosamides, which is here firstly identified in S. aureus ST398.

Conclusion

After two years the ban of colistin and amoxicillin as feed additives had no significant impact on the MRSA nasal carriage rates. Nevertheless, the MRSA strains circulating in those farms showed resistance to a lower number of antibiotic classes.

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Citation: Lopes E, Conceição T, Poirel L, de Lencastre H, Aires-de-Sousa M (2019) Epidemiology and antimicrobial resistance of methicillin-resistant Staphylococcus aureus isolates colonizing pigs with different exposure to antibiotics. PLoS ONE 14(11): e0225497. https://doi.org/10.1371/journal.pone.0225497

Editor: Tara C. Smith, Kent State University, UNITED STATES

Received: September 6, 2019; Accepted: November 6, 2019; Published: November 20, 2019

Copyright: © 2019 Lopes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was partly supported by project PTDC/DTP-EPI/0842/2014 from Fundação para a Ciência e a Tecnologia (FCT), Portugal, and Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT. This work was also partially supported by ONEIDA project (LISBOA-01-0145-FEDER-016417) co-funded by FEEI – “Fundos Europeus Estruturais e de Investimento” from “Programa Operacional Regional Lisboa 2020” and by national funds from FCT. Elizeth Lopes was supported by grant 03/BI/2017 from FCT, Portugal.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Antibiotics; Drugs Resistance; Amoxicillin; Colistin; Staphylococcus aureus; Pigs; MRSA; Portugal.

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#Prevalence and #clinical associations of #Staphylococcus aureus small-colony variant #respiratory #infection in #children with cystic fibrosis (SCVSA): a multicentre, observational study (Lancet Resp Med., abstract)

[Source: The Lancet Respiratory Medicine, full page: (LINK). Abstract, edited.]

Prevalence and clinical associations of Staphylococcus aureus small-colony variant respiratory infection in children with cystic fibrosis (SCVSA): a multicentre, observational study

Daniel J Wolter, PhD, Frankline M Onchiri, PhD, Julia Emerson, MD, Mimi R Precit, PhD, Michael Lee, BS, Sharon McNamara, RN, Laura Nay, BS, Marcella Blackledge, BS, Ahmet Uluer, MD, Prof David M Orenstein, MD, Michelle Mann, MD, Prof Wynton Hoover, MD, Prof Ronald L Gibson, MD, Prof Jane L Burns, MD, Prof Lucas R Hoffman, MD, on behalf of theSCVSA study group †

Published: November 11, 2019 / DOI: https://doi.org/10.1016/S2213-2600(19)30365-0

 

Summary

Background

Staphylococcus aureus is the bacterium cultured most often from respiratory secretions of people with cystic fibrosis. Both meticillin-susceptible S aureus and meticillin-resistant S aureus (MRSA) can adapt to form slow-growing, antibiotic-resistant isolates known as small-colony variants that are not routinely identified by clinical laboratories. We aimed to determine the prevalence and clinical significance of S aureus small-colony variants and their subtypes among children with cystic fibrosis.

Methods

The Small Colony Variant Staphylococcus aureus (SCVSA) study was a 2-year longitudinal study of children aged 6–16 years at five US cystic fibrosis centres, using culture methods sensitive for small-colony variants. Children were eligible if they had a documented diagnosis of cystic fibrosis and a minimum of two cystic fibrosis clinic visits and two respiratory cultures in the previous 12 months at enrolment. Participants attended clinic visits quarterly, at which respiratory tract samples were taken and measures of lung function (percentage of predicted forced expiratory volume in 1 s [FEV 1] and frequency of respiratory exacerbations) were recorded. We determined the prevalence of small-colony variants and their subtypes, and assessed their independent associations with lung function and respiratory exacerbations using linear mixed-effects and generalised estimating equation logistic regression models. Analyses included both univariate models (unadjusted) and multivariate models that adjusted for potential confounders, including age, sex, race, baseline microbiology, treatment with CFTR modulator, and CTFR genotype.

Findings

Between July 1, 2014, and May 26, 2015, we enrolled 230 children. Participants were followed-up for 2 years, with a mean of 6·4 visits (SD 1·14) per participant (range 2–9 visits) and a mean interval between visits of 3·94 months (SD 1·77). Across the 2-year period, S aureus small-colony variants were detected in 64 (28%) participants. Most (103 [56%] of 185) of the small-colony variants detected in these participants were thymidine dependent. Children with small-colony variants had significantly lower mean percentage of predicted FEV 1 at baseline than did children without small-colony variants (85·5 [SD 19] vs 92·4 [SD 18·6]; p=0·0145). Small-colony variants were associated with significantly lower percentage of predicted FEV 1 throughout the study in regression models, both in univariate analyses (regression coefficient −7·07, 95% CI −12·20 to −1·95; p=0·0068) and in multivariate analyses adjusting for potential confounders (−5·50, −10·51 to −0·48; p=0·0316). Small colony variants of the thymidine-dependent subtype had the strongest association with lung function in multivariate regression models (regression coefficient −10·49, −17·25 to −3·73; p=0·0024). Compared with children without small-colony variants, those with small-colony variants had significantly increased odds of respiratory exacerbations in univariate analyses (odds ratio 1·73, 95% CI 1·19 to 2·52; p=0·0045). Children with thymidine-dependent small-colony variants had significantly increased odds of respiratory exacerbations (2·81, 1·69–4·67; p=0·0001), even after adjusting for age, sex, race, genotype, CFTR modulator, P aeruginosa culture status, and baseline percentage of predicted FEV 1 (2·17, 1·33–3·57; p=0·0021), whereas those with non-thymidine-dependent small-colony variants did not. In multivariate models including small-colony variants and MRSA status, P aeruginosa was not independently associated with lung function (regression coefficient −4·77, 95% CI −10·36 to 0·83; p=0·10) and was associated with reduced odds of exacerbations (0·54, 0·36 to 0·81; p=0·0028). Only the small-colony variant form of MRSA was associated with reduced lung function (−8·44, −16·15 to −0·72; p=0·0318) and increased odds of exacerbations (2·15, 1·24 to 3·71; p=0·0061).

Interpretation

Infection with small-colony variants, and particularly thymidine-dependent small-colony variants, was common in a multicentre paediatric population with cystic fibrosis and associated with reduced lung function and increased risk of respiratory exacerbations. The adoption of small-colony variant identification and subtyping methods by clinical laboratories, and the inclusion of small-colony variant prevalence data in cystic fibrosis registries, should be considered for ongoing surveillance and study.

Funding

The Cystic Fibrosis Foundation and the National Institutes of Health.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA; Pediatrics; Cystic fibrosis.

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