OBJECTIVES: Denmark and several other countries experienced the first epidemic of methicillin-resistant Staphylococcus aureus (MRSA) during the period 1965-75, which was caused by multiresistant isolates of phage complex 83A. In Denmark these MRSA isolates disappeared almost completely, being replaced by other phage types, predominantly only penicillin resistant. We investigated whether isolates of this epidemic were associated with a fitness cost, and we employed a mathematical model to ask whether these fitness costs could have led to the observed reduction in frequency. METHODS: Bacteraemia isolates of S. aureus from Denmark have been stored since 1957. We chose 40 S. aureus isolates belonging to phage complex 83A, clonal complex 8 based on spa type, ranging in time of isolation from 1957 to 1980 and with various antibiograms, including both methicillin-resistant and -susceptible isolates. The relative fitness of each isolate was determined in a growth competition assay with a reference isolate. RESULTS: Significant fitness costs of 2%-15% were determined for the MRSA isolates studied. There was a significant negative correlation between number of antibiotic resistances and relative fitness. Multiple regression analysis found significantly independent negative correlations between fitness and the presence of mecA or streptomycin resistance. Mathematical modelling confirmed that fitness costs of the magnitude carried by these isolates could result in the disappearance of MRSA prevalence during a time span similar to that seen in Denmark. CONCLUSIONS: We propose a significant fitness cost of resistance as the main bacteriological explanation for the disappearance of the multiresistant complex 83A MRSA in Denmark following a reduction in antibiotic usage.
OBJECTIVES: Denmark and several other countries experienced the first epidemic of methicillin-resistant Staphylococcus aureus (MRSA) during the period 1965-75, which was caused by multiresistant isolates of phage complex 83A. In Denmark these MRSA isolates disappeared almost completely, being replaced by other phage types, predominantly only penicillin resistant. We investigated whether isolates of this epidemic were associated with a fitness cost, and we employed a mathematical model to ask whether these fitness costs could have led to the observed reduction in frequency. METHODS: Bacteraemia isolates of S. aureus from Denmark have been stored since 1957. We chose 40 S. aureus isolates belonging to phage complex 83A, clonal complex 8 based on spa type, ranging in time of isolation from 1957 to 1980 and with various antibiograms, including both methicillin-resistant and -susceptible isolates. The relative fitness of each isolate was determined in a growth competition assay with a reference isolate. RESULTS: Significant fitness costs of 2%-15% were determined for the MRSA isolates studied. There was a significant negative correlation between number of antibiotic resistances and relative fitness. Multiple regression analysis found significantly independent negative correlations between fitness and the presence of mecA or streptomycin resistance. Mathematical modelling confirmed that fitness costs of the magnitude carried by these isolates could result in the disappearance of MRSA prevalence during a time span similar to that seen in Denmark. CONCLUSIONS: We propose a significant fitness cost of resistance as the main bacteriological explanation for the disappearance of the multiresistant complex 83A MRSA in Denmark following a reduction in antibiotic usage.
Authors: Peter M Kinnevey; Anna C Shore; Grainne I Brennan; Derek J Sullivan; Ralf Ehricht; Stefan Monecke; David C Coleman Journal: Antimicrob Agents Chemother Date: 2014-01-06 Impact factor: 5.191
Authors: C James Manktelow; Elitsa Penkova; Lucy Scott; Andrew C Matthews; Ben Raymond Journal: Antimicrob Agents Chemother Date: 2020-09-21 Impact factor: 5.191
Authors: Karen L Nielsen; Marc Stegger; Paul A Godfrey; Michael Feldgarden; Paal S Andersen; Niels Frimodt-Møller Journal: Int J Med Microbiol Date: 2016-11-04 Impact factor: 3.473
Authors: K M Hare; K Grimwood; A B Chang; M D Chatfield; P C Valery; A J Leach; H C Smith-Vaughan; P S Morris; C A Byrnes; P J Torzillo; A C Cheng Journal: Eur J Clin Microbiol Infect Dis Date: 2015-09-12 Impact factor: 3.267
Authors: Sónia T Almeida; A Cristina Paulo; João Babo; João Borralho; Catarina Figueiredo; Bruno Gonçalves; João Lança; Mónica Louro; Hermes Morais; Joana Queiroz; Hermínia de Lencastre; Raquel Sá-Leão Journal: PLoS One Date: 2021-06-30 Impact factor: 3.240
Authors: Evan S Snitkin; Adrian M Zelazny; Jyoti Gupta; Tara N Palmore; Patrick R Murray; Julia A Segre Journal: Genome Res Date: 2013-04-05 Impact factor: 9.043
Authors: Ewan M Harrison; Lucy A Weinert; Matthew T G Holden; John J Welch; Katherine Wilson; Fiona J E Morgan; Simon R Harris; Anette Loeffler; Amanda K Boag; Sharon J Peacock; Gavin K Paterson; Andrew S Waller; Julian Parkhill; Mark A Holmes Journal: mBio Date: 2014-05-13 Impact factor: 7.867