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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2012

Open Access 01-12-2012 | Research article

Macrolide resistance determinants among Streptococcus pneumoniae isolates from carriers in Central Greece

Authors: Ioanna N Grivea, Alexia Sourla, Eleni Ntokou, Denise C Chryssanthopoulou, Alexandra G Tsantouli, George A Syrogiannopoulos

Published in: BMC Infectious Diseases | Issue 1/2012

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Abstract

Background

We sought to characterize the temporal trends in nasopharyngeal carriage of macrolide-resistant pneumococci during a period with increased heptavalent pneumococcal conjugate vaccine (PCV7) coverage in Central Greece.

Methods

Streptococcus pneumoniae isolates were recovered from 2649 nasopharyngeal samples obtained from day-care center attendees in Central Greece during 2005–2009. A phenotypic and genotypic analysis of the isolates was performed, including the identification of macrolide resistance genes mef(A), subclasses mef(A) and mef(E), as well as erm(B).

Results

Of the 1105 typeable S. pneumoniae isolates, 265 (24%) were macrolide-resistant; 22% in 2005, 33.3% in 2006, 23.7% in 2007, and 20.5% in 2009 (P=0.398). Among these macrolide-resistant pneumococci, 28.5% possessed erm(B), 24.3% erm(B)+mef(E), 41.8% mef(E), and 5.3% mef(A). A mef gene as the sole resistance determinant was carried by 31% of macrolide-resistant isolates belonging to PCV7 serotypes and 75.8% of the non-PCV7 serotypes. Across the 4 annual surveillances, pneumococci carrying mef(A) gradually disappeared, whereas serotype 19F isolates carrying both erm(B) and mef(E) persisted without significant yearly fluctuations. Among isolates belonging to non-PCV7 serotypes, macrolide-resistance was observed in those of serotypes 6A, 19A, 10A, 15A, 15B/C, 35F, 35A, and 24F. In 2009, ie 5 years after the introduction of PCV7 in our country, 59% of macrolide-resistant pneumococci belonged to non-PCV7 serotypes.

Conclusions

Across the study period, the annual frequency of macrolide-resistant isolates did not change significantly, but in 2009 a marked shift to non-PCV7 serotypes occurred. Overall, more than half of the macrolide-resistant isolates possessed erm(B) either alone or in combination with mef(E). erm(B) dominated among isolates belonging to PCV7 serotypes, but not among those of non-PCV7 serotypes.
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Literature
1.
Klein JO: The epidemiology of pneumococcal disease in infants and children. Rev Infect Dis. 1981, 3: 246-253. 10.1093/clinids/3.2.246.CrossRefPubMed
2.
Gray BM, Converse GM, Dillon HC: Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis. 1980, 142: 923-933. 10.1093/infdis/142.6.923.CrossRefPubMed
3.
Faden H, Duffy L, Wasielewski R, Wolf J, Krystofik D, Tung Y, Tonawanda/Williamsville Pediatrics: Relationship between nasopharyngeal colonization and the development of otitis media in children. J Infect Dis. 1997, 175: 1440-1445. 10.1086/516477.CrossRefPubMed
4.
Bogaert D, De Groot R, Hermans PW: Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis. 2004, 4: 144-154. 10.1016/S1473-3099(04)00938-7.CrossRefPubMed
5.
Lin TY, Shah NK, Brooks D, Garcia CS: Summary of invasive pneumococcal disease burden among children in the Asia-Pacific region. Vaccine. 2010, 28: 7589-7605. 10.1016/j.vaccine.2010.07.053.CrossRefPubMed
6.
Dagan R, Givon-Lavi N, Zamir O, Fraser D: Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day-care centers. Pediatr Infect Dis J. 2003, 22: 532-540.PubMed
7.
Cohen R, Levy C, Bonnet E, Grondin S, Desvignes V, Lecuyer A, Fritzell B, Varon E: Dynamic of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 introduction in France. Vaccine. 2010, 28: 6114-6121. 10.1016/j.vaccine.2009.05.037.CrossRefPubMed
8.
Grivea IN, Tsantouli AG, Michoula AN, Syrogiannopoulos GA: Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high heptavalent pneumococcal conjugate vaccine coverage in Central Greece. Vaccine. 2011, 29: 8882-8887. 10.1016/j.vaccine.2011.09.074.CrossRefPubMed
9.
Farrell DJ, Morrissey I, Bakker S, Felmingham D: Molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae and Streptococcus pyogenes isolated from the PROTEKT 1999–2000 study. J Antimicrob Chemother. 2002, 50 (Suppl. S1): 39-47.CrossRefPubMed
10.
Van Eldere J, Meekers E, Lagrou K, Massonet C, Canu A, Devenyns I, Verhaegen J, Syrogiannopoulos G, Leclercq R: Macrolide resistance mechanisms in Streptococcus pneumoniae isolates from Belgium. Clin Microbiol Infect. 2005, 11: 332-334. 10.1111/j.1469-0691.2005.01077.x.CrossRefPubMed
11.
Jacobs MR, Good CE, Beall B, Bajaksouzian S, Windau AR, Whitney CG: Changes in serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae strains in Cleveland: a quarter century of experience. J Clin Microbiol. 2008, 46: 982-990. 10.1128/JCM.02321-07.CrossRefPubMedPubMedCentral
12.
Farrell DJ, Couturier C, Hryniewicz W: Distribution and antibacterial susceptibility of macrolide resistance genotypes in Streptococcus pneumoniae: PROTEKT Year 5 (2003–2004). Int J Antimicrob Agents. 2008, 31: 245-249. 10.1016/j.ijantimicag.2007.10.022.CrossRefPubMed
13.
14.
Imöhl M, Reinert RR, Mutscher C, van der Linden M: Macrolide susceptibility and serotype specific macrolide resistance of invasive isolates of Streptococcus pneumoniae in Germany from 1992 to 2008. BMC Microbiol. 2010, 10: 299-10.1186/1471-2180-10-299.CrossRefPubMedPubMedCentral
15.
Leclercq R, Courvalin P: Resistance to macrolides and related antibiotics in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2002, 46: 2727-2734. 10.1128/AAC.46.9.2727-2734.2002.CrossRefPubMedPubMedCentral
16.
17.
Ambrose KD, Nisbet R, Stephens DS: Macrolide efflux in Streptococcus pneumoniae is mediated by a dual efflux pump (mel and mef) and is erythromycin inducible. Antimicrob Agents Chemother. 2005, 49: 4203-4209. 10.1128/AAC.49.10.4203-4209.2005.CrossRefPubMedPubMedCentral
18.
Sutcliffe J, Tait-Kamradt A, Wondrack L: Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. Antimicrob Agents Chemother. 1996, 40: 1817-1824.PubMedPubMedCentral
19.
Tait-Kamradt A, Clancy J, Cronan M, Dib-Hajj F, Wondrack L, Yuan W, Sutcliffe J: mefE is necessary for the erythromycin-resistant M phenotype in Streptococcus pneumoniae. Antimicrob Agents Chemother. 1997, 41: 2251-2255.PubMedPubMedCentral
20.
Roberts MC, Sutcliffe J, Courvalin P, Jensen LB, Rood J, Seppala H: Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob Agents Chemother. 1999, 43: 2823-2830.PubMedPubMedCentral
21.
Oster P, Zanchi A, Cresti S, Lattanzi M, Montagnani F, Cellesi C, Rossolini GM: Patterns of macrolide resistance determinants among community-acquired Streptococcus pneumoniae isolates over a 5-year period of decreased macrolide susceptibility rates. Antimicrob Agents Chemother. 1999, 43: 2510-2512.PubMedPubMedCentral
22.
Del Grosso M, Iannelli F, Messina C, Santagati M, Petrosillo N, Stefani S, Pozzi G, Pantosti A: Macrolide efflux genes mef(A) and mef(E) are carried by different genetic elements in Streptococcus pneumoniae. J Clin Microbiol. 2002, 40: 774-778. 10.1128/JCM.40.3.774-778.2002.CrossRefPubMedPubMedCentral
23.
Bley C, van der Linden M, Reinert RR: mef(A) is the predominant macrolide resistance determinant in Streptococcus pneumoniae and Streptococcus pyogenes in Germany. Int J Antimicrob Agents. 2011, 37: 425-431. 10.1016/j.ijantimicag.2011.01.019.CrossRefPubMed
24.
Santagati M, Iannelli F, Oggioni MR, Stefani S, Pozzi G: Characterization of a genetic element carrying the macrolide efflux gene mef(A) in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2000, 44: 2585-2587. 10.1128/AAC.44.9.2585-2587.2000.CrossRefPubMedPubMedCentral
25.
Santagati M, Iannelli F, Cascone C, Campanile F, Oggioni MR, Stefani S, Pozzi G: The novel conjugative transposon Tn1207.3 carries the macrolide efflux gene mef(A) in Streptococcus pyogenes. Microb Drug Resist. 2003, 9: 243-247. 10.1089/107662903322286445.CrossRefPubMed
26.
Del Grosso M, Camilli R, Iannelli F, Pozzi G, Pantosti A: The mef(E)-carrying genetic element (mega) of Streptococcus pneumoniae: insertion sites and association with other genetic elements. Antimicrob Agents Chemother. 2006, 50: 3361-3366. 10.1128/AAC.00277-06.CrossRefPubMedPubMedCentral
27.
Varaldo PE, Montanari MP, Giovanetti E: Genetic elements responsible for erythromycin resistance in streptococci. Antimicrob Agents Chemother. 2009, 53: 343-353. 10.1128/AAC.00781-08.CrossRefPubMed
28.
Paraskakis I, Kafetzis DA, Chrisakis A, Papavasilliou H, Kirikou H, Pangalis A, Tzouvelekis LS, Athanasiou T, Legakis NJ, on behalf of the National Surveillance Network for Pneumococcal Resistance: Serotypes and antimicrobial susceptibilities of 1033 pneumococci isolated from children in Greece during 2001–2004. Clin Microbiol Infect. 2006, 12: 490-493. 10.1111/j.1469-0691.2006.01383.x.CrossRefPubMed
29.
Souli M, Volonakis K, Kapaskelis A, Galani I, Grammelis V, Vorou R, Tsivra M, Chryssouli Z, Katsala D, Giamarellou H: Characterisation of macrolide–non-susceptible Streptococcus pneumoniae colonising children attending day-care centres in Athens, Greece during 2000 and 2003. Clin Microbiol Infect. 2007, 13: 70-77. 10.1111/j.1469-0691.2006.01555.x.CrossRefPubMed
30.
Grivea IN, Tsantouli AG, Chryssanthopoulou DC, Syrogiannopoulos GA: Interaction of the heptavalent pneumococcal conjugate vaccine and the use of individual antibiotics among children on nasopharyngeal colonization with erythromycin-resistant Streptococcus pneumoniae. Eur J Clin Microbiol Infect Dis. 2010, 29: 97-105. 10.1007/s10096-009-0826-1.CrossRefPubMed
31.
Hellenic National Committee for Immunization Programs: National Immunization Program. Paediatriki. 2006, 69: 78-82.
32.
Syrogiannopoulos GA, Grivea IN, Davies TA, Katopodis GD, Appelbaum PC, Beratis NG: Antimicrobial use and colonization with erythromycin-resistant Streptococcus pneumoniae in Greece during the first 2 years of life. Clin Infect Dis. 2000, 31: 887-893. 10.1086/318118.CrossRefPubMed
33.
Clinical and Laboratory Standards Institute (CLSI): Performance Standards for Antimicrobial Susceptibility Testing; Eighteenth Informational Supplement. CLSI document M100-S18. 2008, Wayne, PA: CLSI
34.
35.
Sutcliffe J, Grebe T, Tait-Kamradt A, Wondrack L: Detection of erythromycin-resistant determinants by PCR. Antimicrob Agents Chemother. 1996, 40: 2562-2566.PubMedPubMedCentral
36.
Reinert RR, Lütticken R, Bryskier A, Al-Lahham A: Macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes in the pediatric population in Germany during 2000–2001. Antimicrob Agents Chemother. 2003, 47: 489-493. 10.1128/AAC.47.2.489-493.2003.CrossRefPubMedPubMedCentral
37.
American Academy of Pediatrics: Pneumococcal infections. Red Book: 2009 Report of the Committee on Infectious Diseases. Edited by: Pickering LK, Baker CJ, Kimberlin DW, Long SS. 2009, Elk Grove Village, IL: American Academy of Pediatrics, 524-535. 28
38.
Syrogiannopoulos GA, Grivea IN, Beratis NG, Spiliopoulou AE, Fasola EL, Bajaksouzian S, Appelbaum PC, Jacobs MR: Resistance patterns of Streptococcus pneumoniae from carriers attending day-care centers in Southwestern Greece. Clin Infect Dis. 1997, 25: 188-194. 10.1086/514526.CrossRefPubMed
39.
Bogaert D, Hermans PWM, Grivea IN, Katopodis G, Mitchell TJ, Sluijter M, de Groot R, Beratis NG, Syrogiannopoulos GA: Molecular epidemiology of penicillin-susceptible non-β-lactam-resistant Streptococcus pneumoniae isolates from Greek children. J Clin Microbiol. 2003, 41: 5633-5639. 10.1128/JCM.41.12.5633-5639.2003.CrossRefPubMedPubMedCentral
40.
Maraki S, Samonis G, Galanakis E: Serotypes and susceptibilities of paediatric clinical isolates of Streptococcus pneumoniae in Crete, Greece, before and after the heptavalent pneumococcal conjugate vaccine. Eur J Clin Microbiol Infect Dis. 2010, 29: 1449-1451. 10.1007/s10096-010-1005-0.CrossRefPubMed
41.
Sá-Leão R, Nunes S, Brito-Avô A, Frazão N, Simões AS, Crisóstomo MI, Paulo ACS, Saldanha J, Santos-Sanches I, de Lencastre H: Changes in pneumococcal serotypes and antibiotypes carried by vaccinated and unvaccinated day-care centre attendees in Portugal, a country with widespread use of the seven-valent pneumococcal conjugate vaccine. Clin Microbiol Infect. 2009, 15: 1002-1007. 10.1111/j.1469-0691.2009.02775.x.CrossRefPubMed
42.
Hanage WP, Bishop CJ, Huang SS, Stevenson AE, Pelton SI, Lipsitch M, Finkelstein JA: Carried pneumococci in Massachusetts children. The contribution of clonal expansion and serotype switching. Pediatr Infect Dis J. 2011, 30: 302-308. 10.1097/INF.0b013e318201a154.CrossRefPubMedPubMedCentral
43.
Ardanuy C, Fenoll A, Berrón S, Calatayud L, Liñares J, and the Spanish Pneumococcal Infection Study Network: Increase of the M phenotype among erythromycin-resistant Streptococcus pneumoniae isolates from Spain related to the serotype 14 variant of the Spain9V-3 clone. Antimicrob Agents Chemother. 2006, 50: 3162-3165. 10.1128/AAC.00269-06.CrossRefPubMedPubMedCentral
44.
Sogstad MK, Littauer P, Aaberge IS, Caugant DA, Høiby A: Rapid spread in Norway of an erythromycin-resistant pneumococcal clone, despite low usage of macrolides. Microb Drug Resist. 2007, 13: 29-36. 10.1089/mdr.2006.9994.CrossRefPubMed
45.
Bowers JR, Driebe EM, Nibecker JL, Wojack BR, Sarovich DS, Wong AH, Brzoska PM, Hubert N, Knadler A, Watson LM, Wagner DM, Furtado MR, Saubolle M, Engelthaler DM, Keim PS: Dominance of multidrug resistant CC271 clones in macrolide-resistant Streptococcus pneumoniae in Arizona. BMC Microbiol. 2012, 12: 12-10.1186/1471-2180-12-12.CrossRefPubMedPubMedCentral
46.
Aguiar SI, Brito MJ, Gonçalo-Marques J, Melo-Cristino J, Ramirez M: Serotypes 1, 7F and 19A became the leading causes of pediatric invasive pneumococcal infections in Portugal after 7 years of heptavalent conjugate vaccine use. Vaccine. 2010, 28: 5167-5173. 10.1016/j.vaccine.2010.06.008.CrossRefPubMed
47.
Rückinger S, van der Linden M, Reinert RR, von Kries R, Burckhardt F, Siedler A: Reduction in the incidence of invasive pneumococcal disease after general vaccination with 7-valent pneumococcal conjugate vaccine in Germany. Vaccine. 2009, 27: 4136-4141. 10.1016/j.vaccine.2009.04.057.CrossRefPubMed
48.
McGee L, Klugman KP, Wasas A, Capper T, Brink A, and the Antibiotics Surveillance Forum of South Africa: Serotype 19F multiresistant pneumococcal clone harboring two erythromycin resistance determinants [erm(B) and mef(A)] in South Africa. Antimicrob Agents Chemother. 2001, 45: 1595-1598. 10.1128/AAC.45.5.1595-1598.2001.CrossRefPubMedPubMedCentral
49.
Farrell DJ, Morrissey I, Bakker S, Morris L, Buckridge S, Felmingham D: Molecular epidemiology of multiresistant Streptococcus pneumoniae with both erm(B) and mef(A)-mediated macrolide resistance. J Clin Microbiol. 2004, 42: 764-768. 10.1128/JCM.42.2.764-768.2004.CrossRefPubMedPubMedCentral
50.
Farrell DJ, Jenkins SG, Brown SD, Patel M, Lavin BS, Klugman KP: Emergence and spread of Streptococcus pneumoniae with erm(B) and mef(A) resistance. Emerg Infect Dis. 2005, 11: 851-858. 10.3201/eid1106.050222.CrossRefPubMedPubMedCentral
51.
Eskola J, Kilpi T, Palmu A, Jokinen J, Haapakoski J, Herva E, Takala A, Käyhty H, Karma P, Kohberger R, Siber G, Mäkela PH: Efficacy of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med. 2001, 344: 403-409. 10.1056/NEJM200102083440602.CrossRefPubMed
52.
Ekström N, Åhman H, Verho J, Jokinen J, Väkeväinen M, Kilpi T, Käyhty H: Kinetics and avidity of antibodies evoked by heptavalent pneumococcal vaccines PncCRM and PncOMPC in the Finnish otitis media vaccine trial. Infect Immun. 2005, 73: 369-377. 10.1128/IAI.73.1.369-377.2005.CrossRefPubMedPubMedCentral
53.
Xu X, Cai L, Xiao M, Kong F, Oftadeh S, Zhou F, Gilbert GL: Distribution of serotypes, genotypes, and resistance determinants among macrolide-resistant Streptococcus pneumoniae isolates. Antimicrob Agents Chemother. 2010, 54: 1152-1159. 10.1128/AAC.01268-09.CrossRefPubMedPubMedCentral
Metadata
Title
Macrolide resistance determinants among Streptococcus pneumoniae isolates from carriers in Central Greece
Authors
Ioanna N Grivea
Alexia Sourla
Eleni Ntokou
Denise C Chryssanthopoulou
Alexandra G Tsantouli
George A Syrogiannopoulos
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2012
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-12-255

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