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Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal A Cluster-Randomized Clinical Trial


Background:
It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities.

Methods and Findings:
In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1–10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%–8.9%) at baseline, to 46.9% (37.5%–57.5%) at month 12 (p = 0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%–13.3%) at month 12, significantly lower than the treated group (p<0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%–4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year.

Conclusions:
This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections.

Trial registration:
www.ClinicalTrials.gov NCT00322972

: Please see later in the article for the Editors' Summary


Vyšlo v časopise: Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal A Cluster-Randomized Clinical Trial. PLoS Med 7(12): e32767. doi:10.1371/journal.pmed.1000377
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1000377

Souhrn

Background:
It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities.

Methods and Findings:
In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1–10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%–8.9%) at baseline, to 46.9% (37.5%–57.5%) at month 12 (p = 0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%–13.3%) at month 12, significantly lower than the treated group (p<0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%–4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year.

Conclusions:
This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections.

Trial registration:
www.ClinicalTrials.gov NCT00322972

: Please see later in the article for the Editors' Summary


Zdroje

1. LipsitchM

SamoreMH

2002 Antimicrobial use and antimicrobial resistance: a population perspective. Emerg Infect Dis 8 347 354

2. GoossensH

FerechM

Vander SticheleR

ElseviersM

2005 Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 365 579 587

3. BronzwaerSL

CarsO

BuchholzU

MolstadS

GoettschW

2002 A European study on the relationship between antimicrobial use and antimicrobial resistance. Emerg Infect Dis 8 278 282

4. Van EldereJ

MeraRM

MillerLA

PoupardJA

Amrine-MadsenH

2007 Risk factors for development of multiple-class resistance to Streptococcus pneumoniae Strains in Belgium over a 10-year period: antimicrobial consumption, population density, and geographic location. Antimicrob Agents Chemother 51 3491 3497

5. MeraRM

MillerLA

WhiteA

2006 Antibacterial use and Streptococcus pneumoniae penicillin resistance: a temporal relationship model. Microb Drug Resist 12 158 163

6. ArasonVA

SigurdssonJA

ErlendsdottirH

GudmundssonS

KristinssonKG

2006 The role of antimicrobial use in the epidemiology of resistant pneumococci: a 10-year follow up. Microb Drug Resist 12 169 176

7. ChenDK

McGeerA

de AzavedoJC

LowDE

1999 Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Canadian Bacterial Surveillance Network. N Engl J Med 341 233 239

8. PihlajamakiM

KotilainenP

KaurilaT

KlaukkaT

PalvaE

2001 Macrolide-resistant Streptococcus pneumoniae and use of antimicrobial agents. Clin Infect Dis 33 483 488

9. GranizoJJ

AguilarL

CasalJ

Dal-ReR

BaqueroF

2000 Streptococcus pyogenes resistance to erythromycin in relation to macrolide consumption in Spain (1986-1997). J Antimicrob Chemother 46 959 964

10. BergmanM

HuikkoS

PihlajamakiM

LaippalaP

PalvaE

2004 Effect of macrolide consumption on erythromycin resistance in Streptococcus pyogenes in Finland in 1997-2001. Clin Infect Dis 38 1251 1256

11. ArasonVA

KristinssonKG

SigurdssonJA

StefansdottirG

MolstadS

1996 Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. BMJ 313 387 391

12. VanderkooiOG

LowDE

GreenK

PowisJE

McGeerA

2005 Predicting antimicrobial resistance in invasive pneumococcal infections. Clin Infect Dis 40 1288 1297

13. MetlayJP

FishmanNO

JoffeMM

KallanMJ

ChittamsJL

2006 Macrolide resistance in adults with bacteremic pneumococcal pneumonia. Emerg Infect Dis 12 1223 1230

14. CarmeliY

SamoreMH

HuskinsC

1999 The association between antecedent vancomycin treatment and hospital-acquired vancomycin-resistant enterococci: a meta-analysis. Arch Intern Med 159 2461 2468

15. BolonMK

WrightSB

GoldHS

CarmeliY

2004 The magnitude of the association between fluoroquinolone use and quinolone-resistant Escherichia coli and Klebsiella pneumoniae may be lower than previously reported. Antimicrob Agents Chemother 48 1934 1940

16. WrightHR

TurnerA

TaylorHR

2008 Trachoma. Lancet 371 1945 1954

17. MeleseM

ChidambaramJD

AlemayehuW

LeeDC

YiEH

2004 Feasibility of eliminating ocular Chlamydia trachomatis with repeat mass antibiotic treatments. JAMA 292 721 725

18. MeleseM

AlemayehuW

LakewT

YiE

HouseJ

2008 Comparison of annual and biannual mass antibiotic administration for elimination of infectious trachoma. JAMA 299 778 784

19. LietmanT

PorcoT

DawsonC

BlowerS

1999 Global elimination of trachoma: how frequently should we administer mass chemotherapy? Nat Med 5 572 576

20. HongKC

SchachterJ

MoncadaJ

ZhouZ

HouseJ

2009 Lack of macrolide resistance in Chlamydia trachomatis after mass azithromycin distributions for trachoma. Emerg Infect Dis 15 1088 1090

21. SolomonAW

MohammedZ

MassaePA

ShaoJF

FosterA

2005 Impact of mass distribution of azithromycin on the antibiotic susceptibilities of ocular Chlamydia trachomatis. Antimicrob Agents Chemother 49 4804 4806

22. LeachAJ

Shelby-JamesTM

MayoM

GrattenM

LamingAC

1997 A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae. Clin Infect Dis 24 356 362

23. GaynorBD

ChidambaramJD

CevallosV

MiaoY

MillerK

2005 Topical ocular antibiotics induce bacterial resistance at extraocular sites. Br J Ophthalmol 89 1097 1099

24. FryAM

JhaHC

LietmanTM

ChaudharyJS

BhattaRC

2002 Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal. Clin Infect Dis 35 395 402

25. HouseJI

AyeleB

PorcoTC

ZhouZ

HongKC

2009 Assessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomised trial. Lancet 373 1111 1118

26. ZerihunN

1997 Trachoma in Jimma zone, south western Ethiopia. Trop Med Int Health 2 1115 1121

27. O'BrienKL

BronsdonMA

DaganR

YagupskyP

JancoJ

2001 Evaluation of a medium (STGG) for transport and optimal recovery of Streptococcus pneumoniae from nasopharyngeal secretions collected during field studies. J Clin Microbiol 39 1021 1024

28. FarrellDJ

MorrisseyI

BakkerS

FelminghamD

2002 Molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae and Streptococcus pyogenes isolated from the PROTEKT 1999–2000 study. J Antimicrob Chemother 50 Suppl S1 39 47

29. FarrellDJ

MorrisseyI

BakkerS

MorrisL

BuckridgeS

2004 Molecular epidemiology of multiresistant Streptococcus pneumoniae with both erm(B)- and mef(A)-mediated macrolide resistance. J Clin Microbiol 42 764 768

30. LeclercqR

CourvalinP

1991 Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother 35 1267 1272

31. SutcliffeJ

Tait-KamradtA

WondrackL

1996 Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. Antimicrob Agents Chemother 40 1817 1824

32. SutcliffeJ

GrebeT

Tait-KamradtA

WondrackL

1996 Detection of erythromycin-resistant determinants by PCR. Antimicrob Agents Chemother 40 2562 2566

33. HaugS

LakewT

HabtemariamG

AlemayehuW

CevallosV

2010 The decline of pneumococcal resistance after cessation of mass antibiotic distributions for trachoma. Clin Infect Dis 51 571 574

34. SeppalaH

KlaukkaT

Vuopio-VarkilaJ

MuotialaA

HeleniusH

1997 The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. Finnish Study Group for Antimicrobial Resistance. N Engl J Med 337 441 446

35. GuillemotD

VaronE

BernedeC

WeberP

HenrietL

2005 Reduction of antibiotic use in the community reduces the rate of colonization with penicillin G-nonsusceptible Streptococcus pneumoniae. Clin Infect Dis 41 930 938

36. Malhotra-KumarS

LammensC

CoenenS

Van HerckK

GoossensH

2007 Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet 369 482 490

37. PorcoTC

GebreT

AyeleB

HouseJ

KeenanJ

2009 Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial. JAMA 302 962 968

38. GaynorBD

HolbrookKA

WhitcherJP

HolmSO

JhaHC

2003 Community treatment with azithromycin for trachoma is not associated with antibiotic resistance in Streptococcus pneumoniae at 1 year. Br J Ophthalmol 87 147 148

39. BattSL

CharalambousBM

SolomonAW

KnirschC

MassaePA

2003 Impact of azithromycin administration for trachoma control on the carriage of antibiotic-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother 47 2765 2769

40. SolomonAW

HollandMJ

AlexanderND

MassaePA

AguirreA

2004 Mass treatment with single-dose azithromycin for trachoma. N Engl J Med 351 1962 1971

41. WestSK

MunozB

MkochaH

GaydosC

QuinnT

2007 Trachoma and ocular Chlamydia trachomatis were not eliminated three years after two rounds of mass treatment in a trachoma hyperendemic village. Invest Ophthalmol Vis Sci 48 1492 1497

42. BiebesheimerJB

HouseJ

HongKC

LakewT

AlemayehuW

2009 Complete local elimination of infectious trachoma from severely affected communities after six biannual mass azithromycin distributions. Ophthalmology 116 2047 2050

43. FeikinDR

DowellSF

NwanyanwuOC

KlugmanKP

KazembePN

2000 Increased carriage of trimethoprim/sulfamethoxazole-resistant Streptococcus pneumoniae in Malawian children after treatment for malaria with sulfadoxine/pyrimethamine. J Infect Dis 181 1501 1505

44. HillPC

AkisanyaA

SankarehK

CheungYB

SaakaM

2006 Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian villagers. Clin Infect Dis 43 673 679

45. ThyleforsB

DawsonCR

JonesBR

WestSK

TaylorHR

1987 A simple system for the assessment of trachoma and its complications. Bull World Health Organ 65 477 483

Štítky
Interné lekárstvo

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PLOS Medicine


2010 Číslo 12
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Autori: MUDr. Tomáš Ürge, PhD.

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