Macrolide- and telithromycin-resistant Streptococcus pyogenes, Belgium, 1999-2003 (1).We found a 13% macrolide resistance in 3,866 Streptococcus pyogenes Streptococcus py·og·e·nes n. A bacterium that causes the formation of pus or of fatal septicemias. Streptococcus pyogenes A common bacterium that causes strep throat and can also cause tonsillitis. isolated from tonsillopharyngitis patients; 59% macrolide-resistant isolates were distributed in 5 clones, suggesting the importance of both resistance gene transfer and clonal dissemination in the spread of these organisms. We also report one of the largest collections of telithromycin-resistant isolates. ********** Streptococcus pyogenes causes several million cases of upper respiratory tract infection upper respiratory tract infection URI Infectious disease A nonspecific term used to describe acute infections involving the nose, paranasal sinuses, pharynx, and larynx, the prototypic URI is the common cold; flu/influenza is a systemic illness involving the URT each year. The problem of these infections is growing as resistance increases among S. pyogenes to the macrolide group of antimicrobial drugs commonly used to treat such infections (1-4). S. pyogenes acquires resistance by 2 main mechanisms. The first is active drug efflux efflux Medtalk That which flows outward mediated by an ATP-binding cassette transporter ATP-binding cassette transporters (ABC-transporter) are members of a superfamily which is one of the largest, and most ancient families with representatives in all extant phyla from prokaryotes to humans. [1]. wherein mef(A) encodes the transmembrane domains and msr(D) encodes the ATP-binding domains (5). This pattern of resistance is demonstrated by an M phenotype. In the second mechanism, gene products of erm(B) or erm(A) methylate methylate /meth·yl·ate/ (meth´i-lat) 1. a compound of methyl alcohol and a base. 2. to add a methyl group to a substance. meth·yl·ate v. 1. the macrolide-binding site on 23S rRNA and stall bacterial protein Bacterial protein a protein formed by bacterial activity.[1]. Examples
[2] synthesis. This pattern of resistance is demonstrated by either a constitutive constitutive /con·sti·tu·tive/ (kon-stich´u-tiv) produced constantly or in fixed amounts, regardless of environmental conditions or demand. (cMLS) or an inducible (iMLS) phenotype. A third, rare, mechanism is modification of the drug binding site on rRNA by mutation that is expressed as an M or a cMLS phenotype. The newest generation of macrolides, the ketolides, are also active against macrolide-resistant strains; however, few S. pyogenes strains of the cMLS phenotype have been found to be ketolide resistant (6). In Belgium, the first ketolide to be used clinically, telithromycin, was approved in October 2002 to treat community-acquired respiratory infections in patients >12 years of age. We investigated the temporal trends in resistance and clonality among macrolide (including telithromycin)-resistant S. pyogenes recovered from patients with tonsillopharyngitis during surveillance studies conducted in Belgium. The Study During 1999-2003, a total of 4,031 nonduplicate, putative S. pyogenes isolates were collected from 10 Belgian provinces This is a list of the Belgian provinces: Belgian provinces
n. A nutrient culture medium that is enriched with whole blood and used for the growth of certain strains of bacteria. , Gram stain gram stain Staining technique for the initial identification of bacteria, devised in 1884 by the Danish physician Hans Christian Gram (1853–1938). The stain reveals basic differences in the biochemical and structural properties of a living cell. , catalase catalase /cat·a·lase/ (kat´ah-las) a hemoprotein enzyme that catalyzes the decomposition of hydrogen peroxide to water and oxygen, protecting cells. production, pyrrolidonyl arylamidase, presence of Group A antigen A antigen A major blood group–ABO antigen that defines the blood type A, which assumes the codominant allele at the ABO locus is either blood group A or H. Cf B antigen, Bombay phenotype, H antigen. , and bacitracin bacitracin (băs'ĭtrā`sĭn), antibiotic produced by a strain of the bacterial species Bacillus subtilis. It is widely used for topical therapy such as for skin and eye infections; it is effective against gram-positive bacteria, susceptibility, 3,866 isolates were confirmed to be S. pyogenes. The age of the patient was known in 3,654 cases. Population statistics are detailed in the first half of Table 1. By using erythromycin erythromycin (ĭrĭth'rōmī`sĭn), any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic). (78 [micro]g) and clindamycin (25 [micro]g) double-disk diffusion (Neo-Sensitab discs; Rosco, Taastrup, Denmark), all 3,866 S. pyogenes isolates were further screened for a phenotypic expression of macrolide resistance, which was identified in 506 (13%) isolates. The proportion of macrolide-resistant isolates among the total S. pyogenes isolated from each of the 10 Belgian provinces fluctuated from 0% to 40% over the 5 years studied. The 3 known phenotypes, cMLS, iMLS, and M, were identified in 209 (41%), 18 (4%), and 279 (55%) isolates, respectively. Changes in prevalence of the 3 phenotypes among macrolide-resistant S. pyogenes over 5 years are presented in the second half of Table 1. MICs of erythromycin, clindamycin, tetracycline tetracycline (tĕ'trəsī`klēn), any of a group of antibiotics produced by bacteria of the genus Streptomyces. They are effective against a wide range of Gram positive and Gram negative bacteria, interfering with protein (Sigma-Aldrich, St. Louis, MO, USA), clarithromycin (Abbott, Louvain-la-Neuve, Belgium), azithromycin (Pfizer, Groton, CT, USA), and telithromycin (Aventis, Romainville, France) were further determined by agar dilution (7). Susceptible and resistance breakpoints for telithromycin were [less than or equal to] 1 [micro]g/mL and [greater than or equal to] 4 [micro]g/mL, respectively. Briefly, a [10.sup.4] CFU/spot inoculum inoculum /in·oc·u·lum/ (-ok´u-lum) pl. inoc´ula material used in inoculation. in·oc·u·lum n. pl. was incubated at 37[degrees]C for 18-24 h in ambient air. The MIC profiles of the 3 macrolide-resistant phenotypes to various antimicrobial drugs are presented in the online Appendix Table 1 (available at http://www.cdc.gov/ncidod/eid/vol11no06/04-1247_app1.htm). The yearly prevalence (1999-2003) of telithromycin resistance (MIC [greater than or equal to] 4 [micro]g/mL) among macrolide-resistant S. pyogenes was 2%, 7%, 11%, 13%, and 10%, respectively. Thus, the total telithromycin-resistant isolates (N = 50) identified here constitute the largest collection reported. Of the 50 telithromycin-resistant S. pyogenes, 49 belonged to the cMLS and 1 to the iMLS phenotype. These isolates exhibited erythromycin MICs of 128->512 [micro]g/mL. Thirty (60%) telithromycin-resistant S. pyogenes were isolated from children, of which 28 (56%) were [less than or equal to] 12 years of age. We further investigated clonality in all macrolide-resistant isolates and in a random selection of 331 macrolide-susceptible isolates by pulsed-field gel electrophoresis gel electrophoresis n. Electrophoresis performed in a gel composed of agarose, polyacrylamide, or starch. (PFGE PFGE Pulsed-Field Gel Electrophoresis ) and emm typing on reverse line blotting as described previously (1). PFGE was performed by using SmaI; however, for most mef(A)-positive isolates that proved refractory to Sinai restriction, SfiI restriction was utilized. PFGE patterns were analyzed by using GelCompar software 4.0 (Applied Maths, Kortrijk, Belgium). The 506 macrolide-resistant S. pyogenes were typed into 17 emm types and 76 PFGE types, of which 53 (70%) types were distributed among M phenotype isolates (Appendix Table 2 available at http://www.cdc.gov/ncidod/eid/vol11no06/04-1247_app2.htm). Ratios of PFGE types to number of S. pyogenes isolates were 0.18 and 0.09 for the M and cMLS phenotypes, respectively. Table 2 shows the temporal evolution over 5 years of the 5 major cMLS and M phenotype clones. Clones 1, 4, and 23 constituted 99%, 98%, and 100% of all the macrolide-resistant emm22, emm28, and emm11, respectively, isolated during the course of this study, while clones 1,001 and 1,002 constituted 97% and 39% of the emm1 and emm4 macrolide-resistant S. pyogenes serotypes, respectively. Serotypes emm1, emm4, emm11, emm22 and emm28 formed 70% of the total macrolide-resistant S. pyogenes. Among the 331 macrolide-susceptible S. pyogenes analyzed, the prevalence of clones 1,4, 23, 1,001, and 1,002 was 5% (n = 18), 1% (n = 3), 0.3% (n = 1), 2% (n = 5), and 0.3% (n = 1), respectively (data not shown). Telithromycin resistance was distributed among 7 cMLS serotypes (emm22, emm28, emm11, emm12, emm77, emm6, and, emm2). We next studied the genotype genotype (jēn`ətīp'): see genetics. genotype Genetic makeup of an organism. The genotype determines the hereditary potentials and limitations of an individual. for the 3 macrolide-resistant phenotypes. Polymerase chain reaction polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is was performed for erm(A), erm(B), and mef(A) (1,9,10). Isolates negative for all 3 genes were screened for ribosomal mutations in L4, L22, and portions of 23S RNA RNA: see nucleic acid. RNA in full ribonucleic acid One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic genes by using published primers (11). Amplimers were analyzed by direct double-strand sequencing (3730 DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. Analyzer, Applied Biosystems Applied Biosystems, Inc. (formerly NASDAQ: ABIO) is the original name of a pioneer biotechnology company founded in 1981 in Foster City, California, among the Silicon Valley cities of the southern San Francisco Bay Area. , Foster City, CA, USA) with the BigDye Terminator Version 3.1 Kit (Applied Biosystems). Nucleotide sequence alignment was done with SeqMan (DNASTAR Inc., Madison, WI, USA). Phenotypic and genotypic profiles of the macrolide-resistant S. pyogenes were generally consistent; however, 3% of the resistant isolates carried 2 resistance genes. Of the 209 cMLS isolates, 199 carried erm(B), 9 carried erm(B)+mef(A), and 1 carried erm(B)+erm(A). Of the 279 M phenotype isolates, 273 carried mef(A), 1 carried erm(B)+mef(A), and 4 carried mef(A)+erm(A). The 1 isolate that was negative for all 3 genes carried a single A2059G (Escherichia coli Escherichia coli (ĕsh'ərĭk`ēə kō`lī), common bacterium that normally inhabits the intestinal tracts of humans and animals, but can cause infection in other parts of the body, especially the urinary tract. numbering system) mutation in the 23S rRNA gene. The A2059G mutation, although quite frequent in S. pneumoniae, has been rarely observed in S. pyogenes. Finally, of the 18 iMLS isolates, 5 carried erm(B) and 13 carried erm(A). Ten percent of the macrolide-resistant strains harboring erm(B) alone or with mef(A) were also telithromycin-resistant, and telithromycin has additional binding sites on 23S rRNA. Therefore, we hypothesized that either mutations in the erm gene promoter region have upregulated methylase expression or that mutations in the coding region The coding region of a gene is the portion of DNA that is transcribed into mRNA and translated into proteins. This does not include such regions as a recognition site, initiator sequence, or termination sequence, only the region that will directly code for amino acid linkage. have changed the methylase specificity to include the additional binding sites of telithromycin. Alternatively, mutations at the additional binding sites on the 23S rRNA genes might also disable the binding arm; however, a recent study described only a low level of telithromycin resistance in the presence of these mutations (12). Utilizing 3 pairs of overlapping primers (primer sequences available on request), DNASTAR software, and sequence data of Tn1545 (National Center for Biotechnology Information The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988. , Rockville, MD, USA, accession no. X52632), the entire erm(B) gene, including the promoter and control peptides, were sequenced from 10 telithromycin-resistant isolates. In addition, L4, L22, and portions of 23S rRNA genes were also amplified as above. Analysis of the sequencing data showed a single Hll8R (A677G) substitution in the erm(B) coding region of all 10 telithromycin-resistant isolates. While our study was ongoing, the HI I8R substitution in erm(B) was also confirmed independently for 2 telithromycin-resistant isolates (6). Conclusions We demonstrated in this study that overall macrolide resistance in Belgium is driven by an epidemic spread of a few major clones as well as by resistance gene transfer among genetically diverse S. pyogenes. On average, we demonstrated a 2-fold (13%) increase in macrolide resistance in Belgium from 1999 to 2003, compared to that observed from 1995 to 1997 (6.5%) (1). Although, a general increase in macrolide-resistance in Europe has been observed during the last few years, resistance levels tend to differ considerably between countries. For instance, while resistance rates in Germany (6) and Poland (4) were similar to those observed in Belgium, considerably higher resistance levels were observed in Spain and Portugal (2), as well as in Italy (3). Provincial variations in macrolide-resistance observed in Belgium have also been reported in other countries (3); however, the precise causes underlying such variations within or between countries are not fully understood. Macrolide consumption might be one factor that explains the regional variations in macrolide-resistant S. pyogenes in Spain and Finland (13,14), especially when consumption surpasses a critical threshold Critical threshold, a notion derived from the percolation theory, refers to a threshold, that summons up to a critical mass. Under the threshold the phenomenon tends to abort, above the threshold, it tends to grow exponentially. (15). However, in France, one of the highest macrolide consumption within Europe is not paralleled by an equally high resistance in S. pyogenes (16,17). The identification of telithromycin-resistant S. pyogenes in our study, many of which were already present in the community before the introduction of telithromycin in Belgium, also suggest that antimicrobial drug use and development of resistance might be dissociated dis·so·ci·ate v. dis·so·ci·at·ed, dis·so·ci·at·ing, dis·so·ci·ates v.tr. 1. To remove from association; separate: to some extent. Clearly, other factors like natural fluctuations in prevalence of clones (18), patient compliance with antimicrobial drug regimens, fitness costs of drug resistance, or even tetracycline consumption (tetracycline and macrolide-resistance genes cosegregate) (19) might be important determinants for the development and spread of macrolide-resistant S. pyogenes. Thus, any direct link between macrolide use and resistance in S. pyogenes should be interpreted cautiously.
Table 1. Yearly prevalence of Streptococcus pyogenes isolates
screened and of macrolide-resistant S. pyogenes distributed by
patient age group and phenotype, 1999-2003
1999 2000
Total S. pyogenes screened 598 336
Isolated from adults (mean 220 (36.7%) 144 (43.1%)
age, 34.7 y; SD, 11.1 y;
range, 17 to 91 y)
Isolated from children (mean 357 (59.6%) 172 (51.2%)
age, 7.2 y; SD, 3.5 y,
range, 3 mo to 16.9 y)
Macrolide-resistant S. pyogenes 81 (14%) 41 (12%)
Isolated from adults 23 (4%) 16 (5%)
Isolated from children 56 (9%) 22 (7%)
Constitutive phenotype 49/81 (8%) 10/41
([section]) (3%)
M phenotype 32/81 (5%) 29/41 (9%)
Inducible phenotype -- 2/41 (1%)
2001 2002
Total S. pyogenes screened 633 1,226
Isolated from adults (mean 245 (38.7%) 469 (38.2%)
age, 34.7 y; SD, 11.1 y;
range, 17 to 91 y)
Isolated from children (mean 367 (58.0%) 675 (55.0%)
age, 7.2 y; SD, 3.5 y,
range, 3 mo to 16.9 y)
Macrolide-resistant S. pyogenes 73 (12%) 215 * (18%)
Isolated from adults 29 (5%) 82 (7%)
Isolated from children 44 (7%) 126 ([double
dagger]) (10%)
Constitutive phenotype 28/73 (4%) 68/215 (6%)
M phenotype 39/73 (6%) 141/215 (12%)
Inducible phenotype 6/73 (1%) 7/215 (1%)
2003
Total S. pyogenes screened 1,073
Isolated from adults (mean 453 (42.0%)
age, 34.7 y; SD, 11.1 y;
range, 17 to 91 y)
Isolated from children (mean 552 (51.0%)
age, 7.2 y; SD, 3.5 y,
range, 3 mo to 16.9 y)
Macrolide-resistant S. pyogenes 96 * (9%)
Isolated from adults 38 ([dagger]) (4%)
Isolated from children 50 ([dagger]) (5%)
Constitutive phenotype 54/96 (5%)
M phenotype 38/96 ([section]) (4%)
Inducible phenotype 4/96 (0.4%)
* Increase and decrease in macrolide resistance from 2001 to 2002
and from 2002 to 2003, respectively, was significant (p<0.001).
([dagger]) Prevalence of macrolide-resistant S. pyogenes decreased
significantly among both children and adults from 2002 to 2003
(p<0.0001).
([double dagger]) Prevalence of macrolide-resistant S. pyogenes
increased significantly among children from 2001 to 2002 (p = 0.005).
([section]) Decrease in prevalence of cMLS isolates from 1999 to
2000 (p = 0.005) and of M phenotype isolates from 2002 to 2003
(p<0.0001) was significant.
Pearson's [chi square]-test with Bonferonni post-hoc adjustments was
used for all multiple comparisons. p<0.05 (2-sided) was significant.
Table 2. Temporal changes in the distribution of major pulsed-field
gel electrophoresis and emm types among the 3 macrolide-resistant
Streptococcus pyogenes phenotypes *
No. (%) of
macrolide-resistant
S. pyogenes
Pulsed-field
Macrolide- gel electropho-
resistant resis cluster Frequency
phenotype (emm type) (n = 506) 1999 (n = 81)
Constitutive 1 (emm22) 70 45 (56%)
4 (emm28) 45 --
23 (emm11) 28 --
M 1001 (emm1) 128 7 (9%)
1002 (emm4) 28 2 (2.5%)
No. (%) of macrolide-resistant
S. pyogenes
Pulsed-field
Macrolide- gel electropho-
resistant resis cluster
phenotype (emm type) 2000 (n = 41) 2001 (n = 73)
Constitutive 1 (emm22) 7 (17%) ([dagger]) 9 (12%)
4 (emm28) -- 4 (5%)
23 (emm11) -- 1 (1%)
M 1001 (emm1) 12 (29%) 23 (32%)
1002 (emm4) 2 (5%) 7 (10%)
No. (%) of macrolide-resistant
S. pyogenes
Pulsed-field
Macrolide- gel electropho-
resistant resis cluster
phenotype (emm type) 2002 (n = 215) 2003 (n = 96)
Constitutive 1 (emm22) 7 (3%) 2 (2%)
4 (emm28) 15 (7%) 26 (27%)
23 (emm11) 6 (3%) 21 (22%)
M 1001 (emm1) 80 (37%) 6 (6%)
([double dagger]) ([double dagger])
1002 (emm4) 7 (3%) 10 (10%)
* A [less than or equal to] 6-band difference was employed to assign
isolates to a clone according to Tenover et al. (8). PFGE clusters up
to 100 designate restriction with SmaI and clusters [greater than or
equal to] 1,000 designate restriction with SM.
([dagger]) Decrease in prevalence of the 1/emm22 clone from 1999 to
2000 was highly significant (p<0.001).
([double dagger]) Both the increase and decrease in prevalence of the
1001/emm1 clone from 2001 to 2002 and from 2002 to 2003, respectively,
were significant (p<0.01).
Acknowledgments We thank the following centers in Belgium for their participation in this study: AML AML - A Manufacturing Language BVBA BVBA Besloten Vennootschap met Beperkte Aansprakelijkheid , Antwerp; Laboratoire de Biologie Clinique et Hormonale--S.P.R.L., Couillet; Centraal Laboratorium, Hasselt; Medisch Centrum centrum /cen·trum/ (sen´trum) pl. cen´tra [L.] 1. a center. 2. the body of a vertebra. cen·trum n. pl. cen·trums or cen·tra 1. Huisarten, Leuven; Centre Hospitalier de L'Ardenne Laboratoire de Biologie Clinique et de Ria, Libramont; Laboratoire Marchand, Liege liege In European feudal society, an unconditional bond between a man and his overlord. Thus, if a tenant held estates from various overlords, his obligations to his liege lord, to whom he had paid “liege homage,” were greater than his obligations to the other . This study was partly funded by the Belgian Antibiotic Policy Co-ordination Committee (BAPCOC). (1) A preliminary account of this work was presented at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy (print-ISSN 0066-4804, CODEN AMACCQ; canceled ISSN 0074-9923, canceled CODEN AACHAX) is an academic journal published by the American Society for Microbiology. , October 30-November 2, 2004, Washington DC, USA. References (1.) Descheemaeker P, Chapelle S, Lammens C, Hauchecorne M, Wijdooghe M, Vandamme P, et al. Macrolide resistance and erythromycin resistance determinants among Belgian Streptococcus pyogenes and Streptococcus pneumoniae Streptococcus pneu·mo·ni·ae n. Pneumococcus. Streptococcus pneumoniae Microbiology A pathogenic streptococcus with 90 serotypes associated with pneumonia, bacteremia, meningitis Transmission Person to person Incidence isolates. J Antimicrob Chemother. 2000;45:167-73. (2.) Canton R, Loza E, Morosini MI, Baquero F. Antimicrobial resistance amongst isolates of Streptococcus pyogenes and Staphylococcus aureus Staphylococcus au·re·us n. A bacterium that causes furunculosis, pyemia, osteomyelitis, suppuration of wounds, and food poisoning. Staphylococcus aureus Staphylococcus pyogenes in the PROTEKT PROTEKT Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin antimicrobial surveillance programme during 1999-2000. J Antimicrob Chemother. 2002;50(Suppl S1):9-24. (3.) Cornaglia G, Ligozzi M, Mazzariol A, Masala L, Lo CG, Orefici G, et al. Resistance of Streptococcus pyogenes to erythromycin and related antibiotics in Italy. The Italian Surveillance Group for Antimicrobial Resistance. Clin Infect Dis. 1998;27(Suppl 1):S87-S92. (4.) Szczypa K, Sadowy E, Izdebski R, Hryniewicz W. A rapid increase in macrolide resistance in Streptococcus pyogenes isolated in Poland during 1996-2002. J Antimicrob Chemother. 2004;54:828-31. (5.) Iannelli F, Santagati M, Docquier JD, Cassone cassone (käs-sô`nā), the Italian term for chest or coffer, usually a bridal or dower chest, highly ornate and given prominence in the home. M. Oggioni MR, Rossolini G, et al. Type M resistance to macrolides in streptococci Streptococcus (plural, streptococci) A genus of spherical-shaped anaerobic bacteria occurring in pairs or chains. Sydenham's chorea is considered a complication of a streptococcal throat infection. is not due to the mef(A) gene, but to mat(A) encoding an ATP-dependent efflux pump [Abstract C1-1188]. Presented at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC ICAAC Interscience Conference on Antimicrobial Agents and Chemotherapy ICAAC Iowa Community College Athletic Conference ); Washington; 2004 Oct 30-Nov 2. (6.) Reinert RR, Lutticken R, Sutcliffe JA, Tait-Kamradt A, Cil MY, Schom HM, et al. Clonal relatedness of erythromycin-resistant Streptococcus pyogenes isolates in Germany. Antimicrob Agents Chemother. 2004;48:1369-73. (7.) NCCLS NCCLS National Committee for Clinical Laboratory Standards . National Committee for Clinical laboratory Standards. Performance standards for antimicrobial susceptibility testing. Twelfth informational supplement, M100-S12. Wayne (PA): The Committee; 2002. (8.) Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995;33:2233-9. (9.) Sutcliffe J, Grebe grebe (grēb), common name for swimming birds found on or near quiet waters in most parts of the world. Grebes resemble the loon and the duck; they have short wings, vestigial tails, and long, individually webbed toes on feet that are set far back T, Tait-Kamradt A, Wondrack L. Detection of erythromycin-resistant determinants by PCR PCR polymerase chain reaction. PCR abbr. polymerase chain reaction Polymerase chain reaction (PCR) . Antimicrob Agents Chemother. 1996;40:2562-6. (10.) Malhotra-Kumar S, Wang S, Lammens C, Chapelle S, Goossens H. Bacitracin-resistant clone of Streptococcus pyogenes isolated from pharyngitis pharyngitis Inflammation and infection (usually bacterial or viral) of the pharynx. Symptoms include pain (sore throat, worse on swallowing), redness, swollen lymph nodes, and fever. patients in Belgium. J Clin Microbiol. 2003:41:5282-4. (11.) Malbruny B, Nagai K, Coquemont M, Bozdogan B. Andrasevic AT, Hupkova H, et al. Resistance to macrolides in clinical isolates of Streptococcus pyogenes due to ribosomal mutations. J Antimicrob Chemother. 2002;49:935-9. (12.) Novotny GW, Jakobsen L, Andersen NM, Poehlsgaard J, Douthwaite S. Ketolide antimicrobial activity persists alter disruption of interactions with domain II of 23S rRNA. Antimicrob Agents Chemother. 2004;48:3677-83. (13.) Garcia-Rey C, Aguilar L, Baquero F, Casal J, Martin JE. Pharmacoepidemiological analysis of provincial differences between consumption of macrolides and rates of erythromycin resistance among Streptococcus pyogenes isolates in Spain. J Clin Microbiol. 2002;40:2959-63. (14.) Bergman M, Huikko S, Pihlajamaki M, Laippala P, Palva E, Huovinen P, et al. Effect of macrolide consumption on erythromycin resistance in Streptococcus pyogenes in Finland in 1997-2001. Clin Infect Dis. 2004:38:1251-6. (15.) Granizo JJ, Aguilar L, Casal J, Dal Re R, Baquero F. Streptococcus pyogenes resistance to erythromycin in relation to macrolide consumption in Spain (1986 1997). J Antimicrob Chemother. 2000;46:959-64. (16.) Goossens H, Ferech M, Vander Stichele R, Elseviers M. Outpatient antibiotic use in Europe and association with resistance. Lancet. 2005:365:579-87. (17.) Weber P, Filipecki J, Bingen E, Fitoussi F, Goldfarb G, Chauvin JP, et al. Genetic and phenotypic characterization of macrolide resistance in group A streptococci isolated from adults with pharyngo-tonsillitis in France. J Antimicrob Chemother. 2001;48:291-4. (18.) Kaplan EL, Wotton JT, Johnson DR. Dynamic epidemiology of group A streptococcal streptococcal /strep·to·coc·cal/ (-kok´al) pertaining to or caused by a streptococcus. Streptococcal (Streptococcus) Pertaining to any of the Streptococcus bacteria. serotypes associated with pharyngitis. Lancet. 2001;358:1334-7. (19.) Nielsen HU, Hammerum AM, Ekelund K. Bang D, Pallesen LV, Frimodt-Moller N. Tetracycline and macrolide co-resistance in Streptococcus pyogenes: co-selection as a reason for increase in macrolide-resistant S. pyogenes? Microb Drug Resist. 2004:10:231-8. Surbhi Malhotra-Kumar, * Christine Lammens, * Sabine Chapelle, * Monique Wijdooghe, * Jasper Piessens, * Koen Van Herck, * and Herman Goossens * * University of Antwerp University of Antwerp (Dutch: Universiteit Antwerpen) is a university located in Antwerp, Belgium. History It was founded in 2003 after the merger of the three universities that were previously known as RUCA (State University Centre Antwerp), UFSIA (University Faculties , Antwerp, Belgium Ms. Malhotra-Kumar holds a double master's degree master's degree n. An academic degree conferred by a college or university upon those who complete at least one year of prescribed study beyond the bachelor's degree. Noun 1. in medical microbiology Medical microbiology is a branch of microbiology which deals with the study of microorganisms including bacteria, viruses, fungi and parasites which are of medical importance and are capable of causing diseases in human beings. and molecular biology molecular biology, scientific study of the molecular basis of life processes, including cellular respiration, excretion, and reproduction. The term molecular biology was coined in 1938 by Warren Weaver, then director of the natural sciences program at the Rockefeller and is a final-year PhD student at the University of Antwerp. Her main research focuses on the epidemiology and molecular genetics molecular genetics n. The branch of genetics that deals with hereditary transmission and variation on the molecular level. of antimicrobial resistance in oral streptococci. Address for correspondence: Surbhi Malhotra-Kumar, Department of Medical Microbiology, Campus Drie Eiken, University of Antwerp, S3, Universiteitsplein 1, B-2610 Wilrijk, Antwerp, Belgium; tax: 32-3-820-26-63; email: surbhi.malhotra@ua.ac.be |
|
||||||||||||||||||||
Printer friendly
Cite/link
Email
Feedback
Reader Opinion