Macrolide-resistance genes in clinical isolates of Streptococcus pyogenes

Macrolide-resistance genes were investigated in 103 macrolide-resistant strains of Streptococcus pyogenes, isolated from children with pharyngotonsillitis. The presence of mef(A), erm(B), and erm(TR) genes was detected by PCR. mef(A) was found in 48 out of 103 (46.6%) strains, whereas erm(B) was detected in 43 isolates (41.7%). All mef(A) strains showed a typical M phenotype (resistance to 14- and 15-membered macrolides, and sensitivity to lincosamides and streptogramin B), whereas erm(B) strains had the MLSB phenotype (resistance to macrolides, lincosamides, and streptogramin B antibiotics). erm(TR) was found in 10 strains, always together with other resistance genes. In seven cases erm(TR) was associated with erm(B), and three cases with mef(A). In two isolates with the M phenotype (1.9%), it was not possible to detect the presence of any of the three macrolide resistance genes tested. Inducible resistance to macrolides was shown for 24 out of the 53 MLSB strains. Analysis of macrorestriction fragment patterns by pulsed-field gel electrophoresis showed that erythromycin-resistant S. pyogenes are polyclonal, however each phenotype, MLSB and M, formed essentially homogeneous groups.     

Differentiation of resistance phenotypes among erythromycin-resistant Pneumococci

Laboratory differentiation of erythromycin resistance phenotypes is poorly standardized for pneumococci. In this study, 85 clinical isolates of erythromycin-resistant (MIC > or = 1 microg/ml) Streptococcus pneumoniae were tested for the resistance phenotype by the erythromycin-clindamycin double-disk test (previously used to determine the macrolide resistance phenotype in Streptococcus pyogenes strains) and by MIC induction tests, i.e., by determining the MICs of macrolide antibiotics without and with pre-exposure to 0.05 microg of erythromycin per ml. By the double-disk test, 65 strains, all carrying the erm(AM) determinant, were assigned to the constitutive macrolide, lincosamide, and streptogramin B resistance (cMLS) phenotype, and the remaining 20, all carrying the mef(E) gene, were assigned to the recently described M phenotype; an inducible MLS resistance (iMLS) phenotype was not found. The lack of inducible resistance to clindamycin was confirmed by determining clindamycin MICs without and with pre-exposure to subinhibitory concentrations of erythromycin. In macrolide MIC and MIC-induction tests, whereas homogeneous susceptibility patterns were observed among the 20 strains assigned to the M phenotype by the double-disk test, two distinct patterns were recognized among the 65 strains assigned to the cMLS phenotype by the same test; one pattern (n = 10; probably that of the true cMLS isolates) was characterized by resistance to rokitamycin also without induction, and the other pattern (n = 55; designated the iMcLS phenotype) was characterized by full or intermediate susceptibility to rokitamycin without induction turning to resistance after induction, with an MIC increase by more than three dilutions. A triple-disk test, set up by adding a rokitamycin disk to the erythromycin and clindamycin disks of the double-disk test, allowed the easy differentiation not only of pneumococci with the M phenotype from those with MLS resistance but also, among the latter, of those of the true cMLS phenotype from those of the iMcLS phenotype. While distinguishing MLS from M resistance in pneumococci is easily and reliably achieved, the differentiation of constitutive from inducible MLS resistance is far more uncertain and is strongly affected by the antibiotic used to test inducibility.     

Unusual inducible cross resistance to macrolides, lincosamides, and streptogramins B by methylase production in clinical isolates of Staphylococcus aureus

Clinical strains of Staphylococcus aureus UCN7 and UCN8 were inducibly resistant to erythromycin, clindamycin, lincomycin, and quinupristin. This unusual inducible MLS(B) resistance was due to the presence of an erm(A) or an erm(B) gene, which both encode a ribosomal methylase, in S. aureus UCN8 and UCN7, respectively. The inducible cross resistance expressed by S. aureus UCN8 was associated with an 83-bp deletion in the attenuator of the erm(A) gene that removed the second of the two leader peptides and several inverted repeats. The presence of an inducible erm(B) gene in S. aureus UCN7 conferred a cross-resistance MLS(B) phenotype, similar to that usually observed in streptococci. Therefore, in S. aureus, besides the classical inducible MLS(B) phenotype characterized by inducible resistance to 14- to 15-membered ring macrolides, an additional type of inducible cross resistance to macrolides, lincosamides, and streptogramins B due to variants of erm(A) or erm(B) genes exist.     

Molecular epidemiology of erythromycin resistance in Streptococcus pneumoniae isolates from blood and noninvasive sites

Erythromycin-resistant isolates of Streptococcus pneumoniae from blood cultures and noninvasive sites were studied over a 3-year period. The prevalence of erythromycin resistance was 11.9% (19 of 160) in blood culture isolates but 4.2% (60 of 1,435) in noninvasive-site isolates. Sixty-two of the 79 resistant isolates were available for study. The M phenotype was responsible for 76% (47 of 62) of resistance, largely due to a serotype 14 clone, characterized by multilocus sequence typing as ST9, which accounted for 79% (37 of 47) of M phenotype resistance. The ST9 clone was 4.8 times more common in blood than in noninvasive sites. All M phenotype isolates were PCR positive for mef(A), but sequencing revealed that the ST9 clone possessed the mef(A) sequence commonly associated with Streptococcus pyogenes. All M phenotype isolates with this mef(A) sequence also had sequences consistent with the presence of the Tn1207.1 genetic element inserted in the celB gene. In contrast, isolates with the mef(E) sequence normally associated with S. pneumoniae contained sequences consistent with the presence of the mega insertion element. All MLS(B) isolates carried erm(B), and two isolates carried both erm(B) and mef(E). Fourteen of the 15 MLS(B) isolates were tetracycline resistant and contained tet(M). However, six M phenotype isolates of serotypes 19 (two isolates) and 23 (four isolates) were also tetracycline resistant and contained tet(M). MICs for isolates with the mef(A) sequence were significantly higher than MICs for isolates with the mef(E) sequence (P < 0.001). Thus, the ST9 clone of S. pneumoniae is a significant cause of invasive pneumococcal disease in northeast Scotland and is the single most important contributor to M phenotype erythromycin resistance.     

Characterization of erythromycin-resistant Streptococcus pneumoniae in Korea, and In Vitro activity of telithromycin against erythromycin-resistant Streptococcus pneumoniae

To characterize the phenotypes and genotypes of erythromycin-resistant clinical isolates of Streptococcus pneumoniae in Korea and to evaluate the in vitro activity of telithromycin against these erythromycin-resistant isolates, we tested a total of 676 isolates of S. pneumoniae collected from 1997 to 2002 in a tertiary hospital in Seoul, Republic of Korea. MICs for erythromycin and telithromycin were determined by the agar dilution method. The macrolide resistance phenotypes of erythromycin-resistant isolates were determined by the erythromycin- clindamycin-rokitamycin triple disk (ECRTD) and MIC induction tests, whereas their macrolide resistance genotypes were determined by PCR for the erm(B), erm(A), subclass erm(TR), and mef genes. To discriminate between mef(A) and mef(E), PCR-restriction fragment length polymorphism (RFLP) analyses were performed. Of the 676 S. pneumoniae isolates, 459 (67.9%) were resistant to erythromycin. Of the 459 erythromycin-resistant isolates, 343 (74.7%) were assigned to the cMLS phenotype, 48 (10.4%) to the iMcLS phenotype, 4 (0.9%) to the iMLS phenotype, and 64 (14.0%) to the M phenotype. The erm(B) gene was detected in 251 (54.6%) isolates, the mef gene was detected in 64 (14.0%), and both the erm(B) and mef genes were detected in 144 (31.4%) isolates. All of the mef genes detected were identified as mef(E). Of the 459 erythromycin- resistant isolates, all but one were susceptible to telithromycin. The MIC(50)/MIC(90) to telithromycin of isolates carrying erm(B), mef(E), and both genes was 0.06/0.5 microg/ml, 0.03/0.125 microg/ml, and 0.5/1.0 microg/ml, respectively. Although the MICs of telithromycin for the erythromycin-resistant isolates varied according to genotype, telithromycin was very active against these erythromycin-resistant S. pneumoniae.     

Increased prevalence of erythromycin resistance in streptococci: substantial upsurge in erythromycin-resistant M phenotype in Streptococcus pyogenes (1979-1998) but not in Streptococcus pneumoniae (1985-1999) in Taiwan

A total of 394 nonduplicate isolates of Streptococcus pyogenes collected from 1979 to 1998 and 267 nonduplicate isolates of Streptococcus pneumoniae collected from October, 1998, to May, 1999, in Taiwan were evaluated. Among the 220 erythromycin-resistant (MIC, > or =1 microg/ml) S. pyogenes isolates, 35% had an M phenotype and 65% had an ML phenotype (inducible resistance [iML], 0.5%, and constitutive resistance [cML], 64.5%). Among the 243 erythromycin-resistant S. pneumoniae isolates, the majority (65.4%) had an ML phenotype (iML, 0.4%, and cML, 65%) and 34.6% had an M phenotype. A substantial upsurge in the incidence of M-phenotype erythromycin-resistant isolates was found with time for S. pyogenes (0% in 1979-1984 and 100% in 1997-1998), and an increasing incidence of M-phenotype among erythromycin-resistant S. pneumoniae was also noted (<20% before 1994 and 45.4% in 1999). All S. pyogenes and all but four S. pneumoniae isolates exhibiting a cML or iML phenotype had harbored the ermAM gene. The presence of the mefA gene was demonstrated in all isolates of S. pyogenes and the mefE gene in all but four S. pneumoniae isolates exhibiting the M phenotype. Due to the increasing susceptibility of S. pyogenes and S. pneumoniae isolates to clindamycin, susceptibility tests of these two organisms to macrolides and clindamycin should be performed simultaneously in the clinical microbiology laboratory, particularly in areas with high rates of macrolide resistance.     

Phenotypic and genotypic characterization of macrolide resistant Streptococcus pneumoniae in Tunisia

One hundred of non duplicate Streptococcus pneumoniae resistant to erythromycin collected from three teaching hospitals in Tunisia from January 1998 to December 2004 were investigated to evaluate determine their resistance level to different macrolides and the mechanisms involved. Most erythromycin resistant S. pneumoniae were isolated from respiratory tract (34%). Eighty-three percent showed constitutive MLS(B) phenotype with high MICs of macrolides and lincosamides (MIC90 >256 microg/ml), 12% M phenotype with moderately increased MICs of macrolides (MIC90: 12 microg/ml) and low MICs of lincosamides (MIC90=0.75 microg/ml) and 5% inducible MLS(B) with high MICs of macrolides (MIC90 >256 microg/ml) and moderately increased MICs of lincosamides (MIC90=8 microg/ml). All strains were susceptible to quinupristun-dafopristin association and linezolid (MIC90=1 microg/ml). Strains belonging to MLS(B) phenotype were PCR positive for the erm B gene (88%). Twelve percent categorized as M phenotype carried the mef A gene. The rates of associated resistance were 68% to penicillin G, 53% to tetracyclines, 61% to cotrimoxazole, 21% to chloramphenicol and 13% to ciprofloxacin. MLS(B) constitutive phenotype conferring cross resistance to macrolides, lincosamides and streptogramins B with high level of resistance was the most prevalent. Thus, quinupristin-dalfopristin association and linezolid remain the most active molecules.     

Distribution of macrolide resistance genes erm(B) and mef(A) among 160 penicillin-intermediate clinical isolates of Streptococcus pneumoniae isolated in southern France

Two prevalent mechanisms of macrolide resistance are currently described in pneumococci: production of rRNA methylase that modify 23S ribosomal RNA resulting in MLSB phenotype, and an active efflux system resulting in M-phenotype. These two mechanisms are mediated by erm(B) and mef(A) genes respectively. Several studies reported a predominance of mef(A) gene in United-States and Canada. In European countries, erm(B) determinant is prevalent and mef(A)-mediated erythromycin resistance was recently reported in about 10% of strains in Belgium and Italy. In order to evaluate implication of mef(A) gene in pneumococci erythromycin resistance, 160 clinical isolates of S. pneumoniae with low-level of penicillin resistance and resistance to macrolides recovered between April 1999 and April 2000 were collected. These isolates were tested for their macrolide susceptibility by disc diffusion method, 155 showed the MLSB phenotype and 5 the M phenotype. Genotypic analysis was performed by erm(B) and mef(A) specific-mediated PCR: erm(B) gene was detected in 154 isolates, mef(A) gene in 5 isolates, and both genes in one strain. The phenotype seems to be well correlated to the genotyping result except for strain harboring both resistance determinants. Molecular typing of isolates harboring mef(A) gene performed by pulsed-field gel electrophoresis (PFGE) after restriction by Smal shows these strains to be epidemiologically unrelated. Our results show the predominance of the erm(B) gene in erythromycin resistant S. pneumoniae isolates. mef(A)-mediated resistance is effective in Southern France (3.7%) but this rate is the lowest published from European countries.     

Antimicrobial susceptibility patterns and macrolide resistance genes of beta-hemolytic viridans group streptococci in a tertiary Korean hospital

The aim of this study was to investigate antimicrobial susceptibilities and macrolide resistance mechanisms of beta-hemolytic viridans group streptococci (VGS) in a tertiary Korean hospital. Minimum inhibitory concentrations (MICs) of seven antimicrobials were determined for 103 beta-hemolytic VGS isolated from various specimens. The macrolide resistance mechanisms of erythromycin-resistant isolates were studied by the double disk test and polymerase chain reaction (PCR). The overall resistance rates of beta-hemolytic VGS were found to be 47.5% to tetracycline, 3.9% to chloramphenicol, 9.7% to erythromycin, and 6.8% to clindamycin, whereas all isolates were susceptible to penicillin G, ceftriaxone, and vancomycin. Among ten erythromycin-resistant isolates, six isolates expressed a constitutive MLS(B) (cMLS(B)) phenotype, and each of the two isolates expressed the M phenotype, and the inducible MLS(B) (iMLS(B)) phenotype. The resistance rates to erythromycin and clindamycin of beta-hemolytic VGS seemed to be lower than those of non-beta-hemolytic VGS in our hospital, although cMLSB phenotype carrying erm(B) was dominant in beta-hemolytic VGS.     

Macrolide resistance in beta-hemolytic streptococci: changes after the implementation of the separation of prescribing and dispensing of medications policy in Korea

This study evaluated the antimicrobial susceptibilities and macrolide resistance mechanisms of beta-hemolytic streptococci (BHS), and an additional objective was to assess the effects of 'the separation of prescribing and dispensing (SPD) of medications' on bacterial resistance rate and distribution of phenotypes and genotypes of erythromycin-resistant BHS by comparing the antimicrobial susceptibility data before (1990- 2000) and after the implementation of SPD at one tertiary care hospital in South Korea. Between the period of January 2001 and December 2002, the minimal inhibitory concentrations of six antimicrobials were determined for 249 clinical isolates of BHS. Resistance mechanisms of erythromycin-resistant (intermediate and resistant) isolates were studied by using the double disk test and PCR. Overall, the resistance rates to tetracycline, erythromycin, and clindamycin were 75.5%, 32.9%, and 32.5%, respectively. Sixty-seven (81.7%) of 82 erythromycin- resistant isolates expressed constitutive resistance to macrolide- lincosamide-streptogramin B antibiotics (a constitutive MLSB phenotype); 11 isolates (13.4%) expressed an M phenotype; and four isolates (4.9%) had an inducible MLSB resistance phenotype. erm(A) was found in isolates with constitutive/ inducible MLSB phenotypes, erm(B) with the constitutive/ inducible MLSB phenotype, and mef(A) with the M phenotype. We found that resistance rates to erythromycin and clindamycin among S. agalactiae, S. pyogenes, and group C streptococci isolates were still high after the implementation of the SPD policy in Korea, and that the constitutive MLSB resistance phenotype was dominant among erythromycin- resistant BHS in this Korean hospital.     

Streptococcus agalactiae in a large Portuguese teaching hospital: antimicrobial susceptibility, serotype distribution, and clonal analysis of macrolide-resistant isolates

Group B streptococci are emerging as a cause of serious infection worldwide. The capsular polysaccharides are not only important virulence factors but also the target of vaccine development efforts. Serotypes III (24.6%), V (23.4%), Ia (17.8%), and II (16.3%) were the most prevalent among 252 Streptococcus agalactiae isolates collected during 1999-2002 in the largest hospital of Lisbon, Portugal. The substantial proportion of bacteremic patients (17 neonates and 21 adults) in this period illustrates the present importance of S. agalactiae as a cause of invasive disease. All isolates were fully susceptible to penicillin (MIC(50) = 0.064 microg/ml; MIC(90) = 0.094 microg/ml, range 0.008-0.094), cefotaxime, chloramphenicol, ofloxacin, and vancomycin. Resistance was found to tetracycline (75.4%), erythromycin (10.7%), and clindamycin (9.9%). Of the 27 erythromycin-resistant isolates, 70.4% had the cMLS(B), 22.2% the iMLS(B), and 7.4% the M phenotype. All isolates presenting the M phenotype carried the mef(A) gene, whereas the erm(B) gene was found in a large fraction of MLS(B) isolates (n = 17) and only a small proportion (n = 7) the erm(A) gene [erm(TR) variant]. All isolates carried a single macrolide-resistance determinant. Macrolide resistance was not attributable to a single clone as evidenced by distinct serotype and pulsed-field gel electrophoretic profiles. Careful surveillance of S. agalactiae invasive infections in Portugal is essential, and the treatment or intrapartum prophylaxis of patients who are allergic to penicillin should be guided by contemporary resistance patterns observed in the country.     

Detection of multiple macrolide- and lincosamide-resistant strains of Streptococcus pyogenes from patients in the Boston area

Macrolide (including erythromycin and azithromycin) and lincosamide (including clindamycin) antibiotics are recommended for treatment of penicillin-allergic patients with Streptococcus pyogenes pharyngitis. Resistance to erythromycin in S. pyogenes can be as high as 48% in specific populations in the United States. Macrolide and lincosamide resistance in S. pyogenes is mediated by several different genes. Expression of the erm(A) or erm(B) genes causes resistance to erythromycin and inducible or constitutive resistance to clindamycin, respectively, whereas expression of the mef(A) gene leads to resistance to erythromycin but not clindamycin. We studied the resistance of S. pyogenes to erythromycin and clindamycin at an urban tertiary-care hospital. Of 196 sequential isolates from throat cultures, 15 (7.7%) were resistant to erythromycin. Three of these were also constitutively resistant to clindamycin and had the erm(B) gene. Five of the erythromycin-resistant isolates were resistant to clindamycin upon induction with erythromycin and had the erm(A) gene. The remaining seven erythromycin-resistant isolates were susceptible to clindamycin even upon induction with erythromycin and had the mef(A) gene. Pulsed-field gel electrophoresis analysis and emm typing demonstrated that the erythromycin-resistant S. pyogenes comprised multiple strains. These results demonstrate that multiple mechanisms of resistance to macrolide and lincosamide antibiotics are present in S. pyogenes strains in the United States.     

emm Gene distribution among erythromycin-resistant and -susceptible Italian isolates of Streptococcus pyogenes

The phenotypes and genetic determinants for macrolide resistance were determined for 167 erythromycin-resistant Streptococcus pyogenes strains. A cMLS phenotype was shown in 18% of the erythromycin-resistant strains, while inducible resistance was apparent in 31% and the M phenotype was apparent in 50%. The emm gene type of this set of resistant isolates and that of 48 erythromycin-sensitive isolates were determined. emm2 and emm48 were recorded only in the resistant strains of the M phenotype, while approximately all of the strains harboring the emm22 gene had the cMLS phenotype. More than 80% of the emm89-positive strains had the iMLS phenotype, and the same portion of emm4 strains presented the M phenotype. emm3 is recorded only among sensitive strains. The distribution of frequencies of the genetic determinant for the virulence factor M protein was significantly different both among organisms of different types of resistance and between resistant and sensitive populations of S. pyogenes under study.     

Prevalence of Streptococcus pneumoniae isolates bearing macrolide resistance genes in association with integrase genes of conjugative transposons in Japan

The relationship between susceptibility to macrolides and tetracycline, and the distribution of the resistance genes erm(B), mef(A) and tet(M) and the integrase gene of the conjugative transposon, Int-Tn, was examined in 43 isolates of Streptococcus pneumoniae from Gunma Prefecture, Japan. Thirty-five isolates were resistant to both macrolides and tetracycline and carried tet(M); erm(B) and mef(A) were detected in 19 and 16, respectively, of these isolates. Sixteen mef(A)-positive isolates were all identified as mef(E) variants. Int-Tn of Tn1545 was associated with 17 erm(B)- and 14 mef(A)-bearing isolates, and Int-Tn of Tn5252 was found in the remaining two mef(A)-carrying isolates. Pneumococcal strains with resistance to macrolides conferred by erm(B) or mef(A) in association with the integrase gene of conjugative transposon Tn1545 or Tn5252 appear to be prevalent in Japan.     

Macrolide-resistance mechanisms in Streptococcus pneumoniae isolates from Belgium

Of 233 erythromycin-resistant pneumococcal isolates collected in Belgium in 1999-2000, 89.7% carried the erm(B) gene, 6% the mef(A) gene, and 3.5%erm(B) plus mef(A). Two isolates contained neither erm(B) nor mef(A); one contained an erm(A) subclass erm(TR) gene, while the other contained an A2058G mutation in domain V of the 23S rRNA gene. Of 209 erm(B)-positive isolates, 191 had clindamycin MICs > 16 mg/L and 18 had MICs < or = 16 mg/L. Mef(A)-positive isolates all displayed the M resistance phenotype. Telithromycin remained active against erythromycin-resistant isolates, with the highest telithromycin MIC50 being found in mef(A)-positive isolates. No difference in the prevalence of different resistance mechanisms was observed compared to isolates collected in 1995-1997.     

The novel conjugative transposon tn1207.3 carries the macrolide efflux gene mef(A) in Streptococcus pyogenes

The macrolide efflux gene mef(A) of the Streptococcus pyogenes clinical strain 2812A was found to be carried by a 52-kb chromosomal genetic element that could be transferred by conjugation to the chromosome of other streptococcal species. The characteristics of this genetic element are typical of conjugative transposons and was named Tn1207.3. The size of Tn1207.3 was established by pulsed-field gel electrophoresis (PFGE), and DNA sequencing analysis showed that the 7,244 bp at the left end of Tn1207.3 were identical to those of the pneumococcal Tn1207.1 element. Tn1207.3-like genetic elements were found to be inserted at a single specific chromosomal site in 12 different clinical isolates S. pyogenes exhibiting the M phenotype of resistance to macrolides and carrying the mef(A) gene. Tn1207.3 was transferred from S. pyogenes 2812A to Streptococcus pneumoniae, and sequence analysis carried out on six independent transconjugants showed that insertion of Tn1207.3 in the pneumococcal genome always occurred at a single specific site as in Tn1207.1. Using MF2, a representative S. pneumoniae transconjugant, as a donor, Tn1207.3 was transferred again by conjugation to S. pyogenes and Streptococcus gordonii. The previously described nonconjugative element Tn1207.1 of S. pneumoniae appears to be a defective element, part of a longer conjugative transposon that carries mef(A) and is found in clinical isolates of S. pyogenes.     

Activity of quinupristin–dalfopristin in invasive isolates of Streptococcus pneumoniae from Italy

Eighty-five recent isolates of Streptococcus pneumoniae from patients with invasive disease were examined for their susceptibility to erythromycin, clindamycin, penicillin and quinupristin-dalfopristin by E test. A novel duplex PCR assay was used to detect the presence of the erm (B) or mef (A) genes in all of the erythromycin-resistant isolates. All of the strains tested were susceptible to the combination quinupristin–dalfopristin, regardless of their susceptibility to penicillin or to erythromycin. By duplex PCR, two-thirds of the erythromycin-resistant strains harbored erm , and one-third harbored mef . The activity of quinupristin–dalfopristin was not influenced by the genetic determinant of erythromycin resistance. The in vitro susceptibility of S. pneumoniae to quinupristin–dalfopristin is promising for future use; however, it is important to monitor the possible emergence of resistance.     

In vitro activity of telithromycin (HMR 3647) against Greek Streptococcus pyogenes and Streptococcus pneumoniae clinical isolates with different macrolide susceptibilities

The susceptibilities to macrolides and telithromycin of 161 Streptococcus pyogenes and 145 Streptococcus pyogenes strains, consecutively isolated from five Greek hospitals, were determined by Etest. Moreover, mechanisms of resistance to macrolides were phenotypically and genetically determined by double disk induction test and PCR, respectively. Of the S. pneumoniae and S. pyogenes isolates, 42.8% and 30.8%, respectively, were found to be resistant to erythromycin. Of the erythromycin-resistant S. pneumoniae and S. pyogenes isolates, 57.5% and 59.5%, respectively, displayed the M phenotype and harbored the mefA/E gene. Telithromycin was found to be more active than both erythromycin and clarithromycin against both species, with considerably lower MIC₅₀ and MIC₉₀ values.     

Prevalence of polyclonal mefA-containing isolates among erythromycin-resistant group A streptococci in Southern Taiwan

A total of 204 nonrepetitive isolates of group A streptococci (GAS), including 107 randomly collected between 1992 and 1995 and 66 and 31 consecutively collected in 1997 and 1998, respectively, from a university hospital in southern Taiwan were examined to determine the prevalence and mechanisms of erythromycin resistance among these isolates. Resistance to erythromycin was detected in 129 isolates (63.2%) by the agar dilution test. Of these, 42 isolates (32.6%) were assigned to the constitutive macrolide, lincosamide, and streptogramin B resistance (cMLS) phenotype, and all carried the ermB gene; 4 (3.1%) were assigned to the inducible MLS resistance (iMLS) phenotype, and all harbored the ermTR gene; and 83 (64.3%) were erythromycin resistant but susceptible to clindamycin (M phenotype), and all possessed the mefA gene. Distributed by years, the rates of erythromycin resistance and different phenotypes were 61.7% (53.0% cMLS, 6.1% iMLS, and 40.9% M phenotype) between 1992 and 1995, 62.1% (12.2% cMLS and 87.8% M phenotype) in 1997, and 71. 0% (9.1% cMLS and 90.9% M phenotype) in 1998. Pulsed-field gel electrophoresis showed that all but 2 cMLS isolates were clonal in origin, and 17 clones were detected among the M-phenotype isolates. These results indicate that the high incidence and increasing rate of erythromycin-resistant GAS in southern Taiwan are due to the prevalence of multiple M-phenotype clones and that clindamycin may be the drug of choice for the treatment of infections with GAS in penicillin-hypersensitive patients in this area.     

A high frequency of macrolide-lincosamide-streptogramin resistance determinants in Staphylococcus aureus isolated in South Korea

Genes conferring resistance to one of the macrolide-lincosamide-streptogramin (MLS) antibiotics may confer cross-resistance to others, because they have similar effects on bacterial protein synthesis. In Korea, over 70% of Staphylococcus aureus isolates are methicillin-resistant and erythromycin-resistant methicillin-resistant S. aureus (MRSA) is also prevalent. We investigated the frequency of MLS resistance in erythromycin-resistant S. aureus isolates. A total of 682 isolates of S. aureus were collected in a nationwide antibiotic resistance survey. Susceptibility to erythromycin, clindamycin, and quinupristin/dalfopristin was tested by disk diffusion. In all, 37% of the methicillin-susceptible S. aureus (MSSA) and 97% of the MRSA isolates were resistant to at least one of the MLS antibiotics, whereas all were susceptible to quinupristin/dalfopristin. Out of 518 strains that were resistant to erythromycin, 60 clindamycin-susceptible (30 MSSA, 30 MRSA) and 44 clindamycin-resistant isolates (14 MSSA, 30 MRSA) were selected at random from these strains. Thirteen genes related to MLS resistance were detected in these isolates by PCR. Of the 104 MSSA and MRSA strains tested, 98 harbored one or more erm gene. The most common was erm(A), with erm(C) next. But, msr(A), lnu(A), and mef(A) were rare and no resistance to streptogramin A was encountered.