Abstract

Coagulase-negative staphylococci (CoNS), particularly Staphylococcus epidermidis, belong to the microbiota of human skin and the mucosal membrane of the upper respiratory tract, and they express low pathogenic potential as commensals in healthy people (Voung & Otto 2002Voung C, Otto M 2002. Staphylococcus epidermidisinfections. Microbes Infect 4: 481-489., Otto 2009)Otto M 2009. Staphylococcus epidermidis - the “accidental” pathogen. Nat Rev Microbiol 7: 555-567.. However, they can be responsible for several serious infections in immunocompromised patients, particularly those associated with biomaterials (e.g., catheters, prosthetics etc.), leading to bacteraemia and sepsis (Ziebuhr et al. 2006Ziebuhr W, Henning S, Eckart M, Kränzler H, Batzilla C, Kozitskaya S 2006. Nosocomial infections by Staphylococcus epidermidis: how a commensal bacterium turns into a pathogen. Int J Antmicrob Agents 28 (Suppl. 1): S14-S20.,Caesy et al. 2007Caesy AL, Lambert PA, Elliott TSJ 2007. Staphylococci. Int J Antimicrob Agents 29 (Suppl. 3): S23-S32., Schoenfelder et al. 2010Schoenfelder SM, Lange C, Eckart M, Hennig S, Kozytska S, Ziebuhr W 2010. Success through diversity - how Staphylococcus epidermidis establishes as a nosocomial pathogen. Int J Med Microbiol 28: 380-386., Castro-Alarcón et al. 2011Castro-Alarcón N, Ribas-Aparicio RM, Silva-Sánchez J, Calderón-Navarro A, Sánchez-Pérez A, Parra-Rojas I, Aparicio-Ozores G 2011. Molecular typing and characterization of macrolide, lincosamide, and streptogramin resistance in Staphylococcus epidermidis strains isolated in a Mexican hospital. J Med Microbiol 60: 730-736.). On the other hand, as a natural part of the microflora, drug resistant strains may be selected during antibiotic therapy, which is a potential source of the resistance genes for pathogenic strains, e.g.,Staphylococcus aureus (Reyes et al. 2007Reyes J, Hidalgo M, Díaz L, Rincón S, Moreno J, Vanegas N, Castañeda E 2007. Characterization of macrolide resistance in Gram-positive cocci from Colombian hospitals: a countrywide surveillance. Int J Infect Dis 11: 329-336., Otto 2013Otto M 2013. Coagulase-negative staphylococci as reservoirs of genes facilitating MRSA infection: staphylococcal commensal species such asStaphylococcus epidermidis are being recognized as important sources of genes promoting MRSA colonization and virulence.Bioessays 35: 4-11., Vitali et al. 2014Vitali LA, Petrelli D, Lamikanra A, Prenna M, Ainkunmi EO 2014. Diversity of antibiotic resistance genes and staphylococcal cassette chromosomemec elements in faecal isolates of coagulase-negative staphylococci from Nigeria. BMC Microbiol 14: 106.).

Resistance to macrolide, lincosamide, and streptogramins B (MLS_B antibiotics) in staphylococci is associated with the following three mechanisms: (i) target modification, (ii) efflux pumps, and (iii) enzymatic modification of antibiotics. The first macrolide-resistant staphylococcal strains were identified in the 1950s (Roberts 2004Roberts MC 2004. Update on macrolide-lincosamide-streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol Lett 282: 147-159.). Currently, a large number of strains exhibit resistance to these antibiotics via different mechanisms. It is known that macrolide-resistant strains often exhibit co-resistance to other MLS_B antibiotics. The most common mechanism is the modification of ribosomes as a result of methylation of adenine within 23S rRNA ribosomal subunits by a methylase encoded by the erm genes (predominantlyermC). Conformational changes in the ribosome result in the reduced binding of all MLS_B antibiotics; these strains are resistant to all MLS_B antibiotics (the combination of quinupristin/dalfopristin loses bactericidal activity as the result of the development of resistance to quinupristin). The phenotypic expression of MLS_B resistance can be either inducible (iMLS_B) (generally induced by 14 and 15-membered macrolides) or constitutive (cMLS_B) (Weisblum 1995Weisblum B 1995. Erythromycin resistance by ribosome modification.Antimicrob Agents Chemother 39: 577-585.). The active efflux of antibiotics is mediated by msr genes (mainlymsrA) and is responsible for resistance only to 14 and 15-membered macrolides and streptogramins B (MS_B) phenotype (Reynolds et al. 2003Reynolds E, Ross JI, Cove JH 2003. msr(A) and related macrolide-streptogramin resistance determinants: incomplete transporters? Int J Antimicrob Agents 22: 228-236.). The third mechanism of resistance is based on the production of antibiotic-inactivating enzymes (e. g., phosphorylase encoded bymph or lin, the gene responsible for inactivation of lincosamides) (Chesneau et al. 2007Chesneau O, Tsvetkova K, Courvalin P 2007. Resistance phenotypes conferred by macrolide phosphotransferases. FEMS Microbiol Lett 269: 317-322., Achard et al. 2008Achard A, Guérin-Faublée V, Pichereau V, Villers C, Leclercq R 2008. Emergence of macrolide resistance gene mph(B) inStreptococcus uberis and cooperative effects withrdmC-like gene. Antimicrob Agents Chemother 52: 2767-2770.).

The aim of this study was to assess the prevalence of different MLS_Bresistance phenotypes among S. epidermidis, together with the evaluation of genes responsible for target modification (ermA,ermB, ermC), antibiotic efflux (msrA) or antibiotic inactivation (mphC,linA/A’). The evaluation of susceptibility to the 16-membered macrolide spiramycin was also performed.

This paper was developed using the equipment purchased within agreement POPW.01.03.00-06-010/09-00 Operational Program Development of Eastern Poland 2007-2013, Priority Axis I, Modern Economy, Operations 1.3. Innovations Promotion.

SUBJECTS, MATERIALS AND METHODS

Bacterial strains - A total of 197 strains of S. epidermidis were obtained from the mucosal membranes of the upper respiratory tracts of patients with nonsmall cell lung cancer who underwent hospitalisation. Nasal and pharyngeal swabs were obtained on the second day of the patients’ stays at the hospital. Among the strains, resistance to erythromycin was detected in 75 isolates.

Isolation and identification - Isolation and identification of bacterial strains were performed using routine microbiological tests. The following tests were used in the identification of CoNS: the coagulase test tube using rabbit plasma (Biomed, Poland) and API Staph strips (bioMérieux, France).

Identification of resistance to MLS_Bantibiotics - Susceptibility to MLS_B antibiotics, including the detection of resistance mechanisms, was based on the D-test according to European Centre for Disease Prevention and Control (EUCAST) recommendations. In addition, disks containing lincomycin (15 mg) were used to identify the L-phenotype. Moreover, for detection of the effects of spiramycin on clindamycin susceptibility, discs containing spiramycin (100 mg) were applied next to clindamycin (2 mg).

Determination of minimal inhibitory concentrations (MICs) to spiramycin - Detection of MICs to spiramycin was based on EUCAST recommendations using the double broth dilution method. In the absence of breakpoints for spiramycin in EUCAST, only the MICs were evaluated without grouping the strains as susceptible or resistant.

Isolation of bacterial DNA - The DNA Genomic Mini Kit (A&A Biotechnology, Poland) was used to isolate S. epidermidis DNA according to the manufacturer’s guidelines.

Identification of genes by polymerase chain reaction (PCR) - The sequences of the primers and the conditions of the PCR reactions are presented inTable I. For the PCR reactions, PCR REDTaq^® Ready Mix^TM PCR Mix with MgCl₂(Sigma-Aldrich, USA) was used. The final volume of each PCR reaction was 25 ml and contained 12.5 ml of REDTaq Ready Mix, 1 ml of each forward and reverse primer (concentration between 0.1-1.0 mM), 1 ml of DNA (50-200 ng), and 9 ml of water. The reactions were performed using a Whatman Biometra thermocycler, whereas the PCR products were subjected to agarose gel electrophoresis (2% agarose, 1xTRIS-acetate-EDTA, 120 mV, 40 min). The gels were stained with ethidium bromide and the PCR products were visualised using a Wilbert Lambert transilluminator and compared with molecular size markers [Gene Ruler^TM 100 bp DNA Ladder (Fermentas, Thermo Scientific, USA)].

Ethics - The study design and protocols were approved by the Ethical Committee of the Medical University of Lublin (KE-0254/75/2011).

RESULTS

The 75 S. epidermidis isolates expressed resistance to erythromycin with the following mechanisms of resistance: 27 (36%) strains exhibited cMLS_B resistance, 14 (18.7%) strains exhibited iMLS_Bresistance, and 34 (45.3%) strains exhibited MS_B resistance (Figure). Twenty-five isolates exhibited L-phenotypes and were determined to be either resistant to only lincomycin (24 strains) or resistant to lincomycin and clindamycin (1 strain).

The MICs of spiramycin among erythromycin-resistant S. epidermidiswere evaluated as follows: > 128 mg/L for all cMLS_B strains, from 4-> 128 mg/L for iMLS_B strains, and from 1-4 mg/L for strains exhibiting the MS_B phenotype. The MIC₅₀ and MIC₉₀values were also calculated. Strains with cMLS_B and iMLS_Bphenotypes exhibited MIC₅₀ and MIC₉₀ values > 128 mg/L, whereas the MIC₅₀ and MIC₉₀ values for the MS_Bstrains were determined to 4 mg/L (Table II). Moreover, for the 11 (78.6%) strains exhibiting iMLS_B phenotypes, the noninhibition zone around the spiramycin disc was found together with a D-shaped zone around the clindamycin disk.

As shown in Table III, among the strains with cMLS_B resistance, the predominant genes were ermCand mphC in 23 (85.2%) and 24 (88.9%) strains, respectively.linA/A’ was found to occur in 14 (51.8%) strains. The presence of other genes (e.g., ermA and ermB) was detected in a few strains; two strains did not possess any of the erm genes. The isolates with iMLS_B possessed the following genes:ermC - 14 (100%) strains, msrA - 7 (50%) strains, mphC - 13 (92.9%) strains, and linA/A’ - 10 (71.4%) strains; ermA and ermB were not detected. The strains exhibiting MS_B resistance were found to possess the following genes: ermC in 20 (58.8%) strains, msrAin 32 (94.1%) strains, mphC in 33 (97.1%) strains, andlinA/A’ in 24 (70.6%) strains; these strains did not carryermA or ermB. The strains exhibiting L-phenotypes contained linA/A’ in 24 (96%) strains,mphC in 23 (92%) strains, and ermC in 24 (96%) strains. ermA, ermB, and msrAwere not detected in the isolates with L-phenotypes. One strain did not carry any of the evaluated genes.

Table IV shows the combination of genes responsible for resistance to MLS_B antibiotics among staphylococci. In isolates exhibiting cMLS_B resistance, 11 different combinations were detected. The most frequent gene combination was ermC,mphC, and linA/A’, which was found in 10 (37%) strains. Among the strains exhibiting iMLS_B resistance, four gene combinations were evaluated. The most frequent combinations contained the following genes: ermC, mphC, and linA/A’ in five (35.7%) isolates and ermC, msrA,mphC, and linA/A’, also in five (35.7%) isolates. The MS_B-positive strains contained six different gene combinations in three major groups: ermC, msrA,mphC, and linA/A’ in 14 (41.2%) strains;msrA, mphC, and linA/A’ in nine (26.5%) strains, and ermC, msrA, andmphC in six (17.6%) strains. In the isolates with L-phenotypes, the most significant three-gene combination was ermC,mphC, and linA/A’ in 21 (84%) strains.

DISCUSSION

CoNS are potential reservoirs of antibiotic resistance genes, which can be transferred to S. aureus not only in vitro but also in vivo (Reyes et al. 2007Reyes J, Hidalgo M, Díaz L, Rincón S, Moreno J, Vanegas N, Castañeda E 2007. Characterization of macrolide resistance in Gram-positive cocci from Colombian hospitals: a countrywide surveillance. Int J Infect Dis 11: 329-336., Otto 2013Otto M 2013. Coagulase-negative staphylococci as reservoirs of genes facilitating MRSA infection: staphylococcal commensal species such asStaphylococcus epidermidis are being recognized as important sources of genes promoting MRSA colonization and virulence.Bioessays 35: 4-11.). Erythromycin resistance among CoNS was previously reported to result from a methylase encoded by different erm family genes that can be horizontally transferred to recipient strains (Zmantar et al. 2011Zmantar T, Kouidhi B, Miladi H, Bakhrouf A 2011. Detection of macrolide and disinfectant resistance genes in clinical Staphylococcus aureus and coagulase-negative staphylococci. BMC Res Notes 4: 453., Vitali et al. 2014Vitali LA, Petrelli D, Lamikanra A, Prenna M, Ainkunmi EO 2014. Diversity of antibiotic resistance genes and staphylococcal cassette chromosomemec elements in faecal isolates of coagulase-negative staphylococci from Nigeria. BMC Microbiol 14: 106.). Hence, surveillance of erythromycin resistance and MLS_B resistance in CoNS at phenotypic and genetic levels can provide important information regarding their current epidemiology.

Among the S. epidermidis strains studied, the most frequently identified gene in strains exhibiting both cMLS_B and iMLS_Bphenotypes was ermC, which is consistent with previous reports (Reyes et al. 2007Reyes J, Hidalgo M, Díaz L, Rincón S, Moreno J, Vanegas N, Castañeda E 2007. Characterization of macrolide resistance in Gram-positive cocci from Colombian hospitals: a countrywide surveillance. Int J Infect Dis 11: 329-336., Gherardi et al. 2009Gherardi G, De Florio L, Lorino G, Fico L, Dicuonzo G 2009. Macrolide resistance genotypes and phenotypes among erythromycin-resistant clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci, Italy. FEMS Immunol Med Microbiol 55: 62-67., Coutinho et al. 2010Coutinho VLS, Paiva RM, Reiter KC, de-Paris F, Barth AL, Mombach AB, Machado P 2010. Distribution of erm genes and low prevalence of inducible resistance to clindamycin among staphylococci isolates. Braz J Infect Dis 14: 564-568., Bouchami et al. 2011Bouchami O, Achour W, Hassen AB 2011. Prevalence of resistance phenotypes and genotypes to macrolide, lincosamide, and streptogramin in Gram-positive cocci isolated in Tunisian Bone Marrow Transplant Center.Pathol Biol 59: 199-206.,Brzychczy-Wloch et al. 2013Brzychczy-Wloch M, Borszewska-Kornacka M, Gulczynska E, Wojkowska-Mach J, Sulik M, Grzebyk M, Luchter M, Heczko PB, Bulanda M 2013. Prevalence of antibiotic resistance in multi-drug resistant coagulase-negative staphylococci isolated from invasive infection in very low birth weight neonates in two Polish NICUs. Ann Clin Microbiol Antimicrob 12: 41., Heb & Gallert 2014Heb S, Gallert C 2014. Resistance behavior of inducible clindamycin-resistant staphylococci from clinical samples and aquatic environments. J Med Microbiol 63: 1446-1453.). Only a few S. epidermidis exhibiting cMLS_B phenotypes possessedermA and/or ermB. Similar data have been previously reported (Bouchami et al. 2011Bouchami O, Achour W, Hassen AB 2011. Prevalence of resistance phenotypes and genotypes to macrolide, lincosamide, and streptogramin in Gram-positive cocci isolated in Tunisian Bone Marrow Transplant Center.Pathol Biol 59: 199-206.,Teodoro et al. 2012Teodoro CRS, Mattos CS, Cavalcante FS, Pereira EM, Santos KRN 2012. Characterization of MLSb resistance among Staphylococcus aureus and Staphylococcus epidermidis isolates carrying different SCCmec types. Microbiol Immunol 56: 647-650., Szczuka et al. 2016Szczuka E, Makowska N, Bosacka K, Słotwińska A, Kaznowski A 2016. Molecular basis of resistance to macrolides, lincosamides, and streptogramins inStaphylococcus hominis strains isolated from clinical specimens. Folia Microbiol (Praha) 61: 143-147.). Moreover, the presence of other erm genes (e.g., ermF) has been rarely detected in Staphylococcus spp (Roberts 2004)Roberts MC 2004. Update on macrolide-lincosamide-streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol Lett 282: 147-159.. Notably, the distribution of erm genes depends on the bacterial species. For example, ermA is more characteristic of S. aureus, whereas ermB is more characteristic of beta-haemolytic streptococci (Roberts 2004Roberts MC 2004. Update on macrolide-lincosamide-streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol Lett 282: 147-159., Buter et al. 2010Buter CCVL, Mouton JW, Klaassen CHW, Handgraaf CMA, Sunnen S, Melchers WJG, Sturm PDJ 2010. Prevalence and molecular mechanism of macrolide resistance in b-haemolytic streptococci in The Netherlands. Int J Antimicrob Agents 35: 590-592.,Meehan et al. 2014Meehan M, Cunney R, Cafferkey M 2014. Molecular epidemiology of group B streptococci in Ireland reveals a diverse population with evidence of capsular switching. Eur J Clin Microbiol Infect Dis 33: 1155-1162., Vitali et al. 2014Vitali LA, Petrelli D, Lamikanra A, Prenna M, Ainkunmi EO 2014. Diversity of antibiotic resistance genes and staphylococcal cassette chromosomemec elements in faecal isolates of coagulase-negative staphylococci from Nigeria. BMC Microbiol 14: 106.). Moreover, among CoNS, the type oferm gene also depends on the geographical region of their isolation. For example, ermC was previously detected in 50% of the strains exhibiting MLS_B resistance in Great Britain, whereas it was detected 90% of those in Denmark (Lim et al. 2002Lim JA, Kwon AR, Kim SK, Chong Y, Lee K, Choi AC 2002. Prevalence of resistance to macrolide, lincosamide, and streptogramin antibiotics in Gram-positive isolated in a Korean hospital. J Antimicrob Chemother 49: 489-495., Gatermann et al. 2007Gatermann SG, Koschinski T, Friedrich S 2007. Distribution and expression of macrolide resistance genes in coagulase-negative staphylococci.Clin Microbiol Infect 13: 777-781., Cetin et al. 2010Cetin ES, Gunes H, Kaya S, Aridogan BC, Demirci M 2010. Distribution of genes encoding resistance to macrolides, lincosamides, and streptogramins among clinical staphylococcal isolates in a Turkish university hospital.J Microbiol Immunol Infect 43: 524-529., Bouchami et al. 2011Bouchami O, Achour W, Hassen AB 2011. Prevalence of resistance phenotypes and genotypes to macrolide, lincosamide, and streptogramin in Gram-positive cocci isolated in Tunisian Bone Marrow Transplant Center.Pathol Biol 59: 199-206.) and in Mexico, ermA was reported as predominant in S. epidermidis (Castro-Alarcón et al. 2011Castro-Alarcón N, Ribas-Aparicio RM, Silva-Sánchez J, Calderón-Navarro A, Sánchez-Pérez A, Parra-Rojas I, Aparicio-Ozores G 2011. Molecular typing and characterization of macrolide, lincosamide, and streptogramin resistance in Staphylococcus epidermidis strains isolated in a Mexican hospital. J Med Microbiol 60: 730-736.).

The MS_BS. epidermidis isolates examined contained anmsrA gene encoding an ATP-dependent efflux pump, which actively removes 14-,15-membered MS_B. The MS_B phenotype observed inmsrA-negative S. epidermidis strains may be the result of the presence of mphC, which encodes for a macrolide-modifying enzyme (Gatermann et al. 2007Gatermann SG, Koschinski T, Friedrich S 2007. Distribution and expression of macrolide resistance genes in coagulase-negative staphylococci.Clin Microbiol Infect 13: 777-781.), thereby resulting in a “false-positive” MS_Bphenotype.

All S. epidermidis isolates with L-phenotypes generally contained the linA/A’ gene. Data from Novotna et al. (2005Novotna G, Adamkova V, Janat J, Melter O, Spižek J 2005. Prevalence of resistance mechanisms against macrolides and lincosamides in methicillin-resistant coagulase-negative staphylococci in the Czech Republic and occurrence of undefined mechanism of resistance to lincosamides.Antimicrob Agents Chemother 49: 3586-3589., 2007Novotna G, Spižek J, Janata J 2007. In vitro activity of telithromycin and quinupristin/dalfopristin against methicillin-resistant coagulase-negative staphylococci with defined resistance genotypes.Folia Microbiol 52: 593-599.) also indicated a connection between the presence of the linA/A’ gene and resistance to only lincomycin among staphylococci. The S. epidermidis strains studied exhibited resistance to lincomycin, but susceptibility to clindamycin as a result of increased enzyme affinity for lincomycin (Achard et al. 2005Achard A, Villers C, Pichereau V, Leclercq R 2005. NewlnuC gene conferring resistance to lincomycin by nucleotidylation in Streptococcus agalactiae UCN36.Antimicrob Agents Chemother 49: 2716-2719.). Resistance both to lincomycin and clindamycin may be a consequence of the presence of otherlin family genes orvga(A)_LC, which encodes a “new” variant of the SgA protein that is responsible for cross-resistance to streptogramins A and all lincosamides (Novotna & Janata 2006Novotna G, Janata J 2006. A new evolutionary variant of the streptogramin A resistance protein, Vga(A)LC, fromStaphylococcus haemolyticus with shifted substrate specificity towards lincosamides. Antimicrob Agents Chemother 50: 4070-4076.).

Among the iMLS_B and cMLS_BS. epidermidisstrains, the erm genes do not exist separately, but in combination with others (predominantly with mphC). Notably, othererm genes (e.g., ermF), which are rarely detected in Sta- phylococcus spp, may encode both the inducible or constitutive MLS_B phenotypes (Roberts 2004Roberts MC 2004. Update on macrolide-lincosamide-streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol Lett 282: 147-159.). In MS_B-positive S. epidermidisstrains, the msrA genes predominantly coexist withermC, mphC, and linA/A’, and the coexistence of msrA and ermC has also been previously reported (Roberts 2004Roberts MC 2004. Update on macrolide-lincosamide-streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol Lett 282: 147-159., Novotna et al. 2007Novotna G, Spižek J, Janata J 2007. In vitro activity of telithromycin and quinupristin/dalfopristin against methicillin-resistant coagulase-negative staphylococci with defined resistance genotypes.Folia Microbiol 52: 593-599., Wang et al. 2008Wang Y, Wu CM, Lu LM, Ren GWN, Cao XY, Shen JZ 2008. Macrolide-lincosamide-resistant phenotypes and genotypes ofStaphylococcus aureus isolated from bovine clinical mastitis. Vet Microbiol 130: 118-125., Teodoro et al. 2012Teodoro CRS, Mattos CS, Cavalcante FS, Pereira EM, Santos KRN 2012. Characterization of MLSb resistance among Staphylococcus aureus and Staphylococcus epidermidis isolates carrying different SCCmec types. Microbiol Immunol 56: 647-650.). Moreover, the presence of the linA/A’ gene inmsrA-positive strains results in resistance to lincomycin. TheS. epidermidis strains exhibiting L-phenotypes correlated with the presence of the linA/A’ gene in most of the strains that also contained the ermC and mphC genes, whereas those strains did not contain the msrA gene. Notably, theermC genes were also detected in both of the MS_B and L-phenotype S. epidermidis strains - but without its expression - suggesting a defect in ermC expression.

Previous studies have reported (Leclercq 2002Leclercq R 2002. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications.Clin Infect Dis 34: 482-492.,Coutinho et al. 2010Coutinho VLS, Paiva RM, Reiter KC, de-Paris F, Barth AL, Mombach AB, Machado P 2010. Distribution of erm genes and low prevalence of inducible resistance to clindamycin among staphylococci isolates. Braz J Infect Dis 14: 564-568.) that 16-membered macrolides (e.g., spiramycin) are not inducers of MLS_B resistance in staphylococci. According to our data, spiramycin is able to induce resistance to clindamycin among the iMLS_BS. epidermidis isolates examined. Moreover, iMLS_BS. epidermidis strains, which contain ermC, exhibited resistance to spiramycin in vitro. These observations contradict previous reports that 16-membered macrolides remain active against staphylococci that exhibit iMLS_B phenotypes (Leclercq 2002Leclercq R 2002. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications.Clin Infect Dis 34: 482-492., Szczuka et al. 2016Szczuka E, Makowska N, Bosacka K, Słotwińska A, Kaznowski A 2016. Molecular basis of resistance to macrolides, lincosamides, and streptogramins inStaphylococcus hominis strains isolated from clinical specimens. Folia Microbiol (Praha) 61: 143-147.). Notably, resistance to spiramycin appears to be characteristic of iMLS_B streptococci containing ermB(Leclercq 2002Leclercq R 2002. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications.Clin Infect Dis 34: 482-492., Acikgoz et al. 2003Acikgoz ZC, Gocer S, Tuncer S 2003. Macrolide resistance determinants of group A streptococci in Ankara, Turkey. J Antimicrob Chemother 52: 110-112.).

The diversity of genes involved in different mechanisms that are responsible for the resistance of S. epidermidis to MLS_B antibiotics suggests that the insensitivity of CoNS strains to these antibacterial drugs is not necessarily a unidirectional process and that the coexistence of various genes may influence the nature of their resistance.

REFERENCES

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