Macrolide, Lincosamide, and Streptogramin B Resistance in Lipophilic Corynebacteria Inhabiting Healthy Human Skin

Szemraj, Magdalena; Kwaszewska, Anna; Pawlak, Renata; Szewczyk, Eligia M.

doi:10.1089/mdr.2013.0192

Cited by 17 publications

(15 citation statements)

References 30 publications

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“…The constitutive MLS B resistance mechanism was also demonstrated in 13 resistant strains isolated from healthy human skin (72%). These strains were harboring only the erm(X) gene what has confirmed our previous observations (Szemraj et al, 2014). It draws the attention that we detected for the first time a large number of clinical isolates of Corynebac te rium spp.…”

supporting

confidence: 91%

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New Gene Responsible for Resistance of Clinical Corynebacteria to Macrolide, Lincosamide and Streptogramin B

Szemraj

Kwaszewska

Szewczyk

2018

Polish Journal of Microbiology

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The subject of the study was phenotypic marking of the antibiotic susceptibility and MLSB resistance mechanism in Corynebacterium spp. isolated from human skin (18 isolates) and from clinical materials (19 isolates). The strains were tested for the presence of the erm(A), erm(B), erm(C), erm(X), lnu(A), msr(A), msr(B) and mph(C) genes. Clinical isolates showed wide resistance to antibiotics. In 89% clinical isolates and 72% skin microbiota a constitutive type of MLSB resistance was found. In 12 clinical isolates the erm(C) gene was detected-eight of which had erm(X) as well as erm(C), two harboured erm(X), erm(C) and erm(A) and two demonstrated only erm(C).

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supporting

confidence: 91%

“…is noticeable especially in clinical multidrug-resistant isolates (Otsuka et al, 2006;Ortiz-Perez et al, 2010). Nevertheless, in a manuscript published in Microbial Drug Resistance in 2014 (Szemraj et al, 2014), we have shown that this resistance may also occur in the skin microbiota e.g. C. tuberculostearicum or C. jeikeium.…”

mentioning

confidence: 83%

New Gene Responsible for Resistance of Clinical Corynebacteria to Macrolide, Lincosamide and Streptogramin B

Szemraj

Kwaszewska

Szewczyk

2018

Polish Journal of Microbiology

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“…As found in this study, strains of C. tuberculostearicum are often multiresistant, demonstrating the macrolide-lincosamidestreptogramin B (MLSB) mechanism conferred by the ermX gene (23,24). While data are limited, antimicrobial susceptibility by nonstandardized disk diffusion has been performed on isolates of C. kroppenstedtii, reporting broad susceptibility to most classes of antimicrobials (9,11).…”

Section: Discussionmentioning

confidence: 62%

“…This inflammatory reaction can be rapid; in our series, the development of granulomata was seen as early as a week from the start of clinical symptoms. In this environment, adequate tissue concentrations for bactericidal activity may be achieved by agents that are highly lipophilic and have a high volume of distribution, which include rifampin, clarithromycin, trimethoprim-sulfamethoxazole, and clindamycin (24,25). In contrast, ␤-lactams and fluoroquinolones have low lipid solubility and therefore are expected to be less effective.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Treatment Options for Granulomatous Mastitis Caused by Corynebacterium Species

et al. 2015

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cCorynebacterium species are increasingly recognized as important pathogens in granulomatous mastitis. Currently, there are no published treatment protocols for Corynebacterium breast infections. This study describes antimicrobial treatment options in the context of other management strategies used for granulomatous mastitis. Corynebacterium spp. isolated from breast tissue and aspirate samples stored from 2002 to 2013 were identified and determined to the species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), 16S RNA sequencing, and rpoB gene targets. The MICs for 12 antimicrobials were performed using Etest for each isolate. Correlations of these with antimicrobial characteristics, choice of antimicrobial, and disease outcome were evaluated. Corynebacterium spp. from breast tissue and aspirate samples were confirmed in 17 isolates from 16 patients. Based on EUCAST breakpoints, Corynebacterium kroppenstedtii isolates (n ‫؍‬ 11) were susceptible to seven antibiotic classes but resistant to ␤-lactam antibiotics. Corynebacterium tuberculostearicum isolates (n ‫؍‬ 4) were multidrug resistant. Two nonlipophilic species were isolated, Corynebacterium glucuronolyticum and Corynebacterium freneyi, both of which have various susceptibilities to antimicrobial agents. Short-course antimicrobial therapy was common (median, 6 courses per subject; range, 1 to 9 courses). Patients with C. kroppenstedtii presented with a hot painful breast mass and underwent multiple surgical procedures (median, 4 procedures; range, 2 to 6 procedures). The management of Corynebacterium breast infections requires a multidisciplinary approach and includes culture and appropriate sensitivity testing to guide antimicrobial therapy. Established infections have a poor outcome, possibly because adequate concentrations of some drugs will be difficult to achieve in lipophilic granulomata. Lipophilic antimicrobial therapy may offer a therapeutic advantage. The role of immunotherapy has not been defined. Granulomatous mastitis (GM) is a rare inflammatory condition that typically occurs in parous women of reproductive age (1). Clinically, it can present as a breast mass with features similar to those of breast malignancy (2). Multiple infective and inflammatory conditions, including tuberculosis (TB), fungal infections, sarcoidosis, amyloidosis, and Wegener's granulomatosis, have been recognized, but recently, attention has been drawn to corynebacterial species as a specific pathogen in this disease. Typically, corynebacterial breast infections are characterized by abscess formation, granulomatous inflammation, and progression to sinus/fistula formation (3). This and other specific diagnoses should be excluded before a diagnosis of idiopathic granulomatous mastitis (IGM) is made (3-5).Commonly, it is the lipophilic species of the Corynebacterium genus that cause mastitis (3, 6-8). As such, a microbiological diagnosis can be challenging, due to their fastidious growth requirements and prolonged incu...

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“…mph(C) has also been identified in corynebacteria from healthy human skin (Szemraj et al 2014) and, interestingly, in Stenotrophomonas maltophilia .…”

Section: Phosphotransferasesmentioning

confidence: 96%

Resistance to Macrolide Antibiotics in Public Health Pathogens

Fyfe

Grossman

Kerstein

et al. 2016

Cold Spring Harb Perspect Med

149

127

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Macrolide resistance mechanisms can be target-based with a change in a 23S ribosomal RNA (rRNA) residue or a mutation in ribosomal protein L4 or L22 affecting the ribosome's interaction with the antibiotic. Alternatively, mono-or dimethylation of A2058 in domain V of the 23S rRNA by an acquired rRNA methyltransferase, the product of an erm (erythromycin ribosome methylation) gene, can interfere with antibiotic binding. Acquired genes encoding efflux pumps, most predominantly mef(A) þ msr(D) in pneumococci/streptococci and msr(A/B) in staphylococci, also mediate resistance. Drug-inactivating mechanisms include phosphorylation of the 2 0 -hydroxyl of the amino sugar found at position C5 by phosphotransferases and hydrolysis of the macrocyclic lactone by esterases. These acquired genes are regulated by either translation or transcription attenuation, largely because cells are less fit when these genes, especially the rRNA methyltransferases, are highly induced or constitutively expressed. The induction of gene expression is cleverly tied to the mechanism of action of macrolides, relying on antibiotic-bound ribosomes stalled at specific sequences of nascent polypeptides to promote transcription or translation of downstream sequences. Macrolide antibiotics are polyketides composed of a 14-, 15-, or 16-membered macrocyclic lactone ring (14-, 15-, and 16-membered) to which several sugars and/or side chains have been attached by the producing organism or as modifications during semisynthesis in the laboratory (Figs. 1 and 2). Newer semisynthetic derivations, like ketolides telithromycin, and solithromycin, have a C3-keto group in place of the C3 cladinose (akin to naturally occurring pikromycin) (Brockmann and Henkel 1950) and an 11,12-cyclic carbamate with an extended alkyl -aryl side chain that increases the affinity of the antibiotic for the ribosome by 10-to 100-fold (Hansen et al. 1999;Dunkle et al. 2010); in the case of solithromycin, a fluorine substituent at C2 provides an additional ribosomal interaction (Llano-Sotelo et al. 2010). Macrolides continue to be important in the therapeutic treatment of community-acquired pneumonia (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and atypicals Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae), sexually transmitted diseases (Neiserria gonorhoeae, Chlamydia trachomatis, Mycoplasma genitalium), shigellosis, and salmonellosis. With solithromycin heading for a new drug application (NDA) filing in 2016 and having the in vitro potency to treat erythromycin-resistant

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Macrolide, Lincosamide, and Streptogramin B Resistance in Lipophilic Corynebacteria Inhabiting Healthy Human Skin

Cited by 17 publications

References 30 publications

New Gene Responsible for Resistance of Clinical Corynebacteria to Macrolide, Lincosamide and Streptogramin B

New Gene Responsible for Resistance of Clinical Corynebacteria to Macrolide, Lincosamide and Streptogramin B

Antimicrobial Treatment Options for Granulomatous Mastitis Caused by Corynebacterium Species

Resistance to Macrolide Antibiotics in Public Health Pathogens

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