Comparative In Vitro Activities of Linezolid, Quinupristin-Dalfopristin, Moxifloxacin, and Trovafloxacin against Erythromycin-Susceptible and -Resistant Streptococci

Betriú, Carmen; Redondo, Montserrat; Palau, M L; Sánchez, A; Gómez, Manuel; Culebras, Esther; Boloix, Ana; Picazo, Juan J.

doi:10.1128/aac.44.7.1838-1841.2000

Cited by 53 publications

(36 citation statements)

References 27 publications

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“…The predominance among erythromycin-resistant pneumococci of the isolates carrying the erm(AM) gene over those carrying the mef(E) gene observed in this study (76.5 versus 23.5%) is consistent with the results of other recent studies from European countries (2,3,13,16,25), South Africa (11), and Japan (15). It is worth noting that in some European reports the rate of isolates carrying the mef(E) gene was particularly low (Ͻ10%) (2, 3, 13, 16).…”

Section: Discussionsupporting

confidence: 82%

“…From a genotypic point of view, in S. pyogenes MLS resistance is mediated by two classes of methylase genes, i.e., the conventional erm(AM) determinant (12), belonging to gene class erm(B) (18), and the recently described erm(TR) determinant (22), belonging to gene class erm(A) (18). In S. pneumoniae, only the former methylase gene has been extensively documented (12,24), even though the presence of erm (TR) has been recently demonstrated in particular isolates of erythromycin-resistant pneumococci (3,25). From a phenotypic point of view, erythromycin-resistant strains of S. pyogenes can be differentiated into three phenotypes (cMLS, iMLS, and M) by a simple double-disk (erythromycin plus clindamycin) test (21) or-as easily but more accurately-into five phenotypes by a triple-disk (erythromycin plus clindamycin and josamycin) test, which allows further differentiation of inducibly resistant strains into three distinct types (iMLS-A, iMLS-B, and iMLS-C) (8).…”

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confidence: 99%

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Differentiation of Resistance Phenotypes among Erythromycin-Resistant Pneumococci

et al. 2001

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Laboratory differentiation of erythromycin resistance phenotypes is poorly standardized for pneumococci. In this study, 85 clinical isolates of erythromycin-resistant (MIC > 1 g/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 g 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.Ribosomal target site modification due to methylases encoded by erm class genes is the most common and extensively investigated mechanism of erythromycin resistance in streptococci (28). It has long been known that ribosome methylation causes reduced binding of and coresistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics and that in streptococci MLS resistance can be expressed either constitutively (cMLS phenotype) or inducibly (iMLS phenotype) (9,12,27). Only recently has a macrolide efflux mechanism been described for streptococci (24), in which it is associated with a new resistance pattern (M phenotype) characterized by resistance to 14-and 15-membered macrolides and susceptibility to 16-membered macrolides, lincosamides, and s...

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Section: Discussionsupporting

confidence: 82%

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confidence: 99%

Differentiation of Resistance Phenotypes among Erythromycin-Resistant Pneumococci

et al. 2001

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“…While efflux-mediated resistance is encoded by the above-mentioned mef genes, methylase-mediated resistance is usually encoded by the conventional erm(AM) gene, which belongs to gene class erm(B) (28). Another methylase, mediated by the erm(TR) gene, belonging to gene class erm(A) (28), was first described (31) and then found to be extensively present (14,19) in S. pyogenes, whereas its presence in S. pneumoniae has been reported only occasionally (4,35). The presence of erythromycin resistance genes was investigated by PCR.…”

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Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy

et al. 2003

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Of 120 erythromycin-resistant pneumococci isolated in Italian hospitals, 39 (32.5%) were M-type isolates, carrying the mef gene alone. The mef gene was also detected, together with erm(AM), in one constitutively resistant isolate and in five isolates of the partially inducible phenotype. Among the 45 mef-positive isolates, 25 (55.6%) carried mef(A) and 20 (44.4%) carried mef(E) as observed from PCR-restriction fragment length polymorphism analysis of a 1,743-bp amplicon. The same result was obtained by a similar method applied to a more common 348-bp amplicon.Macrolide resistance in Streptococcus pneumoniae is due to either target site modification-generally depending on a posttranscriptional modification of 23S rRNA mediated by ermclass methylases (39) or less often on mutations in 23S rRNA or ribosomal proteins (7, 37, 38)-or active efflux. In this study, 120 erythromycin-resistant pneumococci were investigated for macrolide resistance phenotypes and genotypes, with emphasis on the discrimination between mef(A) and mef(E).Efflux-mediated resistance. The efflux mechanism, which reduces the intracellular antibiotic concentration to subtoxic levels (40), is associated with a resistance pattern (M phenotype) characterized by resistance, among macrolides-lincosamidesstreptogramin B (MLS), only to 14-and 15-membered macrolides, usually at a low level (34). M-type resistance is mediated by the mef gene, two variants of which are conventionally described: one, mef(A), originally discovered in Streptococcus pyogenes (5), and the other, mef(E), originally discovered in S. pneumoniae (36). Considering that the mef genes are detected mostly by a PCR method unable to distinguish between the two variants (33) and that mef(A) and mef(E) have 90% identity (36), they are regarded as a single gene class, designated mef(A) (28). However, mef(A) and mef(E) have recently been shown to be carried by different genetic elements in S. pneumoniae, which are inserted at different sites in the chromosome. Both elements carry, adjacent to mef, an open reading frame showing homology to the msr(A) gene associated with macrolide efflux in Staphylococcus aureus (6,12,29). Due to a number of important differences in the properties of mef(A)-and mef(E)-carrying pneumococci, it has been recommended that the distinction between the two genes be maintained (6).Bacterial strains and typing. The 120 erythromycin-resistant pneumococci studied (for which the MIC of erythromycin was Ն1 g/ml) were independent isolates, collected from several laboratories throughout Italy between 1999 and 2002. All were clinical strains, isolated from a variety of clinical specimens (upper respiratory tract material, sputum, blood, cerebrospinal fluid). Multiple isolates from the same patient were excluded.Strain identification was confirmed in our laboratory by conventional tests such as susceptibility to optochin and solubility in bile and by employing the API system (BioMérieux, Marcyl'Etoile, France). Serotyping, done by the capsular swelling test using specific anti...

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“…Infine, diverse ricerche hanno evidenziato l'attività antibatterica della moxifloxacina verso ceppi resistenti a penicillina, eritromicina, ciprofloxacina e vancomicina [39][40][41][42][43][44][45][46][47].…”

Section: Profilo Microbiologicounclassified

“…Numerose ricerche di microbiologia clinica, condotte in diversi paesi negli ultimi anni, hanno ulteriormente documentato, confermando i dati precedenti, che la moxifloxacina mantiene elevata attività battericida anche nei confronti della maggior parte dei ceppi di patogeni d'isolamento clinico risultati resistenti alla penicillina, all'eritromicina, alla vancomicina e alla stessa ciprofloxacina [39][40][41][42][43][44][45][46][47].…”

Section: Tabellaunclassified

Moxifloxacina: profilo farmacologico, terapeutico e farmacoeconomico

Eandi

2003

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PREMESSEMoxifloxacina è un nuovo fluorochinolone di recente introduzione nell'armamentario terapeutico per il trattamento antibiotico delle infezioni delle basse ed alte vie respiratorie [1][2][3][4][5][6][7].Moxifloxacina è un 8-metossichinolone dotato di un ampio spettro d'azione antibatterico nei confronti dei batteri Grampositivi e Gram-negativi, aerobi ed anaerobi e dei patogeni atipici quali micoplasmi, legionelle e clamidie [3, 7, 8]. Questo nuovo antibiotico è tra i farmaci più potenti attualmente disponibili nei confronti dei batteri Gram-positivi, compresi lo Staphylococcus aureus meticillino-resistente e i pneumococchi, sia sensibili che resistenti alla penicillina. La moxifloxacina è attiva quanto la ciprofloxacina verso Legionella spp., ma più attiva verso Chlamydia spp. e Mycoplasma pneumoniae. Moxifloxacina: profilo farmacologico, terapeutico e farmacoeconomicoMario Eandi * Moxifloxacina manifesta minore efficacia rispetto a ciprofloxacina verso le Enterobatteriaceae e verso Pseudomonas aeruginosa. Dotata di una potente e rapida azione battericida concentrazione-dipendente verso i batteri Gram-positivi e di un marcato effetto post-antibiotico, la moxifloxacina si accumula rapidamente nei ceppi sensibili, agisce inibendo in ugual misura sia la DNA girasi sia la topoisomerasi IV e manifesta una ridotta tendenza a selezionare ceppi mutanti resistenti [1, 7].La farmacocinetica della moxifloxacina si caratterizza per la lunga emivita, circa 12 ore, per un'elevata biodisponibilità orale, un'eccellente diffusibilità tissutale extravascolare e per la scarsità di interazioni con altri farmaci [1, 7]. Il profilo di tollerabilità, simile a quello dei fluorochinoloni, si differenzia, tuttavia, per l'assenza di fototossicità [2]. ABSTRACTMoxifloxacin is a new fluorquinolone antibiotic, recently introduced among the treatment options for upper and lower airways infections. It possesses a wide antibiotic spectrum, covering the major pathogens involved in the genesis of community acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) and acute bacterial sinusitis (ABS). It acts in a concentration-dependent manner by inhibition of bacterial DNAgirase and topoisomerase IV, has a long biological half-life (about 12 hours), good oral bioavailability, excellent tissue diffusion and a better safety profile than other quinolones, because of the lack of phototoxicity and the scarsity of clinically significant drug interactions. The clinical results of moxifloxacin in CAP, AECB and ABS have been compared with those of available alternative antibiotics in several multicentric, double-blind studies, and the new fluorquinolone resulted at least as effective as the comparators, with similar tolerability profiles. These studies demonstrated a high correlation among the eradication of the pathogen and the clinical recovery of the patients. The pharmacodynamics, pharmacokinetics and clinical results of moxifloxacin render it one of the most attractive options for the empirical treatment of upper and lower air...

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Comparative In Vitro Activities of Linezolid, Quinupristin-Dalfopristin, Moxifloxacin, and Trovafloxacin against Erythromycin-Susceptible and -Resistant Streptococci

Cited by 53 publications

References 27 publications

Differentiation of Resistance Phenotypes among Erythromycin-Resistant Pneumococci

Differentiation of Resistance Phenotypes among Erythromycin-Resistant Pneumococci

Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy

Moxifloxacina: profilo farmacologico, terapeutico e farmacoeconomico

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