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Characterization of streptococcus pyogenes associated with tonsillo-pharyngitis in Portugal with particular emphasis on macrolide resistance

Costa, Ana Catarina da Silva e, 1976-
Fonte: Universidade de Lisboa Publicador: Universidade de Lisboa
Tipo: Tese de Doutorado
Publicado em //2014 Português
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Tese de doutoramento, Ciências e Tecnologias da Saúde (Microbiologia), Universidade de Lisboa, Faculdade de Medicina, 2014; There are large geographical and temporal variations in the frequency of macrolide-resistant Streptococcus pyogenes, as well in the associated resistance phenotypes. Although decreases in macrolide resistance were often associated with low macrolide consumption, natural fluctuations of macrolide resistant clones were also suggested to play an important role in the prevalence of resistant isolates and of resistance phenotypes. The recent report of heterogeneity found among group A streptococcus (GAS) isolates recovered from the same patient raised the question of whether the strategy used in the microbiology laboratory, the study of microorganisms from a single colony, was leading to the underestimation of macrolide resistance rate. For that purpose, 321 GAS isolates, recovered from 35 pharyngitis patients from one hospital were screened for potential differences in antimicrobial resistance profiles and emm types of up to 10 isolates recovered from the same sample. In our collection, all the isolates recovered from the same patient presented an identical antimicrobial resistance profile and emm type, indicating that the single colony approach was suitable for a correct identification of macrolide resistance rates and other epidemiological studies. In this thesis...

Prevalence of phenotypic resistance of Staphylococcus aureus isolates to macrolide, lincosamide, streptogramin B, ketolid and linezolid antibiotics in Turkey

Adaleti,Riza; Nakipoglu,Yasar; Ceran,Nurgul; Tasdemir,Cihan; Kaya,Fatma; Tasdemir,Semiha
Fonte: Brazilian Society of Infectious Diseases Publicador: Brazilian Society of Infectious Diseases
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2010 Português
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The incidence of drug-resistant pathogens differs greatly between countries according to differences in the usage of antibiotics. The purpose of this study was to investigate the phenotypic resistance of 321 methicillin resistance Staphylococcus aureus (MRSA) and 195 methicillin susceptible S. aureus (MSSA) in a total of 516 S. aureus strains to macrolide, lincosamide, streptogramin B (MLS B), ketolid, and linezolid. Disk diffusion method was applied to determine MLS B phenotype and susceptibility to different antibiotic agents. It was found that 54.6% of the isolates were resistant to erythromycin (ERSA), 48% to clindamycin, 55% to azithromycin, 58.7% to spiramycin, 34.7% to telithromycin, and 0.4% to quinupristin-dalfopristin, respectively. No strain resistant to linezolid was found. The prevalence of constitutive (cMLS B), inducible (IMLS B), and macrolides and type B streptogramins (M/MS B) among ERSA isolates (237 MRSA, 45 MSSA) was 69.6 %, 18.2%, and 12.2 % in MRSA and 28.9%, 40%, and 31.1% in MSSA, respectively. In conclusions, the prevalence of cMLS B was predominant in MRSA; while in MSSA strains, iMLS B and M/MS B phenotype were more higher than cMLS B phenotype resistance. The resistance to quinupristindalfopristin was very low...

Characteristics of hospitalized children infected with macrolide-resistant Mycoplasma pneumoniae

Komatsu,Haruki; Tsunoda,Tomoyuki; Inui,Ayano; Sogo,Tsuyoshi; Fujisawa,Tomoo
Fonte: Brazilian Society of Infectious Diseases Publicador: Brazilian Society of Infectious Diseases
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2014 Português
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BACKGROUND: The aim of this study was to clarify retrospectively the characteristics of children hospitalized for respiratory tract infection caused by macrolide-resistant Mycoplasma pneumoniae (M. pneumoniae). METHODS: Children who were hospitalized for respiratory tract infection due to M. pneumoniae were enrolled in this study. The diagnosis of M. pneumoniae infection was made on the grounds of polymerase chain reaction results. RESULTS: Thirty-three children were hospitalized due to lower respiratory tract infection with M. pneumoniae. Of the 33 children, 31 (median age five years) were identified as being infected with macrolide-resistant M. pneumoniae (A2063G:30, A2064G:1) by sequence analysis. Of the 31 children infected with macrolide-resistant M. pneumoniae, 21 (68%) had received 14- or 15-membered macrolide antibiotics and four (13%) had received minocycline before hospitalization. During hospitalization, minocycline was administered to 16 (52%) of the 31 children infected with macrolide-resistant M. pneumoniae. Of the 20 children infected with macrolide-resistant M. pneumoniae under eight years of age, six (30%) were treated with minocycline during hospitalization. The difference in total febrile days between children receiving minocycline treatment before hospitalization and children not receiving minocycline treatment was three days. CONCLUSIONS: The majority of hospitalized children with respiratory tract infection due to macrolide-resistant M. pneumoniae infection was of preschool age and had received 14- or 15-membered macrolide antibiotics before hospitalization. Because macrolide-resistant M. pneumoniae is widespread in Japan...

Binding Site of Macrolide Antibiotics on the Ribosome: New Resistance Mutation Identifies a Specific Interaction of Ketolides with rRNA

Garza-Ramos, Georgina; Xiong, Liqun; Zhong, Ping; Mankin, Alexander
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/2001 Português
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Macrolides represent a clinically important class of antibiotics that block protein synthesis by interacting with the large ribosomal subunit. The macrolide binding site is composed primarily of rRNA. However, the mode of interaction of macrolides with rRNA and the exact location of the drug binding site have yet to be described. A new class of macrolide antibiotics, known as ketolides, show improved activity against organisms that have developed resistance to previously used macrolides. The biochemical reasons for increased potency of ketolides remain unknown. Here we describe the first mutation that confers resistance to ketolide antibiotics while leaving cells sensitive to other types of macrolides. A transition of U to C at position 2609 of 23S rRNA rendered E. coli cells resistant to two different types of ketolides, telithromycin and ABT-773, but increased slightly the sensitivity to erythromycin, azithromycin, and a cladinose-containing derivative of telithromycin. Ribosomes isolated from the mutant cells had reduced affinity for ketolides, while their affinity for erythromycin was not diminished. Possible direct interaction of ketolides with position 2609 in 23S rRNA was further confirmed by RNA footprinting. The newly isolated ketolide-resistance mutation...

Comparison of In Vitro Activities of ABT-773 and Telithromycin against Macrolide-Susceptible and -Resistant Streptococci and Staphylococci

Shortridge, Virginia D.; Zhong, Ping; Cao, Zhensheng; Beyer, Jill M.; Almer, Laurel S.; Ramer, Nancy C.; Doktor, Stella Z.; Flamm, Robert K.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2002 Português
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The activity of a new ketolide, ABT-773, was compared to the activity of the ketolide telithromycin (HMR-3647) against over 600 gram-positive clinical isolates, including 356 Streptococcus pneumoniae, 167 Staphylococcus aureus, and 136 Streptococcus pyogenes isolates. Macrolide-susceptible isolates as well as macrolide-resistant isolates with ribosomal methylase (Erm), macrolide efflux (Mef), and ribosomal mutations were tested using the NCCLS reference broth microdilution method. Both compounds were extremely active against macrolide-susceptible isolates, with the minimum inhibitory concentrations at which 90% of the isolates tested were inhibited (MIC90s) for susceptible streptococci and staphylococci ranging from 0.002 to 0.03 μg/ml for ABT-773 and 0.008 to 0.06 μg/ml for telithromycin. ABT-773 had increased activities against macrolide-resistant S. pneumoniae (Erm MIC90, 0.015 μg/ml; Mef MIC90, 0.12 μg/ml) compared to those of telithromycin (Erm MIC90, 0.12 μg/ml; Mef MIC90, 1 μg/ml). Both compounds were active against strains with rRNA or ribosomal protein mutations (MIC90, 0.12 μg/ml). ABT-773 was also more active against macrolide-resistant S. pyogenes (ABT-773 Erm MIC90, 0.5 μg/ml; ABT-773 Mef MIC90, 0.12 μg/ml; telithromycin Erm MIC90...

Effects of an Efflux Mechanism and Ribosomal Mutations on Macrolide Susceptibility of Haemophilus influenzae Clinical Isolates

Peric, Mihaela; Bozdogan, Bülent; Jacobs, Michael R.; Appelbaum, Peter C.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2003 Português
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This study investigated macrolide resistance mechanisms in clinical Haemophilus influenzae strains with different levels of susceptibility to macrolides. A total of 6,382 isolates were collected during the Alexander Project from 1997 to 2000. For 96.9% of these isolates, the azithromycin MICs were 0.25 to 4 μg/ml, and these were defined as baseline strains. For 1.8% of the isolates, the azithromycin MICs were lower (<0.25 μg/ml), and for 1.3% of the isolates, the MICs were higher (>4 μg/ml). These isolates were defined as hypersusceptible and high-level macrolide-resistant strains, respectively. To identify the mechanisms associated with these three susceptibility patterns, representative strains were studied for the presence of macrolide efflux pumps and for ribosomal alterations. Macrolide efflux was studied by measuring the accumulation of radioactive azithromycin and clarithromycin in the presence or absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), a protonophore. Treatment with CCCP increased the accumulation of macrolides in baseline as well as high-level resistant strains, demonstrating the presence of an efflux mechanism, but not in the 20 hypersusceptible strains tested. Among the 31 strains studied that showed high-level resistance to both azithromycin and clarithromycin...

Macrolide-lincosamide-streptogramin resistance patterns in Clostridium perfringens from animals.

Dutta, G N; Devriese, L A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1981 Português
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Different patterns of resistance against commonly used macrolide, lincosamide, and streptogramin antibiotics were found in Clostridium perfringens of animal origin. The patterns were designated as (i) macrolide-lincosamide-streptogramin group B generalized resistance, (ii) macrolide-lincosamide generalized resistance, (iii) macrolide-lincosamide inducible resistance, and (iv) macrolide-lincosamide-streptogramin low-level generalized resistance. The strains of the fourth pattern were able to inactivate pristinamycin and virginiamycin. The macrolide-susceptible strains showed a bimodal distribution of lincomycin and clindamycin susceptibility levels. The susceptible strains were inhibited by 0.25 micrograms of lincomycin per ml and 0.03 micrograms of clindamycin per ml. The low-level resistant strains were inhibited at concentrations of 2 to 4 micrograms of lincomycin per ml and 0.5 to 2 micrograms of clindamycin per ml.

Potentiation of antiviral activity of acyclovir by polyene macrolide antibiotics.

Malewicz, B; Momsen, M; Jenkin, H M; Borowski, E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1984 Português
Relevância na Pesquisa
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The potentiation of the antiviral activity of acyclovir [9-[(2-hydroxyethoxy)methyl]guanine] by polyene macrolide antibiotics has been studied as a function of the macrolide structure. The 12 polyenes chosen for this study represented the major structural groups of these antibiotics and induced in mammalian cells repairable membrane alterations or irreversible cell damage. The potentiating activity of the polyene macrolides was determined based on the differential decrease of in vitro production of infectious virions in the presence of acyclovir alone or in combination with the polyene. Pseudorabies virus, a representative herpesvirus susceptible to acyclovir, was replicated in BHK-21 cells grown in serum-free medium to avoid the interference of serum factors in the polyene macrolide-cell interaction. The potentiation activity of the polyene antibiotics was concentration dependent. The enhancement of the antiviral activity of acyclovir was observed at polyene concentrations which had no direct effect on pseudorabies virus replication in BHK-21 cells. The optimal potentiating concentrations of polyenes were 2 to 15 times lower than that inducing 50% of potassium efflux from BHK-21 cells. The highest potentiating activity was observed for the methyl ester of the trimethylammonium derivative of aureofacin B...

Intrinsic Macrolide Resistance in Mycobacterium smegmatis Is Conferred by a Novel erm Gene, erm(38)

Nash, Kevin A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /10/2003 Português
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High-level, acquired macrolide resistance in mycobacteria is conferred by mutation within the 23S rRNA gene. However, several mycobacteria are naturally resistant to macrolides, including the Mycobacterium smegmatis group and Mycobacterium tuberculosis complex. Thus, the aim of this study was to characterize this resistance. Intrinsic macrolide resistance in M. smegmatis was inducible and showed cross-resistance to lincosamides but not to streptogramin B (i.e., ML resistance). A similar phenotype was found with Mycobacterium microti and macrolide-resistant Mycobacterium fortuitum. A search of the DNA sequence data for M. smegmatis strain mc2155 identified a novel erm gene, erm(38), and expression analysis showed that erm(38) RNA levels increased >10-fold after a 2-h incubation with macrolide. Inducible ML resistance was not expressed by an erm(38) knockout mutant, and complementation of this mutant with intact erm(38) in trans resulted in high-level ML resistance (e.g., clarithromycin MIC of >512 μg/ml). Thus, the results indicate that erm(38) confers the intrinsic ML resistance of M. smegmatis. Southern blot analysis with an erm(38)-specific probe indicated that a similar gene may be present in macrolide-resistant M. fortuitum. This finding...

Pharmacodynamic Activity of Telithromycin at Simulated Clinically Achievable Free-Drug Concentrations in Serum and Epithelial Lining Fluid against Efflux (mefE)-Producing Macrolide- Resistant Streptococcus pneumoniae for Which Telithromycin MICs Vary

Zhanel, George G.; Johanson, Christel; Laing, Nancy; Hisanaga, Tamiko; Wierzbowski, Aleksandra; Hoban, Daryl J.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /05/2005 Português
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The present study, using an in vitro model, assessed telithromycin pharmacodynamic activity at simulated clinically achievable free-drug concentrations in serum (S) and epithelial lining fluid (ELF) against efflux (mefE)-producing macrolide-resistant Streptococcus pneumoniae. Two macrolide-susceptible (PCR negative for both mefE and ermB) and 11 efflux-producing macrolide-resistant [PCR-positive for mefE and negative for ermB) S. pneumoniae strains with various telithromycin MICs (0.015 to 1 μg/ml) were tested. The steady-state pharmacokinetics of telithromycin were modeled, simulating a dosage of 800 mg orally once daily administered at time 0 and at 24 h (free-drug maximum concentration [Cmax] in serum, 0.7 μg/ml; half-life [t1/2], 10 h; free-drug Cmax in ELF, 6.0 μg/ml; t1/2, 10 h). Starting inocula were 106 CFU/ml in Mueller-Hinton Broth with 2% lysed horse blood. Sampling at 0, 2, 4, 6, 12, 24, and 48 h assessed the extent of bacterial killing (decrease in log10 CFU/ml versus initial inoculum). Free-telithromycin concentrations in serum achieved in the model were Cmax 0.9 ± 0.08 μg/ml, area under the curve to MIC (AUC0-24 h) 6.4 ± 1.5 μg · h/ml, and t1/2 of 10.6 ± 0.6 h. Telithromycin-free ELF concentrations achieved in the model were Cmax 6.6 ± 0.8 μg/ml...

Molecular Epidemiology of Macrolide-Resistant Isolates of Streptococcus pneumoniae Collected from Blood and Respiratory Specimens in Norway

Littauer, P.; Sangvik, M.; Caugant, D. A.; Høiby, E. A.; Simonsen, G. S.; Sundsfjord, A.;
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /05/2005 Português
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Norway has a low prevalence of antimicrobial resistance, including macrolide-resistant Streptococcus pneumoniae (MRSP). In a nationwide surveillance program, a total of 2,200 S. pneumoniae isolates were collected from blood cultures and respiratory tract specimens. Macrolide resistance was detected in 2.7%. M-type macrolide resistance was found in 60% of resistant isolates, and these were mainly mef(A)-positive, serotype-14 invasive isolates. The erm(B)-encoded macrolide-lincosamide-streptogramin B (MLSB) type dominated among the noninvasive isolates. One strain had an A2058G mutation in the 23S rRNA gene. Coresistance to other antibiotics was seen in 96% of the MLSB-type isolates, whereas 92% of the M-type isolates were susceptible to other commonly used antimicrobial agents. Serotypes 14, 6B, and 19F accounted for 84% of the macrolide-resistant isolates, with serotype 14 alone accounting for 67% of the invasive isolates. A total of 29 different sequence types (STs) were detected by multilocus sequence typing. Twelve STs were previously reported international resistant clones, and 75% of the macrolide-resistant isolates had STs identical or closely related to these clones. Eleven isolates displayed 10 novel STs, and 7/11 of these “Norwegian strains” coexpressed MLSB and tetracycline resistance...

Macrolide Resistance in Campylobacter jejuni and Campylobacter coli: Molecular Mechanism and Stability of the Resistance Phenotype

Gibreel, Amera; Kos, Veronica N.; Keelan, Monika; Trieber, Cathy A.; Levesque, Simon; Michaud, Sophie; Taylor, Diane E.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /07/2005 Português
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A collection of 23 macrolide-resistant Campylobacter isolates from different geographic areas was investigated to determine the mechanism and stability of macrolide resistance. The isolates were identified as Campylobacter jejuni or Campylobacter coli based on the results of the hippurate biochemical test in addition to five PCR-based genotypic methods. Three point mutations at two positions within the peptidyl transferase region in domain V of the 23S rRNA gene were identified. About 78% of the resistant isolates exhibited an A→G transition at Escherichia coli equivalent base 2059 of the 23S rRNA gene. The isolates possessing this mutation showed a wide range of erythromycin and clarithromycin MICs. Thus, this mutation may incur a greater probability of treatment failure in populations infected by resistant Campylobacter isolates. Another macrolide-associated mutation (A→C transversion), at E. coli equivalent base 2058, was detected in about 13% of the isolates. An A→G transition at a position cognate with E. coli 23S rRNA base 2058, which is homologous to the A2142G mutation commonly described in Helicobacter pylori, was also identified in one of the C. jejuni isolates examined. In the majority of C. jejuni isolates, the mutations in the 23S rRNA gene were homozygous except in two cases where the mutation was found in two of the three copies of the target gene. Natural transformation demonstrated the transfer of the macrolide resistance phenotype from a resistant Campylobacter isolate to a susceptible Campylobacter isolate. Growth rates of the resulting transformants containing A-2058→C or A-2059→G mutations were similar to that of the parental isolate. The erythromycin resistance of six of seven representative isolates was found to be stable after successive subculturing in the absence of erythromycin selection pressure regardless of the resistance level...

Expression of the mef(E) Gene Encoding the Macrolide Efflux Pump Protein Increases in Streptococcus pneumoniae with Increasing Resistance to Macrolides

Wierzbowski, Aleksandra K.; Boyd, Dave; Mulvey, Michael; Hoban, Daryl J.; Zhanel, George G.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /11/2005 Português
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Active macrolide efflux is a major mechanism of macrolide resistance in Streptococcus pneumoniae in many parts of the world, especially North America. In Canada, this active macrolide efflux in S. pneumoniae is predominantly due to acquisition of the mef(E) gene. In the present study, we assessed the mef(E) gene sequence as well as mef(E) expression in variety of low- and high-level macrolide-resistant, clindamycin-susceptible (M-phenotype) S. pneumoniae isolates (erythromycin MICs, 1 to 32 μg/ml; clindamycin MICs, ≤0.25 μg/ml). Southern blot hybridization with mef(E) probe and EcoRI digestion and relative real-time reverse transcription-PCR were performed to study the mef(E) gene copy number and expression. Induction of mef(E) expression was analyzed by Etest susceptibility testing pre- and postincubation with subinhibitory concentrations of erythromycin, clarithromycin, azithromycin, telithromycin, and clindamycin. The macrolide efflux gene, mef(E), was shown to be a single-copy gene in all 23 clinical S. pneumoniae isolates tested, and expression post-macrolide induction increased 4-, 6-, 20-, and 200-fold in isolates with increasing macrolide resistance (erythromycin MICs 2, 4, 8, and 32 μg/ml, respectively). Sequencing analysis of the macrolide efflux genetic assembly (mega) revealed that mef(E) had a 16-bp deletion 153 bp upstream of the putative start codon in all 23 isolates. A 119-bp intergenic region between mef(E) and mel was sequenced...

Macrolide and Azithromycin Use Are Linked to Increased Macrolide Resistance in Streptococcus pneumoniae▿

Bergman, Miika; Huikko, Solja; Huovinen, Pentti; Paakkari, Pirkko; Seppälä, Helena;
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Português
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The connection between regional rates of antimicrobial resistance in Streptococcus pneumoniae and regional antimicrobial use in Finland was investigated. During the 6-year study period of 1997 to 2002, a total of 31,609 S. pneumoniae isolates were tested for penicillin resistance and a total of 23,769 isolates were tested for macrolide resistance in 18 central hospital districts in Finland. The regional macrolide resistance rates were compared with the local use of (i) all macrolides pooled and (ii) azithromycin. The penicillin resistance levels were compared with the consumption data for (i) penicillins, (ii) cephalosporins, (iii) all beta-lactams pooled, and (iv) all macrolides pooled. A statistically significant association between macrolide resistance and total use of macrolides and the use of azithromycin was found. Moreover, total use of beta-lactams and total use of cephalosporins were significantly connected to low-level penicillin resistance. A statistically significant association between penicillin-nonsusceptible isolates and penicillin or total macrolide consumption was not found. In conclusion, total macrolide use and azithromycin use are associated with increased macrolide resistance, and beta-lactam use and cephalosporin use are connected to increased low-level penicillin resistance in S. pneumoniae. Unnecessary prescribing of macrolides and cephalosporins should be avoided.

Serotype and Genotype Replacement among Macrolide-Resistant Invasive Pneumococci in Adults: Mechanisms of Resistance and Association with Different Transposons▿

Calatayud, Laura; Ardanuy, Carmen; Tubau, Fe; Rolo, Dora; Grau, Immaculada; Pallarés, Román; Martín, Rogelio; Liñares, Josefina
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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The aim of this study was to analyze trends in adult invasive pneumococcal disease (IPD) due to macrolide-resistant strains and to study the evolution of serotypes, genotypes, and macrolide-resistant determinants of strains collected in a prospective study between 1999 and 2007 in Barcelona, Spain. IPD due to macrolide-resistant strains of serotypes included in the 7-valent conjugate vaccine (PCV7) decreased from 2.16/100,000 (pre-PCV7 period, 1999 to 2001) to 0.80/100,000 (late-PCV7 period, 2005 to 2007) (P = 0.001), whereas IPD due to macrolide-resistant strains of non-PCV7 serotypes increased from 1.08/100,000 to 2.83/100,000 (P < 0.001). These changes were related to a fall of clones of PCV7 serotypes (ST81 [P < 0.05], ST90, ST315, and ST17) and an increase in new clones of serotypes 19A and 24F (ST230) and 33F (ST717) in the late-PCV7 period. The most common phenotype was MLSB (90.9%), related to the erm(B) gene. The frequent association between MLSB phenotype and tetracycline resistance [tet(M) gene], was related to transposons of the Tn916-family such as Tn6002 or Tn3872. In conclusion, overall adult IPD rates due to macrolide-resistant pneumococci stabilized between 1999 and 2007 in Barcelona. The decrease in macrolide-resistant PCV7 pneumococci was balanced by the increase in macrolide-resistant non-PCV7 pneumococci.

Differences between Macrolide-Resistant and -Susceptible Streptococcus pyogenes: Importance of Clonal Properties in Addition to Antibiotic Consumption

Silva-Costa, C.; Friães, A.; Ramirez, M.; Melo-Cristino, J.;
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /11/2012 Português
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A steady decline in macrolide resistance among Streptococcus pyogenes (group A streptococci [GAS]) in Portugal was reported during 1999 to 2006. This was accompanied by alterations in the prevalence of macrolide resistance phenotypes and in the clonal composition of the population. In order to test whether changes in the macrolide-resistant population reflected the same changing patterns of the overall population, we characterized both macrolide-susceptible and -resistant GAS associated with a diagnosis of tonsillo-pharyngitis recovered in the period from 2000 to 2005 in Portugal. Pulsed-field gel electrophoresis (PFGE) profiling was the best predictor of emm type and the only typing method that could discriminate clones associated with macrolide resistance and susceptibility within each emm type. Six PFGE clusters were significantly associated with macrolide susceptibility: T3-emm3-ST406, T4-emm4-ST39, T1-emm1-ST28, T6-emm6-ST382, B3264-emm89-ST101/ST408, and T2-emm2-ST55. Four PFGE clusters were associated with macrolide resistance: T4-emm4-ST39, T28-emm28-ST52, T12-emm22-ST46, and T1-emm1-ST28. We found no evidence for frequent ongoing horizontal transfer of macrolide resistance determinants. The diversity of the macrolide-resistant population was lower than that of susceptible isolates. The differences found between the two populations suggest that the macrolide-resistant population of GAS has its own dynamics...

Decline in macrolide resistance rates among Streptococcus pyogenes causing pharyngitis in children isolated in Italy

Gherardi, G.; Petrelli, D.; Di Luca, M. C.; Pimentel de Araujo, F.; Bernaschi, P.; Repetto, A.; Bellesi, J.; Vitali, L. A.
Fonte: Springer Berlin Heidelberg Publicador: Springer Berlin Heidelberg
Tipo: Artigo de Revista Científica
Português
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Macrolides are often used to treat group A streptococcus (GAS) infections, but their resistance rates reached high proportions worldwide. The aim of the present study was to give an update on the characteristics and contemporary prevalence of macrolide-resistant pharyngeal GAS in Central Italy. A total of 592 isolates causing pharyngitis in children were collected in the period 2012–2013. Clonality was assessed by emm typing and pulsed-field gel electrophoresis (PFGE) for all macrolide-resistant strains and for selected susceptible isolates. Genetic determinants of resistance were screened by polymerase chain reaction (PCR). Forty-four GAS were erythromycin-resistant (7.4 %). Among them, 52.3 % and 50 % were clindamycin- and tetracycline-resistant, respectively. erm(B)-positive isolates (52.3 %) expressed the constitutive cMLSB phenotype. mef(A) and its associated M phenotype were recorded in 40.9 % of the cases. The remaining erm(A)-positive isolates expressed the iMLSB phenotype. Seventeen tetracycline-resistant isolates carried tet(M) and five isolates carried tet(O). Twenty-five emm types were found among all strains, with the predominance of emm types 12, 89, 1, and 4. Eleven emm types and 12 PFGE clusters characterized macrolide-resistant strains...

Total Synthesis of the Proposed Structure of the Macrolide Queenslandonand Towards the Total Synthesis of Natural Products Leiodermatolide and (–)-Englerin A; Totalsynthese der Vorgeschlagenen Struktur des Makrolids QueenslandonundStudien zur Totalsynthese der Naturstoffe Leiodermatolid und (–)-Englerin A

Navickas, Vaidotas
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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The dissertation consists of three parts. The first part deals with the total synthesis of macrolide queenslandon. Key steps in the synthesis were a cross metathesis reaction to construct the aliphatic fragment and a Mitsunobu macrolactonization to give a macrolactone. All chiral centers were established from D-(+)-ribose. The proposed structure of the macrolide queenslandon has been reached and it was proved that the postulated structure was proposed incorrectly. The second part describes a study on the total synthesis of marine natural product leiodermatolide. This macrolide is highly cytotoxic against various cancer cell lines. Biological studies on this molecule, however, were difficult because of the small amount material available so far. Based on a retrosynthetic analysis the molecule was split into two fragments. The key step in the synthesis of the first fragment is a Marshall-Tamaru anti-selective addition of an allenylzinc species to a chiral aldehyde to construct the stereotetrad. The Marshall-Tamaru reaction has been used effectively for a second fragment also. Further Sonogashira coupling was used to couple the two building blocks. Unfortunately, the key step - the ring-closing metathesis reaction to was not effective. The third part on the thesis describes a study on the total synthesis of the terpene (-)-englerin A. The molecule proved to be highly selective and potent against various cell types involved in renal cancer. In the study...

Reemergence of Macrolide Resistance in Pharyngeal Isolates of Group A Streptococci in Southwestern Pennsylvania

Green, Michael; Martin, Judith M.; Barbadora, Karen A.; Beall, Bernard; Wald, Ellen R.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2004 Português
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We previously reported on the emergence of macrolide-resistant pharyngeal isolates of group A streptococci (GAS) in our community. The purpose of the present study was to track longitudinal trends in macrolide resistance in these isolates in southwestern Pennsylvania. Testing for susceptibility to erythromycin and clindamycin was performed for all pharyngeal GAS isolates recovered at the Children's Hospital of Pittsburgh and a local pediatric practice between September 2001 and May 2002. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion and PCR, respectively. Strain relatedness was determined by field inversion gel electrophoresis and emm gene sequence typing. A total of 708 isolates of GAS were recovered during the study period; 68 (9.6%) were macrolide resistant, while all isolates were sensitive to clindamycin. The monthly prevalence of macrolide resistance ranged from 0 to 41%. Only 21 of 573 (3.7%) strains recovered from September 2001 through March 2002 were macrolide resistant. A sudden increase in the rate of macrolide resistance (47 of 135 isolates [35%]) was seen in April and May 2002. Sixty-two isolates demonstrated the M phenotype (resistance to macrolide antibiotics), and six isolates demonstrated the MLSB phenotype (resistance to most macrolide...

Macrolide resistance in Streptococcus pneumoniae isolated from Argentinian pediatric patients suffering from acute otitis media

Reijtman,Vanesa; Gagetti,Paula; Faccone,Diego; Fossati,Sofía; Sommerfleck,Patricia; Hernández,Claudia; Bernáldez,Patricia; Lopardo,Horacio; Corso,Alejandra
Fonte: Revista argentina de microbiología Publicador: Revista argentina de microbiología
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2013 Português
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Macrolide-resistant Streptococcus pneumoniae emerged in Argentina in 1995, representing 26% of invasive infection isolates in children under 5 years old. The objectives of this study were to describe the prevalence of ermB and mefA genes in macrolide-resistant S. pneumoniae isolates from acute otitis media (AOM) and to determine their genetic relatedness. Between May 2009 and August 2010, 126 S. pneumoniae isolates from 324 otherwise healthy children with a first episode of AOM were included. Twenty six of these isolates (20.6%) were resistant to erythromycin. Most frequent serotypes were: 14 (46.2%), 6A (23.1%), 19F (7.7%) and 9V (7.7%). Twenty (76.9%) carried the mefA gene, 5 (19.2%) have the ermB gene, and 1 (3.9%) both ermB + mefA. Ten clonal types were identified, mostly related to Sweden15A-25/ST782 (SLV63), CloneB6A/ST473 and England14-9/ ST9. This is the first study assessing the mechanisms of macrolide resistance in pneumococci isolates from pediatric AOM in Argentina and their genetic relatedness.