Macrolide Resistance Phenotypes Research Articles

Macrolide resistance among Streptococcus agalactiae during COVID-19 public health emergency in Brazil.

During COVID-19 public health emergence, azithromycin was excessively used in Brazil, as part of a controversial "early treatment", recommended by former national health authorities. Excessive usage of macrolides may increase resistance rates among beta-hemolytic streptococci. Therefore, this study aimed to investigate the occurrence of resistance to erythromycin and clindamycin among Streptococcus agalactiae recovered from February 2020 to May 2023. Bacterial isolates (n = 116) were obtained from pregnant women and submitted to antimicrobial susceptibility testing, investigation of macrolide resistance phenotypes and genotypes, and identification of capsular type. The overall rate of erythromycin not susceptible (NS) isolates was 25.9%, while resistance to clindamycin was 5.2%. Drug efflux, associated with the M phenotype and mef(A) gene, was the prevalent mechanism of resistance (80%). Capsular type Ia was predominant (39.8%), followed by II, III, and V (17.7% each). A higher diversity of types was observed in the last years of the study. Type IV has had an increasing trend over time, being the fourth most common in 2023. The majority of the isolates that expressed the M phenotype presented capsular type Ia, while those with iMLS phenotype presented capsular type V. Despite no causal relationship can be established, azithromycin excessive usage may be a possible factor associated with this higher rate of erythromycin NS isolates, compared with most previous national studies. On the other hand, resistance to clindamycin has not changed significantly. Therefore, in the studied clinical setting, clindamycin remains a useful alternative to intrapartum prophylaxis among penicillin-allergic pregnant women.

Hybrid Molecules of Azithromycin with Chloramphenicol and Metronidazole: Synthesis and Study of Antibacterial Properties.

The sustained rise of antimicrobial resistance (AMR) causes a strong need to develop new antibacterial agents. One of the methods for addressing the problem of antibiotic resistance is through the design of hybrid antibiotics. In this work, we proposed a synthetic route for the conjugation of an azithromycin derivative with chloramphenicol and metronidazole hemisuccinates and synthesized two series of new hybrid molecules 4a-g and 5a-g. While a conjugation did not result in tangible synergy for wild-type bacterial strains, new compounds were able to overcome AMR associated with the inducible expression of the ermC gene on a model E. coli strain resistant to macrolide antibiotics. The newly developed hybrids demonstrated a tendency to induce premature ribosome stalling, which might be crucial since they will not induce a macrolide-resistant phenotype in a number of pathogenic bacterial strains. In summary, the designed structures are considered as a promising direction for the further development of hybrid molecules that can effectively circumvent AMR mechanisms to macrolide antibiotics.

National Surveillance of Tetracycline, Erythromycin, and Clindamycin Resistance in Invasive Streptococcus pyogenes: A Retrospective Study of the Situation in Spain, 2007-2020.

This work reports on antimicrobial resistance data for invasive Streptococcus pyogenes in Spain, collected by the 'Surveillance Program for Invasive Group A Streptococcus', in 2007-2020. emm typing was determined by sequencing. Susceptibility to penicillin, tetracycline, erythromycin, and clindamycin was determined via the E-test. tetM, tetO, msrD, mefA, ermB, ermTR, and ermT were sought by PCR. Macrolide-resistant phenotypes (M, cMLSB, and iMLSB) were detected using the erythromycin-clindamycin double-disk test. Resistant clones were identified via their emm type, multilocus sequence type (ST), resistance genotype, and macrolide resistance phenotype. Penicillin susceptibility was universal. Tetracycline resistance was recorded for 237/1983 isolates (12.0%) (152 carried only tetM, 48 carried only tetO, and 33 carried both). Erythromycin resistance was detected in 172/1983 isolates (8.7%); ermB was present in 83, mefA in 58, msrD in 51, ermTR in 46, and ermT in 36. Clindamycin resistance (methylase-mediated) was present in 78/1983 isolates (3.9%). Eight main resistant clones were identified: two that were tetracycline-resistant only (emm22/ST46/tetM and emm77/ST63/tetO), three that were erythromycin-resistant only (emm4/ST39/mefA-msrD/M, emm12/ST36/mefA-msrD/M, and emm28/ST52/ermB/cMLSB), and three that were tetracycline-erythromycin co-resistant (emm11/ST403/tetM-ermB/cMLSB, emm77/ST63/tetO-ermTR/iMLSB, and emm77/ST63/tetM-tetO-ermTR/iMLSB). Tetracycline, erythromycin, and clindamycin resistance rates declined between 2007 and 2020. Temporal variations in the proportion of resistant clones determined the change in resistance rates.

Detekcija rezistencije na antibiotike i kapsularnih tipova streptokoka grupe B izolovanih u vaginalnom brisu trudnica

Introduction: Group B streptococcus (GBS) is an opportunistic pathogen that colonizes the gastrointestinal and genital tract of 10 - 30% of healthy people. It can cause early or late-onset neonatal disease manifested as pneumonia, sepsis, and meningitis. Penicillins are the first-choice therapy and prophylaxis of mother-to-child transmission. In the case of penicillin allergy, macrolides or vancomycin are used. Aim: The objectives of study were to determine antimicrobial susceptibility and macrolides resistance phenotypes of GBS isolates, as well as to determine capsular types (CPS) and detection of hypervirulent ST17 clone. Material and methods: From January 1st to December 31st 2021, 134 GBS isolates were collected from vaginal swabs of pregnant women. Identification was performed using conventional microbiological methods and molecular detection of species-specific dltR gene. The disk diffusion method was used to test antibiotic resistance according to EUCAST standards. Capsular typing was conducted by multiplex PCR method. A hypervirulent ST17 clone was identified by the detection of the hvgA gene using PCR. Results: All isolates were susceptible to penicillin, vancomycin, and fluoroquinolones. Tetracycline resistance was the most common, detected in 81.3% (109/134) strains. Macrolide resistance was detected in 3.3% (50/134) of isolates, while 14.9% (20/134) showed resistance to high doses of gentamicin. Resistance to chloramphenicol was noticed in 1.5% (2/134) isolates. The most common macrolide resistance phenotype was cMLS (31/50, 62.0%). The most identified CPS were V found in 33 isolates (25.0%) and III identified in 30 strains (22.0%). A hypervirulent ST17 clone was detected in 12.7% (17/134) of isolates; 15 belonged to CPS III and 2 to CPS IV. Conclusion: The high frequency of macrolide resistance in group B streptococci isolated from colonized pregnant women is a severe public health concern. Also, the detection of numerous CPS III isolates and ST17 clones indicates the need for continuous screening and monitoring of the prevalence of GBS infections in pregnant women and neonates.

In vitro activity of lactone ketolide nafithromycin (WCK 4873) against Streptococcus pneumoniae isolates enriched with macrolide-resistance phenotype collected from mainland China.

BackgroundWidespread MDR Streptococcus pneumoniae in China translates clinically into a substantial pneumococcal disease burden and related morbidity and mortality, particularly in the elderly and children. Nafithromycin (WCK 4873), a novel lactone ketolide class of antibiotic designed with a 3 day, once-daily regimen is highly active against resistant pneumococci and other community respiratory pathogens. It is currently in clinical development for the treatment of community-acquired bacterial pneumonia (CABP).ObjectivesTo determine the in vitro activity of nafithromycin against clinical S. pneumoniae isolates collected during 2015–21 from three hospitals in mainland China.MethodsA total of 920 clinical isolates (one isolate per patient), which predominantly with the macrolide- and clindamycin-resistant phenotype were included in this study. The MICs of nafithromycin and other antibiotics tested were determined using the reference broth microdilution method.ResultsClinical S. pneumoniae isolates used in this study showed high macrolide and clindamycin resistance (>95% against erythromycin and azithromycin and 80% against clindamycin) for which nafithromycin showed potent activity (MIC50/90; 0.03/0.06 mg/L) with 100% susceptibility at a proposed pharmacokinetics/pharmacodynamics (PK/PD) breakpoint of 0.25 mg/L. Among other classes of antibiotics tested, moxifloxacin also showed good activity while amoxicillin/clavulanate and ceftriaxone showed lower susceptibility.ConclusionsNafithromycin exhibited therapeutically relevant in vitro antibacterial activity against contemporary highly resistant pneumococci collected from mainland China. This study supports the clinical development of nafithromycin for the management of CABP caused by pneumococci in China.

A global snapshot on the prevalent macrolide-resistant emm types of Group A Streptococcus worldwide, their phenotypes and their resistance marker genotypes during the last two decades: A systematic review.

Watchful epidemiological surveillance of macrolide-resistant Group A Streptococcus (MRGAS) clones is important owing to the evolutionary and epidemiological dynamic of GAS. Meanwhile, data on the global distribution of MRGAS emm types according to macrolide resistance phenotypes and genotypes are scant and need to be updated. For this, the present systematic review analyses a global set of extensively characterized MRGAS isolates from patients of diverse ages and clinical presentations over approximately two decades (2000 to 2020) and recaps the peculiar epidemiological features of the dominant MRGAS clones. Based on the inclusion and exclusion criteria, 53 articles (3593 macrolide-resistant and 15,951 susceptible isolates) distributed over 23 countries were dissected with a predominance of high-income countries over low-income ones. Although macrolide resistance in GAS is highly variable in different countries, its within-GAS distribution seems not to be random. emm pattern E, 13 major emm types (emm12, 4, 28, 77, 75, 11, 22, 92, 58, 60, 94, 63, 114) and 4 emm clusters (A-C4, E1, E6, and E2) were significantly associated with macrolide resistance. emm patterns A-C and D, 14 major emm types (emm89, 3, 6, 2, 44, 82, 87, 118, 5, 49, 81, 59, 227, 78) and 3 well-defined emm clusters (A-C5, E3, and D4) were significantly associated with macrolide susceptibility. Scrutinizing the tendency of each MRGAS emm type to be significantly associated with specific macrolide resistance phenotype or genotype, interesting vignettes are also unveiled. The 30-valent vaccine covers ~95% of MRGAS isolates. The presented data urge the importance of comprehensive nationwide sustained surveillance of MRGAS circulating clones particularly in Low and Middle income countries where sampling bias is high and GAS epidemiology is obfuscated and needs to be demystified.

Molecular characterization of virulence (lmb, bca and rib) and macrolid resistance genes (ermB, ermTR and mefA) in clinical isolates of Streptococcus agalactiae

The aim of the study was to molecularly identify virulence and macrolide resistance genes in clinical isolates of Streptococcus agalactiae (GBS), recovered in 2019 from vaginal discharge (n=9) and urine (n=22), from two health facilities in Lima. Identification and antimicrobial susceptibility were determined by the Vitek® 2 automated system, identification was confirmed phenotypically; macrolide resistance was determined by the D-test method. Identification of virulence genes (lmb, bca and rib) and macrolide resistance genes (ermB, ermTR and mefA) was carried out by polymerase chain reaction (PCR). The predominant macrolide resistance phenotype and genotype were cMLSb (12/31) and ermB (11/31); the most frequent virulence gene was lmb (23/31). All were sensitive to penicillin, ampicillin and vancomycin. These findings show the need to implement molecular epidemiology studies that allow adequate knowledge and follow-up of GBS in Peru.

Molecular Characterization of Hospital- and Community-Acquired Streptococcus agalactiae Isolates among Nonpregnant Adults in Isfahan, Iran.

Background:The increasing incidence of Group B Streptococcus (GBS) infection among nonpregnant adults has become of growing clinical and public health concern. The current study investigated the distribution of important virulence determinants and antibiotic susceptibility of GBS isolates causing community acquired (CA) and hospital acquired (HA) infections among nonpregnant adults.Materials and Methods:A total of 62 GBS, including 31 CA GBS and 31 HA GBS, were collected from a teaching hospital in Isfahan, Iran. Capsular polysaccharide genotypes (CPS), PI 1, PI 2a, PI 2b, and hypervirulent GBS adhesin (hvgA) virulence genes and antibiotic resistance profiling were determined.Results:There were 19 (30.6%) cases of underlying disease that diabetes mellitus (20.9%) was most common. The rate of multidrug resistant GBS strains was accounted for 29%. Distribution of macrolide resistant phenotypes was as follows: constitutive macrolides, lincosamides, and streptogramin B (MLSB) (15 isolates); inducible resistance to MLSB; and L phenotype (each 5 isolates) and M phenotype (1 isolate). V and Ia serotypes were the most predominant capsular type in HA GBS and CA GBS isolates, respectively. The most frequent pilus types were PI 1, PI 1+PI 2a, PI 1+PI 2b, and PI 2a. PI 1 and PI 1+PI 2a had significantly different distributions between CA and HA GBS isolates. Three CA GBS isolates (9.6%) were positive for hvgA gene that belonged to clonal complex 17/sequence type 17/CPS III/PI 1+PI 2b lineage.Conclusion:There was a significant difference in the distribution of PIs among CA GBS and HA GBS isolates in our region.

Predominance of emm4 and antibiotic resistance of Streptococcus pyogenes in acute pharyngitis in a southern region of Korea.

Streptococcus pyogenes is the most common cause of bacterial pharyngitis. Genotyping of emm is useful for molecular epidemiological survey of S. pyogenes. Antibiotic resistance data are needed for empirical treatments. In total, 358 children in Changwon, Korea who had pharyngitis symptoms were subjected to throat cultures to isolate S. pyogenes in 2017. emm genotyping was performed by direct sequencing. An antibiotic susceptibility test was performed using the disk diffusion method for erythromycin (ERY), clindamycin (CLI), tetracycline (TET) and ofloxacin (OFX). Screening for macrolide resistance phenotype and its determinants was performed for the ERY-resistant strains. A total of 190 strains (53.1 %) of S. pyogenes were isolated from 358 children. The most frequent emm genotype was emm4 (53.2 %), followed by emm89 (12.6 %), emm28 (11.6 %) and emm1 (10 %). Antibiotic resistance rates to ERY, CLI, TET and OFX were 3.2 %, 2.6 %, 1.1 % and 2.6%, respectively. There were five isolates of the cMLSB phenotype having the ermB gene and one M phenotype harbouring the mefA gene. The distribution of emm genotypes was quite different from those previously reported in Korea. emm4 accounted for more than 50 % of the genotypes. Macrolide resistance rates remained very low, but five of six ERY-resistant strains displayed the cMLSB phenotype.

Molecular Basis of Macrolide Resistance in Campylobacter Strains Isolated from Poultry in South Korea.

We investigated the molecular mechanisms underlying macrolide resistance in 38 strains of Campylobacter isolated from poultry. Twenty-seven strains were resistant to azithromycin and erythromycin, five showed intermediate azithromycin resistance and erythromycin susceptibility, and six showed azithromycin resistance and erythromycin susceptibility. Four Campylobacter jejuni and six Campylobacter coli strains had azithromycin MICs which were 8–16 and 2–8-fold greater than those of erythromycin, respectively. The A2075G mutation in the 23S rRNA gene was detected in 11 resistant strains with MICs ranging from 64 to ≥ 512 μg/mL. Mutations including V137A, V137S, and a six-amino acid insertion (114-VAKKAP-115) in ribosomal protein L22 were detected in the C. jejuni strains. Erythromycin ribosome methylase B-erm(B) was not detected in any strain. All strains except three showed increased susceptibility to erythromycin with twofold to 256-fold MIC change in the presence of phenylalanine arginine ß-naphthylamide (PAßN); the effects of PAßN on azithromycin MICs were limited in comparison to those on erythromycin MICs, and 13 strains showed no azithromycin MIC change in the presence of PAßN. Differences between azithromycin and erythromycin resistance and macrolide resistance phenotypes and genotypes were observed even in highly resistant strains. Further studies are required to better understand macrolide resistance in Campylobacter.

High prevalence of multidrug-resistant international clones among macrolide-resistant Streptococcus pneumoniae isolates in immunocompromised patients in Tunisia

Macrolide-resistant Streptococcus pneumoniae isolates have increased considerably in the last decade, with important geographical variations in involved phenotypes and genotypes. The aim of this study was to investigate phenotypes, genotypes, serotypes and genetic relatedness of macrolide-resistant S. pneumoniae isolated from immunocompromised patients in Tunisia. Antibiotic susceptibility was determined by disk diffusion, and MICs of erythromycin and clindamycin were determined for macrolide-resistant isolates by Etest. Macrolide-resistant isolates were analysed by PCR for ermB, mefA, tetM, tetO and Int-Tn1545. Serotyping was done by multiplex PCR and the Quellung reaction. Multilocus sequence typing (MLST) was performed for molecular typing. Macrolide resistance was observed in 41 (69.5%) of 59 isolates. Of the 41 isolates, 37 (90.2%) had a macrolide-lincosamide-streptogramin B (MLSB) resistance phenotype, with a predominance of high-level inducible MLSB phenotype, and harboured the ermB gene. All isolates with high-level inducible MLSB phenotype were highly resistant to erythromycin and clindamycin. Four isolates (9.8%) had a macrolide (M) resistance phenotype and harboured the mefA gene. Erythromycin-resistant isolates were multidrug-resistant (MDR) in 97.5% of cases and extensively drug-resistant in 12.2%. The isolates belonged essentially to four serotypes (19F, 23F, 14 and 6B). They were mainly assigned to three sequence types (ST81, ST2918 and ST386). Also, 65.9% of the isolates were grouped in three clonal complexes (CC81, CC838 and CC386). These data indicate a high prevalence of Tn1545 transposon and of three MDR international clones contributing to the high frequency of multidrug resistance among S. pneumoniae isolates in our centre.

Trends in Antimicrobial Resistance Patterns of Group A Streptococci, Molecular Basis and Implications

Background: Group A streptococcus (GAS) causes a wide variety of diseases ranging from mild skin and soft-tissue infections to severe, life-threatening conditions. A fluctuating trend has been observed in the antibiotic resistance pattern from different parts of the world. The present study was undertaken to determine the prevalence of antibiotic resistance among GAS isolates and the underlying genetic mechanisms. Materials and Methods: Two hundred and six GAS isolates were characterised by antimicrobial susceptibility pattern, macrolide resistance phenotype (double-disc test) and resistance determinants by multiplex polymerase chain reaction. Results: All the isolates were susceptible to penicillin, vancomycin and linezolid. Erythromycin resistance was found in 53% of isolates with inducible macrolide, lincosamide and streptogramin B the predominant phenotype (63%) with ermB the major genetic determinant. Clindamycin resistance was observed in 33% of isolates with all being inducible resistant. Tetracycline resistance was found in 58% of isolates with tetM as the major genetic determinant (97%). Erythromycin and tetracycline co-resistance was found in 39% of tested GAS isolates. Conclusion: The erythromycin and tetracycline resistance in GAS continues to exist at high levels and may be attributed to the over-prescription and use of these antibiotics. Our findings indicate that the use of these antibiotics especially macrolides as empiric therapy in penicillin-allergic patients may not be appropriate.

Izmena fenotipova rezistencije na makrolide kod faringealnih sojeva streptokoka grupe a u dečijoj populaciji

Izmena fenotipova rezistencije na makrolide kod faringealnih sojeva streptokoka grupe a u dečijoj populaciji

Characterization of Streptococcus pyogenes from Animal Clinical Specimens, Spain.

Streptococcus pyogenes appears to be almost exclusively restricted to humans, with few reports on isolation from animals. We provide a detailed characterization (emm typing, pulsed-field gel electrophoresis [PFGE], and multilocus sequence typing [MLST]) of 15 S. pyogenes isolates from animals associated with different clinical backgrounds. We also investigated erythromycin resistance mechanisms and phenotypes and virulence genes. We observed 2 emm types: emm12 (11 isolates) and emm77 (4 isolates). Similarly, we observed 2 genetic linages, sequence type (ST) 26 and ST63. Most isolates exhibited the M macrolide resistance phenotype and the mefA/ermB genotype. Isolates were grouped into 2 clones on the basis of emm-MLST-PFGE-virulence gene profile combinations: clone 1, characterized by the combined genotype emm12-ST36-pulsotype A-speG; and clone 2, characterized by the genotype emm77-ST63-pulsotype B-speC. Our results do not show conclusively that animals may represent a new reservoir of S. pyogenes but indicate the ability of human-derived S. pyogenes isolates to colonize and infect animals.

Molecular epidemiology of macrolide resistant Group A streptococci from Puducherry, India.

In penicillin allergic patients, macrolides are the most commonly used antibiotics for treating streptococcal infections, irrespective of the higher resistance rates. The objective of this study was to evaluate the comparative prevalence, phenotypes, and genetic determinants of macrolide resistance and associated emm types among different clinical isolates of Streptococcus pyogenes. A total of 173 Streptococcus pyogenes isolates were examined for macrolide resistance phenotype by double-disc test, resistance determinants by multiplex PCR and emm genotyping. Erythromycin resistance was found in 51.4% of isolates, with MIC90 ≥ 256 µg/mL Inducible phenotype was commonly found (iMLS, 67.4%) followed by the M phenotype (32.5%). Among these isolates, 65.1% harboured ermB and 32.5% mefA as sole macrolide resistance gene, whereas presence of both, ermB plus mefA was observed in 2.2% cases. The most common types among resistant strains were emm63 (11.2%), emm44 (6.7%), emm42 (5.6%), and emm75.3, emm82, emm85, emm92, emm111.1 (4.4% each). Statistically significant association was observed between emm63, emm44 and erythromycin resistance (p ≤ 0.05). Association of these emm types and macrolide resistance have not been reported earlier. Higher macrolide resistance in this study can be attributed to overuse and misuse of this antibiotic. These findings indicate that macrolides should not be empirically used for treating severe streptococcal infections.

Throat Carriage Rate and Antimicrobial Resistance of Streptococcus pyogenes In Rural Children in Argentina.

ObjectivesThe aim of this study was to determine the prevalence of asymptomatic carriers of group A β-hemolytic streptococci (GAS) in children living in a rural community and to investigate the association between episodes of acute pharyngitis and carrier status.MethodsThroat swabs were collected from September to November 2013 among children 5-13 years of age from a rural community (Maria Ignacia-Vela, Argentina). The phenotypic characterization of isolates was performed by conventional tests. Antimicrobial susceptibility was assayed for penicillin, tetracycline, chloramphenicol, erythromycin, and clindamycin (disk diffusion). The minimum inhibitory concentration was determined for penicillin, cefotaxime, tetracycline, and erythromycin.ResultsThe carriage of β-hemolytic streptococci was detected in 18.1% of participants, with Streptococcus pyogenes in 18 participants followed by S. dysgalactiae ssp. equisimilis in 5. The highest proportion of GAS was found in 8 to 10-year-old children. No significant association between the number of episodes of acute pharyngitis suffered in the last year and the carrier state was detected (p>0.05). Tetracycline resistance (55.5%) and macrolide-resistant phenotypes (11.1%) were observed. Resistance to penicillin, cefotaxime, or chloramphenicol was not expressed in any streptococcal isolate.ConclusionsThe present study demonstrated significant throat carriage of GAS and the presence of group C streptococci (S. dysgalactiae ssp. equisimilis) in an Argentinian rural population. These results point out the need for continuous surveillance of GAS and non-GAS carriage as well as of antimicrobial resistance in highly susceptible populations, such as school-aged rural children. An extended surveillance program including school-aged children from different cities should be considered to estimate the prevalence of GAS carriage in Argentina.

Survey of strain distribution and antibiotic resistance pattern of group B streptococci (Streptococcus agalactiae) isolated from clinical specimens.

Aim: The aims of the present study were to determine the antibiotic susceptibility profils with particular emphasis on susceptible or resistant strains to macrolides and lincosamids antibiotics and to determine possible antibiotic resistance mechanisms occurring in group B streptococci (GBS) strains using PCR assay and disk diffusion method.Methods: A total of 62 clinical GBS strains were investigated. Antibacterial susceptibility testing was performed using the disk diffusion method and inducible resistance test for clindamycin by standard double disk diffusion or D-zone test for all isolates to differentiate macrolide resistance phenotype (M), constitutive macrolide-lincosamide-streptogramin B phenotype (cMLSB) and induced macrolide-lincosamide-streptogramin B phenotype (iMLSB). In addition, minimum inhibitory concentrations (MIC) of penicillin were determined for all isolates. Finally, possible existence of antibiotic resistance genes for erythromycin (ermTR, ermB and mefA/E) and for clindamycin (linB) were examined among isolates using PCR assay.Results: All 62 isolates were susceptible to penicillin, ampicillin, linezolid, cefazoline and vancomycin. However, 93.5% (n=58) of isolates showed an increased MIC to penicillin. The overall rate of erythromycin resistance was 35.5% (n=22). All erythromycin-resistant isolates displayed the M phenotype (100%, n=22). All three erythromycin resistance genes (i.e. ermTR, ermB and mefA/E) were found in erythromycin-resistant isolates.Conclusion: It was concluded that prescribing antibiotic without antibacterial susceptibility tests should be prevented because of the high prevalence of erythromycin-resistant GBS strains and the fact that erythromycin-resistant GBS strains has shown an increased MIC to penicillin, as the drug of choice for treating GBS infections.

Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains.

High rates of 23S rDNA mutations implicated in macrolide resistance have been identified in Treponema pallidum samples from syphilis patients in many countries. Nonetheless, some clinicians have been reluctant to abandon azithromycin as a treatment for syphilis, citing the lack of a causal association between these mutations and clinical evidence of drug resistance. Although azithromycin resistance has been demonstrated in vivo for the historical Street 14 strain, no recent T. pallidum isolates have been tested. We used the well-established rabbit model of syphilis to determine the in vivo efficacy of azithromycin against 23S rDNA mutant strains collected in 2004 to 2005 from patients with syphilis in Seattle, Wash. Groups of 9 rabbits were each infected with a strain containing 23S rDNA mutation A2058G (strains UW074B, UW189B, UW391B) or A2059G (strains UW228B, UW254B, and UW330B), or with 1 wild type strain (Chicago, Bal 3, and Mexico A). After documentation of infection, 3 animals per strain were treated with azithromycin, 3 were treated with benzathine penicillin G, and 3 served as untreated control groups. Treatment efficacy was documented by darkfield microscopic evidence of T. pallidum, serological response, and rabbit infectivity test. Azithromycin uniformly failed to cure rabbits infected with strains harboring either 23S rDNA mutation, although benzathine penicillin G was effective. Infections caused by wild type strains were successfully treated by either azithromycin or benzathine penicillin G. A macrolide resistant phenotype was demonstrated for all strains harboring a 23S rDNA mutation, demonstrating that either A2058G or A2059G mutation confers in vivo drug resistance.

Drug Resistance Characteristics and Macrolide-Resistant Mechanisms of Streptococcus pneumoniae in Wenzhou City, China.

BackgroundStreptococcus pneumoniae (SP) is a Gram-positive, alpha-hemolytic, facultative anaerobic member of the genus Streptococcus. The erythromycin-resistant methylase (erm) gene and macrolide efflux (mef) gene are the 2 main genes that can mediate SP. Transposon (Tn) also plays an important role in the collection and metastasis of the gene. In the present study we investigated the drug resistance characteristics and the macrolide-resistant mechanisms of SP in Wenzhou City, China.Material/MethodsSixty-eight strains of SP were isolated from sputum samples of hospitalized children in the Second Affiliated Hospital of Wenzhou Medical University. These strains were analyzed using antimicrobial susceptibility tests to determine their drug resistance to 10 kinds of antibacterials. Macrolide-resistant phenotypes were identified using K-B method. PCR method was used to analyze the erm B gene, mef A gene, and int Tn gene.ResultsDrug resistance rates of 68 strains of SP were 98.5%, 100.0%, 63.2%, 52.9%, 94.1%, 89.7%, 0.0%, 0.0%, 16.2%, and 14.7% for clindamycin, erythromycin, penicillin G, cefotaxime, tetracycline, sulfamethoxazole/trimethoprim, levofloxacin, vancomycin, chloramphenicol, and amoxicillin, respectively. Total detection rates of the erm B gene, mef A gene, and int Tn gene were 98.5%, 91.2%, and 100.0%, respectively.ConclusionsSP shows significant multi-drug resistance in Wenzhou City, whereas there is no clinical value of macrolides antibiotics for SP. cMLSB mediated by erm B gene is the most predominant phenotype among macrolide-resistant SP. The int Tn gene may play an important role in horizontal transfer and clonal dissemination of SP drug resistance genes in Wenzhou City.

Erythromycin Resistance in Streptococcus Pyogenes Causing Pharyngotonsillitis in Egyptian Children and Its Association with the Presence of Fibronectin Binding Protein F1 (prtf1) Gene

Background: Erythromycin resistance among Streptococcus pyogenes (S. pyogenes) has been reported with alarming rates throughout the world. Fibronectin-binding proteins, especially F1 (PrtF1) encoded by prtF1 gene have been implicated in mediating internalization of S. pyogenes within epithelial cells. Objectives: the current study aimed to detect erythromycin resistance among S. pyogenes causing acute pharyngo-tonsillitis in Egyptian children and to explore the association between erythromycin resistance and the presence of prtf1 gene. Methodology: Throat swabs were collected from 100 pediatric patients with age ranging from 5 to 12 years and suffering from pharyngo-tonsillitis . s. pyogenes was recovered from samples and identified by conventional methods . In-vitro susceptibility of s. pyogenes isolates to different antimicrobials was done using disk diffusion method. Minimum inhibitory concentration for erythromycin was determined using E test strips. The phenotype of macrolide resistance was determined using the double-disk test. The presence of prtF1 gene was detected by polymerase chain reaction. Results: S. pyogenes were isolated from 45% (45/100) of the patients’ throat swabs. Erythromycin resistance was detected in 11 (24.4%) isolates , among which 5 (45.5%) exhibited the M phenotype of macrolide resistance; 4 isolates had the constitutive phenotype of resistance while 2 isolates had the induced phenotype. prtF1 gene was detected in 16/45 isolates (35.6%). There was statistically significant association between prtF1 gene presence and erythromycin resistance (OR: 4.8611; 95% CI: 1.14-20.63, p= 0.032). Conclusion : The present study provides a preliminary idea about the frequency of macrolide resistance and contribute to a better understanding of the pathogenesis of S. pyogenes causing pharyngo-tonsillitis in Egyptian children.