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Weerasekara M, Vidanapathirana G, Li C, Tennegedara A, Dissanayake R, Ekanayake A, Abeykoon M, Kothalawala M, Liyanapathirana V, Ip M. Characterization of group A streptococci causing invasive diseases in Sri Lanka. Access Microbiol 2024; 6:000697.v4. [PMID: 39045254 PMCID: PMC11261727 DOI: 10.1099/acmi.0.000697.v4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 05/08/2024] [Indexed: 07/25/2024] Open
Abstract
Group A β haemolytic streptococcus (GAS) or Streptococcus pyogenes is a human pathogen that causes an array of infections, including pharyngitis, cellulitis, impetigo, scarlet fever, toxic shock syndrome, and necrotizing fasciitis. The present study characterizes 51 GAS isolates from invasive infections in Sri Lanka, focusing on resistance profiles, genetic determinants of resistance, and virulence markers. Isolates were tested for sensitivity to penicillin, erythromycin, clindamycin, and tetracycline. The presence of erm(A), erm(B), and mef(A) was detected in erythromycin-resistant isolates, while tet(M) was detected in the tetracycline-resistant isolates. PCR was used to identify SpeA, SpeB, SpeC, SpeF, SpeG, smez, and ssa as virulence markers. Selected GAS isolates were emm-typed using the updated CDC protocol. All 51 isolates were susceptible to penicillin. The number of isolates non-susceptible to erythromycin was 16. The commonest resistance determinant identified was erm(B) (11/16). Tetracycline non-susceptibility was found in 36 (70.6 %) isolates and 26 of them contained the tet(M) gene. Thirteen (25.5 %) isolates were resistant to both tetracycline and erythromycin, while 12 (23.5 %) isolates were sensitive to both antibiotics. The commonest virulence markers detected among the isolates were SpeB (44, 86.3 %), SpeG (36, 70.6 %), and SpeF (35, 68.6 %), while SpeJ (15, 29.4 %), SpeA (10, 19.6 %), and ssa (5,9.8 %) were less common. The emm types were diverse. In conclusion, the GAS isolates studied showed resistance to erythromycin and tetracycline, while retaining universal susceptibility to penicillin. Additionally, these isolates exhibited diverse genetic backgrounds, displaying varying patterns of virulence genes and emm types.
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Affiliation(s)
- Madumali Weerasekara
- Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka
| | - Gihani Vidanapathirana
- Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka
- Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Carmen Li
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR
| | - Asanka Tennegedara
- Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Rasadanie Dissanayake
- Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Asela Ekanayake
- Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | | | | | - Veranja Liyanapathirana
- Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Margaret Ip
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR
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Wang YM, Chen MY, Chen J, Zhang XH, Feng Y, Han YX, Li YL. Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates. World J Gastroenterol 2024; 30:184-195. [PMID: 38312120 PMCID: PMC10835524 DOI: 10.3748/wjg.v30.i2.184] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/12/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Resistance to clarithromycin (CLA) and levofloxacin (LFX) of Helicobacter pylori (H. pylori) is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving a large number of patients with previous treatment histories. AIM To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. METHODS We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group. RESULTS A total of 132 individuals tested positive for the H. pylori ureA gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (n = 109), LFX resistance rate was 69.7% (n = 92) and dual resistance was 62.1% (n = 82). Gastric symptoms [odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194; P = 0.035] and rural residence (OR = 5.152; 95%CI: 1.407-18.861; P = 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (P = 0.001) and PP (P = 0.012) analyses. CONCLUSION H. pylori presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.
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Affiliation(s)
- Yan-Meng Wang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Mo-Ye Chen
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Jing Chen
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, The First Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Xin-He Zhang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Yan Feng
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Yu-Xi Han
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
| | - Yi-Ling Li
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning Province, China
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Li J, Liu L, Zhang H, Guo J, Wei X, Xue M, Ma X. Severe problem of macrolides resistance to common pathogens in China. Front Cell Infect Microbiol 2023; 13:1181633. [PMID: 37637457 PMCID: PMC10448830 DOI: 10.3389/fcimb.2023.1181633] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 07/18/2023] [Indexed: 08/29/2023] Open
Abstract
With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as Streptococcus pneumoniae, Streptococcus (including Group A streptococcus, Group B streptococcus), Staphylococcus aureus, Bordetella pertussis, and Mycoplasma pneumoniae, have shown varying degrees of drug resistance. In order to provide such problem and related evidence for rational use of antibiotics in clinic, we reviewed the drug resistance of common bacteria to macrolides in children recent 20 years.
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Affiliation(s)
- Jialin Li
- Department of Respiratory Disease, Children's Hospital Affiliated to Shandong University, Jinan, Shandong, China
- Jinan Key Laboratory of Pediatric Respiratory Diseases, Jinan Children’s Hospital, Jinan, China
| | - Lesen Liu
- Surgical Department, Huaiyin People’s Hospital, Jinan, China
| | - Hua Zhang
- Department of Respiratory Disease, Children's Hospital Affiliated to Shandong University, Jinan, Shandong, China
- Jinan Key Laboratory of Pediatric Respiratory Diseases, Jinan Children’s Hospital, Jinan, China
| | - Jing Guo
- Department of Respiratory Disease, Children's Hospital Affiliated to Shandong University, Jinan, Shandong, China
- Jinan Key Laboratory of Pediatric Respiratory Diseases, Jinan Children’s Hospital, Jinan, China
| | - Xiaoling Wei
- Department of Respiratory Disease, Children's Hospital Affiliated to Shandong University, Jinan, Shandong, China
- Jinan Key Laboratory of Pediatric Respiratory Diseases, Jinan Children’s Hospital, Jinan, China
| | - Min Xue
- Department of Respiratory Disease, Children's Hospital Affiliated to Shandong University, Jinan, Shandong, China
- Jinan Key Laboratory of Pediatric Respiratory Diseases, Jinan Children’s Hospital, Jinan, China
| | - Xiang Ma
- Department of Respiratory Disease, Children's Hospital Affiliated to Shandong University, Jinan, Shandong, China
- Jinan Key Laboratory of Pediatric Respiratory Diseases, Jinan Children’s Hospital, Jinan, China
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Wang X, Cong Z, Huang W, Li C. Molecular characterization of Streptococcus pneumoniae isolated from pediatric patients in Shanghai, China. Pediatr Pulmonol 2020; 55:2135-2141. [PMID: 32470194 DOI: 10.1002/ppul.24877] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 05/26/2020] [Indexed: 11/08/2022]
Abstract
BACKGROUND Streptococcus pneumoniae is a major cause of bacterial infection among infants and young children with high morbidity and mortality. The serotype distribution of S. pneumoniae varies with geography, time, age, and disease. AIM We aimed to investigate the current status of molecular characteristics of S. pneumoniae strains isolated from pediatric patients in Shanghai, China. METHODS Between 2016 and 2018, 73 clinical S. pneumoniae isolates were characterized by capsular serotype, multilocus sequence typing, antibiotic susceptibility, and resistant genes. RESULTS The most common serotypes were 19F (39.7%), 19A (16.4%), 6A (11.0%), 14 (9.6%), and 6B (8.2%). The coverage rates of the 7-, 10- and 13-valent pneumococcal conjugate vaccines were 64.4%, 64.4%, and 91.8%, respectively. The five predominant sequence types were ST271 (37.0%), ST320 (19.2%), ST3173 (11.0%), ST876 (6.8%), and ST81 (4.1%), which were mainly associated with serotypes 19F, 19A, 6A, 14, and 23F, respectively. The rates of resistance to penicillin and ceftriaxone were 21.9% and 39.7%, respectively. All strains displayed resistance to macrolides, 54.8% of which possessed both erm(B) and mef(A/E) genes, and 41.1% carried the erm(B) gene alone. Tn2010 (41.1%) was the most common transposon. CONCLUSIONS Clonal complex 271 (Taiwan19F-14 clone) played a dominant role in the dissemination of pneumococcal isolates. The prevalent serotypes indicated a lack of the 7-valent pneumococcal conjugate vaccine, which has not been included in national immunization programs in mainland China. The high rate of macrolide resistance made the empirical use of macrolides alone not suitable for treating pediatric pneumococcal disease.
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Affiliation(s)
- Xing Wang
- Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Zhilei Cong
- Department of Emergency, Huashan Hospital, Fudan University, Shanghai, China
| | - Weichun Huang
- Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Cong Li
- Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Ubukata K, Wajima T, Morozumi M, Sakuma M, Tajima T, Matsubara K, Itahashi K, Iwata S. Changes in epidemiologic characteristics and antimicrobial resistance of Streptococcus pyogenes isolated over 10 years from Japanese children with pharyngotonsillitis. J Med Microbiol 2020; 69:443-450. [PMID: 32011228 DOI: 10.1099/jmm.0.001158] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Introduction. Pharyngotonsillitis caused by Streptococcus pyogenes (group A streptococci, or GAS) is among the most common infections treated with antibiotics in pediatric patients.Aim. This study aimed to analyse changes in molecular epidemiology and antibiotic susceptibility among GAS isolates in three study periods spanning 10 years.Methodology. GAS isolated from paediatric patients with pharyngotonsillitis during Period I (mid-2007 to 2008, n=235), Period II (2012, n=210), and Period III (2018, n=189) were analysed for emm type, multilocus sequence type (MLST), antibiotic susceptibility, and macrolide (ML)- and quinolone (QL)-resistance genes.Results. Over 20 % of isolates represented emm1 and emm12 types, remaining common in all three periods. Among other emm types, emm4 was common in Period I, emm28 and emm89 in Period II, and emm3 and emm89 in Period III. All isolates remained highly susceptible to penicillins and cephalosporins. Isolates possessing mefA, ermA, or ermB genes mediating ML resistance increased from 34.9 % in Period I to 60.9 % in Period II, but fell to 27.5 % in Period III. QL-resistant isolates with amino acid substitutions affecting ParC and/or GyrA gradually increased from 11.5 to 14.3 %. Specific sequence types identified by MLST and emm typing were associated closely with ML or QL resistance.Conclusion. Our findings indicate that even in ambulatory care, antibiotic choice for these infections should be based on rapid identification and characterization of causative pathogens.
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Affiliation(s)
- Kimiko Ubukata
- Department of Infectious Diseases, Keio University, School of Medicine, Tokyo, Japan
| | - Takeaki Wajima
- Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Miyuki Morozumi
- Department of Infectious Diseases, Keio University, School of Medicine, Tokyo, Japan
| | - Megumi Sakuma
- Department of Infectious Diseases, Keio University, School of Medicine, Tokyo, Japan
| | - Takeshi Tajima
- Department of Pediatrics, Hakujikai Memorial Hospital, Tokyo, Japan
| | - Keita Matsubara
- Department of Pediatrics, Hiroshima City Funairi Citizens Hospital, Hiroshima, Japan
| | - Koju Itahashi
- Pharmaceutical R&D Division, Meiji Seika Pharma, Tokyo, Japan
| | - Satoshi Iwata
- Departments of Infectious Diseases, National Cancer Center Hospital, Tokyo, Japan.,Department of Infectious Diseases, Keio University, School of Medicine, Tokyo, Japan
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Hoban DJ, Nauta J. Clinical And Bacteriological Impact Of Clarithromycin In Streptococcal Pharyngitis: Findings From A Meta-Analysis Of Clinical Trials. DRUG DESIGN DEVELOPMENT AND THERAPY 2019; 13:3551-3558. [PMID: 31802844 PMCID: PMC6801486 DOI: 10.2147/dddt.s205820] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Accepted: 09/11/2019] [Indexed: 11/30/2022]
Abstract
Introduction Among the bacterial upper respiratory tract infections (UTRIs), the most medically significant is pharyngitis due to Group A beta-hemolytic Streptococci (GABHS). A 2012 meta-review and a 2016 Cochrane systematic review reported favorably on the comparative efficacy and safety of clarithromycin in pediatric patients with URTIs and in adults with GABHS pharyngitis. In this paper, the evidence base for clarithromycin in patients with URTIs is augmented by a meta-analysis of comparative studies in GABHS pharyngitis. Methods A series of five outpatient trials of clarithromycin for the treatment of streptococcal pharyngitis from an internal database were subjected to meta-analysis. Active comparators comprised penicillin VK and erythromycin. Results Rates of clinical cure or improvement were very similar in all treatment assignments, but the rates of bacteriological cure were numerically higher with clarithromycin than with comparator antibiotics. Adverse events data indicated that clarithromycin was generally well tolerated in these studies, with a relatively low incidence of adverse events and few severe incidents. Discussion Though currently not advised as a first-line therapy for URTI in most guidelines, the results of the meta-analysis indicate that clarithromycin is nevertheless a valid, effective and largely well-tolerated treatment option for GABHS pharyngitis patients who cannot benefit from other agents.
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Affiliation(s)
- Daryl J Hoban
- Department of Medical Microbiology and Infectious Disease, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Jos Nauta
- Department of Innovation & Development, Established Pharmaceuticals Division, Abbott Healthcare Products B.V., Weesp 1381 CP, The Netherlands
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Huang Y, Wen Y, Jia Q, Wang L, Cheng Q, Liu W, Huang T, Xie L. Genome analysis of a multidrug-resistant Streptococcus sanguis isolated from a throat swab of a child with scarlet fever. J Glob Antimicrob Resist 2019; 20:1-3. [PMID: 31698106 DOI: 10.1016/j.jgar.2019.10.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 10/22/2019] [Accepted: 10/27/2019] [Indexed: 10/25/2022] Open
Abstract
OBJECTIVES A multidrug-resistant strain of the opportunistic pathogen Streptococcus sanguis (S28) was isolated from a throat swab of a child with scarlet fever as a rare case. Genome sequencing and analysis of strain S28 were performed to gain a better understanding of the multidrug resistance mechanisms of S. sanguis and its relationship with scarlet fever. METHODS The genome of S. sanguis S28 was sequenced on a Illumina HiSeq platform. Genome assembly was conducted using SOAPdenovo v.2.04 and the assembled genome sequence was submitted to NCBI for annotation. RESULTS The 1 268 358 696bp genome of S. sanguis S28 contains 2287 coding sequences (CDS) with a GC content of 43.2%. Strain S28 possesses four antimicrobial resistance genes (ARGs), which is consistent with phenotypic analysis. A novel transposon with three genes conferring resistance to macrolide-lincosamide-streptogramin B (MLSB) antibiotics, tetracyclines and aminoglycosides was discovered. CONCLUSION To our knowledge, this is the first report of a S. sanguis genome isolated from a throat swab of a child with scarlet fever and the first report of a transposon with three activated ARGs conferring resistance to MLSB, tetracyclines and aminoglycosides together.
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Affiliation(s)
- Yinyan Huang
- Hangzhou Center for Disease Control and Prevention, No. 568 Mingshi Road, Hangzhou, Zhejiang, China
| | - Yuanyuan Wen
- Hangzhou Center for Disease Control and Prevention, No. 568 Mingshi Road, Hangzhou, Zhejiang, China
| | - Qingjun Jia
- Hangzhou Center for Disease Control and Prevention, No. 568 Mingshi Road, Hangzhou, Zhejiang, China
| | - Le Wang
- Hangzhou Center for Disease Control and Prevention, No. 568 Mingshi Road, Hangzhou, Zhejiang, China
| | - Qinglin Cheng
- Hangzhou Center for Disease Control and Prevention, No. 568 Mingshi Road, Hangzhou, Zhejiang, China
| | - Wei Liu
- Hangzhou Center for Disease Control and Prevention, No. 568 Mingshi Road, Hangzhou, Zhejiang, China; Joinstar Biomedical Technology Co., Ltd., No. 519 XingGuo Road, Hangzhou, Zhejiang, China
| | - Tingting Huang
- School of Marine Sciences, Ningbo University, No. 169 Qixing South Road, Ningbo, Zhejiang, China
| | - Li Xie
- Hangzhou Center for Disease Control and Prevention, No. 568 Mingshi Road, Hangzhou, Zhejiang, China.
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Jendoubi F, Rohde M, Prinz JC. Intracellular Streptococcal Uptake and Persistence: A Potential Cause of Erysipelas Recurrence. Front Med (Lausanne) 2019; 6:6. [PMID: 30761303 PMCID: PMC6361840 DOI: 10.3389/fmed.2019.00006] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 01/10/2019] [Indexed: 12/21/2022] Open
Abstract
Erysipelas is a severe streptococcal infection of the skin primarily spreading through the lymphatic vessels. Penicillin is the treatment of choice. The most common complication consists in relapses which occur in up to 40% or more of patients despite appropriate antibiotic treatment. They cause lymphatic damage resulting in irreversible lymphedema and ultimately elephantiasis nostras and lead to major health restrictions and high socio-medical costs. Prevention of relapses is an unmet need, because even long-term prophylactic penicillin application does eventually not reduce the risk of recurrence. In this article we assess risk factors and causes of erysipelas recurrence. A systematic literature search for clinical studies addressing potential causes and measures for prevention of erysipelas recurrence was combined with a review of experimental and clinical data assessing the ability and clinical relevance of streptococci for intracellular uptake and persistence. The literature review found that venous insufficiency, lymphedema, and intertrigo from fungal infections are considered to be major risk factors for recurrence of erysipelas but cannot adequately explain the high recurrence rate. As hitherto unrecognized likely cause of erysipelas relapses we identify the ability of streptococci for intracellular uptake into and persistence within epithelial and endothelial cells and macrophages. This creates intracellular streptococcal reservoirs out of reach of penicillins which do not reach sufficient bactericidal intracellular concentrations. Incomplete streptococcal elimination due to intracellular streptococcal persistence has been observed in various deep tissue infections and is considered as cause of relapsing streptococcal pharyngitis despite proper antibiotic treatment. It may also serves as endogenous infectious source of erysipelas relapses. We conclude that the current antibiotic treatment strategies and elimination of conventional risk factors employed in erysipelas management are insufficient to prevent erysipelas recurrence. The reactivation of streptococcal infection from intracellular reservoirs represents a plausible explanation for the frequent occurrence erysipelas relapses. Prevention of erysipelas relapses therefore demands for novel antibiotic strategies capable of eradicating intracellular streptococcal persistence.
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Affiliation(s)
- Fatma Jendoubi
- Department of Dermatology, University Clinics, Ludwig-Maximilian University of Munich, Munich, Germany.,Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Manfred Rohde
- Central Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Jörg Christoph Prinz
- Department of Dermatology, University Clinics, Ludwig-Maximilian University of Munich, Munich, Germany
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Wan C, Li Y, Le WJ, Liu YR, Li S, Wang BX, Rice PA, Su XH. Increasing Resistance to Azithromycin in Neisseria gonorrhoeae in Eastern Chinese Cities: Resistance Mechanisms and Genetic Diversity among Isolates from Nanjing. Antimicrob Agents Chemother 2018; 62:e02499-17. [PMID: 29530847 PMCID: PMC5923098 DOI: 10.1128/aac.02499-17] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Accepted: 02/23/2018] [Indexed: 12/20/2022] Open
Abstract
Azithromycin resistance (AZM-R) of Neisseria gonorrhoeae is emerging as a clinical and public health challenge. We determined molecular characteristics of recent AZM-R Nanjing gonococcal isolates and tracked the emergence of AZM-R isolates in eastern Chinese cities in recent years. A total of 384 N. gonorrhoeae isolates from Nanjing collected from 2013 to 2014 were tested for susceptibility to AZM and six additional antibiotics; all AZM-R strains were characterized genetically for resistance determinants by sequencing and were genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST). Among the 384 isolates, 124 (32.3%) were AZM-R. High-level resistance (MIC, ≥256 mg/liter) was present in 10.4% (40/384) of isolates, all of which possessed the A2143G mutation in all four 23S rRNA alleles. Low- to mid-level resistance (MIC, 1 to 64 mg/liter) was present in 21.9% (84/384) of isolates, 59.5% of which possessed the C2599T mutation in all four 23S rRNA alleles. The 124 AZM-R isolates were distributed in 71 different NG-MAST sequence types (STs). ST1866 was the most prevalent type in high-level AZM-R (HL-AZM-R) isolates (45% [18/40]). This study, together with previous reports, revealed that the prevalence of AZM-R in N. gonorrhoeae isolates in certain eastern Chinese cities has risen >4-fold (7% to 32%) from 2008 to 2014. The principal mechanisms of AZM resistance in recent Nanjing isolates were A2143G mutations (high-level resistance) and C2599T mutations (low- to mid-level resistance) in the 23S rRNA alleles. Characterization of NG-MAST STs and phylogenetic analysis indicated the genetic diversity of N. gonorrhoeae in Nanjing; however, ST1866 was the dominant genotype associated with HL-AZM-R isolates.
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Affiliation(s)
- Chuan Wan
- STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Yang Li
- STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Wen-Jing Le
- STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Yu-Rong Liu
- STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Sai Li
- STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Bao-Xi Wang
- STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
| | - Peter A Rice
- Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
| | - Xiao-Hong Su
- STD Clinic, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China
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10
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Delpech G, Sparo M, Baldaccini B, Pourcel G, Lissarrague S, García Allende L. Throat Carriage Rate and Antimicrobial Resistance of Streptococcus pyogenes In Rural Children in Argentina. J Prev Med Public Health 2017; 50:127-132. [PMID: 28372355 PMCID: PMC5398335 DOI: 10.3961/jpmph.15.073] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 12/18/2016] [Indexed: 11/09/2022] Open
Abstract
OBJECTIVES The 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. METHODS Throat 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. RESULTS The 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. CONCLUSIONS The 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.
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Affiliation(s)
- Gastón Delpech
- School of Medicine, Universidad Nacional del Centro de la Provincia de Buenos Aires, Olavarría, Argentina
| | - Mónica Sparo
- School of Medicine, Universidad Nacional del Centro de la Provincia de Buenos Aires, Olavarría, Argentina.,Hospital Ramón Santamarina, Tandil, Argentina
| | - Beatriz Baldaccini
- School of Medicine, Universidad Nacional del Centro de la Provincia de Buenos Aires, Olavarría, Argentina
| | - Gisela Pourcel
- School of Medicine, Universidad Nacional del Centro de la Provincia de Buenos Aires, Olavarría, Argentina
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11
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Tanaka Y, Gotoh K, Teramachi M, Ishimoto K, Tsumura N, Shindou S, Yamashita Y. Molecular epidemiology, antimicrobial susceptibility, and characterization of macrolide-resistant Streptococcus pyogenes in Japan. J Infect Chemother 2016; 22:727-732. [DOI: 10.1016/j.jiac.2016.06.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 06/24/2016] [Accepted: 06/30/2016] [Indexed: 11/28/2022]
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12
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Liu YL, Li DF, Xu HP, Xiao M, Cheng JW, Zhang L, Xu ZP, Chen XX, Zhang G, Kudinha T, Kong F, Gong YP, Wang XY, Zhang YX, Wu HL, Xu YC. Use of next generation sequence to investigate potential novel macrolide resistance mechanisms in a population of Moraxella catarrhalis isolates. Sci Rep 2016; 6:35711. [PMID: 27774989 PMCID: PMC5075928 DOI: 10.1038/srep35711] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 10/04/2016] [Indexed: 01/01/2023] Open
Abstract
Although previous studies have confirmed that 23S rRNA gene mutation could be responsible for most of macrolide resistance in M. catarrhalis, a recent study suggested otherwise. Next generation sequence based comparative genomics has revolutionized the mining of potential novel drug resistant mechanisms. In this study, two pairs of resistant and susceptible M. catarrhalis isolates with different multilocus sequence types, were investigated for potential differential genes or informative single nucleotide polymorphisms (SNPs). The identified genes and SNPs were evaluated in 188 clinical isolates. From initially 12 selected differential genes and 12 informative SNPs, 10 differential genes (mboIA, mcbC, mcbI, mboIB, MCR_1794, MCR_1795, lgt2B/C, dpnI, mcbB, and mcbA) and 6 SNPs (C619T of rumA, T140C of rplF, G643A of MCR_0020, T270G of MCR_1465, C1348A of copB, and G238A of rrmA) were identified as possibly linked to macrolide resistance in M. catarrhalis. Most of the identified differential genes and SNPs are related to methylation of ribosomal RNA (rRNA) or DNA, especially MCR_0020 and rrmA. Further studies are needed to determine the function and/or evolution process, of the identified genes or SNPs, to establish whether some novel or combined mechanisms are truly involved in M. catarrhalis macrolide resistance mechanism.
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Affiliation(s)
- Ya-Li Liu
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China
| | - Dong-Fang Li
- Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.,Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.,Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China
| | - He-Ping Xu
- Department of Clinical Laboratory, the First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Meng Xiao
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China
| | - Jing-Wei Cheng
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China
| | - Li Zhang
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China
| | - Zhi-Peng Xu
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China
| | - Xin-Xin Chen
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China
| | - Ge Zhang
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China
| | - Timothy Kudinha
- Charles Sturt University, Leeds Parade, Orange, New South Wales 2687, Australia.,Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR - Pathology West, Westmead Hospital, University of Sydney, Darcy Road, Westmead, New South Wales 2145, Australia
| | - Fanrong Kong
- Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR - Pathology West, Westmead Hospital, University of Sydney, Darcy Road, Westmead, New South Wales 2145, Australia
| | - Yan-Ping Gong
- Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.,Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China
| | - Xin-Ying Wang
- Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.,Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China
| | - Yin-Xin Zhang
- Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.,Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China
| | - Hong-Long Wu
- Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.,Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.,Tianjin Translational Genomics Center, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China
| | - Ying-Chun Xu
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100736, China
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13
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Magnussen MD, Gaini S, Gislason H, Kristinsson KG. Antibacterial resistance in Streptococcus pyogenes (GAS) from healthy carriers and tonsillitis patients and association with antibacterial sale in the Faroe Islands. APMIS 2016; 124:327-32. [PMID: 26833774 DOI: 10.1111/apm.12513] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 12/10/2015] [Indexed: 12/01/2022]
Abstract
The aim of this study was to investigate the antibacterial resistance of Streptococcus pyogenes (GAS), and correlate the findings with the sales of erythromycin and tetracycline. General practitioners in the Faroe Islands were recruited to send oropharyngeal swabs. From an ongoing pneumococcal study, nasopharyngeal swabs were sampled from healthy children 0-7 years of age. Erythromycin susceptibility data from Iceland were obtained from the reference laboratory at the Landspitali University Hospital. Susceptibility testing in the Faroe Islands and Iceland was performed according to CLSI methods and criteria. The resistance rate to erythromycin and tetracycline found in patients in the Faroe Islands in 2009/2010 was 6% and 30% respectively. Tetracycline resistance in patients declined significantly from 2009 to 2010 (37-10%, p-value = 0.006 < 0.05) and differed significantly between age groups (p-value = 0.03 < 0.05). In Iceland, there was a peak in erythromycin resistance in 2008 (44%) and a substantial decrease in 2009 (5%). Although the prevalence of erythromycin and tetracycline resistance in the Faroe Islands and Iceland may be associated with antimicrobial use, sudden changes can occur with the introduction of new resistant clones.
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Affiliation(s)
- Marita D Magnussen
- Microbiological Department, Faroese Food- and Veterinary Authority, Tórshavn, Faroe Islands.,Medical Faculty, University of Iceland, Reykjavík, Iceland
| | - Shahin Gaini
- Department of Internal Medicine & Research Unit of the Medical Department, National Hospital of the Faroe Islands, Queen Alexandrines Teaching Hospital, Tórshavn, Faroe Islands.,Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.,University of Southern Denmark, Odense, Denmark
| | - Hannes Gislason
- Faculty of Science and Technology, University of the Faroe Islands, Tórshavn, Faroe Islands
| | - Karl G Kristinsson
- Medical Faculty, University of Iceland, Reykjavík, Iceland.,Department of Clinical Microbiology, Landspitali University Hospital, Reykjavík, Iceland
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14
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Hattori T, Minami M, Narita K, Nakata T, Itomi S, Kubota K, Oya T, Nishiyama H, Kato H, Yuasa N. Recurrent bacteremia with different strains of Streptococcus pyogenes in an immunocompromised child. J Infect Chemother 2016; 22:421-3. [PMID: 26846458 DOI: 10.1016/j.jiac.2015.12.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 12/16/2015] [Accepted: 12/25/2015] [Indexed: 10/22/2022]
Abstract
We report an immunocompromised child who experienced two episodes of bacteremia due to Streptococcus pyogenes. Random amplification of polymorphic DNA profiles, emm genotypes, superantigen profiles, antimicrobial susceptibility, and resistance-related genes were investigated, and the results showed different profiles between the two isolates. This is the first report describing recurrent bacteremia caused by different strains of S. pyogenes.
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Affiliation(s)
- Takuya Hattori
- Department of Clinical Laboratory, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
| | - Masaaki Minami
- Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kotaro Narita
- Department of Pediatrics, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
| | - Tomohiko Nakata
- Department of Pediatrics, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
| | - Seiko Itomi
- Department of Pediatrics, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
| | - Kinya Kubota
- Department of Pediatric Cardiology, Social Insurance Chukyo Hospital, Nagoya, Japan
| | - Teruaki Oya
- Department of Clinical Laboratory, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
| | - Hideki Nishiyama
- Department of Clinical Laboratory, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
| | - Hideki Kato
- Department of Clinical Laboratory, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
| | - Norihiro Yuasa
- Department of Clinical Laboratory, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan
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15
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Chazan B, Raz R, Edelstein H, Kennes Y, Gal V, Colodner R. Susceptibility of Group A Streptococcus to Antimicrobial Agents in Northern Israel: A Surveillance Study. Microb Drug Resist 2015; 21:551-5. [PMID: 26430943 DOI: 10.1089/mdr.2015.0040] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Resistant pathogens are an increasing threat affecting millions of people globally. More complicated patients are presented with pathogens harboring new resistance mechanisms, while the pipeline of new antimicrobials hardly proposes solutions. In such a scenario, more severely ill patients remain with no adequate treatment to offer. In addition, massive misuse of antimicrobials, including excessive length of treatment or wrong dosage, also contributes to increasing the rate of pathogens resistance to antimicrobials. Isolation of Streptococcus pyogenes (Group A Streptococcus-GAS) is the main indication for antibiotic treatment to patients diagnosed with acute tonsillitis. Hence, GAS resistance to antibiotics requires periodic monitoring. OBJECTIVES To assess susceptibility rates of GAS to penicillin, macrolides, clindamycin, and tetracycline in northern Israel and to compare the findings to the high antimicrobial susceptibility of GAS isolates reported in the same region in 2004 and to other geographical areas. METHODS Throat samples from 300 outpatients were collected and cultured at the regional laboratory of Emek Medical Center during September to October 2011. RESULTS In 300 samples, the susceptibility rates of GAS to penicillin, erythromycin, azithromycin, clindamycin, and tetracycline in northern Israel still remain very high. CONCLUSIONS Continuous control of antimicrobials usage and periodic surveillance of susceptibility rates, together with educational programs and appropriate and targeted treatment protocols, are essential and highly recommended to keep these high susceptibility rates for as long as possible.
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Affiliation(s)
- Bibiana Chazan
- 1 Infectious Diseases Unit, Emek Medical Center , Afula, Israel .,2 Rappaport Faculty of Medicine, Technion , Haifa, Israel
| | - Raul Raz
- 1 Infectious Diseases Unit, Emek Medical Center , Afula, Israel .,2 Rappaport Faculty of Medicine, Technion , Haifa, Israel
| | - Hana Edelstein
- 1 Infectious Diseases Unit, Emek Medical Center , Afula, Israel
| | - Yoram Kennes
- 3 Microbiology Laboratory, Emek Medical Center , Afula, Israel
| | - Vered Gal
- 3 Microbiology Laboratory, Emek Medical Center , Afula, Israel
| | - Raul Colodner
- 2 Rappaport Faculty of Medicine, Technion , Haifa, Israel .,3 Microbiology Laboratory, Emek Medical Center , Afula, Israel
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16
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Silva-Costa C, Friães A, Ramirez M, Melo-Cristino J. Macrolide-resistant Streptococcus pyogenes: prevalence and treatment strategies. Expert Rev Anti Infect Ther 2015; 13:615-28. [PMID: 25746210 DOI: 10.1586/14787210.2015.1023292] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Although penicillin remains the first-choice treatment for Streptococcus pyogenes infection, macrolides are important alternatives for allergic patients and lincosamides are recommended together with β-lactams in invasive infections. S. pyogenes may exhibit macrolide resistance because of active efflux (mef genes) or target modification (erm genes), the latter conferring cross resistance to lincosamides and streptogramin B. Worldwide, resistance is restricted to a limited number of genetic lineages, despite resistance genes being encoded on mobile genetic elements. For reasons that are not completely clear, resistance and the associated phenotypes are highly variable across countries. Although resistance remains high in several countries, particularly in Asia, an overall decreasing trend of resistance has been noted in recent years, mostly in Europe. This decrease is not always accompanied by declines in macrolide consumption, suggesting significant roles of other factors in determining the dynamics of macrolide-resistant clones. Continued surveillance is needed to obtain further insights into the forces governing macrolide resistance in S. pyogenes.
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Affiliation(s)
- Catarina Silva-Costa
- Faculdade de Medicina, Instituto de Microbiologia, Instituto de Medicina Molecular, Universidade de Lisboa, Av. Prof. Egas Moniz, PT 1649-028 Lisboa, Portugal
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17
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Zhou W, Jiang YM, Wang HJ, Kuang LH, Hu ZQ, Shi H, Shu M, Wan CM. Erythromycin-resistant genes in group A β-haemolytic Streptococci in Chengdu, Southwestern China. Indian J Med Microbiol 2014; 32:290-3. [DOI: 10.4103/0255-0857.136568] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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18
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Disease manifestations and pathogenic mechanisms of Group A Streptococcus. Clin Microbiol Rev 2014. [PMID: 24696436 DOI: 10.1128/cmr.00101-13)] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority.
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19
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Walker MJ, Barnett TC, McArthur JD, Cole JN, Gillen CM, Henningham A, Sriprakash KS, Sanderson-Smith ML, Nizet V. Disease manifestations and pathogenic mechanisms of Group A Streptococcus. Clin Microbiol Rev 2014; 27:264-301. [PMID: 24696436 PMCID: PMC3993104 DOI: 10.1128/cmr.00101-13] [Citation(s) in RCA: 609] [Impact Index Per Article: 55.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority.
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Affiliation(s)
- Mark J. Walker
- School of Chemistry and Molecular Biosciences and the Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia
| | - Timothy C. Barnett
- School of Chemistry and Molecular Biosciences and the Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia
| | - Jason D. McArthur
- School of Biological Sciences and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia
| | - Jason N. Cole
- School of Chemistry and Molecular Biosciences and the Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia
- Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA
| | - Christine M. Gillen
- School of Chemistry and Molecular Biosciences and the Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia
| | - Anna Henningham
- School of Chemistry and Molecular Biosciences and the Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia
- Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA
| | - K. S. Sriprakash
- QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia
| | - Martina L. Sanderson-Smith
- School of Biological Sciences and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia
| | - Victor Nizet
- Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA
- Rady Children's Hospital, San Diego, California, USA
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20
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Yang P, Peng X, Zhang D, Wu S, Liu Y, Cui S, Lu G, Duan W, Shi W, Liu S, Li J, Wang Q. Characteristics of group A Streptococcus strains circulating during scarlet fever epidemic, Beijing, China, 2011. Emerg Infect Dis 2013; 19:909-15. [PMID: 23735582 PMCID: PMC4816378 DOI: 10.3201/eid1906.121020] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Scarlet fever is one of a variety of diseases caused by group A Streptococcus (GAS). During 2011, a scarlet fever epidemic characterized by peak monthly incidence rates 2.9–6.7 times higher than those in 2006–2010 occurred in Beijing, China. During the epidemic, hospital-based enhanced surveillance for scarlet fever and pharyngitis was conducted to determine characteristics of circulating GAS strains. The surveillance identified 3,359 clinical cases of scarlet fever or pharyngitis. GAS was isolated from 647 of the patients; 76.4% of the strains were type emm12, and 17.1% were emm1. Almost all isolates harbored superantigens speC and ssa. All isolates were susceptible to penicillin, and resistance rates were 96.1% to erythromycin, 93.7% to tetracycline, and 79.4% to clindamycin. Because emm12 type GAS is not the predominant type in other countries, wider surveillance for the possible spread of emm12 type GAS from China to other countries is warranted.
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Affiliation(s)
- Peng Yang
- Beijing Center for Disease Prevention and Control, School of Public Health and Family Medicine, Capital Medical University, Beijing, China
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21
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Liu YM, Zhao JZ, Li BB, Yang JY, Dong XG, Zhang JJ, Cao B. A report on the first outbreak of a single clone group A Streptococcus (emm-type 89) tonsillopharyngitis in China. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2013; 47:542-5. [PMID: 24113070 DOI: 10.1016/j.jmii.2013.08.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2013] [Revised: 07/15/2013] [Accepted: 08/08/2013] [Indexed: 10/26/2022]
Abstract
In 2012, 28 out of 140 staff working for a film crew in a Beijing movie and television base experienced a sudden onset of fever, sore throat, and/or tiredness, headache within the 24 hour period of July 26-27. All of the patients visited the hospital and were diagnosed as having tonsillopharyngitis. On July 28, 2012, a team of Centers for Disease Control and Prevention staff arrived and initiated an outbreak investigation. Pharyngeal swabs were obtained from patients for microbiologic analysis. All isolates of the outbreak were analyzed for toxin-genes and drug-resistance genes by polymerase chain reaction, and were performed for the emm typing and pulsed-field gel electrophoresis typing. On July 30, 2012, Group A Streptococcus was isolated from eight of the 16 throat swab specimens obtained on site. These isolates were found to have the same genotype emm 89. This is the first report to identify Group A Streptococcus emm type-89 as a cause of tonsillopharyngitis in Beijing, China.
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Affiliation(s)
- Ying-Mei Liu
- Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Jian-Zhong Zhao
- Center for Disease Control and Prevention, Fengtai, Beijing, People's Republic of China
| | - Bin-Bin Li
- Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Jun-Yong Yang
- Center for Disease Control and Prevention, Fengtai, Beijing, People's Republic of China
| | - Xiao-Gen Dong
- Center for Disease Control and Prevention, Fengtai, Beijing, People's Republic of China
| | - Jian-Jun Zhang
- Center for Disease Control and Prevention, Fengtai, Beijing, People's Republic of China.
| | - Bin Cao
- Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.
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22
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Liang Y, Liu X, Chang H, Ji L, Huang G, Fu Z, Zheng Y, Wang L, Li C, Shen Y, Yu S, Yao K, Ma L, Shen X, Yang Y. Epidemiological and molecular characteristics of clinical isolates of Streptococcus pyogenes collected between 2005 and 2008 from Chinese children. J Med Microbiol 2012; 61:975-983. [PMID: 22442290 DOI: 10.1099/jmm.0.042309-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- Yunmei Liang
- Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, PR China
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
| | - Xiaorong Liu
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
| | - Hesheng Chang
- Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100020, PR China
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
| | - Lili Ji
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
| | - Guoying Huang
- Children’s Hospital of Fudan University, Shanghai 200040, PR China
| | - Zhou Fu
- Chongqing Children’s Hospital Affiliated to Chongqing Medical University, Chongqing 400015, PR China
| | - Yuejie Zheng
- Shenzhen Children’s Hospital, Shenzhen 518035, PR China
| | - Libo Wang
- Children’s Hospital of Fudan University, Shanghai 200040, PR China
| | - Chengrong Li
- Shenzhen Children’s Hospital, Shenzhen 518035, PR China
| | - Ying Shen
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
| | - Sangjie Yu
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
| | - Kaihu Yao
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
| | - Lin Ma
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
| | - Xuzhuang Shen
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
| | - Yonghong Yang
- Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing 100045, PR China
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23
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Wong SS, Yuen KY. Streptococcus pyogenes and re-emergence of scarlet fever as a public health problem. Emerg Microbes Infect 2012; 1:e2. [PMID: 26038416 PMCID: PMC3630912 DOI: 10.1038/emi.2012.9] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 04/16/2012] [Indexed: 11/09/2022]
Abstract
Explosive outbreaks of infectious diseases occasionally occur without immediately obvious epidemiological or microbiological explanations. Plague, cholera and Streptococcus pyogenes infection are some of the epidemic-prone bacterial infections. Besides epidemiological and conventional microbiological methods, the next-generation gene sequencing technology permits prompt detection of genomic and transcriptomic profiles associated with invasive phenotypes. Horizontal gene transfer due to mobile genetic elements carrying virulence factors and antimicrobial resistance, or mutations associated with the two component CovRS operon are important bacterial factors conferring survival advantage or invasiveness. The high incidence of scarlet fever in children less than 10 years old suggests that the lack of protective immunity is an important host factor. A high population density, overcrowded living environment and a low yearly rainfall are environmental factors contributing to outbreak development. Inappropriate antibiotic use is not only ineffective for treatment, but may actually drive an epidemic caused by drug-resistant strains and worsen patient outcomes by increasing the bacterial density at the site of infection and inducing toxin production. Surveillance of severe S. pyogenes infection is important because it can complicate concurrent chickenpox and influenza. Concomitant outbreaks of these two latter infections with a highly virulent and drug-resistant S. pyogenes strain can be disastrous.
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Affiliation(s)
- Samson Sy Wong
- Department of Microbiology, Research Centre for Infection and Immunology, Faculty of Medicine, The University of Hong Kong , Hong Kong, China
| | - Kwok-Yung Yuen
- Department of Microbiology, Research Centre for Infection and Immunology, Faculty of Medicine, The University of Hong Kong , Hong Kong, China
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Molecular analysis of Streptococcus pyogenes strains isolated from Chinese children with pharyngitis. Diagn Microbiol Infect Dis 2011; 69:117-22. [PMID: 21251553 DOI: 10.1016/j.diagmicrobio.2010.09.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2010] [Revised: 09/15/2010] [Accepted: 09/16/2010] [Indexed: 11/20/2022]
Abstract
Streptococcus pyogenes is an important gram-positive bacterial pathogen that causes various human diseases, of which streptococcal pharyngitis is the most common. In this work, a total of 185 S. pyogenes isolated from Chinese children with pharyngitis was analyzed by superantigen (SAg) genes, emm genotyping, and pulsed-field gel electrophoresis (PFGE). Fifty-eight (31.4%) isolates were also typed by multilocus sequence typing (MLST). The results indicate that most of the emm1 isolates possessed speA (88.5%) and speJ (83.6%), and few isolates possessed speI gene (13.1%). In contrast, none of the emm12-type isolates possessed speJ; few isolates possessed speA (5.2%); and most of the isolates possessed speI (91.7%). PFGE analysis revealed 25 different clusters, and MLST was performed for 2 predominant emm-type isolates; emm12 isolates belonged to ST36 while emm1 isolates belonged to ST28. As far as this collection is concerned, emm1 and emm12 are the prevalent genotypes among S. pyogenes strains associated with children's pharyngitis in China. Most of the pharyngitis strains can be covered by a 26-valent vaccine. A strong correspondence is found only in the direction of emm type for both SAg profiles and PFGE types but not in the reverse direction.
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Farmand S, Henneke P, Hufnagel M, Berner R. Significant decline in the erythromycin resistance of group A streptococcus isolates at a German paediatric tertiary care centre. Eur J Clin Microbiol Infect Dis 2011; 31:707-10. [DOI: 10.1007/s10096-011-1362-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2011] [Accepted: 07/14/2011] [Indexed: 11/25/2022]
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Lubell Y, Turner P, Ashley EA, White NJ. Susceptibility of bacterial isolates from community-acquired infections in sub-Saharan Africa and Asia to macrolide antibiotics. Trop Med Int Health 2011; 16:1192-205. [PMID: 21740488 DOI: 10.1111/j.1365-3156.2011.02837.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
OBJECTIVE To review the literature on the susceptibility of common community pathogens in sub-Saharan Africa and Asia to the macrolide antibiotics. METHODS Inclusion criteria required that isolates were collected since 2004 to ensure results were of contemporary relevance. The data were aggregated by region, age group and sterility of site of culture sample. RESULTS A total of 51 studies were identified, which reported the macrolide antimicrobial susceptibilities of common bacterial pathogens isolated since 2004. In general, there was less macrolide resistance in African than in Asian isolates. Most African studies reported high levels of macrolide susceptibility in Streptococcus pneumoniae, whereas most Chinese studies reported high levels of resistance. There was very little information available for Gram-negative organisms. CONCLUSIONS Susceptibility of the pneumococcus to macrolides in SSA remains high in many areas, and good activity of azithromycin has been shown against Salmonellae spp. in Asia. In urban areas where high antibiotic consumption is prevalent, there was evidence of increased resistance to macrolides. However, there is no information on susceptibility from large areas in both continents.
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Affiliation(s)
- Yoel Lubell
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Affiliation(s)
- Michael R Wessels
- Division of Infectious Diseases, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.
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28
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Kouidhi B, Zmantar T, Hentati H, Najjari F, Mahdouni K, Bakhrouf A. Molecular investigation of macrolide and Tetracycline resistances in oral bacteria isolated from Tunisian children. Arch Oral Biol 2010; 56:127-35. [PMID: 20950793 DOI: 10.1016/j.archoralbio.2010.09.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2010] [Revised: 09/03/2010] [Accepted: 09/13/2010] [Indexed: 11/29/2022]
Abstract
OBJECTIVE This study aims to investigate the antibiotic susceptibility of strains isolated from the oral cavity of Tunisian children. DESIGN Strains were isolated from the oral cavity of Tunisian children (60 caries-actives and 30 caries-free). Molecular characterization was assessed by PCR assay to detect erythromycin methylase gene (ermB), macrolide efflux (mefI) and tetracycline resistance genes (tetM and tetO). RESULTS A total of 21 species were isolated and identified. Antimicrobial susceptibility revealed that the resistance rate to antibiotics was as follow: erythromycin (22%), tetracycline (15.6%), cefotaxim, (7.3%), trimethoprim-sulfamethoxazol (37.6%), nitrofurantoine (2.8%), pristinamycin (17.4%), quinupristin-dalfopristin (15.6%), and rifampicin (3.7%). The majority of mefI positive strains (31.2%) were isolated from the carious children (n=34) in comparison with 8.25% from the control group (n=9). In addition, frequency of strains caring resistance genes were as follow: 12.84% for ermB, 9.17% for tetM and 27.52% for tetO from the carious children in comparison to 0.092%, 3.67% and 3.67% from the caries free group respectively. CONCLUSION Multi-resistance strains towards macrolides and tetracycline were recorded. The majority of strains carrying antibiotics resistance genes were isolated from the caries active children. The presence of multi-resistant bacteria in the oral cavity can be the major cause of antibiotic prophylaxis failure in dental practise.
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Affiliation(s)
- Bochra Kouidhi
- Laboratoire d'Analyses, Traitement et Valorisation des Polluants de l'Environnement et des Produits, Faculté de Pharmacie de Monastir, Biologie Clinique, Rue Avicenne, 5000 Monastir, Tunisie.
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Koh E, Kim S. Decline in Erythromycin Resistance in Group A Streptococci from Acute Pharyngitis due to Changes in the emm Genotypes Rather Than Restriction of Antibiotic Use. Ann Lab Med 2010; 30:485-90. [DOI: 10.3343/kjlm.2010.30.5.485] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Affiliation(s)
- Eunha Koh
- Department of Laboratory Medicine, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Sciences, Jinju, Korea
| | - Sunjoo Kim
- Department of Laboratory Medicine, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Sciences, Jinju, Korea
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Gao W, Cheng H, Hu F, Li J, Wang L, Yang G, Xu L, Zheng X. The evolution of Helicobacter pylori antibiotics resistance over 10 years in Beijing, China. Helicobacter 2010; 15:460-6. [PMID: 21083752 DOI: 10.1111/j.1523-5378.2010.00788.x] [Citation(s) in RCA: 100] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVES To evaluate Helicobacter pylori antibiotics resistance evolution from 2000 to 2009 to amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin and moxifloxacin in Beijing, China. METHODS A total of 374 H. pylori strains isolated from 374 subjects who had undergone upper gastrointestinal endoscopy from 2000 to 2009 were collected and examined by E-test method for antibiotics susceptibility. RESULTS The average antibiotics resistance rates were 0.3% (amoxicillin), 37.2% (clarithromycin), 63.9% (metronidazole), 1.2% (tetracycline), 50.3% (levofloxacin) and 61.9% (moxifloxacin). Overall resistance to clarithromycin, metronidazole, and fluoroquinolone increased annually (from 14.8 to 65.4%, 38.9 to 78.8%, and 27.1 to 63.5%, in 2000 or 2006-2007 to 2009, respectively). The secondary resistance rates were much higher than primary rates to these antibiotics, which also increased annually in recent 10 years. CONCLUSIONS The trend of clarithromycin, metronidazole, and fluoroquinolone resistance of H. pylori increased over time and the resistance to amoxicillin and tetracycline was infrequent and stable in Beijing. Clarithromycin, metronidazole, and fluoroquinolone should be used with caution for H. pylori eradication treatment.
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Affiliation(s)
- Wen Gao
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
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Bugrysheva JV, Scott JR. Regulation of virulence gene expression in Streptococcus pyogenes: determinants of differential mRNA decay. RNA Biol 2010; 7:569-72. [PMID: 21037420 DOI: 10.4161/rna.7.5.13097] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Differential mRNA stability is an important mechanism for regulation of virulence factors in Streptococcus pyogenes (group A streptococcus, GAS), a serious and prevalent human pathogen. We have described 2 Classes of mRNA in GAS that are distinguishable by 1) stability in the stationary phase of growth, 2) kinetics of decay in exponential phase, and 3) effect of depletion of RNases J1 and J2 and polynucleotide phosphorylase (PNPase) on decay in exponential phase. We discuss features of the structure of an mRNA that appear to be important for determining the Class to which it belongs and present a model to explain differential mRNA decay.
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Affiliation(s)
- Julia V Bugrysheva
- Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA
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Feng L, Lin H, Ma Y, Yang Y, Zheng Y, Fu Z, Yu S, Yao K, Shen X. Macrolide-resistant Streptococcus pyogenes from Chinese pediatric patients in association with Tn916 transposons family over a 16-year period. Diagn Microbiol Infect Dis 2010; 67:369-75. [DOI: 10.1016/j.diagmicrobio.2010.03.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2009] [Revised: 03/16/2010] [Accepted: 03/30/2010] [Indexed: 12/30/2022]
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Korppi M. Macrolide resistance in Streptococcus pyogenes: a marker of an overuse of macrolides. Pediatr Pulmonol 2009; 44:1246-7; author reply 1248-9. [PMID: 19911358 DOI: 10.1002/ppul.21087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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