|
1
|
Li C, He L, Wang A, Chen S, Fu P, Wang C. Antibiotic resistance and virulence genes in Helicobacter pylori strains isolated from children in Shanghai, China (2019-2022). Int J Med Microbiol 2024; 315:151622. [PMID: 38776570 DOI: 10.1016/j.ijmm.2024.151622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 05/07/2024] [Accepted: 05/20/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND The increasing prevalence of antibiotic-resistant Helicobacter pylori strains poses a significant threat to children's health. This study investigated antibiotic resistance rates in Helicobacter pylori strains isolated from children in Shanghai and analyzed the presence of virulence genes in these strains. METHODS We obtained 201 Helicobacter pylori strains from pediatric patients with upper gastrointestinal symptoms who underwent gastrointestinal endoscopy between 2019 and 2022. Subsequently, we performed antibiotic susceptibility tests and virulence gene PCR assays on these strains. RESULTS Helicobacter pylori resistance rates of 45.8%, 15.4%, 1.0%, and 2.5% were detected for metronidazole, clarithromycin, amoxicillin, and levofloxacin, respectively. Among all isolates, 64.7% exhibited resistance to at least one antibiotic. Resistance to metronidazole and clarithromycin increased from 2019 to 2022. The predominant vacA gene subtype was vacA s1a/m2. The prevalence of vacA m2 and dupA exhibited an upward trend, while oipA presented a decreasing trend from 2019 to 2022. The prevalence of dupA was significantly higher in gastritis than peptic ulcer disease, and in non-treatment compared to treatment groups. CONCLUSIONS Helicobacter pylori antibiotic resistance remains high in children and has risen in recent years. Therefore, the increasing use of metronidazole and clarithromycin requires increased monitoring in children. No association was observed between antibiotic resistance and virulence gene phenotypes.
Collapse
Affiliation(s)
- Chunling Li
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Leiyan He
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Aimin Wang
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Saige Chen
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Pan Fu
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Nosocomial Infection Control Department, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Chuanqing Wang
- Lab of Microbiology, Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Nosocomial Infection Control Department, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
| |
Collapse
|
|
2
|
Gong Y, Zhai K, Sun L, He L, Wang H, Guo Y, Zhang J. RdxA Diversity and Mutations Associated with Metronidazole Resistance of Helicobacter pylori. Microbiol Spectr 2023; 11:e0390322. [PMID: 36943041 PMCID: PMC10100817 DOI: 10.1128/spectrum.03903-22] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 02/15/2023] [Indexed: 03/23/2023] Open
Abstract
Metronidazole (MNZ) is administered as first-line antibiotic for Helicobacter pylori eradication therapy; however, increasing resistance to MNZ impaired the efficacy. Increasing the dose of MNZ was recommended to overcome low-level resistance, but it was difficult to determine MNZ resistance level simply based on the rdxA gene mutation. In this study, the rdxA sequences of 511 clinical H. pylori strains were analyzed to assess the genotypes associated with MNZ resistance. We observed that the prevalences of rdxA sequences with missense, nonsense, and frameshift mutations were 70.25, 11.35, and 17.03%, respectively. Regarding the amino acid substitutions, T31E, H53R, D59N, L62V, S88P, G98S/N, R131K, and V172I were present in most strains regardless of the resistance phenotype. The correlation analysis showed R16H/C, Y47C, A67V/T, and V204I substitutions were associated with MNZ resistance. The mutation resulting in RdxA truncation was observed in 36.29% of the resistant strains, and 83.45% of these strains displayed high-level MNZ resistance (MIC > 256 μg/mL). Moreover, all strains with truncated mutation positions before amino acid 70 expressed high-level MNZ resistance. Our results indicated that most amino acid mutations probably contributed to the sequence diversity of RdxA, while R16H/C, Y47C, A67V/T, and V204I were potentially helpful to identify resistant strains. Although it was difficult to determine the mutations associated with MNZ resistance, the prediction of high-level resistance based on truncated characteristics of RdxA might be an important approach, which can effectively avoid H. pylori eradication therapy with unreasonable of MNZ dose increases for patients with high-level drug resistance. IMPORTANCE The increasing resistance to metronidazole impaired the efficacy of Helicobacter pylori eradication, and increasing the dose of metronidazole was recommended to overcome low-level resistance. For patients infected with highly resistant strains, the current empirical treatments, which generally used metronidazole in double doses or more, appeared impossibly to overcome the resistance and would only increase the incidence of adverse effects. Our results indicated that high-level metronidazole resistance was predominant, and almost half of the patients with high-level drug resistance could avoid usage of metronidazole based on the truncated mutations of RdxA sequences, which can effectively avoid H. pylori eradication therapy with unreasonable increases in the metronidazole dose.
Collapse
Affiliation(s)
- Yanan Gong
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Kangle Zhai
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lu Sun
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lihua He
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Hairui Wang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Yahui Guo
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jianzhong Zhang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| |
Collapse
|
|
3
|
Prevalence, Virulence Genes, Phylogenetic Analysis, and Antimicrobial Resistance Profile of Helicobacter Species in Chicken Meat and Their Associated Environment at Retail Shops in Egypt. Foods 2022; 11:foods11131890. [PMID: 35804706 PMCID: PMC9265416 DOI: 10.3390/foods11131890] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 11/17/2022] Open
Abstract
Helicobacter pylori (H. pylori) and Helicobacter pullorum (H. pullorum) are frequently reported pathogens in humans and poultry, respectively. Nevertheless, the source of H. pylori is still unclear. This study aimed to detect Helicobacter spp. in chicken carcasses and to assess the antibiogram and the virulence genes of Helicobacter isolates. Three hundred chicken meat samples (100 each of chicken breast, liver, and gizzard), besides 60 swab samples from chicken processing surfaces, were collected from retail shops in Qalyubia Governorate, Egypt, and examined for the prevalence of H. pylori and H. pullorum. The 16S rRNA of three H. pylori and two H. pullorum isolates were sequenced to determine the genetic relationship between these two Helicobacter spp. Of the 300 chicken samples tested, 16 (5.33%) and 14 (4.67%) were positive for H. pylori and H. pullorum, respectively. Multiplex PCR revealed that the virulence genes vacuolating cytotoxin A (vacA)s1, cytotoxin-associated gene A (cagA), and restriction endonuclease-replacing gene A (hrgA) were detected in 66.7%, 77.8%, and 100% of H. pylori strains tested, respectively. H. pylori showed the highest resistance for clarithromycin, while H. pullorum exhibited the highest resistance towards erythromycin and ciprofloxacin. The study concluded that the chicken meat and giblets are potential sources of the virulent and antimicrobial-resistant strains of H. pylori of human origin.
Collapse
|
|
4
|
Flavodoxins as Novel Therapeutic Targets against Helicobacter pylori and Other Gastric Pathogens. Int J Mol Sci 2020; 21:ijms21051881. [PMID: 32164177 PMCID: PMC7084853 DOI: 10.3390/ijms21051881] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/04/2020] [Accepted: 03/06/2020] [Indexed: 02/06/2023] Open
Abstract
Flavodoxins are small soluble electron transfer proteins widely present in bacteria and absent in vertebrates. Flavodoxins participate in different metabolic pathways and, in some bacteria, they have been shown to be essential proteins representing promising therapeutic targets to fight bacterial infections. Using purified flavodoxin and chemical libraries, leads can be identified that block flavodoxin function and act as bactericidal molecules, as it has been demonstrated for Helicobacter pylori (Hp), the most prevalent human gastric pathogen. Increasing antimicrobial resistance by this bacterium has led current therapies to lose effectiveness, so alternative treatments are urgently required. Here, we summarize, with a focus on flavodoxin, opportunities for pharmacological intervention offered by the potential protein targets described for this bacterium and provide information on other gastrointestinal pathogens and also on bacteria from the gut microbiota that contain flavodoxin. The process of discovery and development of novel antimicrobials specific for Hp flavodoxin that is being carried out in our group is explained, as it can be extrapolated to the discovery of inhibitors specific for other gastric pathogens. The high specificity for Hp of the antimicrobials developed may be of help to reduce damage to the gut microbiota and to slow down the development of resistant Hp mutants.
Collapse
|
|
5
|
Chu A, Wang D, Guo Q, Lv Z, Yuan Y, Gong Y. Molecular detection of
H. pylori
antibiotic‐resistant genes and molecular docking analysis. FASEB J 2019; 34:610-618. [PMID: 31914672 DOI: 10.1096/fj.201900774r] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 11/04/2019] [Accepted: 11/04/2019] [Indexed: 12/23/2022]
Affiliation(s)
- Aining Chu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery the First Hospital of China Medical University Shenyang China
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department the First Hospital of China Medical University Shenyang China
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province the First Hospital of China Medical University Shenyang China
| | - Dan Wang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery the First Hospital of China Medical University Shenyang China
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department the First Hospital of China Medical University Shenyang China
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province the First Hospital of China Medical University Shenyang China
| | - Qianqian Guo
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery the First Hospital of China Medical University Shenyang China
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department the First Hospital of China Medical University Shenyang China
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province the First Hospital of China Medical University Shenyang China
| | - Zhi Lv
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery the First Hospital of China Medical University Shenyang China
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department the First Hospital of China Medical University Shenyang China
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province the First Hospital of China Medical University Shenyang China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery the First Hospital of China Medical University Shenyang China
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department the First Hospital of China Medical University Shenyang China
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province the First Hospital of China Medical University Shenyang China
| | - Yuehua Gong
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery the First Hospital of China Medical University Shenyang China
- Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department the First Hospital of China Medical University Shenyang China
- Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province the First Hospital of China Medical University Shenyang China
| |
Collapse
|
|
6
|
High Prevalence of Antibiotic Resistance in Iranian Helicobacter pylori Isolates: Importance of Functional and Mutational Analysis of Resistance Genes and Virulence Genotyping. J Clin Med 2019; 8:jcm8112004. [PMID: 31744181 PMCID: PMC6912791 DOI: 10.3390/jcm8112004] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/11/2019] [Accepted: 11/14/2019] [Indexed: 12/14/2022] Open
Abstract
The high prevalence of antibiotic resistance in Helicobacter pylori has become a great challenge in Iran. The genetic mutations that contribute to the resistance have yet to be precisely identified. This study aimed to investigate the prevalence of antibiotic resistance and virulence markers in Iranian H. pylori isolates and to analyze if there is any association between resistance and genotype. Antibiotic susceptibility patterns of 68 H. pylori isolates were investigated against metronidazole, clarithromycin, amoxicillin, rifampicin, ciprofloxacin, levofloxacin, and tetracycline by the agar dilution method. The frxA, rdxA, gyrA, gyrB, and 23S rRNA genes of the isolates were sequenced. The virulence genotypes were also determined using PCR. Metronidazole resistance was present in 82.4% of the isolates, followed by clarithromycin (33.8%), ciprofloxacin (33.8%), rifampicin (32.4%), amoxicillin (30.9%), levofloxacin (27.9%), and tetracycline (4.4%). Overall, 75% of the isolates were resistant to at least two antibiotics tested and considered as a multidrug resistance (MDR) phenotype. Most of the metronidazole-resistant isolates carried frameshift mutations in both frxA and rdxA genes, and premature termination occurred in positions Q5Stop and Q50Stop, respectively. Amino acid substitutions M191I, G208E, and V199A were predominantly found in gyrA gene of fluoroquinolone-resistant isolates. A2143G and C2195T mutations of 23S rRNA were found in four clarithromycin-resistant isolates. Interestingly, significant associations were found between resistance to metronidazole (MNZ) and cagA-, sabA-, and dupA-positive genotypes, with p = 0.0002, p = 0.0001, and p = 0.0001, respectively. Furthermore, a significant association was found between oipA “on” status and resistance to amoxicillin (AMX) (p = 0.02). The prevalence of H. pylori antibiotic resistance is high in our region, particularly that of metronidazole, clarithromycin, ciprofloxacin, and MDR. Simultaneous screening of virulence and resistance genotypes can help clinicians to choose the appropriate therapeutic regime against H. pylori infection.
Collapse
|
|
7
|
Smith S, Fowora M, Pellicano R. Infections with Helicobacter pylori and challenges encountered in Africa. World J Gastroenterol 2019; 25:3183-3195. [PMID: 31333310 PMCID: PMC6626727 DOI: 10.3748/wjg.v25.i25.3183] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 05/02/2019] [Accepted: 06/01/2019] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is the causative agent of gastritis, peptic ulcer disease, mucosa associated lymphoid tissue lymphoma and gastric cancer (GC). While this bacterium infects 50% of the world’s population, in Africa its prevalence reach as high as 80% as the infection is acquired during childhood. Risk factors for H. pylori acquisition have been reported to be mainly due to overcrowding, to have infected siblings or parent and to unsafe water sources. Despite this high H. pylori prevalence there still does not exist an African guideline, equivalent to the Maastricht V/Florence Consensus Report of the European Helicobacter and Microbiota Study Group for the management of this infection. In this continent, although there is a paucity of epidemiologic data, a contrast between the high prevalence of H. pylori infection and the low incidence of GC has been reported. This phenomenon is the so-called “African Enigma” and it has been hypothesized that it could be explained by environmental, dietary and genetic factors. A heterogeneity of data both on diagnosis and on therapy have been published. In this context, it is evident that in several African countries the increasing rate of bacterial resistance, mainly to metronidazole and clarithromycin, requires continental guidelines to recommend the appropriate management of H. pylori. The aim of this manuscript is to review current literature on H. pylori infection in Africa, in terms of prevalence, risk factors, impact on human health, treatment and challenges encountered so as to proffer possible solutions to reduce H. pylori transmission in this continent.
Collapse
Affiliation(s)
- Stella Smith
- Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Lagos PMB 2013, Nigeria
| | - Muinah Fowora
- Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Lagos PMB 2013, Nigeria
| | | |
Collapse
|
|
8
|
Jaka H, Rüttgerodt N, Bohne W, Mueller A, Gross U, Kasang C, Mshana SE. Helicobacter pylori Mutations Conferring Resistance to Fluoroquinolones and Clarithromycin among Dyspeptic Patients Attending a Tertiary Hospital, Tanzania. Can J Gastroenterol Hepatol 2019; 2019:8481375. [PMID: 31355162 PMCID: PMC6634059 DOI: 10.1155/2019/8481375] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 05/06/2019] [Accepted: 06/19/2019] [Indexed: 02/07/2023] Open
Abstract
Objectives. Helicobacter pylori (H. pylori) isolates resistant to clarithromycin and quinolones are increasing worldwide. Data regarding the magnitude of H. pylori resistance are limited in developing countries. Here, we report the prevalence of mutations conferring resistance to clarithromycin and fluoroquinolones among dyspeptic patients attending a tertiary hospital, Tanzania. Methods. Between August 2014 and August 2016, patients undergoing upper gastrointestinal endoscopy at the Bugando Medical Centre were enrolled. Biopsies were taken for polymerase chain reaction (PCR) and sequencing to detect mutations conferring resistance to clarithromycin and fluoroquinolones. Results. A total of 208 nonrepetitive biopsies were examined of which 188 (90.4%) tested positive for H. pylori specific 23S rRNA PCR. Clarithromycin resistance mutations were detected in 54/188 (28.7%) of patients tested. The most frequently detected mutation was A2143G (30) followed by A2142G (20). Out of 131 nonrepetitive biopsies tested for fluoroquinolones resistance mutations, 77/131 (58.8%) were positive, with N87I (20) mutation being the most frequently detected mutation followed by A92T mutation which was detected in 16 samples. Conclusion. A significant proportion of dyspeptic patients attending tertiary hospital in Tanzania are infected with H. pylori strains harbouring clarithromycin or fluoroquinolones resistance mutations. Detection of more than 50% of strains with fluoroquinolones resistance mutations makes the H. pylori second line treatment questionable in our setting. There is a need of surveillance of H. pylori resistance patterns in Tanzania to provide data that can guide empirical treatment to reduce associated morbidity of H. pylori infections. The correlation between A92T fluoroquinolone mutation and phenotypic resistance requires further investigations.
Collapse
Affiliation(s)
- Hyasinta Jaka
- Department of Internal Medicine, Gastroenterology and Hepatology Unit, Catholic University of Health and Allied Sciences, P.O. Box 1464, Bugando, Mwanza, Tanzania
| | - Nele Rüttgerodt
- Tropenmedizin, Missionsärztliche Klinik, Salvatorstr. 7, 97074 Würzburg, Germany
| | | | - Andreas Mueller
- Tropenmedizin, Missionsärztliche Klinik, Salvatorstr. 7, 97074 Würzburg, Germany
| | - Uwe Gross
- Medical Microbiology, Goettingen, Germany
| | - Christa Kasang
- Medical Mission Institute, Hermann Schell Str. 7, 97074 Würzburg, Germany
| | - Stephen E. Mshana
- Department of Microbiology and Immunology, Catholic University of Health and Allied Sciences, P.O. Box 1464, Bugando, Mwanza, Tanzania
| |
Collapse
|
|
9
|
Assessment of Metronidazole and Clarithromycin Resistance Among Helicobacter pylori Isolates of Ahvaz (Southwest of Iran) During 2015 - 2016 by Phenotypic and Molecular Methods. Jundishapur J Microbiol 2019. [DOI: 10.5812/jjm.80156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
|
|
10
|
Chua EG, Debowski AW, Webberley KM, Peters F, Lamichhane B, Loke MF, Vadivelu J, Tay CY, Marshall BJ, Wise MJ. Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in Helicobacter pylori. Gastroenterol Rep (Oxf) 2019; 7:42-49. [PMID: 30792865 PMCID: PMC6375344 DOI: 10.1093/gastro/goy048] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 09/19/2018] [Accepted: 09/26/2018] [Indexed: 01/10/2023] Open
Abstract
Background Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection. Hence, the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals. Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H. pylori. However, metronidazole resistance can also arise in H. pylori strains expressing functional RdxA protein, suggesting that there are other mechanisms that may confer resistance to this drug. Methods We performed whole-genome sequencing on 121 H. pylori clinical strains, among which 73 were metronidazole-resistant. Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed. Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H. pylori. Results Resistance due to RdxA truncation was identified in 34% of metronidazole-resistant strains. Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance. These sites included R16H/C in RdxA, D85N in the inner-membrane protein RclC (HP0565), V265I in a biotin carboxylase protein (HP0370) and A51V/T in a putative threonylcarbamoyl–AMP synthase (HP0918). Conclusions Our approach identified new potential mechanisms for metronidazole resistance in H. pylori that merit further investigation.
Collapse
Affiliation(s)
- Eng-Guan Chua
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, Western Australia, Australia
| | - Aleksandra W Debowski
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, Western Australia, Australia.,School of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia
| | - K Mary Webberley
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, Western Australia, Australia
| | - Fanny Peters
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, Western Australia, Australia
| | - Binit Lamichhane
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, Western Australia, Australia
| | - Mun-Fai Loke
- Department of Medical Microbiology, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
| | - Jamuna Vadivelu
- Department of Medical Microbiology, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
| | - Chin-Yen Tay
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, Western Australia, Australia.,Shenzhen Dapeng New District Kuichong People Hospital, Shenzhen, Guangdong, China
| | - Barry J Marshall
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, Western Australia, Australia.,Shenzhen Dapeng New District Kuichong People Hospital, Shenzhen, Guangdong, China.,UM Marshall Centre, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia
| | - Michael J Wise
- The Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, Western Australia, Australia.,School of Computer Science and Software Engineering, University of Western Australia, Perth, Western Australia, Australia
| |
Collapse
|
|
11
|
Genotyping and antimicrobial resistance patterns of Helicobacter pylori in human and dogs associated with A2142G and A2143G point mutations in clarithromycin resistance. Microb Pathog 2018; 123:330-338. [PMID: 30031039 DOI: 10.1016/j.micpath.2018.07.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 07/12/2018] [Accepted: 07/13/2018] [Indexed: 02/07/2023]
|
|
12
|
Kabakambira JD, Hategeka C, Page C, Ntirenganya C, Dusabejambo V, Ndoli J, Ngabonziza F, Hale D, Bayingana C, Walker T. Efficacy of Helicobacter pylori eradication regimens in Rwanda: a randomized controlled trial. BMC Gastroenterol 2018; 18:134. [PMID: 30165823 PMCID: PMC6117961 DOI: 10.1186/s12876-018-0863-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 08/20/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Successful H. pylori treatment requires the knowledge of local antimicrobial resistance. Data on the efficacy of H. pylori eradication regimens available in sub-Saharan Africa are scant, hence the optimal treatment is unknown. Our goals were to determine the efficacy of available regimens in Rwanda as well as evaluate the effect of treatment on health-related quality of life (HRQoL) in patients undergoing esophagogastroduodenoscopy. METHODS This is a randomized controlled trial conducted from November 2015 to October 2016 at a tertiary hospital in Rwanda. Enrollees were 299 patients (35% male, age 42 ± 16 years (mean ± SD)) who had a positive modified rapid urease test on endoscopic biopsies. After a fecal antigen test (FAT) and HRQoL assessment by the Short Form Nepean Dyspepsia Index (SF-NDI) questionnaire, patients were randomized 1:1:1:1 to either a triple therapy combining omeprazole, amoxicillin and one of clarithromycin/ciprofloxacin/metronidazole or a quadruple therapy combining omeprazole, amoxicillin, ciprofloxacin and doxycycline. All therapies were given for a duration of 10 days. The outcome measures were the persistence of positive FAT (treatment failure) 4 to 6 weeks after treatment and change in HRQoL scores. RESULTS The treatment success rate was 80% in the total population and 78% in patients with a history of prior triple therapy. Significant improvement in HRQoL in the total group (HRQoL mean scores before and after treatment respectively: 76 ± 11 and 32 ± 11, p < 0.001) and the group with functional dyspepsia (HRQoL mean scores before and after treatment respectively: 73 ± 11 and 30 ± 9, P < 0.001) was observed across all treatment groups. Using clarithromycin based triple therapy (standard of care) as a reference, the group treated with metronidazole had worse HRQoL (p = 0.012) and had a trend towards worse treatment outcome (p = 0.086) compared to the ciprofloxacin based combination therapies. CONCLUSION Clarithromycin and ciprofloxacin based combination therapies are effective and safe to use alternatively for H. pylori eradication and improve HRQoL. Among the regimens studied, metronidazole based triple therapy is likely to be clinically inferior. TRIAL REGISTRATION The clinical trial was retrospectively registered ( PACTR201804003257400 ) with the Pan African Clinical Trial Registry database, on April 6th, 2018 in South Africa.
Collapse
Affiliation(s)
| | - Celestin Hategeka
- Centre for Health Services and Policy Research, School of Population and Public Health, Faculty of Medicine, University of British Columbia, Vancouver, BC Canada
- Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC Canada
| | - Cameron Page
- Department of Medicine, University Hospital of Brooklyn, New York, USA
| | | | | | - Jules Ndoli
- Butare University Teaching Hospital (CHUB), Huye, Rwanda
| | | | - DeVon Hale
- Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT USA
| | | | - Tim Walker
- Butare University Teaching Hospital (CHUB), Huye, Rwanda
- School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia
| |
Collapse
|
|
13
|
Sanneh B, Kebbeh A, Jallow HS, Camara Y, Mwamakamba LW, Ceesay IF, Barrow E, Sowe FO, Sambou SM, Baldeh I, Jallow A, Jorge Raul MA, Andremont A. Prevalence and risk factors for faecal carriage of Extended Spectrum β-lactamase producing Enterobacteriaceae among food handlers in lower basic schools in West Coast Region of The Gambia. PLoS One 2018; 13:e0200894. [PMID: 30102698 PMCID: PMC6089431 DOI: 10.1371/journal.pone.0200894] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Accepted: 07/05/2018] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The isolation of Extended spectrum βlactamase (ESBLs) producing Enterobacteriaceae among food handlers and their implication as sources of food borne outbreaks are a public health concern. This study seeks to investigate the prevalence of faecal carriage of these bacteria among food handlers in the West Coast Region of The Gambia. METHOD This study enrolled 600 participants from 60 Lower Basic Schools in West Coast Region of the country. Stool samples collected from the participants were presumptively screened for the ESBLs producing Enterobacteriaceae, using Drigalski agar, supplemented with 2mg/L cefotaxime. The bacterial colonies that grew on each Drigalski agar were tested for ESBL production by the double disk synergy test as recommended by Clinical and Laboratory Standard Institute (CLSI-2015). The confirmatory analysis for ESBL was determined as the zone of inhibition of cefotaxime and/or ceftazidime to ≥5mm from that of cefotaxime /clavulanicacid and/or ceftazidime/clavulanic acid. The presumptive screening of isolates for AmpC phenotypes was done by testing the organism against cefoxitin. The prevalence of the ESBL carriage was presented in percentages. The association of risk factors to the faecal carriage of ESBLs producing Enterobacteriaceae was performed by Pearson Chi-squared and Fishers Exact at (p ≤ 0.05). RESULT The prevalence of faecal carriage ESBL producing Enterobacteriaceae among food handlers was 5.0% (28/565). We found50% (14/28) and3.57% (1/28) ESBL producing bacteria were presumptive AmpC and carbapenemase resistance phenotype. Themost abundant ESBL producing Enterobacteriaceae were Klebsiella spp 32.1% (9/28) and Escherichia spp 28.6% (8/28). The use of antibiotics in the last 3 months was found to be significantly associated (P = 0.012) with the faecal carriage of ESBLs producing Enterobacteriaceae. CONCLUSION The prevalence of faecal carriage of ESBLs producing Enterobacteriaceae among food handlers in the Gambia is low. The history to use of the antibiotics in the last three months was found to be significantly associated with this prevalence. Therefore, the institution of a robust antimicrobial surveillance and treatment of patients with such infections are necessary to curb the spread of these multidrug resistant bacteria in the country. Rational prescription and usage of the antibiotics especially cephalosporin should be advocated both in public and private health facilities.
Collapse
Affiliation(s)
- Bakary Sanneh
- National Public Health Laboratories, Ministry of Health and Social Welfare, Kotu Layout, Kotu, The Gambia
- * E-mail:
| | - Abou Kebbeh
- National Public Health Laboratories, Ministry of Health and Social Welfare, Kotu Layout, Kotu, The Gambia
| | - Haruna S. Jallow
- National Public Health Laboratories, Ministry of Health and Social Welfare, Kotu Layout, Kotu, The Gambia
| | - Yaya Camara
- Epidemiology and disease Control Department, Ministry of Health and Social Welfare, Kotu Layout, Kotu, The Gambia
| | | | - Ida Fatou Ceesay
- National Public Health Laboratories, Ministry of Health and Social Welfare, Kotu Layout, Kotu, The Gambia
| | - Ebrima Barrow
- Medical Microbiology Laboratory, Edward Francis Small Teaching Hospital, Banjul, The Gambia
| | - Fatou O. Sowe
- Department of Health Promotion and Education, Ministry of Health and Social Welfare, Kotu Layout, Kotu, The Gambia
| | - Sana M. Sambou
- Epidemiology and disease Control Department, Ministry of Health and Social Welfare, Kotu Layout, Kotu, The Gambia
| | - Ignatius Baldeh
- National Public Health Laboratories, Ministry of Health and Social Welfare, Kotu Layout, Kotu, The Gambia
| | - Alpha Jallow
- World Health Organization, CountryOffice, The Gambia
| | | | | |
Collapse
|
|
14
|
Antibiotic use on paediatric inpatients in a teaching hospital in the Gambia, a retrospective study. Antimicrob Resist Infect Control 2018; 7:82. [PMID: 30026940 PMCID: PMC6048718 DOI: 10.1186/s13756-018-0380-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 07/11/2018] [Indexed: 02/04/2023] Open
Abstract
Background Antibiotics are useful but increasing resistance is a major problem. Our objectives were to assess antibiotic use and microbiology testing in hospitalized children in the Gambia. Methods We conducted a retrospective analysis of paediatric inpatient data at The Edward Francis Small Teaching Hospital in Banjul, The Gambia. We extracted relevant data from the admission folders of all patients (aged > 28 days to 15 years) admitted in 2015 (January–December), who received at least one antibiotic for 24 h. We also reviewed the microbiology laboratory record book to obtain separate data for the bacterial isolates and resistance test results of all the paediatric inpatients during the study period. Results Over half of the admitted patients received at least one antibiotic during admission (496/917) with a total consumption of 670.7 Days of Antibiotic Therapy/1000 Patient-Days. The clinical diagnoses included an infectious disease for 398/496, 80.2% of the patients on antibiotics, pneumonia being the most common (184/496, 37.1%). There were 51 clinically relevant bacterial isolates, Klebsiella species being the most common (12/51, 23.5%), mainly from urine (11/12, 91.7%). Antibiotic resistance was mainly to ampicillin (38/51, 74.5%), mainly reported as Coliform species 11/51, 21.6%. Conclusions More than half of the admitted patients received antibiotics. The reported antibiotic resistance was highest to the most commonly used antibiotics such as ampicillin. Efforts to maximize definitive antibiotic indication such as microbiological testing prior to start of antibiotics should be encouraged where possible for a more rational antibiotic use.
Collapse
|
|
15
|
Gonzalez-Hormazabal P, Musleh M, Escandar S, Valladares H, Lanzarini E, Castro VG, Jara L, Berger Z. Prevalence of clarithromycin resistance in Helicobacter pylori in Santiago, Chile, estimated by real-time PCR directly from gastric mucosa. BMC Gastroenterol 2018; 18:91. [PMID: 29925321 PMCID: PMC6011593 DOI: 10.1186/s12876-018-0820-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 06/07/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Current available treatments for Helicobacter pylori eradication are chosen according to local clarithromycin and metronidazole resistance prevalence. The aim of this study was to estimate, by means of molecular methods, both clarithromycin and metronidazole resistance in gastric mucosa from patients infected with H.pylori. METHODS A total of 191 DNA samples were analyzed. DNA was purified from gastric mucosa obtained from patients who underwent an upper gastrointestinal endoscopy at an university hospital from Santiago, Chile, between 2011 and 2014. H.pylori was detected by real-time PCR. A 5'exonuclease assay was developed to detect A2142G and A2143G mutations among H.pylori-positive samples. rdxA gene was sequenced in samples harboring A2142G and A2143G mutations in order to detect mutations that potentially confer dual clarithromycin and metronidazole resistance. RESULTS Ninety-three (93) out of 191 DNA samples obtained from gastric mucosa were H.pylori-positive (48.7%). Clarithromycin-resistance was detected in 29 samples (31.2% [95%CI 22.0-41.6%]). The sequencing of rdxA gene revealed that two samples harbored truncating mutations in rdxA, one sample had an in-frame deletion, and 11 had amino acid changes that likely cause metronidazole resistance. CONCLUSIONS We estimated a prevalence of clarithomycin-resistance of 31.8% in Santiago, Chile. Three of them harbor inactivating mutations in rdxA and 11 had missense mutations likely conferring metronidazole resistance. Our results require further confirmation. Nevertheless, they are significant as an initial approximation in re-evaluating the guidelines for H.pylori eradication currently used in Chile.
Collapse
Affiliation(s)
- Patricio Gonzalez-Hormazabal
- Human Genetics Program, Institute of Biomedical Sciences, School of Medicine, University of Chile, Av. Independencia 1027, 8380453, Santiago, CL, Chile.
| | - Maher Musleh
- Department of Gastroenterology, University of Chile Clinical Hospital, Santiago, Chile.,Department of Surgery, University of Chile Clinical Hospital, Santiago, Chile
| | - Susana Escandar
- Department of Gastroenterology, University of Chile Clinical Hospital, Santiago, Chile
| | - Hector Valladares
- Department of Gastroenterology, University of Chile Clinical Hospital, Santiago, Chile.,Department of Surgery, University of Chile Clinical Hospital, Santiago, Chile
| | - Enrique Lanzarini
- Department of Gastroenterology, University of Chile Clinical Hospital, Santiago, Chile.,Department of Surgery, University of Chile Clinical Hospital, Santiago, Chile
| | - V Gonzalo Castro
- Human Genetics Program, Institute of Biomedical Sciences, School of Medicine, University of Chile, Av. Independencia 1027, 8380453, Santiago, CL, Chile
| | - Lilian Jara
- Human Genetics Program, Institute of Biomedical Sciences, School of Medicine, University of Chile, Av. Independencia 1027, 8380453, Santiago, CL, Chile
| | - Zoltan Berger
- Department of Gastroenterology, University of Chile Clinical Hospital, Santiago, Chile
| |
Collapse
|
|
16
|
Jaka H, Rhee JA, Östlundh L, Smart L, Peck R, Mueller A, Kasang C, Mshana SE. The magnitude of antibiotic resistance to Helicobacter pylori in Africa and identified mutations which confer resistance to antibiotics: systematic review and meta-analysis. BMC Infect Dis 2018; 18:193. [PMID: 29699490 PMCID: PMC5921563 DOI: 10.1186/s12879-018-3099-4] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 04/17/2018] [Indexed: 12/19/2022] Open
Abstract
Background Worldwide Helicobacter pylori (H.pylori) treatment is of great challenge due to increased antibiotic resistance. The burden of H. pylori antibiotic resistance in Africa is high with unclear information regarding the real magnitude. This systematic review and meta-analysis was conducted to investigate the magnitude of H.pylori antibiotic resistance in Africa to gain insight of the extent of the problem among H.pylori naïve treatment patients. Method The search was performed in the academic databases, Embase, PubMed, Web of Science and Africa Wide Information. ProQuest Dissertation and Theses, Scopus, Ethos, Africa Index Medicus (WHO), BioMed Central Proceedings, BASE, British Library, Open grey, Library of Congress and the New York Academy of Grey Literature Report were additionally searched for grey literature. Published articles from Africa on H.pylori antibiotic resistance between 1986 and June 2017 were systematically reviewed to estimate the H. pylori extent of resistance to macrolides, quinolones, amoxicillin, tetracycline and metronidazole. Results In 26 articles a total of 2085 isolates were tested for metronidazole, 1530 for amoxicillin, 1277 for tetracycline, 1752 for clarithromycin and 823 for quinolones.The overall pooled proportion of H.pylori resistance to quinolones, clarithromycin, tetracycline, metronidazole and amoxicillin were: (17.4%, 95%CI 12.8 - 21.9), (29.2%, 95%CI:26.7-31.8), (48.7%, 95%CI: 44.5-52.9), (75.8%, 95% CI: 74.1-.77.4) and (72.6%, 95% CI: 68.6-76.6), respectively. The commonest mutation detected were A2143G (49/97) for clarithromycin, RdxA (41/56) for metronidazole and D87I (16/40) for quinolones. Conclusion Prevalence of metronidazole, clarithromycin, and amoxicillin resistance is high in developing world including Africa. This could impair the first line triple therapy of the H.pylori infection. There is a need of conducting surveillance of H.pylori susceptibility pattern in Africa for dual and triple resistance which can be used for the empirical treatment. Electronic supplementary material The online version of this article (10.1186/s12879-018-3099-4) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Hyasinta Jaka
- Gastroenterology and Hepatology Unit, Weill Bugando School of Medicine, Catholic University of Heath and Allied Sciences and Bugando Hospital Mwanza, P.O. BOX 1464, Mwanza, Tanzania.
| | | | - Linda Östlundh
- National Medical Library, United Arab Emirates University, Abu Dhabi, United Arab Emirates
| | - Luke Smart
- Cincinnati Children's Hospital Medical Centre, Cincinnati, Ohio, USA
| | - Robert Peck
- Gastroenterology and Hepatology Unit, Weill Bugando School of Medicine, Catholic University of Heath and Allied Sciences and Bugando Hospital Mwanza, P.O. BOX 1464, Mwanza, Tanzania.,Center for Global Health, Weill Cornell Medicine, New York, NY, USA
| | | | | | - Stephen E Mshana
- Department of Microbiology and Immunology, Weill Bugando School of Medicine, Catholic University of Heath and Allied Sciences Mwanza, Mwanza, Tanzania
| |
Collapse
|
|
17
|
Bachir M, Allem R, Tifrit A, Medjekane M, Drici AEM, Diaf M, Douidi KT. Primary antibiotic resistance and its relationship with cagA and vacA genes in Helicobacter pylori isolates from Algerian patients. Braz J Microbiol 2018; 49:544-551. [PMID: 29452847 PMCID: PMC6066781 DOI: 10.1016/j.bjm.2017.11.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 11/04/2017] [Accepted: 11/27/2017] [Indexed: 01/06/2023] Open
Abstract
The epidemiology of Helicobacter pylori resistance to antibiotics is poorly documented in Africa and especially in Algeria. The aim of our study was to determine the antibiotic resistance rates, as well as its possible relationship with VacA and CagA virulence markers of isolates from Algerian patients. One hundred and fifty one H. pylori isolate were obtained between 2012 and 2015 from 200 patients with upper abdominal pain. Antimicrobial susceptibility testing was performed for amoxicillin, clarithromycin, metronidazole, ciprofloxacin, rifampicin and tetracycline. Molecular identification of H. pylori and the detection of vacA and cagA genes were performed using specific primers. We found that H. pylori was present in 83.5% of collected biopsies, 54.9% of the samples were cagA positive, 49.67% were vacA s1m1, 18.30% were vacA s1m2 and 25.49% were vacA s2m2. Isolates were characterized by no resistance to amoxicillin (0%), tetracycline (0%), rifampicin (0%), a high rate of resistance to metronidazole (61.1%) and a lower rate of resistance to clarithromycin (22.8%) and ciprofloxacin (16.8%). No statically significant relationship was found between vagA and cagA genotypes and antibiotic resistance results (p > 0.5) except for the metronidazole, which had relation with the presence of cagA genotype (p = 0.001).
Collapse
Affiliation(s)
- Meryem Bachir
- Bioresources Laboratory, Department of Biology, Faculty of Natural and Life Sciences, Hassiba Ben Bouali University of Chlef (UHBC), Chlef, Algeria.
| | - Rachida Allem
- Bioresources Laboratory, Department of Biology, Faculty of Natural and Life Sciences, Hassiba Ben Bouali University of Chlef (UHBC), Chlef, Algeria
| | - Abedelkarim Tifrit
- Bioresources Laboratory, Department of Biology, Faculty of Natural and Life Sciences, Hassiba Ben Bouali University of Chlef (UHBC), Chlef, Algeria
| | - Meriem Medjekane
- Bioresources Laboratory, Department of Biology, Faculty of Natural and Life Sciences, Hassiba Ben Bouali University of Chlef (UHBC), Chlef, Algeria
| | - Amine El-Mokhtar Drici
- Laboratory of Molecular Microbiology, Proteomics and Health, Department of Biology, Faculty of Natural and Life Sciences, University of Djillali Liabes (UDL), Sidi-Bel-Abbes, Algeria
| | - Mustafa Diaf
- Laboratory of Molecular Microbiology, Proteomics and Health, Department of Biology, Faculty of Natural and Life Sciences, University of Djillali Liabes (UDL), Sidi-Bel-Abbes, Algeria
| | - Kara Turki Douidi
- Department of Gastroenterology, University Hospital Hassani Abedelkader, Sidi-Bel-Abbes, Sidi-Bel-Abbes, Algeria
| |
Collapse
|
|
18
|
Hamada M, Elbehiry A, Marzouk E, Moussa IM, Hessain AM, Alhaji JH, Heme HA, Zahran R, Abdeen E. Helicobacter pylori in a poultry slaughterhouse: Prevalence, genotyping and antibiotic resistance pattern. Saudi J Biol Sci 2018; 25:1072-1078. [PMID: 30174504 PMCID: PMC6117242 DOI: 10.1016/j.sjbs.2018.02.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 01/02/2018] [Accepted: 02/01/2018] [Indexed: 01/01/2023] Open
Abstract
Although Helicobacter pylori (H. pylori) is a highly significant pathogen, its source remains unclear. Many people consume chicken daily as a source of animal protein worldwide; thus, hygienic methods of supplying chickens for consumption are critical for public health. Therefore, our study examined the distribution of the glmM (ureC), babA2, vacA and cagA virulence genes in H. pylori strains in chicken meat and giblets (gizzards and livers) and the resistance of the strains to various antibiotics. Ninety chicken meat, gizzard and liver samples were obtained from a semi-automatic abattoir in Sadat City, Egypt, and were cultured and preliminarily analyzed using biochemical tests. The presence of the ureC, babA2, vacA and cagA genotypes was tested for in samples positive for H. pylori by multiplex polymerase chain reaction (Multiplex-PCR). The resistance of H. pylori to various antimicrobial drugs was tested using the disc diffusion method. In total, 7 of the 90 chicken samples were positive for H. pylori (7.78%); in 3/7 (42.85%) samples, the bacteria were found in the chicken liver, while the bacteria were found in the meat in 2/7 (28.57%) and in the gizzard in 2/7 (28.57%) samples. The total prevalence of both the ureC and babA2 genes in the isolated H. pylori strains was 100%, while the prevalence of the vacA and cagA genes was 57.1% and 42.9%, respectively. The resistance of H. pylori to the antibiotics utilized in our study was 100% for streptomycin; 85.7% for amoxicillin and penicillin; 71.4% for oxytetracycline, nalidixic acid and ampicillin; 57.1% for sulfamethoxazole and erythromycin; and 42.9% for neomycin, chloramphenicol and norfloxacin. In conclusion, the chicken meat and giblets were tainted by H. pylori, with a higher occurrence of the ureC, babA2, vacA and cagA genotypes. Future investigations should investigate the resistance of H. pylori to various antimicrobial agents in Egypt.
Collapse
Affiliation(s)
- Mohamed Hamada
- Department of Food Hygiene & Control, Faculty of Veterinary Medicine, Sadat City University, Egypt
| | - Ayman Elbehiry
- Department of Bacteriology, Mycology and Immunology, Faculty of Veterinary Medicine, Sadat City University, Egypt.,Department of Public Health, College of Public Health and Health Informatics, Qassim University, Saudi Arabia
| | - Eman Marzouk
- Department of Medical Laboratories, College of Applied Medical Science, Qassim University, Saudi Arabia
| | - Ihab M Moussa
- Department of Botany and Microbiology, College of Science, King Saud University, Saudi Arabia
| | - Ashgan Mohamed Hessain
- Department of Health Science, College of Applied Studies and Community Service, King Saud University, P. O. Box 22459, Riyadh 11495, Saudi Arabia
| | - Jwaher Haji Alhaji
- Department of Health Science, College of Applied Studies and Community Service, King Saud University, P. O. Box 22459, Riyadh 11495, Saudi Arabia
| | - Hassan A Heme
- Department of Medical Technology/Microbiology, College of Applied Medical Science, Taibah University, Madinah, Saudi Arabia
| | - Rasha Zahran
- Department of Bacteriology, Mycology and Immunology, Faculty of Veterinary Medicine, Sadat City University, Egypt
| | - Eman Abdeen
- Department of Bacteriology, Mycology and Immunology, Faculty of Veterinary Medicine, Sadat City University, Egypt
| |
Collapse
|
|
19
|
Gong Y, Yuan Y. Resistance mechanisms of Helicobacter pylori and its dual target precise therapy. Crit Rev Microbiol 2018; 44:371-392. [PMID: 29293032 DOI: 10.1080/1040841x.2017.1418285] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori drug resistance presents a significant challenge to the successful eradication of this pathogen. To find strategies to improve the eradication efficacy of H. pylori, it is necessary to clarify the resistance mechanisms involved. The mechanisms of H. pylori drug resistance can be investigated from two angles: the pathogen and the host. A comprehensive understanding of the molecular mechanisms of H. pylori resistance based on both pathogen and host would aid the implementation of precise therapy, or ideally "dual target precise therapy" (bacteria and host-specific target therapy). In recent years, with increased understanding of the mechanisms of H. pylori resistance, the focus of eradication has shifted from disease-specific to patient-specific treatment. The implementation of "precision medicine" has also provided a new perspective on the treatment of infectious diseases. In this article, we systematically review current research on H. pylori drug resistance from the perspective of both the pathogen and the host. We also review therapeutic strategies targeted to pathogen and host factors that are aimed at achieving precise treatment of H. pylori.
Collapse
Affiliation(s)
- Yuehua Gong
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
| | - Yuan Yuan
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
| |
Collapse
|
|
20
|
Mathias F, Kabri Y, Okdah L, Di Giorgio C, Rolain JM, Spitz C, Crozet MD, Vanelle P. An Efficient One-Pot Catalyzed Synthesis of 2,4-Disubstituted 5-Nitroimidazoles Displaying Antiparasitic and Antibacterial Activities. Molecules 2017; 22:molecules22081278. [PMID: 28771219 PMCID: PMC6152245 DOI: 10.3390/molecules22081278] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 07/29/2017] [Indexed: 11/16/2022] Open
Abstract
A one-pot regioselective bis-Suzuki-Miyaura or Suzuki-Miyaura/Sonogashira reaction on 2,4-dibromo-1-methyl-5-nitro-1H-imidazole under microwave heating was developed. This method is applicable to a wide range of (hetero)arylboronic acids and terminal alkynes. Additionally, this approach provides a simple and efficient way to synthesize 2,4-disubstituted 5-nitroimidazole derivatives with antibacterial and antiparasitic properties.
Collapse
Affiliation(s)
- Fanny Mathias
- Aix Marseille University, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin-CS 30064, 13385 Marseille CEDEX 05, France.
| | - Youssef Kabri
- Aix Marseille University, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin-CS 30064, 13385 Marseille CEDEX 05, France.
| | - Liliane Okdah
- IHU Méditerranée Infection, Aix Marseille University, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, URMITE UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine de la Timone, 19-21 Boulevard Jean Moulin, 13005 Marseille, France.
| | - Carole Di Giorgio
- Aix Marseille University, CNRS, IRD, Avignon Université, IMBE UMR 7263, Laboratoire de Mutagénèse Environnementale, 13385 Marseille, France.
| | - Jean-Marc Rolain
- IHU Méditerranée Infection, Aix Marseille University, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, URMITE UMR 63, CNRS 7278, IRD 198, Inserm 1095, Faculté de Médecine de la Timone, 19-21 Boulevard Jean Moulin, 13005 Marseille, France.
| | - Cédric Spitz
- Aix Marseille University, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin-CS 30064, 13385 Marseille CEDEX 05, France.
| | - Maxime D Crozet
- Aix Marseille University, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin-CS 30064, 13385 Marseille CEDEX 05, France.
| | - Patrice Vanelle
- Aix Marseille University, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin-CS 30064, 13385 Marseille CEDEX 05, France.
| |
Collapse
|
|
21
|
Talebi Bezmin Abadi A. Helicobacter pylori treatment: New perspectives using current experience. J Glob Antimicrob Resist 2017; 8:123-130. [PMID: 28131855 DOI: 10.1016/j.jgar.2016.11.008] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 09/10/2016] [Accepted: 11/20/2016] [Indexed: 02/08/2023] Open
|
|
22
|
Foster-Nyarko E, Kwambana B, Ceesay F, Jawneh K, Darboe S, Mulwa SN, Ceesay B, Secka OO, Adetifa I, Antonio M. Incidence of macrolide-lincosamide-streptogramin B resistance amongst beta-haemolytic streptococci in The Gambia. BMC Res Notes 2017; 10:106. [PMID: 28231812 PMCID: PMC5324333 DOI: 10.1186/s13104-017-2427-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Accepted: 02/14/2017] [Indexed: 01/21/2023] Open
Abstract
Background In West Africa, penicillin, macrolide and lincosamide resistance among beta-haemolytic streptococci (BHS) isolates has rarely been described. However, such data are critical to detect and track the emergence of antibiotic resistance. Methods Beta-haemolytic streptococci were cultured from clinical specimens from patients attending the clinic at the Medical Research Council Unit The Gambia (n = 217) and kept at −70 °C. Of these, 186 were revived and tested for penicillin susceptibility by disc diffusion and E-test methods, and the D-test for determination of constitutive and inducible macrolide–lincosamide (MLSB) resistance phenotypes. Results The majority of BHS isolates from infections were group A streptococci (GAS) (126/186, 67.7%). Of these, 16% were from invasive disease (30/186). Other BHS isolated included lancefield groups B (19, 10.2%); C (9/186, 4.8%), D (3/186, 1.6%), F (5/186, 2.7%), G (16/186, 8.6%) and non-typeable (8/186, 4.3%). Prevalence of BHS isolated from blood cultures ranges from 0% (2005) to 0.5% (2010). Most (85, 45.7%) of the isolates were from wound infections. Of the 186 BHS isolates, none was resistant to penicillin and 14 (6.1%) were resistant to erythromycin. Of these, 8 (4.3%) demonstrated constitutive MLSB resistance, and 5 (2.7%) were inducible MLSB resistant. All the inducible MLSB isolates were GAS, and majority of the constitutive MLSB isolates (6/8, 75.0%) were non-GAS. Conclusions Beta-haemolytic streptococci, predominantly GAS are associated with a wide range of infections in The Gambia. It is reassuring that macrolide and lincosamide resistance is relatively low. However, monitoring of MLSB resistance is necessary with the global spread of resistant BHS strains.
Collapse
Affiliation(s)
- Ebenezer Foster-Nyarko
- Vaccines and Immunity Theme, Medical Research Council Unit The Gambia, Banjul, The Gambia
| | - Brenda Kwambana
- Vaccines and Immunity Theme, Medical Research Council Unit The Gambia, Banjul, The Gambia
| | - Fatima Ceesay
- Vaccines and Immunity Theme, Medical Research Council Unit The Gambia, Banjul, The Gambia
| | - Kaddijatou Jawneh
- Vaccines and Immunity Theme, Medical Research Council Unit The Gambia, Banjul, The Gambia
| | - Saffiatou Darboe
- Clinical Microbiology Department, Medical Research Council Unit The Gambia, Banjul, The Gambia
| | - Sarah N Mulwa
- Vaccines and Immunity Theme, Medical Research Council Unit The Gambia, Banjul, The Gambia
| | - Buntung Ceesay
- Clinical Microbiology Department, Medical Research Council Unit The Gambia, Banjul, The Gambia
| | - Ousman O Secka
- Clinical Microbiology Department, Medical Research Council Unit The Gambia, Banjul, The Gambia
| | - Ifedayo Adetifa
- Disease Control and Elimination Theme, Medical Research Council Unit The Gambia, Banjul, The Gambia.,Infectious Diseases Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
| | - Martin Antonio
- Vaccines and Immunity Theme, Medical Research Council Unit The Gambia, Banjul, The Gambia. .,Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. .,Microbiology and Infection Unit, Warwick Medical School, University of Warwick, Coventry, UK.
| |
Collapse
|
|
23
|
Bouihat N, Burucoa C, Benkirane A, Seddik H, Sentissi S, Al Bouzidi A, Elouennas M, Benouda A. Helicobacter pylori Primary Antibiotic Resistance in 2015 in Morocco: A Phenotypic and Genotypic Prospective and Multicenter Study. Microb Drug Resist 2016; 23:727-732. [PMID: 27996373 DOI: 10.1089/mdr.2016.0264] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Knowledge of local antibiotic resistance is crucial to adaption of the choice of effective empirical first-line treatment for Helicobacter pylori infection. The aim of this study was to evaluate, for the first time in Morocco, the prevalence of the primary resistance of H. pylori to clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and rifamycin. We conducted a 1-year prospective study (2015), including 255 Moroccan patients referred for gastro-duodenal endoscopy to two hospitals of Rabat (Morocco) and never previously treated for H. pylori infection. Three gastric biopsies were collected: one for histology, one for culture, and one for molecular detection of H. pylori and the mutations in 23S rRNA genes that confer resistance to clarithromycin. Antimicrobial susceptibility testing was performed on isolated strains by Etest and disk diffusion methods. One hundred seventy-seven patients were infected (69.4%). The prevalence of primary resistances of H. pylori to clarithromycin was 29%, 40% to metronidazole, 0% to amoxicillin, tetracycline, and rifamycin, and 11% to levofloxacin. Only four isolates (2%) were resistant to both clarithromycin and metronidazole. The high level of primary clarithromycin resistance in the H. pylori strains infecting the Moroccan population leads us to recommend the abandonment of the standard clarithromycin-based triple therapy as a first-line treatment in Morocco and to prefer a concomitant quadruple therapy.
Collapse
Affiliation(s)
- Najat Bouihat
- 1 Laboratoire de Microbiologie, Université Mohammed V, Hôpital Universitaire Cheick-Zaid , Faculté de Médecine de Rabat, Rabat, Morocco
| | - Christophe Burucoa
- 2 EA 4331 LITEC, Université de Poitiers , CHU de Poitiers, Laboratoire de Bactériologie-Hygiène, Poitiers, France
| | - Ahmed Benkirane
- 3 Departement de Gastroentérologie II, Hôpital Militaire d'Instruction Mohammed V , Rabat, Morocco
| | - Hassan Seddik
- 3 Departement de Gastroentérologie II, Hôpital Militaire d'Instruction Mohammed V , Rabat, Morocco
| | - Sara Sentissi
- 3 Departement de Gastroentérologie II, Hôpital Militaire d'Instruction Mohammed V , Rabat, Morocco
| | - Abderrahmane Al Bouzidi
- 4 Pôle des laboratoires, Hôpital Militaire d'Instruction Mohamed V, équipe de recherche en pathologie tumorale, Faculté de Médecine de Rabat , Rabat, Morocco
| | - Mustapha Elouennas
- 5 Laboratoire de Microbiologie, Hôpital Militaire d'Instruction Mohammed V , Rabat, Morocco
| | - Amina Benouda
- 6 Laboratoire de Microbiologie, Hôpital Universitaire Cheick-Zaid, Université Abulcasis des Sciences de la Santé , Rabat, Morocco
| |
Collapse
|
|
24
|
Ranjbar R, Khamesipour F, Jonaidi-Jafari N, Rahimi E. Helicobacter pylori isolated from Iranian drinking water: vacA, cagA, iceA, oipA and babA2 genotype status and antimicrobial resistance properties. FEBS Open Bio 2016; 6:433-41. [PMID: 27419049 PMCID: PMC4856422 DOI: 10.1002/2211-5463.12054] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 03/09/2016] [Accepted: 03/10/2016] [Indexed: 02/05/2023] Open
Abstract
Despite the clinical importance of Helicobacter pylori in human gastric disorders, its exact route of transmission is still uncertain. Based on the contentious hypothesis and findings of previous investigations, water may play an important role in the transmission of H. pylori to humans. This study was carried out to investigate the vacA, cagA, oipA, iceA and babA2 genotype status and antimicrobial resistance properties of H. pylori strains isolated from the drinking water samples of four major provinces in Iran. A total of 400 drinking water samples were cultured and tested. H. pylori-positive strains were analyzed for the presence of various genotypes and antimicrobial resistance. Twelve of 400 (3%) water samples were positive for H. pylori. Samples from Isfahan province had the highest, while those from Shiraz had the lowest prevalence of H. pylori. The seasonal distribution was also determined, with the highest prevalence of bacteria in the summer season (7.36%). H. pylori strains harbored the highest levels of resistance against ampicillin (100%), erythromycin (75%), clarithromycin (75%), and trimethoprim (58.3%). The most commonly detected genotypes were vacAs1a (83.3%), vacAm1a (66.6%), vacAs2 (50%) and cagA (50%). The presence of similar genotypes in the H. pylori strains of drinking water and those of human clinical samples suggest that contaminated water maybe the sources of bacteria. Spiramycin and furazolidone are suggested for the treatment of cases of H. pylori infection.
Collapse
Affiliation(s)
- Reza Ranjbar
- Molecular Biology Research Center Baqiyatallah University of Medical Sciences Tehran Iran
| | - Faham Khamesipour
- Cellular and Molecular Research Center Sabzevar University of Medical Sciences Sabzevar Iran
| | | | - Ebrahim Rahimi
- Department of Food Hygiene Faculty of Veterinary Medicine Shahrekord Branch Islamic Azad University Shahrekord Iran
| |
Collapse
|
|
25
|
Ranjbar R, Khamesipour F, Jonaidi-Jafari N, Rahimi E. Helicobacter pylori in bottled mineral water: genotyping and antimicrobial resistance properties. BMC Microbiol 2016; 16:40. [PMID: 26970903 PMCID: PMC4789264 DOI: 10.1186/s12866-016-0647-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Accepted: 02/29/2016] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Up to now, fecal-oral and oral-oral are the most commonly known routes for transmission of H. pylori, therefore, contaminated water can play an important role in transmission of H. pylori to humans. Genotyping using virulence markers of H. pylori is one of the best approaches to study the correlations between H. pylori isolates from different samples. The present research was carried out to study the vacA, cagA, cagE, oipA, iceA and babA2 genotyping and antimicrobial resistance properties of H. pylori isolated from the bottled mineral water samples of Iran. RESULTS Of 450 samples studied, 8 samples (1.77%) were contaminated with H. pylori. Brand C of bottled mineral water had the highest prevalence of H. pylori (3.63%). The bottled mineral water samples of July month had the highest levels of H. pylori-contamination (50%). H. pylori strains had the highest levels of resistance against metronidazole (62.5%), erythromycin (62.5%), clarithromycin (62.5%), amoxicillin (62.5%) and trimethoprim (62.5%). Totally, 12.5% of strains were resistant to more than 6 antibiotics. VvacAs1a (100%), vacAm1a (87.5%), cagA (62.5%), iceA1 (62.5%), oipA (25%), babA2 (25%) and cagE (37.5%) were the most commonly detected genotypes. M1as1a (62.5%), m1as2 (37.5%), m2s2 (37.5%) and S1a/cagA+/IceA2/oipA-/babA2-/cagE- (50%) were the most commonly detected combined genotypes. CONCLUSIONS Contaminated bottled mineral water maybe the sources of virulent and resistant strains H. pylori. Careful monitoring of bottled mineral water production may reduce the risk of H. pylori transmission into the human population.
Collapse
Affiliation(s)
- Reza Ranjbar
| | - Faham Khamesipour
| | | | - Ebrahim Rahimi
| |
Collapse
|
|
26
|
Hemmatinezhad B, Momtaz H, Rahimi E. VacA, cagA, iceA and oipA genotypes status and antimicrobial resistance properties of Helicobacter pylori isolated from various types of ready to eat foods. Ann Clin Microbiol Antimicrob 2016; 15:2. [PMID: 26792758 PMCID: PMC4719207 DOI: 10.1186/s12941-015-0115-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Accepted: 11/23/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Despite the high clinical standing of Helicobacter pylori, its exact routes of transmission and origin have not been determined. Based on the contentious hypothesis, foods play an important roles in the transmission of H. pylori to humans. The present study was carried out to investigate the vacA, cagA, oipA and iceA genotypes status of H. pylori isolated from the various types of ready to eat foods. METHODS A total of 550 ready to eat food samples were cultured and tested. H. pylori-positive strains were analyzed for the presence of various genotypes and antimicrobial resistance pattern. RESULTS Seventy four out of 550 (13.45 %) samples were positive for H. pylori. Olvie salad (36 %), restaurant salad (30 %), fruit salad (28 %) and soup (22 %) were the most commonly contaminated. H. pylori strains harbored the highest levels of resistance against amoxicillin (94.59 %), ampicillin (93.24 %), metronidazole (89.18 %) and tetracycline (72.97 %). The most commonly detected genotypes were vacA s1a (78.37 %), vacA m2 (75.67 %), vacA m1a (51.35 %) and cagA (41.89 %). The prevalence of iceA1, iceA2 and oipA genotypes were 13.51, 4.05 and 18.91 %, respectively. S1am2 (70.27 %), s1am1a (39.18 %) and m1am2 (31.08 %) were the most commonly detected combined genotypes. Of 40 different genotypic combinations, s1a/cagA+/iceA1/oipA- (12.16 %), s1a/cagA+/iceA1/oipA+ (10.81 %) and s1a/cagA-/iceA1/oipA+ (10.81 %) were the most prevalent. CONCLUSIONS The present investigation showed that some types of ready to eat food samples maybe the sources of resistant and virulent strains of H. pylori. Warily use of antibiotics with respect to the results of disk diffusion method and careful health monitoring on food and staffs of food producing companies maybe reduce the risk of H. pylori in foods.
Collapse
Affiliation(s)
- Behsan Hemmatinezhad
- Graduated Student of Veterinary Medicine, College of Veterinary Medicine, Islamic Azad University, Shahrekord, Iran.
| | - Hassan Momtaz
- Department of Microbiology, College of Basic Sciences, Islamic Azad University, Shahrekord, Iran.
| | - Ebrahim Rahimi
- Department of Food Hygiene and Public Health, College of Veterinary Medicine, Islamic Azad University, Shahrekord, Iran.
| |
Collapse
|
|
27
|
Kim SY, Choi DJ, Chung JW. Antibiotic treatment for Helicobacter pylori: Is the end coming? World J Gastrointest Pharmacol Ther 2015; 6:183-198. [PMID: 26558152 PMCID: PMC4635158 DOI: 10.4292/wjgpt.v6.i4.183] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 08/01/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.
Collapse
|
|
28
|
Ghotaslou R, Leylabadlo HE, Asl YM. Prevalence of antibiotic resistance in Helicobacter pylori: A recent literature review. World J Methodol 2015; 5:164-174. [PMID: 26413490 PMCID: PMC4572030 DOI: 10.5662/wjm.v5.i3.164] [Citation(s) in RCA: 145] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 07/06/2015] [Accepted: 08/21/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To review previous studies (the last 6 years) about the Helicobacter pylori (H. pylori) antibiotic resistance in order to evaluate the trend in antibiotic resistance.
METHODS: In this study, the PubMed, MEDLINE, Science Direct, Google Scholar and Scielo manuscripts were reviewed from 2009 to 2014.
RESULTS: On the whole rates of H. pylori antibiotic resistance were 47.22% (30.5%-75.02%) for metronidazole, 19.74% (5.46%-30.8%) for clarithromycin, 18.94% (14.19%-25.28%) for levofloxacin, and 14.67% (2%-40.87%) for amoxicillin, 11.70% (0%-50%) for tetracycline, 11.5% (0%-23%) for furazolidon and 6.75% (1%-12.45%) for rifabutin. The frequency of tetracycline, metronidazole and amoxicillin resistance was higher in Africa, while clarithromycin and levofloxacin resistance was higher in North America and Asian, respectively.
CONCLUSION: The most sensitive drug is rifabutin and the lowest sensitive drug is metronidazole in the world. The worldwide H. pylori antibiotic resistance to clarithromycin and levofloxacin has increased during the last 6 years. The present systematic review show alarming results and a novel plan is needed for eradication therapy of H. pylori infections.
Collapse
|
|
29
|
Cao Q, Didelot X, Wu Z, Li Z, He L, Li Y, Ni M, You Y, Lin X, Li Z, Gong Y, Zheng M, Zhang M, Liu J, Wang W, Bo X, Falush D, Wang S, Zhang J. Progressive genomic convergence of two Helicobacter pylori strains during mixed infection of a patient with chronic gastritis. Gut 2015; 64:554-61. [PMID: 25007814 PMCID: PMC4392222 DOI: 10.1136/gutjnl-2014-307345] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To study the detailed nature of genomic microevolution during mixed infection with multiple Helicobacter pylori strains in an individual. DESIGN We sampled 18 isolates from a single biopsy from a patient with chronic gastritis and nephritis. Whole-genome sequencing was applied to these isolates, and statistical genetic tools were used to investigate their evolutionary history. RESULTS The genomes fall into two clades, reflecting colonisation of the stomach by two distinct strains, and these lineages have accumulated diversity during an estimated 2.8 and 4.2 years of evolution. We detected about 150 clear recombination events between the two clades. Recombination between the lineages is a continuous ongoing process and was detected on both clades, but the effect of recombination in one clade was nearly an order of magnitude higher than in the other. Imputed ancestral sequences also showed evidence of recombination between the two strains prior to their diversification, and we estimate that they have both been infecting the same host for at least 12 years. Recombination tracts between the lineages were, on average, 895 bp in length, and showed evidence for the interspersion of recipient sequences that has been observed in in vitro experiments. The complex evolutionary history of a phage-related protein provided evidence for frequent reinfection of both clades by a single phage lineage during the past 4 years. CONCLUSIONS Whole genome sequencing can be used to make detailed conclusions about the mechanisms of genetic change of H. pylori based on sampling bacteria from a single gastric biopsy.
Collapse
Affiliation(s)
- Qizhi Cao
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China,Department of Immunology, Binzhou Medical University, Yantai, China
| | - Xavier Didelot
- Department of Infectious Disease Epidemiology, Imperial College London, London, UK
| | - Zhongbiao Wu
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Zongwei Li
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Lihua He
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Yunsheng Li
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Ming Ni
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Yuanhai You
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Xi Lin
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Zhen Li
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Yanan Gong
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Minqiao Zheng
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Minli Zhang
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Jie Liu
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Weijun Wang
- The First People's Hospital of Wenling, the Affiliated Wenling Hospital of Wenzhou Medical College, Zhejiang, China
| | - Xiaochen Bo
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Daniel Falush
- Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany,Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan
| | - Shengqi Wang
- Beijing Institute of Radiation Medicine, Beijing, China
| | - Jianzhong Zhang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| |
Collapse
|
|
30
|
Virulence factors and antibiotic resistance of Helicobacter pylori isolated from raw milk and unpasteurized dairy products in Iran. J Venom Anim Toxins Incl Trop Dis 2014; 20:51. [PMID: 25873940 PMCID: PMC4396062 DOI: 10.1186/1678-9199-20-51] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2014] [Accepted: 11/18/2014] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Despite the high importance of Helicobacter pylori, the origin and transmission of this bacterium has not been clearly determined. According to controversial theories and results of previous studies, animal source foods - especially milk - play an important role in the transmission of H. pylori to humans. The aim of the present study was to determine the distribution of vacA, cagA, iceA and oipA virulence factors in H. pylori strains isolated from milk and dairy products and study their antimicrobial resistance properties. METHODS A total of 520 raw milk and 400 traditional dairy product samples were cultured and tested. Those that were H. pylori-positive were analyzed for the presence of vacA, cagA, iceA and oipA virulence factors. Antimicrobial susceptibility testing was performed by the disk diffusion method. RESULTS One hundred and three out of 520 milk samples (19.8%) and 77 out of 400 dairy products samples (19.2%) were contaminated with H. pylori. The most frequently contaminated samples were ovine milk (35%) and traditional cheese (30%). Total prevalence of vacA, cagA, iceA and oipA factors were 75%, 76.6%, 41.6% and 25%, respectively. H. pylori strains of milk and dairy products harbored high levels of resistance to ampicillin (84.4%), tetracycline (76.6%), erythromycin (70.5%) and metronidazole (70%). CONCLUSIONS High presence of antibiotic-resistant strains of H. pylori suggest that milk and dairy samples may be the sources of bacteria that can cause severe infection. Our findings should raise awareness about antibiotic resistance in H. pylori strains in Iran.
Collapse
|
|
31
|
Ntagirabiri R, Harerimana S, Makuraza F, Ndirahisha E, Kaze H, Moibeni A. Helicobacter pylori au Burundi : première évaluation de la prévalence en endoscopie et de l’éradication. ACTA ACUST UNITED AC 2014. [DOI: 10.1007/s12157-014-0567-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
|
|
32
|
Yahaghi E, Khamesipour F, Mashayekhi F, Safarpoor Dehkordi F, Sakhaei MH, Masoudimanesh M, Khameneie MK. Helicobacter pylori in vegetables and salads: genotyping and antimicrobial resistance properties. BIOMED RESEARCH INTERNATIONAL 2014; 2014:757941. [PMID: 25184146 PMCID: PMC4145543 DOI: 10.1155/2014/757941] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Revised: 05/18/2014] [Accepted: 06/09/2014] [Indexed: 02/08/2023]
Abstract
From a clinical and epidemiological perspective, it is important to know which genotypes and antibiotic resistance patterns are present in H. pylori strains isolated from salads and vegetables. Therefore, the present investigation was carried out to find this purpose. Three hundred eighty washed and unwashed vegetable samples and fifty commercial and traditional salad samples were collected from Isfahan, Iran. Samples were cultured and those found positive for H. pylori were analyzed using PCR. Antimicrobial susceptibility testing was performed using disk diffusion method. Seven out of 50 (14%) salad and 52 out of 380 (13.68%) vegetable samples harbored H. pylori. In addition, leek, lettuce, and cabbage were the most commonly contaminated samples (30%). The most prevalent virulence genes were oipA (86.44%) and cagA (57.625). VacA s1a (37.28%) and iceA1 (47.45%) were the most prevalent genotypes. Forty different genotypic combinations were recognized. S1a/cagA+/iceA1/oipA+ (33.89%), s1a/cagA+/iceA2/oipA (30.50%), and m1a/cagA+/iceA1/oipA+ (28.81%) were the most prevalent combined genotypes. Bacterial strains had the highest levels of resistance against metronidazole (77.96%), amoxicillin (67.79%), and ampicillin (61.01%). High similarity in the genotyping pattern of H. pylori among vegetable and salad samples and human specimens suggests that vegetable and salads may be the sources of the bacteria.
Collapse
Affiliation(s)
- Emad Yahaghi
- Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Faham Khamesipour
- Young Researchers and Elites Club, Islamic Azad University, Shahrekord Branch, P.O. Box 166, Shahrekord, Iran
| | - Fatemeh Mashayekhi
- Intensive and Critical Care Nursing, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Farhad Safarpoor Dehkordi
- Young Researchers and Elites Club, Islamic Azad University, Shahrekord Branch, P.O. Box 166, Shahrekord, Iran
| | - Mohammad Hossein Sakhaei
- Scientific Association of Veterinary Office, College of Veterinary Medicine, Islamic Azad University, Shahrekord Branch, P.O. Box 166, Shahrekord, Iran
| | - Mojtaba Masoudimanesh
- Scientific Association of Veterinary Office, College of Veterinary Medicine, Islamic Azad University, Shahrekord Branch, P.O. Box 166, Shahrekord, Iran
| | | |
Collapse
|
|
33
|
Ierardi E, Giorgio F, Losurdo G, Di Leo A, Principi M. How antibiotic resistances could change Helicobacter pylori treatment: A matter of geography? World J Gastroenterol 2013; 19:8168-8180. [PMID: 24363506 PMCID: PMC3857438 DOI: 10.3748/wjg.v19.i45.8168] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 10/18/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
Therapeutic management of Helicobacter pylori (H. pylori) remains an unsolved issue. Indeed, no therapeutic regimen is able to cure the infection in all treated patients, and in many the infection persists despite the administration of several consecutive standard therapies. Although antibiotic resistance reports describe alarming results, the outcome of therapeutic regimens does not seem to parallel this scenario in most cases, since a successful performance is often reached in more than 80% of cases. However, the phenomenon of increasing antibiotic resistance is being closely studied, and the results show controversial aspects even in the same geographic area. For the continents of Europe, America, Asia, Africa, and Oceania, minimal and maximal values of resistance to the main antibiotics (clarithromycin, amoxicillin, metronidazole, and levofloxacin) feature wide ranges in different countries. The real enigma is therefore linked to the several different therapeutic regimens, which show results that often do not parallel the in vitro findings even in the same areas. A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts. Moreover, not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome. The additional use of probiotics may help to reduce adverse events, but their therapeutic impact is doubtful. In conclusion, the “ideal therapy”, paradoxically, appears to be a “utopia”, despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H. pylori. The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide. On these bases, one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances. In this context, geography must be considered a relevant matter.
Collapse
|
|
34
|
Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity. Proc Natl Acad Sci U S A 2013; 110:17564-9. [PMID: 24101497 DOI: 10.1073/pnas.1302664110] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Metronidazole and other 5-nitroimidazoles (5-NI) are among the most effective antimicrobials available against many important anaerobic pathogens, but evolving resistance is threatening their long-term clinical utility. The common 5-NIs were developed decades ago, yet little 5-NI drug development has since taken place, leaving the true potential of this important drug class unexplored. Here we report on a unique approach to the modular synthesis of diversified 5-NIs for broad exploration of their antimicrobial potential. Many of the more than 650 synthesized compounds, carrying structurally diverse functional groups, have vastly improved activity against a range of microbes, including the pathogenic protozoa Giardia lamblia and Trichomonas vaginalis, and the bacterial pathogens Helicobacter pylori, Clostridium difficile, and Bacteroides fragilis. Furthermore, they can overcome different forms of drug resistance, and are active and nontoxic in animal infection models. These findings provide impetus to the development of structurally diverse, next-generation 5-NI drugs as agents in the antimicrobial armamentarium, thus ensuring their future viability as primary therapeutic agents against many clinically important infections.
Collapse
|
|
35
|
Galano JJ, Alías M, Pérez R, Velázquez-Campoy A, Hoffman PS, Sancho J. Improved Flavodoxin Inhibitors with Potential Therapeutic Effects against Helicobacter pylori Infection. J Med Chem 2013; 56:6248-58. [DOI: 10.1021/jm400786q] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Juan J. Galano
- Departamento
de Bioquímica
y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009, Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Unit BIFI-IQFR (CSIC), Edificio I + D, Mariano Esquillor, 50018, Zaragoza, Spain
| | - Miriam Alías
- Departamento
de Bioquímica
y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009, Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Unit BIFI-IQFR (CSIC), Edificio I + D, Mariano Esquillor, 50018, Zaragoza, Spain
| | - Reyes Pérez
- Departamento
de Bioquímica
y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009, Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Unit BIFI-IQFR (CSIC), Edificio I + D, Mariano Esquillor, 50018, Zaragoza, Spain
| | - Adrian Velázquez-Campoy
- Departamento
de Bioquímica
y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009, Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Unit BIFI-IQFR (CSIC), Edificio I + D, Mariano Esquillor, 50018, Zaragoza, Spain
- Fundación ARAID, Gobierno de Aragon, Aragon, Spain
| | - Paul S. Hoffman
- Department of Medicine, Division
of Infectious Diseases and International Health, University of Virginia Health System, Charlottesville, Virginia
22908, United States
| | - Javier Sancho
- Departamento
de Bioquímica
y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009, Zaragoza, Spain
- Institute for Biocomputation and Physics of Complex Systems (BIFI), Joint Unit BIFI-IQFR (CSIC), Edificio I + D, Mariano Esquillor, 50018, Zaragoza, Spain
| |
Collapse
|