scholarly journals Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in Mycoplasma hominis Topoisomerases

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1379
Author(s):  
Martin Sharratt ◽  
Kirsty Sands ◽  
Edward A. R. Portal ◽  
Ian Boostrom ◽  
Brian A. Mondeja ◽  
...  
Keyword(s):  
Spontaneous Mutation ◽  
Organ Transplant ◽  
Mycoplasma Hominis ◽  
Fluoroquinolone Resistance ◽  
Resistance Screening ◽  
Prolonged Incubation ◽  
High Prevalence ◽  
Immunosuppressed Patients ◽  
Transplant Failure ◽  
Gyra Mutation

Often dismissed as a commensal, Mycoplasma hominis is an increasingly prominent target of research due to its role in septic arthritis and organ transplant failure in immunosuppressed patients, particularly lung transplantation. As a mollicute, its highly reductive genome and structure render it refractile to most forms of treatment and growing levels of resistance to the few sources of treatment left, such as fluoroquinolones. We examined antimicrobial susceptibility (AST) to fluoroquinolones on 72 isolates and observed resistance in three (4.1%), with corresponding mutations in the quinolone resistance-determining region (QRDR) of S83L or E87G in gyrA and S81I or E85V in parC. However, there were high levels of polymorphism identified between all isolates outside of the QRDR, indicating caution for a genomics-led approach for resistance screening, particularly as we observed a further two quinolone-susceptible isolates solely containing gyrA mutation S83L. However, both isolates spontaneously developed a second spontaneous E85K parC mutation and resistance following prolonged incubation in 4 mg/L levofloxacin for an extra 24–48 h. Continued AST surveillance and investigation is required to understand how gyrA QRDR mutations predispose M. hominis to rapid spontaneous mutation and fluoroquinolone resistance, absent from other susceptible isolates. The unusually high prevalence of polymorphisms in M. hominis also warrants increased genomics’ surveillance.

scholarly journals Mycobacterium genavense Infections in a Tertiary Hospital and Reviewed Cases in Non-HIV Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
M. Santos ◽  
A. Gil-Brusola ◽  
A. Escandell ◽  
M. Blanes ◽  
M. Gobernado
Keyword(s):  
Antimicrobial Agents ◽  
Organ Transplant ◽  
Tertiary Hospital ◽  
Favourable Outcome ◽  
Response To Therapy ◽  
Nontuberculous Mycobacterium ◽  
Clinical Samples ◽  
Prolonged Incubation ◽  
Mycobacterium Genavense ◽  
Immunosuppressed Patients

Mycobacterium genavense is a relatively new species of nontuberculous mycobacterium reported to cause disseminated infections in patients with AIDS and later on in non-HIV immunosuppressed patients. We describe clinical and laboratory features and response to therapy in 7 patients, three of them with HIV infection and four non-HIV—three organ transplant recipients and one with hyper-IgE syndrome—in Valencia, Spain, in a ten years period. We then summarize the published cases of M. avium complex infection, with invasion of peripheral blood, liver, spleen, bone marrow, lymph nodes, and lungs. In clinical samples a large number of acid-fast bacilli were observed. M. genavense grew only from liquid media and after a prolonged incubation period. Its identification was accomplished through molecular methods. Patients were treated with prolonged combinations of antimicrobial agents. There was clinical favourable outcome in 4 patients.

scholarly journals High prevalence of qnrA and qnrB genes among fluoroquinolone-resistant Escherichia coli isolates from a tertiary hospital in Southern Nigeria

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Chibuzor M. Nsofor ◽  
Mirabeau Y. Tattfeng ◽  
Chijioke A. Nsofor
Keyword(s):  
Escherichia Coli ◽  
Susceptibility Testing ◽  
Tertiary Hospital ◽  
Vaginal Swab ◽  
Fluoroquinolone Resistance ◽  
E Coli ◽  
Diffusion Technique ◽  
High Prevalence ◽  
Polymerase Chain ◽  
And Control

Abstract Background This study was aimed to determine the prevalence of qnr genes among fluoroquinolone-resistant Escherichia coli (FREC) isolates from Nigeria. Antimicrobial susceptibility testing was performed by disc diffusion technique. Polymerase chain reaction was used to identify Escherichia coli (E. coli) and for the detection of qnr genes. Results A total of 206 non-duplicate E. coli were isolated from 300 clinical specimens analyzed. In all, 30 (14.6%) of these isolates were FREC; the resistance to fluoroquinolones among these 30 FREC showed 80% (24), 86.7% (26), 86.7% (26), 100% (30), 86.7% (26), 93.3% (28) and 86.7% (26) were resistant to pefloxacin, ciprofloxacin, sparfloxacin, levofloxacin, nalidixic acid, ofloxacin and moxifloxacin, respectively. The distribution of FREC among the various sample sources analyzed showed that 14%, 10%, 13.3%, 16.7% and 20% of the isolates came from urine, stool, high vaginal swab, endo cervical swab and wound swab specimens, respectively. More FREC were isolated from female samples 73.3% (22) compared to male samples 26.7% (8) and were more prevalent among the age group 26–35 years (40%). Twenty eight out of the 30 (93.3%) FREC isolates possessed at least one fluoroquinolone resistance gene in the form of qnrA 10 (33.3%) and qnrB 18 (60%), respectively; qnrS was not detected among the FREC isolates analyzed and 13.5% of the isolates possessed both the qnrA and qnrB genes. Phylogenetic analysis showed that these isolates were genetically diverse. Conclusions These findings suggest a possible resistance to fluoroquinolone is of high interest for better management of patients and control of antimicrobial resistance in Nigeria.

scholarly journals Traffic-related air pollution and solid organ transplant failure in Great Britain: A retrospective cohort study

2018 ◽  
Vol 10 ◽  
pp. 124-131 ◽  
Author(s):  
Livia Pierotti ◽  
Susie J. Schofield ◽  
Dave Collett ◽  
Daniela Fecht ◽  
Kees De Hoogh ◽  
...  
Keyword(s):  
Air Pollution ◽  
Cohort Study ◽  
Great Britain ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Failure

scholarly journals Antimicrobial Resistance in Clinical Ureaplasma spp. and Mycoplasma hominis and Structural Mechanisms Underlying Quinolone Resistance

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Ting Yang ◽  
Lianlian Pan ◽  
Ningning Wu ◽  
Lin Wang ◽  
Zhen Liu ◽  
...  
Keyword(s):  
Mycoplasma Hominis ◽  
Quinolone Resistance ◽  
Fluoroquinolone Resistance ◽  
23S Rrna ◽  
Similar Data ◽  
Resistance Mutations ◽  
Erythromycin Resistance ◽  
Topoisomerase Iv ◽  
Content Type ◽  
Broth Microdilution Method

ABSTRACT Antibiotic resistance is a global concern; however, data on antibiotic-resistant Ureaplasma spp. and Mycoplasma hominis are limited in comparison to similar data on other microbes. A total of 492 Ureaplasma spp. and 13 M. hominis strains obtained in Hangzhou, China, in 2018 were subjected to antimicrobial susceptibility testing for levofloxacin, moxifloxacin, erythromycin, clindamycin, and doxycycline using the broth microdilution method. The mechanisms underlying quinolone and macrolide resistance were determined. Meanwhile, a model of the topoisomerase IV complex bound to levofloxacin in wild-type Ureaplasma spp. was built to study the quinolone resistance mutations. For Ureaplasma spp., the levofloxacin, moxifloxacin, and erythromycin resistance rates were 84.69%, 51.44%, and 3.59% in U. parvum and 82.43%, 62.16%, and 5.40% in U. urealyticum, respectively. Of the 13 M. hominis strains, 11 were resistant to both levofloxacin and moxifloxacin, and five strains showed clindamycin resistance. ParC S83L was the most prevalent mutation in levofloxacin-resistant Ureaplasma strains, followed by ParE R448K. The two mutations GyrA S153L and ParC S91I were commonly identified in quinolone-resistant M. hominis. A molecular dynamics-refined structure revealed that quinolone resistance-associated mutations inhibited the interaction and reduced affinity with gyrase or topoisomerase IV and quinolones. The novel mutations S21A in the L4 protein and G2654T and T2245C in 23S rRNA and the ermB gene were identified in erythromycin-resistant Ureaplasma spp. As fluoroquinolone resistance in Ureaplasma spp. and Mycoplasma hominis remains high in China, the rational use of antibiotics needs to be further enhanced.

scholarly journals Reduced Clinical Efficacy of Pazufloxacin against Gonorrhea Due to High Prevalence of Quinolone-Resistant Isolates with the GyrA Mutation

1998 ◽  
Vol 42 (3) ◽  
pp. 579-582 ◽  
Author(s):  
Masatoshi Tanaka ◽  
Tetsuro Matsumoto ◽  
Misao Sakumoto ◽  
Koichi Takahashi ◽  
Takeshi Saika ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Oral Dosage ◽  
Antibiotic Susceptibility Testing ◽  
Wild Type ◽  
Gonococcal Urethritis ◽  
Negative Culture ◽  
High Prevalence ◽  
The Mean ◽  
Gyra Mutation

ABSTRACT Forty-two men with gonococcal urethritis were treated with an oral dosage of 200 mg of pazufloxacin, a new fluoroquinolone, three times daily for 3 days. Only 28 of the 42 men (66.7%) had negative culture results for Neisseria gonorrhoeae during follow-up. Of the 42 isolates, 41 could be recultured for antibiotic susceptibility testing and DNA sequencing. In 26 of the 41 isolates (63.4%), GyrA mutations with or without ParC mutations were identified. Among the 26 isolates, 23 contained a single GyrA mutation, 1 contained two GyrA mutations, and 2 contained three mutations including double GyrA and single ParC mutations. A single Ser-91-to-Phe mutation, which was detected in 14 of the 26 isolates, was the most common GyrA mutation, followed by an Ala-75 to Ser mutation and an Asp-95 to Asn or Gly mutation in GyrA. All three isolates with two or three mutations contained the Ser-91-to-Phe GyrA mutation. Eleven of the 14 isolates with the single Ser-91-to-Phe mutation within GyrA and all 3 isolates with two or three mutations persisted after pazufloxacin treatment. On the other hand, all 15 wild-type and 9 mutant isolates with a substitution at codon Ala-75 or Asp-95 were eradicated. The mean MIC of pazufloxacin for mutants with the single Ser-91-to-Phe mutation in GyrA was 66-fold higher than that for the wild type. The results obtained in this study suggest that a high prevalence of fluoroquinolone-resistant gonococcal isolates with the Ser-91-to-Phe mutation in GyrA reduced the efficacy of pazufloxacin as treatment for gonococcal urethritis.

scholarly journals Mediators of Inflammation in Topical Therapy of Skin Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Vlad Mihai Voiculescu ◽  
Cristina Victoria Lisievici ◽  
Mihai Lupu ◽  
Cristina Vajaitu ◽  
Carmen Cristina Draghici ◽  
...  
Keyword(s):  
Topical Treatment ◽  
Cytotoxic T Lymphocyte ◽  
Topical Therapy ◽  
Novel Therapies ◽  
Skin Cancers ◽  
Mediators Of Inflammation ◽  
High Prevalence ◽  
Immunosuppressed Patients ◽  
Inflammatory Drugs ◽  
Melanoma Skin

Taking into consideration that the immune system plays a very important role in the development of melanoma and non-melanoma skin cancers, which have a high prevalence in immunosuppressed patients and after prolonged ultraviolet radiation, the interest in developing novel therapies, in particular targeting the inflammation in cancer, has increased in the past years. The latest data suggest that therapies such as imiquimod (IMQ), ingenol mebutate (IM), 5-fluorouracil (5-FU), retinoids, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been used with success in the topical treatment of some cancers. Herein, we review the topical treatment targeting the inflammation in skin cancer and the mechanisms involved in these processes. Currently, various associations have shown a superior success rate than monotherapy, such as systemic acitretin and topical IMQ, topical 5-FU with tretinoin cream, or IMQ with checkpoint inhibitor cytotoxic T lymphocyte antigen 4. Novel therapies targeting Toll-like receptor-7 (TLR-7) with higher selectivity than IMQ are also of great interest.

scholarly journals The Importance of Screening Strongyloides stercoralis Infection in Solid Organ Transplant Donors and Recipients

2021 ◽  
Vol 16 (4) ◽  
Author(s):  
Sara Abolghasemi ◽  
Farnaz Zolfaghari ◽  
Shahnaz Sali ◽  
Abdollah Ghaffari ◽  
Mehran Noori
Keyword(s):  
Organ Transplant ◽  
Gastrointestinal Symptoms ◽  
Strongyloides Stercoralis ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Kidney Transplant Recipients ◽  
Place Of Residence ◽  
Birth Place ◽  
Immunosuppressed Patients ◽  
History Of

Background: Strongyloides stercoralis is an intestinal nematode with worldwide distribution which is endemic in tropical and subtropical areas. It is unique in its ability to complete its entire life cycle and reinfect its human host via a phenomenon called autoinfection. The majority of infections are clinically asymptomatic or can manifest with gastrointestinal symptoms, such as heartburn, bloating, diarrhea, abdominal discomfort, gastroesophageal reflux disease (GERD), or symptoms related to the penetration of larvae through skin, including dermatitis and eosinophilia. Immunosuppressed patients, such as solid organ transplant patients with untreated strongyloidiasis are at great risk of hyperinfection, dissemination syndromes, and often fatal conditions associated with strongyloidiasis. Methods: In this retrospective single-center cross-sectional study, we evaluated 157 cases (131 heart, lung, and kidney transplant recipients and 26 kidney donors) in Tehran, Iran, from March 2020 to April 2021. Demographic information including age, gender, place of birth, place of residence, underlying disease, being the donor or recipient, history of previous transplant and type of transplant, travel history to endemic regions, and seropositivity for S. stercoralis were evaluated. Results: Among 157 cases with a mean age of 38.9 years, 40 (25.5%) cases tested positive for S. stercoralis antibodies. Out of 26 donors, eight cases were seropositive, and among 131 recipients, 32 cases were seropositive. There was no significant correlation between birth place and place of residence in endemic areas and seropositivity for S. stercoralis. None of the cases showed hypereosinophilia, hyperinfection, or disseminated syndrome. Also, we found no significant correlation between the type and time of transplant, history of previous transplants, and S. stercoralis infection. Conclusions: Universal screening for S. stercoralis latent infection is important in immunosuppressed patients, especially in solid organ transplants because of the high risk of hyperinfection and disseminated syndrome, which may culminate in death. Furthermore, screening for latent strongyloides infection in donors seems to be necessary because of the possibility of strongyloides infection being transmitted from donors to recipients.

scholarly journals Contribution of Different Mechanisms to Ciprofloxacin Resistance in Salmonella spp.

2021 ◽  
Vol 12 ◽  
Author(s):  
Man-Xia Chang ◽  
Jin-Fei Zhang ◽  
Yin-Huan Sun ◽  
Rong-Sheng Li ◽  
Xiao-Ling Lin ◽  
...  
Keyword(s):  
Resistance Mechanisms ◽  
Quinolone Resistance ◽  
Gene Location ◽  
Fluoroquinolone Resistance ◽  
Salmonella Spp ◽  
Resistance Development ◽  
Bacterial Fitness ◽  
Ciprofloxacin Resistance ◽  
Gyra Mutation ◽  
Chromosomal Mutations

Development of fluoroquinolone resistance can involve several mechanisms that include chromosomal mutations in genes (gyrAB and parCE) encoding the target bacterial topoisomerase enzymes, increased expression of the AcrAB-TolC efflux system, and acquisition of transmissible quinolone-resistance genes. In this study, 176 Salmonella isolates from animals with a broad range of ciprofloxacin MICs were collected to analyze the contribution of these different mechanisms to different phenotypes. All isolates were classified according to their ciprofloxacin susceptibility pattern into five groups as follows: highly resistant (HR), resistant (R), intermediate (I), reduced susceptibility (RS), and susceptible (S). We found that the ParC T57S substitution was common in strains exhibiting lowest MICs of ciprofloxacin while increased MICs depended on the type of GyrA mutation. The ParC T57S substitution appeared to incur little cost to bacterial fitness on its own. The presence of PMQR genes represented an route for resistance development in the absence of target-site mutations. Switching of the plasmid-mediated quinolone resistance (PMQR) gene location from a plasmid to the chromosome was observed and resulted in decreased ciprofloxacin susceptibility; this also correlated with increased fitness and a stable resistance phenotype. The overexpression of AcrAB-TolC played an important role in isolates with small decreases in susceptibility and expression was upregulated by MarA more often than by RamA. This study increases our understanding of the relative importance of several resistance mechanisms in the development of fluoroquinolone resistance in Salmonella from the food chain.

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