scholarly journals Fluoroquinolone Resistance Associated with Target Mutations and Active Efflux in Oropharyngeal Colonizing Isolates of Viridans Group Streptococci

2000 ◽  
Vol 44 (8) ◽  
pp. 2197-2200 ◽  
Author(s):  
François Guerin ◽  
Emmanuelle Varon ◽  
Annie Buu Hoï ◽  
Laurent Gutmann ◽  
Isabelle Podglajen

ABSTRACT Oropharyngeal samples from 60 hospitalized patients (30 fluoroquinolone [FQ]-treated and 30 non-FQ-treated patients) and 30 untreated nonhospitalized healthy control subjects yielded 20 isolates of viridans group streptococci with reduced susceptibility to FQ, mostly from the hospitalized patients. An efflux phenotype was commonly encountered, expressed either alone or with topoisomerase mutations. Interspecies transfer of the efflux phenotype was demonstrated via transformation of Streptococcus pneumoniae R6 with DNA fromS. mitis and S. oralis.

2004 ◽  
Vol 48 (9) ◽  
pp. 3491-3497 ◽  
Author(s):  
Mathias W. R. Pletz ◽  
Lesley McGee ◽  
James Jorgensen ◽  
Bernard Beall ◽  
Richard R. Facklam ◽  
...  

ABSTRACT The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, ≥8 mg/liter) S. pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain23F-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.


2005 ◽  
Vol 49 (10) ◽  
pp. 4315-4326 ◽  
Author(s):  
Michael J. Stanhope ◽  
Stacey L. Walsh ◽  
Julie A. Becker ◽  
Michael J. Italia ◽  
Karen A. Ingraham ◽  
...  

ABSTRACT Fluoroquinolones are an important class of antibiotics for the treatment of infections arising from the gram-positive respiratory pathogen Streptococcus pneumoniae. Although there is evidence supporting interspecific lateral DNA transfer of fluoroquinolone target loci, no studies have specifically been designed to assess the role of intraspecific lateral transfer of these genes in the spread of fluoroquinolone resistance. This study involves a comparative evolutionary perspective, in which the evolutionary history of a diverse set of S. pneumoniae clinical isolates is reconstructed from an expanded multilocus sequence typing data set, with putative recombinants excluded. This control history is then assessed against networks of each of the four fluoroquinolone target loci from the same isolates. The results indicate that although the majority of fluoroquinolone target loci from this set of 60 isolates are consistent with a clonal dissemination hypothesis, 3 to 10% of the sequences are consistent with an intraspecific lateral transfer hypothesis. Also evident were examples of interspecific transfer, with two isolates possessing a parE-parC gene region arising from viridans group streptococci. The Spain 23F-1 clone is the most dominant fluoroquinolone-nonsusceptible clone in this set of isolates, and the analysis suggests that its members act as frequent donors of fluoroquinolone-nonsusceptible loci. Although the majority of fluoroquinolone target gene sequences in this set of isolates can be explained on the basis of clonal dissemination, a significant number are more parsimoniously explained by intraspecific lateral DNA transfer, and in situations of high S. pneumoniae population density, such events could be an important means of resistance spread.


2003 ◽  
Vol 47 (11) ◽  
pp. 3542-3547 ◽  
Author(s):  
Patrick Grohs ◽  
Serge Houssaye ◽  
Agnès Aubert ◽  
Laurent Gutmann ◽  
Emmanuelle Varon

ABSTRACT The activity of garenoxacin, a new quinolone, was determined in comparison with other quinolones against different strains of S. pneumoniae, viridans group streptococci (VGS), and Enterococcus faecalis. Strains were quinolone-susceptible clinical isolates and quinolone-resistant strains with defined mechanisms of resistance obtained from either clinical isolates or derivatives of S. pneumoniae R6. Clinical quinolone-susceptible strains of S. pneumoniae, VGS and E. faecalis showed garenoxacin MICs within a range of 0.03 μg/ml to 0.25 μg/ml. Garenoxacin MICs increased two- to eightfold when one mutation was present in the ParC quinolone resistance-determining region (QRDR), fourfold when one mutation was present in the GyrA QRDR (S. pneumoniae), 8- to 64-fold when two or three mutations were associated in ParC and GyrA QRDR, and 2,048-fold when two mutations were present in both the GyrA and ParC QRDRs (Streptococcus pneumoniae). Increased active efflux had a moderate effect on garenoxacin MICs for S. pneumoniae and VGS. Against S. pneumoniae, garenoxacin behaved like moxifloxacin and sparfloxacin, being more affected by a single gyrA mutation than by a single parC mutation. Although garenoxacin was generally two- to fourfold more active than moxifloxacin against the different wild-type or mutant strains of S. pneumoniae, VGS, and E. faecalis, it was two- to fourfold less active than gemifloxacin. At four times the respective MIC for each strain, the bactericidal effect of garenoxacin, observed at 6 h for S. pneumoniae and at 24 h for S. oralis and E. faecalis, was not influenced by the presence of mutation either in the ParC or in both the ParC and GyrA QRDRs.


2003 ◽  
Vol 47 (7) ◽  
pp. 2072-2081 ◽  
Author(s):  
Luz Balsalobre ◽  
María José Ferrándiz ◽  
Josefina Liñares ◽  
Fe Tubau ◽  
Adela G. de la Campa

ABSTRACT A total of 46 ciprofloxacin-resistant (Cipr) Streptococcus pneumoniae strains were isolated from 1991 to 2001 at the Hospital of Bellvitge. Five of these strains showed unexpectedly high rates of nucleotide variations in the quinolone resistance-determining regions (QRDRs) of their parC, parE, and gyrA genes. The nucleotide sequence of the full-length parC, parE, and gyrA genes of one of these isolates revealed a mosaic structure compatible with an interspecific recombination origin. Southern blot analysis and nucleotide sequence determinations showed the presence of an ant-like gene in the intergenic parE-parC regions of the S. pneumoniae Cipr isolates with high rates of variations in their parE and parC QRDRs. The ant-like gene was absent from typical S. pneumoniae strains, whereas it was present in the intergenic parE-parC regions of the viridans group streptococci (Streptococcus mitis and Streptococcus oralis). These results suggest that the viridans group streptococci are acting as donors in the horizontal transfer of fluoroquinolone resistance genes to S. pneumoniae.


2001 ◽  
Vol 45 (9) ◽  
pp. 2631-2634 ◽  
Author(s):  
Darrin J. Bast ◽  
Joyce C. S. de Azavedo ◽  
Tiffany Y. Tam ◽  
Laurie Kilburn ◽  
Carla Duncan ◽  
...  

ABSTRACT Analysis of 71 ciprofloxacin-resistant (MIC ≥ 4 μg/ml)Streptococcus pneumoniae clinical isolates revealed only 1 for which the quinolone resistance-determining regions of theparC, parE, and gyrB genes were genetically related to those of viridans group streptococci. Our findings support the occurrence of interspecies recombination of type II topoisomerase genes; however, its contribution to the emergence of quinolone resistance among pneumococci appears to have been minimal.


1977 ◽  
Vol 37 (02) ◽  
pp. 329-338 ◽  
Author(s):  
Tadahiro Sano ◽  
Takeshi Motomiya ◽  
Hiroh Yamazaki ◽  
Takio Shimamoto

SummaryA new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points:1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment.2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positive significant correlations between the values obtained by these three methods.3. It was proved to be highly reproducible and is thought to be useful clinically.By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement of platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.


2020 ◽  
pp. 4-6

The present study was carried out in the Labs of collage of education for pure science, during period from January 2017 to endDecember of the same year. The immune status investigates for CLpatients by measuring the levels of cytokines (IL6and IL10) in sera using a technique enzyme-linked immune Sorbent adsorptive (ELISA). The study included 120 subjects with (60 CLpatientsL.majar and 60 CLpatients L. tropica with and (30) were healthy control. Increased mean Serum level of IL6 was in the observed in the total patients as compared to control Subjects (224.53pg/ml,70.70pg/ml), the result indicate there was significant difference at (p<0.05) ,such observation was consistent in the patient infected with L.majar and L. tropica (104 .90 pg/ml and 112.78 pg/ml) respectively. The results of the IL10 showed significant difference at (p<0.05)increased of mean Serum level in the total CL patients as compared to control Subjects(226.90 pg/ml 46.77pg/ml,).Ahighly significant difference at (p<0.05) increased observed in patients group infected with L.majar and followed by patients group infected L. tropica (112.78pg/ml and 114.12pg/ml) respectively.These results revealed that the excessive presence of cytokines might play a role in CL patients.


2020 ◽  
Vol 14 ◽  
pp. 117863022093839
Author(s):  
Tania Rahman ◽  
Ar-Rafi Md. Faisal ◽  
Tahura Khanam ◽  
Hossain Uddin Shekhar

Perennial indoor environmental pollution in the textile industrial area is a potential health hazard for workers engaged in this line of work, resulting in mental aberration to severe health risks. This study was designed to investigate the indoor environmental quality of textile industries and correlate its effect on the occupational health and well-being of the textile workers by measuring plasma oxidative stress status in textile workers and healthy control subjects. Environmental samples were collected from 15 textile industries located in Dhaka division, and 30 volunteer textile workers and 30 volunteer office workers (control) aged 18 to 57 years participated in the study. The concentration of plasma ascorbic acid (P-ASC), plasma malondialdehyde (P-MDA), and plasma conjugated diene (P-CD) was measured in both groups. The noise level (78.0 ± 0.68 dB) and the formaldehyde level (141.80 ± 4.47 µg/m3) were found to be significantly higher in the indoor environmental area compared with those in the control area (70.17 ± 0.25 dB and 108.0 ± 0.76 µg/m3, respectively). Furthermore, the daily average concentration of suspended particulate matters (PMs), that is, PM2.5 (322.2 ± 13.46 µg/m3) and PM10 (411.0 ± 17.57 µg/m3), was also found to be significantly higher in the indoor environmental air compared with that in the control area (78.59 ± 1.66 and 174.0 ± 2.33 µg/m3, respectively). The levels of P-MDA (0.37 ± 0.03 nmol/L) and P-CD (14.74 ± 0.61 nmol/L) were significantly increased, whereas the level of P-ASC level (0.46 ± 0.04 mg/dL) was markedly decreased in the textile workers compared with the healthy control subjects (0.18 ± 0.01 nmol/L of P-MDA, 10.04 ± 0.44 nmol/L of P-CD, and 1.29 ± 0.06 mg/dL of P-ASC). The textile plants were found to have significantly elevated levels of indoor environmental pollutants compared with those in the control area, and the textile workers were significantly exposed to oxidative stresses compared with the control subjects. The use of noise pads and high-efficiency air filters is perhaps highly instrumental to put an end to this prevailing situation. Moreover, to overcome the oxidative stresses among workers, supplementation of antioxidant vitamins (ie, ascorbic acid and/or vitamin E) may be beneficial. In addition, to prevent serious health-related issues, proper precautions should be taken to protect the occupational health of the textile workers.


2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199296
Author(s):  
Juan Wang ◽  
Liu Yang ◽  
Yanjun Diao ◽  
Jiayun Liu ◽  
Jinjie Li ◽  
...  

Objective To evaluate the performance of a DNA methylation-based digital droplet polymerase chain reaction (ddPCR) assay to detect aberrant DNA methylation in cell-free DNA (cfDNA) and to determine its application in the detection of hepatocellular carcinoma (HCC). Methods The present study recruited patients with liver-related diseases and healthy control subjects. Blood samples were used for the extraction of cfDNA, which was then bisulfite converted and the extent of DNA methylation quantified using a ddPCR platform. Results A total of 97 patients with HCC, 80 healthy control subjects and 46 patients with chronic hepatitis B/C virus infection were enrolled in the study. The level of cfDNA in the HCC group was significantly higher than that in the healthy control group. For the detection of HCC, based on a cut-off value of 15.7% for the cfDNA methylation ratio, the sensitivity and specificity were 78.57% and 89.38%, respectively. The diagnostic accuracy was 85.27%, the positive predictive value was 81.91% and the negative predictive value was 87.20%. The positive likelihood ratio of 15.7% in HCC diagnosis was 7.40, while the negative likelihood ratio was 0.24. Conclusions A sensitive methylation-based assay might serve as a liquid biopsy test for diagnosing HCC.


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