- Volume 67, Issue 11, 2018
Volume 67, Issue 11, 2018
- Antimicrobial Resistance
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A carbapenem-resistant clinical isolate of Aeromonas hydrophila in Japan harbouring an acquired gene encoding GES-24 β-lactamase
Several species of Aeromonas produce the enzyme CphA metallo-β-lactamase. This study describes an isolate of Aeromonas hydrophila harbouring an acquired gene encoding the carbapenemase GES-24. This isolate was obtained from an inpatient in Okinawa, Japan, with no apparent record of travelling overseas. The minimum inhibitory concentrations of carbapenems against this isolate were 8 µg ml−1 for imipenem and 16 µg ml−1 for meropenem. Recombinant GES-24 hydrolyzed all of the tested β-lactams, including imipenem and meropenem. The genomic environment surrounding bla GES-24 was intI1-bla GES-24 -aac(6′)-IIc-qacEdelta1-sulI-orfX-tetR-tetE. This is the first report of A. hydrophila producing a GES-type carbapenemase.
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Prevalence and antimicrobial susceptibilities of Acinetobacter baumannii and non-baumannii Acinetobacters from Terengganu, Malaysia and their carriage of carbapenemase genes
A total of 153 non-repeat Acinetobacter spp. clinical isolates obtained in 2015 from Hospital Sultanah Nur Zahirah (HSNZ) in Terengganu, Malaysia, were characterized. Identification of the isolates at species level was performed by ribosomal DNA restriction analysis (ARDRA) followed by sequencing of the rpoB gene. The majority of the isolates (n=128; 83.7 %) were A. baumannii while the rest were identified as A. nosocomialis (n=16), A. calcoaceticus (n=5), A. soli (n=2), A. berezeniae (n=1) and A. variabilis (n=1). Multidrug resistance (MDR) was most prevalent in A. baumannnii (66.4 %) whereas only one non-baumannii isolate (A. nosocomialis) was MDR. The bla OXA-23 gene was the predominant acquired carbapenemase gene (56.2 %) and was significantly associated (P<0.001) with carbapenem resistance. However, no significant association was found for carbapenem resistance and isolates that contained the ISAba1-bla OXA-51 configuration.
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- Clinical Microbiology
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Molecular analysis of Streptococcus pyogenes strains isolated from patients with recurrent pharyngitis after oral amoxicillin treatment
More LessPurpose. The most common illness caused by Streptococcus pyogenes (Group A streptococcus; GAS) is acute pharyngitis. It has been reported that a small percentage of patients experience recurrent GAS pharyngitis after 10 days of treatment with oral amoxicillin. The aim of this study was to clarify whether recurrent GAS pharyngitis is reactivation caused by the primary strain remaining at the infection site, or if the reinfection is caused by newly acquired strains.
Methodology. A total of 135 GAS clinical strains were isolated from the tonsils of 116 pediatric patients with acute GAS pharyngitis between November, 2012 and April, 2014 in Saga, Japan. These strains were analysed by pulsed-field gel electrophoresis (PFGE)-typing methods.
Results. The isolates were grouped into 16 PFGE-types. The epidemic PFGE types that caused pharyngitis were found to change dynamically during 18 months. Eleven strains caused recurrent pharyngitis within 40 days after the last treatment, all of them showing the same PFGE-type as the primary strains. Eight of the strains caused recurrence more than 40 days after the treatment. Among them, six showed different PFGE-types from the primary strains.
Conclusion. When recurrent pharyngitis emerges more than 40 days after the last treatment, penicillin can be prescribed again because reinfection is suspected. However, when recurrent pharyngitis takes place within 40 days after completing the treatment, alternative drugs should be considered for retreatment because the pharyngitis is likely to be due to reactivation.
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Microbiological and clinical characteristics of Group B Streptococcus isolates causing materno-neonatal infections: high prevalence of CC17/PI-1 and PI-2b sublineage in neonatal infections
Purpose. Group B Streptococcus (GBS) is one of the major pathogens in severe materno-neonatal infections. We aimed to describe the clinical and molecular characteristics of GBS isolates causing infections in 45 maternal and 50 neonatal subjects, collected from eight healthcare centres in mainland China over the period 2010– 2017.
Methodology. The phenotypic and genotypic features of the GBS isolates, including capsular polysaccharide (cps) serotypes, pilus island (PI) genes and antibiotic resistance profiles and genes, were characterized by both conventional and molecular methods. The clonal relationship between these strains was investigated using multilocus sequence typing (MLST).
Results. Of the 95 isolates, the predominant serotypes were III (51, 53.7 %), V (13, 13.7 %) and Ib (13, 13.7 %). All GBS strains carried at least one pilus island, with 32.6 % carrying PI-2b and 67.4 % PI-2a, singly or in combination. The most frequently-detected pilus island pattern was the combination of PI-1 and PI-2a, accounting for 56.8 % (54 isolates), followed by PI-1 combined with PI-2b (28, 29.5 %), PI-2a (10, 10.5 %) and PI-2b (3, 3.2 %). The strains were classified into 17 individual sequence types, and further clustered into six clonal complexes (CCs). A high prevalence of CC17/PI-1 and PI-2b (17, 34.0 %) was detected in 50 GBS isolates causing neonatal infections. No strain was resistant to penicillin, ampicillin, ceftriaxone or vancomycin, whereas 78.9, 76.8 and 81.5 % were resistant to erythromycin, clindamycin and tetracycline, respectively.
Conclusion. Our study highlights the high genotypic diversity of GBS strains causing materno-neonatal infections, and the CC17/PI-1 and PI-2b sublineages should be noted in neonatal infections.
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- Disease, Diagnosis and Diagnostics
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Development of a rapid colorimetric multiplex PCR–reverse line blot for the detection and typing of 14 Chlamydia trachomatis genovars
Purpose. Chlamydiatrachomatis is responsible for trachoma-associated blindness as well as the most common sexually transmitted bacterial infection worldwide, although the genovars for the former are typically A–C, whilst for the latter they are D–K and for the uncommon infection lymphogranuloma venereum they are L1–3. Nucleotide variations within the ompA gene facilitate the identification of C. trachomatis genovars. This study describes a colorimetric multiplex PCR/RLB typing assay (mPCR-RLB) directed to the VD2 region of the ompA gene for general C. trachomatis positivity and the identification of 14 individual C. trachomatis genovars.
Methodology. The assay was validated by analysing 40 blinded samples that included reference strains of C. trachomatis genovars and other non-chlamydial micro-organisms that had been analysed previously using quantitative PCR (qPCR). Ninety clinical samples that had previously been found to be C. trachomatis-positive by qPCR were also evaluated using the mPCR-RLB assay.
Results. The mPCR-RLB assay showed 100 % agreement with the qPCR in the detection of C. trachomatis reference strains and no cross-reaction of non-chlamydial micro-organisms was observed. In the analysis of the chlamydial clinical samples, 97.8 % were C. trachomatis-positive by mPCR/RLB assay and there was a 96.6 % concordance with the qPCR at the group identification level and a 92.2 % concordance at the genovar level.
Conclusion. The mPCR-RLB assay is a rapid and sensitive methodology for the identification of C. trachomatis genovars associated with urogenital infections, trachoma or lymphogranuloma venereum diseases that can be implemented in clinical settings, helping to identify reinfections and treatment failures and establish the appropriate treatment course.
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Conventional culture method and qPCR using 16S rDNA for tissue bank: a comparison using a model of cardiac tissue contamination
Real-time polymerase chain reaction (qPCR) using 16S rDNA is an alternative to conventional culture-based tests. The aim of this study was to compare the conventional culture method with qPCR using 16S rDNA in a model of cardiac tissue contamination. Samples of cardiac tissue for artificial contamination with Escherichia coli and control samples were submitted for DNA extraction, which was conducted by selective and alkaline lysis and purification steps. A standard curve for 16S rDNA was constructed to determine the efficiency and analytical sensitivity of the assay in concentrations from 106 to 102 c.f.u. ml−1 using TaqMan Master Mix. 16S rDNA was detected in all contaminated samples; however, it was not detected in the the final washing step solution of the sample with a bioburden of 102 c.f.u. ml−1. Using qPCR is a potential alternative to conventional culture for microbiological safety testing of allograft tissues for biobanking, reducing the time and labour input required.
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Comparison of the Cepheid Xpert Xpress Flu/RSV Assay to in-house Flu/RSV triplex real-time RT-PCR for rapid molecular detection of Influenza A, Influenza B and Respiratory Syncytial Virus in respiratory specimens
More LessThis study compared the performance of the commercially available Xpert Xpress Flu/RSV assay to an in-house FluAB/RSV triplex real-time RT-PCR assay for the detection of influenza A/B viruses and respiratory syncitial virus (RSV) from both nasopharyngeal aspirate (NPA) and nasopharyngeal flocked swab (NPS). A total of 20 external quality assurance (EQA) samples and 172 clinical respiratory samples were tested prospectively using both the Xpert Xpress Flu/RSV assay and the in-house FluAB/RSV triplex assay. For the EQA samples, concordance rate was 100 % when tested with both assays. For clinical samples, there was 100 % agreement between the two assays for detection of influenza A and influenza B, 96.7 % agreement for detection of RSV and 99.7 % agreement for negative results. With a shortened turnaround time and good diagnostic performance, application of the Xpert Xpress Flu/RSV assay can facilitate patient triage for prompt implementation of infection control measures and management of high-risk patients during influenza epidemics.
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Are bacterial culture quantifications reliable? Comparative performance of the WASP automated inoculation instrument in the era of ISO 15189 accreditation
Purpose. Isolating colonies and obtaining accurate colony counts from bacterial cultures are critical steps for the optimal management of infected patients. The uncertainties in the colony count results from the bacterial cultures were evaluated by verifying the performance of the WASP inoculation system according to the International Organization for Standardization (ISO) 15189 standard.
Methodology. We first (i) evaluated the cross-contamination and precision of the WASP instrument (Copan Diagnostics, Italy) and (ii) established enumeration reading grids for urine, swab, bronchopulmonary specimens (BPSs) and catheter tip cultures. Subsequently, 72 clinical samples were tested to compare the results of the WASP, PREVI Isola (bioMérieux, France) and manual inoculation methods.
Results. The WASP method did not show cross-contamination. The coefficient of variation for the colony counts in the repeatability experiment was evaluated for 10 µl and 30 µl loop protocols and determined to be 29 and 14 %, respectively. The agreement between the automated and manual methods and between the automated methods for the colony counts was high (94.4 and 100 %, respectively). The WASP method yielded better isolation quality compared to the manual method (P=0.020) and to the PREVI Isola only when polymicrobial specimens were considered (P=0.014). For quantification evaluation, the measurement uncertainty was evaluated to 1.8×103 c.f.u. ml−1 for a suspension of Escherichia coli at 104 c.f.u. ml−1.
Conclusion. We report the verification of the performance of the WASP instrument and describe a rapid procedure for achieving semi-quantitative cultures from BPSs and catheter tips. Quantitative interpretation of the bacterial cultures should be performed with caution.
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Rapid identification of pathogens from positive blood culture bottles with the MinION nanopore sequencer
Purpose. Bloodstream infections are major causes of morbidity and mortality that lead to prolonged hospital stays and higher medical costs. In this study, we aimed to evaluate the MinION nanopore sequencer for the identification of the most dominant pathogens in positive blood culture bottles.
Methodology. 16S and ITS1-5.8S-ITS2 rRNA genes were amplified by PCR reactions with barcoded primers using nine clinical isolates obtained from positive blood bottles and 11 type strains, including five types of Candida species. Barcoded amplicons were mixed, and multiplex sequencing with the MinION sequencer was performed. In addition, barcoded PCR amplicons were sequenced by Sanger sequencing to validate the performance of the MinION.
Results. The bacterial and Candida spp. identified by MinION sequencing, based on the highest homology of reference sequences from the NCBI gene databases, agreed with the matrix-assisted laser desorption ionization time of flight mass spectrometry results, excepting the closely related species Streptococcusand Escherichia coli. The ‘pass’ reads obtained within about 10 min of sequencing were sufficient to identify the pathogens. The average values of sequence identities with 1D2 chemistry and the R9.5 flow cell were around 99 %; thus, frequent sequence errors did not affect species identification based on amplicon sequencing.
Conclusion. We have established a rapid, portable and economical technique for the identification of pathogens in positive blood culture bottles through a novel MinION nanopore sequencer amplicon sequencing scheme, which replaces traditional Sanger sequencing.
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- Microbial Epidemiology
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An outbreak of Shigella boydii serotype 20 in January 2015 amongst United Kingdom healthcare workers involved in the Ebola response in Sierra Leone
In January 2015, Public Health England and the United Kingdom (UK) Ministry of Defence investigated cases of diarrhoea and fever in military personnel recently returned to the UK after supporting the response to the Ebola epidemic in Sierra Leone. Tests for Ebola virus infection were negative. PCR tests detected the ipaH gene in 10/12 faecal specimens, and Shigella boydii serotype 20 was isolated from 7 patients. A case control study was undertaken and analysed using multivariable logistic regression. Consumption of a coronation chicken lunch at the transit camp in Sierra Leone (SL) 24–48 h prior to departure for the UK was significantly associated with disease [adjusted odds ratio (OR) 28.15, 95 % CI: 1.87–422.65]. In the context of heightened concern during the Ebola epidemic, this outbreak highlights the importance of rapid and effective microbiological and epidemiological investigations to identify the aetiological agent in patients presenting with fever and diarrhoea.
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Candida africana in recurrent vulvovaginal candidiasis (RVVC) patients: frequency and phenotypic and genotypic characteristics
More LessPurpose. Up to 75 % of all women develop vulvovaginal candidiasis (VVC), with symptoms such as vulvar erythema, pruritus and abnormal vaginal discharge. Despite the global distribution of Candida africana, its role in recurrent vulvovaginal candidiasis (RVVC) is still unclear and requires further investigation. Here, we report on the frequency of C. africana among clinical isolates from patients with RVVC in Bushehr in southern Iran.
Methodology. Isolated Candida strains were identified by ITS-PCR-RFLP. Hyphal wall protein 1 (HWP1) was amplified to differentiate C. africana and the resulting sequences were subjected to phylogenetic analyses with a view to identifying similarities and differences in nucleotides.
Results. Ten out of 119 strains originally identified as C. albicans turned out to be C. africana. Pairwise nucleotide alignment of HWP1 DNA sequences showed 100 % similarity between C. africana strains. Inter-species variation between Iranian C. africana HWP1 sequences and the only three available C. africana type sequences in GenBank revealed 99.7–100 % nucleotide similarity. Phylogenetic analysis of the HWP1 DNA sequences of 10 Iranian C. africana isolates, the 3 C. africana sequences available in GenBank and 2 representative Iranian C. albicans sequences revealed that all 11 Iranian C. africana strains formed a well-supported cluster separated from the remaining C. africana.
Conclusion. In our sample, C. africana was only isolated from 7.8 % of the patients with RVVC. While size polymorphisms in HPW1 genes allowed us to differentiate C. africana from C. albicans, no evidence of sequence variation within the Iranian C. africana isolates was observed.
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Evaluating the microbial pattern of periprosthetic joint infections of the hip and knee
Purpose. Periprosthetic joint infection (PJI) is a devastating complication that leads to enormous economic and health care complaints from affected patients. The aim of this study is to identify the causative pathogens responsible for PJI, evaluate temporal trends concerning the pathogen pattern and identify potential risk factors for PJI.
Methodology. This was a retrospective study analysing a total of 937 patients suffering PJI of the hip or knee joint between 2003 and 2011.
Results. In total, 394 patients (42.0 %) with total knee arthroplasty (TKA), 477 patients (50.9 %) with total hip arthroplasty (THA) and 64 patients (6.8 %) receiving a dual-head prosthesis had to be hospitalised due to PJI. In two cases (0.2 %), a simultaneous infection of TKA and THA occurred. The mean age of the study cohort was 70.85±11.68 years. The mean body mass index (BMI) was 28.53±5.7. According to the Charlson comorbidity index, 2.99 % of the patients were classified as severity Grade 1, 13.98 % Grade 2, 40.02 % Grade 3 and 43.0 % Grade 4. Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus epidermidis (MRSE), methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative Staphylococcus (CoNS), Streptococcus, and Enterococcus were the pathogens mainly responsible. An increase in high-resistance pathogens, such as MRSE, extended-spectrum beta-lactamase bacteria (ESBL), ampicillin-resistant Enterococcus, Acinetobacter spp. and vancomycin-resistant Enterococcus (VRE), was found during the study period. Only MRSA showed a declining tendency in a regression model.
Conclusion. Patients suffering PJI present a certain risk profile with many comorbidities, e.g. high age and obesity. The observed microbiological pattern demonstrates the rise of high-resistance pathogens.
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Determination and genome-wide analysis of Epstein-Barr virus (EBV) sequences in EBV-associated gastric carcinoma from Guangdong, an endemic area of nasopharyngeal carcinoma
About 10 % of gastric carcinoma worldwide is associated with EBV, which is defined as EBV-associated gastric carcinoma (EBVaGC). To date, EBV sequence data from EBVaGC in Guangdong, China, an endemic area of nasopharyngeal carcinoma (NPC), are not available. In the present study, two EBV genomes from EBVaGC specimens from Guangdong (designated as GDGC1 and GDGC2) were determined by next-generation sequencing, de novo assembly and joining of contigs by Sanger sequencing. In addition, we sequenced EBV from two Korean EBVaGC cell lines, YCCEL1 and SNU-719. Genomic diversity, including single nucleotide polymorphisms (SNPs) and insertions and deletions (indels), phylogenetic analysis and rates of protein evolution, was performed using bioinformatics software. The four gastric carcinoma-derived EBV (GC-EBV) were all type I. Compared with the reference EBV genome, a total of 1815 SNPs (146 indels), 1519 SNPs (106 indels), 1812 SNPs (126 indels) and 1484 SNPs (106 indels) were found in GDGC1, GDGC2, YCCEL1 and SNU-719, respectively. These variations were distributed across the entire genome, especially in latent genes. In contrast, the sequences of promoters and non-coding RNAs were strictly conserved. Phylogenetic analyses suggested the presence of at least two parental lineages of EBV among the GC-EBV genomes. Rates of protein evolution analyses showed that lytic genes were under purifying selection; in contrast, latency genes were under positive selection. In conclusion, this study determined the EBV genomes in EBVaGC from Guangdong and performed a detailed genome-wide analysis of GC-EBV, which would be helpful for further understanding of the relationship between EBV genomic variation and EBVaGC carcinogenesis.
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- Pathogenicity and Virulence/Host Response
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Gluconeogenic growth of Vibrio cholerae is important for competing with host gut microbiota
Purpose. The gastrointestinal tract is home to thousands of commensal bacterial species. Therefore, competition for nutrients is paramount for successful bacterial pathogen invasion of intestinal ecosystems. The human pathogen Vibrio cholerae, the causative agent of the severe diarrhoeal disease, cholera, is able to colonize the small intestine, which is protected by mucus. However, it is unclear which metabolic pathways or nutrients V. cholerae utilizes during intestinal colonization and growth.
Methodology. In this study, we investigated the effect of various metabolic key genes, including those involved in the gluconeogenesis pathway, on V. cholerae physiology and in vivo colonization.
Results. We found that gluconeogenesis is important for infant mouse colonization. Growth assays showed that mutations in the key components of gluconeogenesis pathway, PpsA and PckA, lead to a growth defect in a minimal medium supplemented with mucin as a carbon source. Furthermore, the ppsA/pckA mutants colonized poorly in the adult mouse intestine, particularly when more gut commensal flora are present.
Conclusion. Gluconeogenesis biosynthesis is important for the successful colonization of V. cholerae in a niche that is full of competing microbiota.
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Polymorphic variability in the exon 19 of the RB1 gene and its flanking intronic sequences in HPV16-associated precancerous lesions in the Greek population
Purpose. The tumour suppressor protein RB plays a decisive role in negative control of the cell cycle, inhibiting tumour development. The present analysis investigated the prevalence of the nucleotide polymorphism A153104G, which is located at intron 18 of the RB1 gene, and investigated the impact of the polymorphic variability in the exon 19 and its flanking intronic sequences on the severity of cervical disease in HPV16-positive Greek women.
Methodology. The nucleotide polymorphism A153104G was detected by PCR-RFLP assay, while the amplicons were further subjected to cloning and sequencing. Moreover, molecular evolutionary analysis was performed using the maximum-likelihood (ML) and empirical Bayesian (EB) methods in order to evaluate the selective pressure acting on exon 19 of the RB1 gene.
Results/Key findings. The A153104G nucleotide polymorphism was only detected in one control case. Moreover, sequence analysis of the amplicons revealed that the polymorphic variability in the RB1 gene increased with the severity of the cervical dysplasia. The link between the observed polymorphic variability and the progress of cervical disease was reflected in the molecular evolutionary analysis that was performed on the exon 19 of the RB1 gene, since negative selective pressure was acting upon exon 19 in the control and low-grade squamous intraepithelial lesion (LSIL) cervical samples, while positive selective pressure was acting upon exon 19 in the high-grade squamous intraepithelial lesion (HSIL) specimens.
Conclusions. The A153104G nucleotide polymorphism did not emerge as a potential biomarker for the development of precancerous lesions in the Greek patients, while the accumulation of sequence variations in RB1 gene might influence patients’ susceptibility towards the progression of cervical neoplasia.
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- Prevention and Therapy
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Human papilloma virus genotype distribution and risk factor analysis amongst reproductive-age women in urban Gambia
More LessPurpose. Cervical cancer is the most frequently diagnosed female cancer in The Gambia, representing approximately 30 % of cases. In 2014, the quadrivalent human papilloma virus (HPV) vaccine was introduced, which offers protection against HPV genotypes 6, 11, 16 and 18. To evaluate the potential effectiveness of this vaccine, genotype distribution and risk factor analysis were assessed.
Methodology. Endocervical samples (n=232) were collected from women aged 20–49 years residing in urban Gambia. A questionnaire was administered to capture socio-demographic and cervical cancer risk factors. HPV detection and genotyping was performed by PCR amplification of the L1 major capsid gene and analysis of sequenced PCR products.
Results/Key findings. The prevalence of HPV was 12 % (28/232), and the high-risk (HR) genotype HPV 52 (5/28) was the most prevalent genotype. HR-HPV sequences had high identity (≥90 %) to isolates which originated from America, Europe and Asia but not from Africa. Half (14/28) of participants were co-infected with Ureaplasma urealyticum/parvum, which increases the risk of progression to cervical cancer. Female genital mutilation and the use of hormone contraception for >5 years were identified as potential risk factors for HPV infection. Ethnicity-associated differences were also noted; participants of the Fula ethnic group had a higher prevalence of HR-HPV infection (31.3 %) compared to the Mandinka (18.8 %) and Wollof (12.5 %) groups.
Conclusion. These data may have a significant public health impact as the HPV quadrivalent vaccine may be of limited value if the circulating non-HPV 16/18 HR-genotypes are responsible for cytological abnormalities of the cervix.
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Clioquinol is a promising preventive morphological switching compound in the treatment of Candida infections linked to the use of intrauterine devices
Purpose. Candida biofilm infections are frequently linked to the use of biomaterials and are of clinical significance because they are commonly resistant to antifungals. Clioquinol is an antiseptic drug and is effective against multidrug-resistant Candida. We investigated the effect of clioquinol and two other 8-hydroxyquinoline derivatives on Candida biofilm.
Methodology. The ability to inhibit biofilm formation, inhibit preformed biofilm and remove established biofilms was evaluated using in vitro assays on microtitre plates. The action of clioquinol on biofilm in intrauterine devices (IUDs) was also investigated, describing the first protocol to quantify the inhibitory action of compounds on biofilms formed on IUDs.
Results. Clioquinol was found to be the most effective 8-hydroxyquinoline derivative among those tested. It prevented more than 90 % of biofilm formation, which can be attributed to blockade of hyphal development. Clioquinol also reduced the metabolic activity of sessile Candida but the susceptibility was lower compared to planktonic cells (0.031–0.5 µg ml−1 required to inhibit 50 % planktonic cells and 4–16 µg ml−1 to inhibit 50 % preformed biofilms). On the other hand, almost complete removal of biofilms was not achieved for the majority of the isolates. Candida spp. also showed the ability to form biofilm on copper IUD; clioquinol eradicated 80–100 % of these biofilms.
Conclusion. Our results indicate a potential application in terms of biomaterials for 8-hydroxyquinoline derivatives. Clioquinol could be used as a coating to prevent morphological switching and thus prevent biofilm formation. Furthermore, clioquinol may have future applications in the treatment of Candida infections linked to the use of IUDs.
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Volumes and issues
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Volume 73 (2024)
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Volume 72 (2023 - 2024)
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