Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli.

Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for blaCTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of blaCTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice.

Analysis of Staphylococcal Toxins and Clinical Outcomes of Methicillin-Resistant Staphylococcus aureus Bacteremia.

It is well known that methicillin-resistant Staphylococcus aureus (MRSA) produces many virulence factors, such as hemolysins, leukocidins, proteases, enterotoxins, exfoliative toxins, and immune-modulatory factors. The aim of study was to identify staphylococcal pathogenicity that may affect the prognosis of patients with MRSA bacteremia. We obtained 149 MRSA strains from blood cultures between January 2009 and December 2014 in our institution. We collected information on patient characteristics, laboratory data, staphylococcal toxin genes, and susceptibility of the strain toward anti-MRSA agent and analyzed them as factors contributing to 30-d mortality. The "survival" and "dead" groups consisted of 103 and 46 patients, respectively. Multiple logistic regression analysis showed a four-fold increase in the risk of mortality in patients exhibiting isolated MRSA with staphylococcal enterotoxins (SEs) genes as well as toxic shock syndrome toxin-1 (TSST-1) genes [odds ratio: 3.89; 95% confidence interval: 1.20-12.60; p=0.024]. Kaplan-Meier analysis also showed significantly higher mortality in patient with isolated MRSA with SEs and TSST-1 genes. After adjusting for confounders, the coexistence of SEs and TSST-1 were independently associated with the 30-d mortality compared with treatment and susceptibility. The coexistence of superantigenic toxin genes greatly affects the clinical course and prognosis of patients with MRSA bacteremia.

Evaluation of new automated syphilis test reagents 'IMMUNOTICLES AUTO3' series: performance, biochemical reactivity, and clinical significance.

BACKGROUND: Automated nontreponemal and treponemal test reagents based on the latex agglutination method (immunoticles auto3 RPR: ITA3RPR and immunoticles auto3 TP: ITA3TP) have been developed to improve the issues of conventional manual methods such as their subjectivity, a massive amount of assays, and so on. We evaluated these reagents in regards to their performance, reactivity to antibody isotype, and their clinical significance. METHODS: ITA3RPR and ITA3TP were measured using a clinical chemistry analyzer. Reactivity to antibody isotype was examined by gel filtration analysis. RESULTS: ITA3RPR and ITA3TP showed reactivity to both IgM- and IgG-class antibodies and detected early infections. ITA3RPR was verified to show a higher reactivity to IgM-class antibodies than the conventional methods. ITA3RPR correlated with VDRL in the high titer range, and measurement values decreased with treatment. ITA3RPR showed a negative result earlier after treatment than conventional methods. ITA3TP showed high specificity and did not give any false-negative reaction. Significant differences in the measurement values of ITA3RPR between the infective and previous group were verified. CONCLUSIONS: The double test of ITA3RPR and ITA3TP enables efficient and objective judgment for syphilis diagnosis and treatments, achieving clinical availability.

Linezolid-resistant Staphylococcus aureus isolated from 2006 through 2008 at six hospitals in Japan.

Limited use of linezolid for treating methicillin-resistant Staphylococcus aureus (MRSA) infection was approved in Japan in 2006. We report here the status of linezolid-resistant MRSAs in Japan. Eleven linezolid-resistant clinical isolates from 11 patients at six hospitals were collected from 2006 through 2008. The minimal inhibitory concentration (MIC) of linezolid in these strains varied from 8 to 64 µg/ml. All strains had at least one G2576T mutation in the chromosomal gene(s) encoding domain V of the 23S ribosomal RNA (rRNA). Chromosomal DNA encoding five copies of the domain V region was analyzed by polymerase chain reaction (PCR). Strains with the linezolid MICs of 64, 32, 16, and 8 µg/ml had the G2576T mutation(s) in four, three (or four), two, and one copy of the 23S rRNA genes, respectively. These results suggest that the level of linezolid resistance seems to be roughly correlated with the number of mutations in the genes encoding 23S rRNA. DNA samples from all 11 strains were subjected to pulsed-field gel electrophoresis and were classified into seven independent clones having >92% identity. Among the 11 patients, five had been treated with linezolid and the remainder, in two hospitals, had no history of prior linezolid use. The results suggested possible nosocomial infections by linezolid-resistant MRSA.

Analysis of OXA23 and AmpCß-Lactamase Genes in Clinically Isolated Multidrug-Resistant Acinetobacter baumannii Clonal Complex 92.

Multidrug-resistant Acinetobacter baumannii, which is resistant to carbapenems, amino glycosides, and fluoroquinolones, was isolated from the wound of an outpatient. We performed Multi Locus Sequence Typing and analyzed the structures of the AmpC ß-lactamase and OXA23 carbapenemase genes. This strain was assigned as ST451, a member of clonal complex 92, by its MLST scheme. The structures of ISAba1-AmpC ß-lactamase and ISAba1-OXA23 carbapenemase were revealed and the major globally prevalent clone of carbapenem-resistant A. baumannii was identified.

A molecular analysis of quinolone-resistant Haemophilus influenzae: validation of the mutations in Quinolone Resistance-Determining Regions.

The mechanism of quinolone-resistance is considered to be amino acid mutations in the type II topoisomerase. We validated the genetic mechanisms of quinolone resistance in Haemophilus influenzae. We obtained 29 H. influenzae strains from a nationwide surveillance program in Japan (including 11 quinolone-resistant strains [moxifloxacin: MFLX or levofloxacin MIC ≥2 µg/ml]). We analyzed the sequences of the Quinolone Resistance-Determining Regions (QRDRs) in GyrA, GyrB, ParC and ParE. Furthermore, we induced resistance in susceptible strains by exposing them to quinolone, and investigated the relationship between mutations in the QRDRs and the MICs. Five amino acid substitutions in GyrA (at Ser84 and Asp88) and ParC (at Gly82, Ser84 and Glu88) were found to be closely related to the MICs. The strains with a MFLX MIC of 0.125-1 and 2-4 µg/ml had one and two mutations, respectively. The strains with a MFLX MIC of ≥8 µg/ml had three or more mutations. The strains with induced resistance with MFLX MICs of 0.5-1 and ≥2 µg/ml also had one and two mutations, respectively. We confirmed that these five mutations strongly contribute to quinolone resistance and found that the degree of resistance is related to the number of the mutations. In addition, the three strains of 18 susceptible strains (16.7%) also had a single mutation. These strains may therefore be in the initial stage of quinolone resistance. Currently, the frequency of quinolone-resistant H. influenzae is still low. However, as has occurred with ß-lactams, an increase in quinolone use may lead to more quinolone-resistant strains.

Antibiotic susceptibility survey of blood-borne MRSA isolates in Japan from 2008 through 2011.

We conducted an antibiotic susceptibility survey of 830 blood-borne methicillin resistant Staphylococcus aureus collected from nationwide hospitals in Japan over a three-year period from January 2008 through May 2011. Antibiotic susceptibility was judged according to the criteria recommended by the Clinical Laboratory Standard Institute. Over 99% of the MRSA showed to be susceptible to teicoplanin, linezolid, sulfamethoxazole/trimethoprim and vancomycin, and over 97% of them were susceptible to daptomycin, arbekacin and rifampin. The majority of the MRSA strains showed resistant to minocycline, meropenem, imipenem, clindamycin, ciprofloxacin, cefoxitin, and oxacillin in the rates of 56.6, 72.9, 73.7, 78.7, 89.0, 99.5, and 99.9%, respectively. Among the MRSA strains, 72 showed reduced susceptibility to vancomycin, including 8 strains (0.96%) of vancomycin-intermediate S. aureus (VISA), 54 (6.51%) of heterogeneous vancomycin-intermediate S. aureus (hVISA), and 55 (5.63%) of ß-lactam antibiotics-induced vancomycin resistant S. aureus (BIVR). Unexpectedly, among the 54 hVISA and 55 BIVR, 45 isolates (83.3% and 81.8%, respectively) showed both hVISA and BIVR phenotypes. A new trend of vancomycin resistance found in this study was that VISA strains were still prevalent among the bacteremic specimens. The high rates of the hVISA/BIVR two-phenotypic vancomycin resistance, and the prevalence of VISA in the bloodborne MRSA call attention in the MRSA epidemiology in Japan.

Detection of metallo-ß-lactamase genes in clinically isolated Klebsiella pneumoniae and Klebsiella oxytoca.

We detected and characterized metallo-ß-lactamase genes (blaIMP-1 and blaIMP-11) in third generation cephalosporin-resistant Klebsiella pneumoniae and Klebsiella oxytoca isolated at Showa University Hospital between January 1, 2011 and December 31, 2012. The cephalosporin-resistant K pneumoniae strains were frequently isolated from the urine, while one strain of K. pneumoniae, which was resistant to carbapenem, was isolated from the stool. We analyzed the phenotypes and genotypes of the metallo-ß-lactamase genes from the 16 strains of cephalosporin-resistant-K pneumoniae and 6 strains of -K. oxytoca isolated from the same ward. The minimum inhibitory concentrations of imipenem were below 4 µg/ml in 21 out of the 22 isolated strains. The double disc synergy test using ceftazidime and sodium mercaptoacetic acid revealed enlargements in the inhibitory zones of 14 of the 16 strains of K. pneumoniae and all 6 strains of K. oxytoca. Metallo-ß-lactamase genes were detected in all of the tested strains, with blaIMP-1 in 3 K. pneumoniae and 1 K. oxytoca, blaIMP-11 in 13 K pneumoniae and 4 K. oxytoca, and both blaIMP-1 and blaIMP-11 in one K. oxytoca. Our results indicate that third generation cephalosporin-resistant and imipenem-susceptible K. pneumoniae and K. oxytoca possess the metallo-ß-lactamase gene. The active surveillance of metallo-ß-lactamase genes should be performed in clinical laboratories. (Original).

MLST analysis of multiple antimicrobial resistant Acinetobacter baumannii.

Multi-locus sequencing typing (MLST) of Acinetobacter baumannii, isolated at Showa University Hospital, was performed between November 2010 and March 2011. A. baumannii was isolated from 15 patients. Among the 15 isolates, the STs of three isolates were able to be determined, ST76, ST92, and ST146, and belonged to Clonal Complex (CC) 92, the global epidemic clone among carbapenem resistant A. baumannii. The other 12 strains were not applicable to the MLST classification. The ST76 strain was resistant to carbapenems, aminoglycosides, and fluoroquinolones. The ST92 strain was resistant to aminoglycosides and fluoroquinolones. The ST146 strain was resistant to fluoroquinolones. The other 12 strains were susceptible to either of the drugs. Neither the metallo beta lactamase gene (IMP type or VIM2) nor the OXA23 gene was detected in carbapenem resistant A. baumannii. These results indicate that A. baumannii of CC92 has spread as the drug resistant strain in Japan. Monitoring A. baumannii using molecular epidemiology is necessary.

[Whipple's disease].

A 36-year-old woman presented with fever, diarrhea, and weight loss in April 2011. Upper GI endoscopy and colonoscopy showed a diffuse yellow-white shaggy mucosa in the second part of the duodenum and the ileum end, respectively. These lesions in these 2 locations were biopsied, and both specimens showed distended epithelial villi and massive infiltration of foamy macrophages in the lamina propria. PCR was performed to identify causative bacilli. DNA extracted from the duodenal mucosa showed a specific PCR product, confirming the diagnosis of Whipple's disease. The patient was treated with a 2-week course of ceftriaxone, followed by sulfamethoxazole/trimethoprim. After we started the treatment, the patient developed complications of infective endocarditis and meningitis. The patient was relieved of her symptoms using a combination of gentamicin, penicillin G, ampicillin, meropenem, and vancomycin.

Chronic neutrophilic leukemia preceded by myelodysplastic syndromes.

Chronic neutrophilic leukemia (CNL) is primarily diagnosed by excluding myelodysplastic syndromes (MDS). We report the case of a patient who developed secondary CNL 3 years after hypoplastic MDS. We used droplet digital polymerase chain reaction mutation detection assay to analyze genomic alterations during the progression from MDS to CNL. At the time of MDS diagnosis, U2AF1 Q157P and SETBP1 D868N were dominant and additional mutation of ASXL1 1934_insG was observed. CSF3R T618I and SETBP1 D868N were increasing at the time of CNL diagnosis. We revealed the accumulation of multiple gene mutations during CNL development from MDS. This suggests that CNL was clonally developed from the founding clone of MDS and CSF3R mutation contributes to the development of CNL in the present case. These findings provide insights into the pathology of CNL.

CD20 gene deletion causes a CD20-negative relapse in diffuse large B-cell lymphoma.

In diffuse large B-cell lymphoma (DLBCL), a CD20-negative relapse is clinically significant because it is associated with chemo-refractory phenotypes and loss of a therapeutic target. The alteration of the CD20 gene is reported as infrequent in CD20-negative relapse in B-cell lymphoma. We established a DLBCL cell line with loss of CD20 expression (SD07) from a patient at CD20-negative relapse. She was initially diagnosed with CD20-positive DLBCL and received repeated immuno-chemotherapy that included rituximab. SD07, which has an immunoglobulin κ rearrangement identical to that of lymphoma cells at CD20-negative relapse, showed homozygous deletion of the CD20 gene with loss of the copy number of 11q12. SD07 is the first case in which it is proven that the loss of CD20 expression in relapsed DLBCL is the result of deletion of the CD20 gene. Deletion of the CD20 gene is a molecular mechanism of CD20-negative relapse in a subset of DLBCL.

[Analysis of the complete hepatitis B virus genomes in a patient for repeated seroconversion to anti-HBe antibody due to co-infection with two virus clones].

We report a case of repeated seroconversion to anti-HBe antibody in a patient with chronic hepatitis B. We amplified and cloned sections of the hepatitis B virus (HBV) genes by polymerase chain reaction (PCR), and sequenced the PCR products. The results were analyzed by connecting all of the sequences to generate complete genomes. As a result, we confirmed the coexistence of two different HBV clones, both of which had the same subtype (adr) and genotype (C2). Neither clone had mutations in the S gene region in sequences involved in gene expression or in sequences involved in drug resistance. However, both clones had mutations in the core promoter(A1762T, G1764A). In one HBe antibody-positive clone, a pre-core mutation associated with HBe antigen negativity (G1896A) was found. In addition, pre-S2 deletion and 6 amino acid substitutions in the core protein gene were detected in this clone. The other HBe antigen-positive clone was essentially wild-type. Interestingly, this clone had accumulated mutations, which participated in DNA polymerase inactivation in the P gene region. Therefore, it is expected that this clone cannot replicate its own DNA polymerase. Consequently, this repeated seroconversion phenomenon was suggested to be responsible for the observed findings. In conclusion, analysis of the complete HBV genome has greatly expanded the number of mutations identified, and this method is useful for understanding the causes of rare cases of hepatitis B.

Characterization of two mobilizable plasmids isolated from enterobacter cloacae.

We isolated two plasmids, pS51A and pS51B which were 5782 bp and 4854 bp in size, respectively, from the third generation cephalosporin-resistant E. cloacae suspected to express metallo-beta-lactamase, and analyzed their structures. These two plasmids encode RNA I/RNA II genes for replication origin, relaxase genes of mobABCD for plasmid transfer, and several open reading frames. According to the classification of mobilizable plasmids by gene organization of the relaxases, pS51A and pS51B belong to the ColE1 superfamily of mobilizable plasmids, commonly detected in Enterobacteriaceae. The metallo-beta-lactamase gene was not identified in either pS51A or pS51B by homology search of the putative open reading frames. Open reading frames encoded in pS51A include E. coli protein L-like, E. coli heat shock protein-like, and E. coli plasmid replication initiation protein-like, and those encoded in pS51B include helix-turn-helix protein-like, E. coli plasmid replication initiation protein-like, and Salmonella replication initiation protein-like. These plasmids are stably maintained in one strain of E. cloacae, thus, the encoded gene functions may confer growth advantage to the host cell.

Classification of gases around Pseudomonas aeruginosa and Acinetobacter baumannii by infrared spectroscopy.

Gas samples were collected from the air surrounding single and mixed laboratory cultures, and preliminary data on human breath samples were also obtained. The infrared spectra of a variety of gasses were measured at high resolution (0.5 cm-1) to obtain information about the infrared absorption bands to be used as indicators. These key bands enable bacterial classification, and the discrimination rates can be improved by observing multiple infrared absorptions. The air around Pseudomonas aeruginosa was distinguished from the other gas samples by the infrared absorptions at wavenumbers of 778.4 cm-1 and 2213.2 cm-1. For Acinetobacter baumannii, infrared absorptions at 1215.0 cm-1 and 2982.3 cm-1 were used; furthermore, adding those at 4768.7 cm-1 and 5353.8 cm-1 was shown to improve identification.

Emergence of linezolid-resistant mutants in a susceptible-cell population of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus with a MIC of linezolid of 4 µg/ml, isolated from a patient who had undergone unsuccessful linezolid therapy, yielded linezolid-resistant mutants in blood agar at 48 h of incubation. The resistant clones showed a MIC of linezolid ranging from 8 to 64 µg/ml and accumulated the T2500A mutation(s) of the rRNA genes. Emergence of these resistant clones appears to be facilitated by a cryptic mutation or mutations associated with chloramphenicol resistance.

Linezolid-resistant Staphylococcus aureus isolated from 2006 through 2008 at six hospitals in Japan.

Limited use of linezolid for treating methicillin-resistant Staphylococcus aureus (MRSA) infection was approved in Japan in 2006. We report here the status of linezolid-resistant MRSAs in Japan. Eleven linezolid-resistant clinical isolates from 11 patients at six hospitals were collected from 2006 through 2008. The minimal inhibitory concentration (MIC) of linezolid in these strains varied from 8 to 64 µg/ml. All strains had at least one G2576T mutation in the chromosomal gene(s) encoding domain V of the 23S ribosomal RNA (rRNA). Chromosomal DNA encoding five copies of the domain V region was analyzed by polymerase chain reaction (PCR). Strains with the linezolid MICs of 64, 32, 16, and 8 µg/ml had the G2576T mutation(s) in four, three (or four), two, and one copy of the 23S rRNA genes, respectively. These results suggest that the level of linezolid resistance seems to be roughly correlated with the number of mutations in the genes encoding 23S rRNA. DNA samples from all 11 strains were subjected to pulsed-field gel electrophoresis and were classified into seven independent clones having >92% identity. Among the 11 patients, five had been treated with linezolid and the remainder, in two hospitals, had no history of prior linezolid use. The results suggested possible nosocomial infections by linezolid-resistant MRSA.

[Four infants with upper urinary tract infection due to extended-spectrum bata lactamase (ESBL)-producing Escherichia coli].

Bacteria producing extended-spectrum beta lactamase (ESBL) are detected mainly in adult urinary specimens, and are believed to cause hospital-acquired infection due to their resistance to many drugs. The incidence of community-acquired infection due to such bacteria is increasing, but few cases of infant upper urinary tract infection (UUTI) have been reported in Japan. We treated four infants with UUTI caused by ESBL-producing Escherichia coli, as determined by genotyping. Using medical records, we retrospectively evaluated the clinical course, antibiotic use and efficacy, antimicrobial susceptibility results, and the presence of underlying disease. One of the four had been previously hospitalized for occult bacteremia. Two developed UUTI after antibiotic treatment, indicating that previous antibiotic use may have been a risk factor in these cases. We could not identify the infection route in all cases. Two of the four had bilateral vesicoureteral reflux (VUR). Renal scintigraphy was done in three. Although an initial dimercaptosuccinic acid (DMSA) defect was detected in all four, only one had renal scarring. E. coli isolates from all four showed PCR signals for blaCTX-M-; one isolate positive for the blaCTX-M3 group and three positive for blaCTX-M14. Antimicrobial susceptibility test results showed all isolates to be resistant to cephalosporins, but discrepancies existed between antimicrobial susceptibility results and actual clinical efficacy. Clinically, cefazolin (CEZ) was effective in two subjects and ceftazidime (CAZ) effective in one. Panipenem/betamipron (PAPM/BP) was effective in one. None of the four developed sepsis or meningitis. Post hospitalization antibiotic prophylaxis showed that none of the four has had UUTI recur. Japan's ESBL-producing bacterial infection incidence is increasing, so medical professionals should watch for such UUTI even in first-case occurrence in infants.

[Validity of using imipenem as a representative carbapenems and levofloxacin as a representative fluoroquinolones in antibiotics susceptibility test for enterobacteriaceae].

In antimicrobial susceptibility test for enterobacteriaceae, the efficacies of carpapenems are predicted by the minimum inhibitory concentration (MIC) of imipenem, and that of fluoroquinolones are predicted by the MIC of levofloxacin. To assess its judgement, we compared the MICs of imipenem, meropenem, panipenem, and doripenem for carbapenems, and ciprofloxacin, levofloxacin, tosufloxacin and pazufloxacin for fluoroquinolones of clinically isolated enterobacteria, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Enterobacter cloacae and Citrobacterfreundii, those resistant to the third generation cephalosporin. MIC distributions in low concentration range are estranged in some strains, conspicuously S. marcescens, E. cloacae and C. freundii: meropenem and doripenem displayed low MIC value than imipenem and panipenem. Since the estrangements are appeared MIC value of less than 8 microg/ml, the interpretive results (susceptible, intermediate, resistant) are not affected. In fluoroquinolones, all 4 agents showed almost identical MIC distributions, thus the MIC of levofloxacin is accepted to use the reference for other fluoroquinolones. The existence of the strains harboring carbapenem-resistant gene displaying low MIC value of carbapenems was reported. For the sensitive detection of the candidate of carbapenem-resistant strains, cut-off value of each carbapenem should be reconsidered, and also other phonotype analysis should be applied. Genomic analysis also would be required to detect the carbapenem-resistant gene.

Lignosulfonate Rapidly Inactivates Human Immunodeficiency and Herpes Simplex Viruses.

Background: Very few studies of the antiviral potential of lignosulfonates have been published. With the aim of oral application, among various groups of natural products, the relative antiviral potency of lignosulfonate and its ability to rapidly inactivate viruses were investigated. Methods: As target cells, MT-4 cells in suspension and attached Vero cells were used for infections with human immunodeficiency virus (HIV) and human herpes simplex type-1 virus (HSV). Mock- or virus-infected cells were incubated for 3-5 days with various concentrations of test samples, and the viable cell number was determined with the MTT method. For the shorter exposure experiments, higher titers of HIV or HSV were exposed to test samples for 10 or 3 min, diluted to a normal multiplicity of infection (MOI), and applied to the cells. Antiviral activity was quantified by using the chemotherapy index. Results: In the long-exposure system, lignosulfonates showed comparable anti-HIV activity with those of AZT, ddC, and sulfated polysaccharides, and it exceeded those of hundreds of tannins and flavonoids. When the exposure time was shortened, the chemotherapeutic index of the lignosulfonates for HIV was increased 27-fold. At a physiological pH, lignosulfonate showed higher anti-HIV activity than commercial alkali-lignin, dealkali-lignin, and humic acid, possibly due to the higher solubility and purity. Conclusions: With their rapid virus-inactivation capabilities, lignosulfonates may be useful for the prevention or treatment of virally induced oral diseases.