Biomedical subjects

Muneki Hotomi

Publications and source records attributed to Muneki Hotomi.

At least 19 recordsLinked to original sources

PubMed2006

Rapid identification of nontypeable and serotype b Haemophilus influenzae from nasopharyngeal secretions by the multiplex PCR.

OBJECTIVE: Heamophilus influenzae (H. influenzae) is an important pathogen responsible for both invasive and non-invasive infectious diseases. While encapsulated type b strain recognized as a major cause of severe invasive diseases, nontypeable strains are the major causes of non-invasive infectious diseases. Detection of this pathogen from nasopharyngeal secretions (NPS) is important. METHODS: We developed a multiplex polymerase chain reaction (PCR) for rapid identification of nontypeable and serotype b H. influenzae from nasopharyngeal secretions. RESULTS: A total 25 nasopharyngeal secretions were evaluated in this study. The multiplex PCR provided rapid and unequivocal results for determining either nontypeable or encapsulated typeable especially type b strains including a determination of beta-lactamase productions. CONCLUSION: The multiplex PCR based serotyping provided more reliable results than slide agglutination test (SAT) and is a valuable and expeditious method for identification of H. influenzae with determining capsular serotypes.

Haemophilus influenzae↗

PubMed2006

In vitro induction and selection of fluoroquinolone-resistant mutants of Streptococcus pyogenes strains with multiple emm types.

OBJECTIVES: To perform a systematic analysis of point mutations in the quinolone resistance determining regions (QRDRs) of the DNA gyrase and topoisomerase genes of emm type 6 and other emm types of Streptococcus pyogenes strains after in vitro exposure to stepwise increasing concentrations of levofloxacin. METHODS: Twelve parent strains of S. pyogenes, each with a different emm type, were chosen for stepwise exposure to increasing levels of levofloxacin followed by selection of resistant mutants. The QRDRs of gyrA, gyrB, parC and parE correlating to mutants with increased MICs were analysed for point mutations. RESULTS: Multiple mutants with significantly increased MICs were generated from each strain. The amino acid substitutions identified were consistent regardless of emm type and were similar to the mechanisms of resistance reported in clinical isolates of S. pyogenes. The number of induction/selection cycles required for the emergence of key point mutations in gyrA and parC was variable among strains. For each parent-mutant set, when MIC increased, serine-81 of gyrA and serine-79 of parC were the primary targets for amino acid substitutions. No point mutations were found in the QRDRs of gyrB and parE in any of the resistant mutants sequenced. CONCLUSIONS: Despite its intrinsic polymorphism in the QRDR of parC, emm type 6 is not more likely to develop high-level resistance to fluoroquinolones when compared with other emm types. All emm types seem equally inducible to high-level fluoroquinolone resistance.

Anti-Infective Agents↗

PubMed2006

Efficacy of a novel oral carbapenem, tebipenem pivoxil (TBM-PI), against experimental otitis media caused by penicillin resistant Streptococcus pneumoniae in chinchilla.

An animal model of otitis media using chinchillas was developed to evaluate the efficacy of tebipenem pivoxil (TBM-PI) against experimental otitis media. Chinchillas inoculated via the transbullar approach with Streptococcus pneumoniae serogroup 6 were included in the efficacy study with TBM-PI, amoxicillin (AMX) or untreated as controls. TBM-PI resulted in survival rate of 83%, compared with 25% survival for AMX and 0% survival for controls (p<0.01). Quantitative cultures in the middle ear effusions at day 5 of the TBM-PI group yielded 3.5+/-2.4log(10)CFUs/ml. TBM-PI is a promising antibiotic for the treatment of acute otitis media.

Administration, Oral↗

PubMed2006

Maternal intranasal immunization with outer membrane protein P6 maintains specific antibody level of derived offspring.

Acute otitis media is one of the most common infectious diseases in children younger than 2 years of age. Immunological studies in young children have revealed that immature antibody-responses to major pathogens, such as S. pneumoniae, H.influenzae, would cause the vulnerability to upper respiratory tract infections. Thus, it is very important to induce effective protective immunity among children younger than 2 years of age. In this study, we evaluated the capacity of maternal immunization with P6 of H. influenzae to evoke specific antibody to P6 and to transfer it to offspring. We intranasally immunized mother mice with P6 and investigated the induction of specific antibody in sera and breast milk. The specific antibody among offspring delivered by immunized mother was also investigated according to the nursing status to evaluate the importance of breast feedings by immunized mothers. Anti-P6 specific IgG in sera were high at delivery and maintained during nursing periods among P6-immunized mother mice. Anti-P6 specific IgG were predominantly induced in breast milk. IgG subclass induced in sera and breast milk from P6-immunized mother mice were IgG2b, followed by IgG1 and IgG2a subclass. Offspring delivered by P6-immunized mothers had anti-P6 specific IgG in sera at the birth. The levels of anti-P6 specific IgG in sera from offspring breast-fed by P6-immunized mothers were then increased until day 14 and then decreased on day 21. The anti-P6 specific IgG in sera from offspring breast-fed by sham-immunized mothers were rapidly decreased after birth. The current findings strongly suggest that maternal intranasal immunization with P6 would be an attractive strategy against NTHi infections during early childhood. It can supply protective antibodies via transplacental transfer during pregnancy and via breast milk after birth.

Administration, Intranasal↗

PubMed2006

High prevalence of Streptococcus pneumoniae with mutations in pbp1a, pbp2x, and pbp2b genes of penicillin-binding proteins in the nasopharynx in children in Japan.

OBJECTIVE: To evaluate the resistances of Streptococcus pneumoniae to beta-lactams developed by stepwise alterations in high-molecular-weight penicillin-binding proteins (PBPs) with a reduced binding affinity of beta-lactams. Among the numerous mutations in pbp genes that alter the affinity for beta-lactams, the decreased affinity of PBP1A, 2X and 2B is especially important in the development of resistances to beta-lactams. STUDY DESIGN: Retrospective review. METHODS: In this study, we investigated the mutations in pbp1a, pbp2x, and pbp2b genes evaluated by polymerase chain reaction (PCR) in 866 pneumococcal isolates collected from the nasopharynx of Japanese children with acute otitis media. RESULTS: 210 strains (24.3%) exhibited no mutations in the three pbp genes. 333 strains (38.5%) had mutations in the three pbp genes, 78 (9.0%) in two pbp genes, whereas 245 (28.3%) displayed mutations in only one pbp gene. Among the 656 strains with mutations in pbp genes, 620 (94.5%) strains had mutations in pbp2x. The annual prevalence of antimicrobial-resistant S. pneumoniae showed a gradual increase in strains with mutations in the three pbp genes and a parallel decrease in strains without mutations. CONCLUSIONS: PCR-based genotyping can characterize the antimicrobial resistances in pneumococci along with minimal inhibitory concentrations (MICs). Physicians should pay attention to the recent increase in antimicrobial-resistant S. pneumoniae when treating pediatric acute otitis media.

Acute Disease↗

PubMed2006

Evaluation of serotypes of Streptococcus pneumoniae isolated from otitis media patients by multiplex polymerase chain reaction.

The increasing difficulty in the management of pneumococcal acute otitis media in parallel with increases in antimicrobial-resistant strains has led to much interest in pneumococcal capsular types for the adoption of effective prevention by vaccines. This study shows that multiplex polymerase chain reaction is a valuable and expeditious method for the capsular typing of pneumococci. The multiplex polymerase chain reaction method accurately detects the majority of serotypes and serogroups frequently isolated from pediatric patients with acute otitis media, allowing the characterization of the colonization patterns for further implications of pneumococcal vaccines.

Bacterial Capsules↗

PubMed2006

Antimicrobial resistance in Haemophilus influenzae isolated from the nasopharynx among Japanese children with acute otitis media.

CONCLUSION: High prevalence of penicillin-binding protein (PBP) gene mutated (PGM) strains of H. influenzae should be taken into account when treating otitis media in children. OBJECTIVE: To evaluate prevalence of ss-lactamase nonproducing ampicillin-resistant (BLNAR) strains of Haemophilus influenzae with mutations in ftsI gene encoding penicillin-binding protein 3 (PBP3) among children with otitis media. METHODS: A total of 644 nasopharyngeal isolates of H. influenzae was collected from pediatric acute otitis media (AOM) patients with or without otitis media with effusions (OME) at the clinics of Otolaryngology-Head and Neck Surgery, Wakayama Medical University Hospital and six affiliated hospitals in Wakayama prefecture between January 1999 and December 2003. Minimal inhibitory concentrations (MICs) of ampicillin (AMP), cefditoren (CDN), cefdinir (CFD), cefaclor (CCL), cefpodoxime (CPD), and cefcapene (CFPN) were determined by the microbroth dilution method according to the recommendations of the National Committee for Clinical Laboratory Standards (NCCLS). Types of mutations in PBP3 gene (ftsI) were evaluated by a polymerase chain reaction (PCR)-based genotyping method. ss-Lactamase gene (bla) was also identified by PCR. RESULTS: ss-Lactamase-producing (BLP) strains with the bla gene were identified in 16 (2.5%) of isolates. PGM strains were identified in 279 (43.3%) isolates. There were 242 (37.6%) PGM1-nonBLP strains with mutations in variable mutated locus of ftsI, 35 (5.4%) PGM2-nonBLP strains with mutations in highly mutated locus of ftsI, 2 (0.3%) BLP-PGM strains with mutations in ftsI and producing ss-lactamase. BLP-nonPGM strains producing ss-lactamase without mutations in ftsI were identified in 14 (2.2%) isolates. MICs of PGM1-nonBLP strains to AMP were 0.5-2.0 microg/ml. The MIC(90) of CDN to the PGM1-nonBLP strains was lowest (0.06 microg/ml). Proportions of PGM1-nonBLP strains rapidly increased during 1999 to 2002 and then decreased in 2003. In contrast, PGM2-nonBLP strains increased in 2003.

Acute Disease↗

PubMed2006

Antimicrobial resistance of Haemophilus influenzae isolated from the nasopharynx of Japanese children with acute otitis media.

CONCLUSION: A high prevalence of penicillin-binding protein gene-mutated (PGM) strains of Haemophilus influenzae should be taken into account when treating otitis media in children. OBJECTIVE: To evaluate the prevalence of beta-lactamase-non-producing ampicillin-resistant strains of H. influenzae with mutations in the ftsI gene encoding penicillin-binding protein 3 (PBP3) among children with otitis media. MATERIAL AND METHODS: A total of 644 nasopharyngeal isolates of H. influenzae were collected from pediatric acute otitis media patients with or without otitis media with effusion at the clinics of the Department of Otolaryngology-Head and Neck Surgery, Wakayama Medical University Hospital and 6 affiliated hospitals in Wakayama Prefecture between January 1999 and December 2003. MICs to ampicillin (AMP), cefdinir (CFD), cefaclor (CCL), cefpodoxime (CPD) and cefcapene (CFPN) were determined by a microbroth dilution method according to the recommendations of the National Committee for Clinical Laboratory Standards. Types of mutations in the PBP3 gene (ftsI) were evaluated by means of a polymerase chain reaction (PCR)-based genotyping method. The beta-lactamase gene (bla) was also identified by means of PCR. RESULTS: Beta-lactamase-producing (BLP) strains having the bla gene were identified in 16 isolates (2.5%). PGM strains were identified in 279 isolates (43.3%). There were 242 PGM1-non-BLP strains (37.6%) with mutations in the variable mutated locus of ftsI, 35 PGM2-non-BLP strains (5.4%) with mutations in the highly mutated locus of ftsI and 2 BLP-PGM strains (0.3%) with mutations in ftsI that produced beta-lactamase. BLP-non-PGM strains producing beta-lactamase without mutations in ftsI were identified in 14 isolates (2.2%). MICs of PGM1-non-BLP strains to AMP were 0.5-2.0 microg/ml. The MIC90 of CDN to the PGM1-non-BLP strains was the lowest (0.06 microg/ml). The proportion of PGM1-non-BLP strains increased rapidly during 1999-2002 and then decreased in 2003. In contrast, the proportion of PGM2-non-BLP strains increased in 2003.

Acute Disease↗

PubMed2006

Functions of tonsils in the mucosal immune system of the upper respiratory tract using a novel animal model, Suncus murinus.

CONCLUSION: The human palatine tonsils and the nasopharyngeal tonsil were considered the defense mechanism against ingested or inhaled foreign pathogens. The current findings suggest that the tubal tonsils possess abilities of active transportation of foreign antigens, and will act as inductive and effector sites in the mucosal immune system. Our results also indicated a significant difference in roles of immune responses among individual tonsillar organs, suggesting functional sub-compartmentalization. OBJECTIVES: To address the function of tonsils in inducing local immune responses, we evaluated the antigen uptake of tubal tonsils and the induction of specific immune responses in a small laboratory animal with both tubal and palatine tonsils, i.e. Suncus murinus. MATERIALS AND METHODS: S. murinus were injected with 2 x 10(6) CFU of FITC-labeled Staphylococcus aureus via the right tympanic cavity. The distribution of the FITC-labeled S. aureus was examined under a fluorescent microscope. S. murinus were also immunized with 100 microg of ovalbumin (OVA) mixed with 2 microg of cholera toxin (CT) via the right external ear meatus every 2 days for 2 weeks. One week after the final immunization, sera, pairs of tubal and palatine tonsils, and the neck lymph nodes were obtained to evaluate the induction of specific immune responses. RESULTS: The FITC-labeled S. aureus particles were detected in tubal tonsils and also in cervical lymph nodes. Total IgA-producing cells and OVA-specific antibody-producing cells were identified in the immunized tubal tonsils. Trans-external ear meatus immunization of tubal tonsils also evoked systemic antibody responses.

Adenoids↗

PubMed2005

Tonsillitis index: an objective tool for quantifying the indications for tonsillectomy for recurrent acute tonsillitis.

This report is a preliminary exploration of the concept of a "Tonsillectomy Index" (TI) as an objective tool for quantifying the indications for tonsillectomy for recurrent acute tonsillitis (AT). The TI is derived by multiplying the number of episodes of AT by the number of years during which the episodes of AT occurred. Our objective in this study was to investigate whether there is a relationship between the natural history of AT, the immunological functions of tonsils and our proposed TI. For the natural history of AT, we medically followed 11 children with a history of AT for 5 years. When TI was equal to or greater than 8 (TI> or =8), the children suffered a significantly greater number of episodes of AT. For the immunological portion of our study, we enrolled 36 children and 46 adults undergoing tonsillectomy for either AT (study group) or tonsillar hypertrophy (control group, CG). We analyzed the co-stimulatory signals, CD80 and CD86 on tonsillar B-lymphocytes. The expression rates of CD80 and CD86 in the AT group with TI> or =8 were significantly decreased compared to those with TI was less than 8 (TI<8), as well as with those in control (tonsillar hypertrophy) group. Our preliminary findings suggest that when the TI> or =8, the tonsils have deteriorated immunologically and spontaneous resolution of recurrent AT is less likely to occur, hence tonsillectomy is appropriate. TI may be a useful tool for surgical decision making.

Acute Disease↗

PubMed2005

A recombinant P4 protein of Haemophilus influenzae induces specific immune responses biologically active against nasopharyngeal colonization in mice after intranasal immunization.

Outer membrane protein P4, together with P6, is highly conserved among all typeable and nontypeable strains of Haemophilus influenzae (H. influenzae). Thus, the protein is an attractive antigen for the inclusion in a vaccine against nontypeable H. influenzae (NTHi). However, the ability of P4 to induce antibodies protective against NTHi infections is still controversial. In this study, we investigated the specific mucosal immune responses against NTHi induced by intranasal immunization with the lipidated form of recombinant P4 protein (rP4) and non-fatty acylated recombinant P6 protein (rP6) with or without cholera toxin (CT) in BALB/c mice model. Intranasal immunization with either rP4+CT, a mixture of rP4 and rP6+CT, or rP4 and rP6 without CT elicited anti-rP4 specific IgG antibody in serum of mice. Intranasal immunization with either rP4+CT or a mixture of rP4, rP6+CT elicited anti-rP4 specific IgA antibody in nasopharyngeal washing (NPW), while intranasal immunization with rP4 and rP6 without CT did not induced anti-rP4 specific IgA antibody responses in NPWs. Sera from mice intranasally immunized with rP4+CT and a mixture of rP4, rP6+CT also showed bactericidal activity. Significant clearance of NTHi in nasopharynx was seen 3 days after the inoculation of live NTHi in mice intranasally immunized with rP4+CT. The current findings suggested that P4 would be a useful antigen as the component of the vaccine to induce protective immune responses against NTHi. The use of an intranasal vaccine composed of the different surface protein antigens is an attractive strategy for the development of a vaccine against NTHi.

Adjuvants, Immunologic↗

PubMed2005

Current status of antimicrobial susceptibility of clinical isolates of Streptococcus pyogenes in Japan: report of a countrywide surveillance study.

The growing number of macrolide-resistant strains of Streptococcus pyogenes is an increasing problem worldwide. In this study, we evaluated 62 clinical isolates of S. pyogenes obtained from the upper respiratory tract. Susceptibilities to penicillins, cephalosporins, fluoroquinolones, macrolides, and carbepenems were determined by minimal inhibitory concentrations (MICs). Expressions of macrolide-resistance genes (mefA, ermB, and ermTR) were also examined, by polymerase chain reaction (PCR). All strains were susceptible to beta-lactams. On the other hand, of the 62 S. pyogenes isolates, 6.5%, 6.5%, 6.5%, and 3.2% of the strains were resistant to azithromycin (AZM), roxithromycin (RXM), clarithromycin (CAM), and telithromycin (TEL), respectively. Four (6.5%) strains had a type of macrolide-resistance gene; there were two strains with ermB and two strains with ermTR, and these four strains were resistant to AZM, CAM (one strain was intermediately resistant), and RXM. Strains having ermB were resistant to TEL (MIC, > or = 8 microg/ml), while strains having ermTR were susceptible to TEL. Physicians and researchers need to take into consideration the macrolide resistance of some strains of S. pyogenes.

Anti-Bacterial Agents↗

PubMed2005

Evaluation of mutations in penicillin binding protein-3 gene of non-typeable Haemophilus influenzae isolated from the nasopharynx of children with acute otitis media.

CONCLUSION: Younger children tend to harbor more resistant strains because they are exposed to these pathogens more often through contacts with siblings or attendance at day-care centers and are frequently treated with antibiotics. The high prevalence of BLNAR strains should be taken into account in the treatment of AOM in young children. OBJECTIVE: Non-beta-lactamase-producing ampicillin-resistant (BLNAR) strains with mutations in penicillin-binding protein (PBP) genes of Haemophilus influenzae have been prevalent recently among younger children. MATERIAL AND METHODS: We investigated mutations in the ftsI gene encoding PBP-3 of H. influenzae isolated from the nasopharynx of children with acute otitis media (AOM) using polymerase chain reaction (PCR). RESULTS: Strains containing the bla gene (beta-lactamase-producing ampicillin-resistant) were identified in 4.7% of cases. Strains with mutations in the ftsI gene (BLNAR) were identified in 23.3% of cases. Strains without mutations in the ftsI gene and that did not contain the bla gene (non-beta-lactamase-producing ampicillin-susceptible) were identified in 70.7% of cases. Strains with both expression of the bla gene and mutations in the ftsI gene (beta-lactamase-producing amoxicillin clavulanate-resistant) were identified in 1.3% of cases. The MICs of ampicillin against the strains evaluated in this study were 0.5-2.0 microg/ml. Cefditoren-pivoxil had the lowest MIC90 against the strains (0.06 microg/ml). Strains with mutations in the ftsI gene (BLNAR) were broadly identified among young children.

Acute Disease↗

PubMed2005

Increase of macrolide-resistant Streptococcus pneumoniae-expressing mefE or ermB gene in the nasopharynx among children with otitis media.

OBJECTIVE: To evaluate prevalence of macrolide resistant strains and the genotypes of the resistance among Streptococcus pneumoniae isolated from the nasopharynx of children with otitis media. STUDY DESIGN: Retrospective review. METHODS: A total of 858 S. pneumoniae isolates were collected from the nasopharynx of pediatric patients with acute otitis media at the clinics of Otolaryngology-Head and Neck Surgery, Wakayama Medical University Hospital and six affiliated hospitals in Wakayama prefecture between January 1998 and December 2002. The antibiotic susceptibility patterns were analyzed for penicillin, erythromycin, and clindamycin according to the National Committee for Clinical Laboratory Standards. Macrolide resistance genes of mefE and ermB were determined by polymerase chain reaction of all S. pneumoniae. RESULTS: Of 858 clinical isolates, 259 (30.1%) were strains without ermB or mefE gene, 279 (32.5%) carrying mefE, 292 (34.0%) carrying ermB, and 28 (3.4%) carrying both genes. There was a strong correlation between phenotypes and the presence of macrolide resistance genes. The macrolide resistance genes were especially frequently identified among penicillin-resistant S. pneumoniae. Strains carrying ermB gene gradually increased from 25% in 1998 to 45% in 2002, with a concurrent decrease in strains carrying mefE from 36% in 1998 to 1999 to 19% in 2002. Strains having mefE were frequently identified among children younger than 2 years old. The current finding suggested that high-level ermB-mediated macrolide resistance in S. pneumoniae is increasing at an alarming rate in pediatric patients with otitis media, especially among young children. Physicians should pay close attention to such macrolide-resistant bacterial pathogens in the antimicrobial treatment of pediatric patients with otitis media.

Bacterial Proteins↗

PubMed2005

Nasal colonization with Streptococcus pneumoniae includes subpopulations of surface and invasive pneumococci.

We demonstrated that during colonization with Streptococcus pneumoniae the nasal mucosal tissues of mice support two populations of pneumococci. Transparent-phase pneumococci can be readily washed from the outer surface, while a second population composed of primarily opaque-phase pneumococci is released only by homogenization of the nasal tissue. The fact that the opaque phase has previously been associated with invasion and the fact that opaque-phase pneumococci were released by homogenization of previously washed nasal tissue suggest that the opaque-phase pneumococci may have invaded the nasal tissue. Consistent with this hypothesis was our observation that there was inflammation in portions of the nasal mucosa of the colonized mice but not in the mucosa of noncolonized mice, but this observation did not prove the hypothesis. If the opaque-phase pneumococci released from the nasal tissue were from within the tissue and/or if resistance of the opaque-phase subpopulation to antibody, complement, and phagocytes is essential for long-term carriage, it seems likely that the virulence factors of S. pneumoniae that are necessary for killing humans exist to facilitate carriage. Although this speculation is unproven, the observation that there are separate populations of pneumococci during colonization may help guide future attempts to understand the biology of nasal colonization by this pathogen.

Animals↗

PubMed2005

Recent advances in otitis media. 6. Vaccine.

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Animals↗

PubMed2004

Treatment and outcome of severe and non-severe acute otitis media.

UNLABELLED: To determine outcomes in acute otitis media (AOM) according to severity of disease and to assess different initial treatment regimens, 308 with AOM were enrolled and divided into severe (n = 277; 89.9%) and non-severe (n = 31; 10.1%) groups based on symptoms and tympanic membrane changes. Children in the severe group were initially managed with amoxicillin (AMPC) whereas children in the non-severe group were initially managed without antibiotics. Children were monitored on days 1, 5, 10, 14 and 28. Five outcome measures were assessed: disappearance of symptoms at day 5, resolution of tympanic membrane changes by day 28, disappearance of middle ear effusions by day 28, recurrence of acute symptoms prior to day 28, and need to change treatment regimens. Children with severe disease were more often male (57% versus 36%, P < 0.05) and more often colonized with pathogens (77% versus 55%, P < 0.05 than children with non-severe disease. The two groups were similar with respect to age and day care attendance. Despite differences in initial treatment regimens between the two groups, symptoms improved at the same rate for severe and non-severe disease, 94% by day 5. In contrast, tympanic membranes returned to normal in 69% of the severe and 81% of the non-severe groups by day 28; however, as early as day 5, 10% of the severe and 55% of the non-severe groups demonstrated normal tympanic membranes. Middle ear effusions similarly disappeared more slowly in the severe group, 52% versus 74% by day 14 and 76% versus 84% by day 28. Recurrence rates of acute symptoms occurred with equal frequency in the severe, 15%, and non-severe groups, 10%. Failure of the symptoms or the tympanic membranes to improve led to antibiotic changes in 59.9% of the severe group and to the addition of antibiotics in 51.6% of the non-severe group. Children in the severe group who failed to improve with an initial course of amoxicillin were younger (40.2 months versus 45.8 months, P < 0.05), had higher tympanic membrane scores (4.5 versus 4.1, P < 0.05), and were more often colonized with penicillin-resistant Streptococcus pneumoniae (33.8% versus 6.5%, P < 0.01) than children who responded to AMPC. In a similar manner, children with non-severe disease who failed to improve without antibiotics were younger (40.7 months versus 54.8 months, P < 0.05) and more often colonized with pathogens (75.0% versus 33.4%, P < 0.05). CONCLUSION: Severe disease occurred more often among males and among children colonized with pathogens. Response to treatment was impaired in younger children and in children colonized with pathogens, especially penicillin-resistant Streptococcus pneumoniae.

Acute Disease↗

PubMed2004

Macrolide-resistant genes of Streptococcus pyogenes isolated from the upper respiratory tract by polymerase chain reaction.

The growing number of macrolide-resistant strains of Streptococcus pyogenes is an increasing problem worldwide. This study evaluated 300 clinical isolates obtained from the upper respiratory tract. Minimal inhibitory concentrations (MICs) of erythromycin (EM), azithromycin (AZM), and clindamycin (CLDM), serotypes, and macrolide resistance genes of mefA, ermB, and ermTR were determined. The genetic relationship of EM-resistant and susceptible strains were also analyzed by pulsed-field gel electrophoresis (PFGE). Twenty-nine (9.7%) EM-resistant S. pyogenes were identified. Of the 29 strains showing resistance to EM, 22 isolates (7.3%, MIC 3.13-12.5 microg/ml) expressed the mefA gene. The predominant serotypes among the mefA-positive isolates were T12, emm9 or T25, emm75-1. The two isolates (0.1%) that possessed the ermB gene were highly resistant to EM (MIC > 100 microg/ml). The remaining five strains (1.6%) possessed the ermTR gene (MIC 3.13-100 microg/ml). Restriction fragment polymorphism analyzed by pulsed-field gel electrophoresis (PFGE) by SmaI and ApaI digestions showed several clones among the mefA-positive S. pyogenes. Our findings suggest that the mefA gene is the predominant mechanism for macrolide resistance and that this gene is horizontally transmitted among M phenotype strains of S. pyogenes. Consequently, macrolides would not be the first drug of choice for treatment of tonsillitis and other S. pyogenes-related diseases. Physicians and researchers need to take into consideration the macrolide resistance of some strains of S. pyogenes.

Adolescent↗