Molecular Evolution of GII.P31/GII.4_Sydney_2012 Norovirus over a Decade in a Clinic in Japan.

Norovirus (NoV) genogroup II, polymerase type P31, capsid genotype 4, Sydney_2012 variant (GII.P31/GII.4_Sydney_2012) has been circulating at high levels for over a decade, raising the question of whether this strain is undergoing molecular alterations without demonstrating a substantial phylogenetic difference. Here, we applied next-generation sequencing to learn more about the genetic diversity of 14 GII.P31/GII.4_Sydney_2012 strains that caused epidemics in a specific region of Japan, with 12 from Kyoto and 2 from Shizuoka, between 2012 and 2022, with an emphasis on amino acid (aa) differences in all three ORFs. We found numerous notable aa alterations in antigenic locations in the capsid region (ORF2) as well as in other ORFs. In all three ORFs, earlier strains (2013-2016) remained phylogenetically distinct from later strains (2019-2022). This research is expected to shed light on the evolutionary properties of dominating GII.P31/GII.4_Sydney_2012 strains, which could provide useful information for viral diarrhea prevention and treatment.

Sapovirus infections in Japan before and after the emergence of the COVID-19 pandemic: An alarming update.

An increasing trend of sapovirus (SaV) infections in Japanese children during 2009-2019, particularly after the introduction of the voluntary rotavirus (RV)-vaccination program has been observed. Herein, we investigated the epidemiological situation of SaV infections from 2019 to 2022 when people adopted a precautionary lifestyle due to the emergence of the COVID-19 pandemic, and RV vaccines had been implemented as routine vaccines. Stool samples were collected from children who attended outpatient clinics with acute gastroenteritis and analyzed by reverse transcriptase-polymerase chain reaction to determine viral etiology. Among 961 stool samples, 80 (8.3%) were positive for SaV: 2019-2020 (6.5%), 2020-2021 (0%), and 2021-2022 (12.8%). The trend of SaV infection in Japanese children yet remained upward with statistical significance (p = 0.000). The major genotype was GI.1 (75%) which caused a large outbreak in Kyoto between December 2021 and February 2022. Phylogenetic, gene sequence and deduced amino acid sequence analyses suggested that these GI.1 strains detected in the outbreak and other places during 2021-2022 or 2019-2020 remained genetically identical and widely spread. This study reveals that SaV infection is increasing among Japanese children which is a grave concern and demands immediate attention to be paid before SaV attains a serious public health problem.

Distribution of rotavirus genotypes in Japan from 2015 to 2018: Diversity in genotypes before and after introduction of rotavirus vaccines.

BACKGROUND: Diversity in group A rotavirus (RVA) strains after introduction of RV-vaccines remains an emerging concern worldwide. In this study, we investigated the prevalence and distribution of RVA genotypes in Japanese children with acute gastroenteritis (AGE) from 2015 to 2018. In addition, a comparison of the genotypes in pre-vaccination (2006-2012) and post-vaccination (2012-2018) periods was conducted to understand the impact of these vaccines on genotype distribution. METHODS: Fecal samples were collected regularly from outpatient clinics in six localities: Hokkaido, Tokyo, Shizuoka, Osaka, Kyoto, and Saga. RVA were screened and genotyped by RT-PCR and sequence-based genotyping. RESULTS: During the period 2015-2018, RVA was detected in 307 (19.7%) samples out of 1557 specimens: 29.9% (95% CI: 25.8% to 34.3%), 17.9% (95% CI: 14.7% to 21.5%), and 13% (95% CI: 10.3% to 16.0%) were detected RVA-positive in 2015-2016, 2016-2017 and 2017-2018, respectively. The average detection of RVA in pre-vaccination (2006-2012) and post-vaccination (2012-2018) era remained almost similar (18%-20%). The G2P[4]I2 (52.1%, 95% CI: 43.5%-60.6%) remained the most common genotype in 2015-2016, whereas G8P[8]I2 (55.9%, 95% CI: 45.2%-66.2%) dominated in 2016-2017. In 2017-2018, G9P[8]I2 (42.0%, 95% CI: 30.5%-53.9%) prevailed, followed by G9P[8]I1 (23.0%, 95% CI: 14.0%-34.2%). The detection rate of some common genotypes of pre-vaccination era like G1P[8] and G3P[8] has been reduced after introduction of RV-vaccine, whereas genotypes that were sporadic before the introduction of vaccines like G2P[4], G2P[8], G9P[8] and G8P[8] were emerged/reemerged in post-vaccination period. CONCLUSIONS: Our study presented the diversity in circulating RVA genotypes in Japan before and after introduction of RV-vaccines. Sudden emergence of DS-1-like (I2) unusual strains in post-vaccination era remains alarming. Continuous monitoring of RVA genotypes is therefore indispensable to refine future vaccine strategy.

Molecular epidemiology of rotavirus gastroenteritis in Japan during 2014-2015: Characterization of re-emerging G2P[4] after rotavirus vaccine introduction.

Rotavirus vaccines have been available in Japan since 2011. This study conducted to monitor the trend of group A rotavirus (RVA) genotypes 3 years after vaccine introduction. A total of, 539 fecal samples were collected from children with acute gastroenteritis in six regions during July 2014-June 2015. Among them, 178 samples (33.0%) were positive for RVA. The most predominant genotype was G1P[8] (35.9%) followed by G2P[4] (26.4%), G9P[8] (21.3%), G3P[8] (4.5%), and G3P[9] (4.5%). The detection rate of G2P[4] was increased soon after vaccine introduction. Sequence analyses of VP7 and VP4 genes of the representative G2P[4] strains were found to be clustered in sub-lineage IVa of lineage IV. It is noteworthy that one amino acid substitution in the antigenic epitope (Q114P) of VP4 gene was found in representative G2P[4] strains of the current study. However, it is unclear whether the change in antigenic epitope is due to the effect of vaccination or due to natural variation, warranting further continuous monitoring of rotavirus evolution after vaccine introduction.

Molecular Epidemiological Traits of Group A Rotaviruses in Japanese Children During Transitional Period of Rotavirus Vaccine Implementation, 2011 - 2014.

BACKGROUND: Group A rotavirus (RVA) vaccines have been introduced in Japan since 2011. To investigate the molecular epidemiological traits of RVA during the transitional period of rotavirus vaccine implementation in Japan, this study was undertaken by following up three-decade long surveillance conducted in the same regions. METHODS: RVA were screened and genotyped by RT-PCR from diarrheal samples collected from non-hospitalized patients in six localities (Hokkaido, Tokyo, Shizuoka, Osaka, Kyoto, and Saga) during 2011 - 2014. Selected samples were sequenced to elucidate the evolutionary trend. RESULTS: Among 1858 specimens, the detection rate of RVA declined to 4.0% in 2013 - 2014 from 17.9% in 2011 - 2012 and 22.1% in 2012 - 2013. G1P[8] was the most predominant genotype in the first two years accounting for more than half, and G9P[8] showed the highest detection rate as 35.0% in the last year. Interestingly, the proportional rate of G2 strains in the studied period increased from 0% to 25%. VP6 genotyping revealed that DS-1 like reassortant G1P[8] strains were detected all over Japan and their prevalence fluctuated greatly from 35.0% to 89.5%. Sequence analysis of VP6 showed that strains in the current strains were closely related but distinct from the original reference strains, namely Wa and DS-1. CONCLUSIONS: The detection rates of RVA, their GP combinations, prevalence of reassortant strains varied greatly after the introduction of rotavirus vaccines in Japan. Continuous monitoring is warranted to refine future vaccine strategy.

Reemergence of new variant G3 rotavirus in Japanese pediatric patients, 2009-2011.

The molecular epidemiology and characterization of rotaviruses obtained from non-hospitalized children with acute gastroenteritis in five different prefectures (Hokkaido, Saga, Tokyo, Osaka, and Kyoto) from July 2009 to June 2011 was investigated. Among 831 fecal specimens tested, rotavirus was found in 165 specimens (19.9%). The rotavirus detection rate in 2010-2011 (23.3%) was higher than those in 2009-2010 (16.0%). The highest prevalence of rotavirus was found in children aged 12 to 23 months. Rotavirus could be detected throughout the 8 month period with a peak in April. We found that G3P[8] was the most prevalent genotype (54.5%), followed by G1P[8] (29.1%), G9P[8] (9.1%), G3P[4] (3.0%), G2P[4] (2.5%), G1P[4] (1.2%), and G4P[8] (0.6%), respectively. Interestingly, G3 strains emerged as the most predominant genotype and replaced G1 rotavirus which had been reported as the most predominant genotype in the previous studies. Phylogenetic analysis revealed that G3 rotavirus strains were closely related to the "new variant G3" 5091 strain, which emerged in Japan in 2003-2004. A significant increase in the prevalence of rotavirus G3 found in this study indicates that rotavirus G3 strain is the major cause of infection in five geographical areas of Japan and may distribute globally in the near future.

Three clusters of Saffold viruses circulating in children with diarrhea in Japan.

Saffold virus (SAFV) is a newly discovered human virus in the genus Cardiovirus, family Picornaviridae. The virus was first described from fecal specimens of a child with fever of unknown origin in 2007. A total of 454 fecal specimens were collected from children with diarrhea attended clinics in Japan, 2010-2011, 7 (1.5%) were positive for SAFV. Mixed-infections of SAFV and other enteric viruses (rotavirus, norovirus, and bocavirus) were found in four out of seven cases, while monoinfection by SAFV alone was detected in three cases. In addition to diarrhea, fever and vomiting were observed in three children and mild dehydration in one case. No particular symptoms of cough and rhinorrhea were noted. Analysis of partial VP1 nucleotide sequence of 7 Japanese SAFV strains revealed that 5 SAFV sequences were most closely related with SAFV2 reference strains, but separated into SAFV2-A (3 strains) and SAFV2-B (2 strains). In addition, the other two strains were classified as SAFV3. Our results indicated that SAFVs (SAFV2 and SAFV3) were circulated in children with acute gastroenteritis in Japan during 2010 and 2011 epidemic season.

Detection and genetic characterization of norovirus infections in children with acute gastroenteritis in Japan, 2007-2009.

BACKGROUND: Noroviruses are a major cause of epidemic gastroenteritis in children and adults. The aim of the present study was to investigate the molecular epidemiology of norovirus gastroenteritis in Japan. METHODS: A total of 954 fecal specimens collected from infants and children with acute gastroenteritis from five different regions (Tokyo, Sapporo, Saga, Osaka, and Maizuru) of Japan during 2007-2009 were identified by multiple RT-PCR and semi-nested PCR. RESULTS: Norovirus was detected in a relatively high detection rate (26.6%; 254 of 954). Of the identified NoV, 9.5% (91 of 954) were positive by semi-nested PCR. Norovirus GII (97.3%) was more prevalent than GI (2.7%). Norovirus infections were very common in the patients aged 12-23 months (44.5%; 113 of 254). Winter month seasonality supported norovirus infection in Japan. All 7 GI sequences (100%) detected only in 2007-2008 clustered with Chiba 407 known as GI.4 genotype. Most of the norovirus GII sequences in 2007-2008 belonged to GII.4 (77.9%), followed by GII.14 (11.9%), and GII.3 and GII.6 (5.1% each). In 2008-2009, norovirus sequences were classified into eight distinct genotypes (GII.1, GII.2, GII.3, GII.4, GII.6, GII.7, GII12, and GII.14). GII.4/2006b variant was responsible for 100% among the detected GII.4 strains in both seasons. Interestingly, GII.6/GII.14 recombinant strains emerged, for the first time in Japanese children, as the second prevalent genotype (11.9%) in 2007-2008 and then dropped rapidly to 2.3% in a year after. In addition, GII.b/GII.3 and GII.4/GII.3 recombinant strains that had been described previously were also found in this study. CONCLUSIONS: This is the first report to demonstrate the co-circulation of the predominant GII.4/2006b variant and the emerging GII.6/GII.14 recombinant strains and supports the importance of norovirus as a causative agent of diarrhea in Japanese children with acute gastroenteritis.

Detection and genetic characterization of rotavirus infections in non-hospitalized children with acute gastroenteritis in Japan, 2007-2009.

The molecular epidemiology of rotavirus infections in non-hospitalized children in five different regions (Sapporo, Saga, Tokyo, Osaka, and Maizuru) of Japan during 2007-2009 was investigated. Overall, rotavirus was detected in 156 out of 1008 (15.5%) specimens. The rotavirus infection in 2007-2008 (19.3%) was higher than those in 2008-2009 (12.1%). G1P[8] was the most prevalent (62.8%), followed by G3P[8] (21.8%), G9P[8] (14.7%), and G2P[4] (0.7%). Interestingly, the number of G3P[8] strains increased threefold from the former season (2006-2007) from 7.3% to 21.8%, whereas G2P[4] and G9P[8] decreased from 11.4% to 0.7% and 20.3% to 14.7%, respectively. In the phylogenetic analysis, G3 rotaviruses were closely related to "the new variant G3" 5091 strain, which previously emerged in Japan and China. G9 viruses isolated in 2007-2008 were genetically close to the Thai strain, while those isolated in 2008-2009 had a close relationship with Chinese strains. G1 viruses appeared to be more similar to the recently reported G1 strain in China. Nucleotide sequence analysis of 33 P[8]-nontypeable strains revealed 5 nucleotide mismatches at the primer binding site. Based on previously reported (2003-2007) and current (2007-2009) data of rotavirus surveillance in the five areas of Japan, it was revealed that in Sapporo, Osaka, and Maizuru, G1P[8] and G3P[8] were detected at high frequencies, ranging from 47.2 to 57.7% and 31.7 to 47.4%, respectively. In Tokyo, G1P[8] (47.4%) was the predominant strain, followed by G9P[8] (20.6%), whereas in Saga, G3P[8] (38.9%) and G9P[8] (36.1%) were identified as the most dominant types. None of G9P[8] was detected in Sapporo. This study highlights the genetic diversity and the significance of rotavirus diarrhea in Japan.

Human bocavirus infection in children with acute gastroenteritis in Japan and Thailand.

A total of 329 fecal specimens, which had been known to be negative for rotavirus, adenovirus, norovirus, sapovirus, and astrovirus, and which were collected from infants and children with acute gastroenteritis in Japan and Thailand during 2005-2008 were screened for human bocavirus (HBoV). HBoV was detected by PCR with a primer pair that amplified the NP1 region of its genome and was genotyped by sequencing of the VP1/VP2 region. Of the 329 samples tested, 6 (1.8%) were positive for HBoV. Of these, five samples were collected from Japan and one sample was from Thailand, and the detection rates of HBoV in each country were 2% and 1.2%, respectively. For the detected HBoV, the capsid VP1/VP2 gene of all HBoV strains was successfully sequenced. Four Japanese HBoV strains studied were clustered into group 1, while the remaining Japanese strain and a unique Thai strain belonged to group 2. No severe acute gastroenteritis associated with HBoV was noted. This study provides better understanding on the epidemiology of HBoV infections in children with acute gastroenteritis in Japan and Thailand.

Detection of human parechovirus in stool samples collected from children with acute gastroenteritis in Japan during 2007-2008.

Of 477 stool specimens, which had been screened for rotavirus, adenovirus, norovirus, sapovirus and astrovirus, collected from infants and children with acute gastroenteritis in pediatric clinics encompassing five localities (Sapporo, Tokyo, Maizuru, Osaka, and Saga) in Japan from July 2007 to June 2008, 247 negative samples (51.7%) were subjected to screening for human parechovirus. Human parechovirus (HPeV) was detected by RT-PCR using a primer pair to amplify 5'UTR region of its genome and was genotyped by sequencing of the VP1 gene. HPeV was detected in 20 of 247 specimens tested, and the detection rate was found to be 8.1%. Seventeen of the 20 strains that tested positive for HPeV were sequenced successfully the VP1 gene. The majority of the HPeV strains (n = 15) could be identified as HPeV1, and the remaining 2 strains could be typed as HPeV3. By phylogenetic and identical matrix analyses of HPeV VP1 sequences, HPeV1 should be divided into two lineages, and all of the Japanese studied HPeV1 strains belong to the lineage 2 accordingly. This is the first report of the circulation of HPeV, especially HPeV1 in Japan.

Genetic heterogeneity, evolution, and recombination in noroviruses.

Norovirus is one of the most common causes of nonbacterial gastroenteritis in humans. A total of 603 fecal specimens collected from sporadic pediatric cases of acute gastroenteritis in Japan from 2004 to 2005 were tested for the presence of norovirus by RT-PCR. It was found that 51 (8.5%) specimens were positive for norovirus. The norovirus genotypes detected in this study were GII/1, GII/2, GII/3, GII/4, GII/6, and GII/7. Of these, GII/3 was the most predominant (52.9%), followed by GII/4 (37.2%) and others. It was noticed that four distinct types of recombinant noroviruses were co-circulating and the variant norovirus GIIb suddenly emerged to be the leading strain in Japan for the first time. A novel norovirus nomenclature was proposed, in which worldwide noroviruses were classified into seven distinct genogroups (I-VII). Norovirus GI and GII consisted of 16 genotypes with 32 subgenotypes and 23 genotypes with 34 subgenotypes, respectively. Of note, human and porcine noroviruses had a close genetic relationship within GII. Interestingly, multiple short amino acid motifs located at N terminus, S domain, P1 domain, P2 domain, and C terminus of capsid gene correctly defined the phylogenetic norovirus genogroups, genotypes, and subgenotypes. Another interesting feature of the study was the identification of eight hitherto unreported recombinant noroviruses. It was noteworthy that three different types (intergenogroup, intergenotype, and intersubgenotype) of recombination in noroviruses were also found. This is the first report to demonstrate the existence of intergenogroup and intersubgenotype recombinations in noroviruses and highlights a possible route of zoonoses in humans because porcine, bovine and murine noroviruses belong to genogroups II, III, and V, respectively.

Emergence of new variant rotavirus G3 among infants and children with acute gastroenteritis in Japan during 2003-2004.

A total of 402 fecal specimens from infants and children with acute gastroenteritis in five places (Tokyo, Maizuru, Saga, Sapporo, and Osaka) in Japan from July 2003 to June 2004 were collected and then tested for the presence of rotavirus by RT-PCR. Of these, 83 were positive for rotavirus and this accounted for 20.6%. Rotavirus was further characterized to G-types (VP7 genotypes) and P-types (VP4 genotypes). Interestingly, an emergence of rotavirus G3 was identified with an exceptionally high prevalence (97.5%; 81 of 83), followed by rotavirus G2 (2.5%; 2 of 83). The P-types of 19 rotavirus strains, which could not be typed by RT-PCR, were determined as P[8] with multiple point mutations at the VP4 primer-binding site by sequencing analysis. The predominant genotype was G3P[8] (95.2%, 79 of 83), followed by a number of unusual combinations G3P[4] (2.4%, 2 of 83), and G2P[8] (2.4%, 2 of 83). Another interesting feature of the study was the demonstration of a great genetic diversity in new variant rotavirus G3 strains circulating in Japan. In comparison with rotavirus G3 strains circulating in 1990-1995 in Japan, a wide range of amino acid substitutions (up to 16) of new variant rotavirus G3 VP7 genes was identified. Of note, the changes at positions 96, 99, and 100 were revealed to be located in the antigenic region A, and 213 in the antigenic region C. To the best of our knowledge, this is the first reporting of an emergence of new variant rotavirus G3 together with a sudden disappearance of G1, G4, and G9 in infants and children with rotavirus infection-associated gastroenteritis in Japan.

Multiple recombinant noroviruses in Japan.

A total of 417 fecal specimens collected from sporadic pediatric cases of acute gastroenteritis in Japan from 2005 to 2006 were tested for noroviruses by RT-PCR. Noroviruses were detected in 44 of 417 (10.1%) fecal specimens tested. Of these, the GII/3 was the most predominant genotype with a prevalence rate of 56.8%, followed by 34% of the GII/4 and others. Phylogenetic analysis reveals that multiple recombinant noroviruses, which were both dependently and independently introduced from four different continents (Asia, America, Europe, and Oceania), emerged to cause acute gastroenteritis among Japanese children. Of these, "new variant" noroviruses suddenly emerged to become the leading strain in Japan for the first time. This report is also the first indication of the existence of multiple recombinant noroviruses co-circulating in Japan.

Detection and genetic characterization of norovirus strains circulating among infants and children with acute gastroenteritis in Japan during 2004-2005.

A total of 752 fecal specimens collected during the period of July 2004 to June 2005 from infants and children with acute gastroenteritis from four different regions (Maizuru, Tokyo, Sapporo, and Osaka) of Japan were tested for the presence of norovirus by RT-PCR. It was found that 139 (18.5%) fecal specimens were positive for norovirus. Norovirus infection was detected almost all year round with the highest prevalence in January. Norovirus GII was the most predominant genogroup (98.6%; 137 of 139). The genotypes detected in this study were GI/1, GII/1, GII/3, GII/4, and GII/6. Of these, NoV GII/4 (known as the Lordsdale virus cluster) was re-emerging and became the leading genotype (77.7%). Meanwhile, the incidence of NoV GII/3 (known as the Arg320 virus cluster) has dropped rapidly, accounting for only 15.8%. Another interesting feature of the study was the identification of Picton03/AU-like recombinant NoV for the first time in Japan. Based on the genetic analysis, it was interesting to note that NoV GII/4 in 2004-2005 made a distinct cluster in comparison to other NoV GII/4 circulating in 2002-2003 and 2003-2004. Of note, "new recombinant variant designated GIIb" within NoV GII/3, which was first detected in Saga City, Japan in 2003-2004 in only one case, had increased, spreading widely in Japan and representing 45.5% (10 of 22). Further epidemiological studies should be conducted to determine whether this new recombinant variant strain will be dominant in Japan in the coming year.

Changing distribution of norovirus genotypes and genetic analysis of recombinant GIIb among infants and children with diarrhea in Japan.

A total of 402 fecal specimens collected during July 2003-June 2004 from infants and children with acute gastroenteritis, encompassing five localities (Maizuru, Tokyo, Sapporo, Saga, and Osaka) of Japan, were tested for the presence of norovirus by RT-PCR. It was found that 58 (14.4%) fecal specimens were positive for norovirus. Norovirus infection was detected throughout the year with the highest prevalence in December. Norovirus GII was the most predominant genogroup (98.3%; 57 of 58). The genotypes detected in this study were GI/4, GII/2, GII/3, GII/4, and GII/6. Of these, NoV GII/3 (known as the Arg320 virus cluster) was the most predominant genotype (43.9%), followed by NoV GII/4 (the Lordsdale virus cluster; 35.1%) and others. Two norovirus strains clustered with a "new variant designated GIIb" and a "new variant of GII/4" were found circulating in Japan for the first time. It was interesting to note that NoV GIIb and NoV GII/3 appeared to be the recombinant strains and the recombination site was demonstrated at the overlap of ORF1 and ORF2. The majority (96%) of the dominant norovirus strains were identified as the recombination of GII/3 capsid and GII/12 polymerase. The recombination in the NoV GIIb capsid gene at the breakpoint located at P1 domain was also identified. Obviously, NoV GIIb isolate in Japan had double recombination. This is the first report demonstrating the existence of different "new variants" co-circulating in Japanese infants and children with acute gastroenteritis.

Outbreak of sapovirus infection among infants and children with acute gastroenteritis in Osaka City, Japan during 2004-2005.

One hundred and twenty five fecal specimens were collected from sporadic cases of acute gastroenteritis in a pediatric clinic in Osaka City, Japan from July 2004 to June 2005 and tested for the presence of rotavirus, norovirus, sapovirus, astrovirus, and adenovirus by RT-multiplex PCR. Among diarrheal viruses detected, norovirus was the most prevalent (19.2%, 24 of 125), followed by group A rotavirus (18.4%, 23 of 125), astrovirus (1.6%, 2 of 125), and adenovirus (0.8%, 1 of 125), respectively. Interestingly, sapovirus infection was identified with high incidence of 17.6% (22 of 125). Sapovirus was subjected to molecular genetic analysis by sequencing. It was found that sapovirus detected in this study was classified into four genotypes (GI/1, GI/4, GI/6, and GI/8), and sapovirus GI/6 was predominant, followed by GI/8 and accounted for 81.8% (18 of 22) and 9.1% (2 of 22), respectively. It was noteworthy that sapovirus GI/6 infection was apparently confined within the period of 5 months (August 2004 through December 2004). This pattern of infection implied the outbreak of sapovirus GI/6 in these patients, which was the first outbreak of acute gastroenteritis attributed to sapovirus in Osaka City. Another interesting feature of the study was the appearance of two novel, naturally occurring recombinant sapoviruses circulating in the Japanese population studied. This report confirmed the presence as well as the importance of sapovirus causing acute gastroenteritis among Japanese infants and children.

[Clinical efficacy and bacteriological studies of clarithromycin and cefdinir against group A beta-hemolytic streptococcal tonsillopharyngitis].

The clinical efficacy and safety of clarithromycin (CAM) and cefdinir (CFDN) were evaluated in 65 pediatric outpatients with group A beta-hemolytic streptococcal tonsillopharyngitis. Treatment was "effective" or better in 26 (78.8%) children receiving CAM and in 27 (87.1%) receiving CFDN based on antigen clearance and the "Criteria for Evaluation in Clinical Trials of Antibacterial Agents in Children" proposed by Japan Society of Chemotherapy (p = NS). The causative organisms were eradicated in 94.7% and 93.8% of subjects in the CAM and CFDN groups, respectively (p = NS). Adverse drug reactions were limited to moderate diarrhea in one patient in each group, and subsided during treatment. Causative organisms exhibited good susceptibility to CAM and CFDN. These results suggest excellent efficacy, safety and usefulness of CAM and CFDN in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitsis in children.

[Survey of susceptibility of methicillin-resistant Staphylococcus aureus to antimicrobial agents in Hokusetsu General Hospital].

We examined the annual isolation rate, susceptibility to antimicrobial agents and coagulase types of methicillin-resistant Staphylococcus aureus (MRSA) isolated from inpatients in Hokusetsu General Hospital to ascertain the situation of MRSA isolates between 1992 and 2001. The isolation rate of MRSA in S. aureus increased annually from 1992, reaching 65.3% in 2001. The isolation rates of MRSA in the inpatients were 3.2 times greater than those in the outpatients. In the clinical specimens the isolation rate of MRSA from sputum was the highest, i.e., 32.9%. In respect of the coagulase types, type II accounted for 85.7% of the all types. MIC90 values of arbekacin, sulfmethoxazole-trimethoprin, vancomycin, teicopranin and minocycline were 4.0, 2.0, 2.0, 2.0, and 8.0 micrograms/ml, respectively.