石和田 稔彦

溶連菌による扁桃炎治療として, ペニシリン系薬の10日間投与が標準的治療として行われてきた. しかし, 最近海外で, これまでの臨床試験のメタ解析から, 短期療法も含めセフェム系薬の方がペニシリン系薬よりも臨床効果がすぐれるという報告がなされ, ペニシリン主体の治療方針を見直す必要が生じてきた. そこで, 本邦における現況を中心に解析したところ, ペニシリン系抗菌薬の除菌率は, 85%程度であるが, 臨床的再燃率はセフェム系短期療法と同等であり, 感受性の低下も認められていなかった. また, リウマチ熱の出現は極めて低く, 溶連菌による扁桃炎抗菌薬治療後の腎炎発症も少なかった. 以上の状況を考えると, ペニシリン系薬は, 溶連菌による扁桃炎の治療薬として現在でも有効であると考えられた. ただし, 溶連菌による扁桃炎再燃の原因として, 服薬コンプライアンスの低下, 抗菌薬の作用から逃れる溶連菌の存在 (細胞内侵入菌, バイオフィルム産生菌) などが考えられており, 症例に合わせて, セフェム系抗菌薬やマクロライド系抗菌薬 (耐性菌が増加しており使用にあたっては注意が必要) を上手に選択して使用していくことも大切である.

BACKGROUND: Infective endocarditis (IE) due to Streptococcus pneumoniae (S. pneumoniae) carries a high mortality rate. However, little is known about pneumococcal IE in children and no optimal therapy has been established. Thus, we attempted to identify the clinical features of this disorder through a Japanese nationwide survey. METHODS: Members of the Japanese Society of Pediatrics Cardiology and Cardiac Surgery registered 170 pediatric patients with IE diagnosed during a 5-year period (1997-2001). Nine of these patients (5.3%) had pneumococcal IE. The clinical course, treatment and outcome of these 9 patients, aged 7 months to 4 years, were analyzed. RESULTS: Pneumococcal IE was associated with congenital heart disease in 7 patients and accompanied by other systemic infections including meningitis, pneumonia and otitis media, in 4 patients. Five of the 9 (55.6%) strains isolated by blood culture were penicillin-resistant S. pneumoniae strains. Seven patients were treated with carbapenem. Three underwent cardiac surgery due to cardiac failure and/or vegetation. One died due to septic shock on the first day of hospitalization. CONCLUSIONS: In children, pneumococcal endocarditis is often accompanied by severe systemic infections. The majority of pediatric cases are caused by penicillin-resistant S. pneumoniae strains. Carbapenem is an effective for IE caused by penicillin-resistant S. pneumoniae. This survey might be helpful to establish proper management strategies for pediatric pneumococcal IE.

乳幼児のマイコプラズマ肺炎の臨床像を検討するため, 5歳以下43例を6歳以上40例と比較した。6歳以上に比べ5歳以下では咳噺の性状は湿性咳噺が90.0%を占め, 肺副雑音も83.7%に聴取し, 末梢血白血球数も10, 000/μL以上を示す症例がみられ成人市中肺炎診療ガイドラインに記載されている非定型肺炎の特徴とは異なる臨床像を認めた。また5歳以下の乳幼児では細気管支炎, 気管支喘息発作を合併する割合や, ウイルスや細菌の混合感染の割合が6歳以上より高率に認められ, 臨床像が成人と異なる要因と考えられた。年齢による微粒子凝集 (PA) 法による抗体価上昇の遅延は認めないが, 診断基準を満たす抗体価上昇に15日以上要した症例がみられた。以上より5歳以下のマイコプラズマ肺炎の臨床像は非典型的であり, 急性期に診断ができる感度のよい検査法もないため, 早期に有用な検査法の確立が望まれる。

Despite developments in preventative and medical therapy, infective endocarditis (IE) carries a high rate of mortality. Risk factors for mortality are unknown in pediatric and adult patients with congenital heart disease (CHD). We determined the risk factors for in-hospital mortality in pediatric and adult patients with CHD. A retrospective observational cohort study was conducted from January 1997 to December 2001 in Japan. Of the 239 patients for whom complete data were available, 216 patients with CHD were identified. Outcomes were alive or deceased. The proposed modified Duke's criteria identified 137 patients, aged 1 month to 62 years with a median of 12 years, with IE. In-hospital mortality was 10%. Four risk factors were independently associated with mortality by stepwise logistic regression analysis: (1) vegetation size > or =20 mm (odds ratio 40.6, 95% confidence interval 2.42 to 681); (2) age <1 year (odds ratio 19.5, 95% confidence interval 1.74 to 219); (3) presence of heart failure (odds ratio 7.16, 95% confidence ratio 1.34 to 38.4); and (4) Staphylococcus aureus as a causative organism (odds ratio 5.68, 95% confidence interval 1.16 to 27.9). Surgical intervention emerged as a predictive factor for lower in-hospital mortality (odds ratio 0.045, 95% confidence interval 0.003 to 0.70) by stepwise logistic regression analysis. In conclusion, surgical intervention, which decreases the risk of in-hospital mortality, should always be considered.

Conventional polymerase chain reaction (PCR) used to identify mycobacterial species does not distinguish between Mycobacterium tuberculosis and M. bovis BCG, and several weeks or months may be needed to identify individual slow-growing Mycobacterial species. We report a 4-year-old girl who had subcutaneous abscess and sternal osteomyelitis after BCG vaccination at 4 month of age. We directly identified M. bovis BCG genome in the punctured abscess within a few days using PCR and PCR-restriction fragment length polymorphism. Such PCR is useful for rapidly diagnosing and managing of appropriate therapy in patients with infection due to M. bovis BCG.

BACKGROUND: Hemophilus influenzae type b (Hib) infection has a high morbidity and mortality rate in children. The frequency of natural immunity against Hib in Japanese children is not known, and Hib vaccine has not yet been introduced in Japan. METHODS: Anti-capsular polysaccharide-specific IgG (anti-CP) antibody titers were examined in serum samples from 100 children and 107 young adults who were not vaccinated against Hib, in serum samples from eight patients with Hib systemic infection and in 10 commercially available human immune globulin preparations on enzyme-linked immunosorbent assay. RESULTS: A total of 44% (44/100) of Japanese children and all patients with Hib systemic infection in the acute phase did not have the minimum protective level of anti-CP antibodies (>0.15 microg/mL). The rate of natural Hib immunity was lowest in children under 1 year of age and gradually increased with age. Only 3.74% (4/107) of Japanese young adults did not have the minimum protective level of anti-CP antibodies. Analysis of 10 commercially available human immune globulin preparations indicated an average level of 28.25 microg anti-CP antibody/mL immune globulin (range 14.96-44.17 microg/mL). CONCLUSIONS: Approximately half of Japanese children are not protected against Hib infection. Therefore, Hib vaccine should immediately be included as part of the routine immunization program in Japan. It was also found that all tested commercially available immune globulin preparations had high anti-CP titers. Well-controlled clinical trials of i.v. immune globulin administration for prevention and treatment of Hib systemic infection are needed in Japan.

Leukocyte adhesion deficiency type I (LAD-I) is an inherited immunodeficiency disorder caused by defective expression of the leukocyte integrins, namely, lymphocyte function-associated antigen 1, Mac-1, and p150, 95, and is associated with obstructed cell adhesion, migration, and phagocytosis. Patients suffer from various bacterial or fungal infections and their prognoses are poor. The only curative treatment is hematopoietic stem cell transplantation. Conventional myeloablative transplantations have been performed, but with unsatisfactory results. We performed the first successful nonmyeloablative unrelated marrow transplantation for a 20-year-old female LAD-I patient, who suffered from recurrent and occasionally life-threatening infections such as cellulitis, gingivostomatitis, and sepsis. We adopted a preparative regimen with fludarabine, cyclophosphamide, and low-dose total-body irradiation, and tacrolimus and short-term methotrexate as immunosuppressants. This procedure was sufficiently immunosuppressive to obtain stable engraftment without remarkable complications, and graft-versus-host disease was controllable. Dramatic improvement of her disease was observed, supported by the normal expressions of integrins. Twenty one months after transplantation, she is well with a Karnofsky score of 100. Thus, nonmyeloablative transplantation is considered a feasible method for LAD-I.

There are lots of infectious diseases accompanied with exanthema. When the physicians see the patients with exanthema, they should carefully examine the form of exanthema and accessory symptoms. The physicians also should inquire of the patients about past history, history of vaccination and situation of current infectious disease epidemic in surrounding area. These clinical approaches lead to specific diagnosis. On this manuscript, I show the photos of several major infectious exanthema caused by viral, bacterial, bacterial toxin and so on.

Cat scratch disease is associated with a variety of systemic manifestations. We report a pediatric case associated with pneumonia, pleural effusion, and pericarditis. A 3-year-old boy developed prolonged fever unresponsive to antibiotic treatment, including azithromycin and minocycline. Although the fever resolved with corticosteroid treatment, Bartonella henselae IgG titer was positive in indirect fluorescence antibodies, as was Rickettsia japonica IgG titer. Both titers were significantly reduced by serum absorption with B. henselae antigens, and we observed a serological cross-reaction between B. henselae and R. japonica.

We analyzed the clinical and bacterial backgrounds of 120 patients with pediatric urinary tract infection (UTI). Escherichia coli was the main pathogen recovered from 98 patients (81.7%). All causative agents isolated from 50 uncomplicated UTI cases were E. coli. Of 98 cases of E. coli UTI, 71 were treated with second-generation cephems, whose therapeutic effect was equal to that of third and fourth-generation cephems. MIC50 and MIC90 (microg/mL) for E. coli were as follows: cefazolin :2, 4; cefmetazole: < or = 0.5, 2; and ceftazidime: < or = 0.25, < or = 0.25. Yearly decline in susceptibility was not observed, but MIC elevation for third generation cephems (< or = 2 microg/mL) including ceftazidime was seen in six isolates. Careful monitoring of susceptibility trends is therefore necessary for appropriate antimicrobial therapy.

We summarize 41 cases of bacterial meningitis in the last 11 years caused by Haemophilus influenzae. All isolates were serotype b strain (Hib). Initial chemotherapy was started with ceftriaxone (CTRX) in 22 cases, ampicillin plus cefotaxime (CTX) in 9, CTRX plus panipenem/betamipron in 5, and CTX in 2. Some 31 cases were treated mainly with CTRX. Although therapeutic antibiotics showed good susceptibility for isolates, 8 complicated cases (19.5%) occurred. Sequalae were observed in 7 (17.1%) but none were fatal. Five strains with elevated MIC of CTX (0.12 to 1 microg/mL) recovered after 2001, and 3 of 5 strains also showed elevated MIC of CTRX (0.12 to 0.5 microg/mL), but all were cured completely with CTRX. At present, no treatment failures due to antibiotic resistance have been observed, and CTRX remains suitable as initial therapy for Hib meningitis. A decline in susceptibility for third-generation cephalosporin against beta-lactamase-nonproducing ampicillin-resistant H. influenzae is emerging, however, so it will be necessary to consider combination therapy with CTRX given the foreseeable trend in MICs.

We present 2 cases of meningitis caused by the same Haemophilus influenzae type b (Hib) strain in a nursery at a 3-month interval. Causative agents isolated showed good susceptibility to beta-lactams and both patients recovered without any sequelae. Survey culture at each occurrence of meningitis showed 10 asymptomatic nasopharyngeal carriers. Oral rifampin was administrated to all staff and infants, but 2 carriers were found a month later from chemoprophylaxis. Pulsed-field gel electrophoresis analysis showed that the two strains isolated from meningitis patients and 12 from asymptomatic carriers were apparently identical. When systemic Hib infection occurs in a nursery, other infants may be at high risk for secondary disease. It is difficult, however, to eliminate Hib carriage by chemoprophylaxis, indicating that Hib vaccination to prevent systemic Hib infection is necessary in Japan.

BACKGROUND: Despite availability and wide vaccine coverage, measles infections still occur especially in developing countries. An outbreak of measles occurred among previously immunized older Ghanaian children who had milder clinical symptoms with measles-specific IgG antibodies that could have been attributed to secondary vaccine failure, suggesting that the infection was vaccine-modified measles (VMM). METHODS: Two-color immunophenotyping of the peripheral blood mononuclear cells was performed at acute, recovery and convalescence phases for 19 VMM patients (mean age 6.2 +/- 3.5 years) using flow cytometry, and compared with that of 20 healthy, sex- and age-matched controls. RESULTS: The results showed a significantly higher memory helper (CD4(+)/CD45RO(+)) cell frequency and increased suppressor cell (CD8(+)/CD45R0(+)) frequency in VMM patients compared to healthy controls. There were no complications and all the patients recovered completely. CONCLUSIONS: These findings show that the mild symptoms in patients with VMM may have correlated with the increase of memory T cells, which is in sharp contrast with previous reports on acute measles infection. This may suggest that the intact immunologic memory cells could have been crucial for the resolution of VMM.

This aim of this study was to reveal annual changes in antibiotic susceptibility, especially the macrolide susceptibility of Streptococcus pyogenes. A total of 755 strains of S. pyogenes were clinicaly isolated from throat swabs of children from 1995 through 2004 in Chiba Municipal Kaihin Hospital. All isolates were fully susceptible to benzylpenicillin, cefotaxim and cefaclor. The rate of resistance to erythromycin (EM) was over 10% every year after 2001 and 19% in 2004, and the rate of high resistance (MIC > or =16 microg/mL) has been increasing. A significant increase in EM resistance was observed over a 10-year period. There were 118 strains (15.6%) that persisted after treatment with beta-lactams. In the past few years it has been discovered that some S. pyogenes can be internalized by human cells of respiratory tract origin and survive within them. Since beta-lactams do not reach high intracellular concentrations, this ability of S. pyogenes may be related to treatment failure. Since macrolides can enter eukaryotic cells and remain active in intracellular compartments, they will be effective for these S. pyogenes. In case of pharyngitis which againist treatment with beta-lactams, there is a possibility macrolides are effective. Macrolides may be effective in pharyngitis resistant to treatment with beta-lactams. However, macrolide resistance is not rare, susceptibility must be tested.

OBJECTIVE: The prevalence of beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae (H. influenzae) has been increasing in recent years. Piperacillin (PIPC) is one of a few beta-lactams possessing good activity against BLNAR H. influenzae. We studied clinical efficacy of piperacillin and its beta-lactamase inhibitor, tazobactam/piperacillin (TAZ/PIPC) in children with lower respiratory tract infection caused by H. influenzae including resistance strains. METHODS: Subjects were 20 children with lower respiratory tract infection caused by H. influenzae treated with PIPC 100mg/kg/day (7 cases) or TAZ/PIPC 125mg/kg/day (13 cases). We selected cases from which resistant H. influenzae strains might be detected. Patients received prior antimicrobial therapy within two weeks before admission, or with underlying diseases. We examined patient profiles, clinical efficacy, susceptibilities for 6 beta-lactam antibiotics [PIPC, TAZ/PIPC, ampicillin (ABPC), cefotaxime (CTX), ceftriaxone (CTRX), and meropenem (MEPM)] and analyzed 6 genotype patterns of beta-lactam resistant genes by PCR. RESULTS: Efficacy was 7/7 in patients in PIPC group and 12/13 in patients in TAZ/PIPC group. Diminished efficacy was seen in only one case complicated with severe RSV infection. The susceptibility of all strains but one beta-lactamase producing, ABPC resistant (BLP) strain to PIPC and of all to TAZ/ PIPC was below 0.25 microg/mL. The genotype of the 15 strains isolated from the sputum on administration was as follows; beta-lactamase nonproducing, ABPC-susceptible (gBLNAS) strains were 4, gBLP strain was 1, beta-lactamase nonproducing, and ABPC-resistant (gLow-BLNAR) strains were 2, beta-lactamase nonproducing, ABPC resistant (gBLNAR) strains were 8. CONCLUSION: PIPC and TAZ/PIPC were useful against lower respiratory tract infection caused by H. influenzae including BLNAR in children.

Haemophilus influenzae type b (Hib) is the most frequent pathogen of bacterial meningitis in Japanese children. The prevalence of beta-lactamase-negative ampicillin-resistant (BLNAR) Hib strain has been increasing in recent years. Furthermore, antibiotic activities of cefotaxime (CTX) and ceftriaxone (CTRX) have decreased against some of those BLNAR strains. We report a case of one-year-old boy who suffered from meningitis caused by BLNAR Hib. The MICs of CTX and CTRX for the strain isolated from cerebrospinal fluid was 1.0 and 0.5 microg/ml, respectively. The patient was administered high-dose CTRX (150 mg/kg/day) and recovered completely without any sequela. The high-dose CTRX administration may be a considerable choice of the treatment of BLNAR meningitis.

Two cases of Haemophilus influenzae type b (Hib) meningitis were occurred continuously in a day nursery. Both isolates obtained from cerebrospinal fluids of 2 patients were beta lactamase producing amoxicillin/clavulanic acid sensitive strains. But biotypes and restriction fragment length polymorphism patterns by SmaI digested pulse-field gel electrophoresis of two isolates were different, respectively. Although it was already reported simultaneous occurrence of two cases of Hib meningitis caused by same strain through the nursery contact, none were reported by different strains. It was considered that two colonized strains had caused meningitis in two patients continuously.

95 strains of Haemophilus influenzae (H. influenzae) isolated from blood of the patients with systemic infections were serotyped by staphylococcal coagglutination during the ten years from 1992 through 2001. As a result, 92 (96.8%) cases were caused by type b strains and 3 (3.2%) cases were caused by non-typeable strains. Three cases with systemic infection due to non-typeable H. influenzae were reported. One patient was a premature neonate with sepsis and respiratory failure who had a fulminant course and died. The other two patients were a 3-year-old girl and a 1-month-old boy both with pneumonia. About their underlying conditions, one received intravenous steroid therapy and the other suffered from respiratory syncytial virus infection. They were treated with appropriate antibiotics and their clinical courses were satisfactory and uncomplicated. Non-typeable H. influenzae was isolated from not only blood but also the lower respiratory tract in all three cases. Systemic infection due to non-typeable strain is rare. But, it should be recognized as a substantial proportion of the serious infections caused by H. influenzae.