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While most systemic pediatric Haemophilus influenzae infections are caused by the type b strain (Hib), nontypeable H. influenzae: (NTHi) has been considered a respiratory tract pathogen common in local infection such as acute otitis media, acute pneumonia, secondary chronic respiratory disease and other otorhinolaryngologic infections. Recent findings show, however, that NTHi also causes invasive infections such as meningitis, bacteremia, and lower respiratory tract infections such as pneumonia. A review of NTHi epidemiology from the 1990s onward shows that NTHi causes significant morbidity in pediatric acute otitis media, sinusitis, conjunctivitis and lower respiratory diseases such as pneumonia in Japan. This summary also reviews the worldwide influence of Streptococcus pneumoniae and Hib vaccines on causative pathogens, and several studies about increasing incidence of invasive infections due to NTHi. This review also touches on the emergence of treatment- and drug-resistant H. influenzae, which are now major public health challenges. As a cause of bacterial pediatric infection, NTHi is an important target for prevention.

We report a 4-year-old boy with fulminating meningitis caused by Haemophilus influenzae (Hib). He suddenly developed fever, vomiting and then somnolence. As bacterial meningitis was suspected, treatment with antibiotics was started at 12 hours after the onset. However, there was a rapid progression of severe brain edema and brain hernia, leading to clinical brain death. His clinical course and neuroradiological findings mimicked those in patients with acute encephalopathy, with cytokine profiles in cerebrospinal fluid demonstrating a marked increase of inflammatory cytokines. From a review of the literature, fulminating Hib meningitis may be classified into two disease types: DIC plus multiple organ failure and acute brain swelling types. The present case belongs to the latter type, in which cytokine storm seems to play an important pathogenic role.

A 25-year-old man undergoing splenectomy at 3 years of age to treat idiopathic thrombocytopenic purpura but no history of Streptococcus pneumonia vaccination, and reporting high fever, nausea, and headache developed purpura, confusion, and hypotension the next day and was admitted. Detailed examination showed disseminated intravascular coagulation and multiple-organ dysfunction. Chest X-ray and computed tomography (CT) showed pneumonia and pleural effusion. Blood culture was positive for S. pneumoniae. Gram staining of sputa yielded numerous white blood cells and gram-negative rods, and sputa culture was positive for Pasteurella multocida and Haemophilus influenzae. The medical history and presence of these organisms yielded a diagnosis of overwhelming postsplenectomy infection (OPSI), and the patient responded to treatment with a combination of benzylpenicillin, cefotaxime, and meropenem. This case suggests that patients with a history of splenectomy may benefit from vaccination for S. pneumoniae and adequate education on OPSI.

Aim: To study the epidemics of the hemophilus influenzae (HI) infection in the summer, 2005 among 46 residents in the second floor of our insurance care facility, Mam Cuore., Methods: The spreading pattern of HI infection, antibiotic susceptibility and serological identification of HI isolated from sputum culture were investigated, and underlying diseases, functional disorders, body weight, age, sex, ADL- and dementia-scores were compared among patients with the non-symptomatic group, HI infection and severe HI pneumonia groups., Results: Lower ADL and body weight were noted to suffer significantly more HI infection and severe pneumonia. Furthermore, stroke patients tended to suffer more HI infection. Dementia patients suffered significantly more severe pneumonia. Residents of rooms close to the room of original patient showed symptoms earlier than patients in more distant rooms. While the numbers of patients with HI infection were 15 (60%) and 10 (40%) before and after the first isolation of HI, 5 out of 15 patients (33%) and one out of 10 patients (10%) progressed to severe pneumonia, respectively. Although these results did not have statistical significance, they suggests that rapid assessment and therapy of HI infection tended to prevent aggravation. Non-typeable strains were detected and were all beta-lactamase nonproducing ampicillin resistant (BLNAR) without susceptibilities to cefaclor (CCL) and cefdinir (CFDN). Preceding the epidemic, an outbreak of the common cold syndrome was recognized., Conclusion: Assessing elderly patients suspected of the HI infection, and organized management for treatment are essential to improving outcome.

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.

Most of Bartholin's gland abscesses have been thought to be caused by microorganisms found in opportunistic infections. However, we have encountered two very interesting cases of Bartholin's gland abscesses caused by Streptococcus pneumoniae and Haemophilus influenzae, two major pathogens of respiratory tract infections. In the first case, since abscess formation was not observed due to disintegration, cefdinir (CFDN), 300 mg/day, t.i.d. for 5 days was administered. The treatment improved clinical symptoms, but relapse occurred 3 days after the administration was discontinued. Microbiological examination of pus revealed the presence of Streptococcus pneumoniae and Finegoldia magna, and it also showed that the isolated S. pneumoniae was penicillin-resistant S. pneumoniae (PRSP). After an incision and drainage of abscess, cefteram pivoxil (CFTM-PI), 300 mg/day t.i.d. for 7 days, was administered, and the cure was confirmed. In the second case, after an incision and drainage of Bartholin's gland abscess, amoxicillin (AMPC), 750 mg/day, t.i.d. for 5 days, was administered. The treatment improved clinical symptoms temporarily. However, the symptoms deteriorated 7 days after the operation, and the patient was diagnosed with relapse. Microbiological examination of pus revealed the presence of Haemophilus influenzae and Peptostreptococcus anaerobius, and it also showed that the isolated H. influenzae was beta-lactamase-nonproducing ampicillin-resistant H. influenzae (BLNAR). After performing additional incision and drainage of abscess again, CFTM-PI, 300 mg/day, t.i.d. for 7 days, was administered, and the cure was confirmed. In addition, the analysis of these two cases using PK/PD theory revealed that the time above MIC reached 100% with administration of CFTM-PI 300mg, t.i.d. suggesting that the dosage is sufficient for treating these infections. There are other cases of external genitalia infections caused by microorganisms usually associated with respiratory tract infections like cases that we are reporting here. Therefore, it is necessary to consider a possible infection by drug-resistant bacteria even for a case of external genitalia infection. In addition, it was thought that adjusting dosage and method for administration of antibacterial agents based on PK/PD theory would help to rovide efficient treatment.

A surgical case of acute purulent pericarditis in 1-year 2-month old boy who developed pericardial tamponade rapidly is reported. A subxiphoid pericardiectomy through a median incision was performed. Haemophilus influenzae was isolated from the effusion. He recovered successfully with an administration of antibiotics after the drainage procedures and did not develop constructive pericarditis. Our experience suggested that early subxiphoid pericardial drainage was effective in treatment of acute purulent pericarditis.

A 32-year-old male was admitted to our hospital complaining of fever and dyspnea on effort. Laboratory data on admission indicated leukocytosis and elevation of C-reactive protein. A chest radiograph showed diffuse reticulonodular shadows in both lower lung fields, and a chest computed tomography showed centrilobular reticulonodular opacity. Bronchoscopic findings revealed a large amount of slightly yellowish secretion in all bronchi. Cells found in the bronchoalveolar lavage fluid (BALF) included 61% neutrophils. Haemophilus influenzae was isolated from cultures of the BALF and sputum. Transtracheal lung biopsy specimens showed focal infiltration of neutrophils in the alveoli, and the pathological findings in the lung were compatible with bronchiolopneumonia. Since the CD4/CD8 ratio was 0.09 and a positive reaction was obtained for anti-human immunodeficiency virus (HIV) antibody, HIV-associated pneumonia due to H. influenzae was diagnosed. Seven days' administration of cefozopran improved the patient's condition. It is interesting that radiological findings are often unusual in HIV-infected patients with H. influenzae pneumonia.

We report a case of Fisher's syndrome with serological evidence of antecedent Haemophilus influenzae infection. A 66-year-old woman developed unsteady gait and multiple cranial nerve palsies after upper respiratory infection. Serum anti-GQ 1 b and anti-GT 1 a IgG antibodies were positive. In the acute phase of the illness, her serum had high titers of IgM, IgG and IgA anti-H. influenzae antibodies, which significantly decreased during the clinical course. Further study is needed to clarify the clinical and immunological features of Fisher's syndrome after H. influenzae infection.

A 47-year-old woman developed consciousness disturbance, and experienced hallucinations while traveling abroad, and then went into critical condition. She was placed in the critical care unit, and had flaccid tetraparesis requiring mechanical ventilation. Haemophilus influenzae was cultured from the sputum. The level of protein of the cerebrospinal fluid was elevated to 114 mg/dl, nerve conduction study showed findings of pure axonal damage, and the sural nerve biopsy revealed severe axonal degeneration. She improved gradually by plasma exchange. The diagnosis of acute motor sensory axonal polyneuropathy (AMSAN) based on autoimmune mechanism was made. We speculate that H. influenzae infection may have elicited AMSAN in this case.

In the present study, we assessed the serum level of IL-6 and TNF-alpha by ELISA in patients with chronic lower respiratory tract infection. The serum levels of IL-6 and TNF-alpha of patients in acute exacerbation phase are higher than that of in stable phase. We also classified patients in acute exacerbation phase into two groups according to the microorganism of persistent infection. The serum level of IL-6 and TNF-alpha in the patients with persistent infection with Pseudomonas aeruginosa were higher than that with Haemophilus influenzae. Moreover, the serum level of IL-6 and TNF-alpha were found to be related with malnutrition which assessed by clinical indices such as the serum level of albumin and cholinesterase. The present result suggests that IL-6 and TNF-alpha may have relationship with not only inflammation in airway but also indices of nutrition in patients with chronic lower respiratory tract infection.

A new oral cephem antibiotic, S-1108, was evaluated for its clinical efficacy and safety in children. S-1108 was effective in 95% of the 59 examined cases of respiratory, middle ear, skin and urinary tract infections. S-1108 was highly effective in infections of Streptococcus pyogenes, Haemophilus influenzae and Escherichia coli, but was less effective in penicillin-resistant Streptococcus pneumoniae and Staphylococcus aureus infections. The serum half-life was 1.26 +/- 0.36 hours upon after meal administration of 4 mg/kg. No severe adverse reaction was encountered. From these data, S-1108 appears to be safe and effective in children with susceptible bacterial infections.

The etiology of acute pneumonia was studied in 596 pediatric inpatients at Chiba Municipal Kaihin Hospital between January 1990 and December 1991. A pathogen was identified in 389 (64.4%) episodes of pneumonia. Evidence of bacterial infection was present in 167 (28.8%) episodes, viral infection in 178 (29.9%) and Mycoplasma pneumoniae infection in 89 (14.9%). The major bacterial pathogens were H. influenzae 117 (19.6%), S. pneumoniae 51 (8.6%), M (B). catarrhalis 24 (4.0%). RS virus was the most common respiratory virus. The peak age of the patients was 7 months to 2 years old. For bacterial pneumonia, the highest rates occurred in infants. Mycoplasma pneumonia produced the highest rates in school-age children. Mycoplasma pneumonia was prevalent at two distinct times, the first emerging in the spring of 1990 and emerging again in the autumn of 1991. RS virus and influenza virus epidemics occur during the winter. Most of the parainfluenza virus have been observed during the early summer season.

Meropenem (MEPM) was evaluated for its efficacy and safety. The following results were obtained. MEPM was given to 12 patients with infections: 5 with pneumonia, 1 with bacterial meningitis, 2 with pharyngitis, 4 with skin and soft tissue infections. Therapeutic responses were "excellent" in 5, "good" in 4 and "fair" in 3, with an efficacy rate of 75%. Adverse reactions were not noted. No abnormalities were shown in laboratory data. It has been concluded that MEPM is a useful drug for the treatment of bacterial infections in children.

Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacokinetics and clinical effects of cefpirome (CPR, HR 810) in children were studied. When 20 mg/kg and 40 mg/kg doses of CPR were administered to 4 children through 30 minutes' drip infusion, half-lives were 1.23 +/- 0.23 (mean +/- S.D.) hours and 1.37 +/- 0.35 (mean +/- S.D.) hours, respectively for the 2 dose levels, and recovery rates in urine in the first 6 hours after administration were 74.8% and 56.1%, respectively. CPR was administered to 15 cases (3 tonsillitis, 3 bronchitis, 5 bronchopneumonia, 1 acute cystitis, 1 coxoiliatitis, 1 otitis media, 1 otitis externa). The efficacy rate was 86.7%. Seven strains of bacteria were isolated and identified 4 Haemophilus influenzae, 3 Staphylococcus aureus, 1 Pseudomonas sp. from these cases. These bacteria in children were followed after administration of CPR. Six strains were eradicated and one was reduced in number. No adverse effects of CPR were observed except in 2 cases, one of which showed transient eosinophilia and the other showed a transient increase of transaminase. These results suggest that CPR may be an effective and safe drug to use on children clinically.

In 1987, the most frequently identified pathogens in chronic respiratory tract infections in our clinic were Haemophilus influenzae, Pseudomonas aeruginosa, Branhamella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae. Recurrent infection is a common phenomenon in patients with chronic respiratory tract infections, including chronic bronchitis, chronic bronchiolitis and bronchiectasis. H. influenzae is the most common pathogen in such patients. Macrolides, tetracyclines and new quinolones were effective to protect against recurrent infection of H. influenzae and these finding suggested that L-forms of H. influenzae may be significant in the recurrence of infection in patients with chronic respiratory tract infection. Bacterial colonization of the oropharynx is the initial event in most lower respiratory tract infections. Gargling protects against bacteria colonization of the oropharynx and occurrence of acute exacerbation.