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K Tateda

Publications and source records attributed to K Tateda.

At least 37 records · Page 2Linked to original sources

Potential of macrolide antibiotics to inhibit protein synthesis of Pseudomonas aeruginosa: suppression of virulence factors and stress response.

Recently we have reported that sub-minimum inhibitory concentrations (MICs) of macrolide antibiotics, such as erythromycin, clarithromycin, and azithromycin, induce loss of viability of Pseudomonas aeruginosa with longer incubation periods. In the present study we examined the effects of sub-MICs of macrolide antibiotics on protein synthesis and the expression of heat shock proteins (Gro-EL) in P. aeruginosa and the association of these factors with the viability of P. aeruginosa. In seven strains of P. aeruginosa clinical isolates, inhibition of protein synthesis was generally observed in bacteria grown on agar with sub-MIC azithromycin (8 microg/ml) at 24 h, and this was followed by loss of viability after an additional 24-h incubation. The inhibition of protein synthesis was shown in bacteria treated with sub-MICs of erythromycin and clarithromycin, but not with sub-MICs of other antibiotics examined (josamycin, tobramycin, ofloxacin, clindamycin, and ceftazidime) even at relatively high sub-MICs. In the heat shock condition (45 degrees C), strong expression of the heat shock protein Gro-EL was induced in bacteria grown on antibiotic-free medium, whereas there was a delay of such a response in bacteria exposed to 4 microg/ml of azithromycin. Reflecting these results, an abrupt reduction of viability in azithromycin-treated bacteria was observed within 3 h in the heat shock condition. Western blot analysis, using specific antibody for Gro-EL, demonstrated that erythromycin, clarithromycin, and azithromycin, at concentrations of 0.5-2 microg/ml, inhibited the expression of lower-molecular weight Gro-EL bands in the constitutive state. These results indicated that macrolides, at concentrations far below the MICs, suppressed protein synthesis in P. aeruginosa, an effect which may be associated with the inhibition of P. aeruginosa virulence and its loss of viability with longer incubation. Moreover, it is likely that the macrolides may sensitize bacteria to stresses, as these antibiotics induced alterations in a major stress protein, Gro-EL, in constitutive and inducible states.

Anti-Bacterial Agents↗

Efficacy of a novel tetracycline derivative, glycylcycline, against penicillin-resistant Streptococcus pneumoniae in a mouse model of pneumonia.

The MIC90 of glycylcycline (< or =0.06 mg/L) against 55 strains of Streptococcus pneumoniae was 100-fold lower than that of minocycline or tetracycline. In a mouse model of penicillin-resistant S. pneumoniae (PRSP) pneumonia, glycylcycline (10 mg/kg) decreased bacterial counts in the lungs from 10(6) cfu to <10(2) cfu, whereas no apparent reduction of bacterial numbers was observed with minocycline or penicillin G. Pharmacokinetic studies showed that the half-life and area under the curve of glycylcycline were superior to those of minocycline and penicillin G in the lungs. These results show a preferential distribution of glycylcycline in the lungs and potent in vivo bactericidal activity in PRSP pneumonia.

Animals↗

Comparative in vitro activity of telithromycin (HMR 3647), three macrolides, amoxycillin, cefdinir and levofloxacin against gram-positive clinical isolates in Japan.

The in vitro activities (MIC and MBC) of telithromycin (HMR 3647) against clinical isolates in Japan were investigated in comparison with those of erythromycin A, clarithromycin, azithromycin, amoxycillin, cefdinir and levofloxacin. Telithromycin was more potent than the reference compounds against erythromycin A-susceptible or resistant Streptococcus pneumoniae isolates possessing either mef (mefA or mefE) genes or the ermB gene. Against erythromycin A-susceptible or inducibly resistant Staphylococcus aureus and erythromycin A-susceptible and intermediate Enterococcus faecalis, telithromycin was highly active.

Amoxicillin↗

[A case report of pneumococcal pneumonia diagnosed by urinary antigen].

Using a kit for the rapid detection of Streptococcus pneumoniae, we examined 3 clinical cases, clearly diagnosed as pneumococcal pneumonia. Case 1 was a 63-year-old man hospitalized for right middle lobular pneumonia. Streptococcus pneumoniae was detected by blood culture initiated on the day of admission. His urine sample was found to have Streptococcus pneumoniae antigen at hospital day 4, and positive test results were observed 3 times thereafter. The other 2 cases had negative sputum and blood cultures, but they were positive for urine antigen, with clinical courses consistent with those of pneumococcal pneumonia. The kit used was determined to provide a test result within 15 min for each urine sample, and it was easy to perform. Thus, this kit is expected to serve as a very useful clinical tool.

Antigens, Bacterial↗

[In vitro activities of carbapenem antibiotics against the various clinical isolates].

The annual changes of antibacterial activities of beta-lactam antibiotics, mainly carbapenem antibiotics, were investigated against 5 bacterial species, S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa, which had been isolated from the clinical materials at Toho University Omori Hospital during the period of 1995 to 1997. In addition, antibacterial activities against other main bacterial strains isolated from the clinical materials during 1997 were also determined. The five bacterial species on which annual changes of the sensitivity were investigated did not show any remarkable trend to increase in resistance to the carbapenem antibiotics tested. The antibacterial activities of the carbapenem antibiotics against MRSA were weak, and MIC90 values were between 25 and 50 micrograms/ml. In S. marcescens and P. aeruginosa on which high resistance by the production of metallo-beta-lactamase has become a problem in recent years, there were no remarkable changes in annual changes of sensitivities. Especially, MIC90 valuses of the carbapenem antibiotics against P. aeruginosa were between 12.5 and 25 micrograms/ml, 4 to 8 times better than that of PIPC, like the case of CAZ. Furthermore, the carbapenem antibiotics showed strong antibacterial activities against clinically important 16 bacterial species, from Gram-positive to Gram-negative bacteria.

Carbapenems↗

Comparative evaluation of conjugate vaccines in the Haemophilus influenzae infection model.

We used a murine model of Haemophilus influenzae type b (Hib) infection to analyze the immunologic response to two commercially available PRP conjugate vaccines (HbOC, PRP-T). The mortality rate in mice infected with a large dose of the bacteria after vaccination with HbOC or PRP-T at two and three doses was significantly lower than in non-vaccinated mice and mice vaccinated by one dose. Furthermore, for infections caused by a small bacterial dose, the mortality rate in mice vaccinated with one, two, or three doses was significantly lower than in non-vaccinated mice. The induction level of anti-PRP antibodies, especially IgG, in serum of mice vaccinated by two or three doses was higher than in those vaccinated with a single dose. Our results indicate that the dose of vaccine influences its efficacy in protecting against Hib infection. Our results also showed a lack of difference between two different PRP conjugate vaccines.

Animals↗

[Fibrosing alveolitis following Legionella pneumonia].

We reported a case of fibrosing alveolitis following Legionella pneumonia. A 62-year-old man was admitted to our hospital with fever after a visit to a hot spring. Chest X-ray films on admission demonstrated air-space consolidation in the right lower lung. Legionella pneumonia was diagnosed because the patient had elevated serum antibody to Legionella pneumophila serogroup Ia and tested positive for urinary antigen. Although he was initially treated with rifampicin and erythromycin, he experienced drug-induced eruptions. Antibiotic therapy was accordingly changed to clarithromycin, levofloxacin, and minocycline, which together alleviated the patient's clinical symptoms but delayed radiologic regression. Chest X-ray films 2 months after the onset of illness revealed diffuse ground-glass opacities and progressive reduction of volume in the right lung. Long-term corticosteroid treatment was required. Three and half months after disease onset, fever recurred with the appearance of interstitial shadows in the left lung and positive tests for urinary antigen. Increasing the corticosteroid dose resolved the patient's symptoms.

Anti-Inflammatory Agents↗

[Peripartum cardiomyopathy].

Heart failure in the last month of pregnancy or with in 5 months after delivery has long been recognized as peripartum cardiomyopathy. Additional criteria include the absence of other identifiable causes of heart failure and the absence of other prior heart disease. Estimate of the incidence vary from 1 in 1300 to 4000 pregnancies. The mortality rates of this disorder in the acute phases and subacute phases range from 25 to 50 percent the prognosis is especially poor in patients with cardiomegaly persisting > 6 months and in patients with low left ventricular ejection fraction.

Cardiomyopathies↗

[A case of Klebsiella pneumoniae infection causing a buccal abscess complicated with multiple lung abscesses].

A 51 year-old man fitted with a dental prosthesis was hospitalized with buccal swelling, fever and chest pain. Laboratory data showed marked inflammatory changes, and chest radiography and CT scanning revealed small nodular shadows within the lung. A diagnosis of multiple lung abscesses secondary to a buccal abscess possibly caused by the prosthesis was made from needle aspiration biopsies of the lung nodules and of a buccal lesion. Klebsiella pneumoniae was isolated from these lesions and from a blood culture. The patient was successfully treated with antibiotics and by surgical drainage of the buccal abscess. It is important to note that the patient was immunodeficient at the time as a result of diabetes and alcohol intoxication.

Abscess↗

[A case report of pulmonary nocardiosis successfully treated with a combination of sulfamethoxazole-trimethoprim (ST) and sparfloxacin].

We encountered a case of pulmonary nocardiosis that responded dramatically to combined ST and sparfloxacin treatment. A 55-year-old woman presented with fever, cough and yellowish sputum. She had been under treatment with oral prednisolone (15 mg per day) since July 1997 after a diagnosis of Evans syndrome. A high fever of 39.8 degrees C was noted on January 30, 1998. The patient was hospitalized for bloody sputum, bilateral hypochondriac pain and evidence of infiltrative opacities in the left lower lobe on chest radiography. Bacterial pneumonia was suspected, and she was treated with piperacillin, but her clinical symptoms did not improve. Sputum culture and serologic examination failed to lead to a definitive diagnosis. Nocardia farcinica was isolated by culturing tissue obtained by CT-guided transcutaneous pulmonary biopsy, leading to a diagnosis of pulmonary nocardiosis. The results of an MIC test for antimicrobial agents led to treatment with a combination of ST and sparfloxacin, and the clinical symptoms improved. These clinical observations suggest that, when pneumonia is diagnosed in patients who have been receiving oral steroids for a prolonged period, pulmonary nocardiosis should be considered in the differential diagnosis to enable selection of appropriate antimicrobial agents.

Anti-Infective Agents↗

[Penicillin-resistant Streptococcus pneumoniae infections: current trends in epidemiology and antibiotic chemotherapy].

The world-wide emergence of penicillin-resistant Streptococcus pneumoniae has led to dilemmas in the management of pneumococcal infections. Furthermore, most penicillin-resistant pneumococci are simultaneously resistant to a wide variety of other antibiotics, including cephalosporins, macrolides and tetracyclines. Epidemiological surveys in Japan demonstrated that 30-50% of clinical isolates were penicillin-insusceptible(MIC: > or = 0.125 microgram/ml). At present time most penicillin-resistant pneumococcal pneumonia cases are well treated with penicillin or cephalosporin, but significant numbers of treatment failures were reported in meningitis patients. Data from healthy mice model of pneumonia clearly showed that carbapenems and vancomycin are more active than cefotaxime or penicillin in high dose. Careful and continuous surveys for trends in antibiotic resistance and clinical impacts of antibiotic-resistant pneumococci are warranted.

Animals↗

Paradoxical synergistic effects of tumour necrosis factor and interleukin 1 in murine gut-derived sepsis with Pseudomonas aeruginosa.

The authors evaluated the synergistic effect of tumour necrosis factor (TNF) and interleukin 1 (IL-1) in gut-derived sepsis in mice. After colonization of Pseudomonas aeruginosa strain D4 in the gastrointestinal tract, cyclophosphamide was administered to induce bacterial translocation of the P. aeruginosa and thereby to cause gut-derived sepsis. In this model, treatment either with 8 microg/kg of recombinant human TNF-alpha (rhTNF-alpha) or 2 microg/kg of recombinant human interleukin 1alpha (rhIL-1alpha) solely did not affect the mortality, whereas combined administration of the same doses of rhTNF-alpha and rhIL-1alpha significantly increased the mortality rate in comparison with saline-treated mice. Bacterial counts in liver and blood were significantly higher in rhTNF-alpha and rhIL-1alpha treated mice than in saline-treated mice. Endogenous TNF-alpha and IL-1beta productions were stimulated after combined treatment with rhTNF-alpha and rhIL-1alpha. On the contrary to these adverse effects, combined treatment with 500 microg/kg of rhTNF-alpha and 50 microg/kg of rhIL-1alpha on the day before the administration of cyclophosphamide significantly reduced the mortality from septic infection. We conclude that TNF and IL-1 synergistically affect the mortality of mice after gut-derived sepsis due to P. aeruginosa in mice and the timing of treatment with these cytokines causes both extremes in their effects.

Animals↗

Efficacy of beta-lactam antibiotics combined with gentamicin against penicillin-resistant pneumococcal pneumonia in CBA/J mice.

We examined the efficacy of gentamicin combined with beta-lactam antibiotics against penicillin-resistant Streptococcus pneumoniae (PRSP) in a noncompromised mouse model of pneumonia. In the presence of 8 mg/L (0.25 x MIC) and 16 mg/L (0.5 x MIC) of gentamicin, MICs of penicillin G against 23 strains of PRSP decreased from 1-4 mg/L to 0.03 mg/L in 14 (61%) and 23 strains (100%), respectively. A short-time killing study using strain 741 showed that 8 mg/L of gentamicin (0.25 x MIC) increased the killing activity of penicillin G, cefotaxime and imipenem (at 0.25, 1 and 4 x MIC) during a 6 h incubation period. Survival studies showed that the combined treatment of penicillin-G (160 mg/kg) and gentamicin (10 mg/kg), which commenced 2 days after infection (twice a day for 5 days), provided complete protection, while no animal survived when either antibiotic was used alone. A significant improvement in mortality was observed when a small dose of imipenem (2.5 and 10 mg/kg) was used with gentamicin. Our results suggest that gentamicin, when combined with beta-lactam antibiotics, especially imipenem, may be potentially useful against PRSP pneumonia in noncompromised individuals.

Animals↗

Fosfomycin alters lipopolysaccharide-induced inflammatory cytokine production in mice.

To determine the mechanisms of immunomodulating action of fosfomycin (FOF), we examined its effect on the production of inflammatory cytokines in mice injected with lipopolysaccharide (LPS). Treatment with FOF significantly lowered the peak serum levels of tumor necrosis factor alpha and interleukin-1 beta, indicating that FOF alters inflammatory cytokine production after LPS stimulation.

Animals↗

Effect of antiflagellar human monoclonal antibody on gut-derived Pseudomonas aeruginosa sepsis in mice.

We evaluated the effect of antiflagellar human monoclonal antibody on gut-derived Pseudomonas aeruginosa sepsis. Mice were given a suspension of P. aeruginosa SP10052 in their drinking water and were simultaneously treated with ampicillin (200 mg/kg of body weight) to disrupt the normal bacterial flora. Cyclophosphamide was then administered to induce leukopenia and translocation of the P. aeruginosa that had colonized the gastrointestinal tract, thereby producing gut-derived generalized sepsis. In this model, intraperitoneal injection of 100 microg of antiflagellar human monoclonal antibody (SC-1225) per mouse for 5 consecutive days significantly (P < 0.01) increased the survival rate compared with that for mice treated with bovine serum albumin (BSA). Treatment with SC-1225 significantly reduced the average number of viable bacteria in portal blood, liver, and heart blood compared with the average number after treatment with BSA. Furthermore, the presence in serum of the inflammatory cytokines tumor necrosis factor alpha and interleukin 6 were evaluated as markers of severity of infection, and the results showed that the levels of these cytokines in mice treated with SC-1225 were significantly decreased in comparison with those in BSA-treated control mice. Although there was no significant difference in the number of bacteria that colonized the intestine, SC-1225 treatment significantly increased bacterial opsonophagocytosis by cultured peritoneal macrophages from mice with or without cyclophosphamide pretreatment. Our results indicate that antiflagellar human monoclonal antibody SC-1225 protects mice against gut-derived sepsis caused by P. aeruginosa and suggest that such an effect is due to its opsonophagocytic activity and the reduced motility of the translocated bacteria once the bacteria move from the intestine into the bloodstream.

Animals↗