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Background: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP., Methods: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis., Result: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed., Conclusion: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications., Competing Interests: Declaration of competing interest Hiroshi Mukae received lecture honoraria and research grants from KYORIN Pharmaceutical Co., Ltd. Outside of the submitted work., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Oral antibiotic therapy for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves an aminopenicillin with clavulanic acid, a macrolide, or a quinolone. To date, however, the clinical efficacy and safety of the oral cephalosporin cefditoren pivoxil has not been evaluated in Japanese patients with acute exacerbations of COPD. We conducted a prospective, multicenter, single arm, interventional study from January 2013 to March 2017 to determine the efficacy and safety of oral administration of 200 mg cefditoren pivoxil three times daily for 7 days in a cohort of 29 eligible patients from 15 hospitals. The mean age (SD) of participants was 73.1 (8.1) years and 28 had a smoking history (the mean [SD] of smoking index, 1426.7 [931.7]). The primary efficacy endpoint was clinical response (cure rate) at test of cure, which was set at 5-10 days after treatment ceased. Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured. Previous experience of acute exacerbations significantly affected the cure rate: none of the three patients who had at least two prior exacerbations were cured, while 15 of the 20 patients with one or fewer prior exacerbations were cured (p = 0.032). The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%) but resolved within 10 days of onset. We conclude that cefditoren pivoxil represents a viable alternative for antibiotic therapy in patients with few prior exacerbations., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The presence of antibiotics in the environment and their subsequent impact on the development of multi-antibiotic resistant bacteria has raised concerns globally. Consequently, much research is focused on a method to produce a better disinfectant. We have established a disinfectant system using UVA-LED that inactivates pathogenic bacteria. We assessed the bactericidal efficiency of a combination of UVA-LED and antibiotics against Vibrio parahaemolyticus. Combined use of antibiotic drugs and UVA irradiation was more bactericidal than UVA irradiation or antibacterial drugs alone. The bactericidal synergy was observed at low concentrations of each drug that are normally unable to kill the bacteria. This combination has the potential to become a sterilization technology.

Pseudomonas aeruginosa bacteremia occurs mainly in immunocompromised patients. However, P. aeruginosa bacteremia in immunocompetent patients has also been reported. The aim of this study was to evaluate the clinical characteristics of P. aeruginosa bacteremia in relation to the immune status of the patients. The medical records of 126 adult patients with P. aeruginosa bacteremia in Nagasaki University Hospital were retrospectively reviewed between January 2003 and December 2012. Of 126 patients with P. aeruginosa bacteremia, 60 patients (47.6%) were classified as immunocompetent. Mortality in immunocompetent patients tended to be lower than in immunocompromised patients (7-day mortality, 8% vs. 30%, P < 0.01; 30-day mortality, 23% vs. 39%, P = 0.053). Multivariate analysis showed that a higher sequential organ failure assessment score (hazard ratio [HR]: 1.27, P < 0.01) and underlying malignancies (HR: 3.33, P < 0.01) were independently associated with 30-day mortality. Initial antibiotic therapy (HR: 0.21, P < 0.01) and patients' immune status (HR: 0.29, P = 0.02) also had a significant impact on survival. However, there was a significant interaction between these 2 variables (P = 0.03 for interaction). A subgroup analysis showed that in immunocompromised, but not immunocompetent patients, initial appropriate antibiotic therapy was associated with lower mortality (30-day mortality 20.5% vs. 66.7%, P < 0.01 by log-rank test).

The inoculum effect is a laboratory phenomenon in which the minimal inhibitory concentration (MIC) of an antibiotic is increased when a large number of organisms are exposed. Due to the emergence of extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-Kpn) infections, the inoculum effect of ESBL-Kpn on β-lactams was studied in vitro and in vivo using an experimental model of pneumonia. The in vitro inoculum effect of 45 clinical ESBL-Kpn isolates on β-lactams was evaluated at standard (10(5) CFU/mL) and high (10(7) CFU/mL) organism concentrations. The MIC50 of piperacillin-tazobactam, cefotaxime and cefepime was increased eight-fold or more and that of meropenem was increased two-fold. The in vivo inoculum effect was evaluated in an ESBL-Kpn pneumonia mouse model treated with bacteriostatic effect-adjusted doses of piperacillin-tazobactam (1000 mg/kg four times daily, %T>MIC; 32.60%) or meropenem (100 mg/kg twice daily, %T>MIC; 28.65%) at low/standard (10(4) CFU/mouse) and high (10(6) CFU/mouse) inocula. In mice administered a low inoculum, no mice died after treatment with piperacillin-tazobactam or meropenem, whereas all the control mice died. In contrast, in the high inoculum model, all mice in the piperacillin-tazobactam-treated group died, whereas all meropenem-treated mice survived and had a decreased bacterial load in the lungs and no invasion into the blood. In conclusion, meropenem was more resistant to the inoculum effect of ESBL-Kpn than piperacillin-tazobactam both in vitro and in vivo. In the management of severe pneumonia caused by ESBL-Kpn, carbapenems may be the drugs of choice to achieve a successful outcome., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Linezolid is the first member of the oxazolidinones and is active against drug-resistant Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA). Additionally, linezolid shows an immunomodulatory effect, such as inhibition of inflammatory cytokine production. In this study, we examined the effect of linezolid on MRSA-induced MUC5AC overexpression in airway epithelial cells. In this study, an MRSA supernatant was used to avoid the direct effect of linezolid on MRSA. MUC5AC protein production was significantly increased with a 40-fold dilution of MRSA supernatant. At the mRNA level, MUC5AC gene expression was significantly increased 6 and 9 h after stimulation. In an inhibition study, linezolid significantly reduced MRSA-induced MUC5AC protein and mRNA overexpression at concentrations of 5 and 20 μg/ml, which were the same as the trough and peak concentrations in human epithelial lining fluid. In an analysis of cell signaling, among the mitogen-activated protein kinase inhibitors, only the extracellular signal-regulated protein kinase 1/2 (ERK1/2) inhibitor reduced the MUC5AC protein production to the same level as that of the control; on Western blot analysis, only ERK1/2 was phosphorylated by the MRSA supernatant. In addition, the ERK1/2 phosphorylation was inhibited by linezolid. MUC5AC and MUC5B are the major barrier that traps inhaled microbial organisms, particulates, and foreign irritants. However, in patients with chronic respiratory diseases, pathogen-induced MUC5AC overexpression causes many problems, and control of the overexpression is important. Thus, this study revealed that linezolid showed a direct immunomodulatory effect in airway epithelial cells., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Daptomycin is inactivated by pulmonary surfactant, but its effectiveness in hematogenous pulmonary infection has been poorly studied. The potential therapeutic application was evaluated in a methicillin-resistant Staphylococcus aureus (MRSA) hematogenous pulmonary infection mouse model. Compared with control results, daptomycin improved survival (P < 0.001) and decreased the number of abscesses and bacteria in the lungs (P < 0.01). Daptomycin may be an effective therapeutic option for MRSA hematogenous pulmonary infection.

Biapenem (BIPM) has high bactericidal activity against Pseudomonas aeruginosa and similar activity in vitro as meropenem (MEPM). We used a murine model to examine the efficacy of biapenem against ventilator-associated pneumonia (VAP) caused by P. aeruginosa. Mice were treated by intraperitoneal injection with 100 mg/kg BIPM or MEPM every 12 h beginning 12 h after inoculation with P. aeruginosa. Survival was evaluated for 7 days, and 24 h after infection, lung histopathology was analyzed and the number of viable bacteria in the lungs and blood was counted. In addition, the pharmacokinetics of BIPM and MEPM were analyzed after the initial treatment. BIPM and MEPM significantly prolonged survival compared to control (P < 0.05). The lungs of mice treated with BIPM or MEPM had significantly fewer viable bacteria (3.54 ± 0.28 vs. 3.77 ± 0.14 log(10) CFU/ml) than in the lungs of control mice (6.65 ± 0.57 log(10) CFU/ml) (P < 0.05). Furthermore, viable bacteria were not detected in the blood of mice treated with BIPM or MEPM (control 2.85 ± 0.85 log(10) CFU/ml) (P < 0.05). Histopathological examination of lung specimens indicated that BIPM and MEPM prevent the progression of lung inflammation, including alveolar neutrophil infiltration and hemorrhage. The % time above MIC for BIPM and MEPM was 15.4% and 18.3% in plasma and 19.8% and 19.8% in lungs, respectively. These results show that BIPM and MEPM significantly prolongs survival and reduces the number of viable bacteria in a murine model of VAP caused by P. aeruginosa. Therefore, BIPM might be a potent and effective treatment for VAP caused by this bacterium.

Using 49 clinical methicillin-susceptible Staphylococcus aureus isolates (MSSA) and 54 clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, we examined the change of MIC using five different inocula (2.5-4 x 10(2) cfu/spot-2.5-4 x 10(6) cfu/spot). We found the big change of the MIC with the increase of the inoculum size in ampicillin against MSSA, and the change was small in cefazolin, meropenem, ciprofloxacin. For anti-MRSA antibiotics, we found the small change with the increase of the inoculums size in vancomycin and arbekacin, and the middle change in teicoplanin and linezolid against MSSA and MRSA. The data from this study suggest that in serious and high inocula infections caused by S. aureus, the presence of an inoculum effect should be considered in curing.

Background: Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) has been shown to improve oxygenation in cases of diffuse alveolar damage, but little is known about its effectiveness in treating pneumocystis pneumonia (PCP) in HIV-negative immunosuppressed patients., Objectives: This study was aimed at investigating the effect of PMX-DHP in treating non-HIV-related PCP., Methods: Between October 2005 and September 2008, 6 patients with non-HIV-related PCP were treated with 2 sessions of PMX-DHP at an attending physician's discretion when severe hypoxemia developed despite conventional treatments including high-dose corticosteroid, whereas 9 patients in a similar condition were treated without PMX-DHP. Changes in oxygenation and radiographic findings in the PMX-DHP group and adverse events associated with PMX-DHP were investigated retrospectively, as were the outcomes for both treatment groups., Results: There was an improvement in PaO(2)/FiO(2) during each PMX-DHP session, from 148.8 ± 52.5 to 188.2 ± 79.3 mm Hg (p = 0.02). After 2 sessions of PMX-DHP, an improvement in PaO(2)/FiO(2), from 131.8 ± 37.4 to 213.3 ± 87.3 mm Hg, was observed (p = 0.04), but no significantly different improvement was detected on the following day. The radiographic findings improved in 4 patients during PMX-DHP. The in-hospital mortality was similarly high in both groups (50% in the PMX-DHP group vs. 67% in the non-PMX-DHP group). No significant adverse events associated with PMX-DHP were observed except for advanced thrombocytopenia in 1 patient., Conclusion: PMX-DHP may serve as an adjunct in the treatment of non-HIV-related PCP, temporarily alleviating severe hypoxemia even in cases refractory to conventional treatments., (Copyright © 2010 S. Karger AG, Basel.)

To investigate whether or not the combined ultrasound and antibiotic treatment is effective against chlamydial infection, a new ultrasound exposure system was designed to treat chlamydia-infected cells. First, the minimum inhibitory concentrations of antibiotics against Chlamydia trachomatis were determined. Infected cultures were treated with antibiotics then sonicated at intensity of 0.15 or 0.44 W/cm(2) with or without Bubble liposomes. After 48 or 72 h after infection, chlamydial inclusions were stained and examined by fluorescence microscopy. The internalization of dextran-fluorescein conjugates by ultrasound irradiation with Bubble liposomes was observed by fluorescence microscopy. The results showed that application of nanobubble-enhanced ultrasound caused no significant effect on cell viability and chlamydial infectivity. However, Doxycycline (1/2 MIC) or CZX (1.0 μg/ml) in combination with nanobubble-enhanced ultrasound dramatically reduced the number of inclusions compared with that administered with antibiotics only. Bubble dose-dependent synergy was also observed. After ultrasound irradiation at intensity of 0.44 W/cm(2) on the presence of Bubble liposomes, 10% of HeLa cells were observed to have internalized the dextran molecules. This study suggests the possibility of using nanobubble-enhanced ultrasound to deliver antibiotic molecules into cells to eradiate intracellular bacteria, such as chlamydiae, without causing much damage to the cells itself., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Fluoroquinolone (FQ) resistance is usually caused by point mutations within the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and/or parE. However, little is known about the worldwide increase in FQ-resistant Escherichia coli or, more specifically, about the geographical distribution of QRDR mutations and the clonal spread of isolates. In this study, we analysed 68 FQ-resistant E. coli isolates from eight Asian countries using QRDR amino acid mutation patterns and examined their susceptibility to FQs. Of the isolates, 38% had mutations at S83 and D87 of GyrA and S80 of ParC (MM/-/M-/-) and 34% had mutations at S83 and D87 of GyrA, S80 of ParC and S458 of ParE (MM/-/M-/M). MIC(50) values (minimum inhibitory concentrations for 50% of the isolates) for isolates with at least mutation at S458 of ParE for ciprofloxacin and prulifloxacin were relatively higher than MIC(50) values of isolates without this mutation. Based on their geographic distribution and the QRDR mutation patterns, the isolates were divided into a common type in which the organisms were isolated from three or more countries, and a local type in which the isolates were from one or two countries. Mutation types at S83L and D87N in GyrA and S80I in ParC with no or another site in the QRDR were the most frequent among the FQ-resistant isolates, especially among the common type. Gene typing indicated that isolates in the common type were not similar between countries. These data suggest that the increase in FQ-resistant E. coli strains is mainly generated by mutations in the QRDR in each geographical area rather than through intercontinental spread., ((c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

The filamentous fungus, Lambertella corni-maris (L. corni-maris), a mycoparasite on Monilinia fructigena, produces the antibiotics, lambertellols A (1), B (2), and lambertellin (3), in a substantial amounts under acidic conditions, whereas these antibiotics were hardly detected when the fungus was cultured on a potato-sucrose (PS) medium without added acids. Our investigations also revealed that the host, M. fructigena, changed its surroundings into acidic conditions, suggesting that the acidic conditions acted as kairomones that stimulated the production of 1-3.

A 47-year-old man who had been taking minocycline for palmoplantar pustulosis developed fever, myalgias, polyneuropathy, and testicular pain, with elevated C-reactive protein (CRP). Neither myeloperoxidase- nor proteinase-3-antineutrophil cytoplasmic antibody was positive. These manifestations met the American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Stopping minocycline led to amelioration of symptoms and normalization of CRP level. To our knowledge, this is the second case of minocycline-induced vasculitis satisfying the criteria. Differential diagnosis for drug-induced disease is invaluable even for patients with classical polyarteritis nodosa.

Clarithromycin (CAM) and rifampicin (RFP) have both been recognized to be effective antibiotic agents against Mycobacterium avium complex (MAC) infection. Rifamycin derivatives including RFP and rifabutin modulate the CAM metabolism by inducing the hepatic cytochrome p-450 3A4. To clarify the effect of RFP on the CAM metabolism, we measured the plasma concentration of CAM and 14-R-hydroxyclarithromycin (M-5), the major metabolite of CAM, in 9 patients suffering from MAC infection before and after the addition of RFP. After the addition of RFP, the mean plasma concentration of CAM significantly decreased, while that of M-5 did not. In addition, the amount of CAM + M-5 concentration also significantly decreased. As M-5 is less effective against MAC infection than CAM, more attention should thus be paid to the plasma CAM concentration in patients administered CAM and RFP concomitantly.

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.

The efficacy of antimicrobial regimens for the treatment of uncomplicated gonococcal urethritis depends partially upon the period of time (therapeutic time) during which the drug concentration in the blood after the concentration peak is greater than four times the minimum inhibitory concentration for 90% of clinical isolates of Neisseria gonorrhoeae (MIC(90)). A therapeutic time of at least 10 h is suggested as an important determinant for elimination of 95% or more of the infection. In this study, therapeutic times for a single 400-mg dose of cefixime at various MIC(90)s were calculated, and pharmacokinetic profiles of double-dosing of 200 mg cefixime at various intervals were simulated. Subsequently, a dosing interval of 6 h was tested in 6 healthy Japanese men, and then 93 Japanese men with gonococcal urethritis were treated with a regimen of two 200-mg doses of cefixime given at a 6-h interval. For a single dose of 400 mg cefixime, therapeutic times were calculated to be 12.8, 9.1, 5.4, and 1.7 h for MIC(90)s of 0.06, 0.125, 0.25, and 0.5 microg/ml, respectively. In the simulation study of double-dosing of 200 mg cefixime at a 6-h interval, the therapeutic times for the MIC(90)s of < or =0.125 microg/ml were longer than 10 h. Of the 93 patients, 68 were evaluated for microbiological outcome, and N. gonorrhoeae was eradicated in 60 (88.2%). The MIC(90) of cefixime for the 61 isolates tested was 0.125 microg/ml. All strains with MICs of < or =0.06 microg/ml were eradicated, whereas 8 of 16 strains with MICs of > or =0.125 microg/ml persisted after treatment. This regimen would not be effective against infection by strains exhibiting cefixime MIC(90)s of > or =0.125 microg/ml. For such strains, a different regimen with a higher dose of cefixime would be required.

We studied clinical effect of a combination therapy with cefozopran (CZOP) and tobramycin (TOB) for infections in 80 patients with hematologic diseases in 15 institutes. Combined doses with CZOP 2 g and TOB 60-90 mg twice a day had been given intravenously. Of the 80 patients, 61 patients (42 with acute leukemia, 10 with malignant lymphoma, 3 with aplastic anemia, 2 with chronic myeloid leukemia, 2 with multiple myeloma, and 2 with myelodysplastic syndrome) were evaluable. Those consisted of 6 patients with septicemia, 49 with suspected septicemia, 3 with pneumonia, and 3 with other infections. Clinical efficacy by the treatment was excellent in 24, good in 17, fair in 9, and poor in 11 patients, and the overall efficacy rate including excellent and good was 67.2%. Microbiologically, 5 of the 6 patients with septicemia (1 coagulase negative Staphylococcus, 2 S. pneumoniae, 1 S. oralis, and 1 E. coli) were responded. The efficacy rate in patients with severe granulocytopenia showing 100/microliter or lesser neutrophil counts during the drug administration was 57.1% (12/21). Side effects and abnormal changes of clinical laboratory findings were observed in 5 patients, and 16 patients, respectively, but most of them were mild. The findings above suggested that the combination therapy with CZOP and TOB is useful as an empiric therapy for severe infections in patients with hematologic diseases.

The effects of streptomycin on the otoconial layer of the adult guinea pig were investigated using scanning electron microscopy. Administration of streptomycin induced a reduction of otoconia with formation of giant otoconia. These phenomena reached their maximum 4 weeks after the cessation of streptomycin intoxication in the utricle and between 2 and 6 weeks after in the saccule. Otoconia began to recover in the utricle 4 weeks and in the saccule 6 weeks after the cessation of streptomycin intoxication with an increasing number of small otoconia. Eight or 10 weeks after the cessation of streptomycin intoxication, the otoconial layer has completely recovered in both the utricle and saccule.

Formation and fate of abnormal (giant) otoconia of the guinea pig following streptomycin intoxication were investigated using scanning electron microscopy. The giant otoconia formed as multifaceted morphology in their early developmental period. They grew up the the transitional type and finally to the cylindrical type. It has been suggested that the giant otoconia found following streptomycin intoxication may be formed mainly by dissolution of normal otoconia due to the loss of environmental calcium, followed by recrystallization as giant crystals. These phenomena seemed to be closely related to the otoconial dynamics which may regulate calcium ion homeostasis of the endolymph.

The action of streptomycin sulfate (SM) on the regenerative process of the vestibular nerve and posture recovery was studied, using bull frogs. The vestibular nerve was sectioned in various conditions with intact endorgan or with SM intoxication. When the nerve was sectioned with the hair cells left intact, the nerve regenerated well and body balance recovered to normal. However, when neural regeneration was blocked, recovery was incomplete. SM intoxication resulted in various degrees of hair cell damage. Degree of posture recovery correlated well with the number of hair cells. When the nerve was sectioned after damaging the hair cell, the nerve failed to regenerate and posture recovery was incomplete. These results suggest that the degree of posture recovery depends on hair cell function and neural regeneration. Furthermore, neural regeneration is strongly influenced by hair cell function.

Effect of temperature changes on the vestibular receptor was studied using isolated posterior semicircular canals (PSC) of bull frogs. Cupula was removed from the crista. PSC was placed in the inner compartment of the double chamber. Warm or cool water was filled in the outer compartment to change the temperature of the inner compartment. Changes of the spontaneous discharge were recorded from the ampullary nerve. When cooled, the discharge temporarily increased, followed by a gradual decrease. When warmed, it temporarily decreased and then increased, forming response curves of a mirror image. After addition of streptomycin, the temperature dependent response disappeared. These results suggest that the semicircular canal receptor is activated by direct temperature effects.

Azithromycin (AZM), 10% fine granules or 100 mg capsules, were given orally to 27 children with various pediatric infections. The results of the study are shown below. 1. Pharmacokinetic investigation. We studied plasma and urinary concentrations after 100 mg AZM capsules were given. One patient received 8.3 mg/kg of AZM once a day for 3 days, and AZM concentration in plasma was 0.033 microgram/ml 48 hours after the final dosing. Doses of 8.3 and 12.5 mg/kg body weight of AZM were respectively given to two patients once daily for 3 days. As a result, AZM concentrations in urine during a period between 96 and 120 hours post-dosing were 1.67 and 4.53 micrograms/ml, respectively, and urinary excretion rate in 120 hours after the first dosing was 10.54% in the patient that was given 12.5 mg/kg. 2. Clinical investigation. Clinical efficacies were examined in 24 patients. Excellent results were obtained in 7 patients, good results in 14 patients, hence the clinical efficacy rate was 87.5%. Bacteriologically, Haemophilus influenzae strains isolates from 2 patients were eradicated in 1 and decreased in the other. Safety was evaluated in 26 patients. An adverse reaction was observed in 1 patient (urticaria). Abnormal laboratory test results were observed in 2 patients, decreased WBC in 1 and elevation of eosinophils in the other. The above results suggest that AZM is a useful oral antibiotic for pediatric patients with infection with susceptible organisms.

Azithromycin (AZM) is a new oral macrolide antibiotic drug. AZM either in 10% fine granules form or in 100 mg capsule form was studied for its pharmacokinetics and treatment efficacy in pediatric patients with various infections. 1. Pharmacokinetics. Plasma and urine samples were collected from four patients with pharyngitis and post-dosing drug levels were determined. The drug was given once daily at 10 mg/kg body weight for 3 days. The drug concentrations found in plasma at 96 hours after the first dosing (48 hours after the final dosing) lay in a range of 0.02 and 0.04 microgram/ml and in urine at 120 hours after the first dosing (72 hours after the final dosing) in a range between 3.2 and 7.7 micrograms/ml. AZM was found in two patients but no effect was observed on blood levels of theophylline determined between 48 and 96 hours after the first dosing in the treatment of underlying bronchial asthma. 2. Clinical study results. Clinical studies of AZM was carried out in 25 pediatric patients with bacterial infections that mainly affected the respiratory tract. The patients received either 10% fine granules at 10 or 20 mg/ kg body weight or 100 mg capsules at 10 mg/kg body weight once daily over 3 to 6 days. The drug was found markedly effective in six patients, moderately effective in thirteen patients, while the investigators could not assess the drug efficacy in six patients. Although no side effect was reported in the study, two patients experienced slight decrease in WBC.

The effects of streptomycin on the calcium ion turnover into otoconia of adult guinea-pigs investigated by the use of tetracycline. The oral administration of tetracycline induced the deposition of tetracycline (fluorescence) on the outer surface of otoconia indicating the existence of dynamic exchange and/or uptake of calcium ions in the otoconia. The significant finding is that streptomycin specifically interfered with calcium uptake into the otoconia which indicated that the decrease in calcium uptake caused by streptomycin may be closely related to the loss of otoconia as well as to a decrease in the calcium contents of otoconia. The decrease in calcium incorporation into otoconia caused by streptomycin was recovered within 6 weeks after the last injection of streptomycin. The number of otoconia with fluorescence in the central portion as well as their outer surface was increased. It is therefore suggested that the recovery of calcium uptake as well as new otoconial regeneration may play an important role for the recovery from loss of otoconia.

The inducibility of SOS responses by Panfuran-S, which has been used as an antimicrobial medicine in Japan, was studied in Escherichia coli cells having different DNA-repair capacities for UV lesions. Panfuran-S induced mutations at high frequencies in uvrA and the wild-type strains, and significant killing effects of Panfuran-S were detected in DNA-repair-deficient strains, uvrA and recA. The effective prophage induction was detected in two kinds of lambda-lysogenized cells treated with Panfuran-S. The expression of the umuC+ gene was apparently induced in uvrA and the wild-type strains, but not induced in lexA and recA strains. In particular, high inducibility of the gene expression was detected in uvrA strain as compared with the wild-type strain. From these results, we conclude that Panfuran-S is a DNA-damaging agent and may induce the error-prone SOS responses.

The new thiolactone antibiotic, thiolactomycin, is rapidly absorbed in rats when administered either orally or by intramuscular injection. A peak in concentration of the drug is reached in the blood and in various visceral organs within 15 minutes after administration. The concentration decreases rather rapidly and about 51-69% of the drug is excreted in urine during the first 24 hours. Though the in vitro effect of thiolactomycin is moderate, it effectively protected mice challenged intraperitoneally with several strains of S. marcescens and K. pneumoniae and more effective than carbenicillin in treating experimental acute urinary tracts infected with S. marcescens. Also, in mice whom immunodefense was decreased by treatment with cyclophosphamide, thiolactomycin was more effective than carbenicillin against S. marcescens challenge.

I. The nephrotoxic potential of latamoxef (LMOX, 6059-S) was evaluated in male rabbits after combined administration of 500 or 2,000 mg/kg of the compound (ear vein) with subcutaneous injection of furosemide (FUR) at 50 mg/kg. Histological examination of kidney tissues of all animals were performed after 72 hours. Three rabbits were used at each dose level, and comparative studies were performed using several cephalosporins, such as CET and CEZ. Neither LMOX nor CET produced nephrotoxic effects at 500 mg/kg when given in combination with FUR. Although slight elevation of BUN and creatinine in plasma and hyaline casts in lumen of the distal tubules were observed in animals receiving 2,000 mg/kg of LMOX or CET when dosed with FUR, no histological changes were found in renal tissues. Significantly more nephrotoxicity was observed with the treatment of CEZ alone, and this toxicity was augmented in combination with FUR. II. Concomitant administration of LMOX with intramuscular injection of tobramycin (TOB) was estimated in male rabbits. Rabbits received daily intramuscular injection of TOB at 50 mg/kg for 10 days in combination with single dosing of LMOX (500 or 2,000 mg/kg) on the 8th day after the start of TOB treatment. Three rabbits were used at each dose level, and comparative studies were conducted using CET or CEZ. All rabbits were killed 48 hours after the last injection of TOB and examined histopathologically. Combined administrations of LMOX or CET did not aggravate the nephrotoxicity induced by TOB. However, CEZ enhanced renal injuries produced by TOB injection.

Mannopeptins show in vitro antimicrobial activity against gram-positive and some gram-negative bacteria. The antimicrobial activity is unaffected by the addition of serum, and potentiated by alkaline pH or decrease in inoculum size. The antibiotics exert bectericidal effect at doses twice as high as the minimum inhibitory concentration. When the antibiotics were injected into mice through either intravenous, intraperitoneal, intramuscular or subcutaneous routes, the antimicrobial activity appeared within 15 minutes in the serum of mice and was slowly excreted in the urine. However, the antibiotics were poorly absorbed by the oral route. The antibiotics were capable of protecting mice from lethal infection produced by the intravenous injection of Staphylococcus aureus, Streptococcus pyogenes and the intraperitoneal injection of Shigella sp. and Escherichia coli, but ineffective against Salmonella typhosa.

New antibiotics, mannopeptins A and B, were isolated from the fermented broth of Streptomyces platensis strain FS-351. Ferrous ion is essential for the antibiotic production, since no productivity was noted with media containing less than 0.11 mM ferrous ion and maximum production was achieved at a concentration of 1.8 mM. The antibiotics are basic glycopeptides with relatively high molecular weight and are similar to ristocetin and vancomycin but can be differentiated from them in view of their chemical composition and chromatographic behavior. The antibiotics were named mannopeptin after the glycopeptide containing mannose.