Microbiological and pathological examinations of the respiratory tract of young hamsters infected with Mycoplasma pneumoniae by inhalation of aerosol were carried out for up to a maximum of 98 days ...after infection. Mycoplasma pneumoniae organisms were found mainly in the pharynx and larynx for the first two weeks, then they continued to proliferate in the main bronchi or intrapulmonary bronchi for up to 98 days. On the third day after infection, inflammatory changes consisting mostly of infiltration with lymphocytes and monocytes appeared in the bronchial epithelium. These inflammatory changes proceeded to the peribronchial or interstitial tissues and reached a maximum on the 21st day after infection. After that, they showed a tendency to decrease and were replaced partially by atelectatic and emphysematous changes. These pathological processes seemed to be associated with the presence of Mycoplasma pneumoniae. On electron microscopic examination by the double staining and the ferritinantibody method, Mycoplasma pneumoniae organisms were found among cilia and microvilli of the bronchial epithelium during the first two weeks. Structures resembling mycoplasmas, which bound ferritin were also located among the debris of exfoliated cells from epithelium. As the inflammatory process spread, exfoliation and desquamation of bronchial epithelium and increase of mucus-secreting cells, became more marked and eventually vacuolation in the remaining epithelial cells, with an increased number of basal cells was seen throughout the epithelium. In the terminal stage the ciliary epithelium was replaced partially by squamous epithelium. These studies, especially the identification of intact mycoplasma organisms at the surface of the epithelial cells, suggested that this may be the site of growth of this organism in the respiratory tract.
Bacampicillin (BAPC) is a newly developed derivative of ampicillin which is well absorbed when given orally and is hydrolyzed to ampicillin in the body to give peak levels of ampicillin higher than ...those obtained with ampicillin itself. Fundamental and clinical studies on this drug were carried out and the results were as follows: 1) Absorption and excretion in man Three healthy male adults volunteers were given orally 250 mg of BAPC after fasting and peak levels of BAPC in the blood of two volunteers were 3.5μg/ml and 4.8μg/ml one hour after administration of BAPC. Residual one has 2.1μg/ml of peak level two hours afterwards. Urinary recovery rate during the initial two hours after administration of BAPC was 40-50 percent and 59-67 percent, 62 on the average were excreted by the end of the study for 6 hours. 2) Clinical study Thirty one patients with pulmonary infection including one case with lung cancer and one with pulmonary tuberculosis respectively, were treated with one gram of BAPC daily for 3-21 days and good results were obtained in 21 cases with efficacy rate being 75 percent. In five cases out of six patients with chronic bronchitis due to Haemophilus influenzae, this organism was eliminated completely with BAPC. 3) Adverse reaction Two patients complained of mild diarrhea and one heart burn. Eosinophilia was seen in one case.
Fundamental and clinical studies on CS-1170, a new semisynthetic cephalosporin were carried out and the results were as follows. 1) Antibacterial activity: The in vitro antibacterial activity of ...CS-1170 was tested by the serial agar dilution method. The minimal inhibitory concentrations (MICs) against 22 standard strains and 830 clinical isolates (Staphylococcus aureus 54, Salmonella 36, Citrobacter freundii 38, Citrobacter diversus 32, Citrobacter amalonatica 11, E.coli 54, Shigella 45, Klebsiella aerogenes 53, Enterobacter aerogenes 54, Enterobacter cloacae 54, Serratia marcescens 54, Proteus vulgaris 12, Proteus mirabilis 42, Proteus rettgeri 22, Proteus inconstans 16, Proteus morganii 43, Aeromonas 20, Pseudomonas aeruginosa 54, Pseudomonas putida 31, Pseudomonas maltophilia 33, Pseudomonas putrefaciens 14, Flavobacterium 50 and Acinetobacter anitratus 8.) were compared with those of cefazolin (CEZ) MICs against 22 standard strains were *lost same as those of CEZ with the exception of those of Staphylococci. MICs against clinical isolates were 2-4 times lower than those of CEZ in almost all bacteria except for Staphylococcus. 2) Serum levels in man: Two patients with pulmonary infections were injected 1 gram of CS-1170 by intravenous drip infusion with normal saline solution for 1-2 hours. Peak serum levels were 120-130μg/ml at the end of infusion. A 74y.o. male patient with pulmonary infection was given 2 grams of CS-1170 by drip infusion for 2 hours and peak serum level was 270μg/ml at the end of injection. Serum levels were around 10μg/ml even six hours after drip infusion. 3) Penetrations into sputum: A 46y.o. male patient with lung abscess who had purulent sputum was given 1 gram of CS-1170 by drip infusion for 2 hours with 5% glucose solution. Peak sputum level of the drug was about 3.8μg/ml at 3 hours after injection. 4) Biliary excretion: A 63y.o. female patient with common bile duct cancer was injected 1 gram of CS-1170 by drip infusion for one hour. Peak biliary level was 20μg/ml 2 hours after injection, The drug was still detected in small amount at seven hours after administration.
Hayflick et al. (1965) reported that mycoplasma (M.) orale was isolated directly on PPLO agar from the bone marrow samples of patients with acute leukemia, but it has been still unknown whether M. ...orale has been identified as a pathogen in some kinds of human diseases. However, it has been generally accepted that M. orale does not have a pathogenicity in the human. In order to determine the significance of the existence of M. orale in the respiratory tract, experiments in the hamster infected with M. orale were performed. Materials and Methods; Young hamsters, 3 weeks old, were utilized. A suspension of M. orale strain containing 1.6-107 colony forming unit (CFU) per ml was introduced into the hamster by the inhalation of an aerosol spray. Throat swabs were cultured onto each of two PPLO agar plates at intervals of 2-3 days for up to 42 days after exposure. The hamsters were also sacrificed at intervals of 2 to 3 days. During this time, blood samples were taken for serological studies. Both lungs were removed aseptically for bacteriological and histological studies. For controls, a group of hamsters was infected with M. pneumoniae and a 2nd group was given PPLO broth alone. Then these animals were killed and evaluated by the same methods. Results; In the groups infected with M. orale and in those exposed to PPLO broth alone, only one hamster organisms isolated from the nasopharynx or from the lungs for up to 42 days after inoculation. In the M. orale group minimal histopathologic inflammatory changes including edema in the bronchus observed from 2 to 21 days after infection. In contrast, in the group infected with M. pneumoniae, organisms were present in cultures of the lungs of all of the hamsters in the maximum concentration of 108 CFU per ml during the period of observation. Further findings such as peribronchitis and interstitial pneumonitis were present in this group for up to 28 days. No significant differences were recognized in the serological and the hematological studies in these three groups.
As shown in the results reported in the previous part 1, M. orale had no pathogenicity for the hamster. In this report it was investigated whether the existence of M. orale and M. salivarium in the ...respiratory tract is common in normal asymptomatic individuals and in patients with respiratory diseases and if these organisms play any pathogenic role in the acute exacerbations of respiratory diseases. (a) Role of M. orale and M. salivarium in normal individuals. In 564 university students and 162 middle school students, mycoplasma isolations were made using TSB solution under aerobic and anaerobic (95% N2 + 5% CO2) conditions. Of the 726 isolations made, 541 (74.5%) were M. salvarium, 26 (3.6%), M. orale, 2 (0.3%), M. pneumoniae, and 77 (10.6%) were others and 80 (11.0%) showed no growth. There was no relationship between the mycoplasma isolations and the complement-fixation titers. M. orale and M. salivarium were not isolated more frequently from the patients with oropharyngeal pathology than from normal individuals. (b) Role of M. orate and M. salivarium of the patients with respiratory diseases. Six hundred forty-four specimens from the patients with respiratory diseases have been studied for mycoplasma. Mycoplasma species were isolated in 47.2% of total patients which included 37.6% of M. salivarium, 7.9% of M. orale, and 1.7% of M. pneumoniae. As shown in table 3, mycoplasma species have been isolated most frequently (61.5%) in the patients with bronchial asthma, followed by bacterialpneumonia (50.0%), and chronic obstructive lung diseases (49.0%). The isolation rate was lower in the patients with pulmonary tuberculosis and bronchiectasis. M. salivarium could be cultivated from only one of 18 specimens obtained by aspiration through a vinyl tube inserted transorally. No pathogenic correlation was noted between mycoplasma and bacterial organisms present in the oropharynx of the patients with respiratory diseases. However, from the group of patients treated with some antibiotics prior to specimen collection especially macrolide derivatives, tetracycline and kanamycin, lower mycoplasma isolation rates were found. The results reported in this study did not indicate that M. orale and M. salivarium had a significant pathogenic role in the respiratory tract diseases.
Tetracycline is expected to be as effective as erythromycin in the treatment of pneumonia due toMycoplasma pneumoniae. In this clinical trial 12 cases with pneumonia due to Mycoplasma pneumoniaewere ...given doxycycline (Vibramycin ‘Pfizer’), a long-acting derivative of tetracycline. Judging from time periods required for defervescence, improvement in symptoms such as cough and disappearance of shadows on chest X-ray, the therapeutic effect of doxycycline was excelletit in 8 cases and good in 4 cases.
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