In 1979, systemic infections due to ampicillin-resistant H.influenzae were reported in Japan. Rapid detection of ampicillin resistance would be fascilitate to initiate adequate chemotherapy. A total of 94 strains of H.influenzae isolated from clinical specimens out of children were tested with repid slide test, a modification of iodometric method (according to Rosenblatt, 1978), and chromogenic method using Glaxo compound 87/312, for detection of beta-lactamase. The minimum inhibitory concentration (MIC) was determined by an agar dilution method. The inoculum size was approximately 106 CFU/ml. The results of rapid beta-lactamase tests were compared with an ampicillin MIC. Twenty-one strains of H.influenzae were proved to be beta-lactamase positive by both methods. These strains showed ampicillin MICs of≥1.56μg/ml. Seventy-three strains were negative beta-lactamase tests, which presented ampicillin MICs of≤0.78μg/ml. The 21 ampicillin-resistant strains were readily distinguished from 73 sensitive strains. Rapid betalactamase tests were confirmed to be reliable indicators of ampicillin-resistant H.influenzae. These methods for rapid beta-lactamase detection can be applied in routine laboratory examinations.
In an attempt to evaluate effective measures for infection prevention in bonemarrow transplantation, the incidence and types of infection were investigated on 15 patients with severehematologic disorders and solid tumors treated by this procedure during a period from October 1977 to January1981. Within the first month following marrow gafting, 11 episodes of gingivo-stomatitis due to herpes simplex virus (HSV) and only 3 of bacterial infections were observed on the protectedenvironment-prophylactic antibiotic progran, which covered a critical period of granulocytopeni of <500/mm3.Seven (54%) of the 13 patients survibing more than a month following marrow grafting developed interstitial pneumonia due to either cytomegalovirus (CMV) or Pneumocystis carinii or both. It was the major cause of death in 4 (57%) of these 7 patients. The development of interstitial peeumonia was associated with allogeneic transplantation and prolonged lymphopenia of <1000/mm3, but in lower incidence with autologous transplantation. Among several protocols for infection prevention during an early post-transplantation period, both the protected enviroment-prophylactic antibiotic program against bacterial or fungal infections and interferon (IF) prophylaxis against viral infections were found to be of clinical vlue. Moreover, topical IF was quite effective. for oral herpetic lesions, relieving from a pain and accelerating healing process, while systemic IF did not show any effcet on the establishedHSV infection. The efficacy of IF and trimethoprim/sulfamethoxazole in the prophylaxis of interstitial pneumonia caused by CMV and P. carinii, respectively, is under investigation.
The efficacy and safety of a new anti-inflammatory agent, K-708 (acemetacin), was evaluated in patients with acute upper respiratory inflammation, placing special emphasis on its antipyretic effect. The studies were performed on an open basis at the beginning, followed by a double blind comparison using ibuporfen as a standard drug. As for the antipyretic effect, a single dose of K-708 (30 mg) was as effective as that of ibuprofen (300 mg) in relieving the feverish conditions caused by various infectious diseases. In case of ibuprofen, the patients' mean body temperature reached the lowest level two hours after the administration and then it began to rise again gradually, on the other hand, the antipyretic effect of K-708 atained its maximum level three hours after the administration and the body temperature was kept at the same level up to four hours after dosing. Thus, it is clear from the above that the antipyretic effect of K-708 is apparently long-lasting as compared with that of ibuprofen. In a double blind controlled study in 230 patients, the global improvement rate in the K-708 group (90 mg/day), was 71.6% and 71.7% in the ibuprofen group (900 mg/day), no significant differnce was noted between the two groups. As for the global improvement rating of each symptom, antipyretic effect and utlity, the both groups gave almost the same results, again no significant difference was seen between the groups. The incidence of side effects in the K-708 group was 6.0% and 3.5% in the ibuprofen group, and there was no significant difference between the groups. Most of the side effects observed ere mild in nature and disappeared spontaneously without any special treatment. From the foregoing it can be concluded that K-708 is a useful drug for the treatment of acute upper respiratory inflammation and that K-708 has the potential for exerting ten times greater maximum effect as compared with ibuprofen. In this double blind study, the objective evaluation by the committee members was also prformed tentatively in accordance with the standardized clinical criteria, and was compared with that by the attending pysicians.
In Japan, tobramycin, one of the aminoglycoside antibiotics, is permitted to be administered only by intramuscular injection when it is used parenterally. But for pediatric patients, intravenous administration of antibiotics, if possible, is more acceptable than intramuscular use In this study, we compared the efficacy of intravenously and intramuscularly administered tobramycin by the experimental system using diffusion chambers. A 1.2×104 cfu/chamber of Pseudomonas aeruginosa and a 5×105/chamber of rabbit's peritoneal polymorphonuclear leukocytes or only pseudomonas were infused in diffusion chambers with 0.22μm pore sized micropore filters. Then the bacteria and leukocytes were incubated in live peritoneal cavity of the rabbit's and a 2.5 mg/kg of tobramycin was administered by both routes. Intravenous injection was done in 45 minutes using a constant fuel injector. Minimum inhibitory concentration of tobramycin for the test organism was 0.78μg/ml. Viable bacterial number in the leukocytes containing chambers similarly decreased to 5×102 cfu/chamber by 3 hours after intramuscular and intravenous administration, and slowly increased to reach 1×104cfu/chamber by 12 hours. When leukocytes were not contained in the chambers, viable bacterial numbers decreased to 2×103 cfu/chamber by 3 hours, but increased rapidly to reach more than 3×105 cfu/chamber by 12 hours after both intramuscular and intravenous injections. The peak concentration in the serum after intramuscular injection was 6.4μug/ml at 15 minutes, and 7.3μg/ml at 45 minutes after intravenous administration. Almost same concentration-time curves of tobramycin in peritoneal fluid were revealed after intramuscular and intravenous administrations. As a result, tobramycin can be used intravenously as effectively as intramuscular use. Considering the changes of viable bacterial numbers in no-leukocytes containing chambers, short interval between the peak concentrations in the serum might be needed for leukopenic patients. For this purpose, intravenous administration is more suitable than intramuscular injection, which might be acompanied with sever pain, subcutaneous bleeding and contracture of injected muscle.
Using formalinized sheep erythrocytes treated with tannic acid and coated with OEP (protein moiety of endotoxin), protease and elastase of Pseudomonas aeruginosa, passive hemagglutination titer was measured on three kinds of gamma-globulin preparations (13 lots from each maker). 67%(26/39) of gamma-globuin preparations had detectable HA antibody against OEP. 97%(38/39) had HA antibody against protease, and 92%(33/36) against elastase. No significant difference was found between mean value of OEP-HA of pepsin treated and polyethyleneglycol (PEG) treated preparations. Sulfonated preparations had a tendency to have a low OEP-HA and the difference was significant (p<0.05) compared with pepsin treated preparations. In the case of protease-HA, pepsin treated treated preparation had the highest mean value and sulfonated preparation had lowest mean value. The difference was significant. No difference in elastase HA was noted among all three gamma-globulin preparations.
In a review of 123 cases (including 4 deaths) of tsutsugamushi disease which occurred in Akita and Niigata Prefectures during a period from 1976 to 1980, we found 5 cases (died: 4, recovered: 1) which showed a hemorrhagic tendency in the course of illness. Consequently, it was considered that this symptom might be caused by the disseminated intravascular coagulation (DIC) in reviewing carefully the clinical records of those cases, especially on the subject of coagulation studies.