The bacteria isolated from 6 cases of odontogenic infection were identified, and the susceptibility of these bacteria to some antibiotics, the rate of ampicillin (ABPC) resistant bacteria and the β-lactamase producer were determined in each case. All isolates were anaerobic Gram-negative rods, and Prevotella intermedia was predominant in 3 cases. Isolates from 2 cases in which P.intermedia was predominant showed low susceptibility to β-lactams, and a high rate of isolation of ABPC resistant bacteria. In addition, the rates of β-lactamase producers were 59.6 and 29.8%, respectively. Isolates from another case showed moderate susceptibility to β-lactams, but ABPC resistant isolates were not found. Isolates from 3 cases which anaerobe Gram-negative rods besides P.intermedia were isolated were highly susceptible to β-lactams, and β-lactamase producers were not detected. Isolates from one case, however, showed low susceptibility to cefaclor, cefmetazole and latamoxef, and the susceptibility of isolates to erythromycin in another case was low. The results suggest that there are two mechanisms of β-lactam resistant bacteria originating the odontogenic infections; one in which the resistance is closely related toβ-lactamase, and another in which it is not related to this enzyme. Furthermore, there are cases in which detection of the β-lactamase producer decreases after the drug is changed.

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We assessed the direct detection of Streptococcus pneumoniae in clinical samples using the polymerase chain reaction (PCR) method. A total of 288 throat swab specimens were collected from children with acute respiratory infection. A set of primers for the PCR was designed to amplify the region between position 694-bp and 966-bp in the autolysin gene (lytA), which is specific for S.pneumoniae. The sentitivity of detection was 1.2×10² CFU/ml. The PCR procedure, including pretreatment of the sample, took about 2.5 hours. Bacterial cultures were performed from the same specimen in parallel with the PCR to compare the individual detection efficiencies. Cultivation revealed S.pneumoniae in only 59 (20.5%) of the 288 specimens, whereas the PCR revealed 188 (41.1%) to be positive. PCR was also positive in all samples containing at least 10³CFU/ml of bacteria. An obvious DNA fragment was detected by PCR in some culture-negative samples. These results suggest that PCR is clinically useful for detecting S.pneumoniae directly.

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The in vitro antibactericidal activity of cefepime (CFPM) was compared with that of cefpirome (CPR) and ceftazidime (CAZ) against imipenem/cilastatin (IPM/CS)-resistant Pseudomonas aeruginosa. The MIC₉₀ of CFPM, CPR, CAZ and IPM/CS was 32, 128, 64 and 64μg/ml respectively against 50 clinical isolates of P.aeruginosa. Fourteen of the 50 strains were IPM/CS-resistant. The MIC₉₀ of CFPM, CPR and CAZ was 16, 32 and 32μg/ml respectively against IPM/CS-resistant P.aeruginosa. The IPM/CS-resistant strains showed no cross-resistance between IPM/CS and CFPM. We observed a lack of the outer membrane protein D₂ in the IPM/CS resistant strains using SDS-PAGE. The time courses of CFPM, CPR and CAZ bactericidal activities against 2 strains of IPM/CS-resistant strains were determined. The bactericidal activity of CFPM was equal to or somewhat superior to those of CPR and CAZ at concentration of MIC or subMIC. On the other hand, inducer activities of CFPM and CAZ for β-lactamase were lower than that of CPR. In an inhibition study, CFPM showed a much higher Ki value for cephalosporinase of P.aeruginosa PRC 316 than did CPR and CAZ. An extremely lower affinity of CFPM was demonstrated.

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A simplified microbiological detection method for aminoglycoside antibiotics, using Bacillus subtilis and thymolphthalein as calorimetric indicator, is described. In each test, netilmicin, gentamicin and isepamicin were sufficiently recovered from individual blood spots during incubation in the same medium. After incubation, the concentration of blue-colored thymolphthalein was determined by both fluorescence polarization immunoassay and a spectrophotometer equipped with a multichannel photodiode array detector for each aminoglycoside. There was proportionality between the concentration of each aminoglycoside and the degree of discoloration of thymolphthalein. No difference was found between these two methods. The advantage of this method is that the approximate individual concentration ofnetilmicin, gentamicin or isepamicin can also be detected visually by using a paper disc containing thymolphthalein for the individual aminoglycoside as follows: navy blue, more than peak concentration; light blue, within therapeutic range; white, less than trough concentration, and ready for injection.

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Vancomycin hydrochloride (VCM) for injection has been marketed since November 1991 as an indication severe for infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The overall results of post-marketing surveillance for the past three years are shown below.The subjects were 1, 354 patients to whem the drug was intravenously administered in a study period from December 1991 to October 1994 in 650 facilities, and a total of 1, 255 cases were chosen among them as the subjects for evaluation of efficacy excluding 99 cases which the physicians in charge had classified as unable to judge. Daily doses of the drug were 40 mg/kg for children, and 1 g or 2 g for adults for a period of 1-3 weeks. In addition, decrease in daily dose as well as shortening of the administration period were observed with time. When observed improvement rates according to diseases, the improvement rate was 78. 7% for pneumonia, and 87.5% for sepsis, exhibiting an improvement rate of 81.7% as a whole. On the other hand, the improvement rates were higher for the patients who had not been given a previous drug, but, no difference was observed in the improvement rates among daily doses or in patients with or without concomitant drugs. The antibacterial effect was 64.2% for pneumonia, and 88.5% for sepsis, 69.8% bacterial eradication rate as a whole. There were 271 episodes of subjective or objective adverse reactions and abnormal laboratory findings in 191 patients (14.1%). Especially for the abnormal laboratory findings on renal function, the incidence in the adult and elderly patients was higher for the patients daily dose of 2 g than that for those with 1 g daily. The plasma level monitoring was performed in 1, 082 cases in 500 patients out of 1, 354 patients (36.9%)(2.2 cases per 1 patient). The rates of monitoring practice were showing an increasing trend in accordance with progress of year. Pharmacokinetics analysis revealed decrease in creatinine clearance (Ccr) in many cases of the elderly patients. A linear relationship was observed among elimination constant (e), VCM clearance, and Ccr. A β-phase elimination half-life (t_1/2 β) was extended, accompanying with decrease in Ccr, and even for the cases withmild decrease in renalfunction the elimination half-life was prolonged to nearly three times the value of healthy adults. The above results thus obtained prove that the VCM injection is a highly useful drug showing the sufficient effects for MRSA infection and is thereby considered best to immediately administer to the cases in which phlogogenous bacteria is identified as MRSA. Adverse reaction can be minimized when in use, if appropriate use and dose are applied by performing the plasma level monitoring along with consideration of ages and renal function.

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Imipenem/cilastatin sodium (IPM/CS) was used as an initial antibacterial therapy for infections in granulocytopenic patients undergoing ciprofloxacin (CPFX) prophylaxis. Oral CPFX was started at 600 mg daily when peripheral blood granulocytes dropped below 500/μl. As soon as febrile episodes developed, IPM/CS 1g×2/d d.i.v. was instituted. As underlying diseases, 28 patients had acute leukemia, myeloblastic or lymphoblastic, 1 chronic melogenous leukemia in blast crisis, 3 myelodysplastic syndrome, and 15 malignant lymphoma. Bacterial infections diagnosed were sepsis in 8 patients, suspected sepsis in 36, and other infections in 3. The overall response rate to this treatment was 80.9%, and those for sepsis, suspected sepsis, and other infectious diseases were 62.5%, 83.3%, and 100%, respectively. This regimen was also effective in 76.9%(10/13) of patients whose granulocyte count remained below 100/μl throughout the course of IPM/CS therapy. The causative organism was identified in 10 infections including 8 sepsis cases; 8 organisms were gram-positive bacteria, and 7 were susceptible. There was no difference in effectiveness between those patients who were receiving G-CSF and those who were not (20/27, 74.1% vs 18/20, 90.0%). As adverse reactions, gastrointestinal tract symptoms such as nausea, vomiting, or anorexia were observed in 7 patients (11.7%), liver function disturbance in 3 (5.0%), and proteinuria in 1 (1.7%), among 60 evaluable episodes. Thus, initial antibacterial therapy with IPM/CS following oral prophylactic use of CPFX is an effective and safe regimen for the treatment of febrile granulocytopenic infections in patients with hematological malignancies.

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Azithromycin (AZM), a 15-membered new macrolide, was compared with cefaclor (CCL) in a multicenter, double-blind, double-placebo trial in the treatment of skin and skin structure infections. Patients, more than 16 years of age, with hair follicle- and nailassociated deep infections (furuncle, furunculosis, carbuncle, sycosis barbae, and acute suppurative paronychia: group II a), diffuse deep infections (lymphangitis, erysipelas, and cellulitis: group II b), and cutaneous and subcutaneous abscesses (infected atheroma, suppurative hidradenitis, and miscellaneous abscesses: group 111) were enrolled after informed consent had been obtained. Patients assigned to the AZM group received two 250 mg tablets once a day for three days and one CCL placebo capsule three times a day for seven days. Patients assigned to the CCL group received two AZM placebo tablets once a day for three days and one CCL 250 mg capsule three times a day for seven days. The patients were observed on day 4 (3-5) and day 7 (6-8). Cure on day 4 or an apparent improvement on day 4 followed by a further improvement was evaluated as “markedly effective”. An apparent improvement on day 7 was evaluated as “effective”. Aslight improvement on day 7 was evaluated as “slightly effective” The absence of improvement or aggravation after three days of the treatment, therapeutic incision or paracentesis during the course of treatment, or development of new infectious lesions were evaluated as “not effective”. The clinical efficacy rates were 90.6%(77/85) for the AZM group and 80.5%(70/87) for the CCL group. The difference was not statistically significant. However, the clinical equivalence of the two drug groups was statistically demonstrated (Δ10%, p<0.001). The efficacy retes, classified according to the disease group, were 94.4%(34/36) for the AZM group and 89.5%(34/38) for the CCL group in group II a, 100%(18/18) for the AZM group and 84.2%(16/19) for the CCL group in group fib, and 80.6%(25/31) for the AZM group and 66.7%(20/30) for the CCL group in group Ill. Differences was not statistically significant among disease groups. The bacteriologic response retes were 87.3%(48/58) for the AZM group and 82.4%(42/51) for the CCL group. The difference was not statistically significant. Adverse reactions were seen in 10.6%(11/104) of the AZM group and in 10.2%(11/108) of the CCL group. The difference was not statistically significant. The incidences of abnormal laboratory findings were 4.3%(4/93) for the AZM group and 3.1%(3/96) for the CCL group showing no statistically significant difference. Neither the general safety rate nor the usefulness rate were not statistically different between the two drug groups. These results suggest that AZM at a dosage of 500 mg once a day for three days is as effective, safe and useful as CCL at a dosage of 250 mg t.i.d. for seven days in the treatment of skin and skin structure infections.

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