From September 1986 to May 1987, 269 strains of Staphylococcus aureus were collected from 19 hospitals. Forty three percent of the strains were resistant to methicillin (MRSA). The incidence of MRSA in S. aureus increased during the previous four years.
These strains were multi-resistant, also to β-lactams and one or more antimicrobial agents, but were susceptible to vancomycin, habekacin, rifampicin, ofloxacin, minocycline and sulphamethoxazoletrimethoprim. Staphylococci were among the most resistant clinical isolates in sputum and pus, with about 45% resistant to methicillin while most were multi-resistant.
The coagulase typing of 269 strains was done. The coagulase types in MSSA and MRSA were different, and the multiple-resistant strains were related to coagulase type II.
We conclude that methicillin-resistant S. aureus are important etiological agents of nosocomial infections and that the incidence of these infections has increased during the past four years.

View full abstract

We investigated the correlation between β-lactamase activity and disk-sensitivity of 271 clinical pathogens isolated from the sputum of patients in Sendai Kosei Hospital during the period from January to June 1988. The β-lactamase activity was qualitated by the pH-disk method using bromocresol purple as pH-indicator and penicillin G or cefazolin as substrate. Antibiotic sensitivity was measured by sensitivity disks (SHOWA, Japan) containing ampicillin (ABPC), piperacillin (PIPC), cefazolin (CEZ), cefotiam (CTM), cefmetazole (CMZ), cefoperazone (CPZ), latamoxef (LMOX=moxalactam), cefuzonam (CZON), imipenem (IPM) and sulbactam/cefoperazone (SBT/CPZ). Of 271 isolates, 171 (63.1%) were positive for 9-lactamase activity, as were 122 (61.3%) of 199 strains of Gram-negative bacteria and 49 (68.1%) of 72 strains of Gram-positive cocci. Forty-nine (55.1%) of 89 strains isolated from outpatients and 122 (67.0%) of 182 strains isolated from inpatients produced β-lactamase. As compared with β-lactamase non-producing strains, β-lactamase producing strains were generally less sensitive to ABPC and CEZ. Some were less sensitive toPIPC, CTM, CMZ, CPZ, LMOX and CZON. On the other hand, both the β-lactamase positive and negative strains were usually very sensitive to IPM and SBT/CPZ. We conclude from the above results that IPM and SBT/CPZ are more effective than other antibiotics against infections in immunocompromised hosts in whom the majority of pathogens are presumably producing β-lactamase.

View full abstract

We have developed a simple method for monitoring aminoglycoside antibiotic concentrations in dried blood spots on filter paper. Gentamicin was recovered from the blood spots most effectively by incubation for 60 min at 35°C in an ultrafiltration tube containing 500μl of 0.5M Na₂HPO₄ solution. The eluates from the paper were centrifuged and transferred to an Abbott TDX cartridge for measurement by fluorescence polarization immunossay.
Gentamicin in the dried blood spots on filter paper was stable for at least ten days at ambient temperature. The inter-run precision (RSD) was below 8.5%. Analytical recovery of gentamicin from the filter paper exceeded 92%. Although the applicability of the method is limited because the quantitation limit of this method is more than 1μg/ml for whole blood (2μg/ml when the hematocrit value of whole blood was taken into account) this method permits simple blood collection.
For monitoring the effective concentration of gentamicin in serum, particularly for newborns.

View full abstract

Chemiluminescence (CL) is a sensitive indicator of phagocytosis and intracellular killing. The effect of forty-two antimicrobial agents on the luminol-enhanced CL of polymorphonuclear leukocytes (PMN) or whole blood was studied. After 10 min preincubation of cells with each drug at various concentrations, the CL response of phagocytic cells stimulated with non-opsonized zymosan or phorbol myristate acetate (PMA) was measured for 20 min. At therapeutic concentrations, sulfamethoxazole (SMX) and trimethoprim (TMP) showed significant CL suppression. Minocycline (MINO) and doxycycline (DOXY) also reduced CL at rather high concentrations (more than 12.5μg/ml). However, twenty-seven β-lactam antibiotics, four aminoglycosides, erythromycin, clindamycin, fosfomycin, vancomycin and three antifungal agents did not inhibit CL at therapeutic concentrations. None of the antimicrobial agents enhanced the CL response from phagocytic cells in our study.
These results suggest that MINO, DOXY, SMX and TMP clinically cause a reduction in the antimicrobicidal activity of phagocytic cells. Especially in the treatment of immunocompromised patients with already-impaired antimicrobicidal activity, those drugs that inhibit the CL response in vitro may further reduce or suppress the function of phagocytic cells. However, the clinical significance of these observations remains to be determined.

View full abstract

Ceftriaxone (CTRX) was administered at a single 1.0 g dose by intravenous injection to investigate its usefulness, concentration in serum, saliva and oral tissues, and effect on the normal human salivary flora.
The following results were obtained,
1. The pharmocokinetic parameters in serum in three healthy volunteers were: a peak concentration of 282μg/ml; an elimination half-life of 7.79 h; an area under the concentration curve of 1289.6μg·h/ml.
2. The highest concentration in saliva in three healthy volunteers was 0.16μg/ml, but the drug was not detected in the majority of saliva samples. Very little change was observed in the number of microorganisms in the saliva after administration of CTRX.
3. Concentrations of CTRX in maxillary bone, gum and cyst wall in 20 patients were 13.5±3.3%, 30.2±4.57%, and 25.1±3.2% each of the serum value.

View full abstract

Six cases with pleural effusion were given cefbuperazone 1 g (5 cases) or 2 g (5 cases) by drip infusion and were determined for its concentrations in serum and pleural effusion.
The results obtained were as follows:
1) The serum concentration peak occurred immediately after drip infusion at both doses of 1 g and 2 g and averaged 84.6 and 165μg/ml, respectively, indicating the dose-response.
2) The pleural effusion concentration peak occurred 2-6 hours after drip infusion, being 3.08-12.4 and 4.88-21.0μg/ml at doses of 1 g and 2 g, respectively. Even 24 hours after drip infusion, comparatively high pleural effusion concentrations (1.32-2.25 and 1.39-5.42μg/ml at doses of 1 g and 2 g, respectively) were noted, also indicating the dose-response.
3) The rate of the peak pleural effusion concentration/peak serum concentration was 2.8-13.9%(averaging 8.1%) and 3.4-19.6%, (averaging 9.2%) at doses of 1 g and 2 g, respectively.

View full abstract

We assayed the salivary concentrations of new quinolone derivatives (OFLX, ENX, NY-198 and T-3262) to evaluate the usefulness of these drugs in the treatment of oral infections and the feasibility of this assay for therapeutic drug monitoring. The new quinolone preparations were detected in the salivary samples at sufficiently high concentrations, though different for each of the drugs measured. The salivary concentrations changed parallel to the blood concentrations, which is characteristic of these drugs, unlike other antimicrobial agents. Our findings affirm the usefulness of the new quinolones in chemoprophylaxis of oral infections. Furthermore, estimation of the blood concentration from the salivary concentration was considered possible, since there was a close correlation between the two.

View full abstract

The purpose of this study was to investigate drug concentration profiles of an oxacephem antibiotic, latamoxef (LMOX), in serum and right appendage during open heart surgery. LMOX concentrations in serum and right appendage were determined during and after cardiopulmonary bypass following an intravenous 1 g bolus injection of LMOX. The following results were obtained by pharmacokinetic analysis of LMOX concentrations in serum and right appendage.
1. LMOX concentration in serum during cardiopulmonary bypass was described by two exponential equations as follows: C=47.67 e^-3.66t+44.15 e^-0.15t (C: concentration μg/ml, t: h).
The concentration extrapolated to time zero was calculated as 91.82μg/ml, which was about half that in healthy volunteers. Half-life (T_1/2 (β)) was 4.65 h, which was about 3 times longer than in volunteers.
2. The elimination rate of LMOX after cardiopulmonary bypass was higher than that during cardiopulmonary bypass, which was caused by increase of urinary excretion.
3. The distribution equilibrium of LMOX between the blood and the right appendage was achieved rapidly and the concentration in the right appendage was almost parallel with that in the serum.

View full abstract

To evaluate the efficacy, safety and usefulness of lomefioxacin (NY-198), a new synthetic quinolone antimicrobial agent, in respiratory tract infections (bacterial pneumonia and chronic respiratory infections), we carried out a double-blind comparative study with cefaclor (CCL) as a reference drug. NY-198 at daily doses of 600 mg (3 divided doses) and 1, 500 mg of CCL (3 divided doses) were orally administered for 14 days, and the following results were obtained:
1) Of a total of 358 patients (180 in the NY-198 group and 178 in the CCL group), 290 (146 in the NY-198 group and 144 in the CCL group) were assigned by the committee for the evaluation of efficacy, 333 (167 and 166, respectively) for evaluation of side effects, 305 (156 and 149, respectively) for evaluation of abnormal changes in laboratory findings and 298 (152 and 146, respectively) for evaluation of usefulness. There were no significant differences between the two groups with respect to the rate of exclusions and dropouts or background factors of patients.
2) The efficacy rate determined by the committee was 73.3% in the NY-198 group and 70.8% in the CCL group with no significant difference between the two groups. As for the bacteriological effiect, the elimination rate of organisms was 78.3%(54/69 isolates) in the NY-198 group and 61.8%(42/58 isolates) in the CCL group, with a significant difference (p=0.041).
3) There were no significant differences between the two groups with respect to the degree of improvement in various symptoms, signs and laboratory findings.
4) Side effects were observed in 12 patients (7.2%) of the NY-198 group and 10 (6.0%) of the CCL group, and abnormal changes in laboratory findings in 21 patients (13.5%) of the NY-198 group and 23 (15.4%) of the CCL group, with no significant difference in incidence.
5) The utility rate (satisfaction rate) calculated by the committee was 68.4% in the NY-198 group and 67.1% in the CCL group, with no significant difference between the two groups.
The above results indicate that NY-198 in daily doses of 600 mg is as useful as CCL in daily doses of 1, 500 mg. Especially against Gram-negative bacteria, NY-198 has a higher elimination rate than CCL in the treatment of respiratory tract infections (pneumonia and chronic respiratory infection).

View full abstract

We carried out a double-blind comparison of T-3262 (tosufloxacin tosilate), a new pyridonecarboxylic acid, and norfloxacin in the treatment of complicated urinary tract infections.
Patients received either 150 mg t. i. d. of T-3262 or 200 mg q. i. d. of norfloxacin orally for 5 days.
All patients had pyuria of at least 5 WBCs per high power field, bacteriuria of at least 104 bacteria per ml of urine and identifiable underlying urinary tract disease. The overall clinical efficacy of the treatment was evaluated using the criteria proposed by the Japanese UTI Committee as excellent, moderate or poor based on the combination of changes in pyuria and bacteriuria.
Of the 253 patients evaluated for clinical efficacy, 129 patients received T-3262 and 124 received norfloxacin. No significant difference in background characteristics was observed between the two treatment groups. Excellent and moderate responses were obtained in 79. 1% of the patients receiving T-3262 and in 66.1% of the patients receiving norfloxacin. This difference was statistically significant (p<0.05). The overall bacteriological eradication rates obtained were 90.8% of 218 strains in the T-3262 group and 82.7% of 197 strains in the norfloxacin group. This difference was also statistically significant (p<0.05). A significantly higher eradication rate for E. faecalis was obtained in the T-3262 group (p<0.05).
Clinical adverse reactions were observed in one patient (0.6%) in the T-3262 group and in two. patients (1.3%) in the norfloxacin group. No significant differences in the incidence of both clinical and laboratory adverse reactions were observed between the two treatment groups.
From the results obtained in this study, we concluded that T-3262 was as well tolerated as and more effective than norfloxacin in the treatment of complicated urinary tract infections.

View full abstract