We have previously reported that itraconazole (ITCZ) at a dose of 200mg/day is more effective than ITCZ at a dose of 100mg/day and is safe for prophylaxis of mycosis. In this prospective study, 37 patients with hematological malignancies were administered 200mg/day of ITCZ for prophylaxis of mycosis during neutropenia. Although none of the patients developed mycosis, 31 patients (83.8%) of the ITCZ administered patients developed neutropenia (neutrophil <1000/μL), and 12 patients of them showed the possibility of fugitive fungal infection. The prolonged neutropenia and low neutrophil level were observed in the patients with malignant lymphoma at stage which suggested the necessity of prophylactic antifungal drugs. Four patients showed the adverse events which might be caused by drug interactions between ITCZ and vinca alkaloid. However adequately modified administration of ITCZ prevented these effect. There were no other obvious side effects which were supposed to be caused by prophylactic ITCZ administration. Twenty-eight patients were measured plasma concentration of ITCZ about 10 days after the beginning of administration and mean trough ITCZ level was expected to be above the effective level (250ng/ml). These results suggested that ITCZ is effective and safe for prophylaxis of mycosis during neutropenia in patients with hematological malignancies.

View full abstract

The bacterial strains isolated from 565 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2003 and July 2004. The susceptibilities of them to many kinds of antimicrobial agents were investigated. Of them, 701 strains were estimated as prophlogistic bacteria and used for the investigation. The strains consisted of 258 Gram-positive bacterial strains (36.8%) and 443 Gramnegative bacterial strains (63.2%).
Against Staphylococcus aureus, vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2μg/mL. Against Streptococcus agalactiae, ampicillin (ABPC), cefozopran (CZOP), imipenem (IPM), and clarithromycin (CAM) showed a strong activity and the MIC₉₀ was 0.125μg/mL or less. Against Enterococcus faecalis, VCM, ABPC, and IPM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially CZOP and cefpirome (CPR) showed the strongest activity (MIC₉₀: ≤0.125μg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): ≥4μg/mL] was detected at frequency of 15.7%, which was higher than that in the last year. Against Klebsiella pneumoniae, meropenem (MEPM) showed the strongest activity and next, the antibacterial activity of CRMN and CZOP was good. The antibacterial activity of the other cephems, however, significantly decreased, compared with that evaluated in last year. Against Serratia marcescens, MEPM had the strongest antibacterial activity. Against Proteus mirabilis, MEPM and CRMN showed the strongest activity and prevented the growth of all strains with 0.125μg/mL or less. Nest, cefmenoxime (CMX), ceftazidime (CAZ), cefixime (CFIX), cefpodoxime (CPDX), CPR, CZOP, and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC₉₀ of all the drugs was ranged from 32 to ≥256μg/mL except IPM and amikacin (AMK) having 16μg/mL. The antibacterial activity of CZOP was relatively good (MIC₅₀: 2μg/mL).

View full abstract

Seven hundred and nineteen bacterial strains isolated from 565 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2002 and July 2003. The frequency of bacteria isolation divided with patient clinical background was compared. The clinical background investigated included sex, age, type of infections, timing of antibiotics administration, and presence or absence of surgery affecting a decrease in defense against infection.
The bacterial strains were divided with the age and sex of the patients and the types of infections. In males, the number of patients aged less than 50 years was few and the complicated UTIs without indwelling catheter was observed most frequently. Number of patients aged 20-39 years was greater in female than male. In all of ages except 0-9 and 70-79 years, the ratio of the uncomplicated UTIs was high, accounting for 44.4-91.7% of all types of infections. In the present time, the bacteria most frequently isolated were Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis also were relatively frequently isolated. E. coli was most frequently isolated from the uncomplicated UTIs, and P aeruginosa and E. faecalis were frequently isolated from the complicated UTIs with indwelling catheter. With respect to the relation of these results to the age of the patients, in the uncomplicated UTIs, the isolation frequency of E. coli was the highest in all age groups, accounting for 40% or higher. In the complicated UTIs without indwelling catheter, the isolation frequency of E. coli decreased with aging of the patients but still was the highest in all age groups. In the complicated UTIs with indwelling catheter, the isolation frequency of E. coli was lower than in the uncomplicated UTIs in all age groups and P. aeruginosa and E. faecalis were more frequently isolated. In comparison of causative bacteria in UTIs between before and after the administration of antibiotics, P. aeruginosa increased after the administration in any types of UTIs. In comparison of causative bacteria in UTIs with or without surgery, E. coil was more frequently isolated in the patients without surgery, while P. aeruginosa and E. faecalis were more frequently isolated in the patients with surgery in any UTIs.

View full abstract

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from 565 patients diagnosed as urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2003 and July 2004. The susceptibilities of these bacteria to various antimicrobial agents were examined. The bacteria were divided into 2 groups consisting of uncomplicated UTIs and complicated UTIs (with and without indwelling catheter) based on their isolation origins. The results were compared with those obtained between 1994 and 2002.
The drug sensitivity of S. aureus in this year was similar to those in up to the previous years and S. aureus showed the best susceptibility to vancomycin. The drug sensitivity of E. faecalis in this year also was similar to those in up to the previous years. The drug sensitivity of E. coli in this year was generally good except penicillins and was similar to those in up to the previous years. Among cephems, cefozopran (CZOP) and cefpirome (CPR) showed the highest potency activity (MIC₉₀: ≤0.125μg/mL). An antibacterial activity of cefotiam (CTM) was stable for 10 years and was fine (MIC₉₀: ≤0.5μg/mL). The sensitivity of E. coli to carbapenems and carumonam (CRMN) also was good like to CZOP. The sensitivity of the complicated UTIs group to quinolones, however, has decreased after 2000 and it was suggested that the resistance to the drug has developed. Klebsiella spp. showed a decrease in the susceptibility to some of cephems. The drugs indicating a big decrease in the sensitivity were cefazolin, CTM, cefaclor, and cefpodoxime. Imipenem, carbapenems, also indicated a decrease in the sensitivity. The susceptibility of the strain to the other drugs was similar to that in up to the previous years. Among them, CZOP maintained good susceptibility (MIC₉₀: ≥0.125μg/mL against uncomplicated UTIs, 0.25μg/mL against complicated UTIs) like meropenem. The drug sensitivity of P aeruginosa was generally low and was not much different from that in up to the previous years.

View full abstract

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 907 strains of Gram-positive bacteria, 1790 strains of Gram-negative bacteria, and 192 strains of anaerobic bacteria obtained from 30 medical institutions during 2004 was measured. The results were as follows;
1. MIC₉₀, of MEPM for almost all of enterobacteriaceae and Haemophilus influenzae were 4-fold to 32-fold lower than those of other carbapenems. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and H. influenzae. MEPM were active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus.
2. As for Pseudomonas aeruginosa, imipenem (IPM) showed high cross-resistant rate againt meropenemresistant P. aeruginosa (87.9%). MEPM showed low cross-resistant rate both againt IPM-resistant P. aeruginosa (49.2%) and ciprofloxacin-resistant P. aeruginosa (38.0%).
3. The proportion of extended-spectrum β-lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli, 8.0% (2 strains) in Citrobacter koseri, 2.5% (3 strains) in Klebsiella pneumoniae, 2.5% (2 strains) in Enterobacter cloacae, 0.9% (1 strains) in Serratia marcescens,. and 2.2% (2 strains) in Proteus mirabilis. The proportion of metallo-β-lactamase strains was 1.6% (5 strains) in P. aeruginosa.
4. Of all species tested, Peptostreptococcus spp. was the only species, which MIC₉₀ of MEPM was more than 4-fold higher than that in our previous study using clinical isolates during 2002 (0.25μg/ml→1μg/ml). Therefore, there is almost no siginificant decrease in susceptibility of clinical isolates to meropenem.
In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem at present, 9 years after available for commercial use.

View full abstract