It has been reported that the blood levels of carbapenems decline markedly when they are administered in combination with amino acid infusions, including those of L-cysteine and L-cystine. However, although antibiotic injections are widely administered through a Y-site with total parenteral nutrient (TPN) and peripheral parenteral nutrient (PPN) solutions containing amino acids in many clinical situations, there have beenno reports of the influence of such administration on the clinical efficacy of the drugs. We studied the influence of carbapenem injection at the Y-site on the clinical efficacy of the drugs, by injection of doripenem (DRPM), which is a carbapenem drug, through the Y-site with TPN and PPN solutions containing amino acids, and determining if this method of injection increased the risk of decline in the blood levels of carbapenems. We enrolled 97 cases in which DRPM injections were given during the 6 monthsfrom May to October 2006. The patients were classified into a contact group (or Amino acid group), in which the DRPM injections were injected at the Y-site with amino acid infusions, and a non-contact group (or Non amino acid group), in which DRPM injections were administered through a separate dedicated line. There were 47 cases in the Amino acid group and 50 cases in the Non amino acid group. The study on the risk factors indicated that the odds ratio of DRPM injection through the Y-site along with amino acid infusions for the decline of fever was 0249 (95% confidence interval: 0.088-0.708), demonstrating that injection through the Y-site was an obvious risk factor for drug level decline.
Furthermore, the rates of resolution of fever and decrease of the WBC counts after DRPM treatment in the Amino acid group were significantly lower than those in Non amino acid group (P<0.05). Our results suggested that TPN and PPN solutions containing amino acids decreased the clinical efficacy of DRPM.
In conclusion, carbapenems should be administered through a separate dedicated line or through a Y-site after temporary discontinuation of TPN or PPN infusion.

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We examined the clinical efficacy of gatifloxacin (GFLX) against adult acute rhinosinusitis by disease severity using clinical scoring based on clinical symptoms (rhinorrhea and/or postnasal drip, fever, facial pain and/or forehead pain) and nasal findings (muco-purulent rhinorrhea and/or postnasal drip, serous rhinorrhea and/or postnasal drip, hypertrophy of nasal mucosa, redness of nasal mucosa). Significant relevance was shown between the severity of the disease determined by clinical scoring and experimental definitions. Clinical scoring for adult acute rhinosinusitis will represent the clinical course of the diseases.
Clinical symptoms were significantly improved 7 days after the treatment with GFLX regardless of disease severity. Nasal findings were improved only in moderate and severe cases. The nasal finding of mild acute rhinosinusitis was not changed before and after GFLX treatment. Causative pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were identified in about 54.0% of the cases and all were dramatically eliminated after treatment.
The total efficacy of GFLX for adult acute rhinosinusitis according to both clinical and bacteriological efficacy was 98%(48 of 49 cases). This study suggested that GFLX may be an effective antimicrobial agent against adult acute rhinosinusitis.

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In vitro antibacterial activity of gemifloxacin, a new fluoro quinolone agent, and other drugs was determined against clinical isolates in 2005 Japan and clinical isolates of levofloxacin-resistant Streptococcus pneumoniae after 2003.
Gemifloxacin MIC₉₀ was 0.031μg/mL, higher than other fluoro quinolone agents. Gemifloxacin activity is good in levofloxacin-resistant S. pneumoniae because gemifloxacin MIC₉₀ of levofloxacin-resistant Streptococcus pneumoniae was 0.5μg/mL, higher than other fluoro quinolone agents. Gemifloxacin MIC₉₀ against Haernophilus influenzae was 0.015μg/mL. Gemifloxacin MIC₉₀ against ampicillin-resistant β-lactamase negative Haemophilus influenzae (BLNAR) was 0.063μg/mle. Gemifloxacin MIC₉₀ against methicillin-resistant Staphylococcus aureus was low the same as for other fluoro quinolone agents. Gemifloxacin activity was shown in Moraxella (Branhamella) catarrhalis, Kiebsiella pneumoniae, and Pseudomonas aeruginosa similar to other fluoro-quinolone agents. Our results suggest that gemifloxacin effective clinical respiratory organ infectious disease treatment.

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In the present study conducted during actual clinical use, we obtained data on the administration of levofloxacin (LVFX) at the maximum dose approved in Japan, which is 600 mg/day (200 mg tds), to patients with moderately severe community-acquired pneumonia. Both LVFX monotherapy and LVFX combined with initial short-term parenteral therapy (for a maximum of 3 days) with other antibiotics were evaluated for clinical efficacy and safety.
Among the patients included in the evaluation of clinical efficacy, the efficacy rate of LVFX was 90.3%(84/93). LVFX monotherapy was given to 55 patients (59.1%), combined therapy was administered to 28 patients (30.1%), and therapy switching was conducted in 10 patients (10.8%). The efficacy rates of these three regimens were 90.9%, 89.3%, and 90.0%, respectively.
Causative organisms were isolated in 51.6%(33/64) of the patients, with the most common being Streptococcus pneumoniae (20.3%), Haemophilus influenzae (17.2%), and Moraxella catarrhalis (4.7%). The microbiological efficacy rate was 100%(13/13) in the LVFX monotherapy group, 91.7%(11/12) in the combined therapy group, and 100%(1/1) in the therapy switching group. With respect to atypical pathogens, Legionella pneumophila was not detected, whereas Mycoplasma pneumoniae and Chiamydia pneumoniae were detected by antibody assays in 6.8%(3/44) and 16.7%(6/36) of the patients, respectively. The LVFX therapy was classified as “effective” in all 9 patients with M. pneumoniae or C. pneumoniae infection.
Adverse drug reactions occurred in 10.0%(12/120) of the patients, with 9 showing only mild reactions. Treatment with LVFX could be continued in all of these patients. Three patients had moderate adverse drug reactions that resolved rapidly after completion of LVFX administration. Over half of the patients included in the study were elderly, but no specific safety problems were observed among the elderly subjects during administration of levofloxacin at 600 mg/day in divided doses.
Based on the above results, LVFX monotherapy at 600 mg/day (200 mg tds) and LVFX combined with initial short-term parenteral therapy (≤3 days) are considered to be useful regimens for the treatment of moderately severe community-acquired pneumonia. These regimens are expected to allow ambulatory treatment at an early stage and to be more efficient in terms of medical costs.

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The NICE study suggested that there are approximately 5.3 million patients with chronic obstructive pulmonary disease (COPD) in Japan. Therefore, morbidity due to COPD is also high in Japan as it is in the USA and Europe. However, the presence of COPD has not been detected in the majority of these potential Japanese patients, and there are only about 0.2 million patients with a diagnosis of COPD in Japan.
The Japanese treatment guidelines for COPD recommend oral therapy with new quinolones or β-lactams. We conducted the present study to compare the efficacy of a new quinolone (levofloxacin: LVFX) with that of β-lactams for the treatment of patients with acute exacerbation of COPD on an outpatient basis.
There were 249 patients evaluable for clinical efficacy, comprising 191 treated with LVFX and 58 treated with β-lactam therapy. Efficacy was noted in 812%(155/191 patients) of the LVFX group versus 48.3%(28/58 patients) of the β-lactam group, with the efficacy rate being significantly higher in the LVFX group. The improvement rates for sputum volume, sputum color, and cough were all significantly higher in the LVFX group than in the β-lactam group. Regarding the improvement of QOL, the efficacy rate achieved with LVFX was also significantly higher than that obtained with β-lactams. In 10.5%(20/191 patients) of the LVFX group and 22.4%(13/58 patients) of the β-lactam group, another treatment was requested due to lack of improvement of symptoms caused by the exacerbation of COPD, and the readmission rate was significantly lower in the LVFX group.
Causative bacteria were isolated in 40.0%(32/80). The most frequent isolates were Streptococcus pneumoniae (8.8%), Haemophilus influenzae (10.0%), and Moraxella catarrhalis (15.0%). Among the atypical bacteria, Mycoplasma pneumoniae was detected in 1.1%(1/95), while Chiamydia pneumoniae was not detected (0/95 patients). Influenza virus, adenovirus, and respiratory syncytial (RS) virus were found in 9.0%(8/89), 12%(1/83), and 1.2%(1/83) of the patients, respectively.
The incidence of adverse drug reactions was 2.4%(7/296) in the LVFX group and 4.5%(4/88) in the β-lactam group. None of the patients experienced serious adverse drug reactions. Although about a half of the present subjects were very elderly (≥ 75 years old), the incidence of adverse reactions was not increased in the elderly subgroups receiving either LVFX or β-lactam therapy.
These results suggest that LVFX, which exhibits strong antibacterial activity and effectively penetrates the sputum, may be the treatment of choice for Japanese patients with exacerbation of COPD.

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[in Japanese]

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