Clinical evaluation of levofloxacin versus oral .BETA.-lactams for acute exacerbation of COPD

• Published in: Japanese Journal of Chemotherapy Vol. 56; no. 1; pp. 33 - 48
• Main Authors: Higashiyama Yasuhito, Watanabe Akira, Aoki Nobuki, Niki Yoshihito, Kohno Shigeru
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 2008; 公益社団法人 日本化学療法学会
• Subjects: COPD; efficacy; levofloxacin; safety; β-lactam
• ISSN: 1340-7007; 1884-5886
• DOI: 10.11250/chemotherapy1995.56.33

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. NICE Studyの結果, 本邦におけるCOPDの患者数は約530万人であり, 欧米と同様に罹患率が高いことが明らかになったが, その多くは潜在患者であり, 実際にCOPDと診断されている患者数は20万人程度である。今回, われわれは, 使用実態下において, すでにCOPDと診断されている患者のうち, 外来治療が可能な急性増悪患者を対象に, 本邦のガイドラインで推奨されている経口ニューキノロン系抗菌薬 (levofloxacin: LVFX) と経口β-ラクタム系抗菌薬の有用性を比較検討した。臨床効果解析例249例の有効率はLVFX投与群で81.2%(155/191), β-ラクタム系抗菌薬投与群483%(28/58) であり, 両群間に有意差が認められた。各臨床症状の改善率を比較した結果, LVFX投与群の喀痰量, 喀痰色調, 咳徽の改善率はβ-ラクタム系抗菌薬投与群に比べ有意に高く, QOL改善効果においても, LVFX投与群は有意に高い改善効果を示した。また, 急性増悪の症状が改善しないため再受診した患者の割合は, LVFX投与群10.5%(20/191), β-ラクタム系抗菌薬投与群22.4%(13/58) であり, LVFX投与群の再診率は有意に低かった。原因菌は40.0%(32/80) で検出され, 主な原因菌はStreptococcus pneumoniae (8.8%), Haemophilus influenzle (10.0%), Moraxella catarrhalis (15.0%) であった。Mycoplasma pneumoniae, Chlamydia pneumoniaeの陽性率はおのおの1.1%(1/95), 0%(0/95), インフルエンザウイルス, アデノウイルス, RSウイルスの陽性率はおのおの9.0%(8/89), 1.2%(1/83), 1.2%(1/83) であった。副作用発現率はLVFX投与群で2.4%(7/296), β-ラクタム系抗菌薬投与群4.5%(4/88) であり, 各投与群とも重篤な副作用は認められなかった。また, 約半数が75歳以上の後期高齢者であったが, 各投与群とも高齢者で副作用発現率が高くなる傾向は認めらなかった。以上より, 本調査は使用実態下で行ったため, 無作為比較試験ではないものの, 本調査で対象としたCOPDの急性増悪患者に対しては, 強い抗菌力と良好な喀痰内移行性を有するLVFXを優先して選択すべきと考えられた。