Fritsche Thomas R, Sader Helio S, Stilwell Matthew G, Dowzicky Michael J, Jones Ronald N
JMI Laboratories, North Liberty, IA 52317, USA.
Diagn Microbiol Infect Dis. 2005 Jul;52(3):187-93. doi: 10.1016/j.diagmicrobio.2005.05.004.
Emerging antimicrobial resistance among respiratory tract pathogens has created a critical need for development of new antimicrobial agents that are not affected by the commonly occurring genetic resistance mechanisms. Tigecycline, a novel broad-spectrum parenteral glycylcycline, has been shown to be active against many of Gram-positive, Gram-negative, atypical, and anaerobic organisms, including strains highly resistant to commonly prescribed antimicrobials and was recently approved by the US Food and Drug Administration for treating infections of skin and skin structures, and for intra-abdominal infections. In this study, tigecycline spectrum and potency were evaluated against a global collection of pathogens (2000-2004) recovered from community-acquired respiratory infections (7580 strains) or from hospitalized patients with pneumonia (3183 strains). Among community-acquired infections, the ranking pathogens were Haemophilus influenzae (52.9%; 21% ampicillin-resistant), Streptococcus pneumoniae (39.2%; 23.7% penicillin-nonsusceptible), and Moraxella catarrhalis (7.9%). Tigecycline displayed potent activity by inhibiting 100% of the 3 species at clinically achievable concentrations (2, 1, and 0.5 microg/mL, respectively). The 10 most prevalent pathogens producing 94.3% of pneumonias in hospitalized patients were Staphylococcus aureus (48.5% of strains; 49.4% oxacillin-resistant), Pseudomonas aeruginosa (15.6%), Klebsiella spp. (5.6%), S. pneumoniae (4.6%), Acinetobacter spp. (4.5%), Enterobacter spp. (4.0%), Escherichia coli (3.8%), Serratia marcescens (2.5%), Enterococcus spp. (2.3%), Stenotrophomonas maltophilia (1.8%), and beta-hemolytic streptococci (1.1%). At a concentration of 4 microg/mL, tigecycline inhibited >96% of these pathogens (exception, P. aeruginosa). S. aureus was readily inhibited by tigecycline (MIC50 and MIC90, 0.25 and 0.5 microg/mL, respectively) with all strains inhibited at < or =1 microg/mL. Streptococci recovered from hospitalized patients (beta-hemolytic and S. pneumoniae) were also very susceptible to tigecycline with the highest MIC being 0.12 microg/mL. All E. coli (including 13.3% with an extended-spectrum beta-lactamase [ESBL] phenotype) were inhibited by < or =1 microg/mL, and all Klebsiella (25.8% ESBL phenotype) and Enterobacter spp. plus 97.0% of Serratia spp. were inhibited by < or =4 microg/mL. Tigecycline was also active against Acinetobacter spp. and S. maltophilia strains (MIC50 and MIC90, 1 and 4 microg/mL, respectively). Further clinical studies should consider the role that tigecycline may play in the therapy for severe respiratory tract infections, both of nosocomial and community origin.
呼吸道病原体中不断出现的抗菌药物耐药性使得开发不受常见遗传耐药机制影响的新型抗菌药物成为当务之急。替加环素是一种新型的胃肠外给药的广谱甘氨酰环素，已显示对许多革兰氏阳性菌、革兰氏阴性菌、非典型菌和厌氧菌具有活性，包括对常用抗菌药物高度耐药的菌株，并且最近被美国食品药品监督管理局批准用于治疗皮肤及皮肤结构感染和腹腔内感染。在本研究中，对从社区获得性呼吸道感染（7580株）或住院肺炎患者（3183株）中分离出的全球病原体样本（2000 - 2004年）评估了替加环素的抗菌谱和效力。在社区获得性感染中，主要病原体依次为流感嗜血杆菌（52.9%；21%对氨苄西林耐药）、肺炎链球菌（39.2%；23.7%对青霉素不敏感）和卡他莫拉菌（7.9%）。替加环素在临床可达到的浓度（分别为2、1和0.5微克/毫升）下对这三种菌的抑制率达100%。在住院患者中引发94.3%肺炎的10种最常见病原体为金黄色葡萄球菌（48.5%的菌株；49.4%对苯唑西林耐药）、铜绿假单胞菌（15.6%）、克雷伯菌属（5.6%）、肺炎链球菌（4.6%）、不动杆菌属（4.5%）、肠杆菌属（4.0%）、大肠埃希菌（3.8%）、粘质沙雷菌（2.5%）、肠球菌属（2.3%）、嗜麦芽窄食单胞菌（1.8%）和β溶血性链球菌（1.1%）。在4微克/毫升的浓度下，替加环素对这些病原体（铜绿假单胞菌除外）的抑制率>96%。替加环素能轻易抑制金黄色葡萄球菌（MIC50和MIC90分别为0.25和0.5微克/毫升），所有菌株在≤1微克/毫升时均被抑制。从住院患者中分离出的链球菌（β溶血性链球菌和肺炎链球菌）对替加环素也非常敏感，最高MIC为0.12微克/毫升。所有大肠埃希菌（包括13.3%具有超广谱β内酰胺酶[ESBL]表型的菌株）在≤1微克/毫升时被抑制，所有克雷伯菌（25.8%为ESBL表型）和肠杆菌属以及97.0%的粘质沙雷菌在≤4微克/毫升时被抑制。替加环素对不动杆菌属和嗜麦芽窄食单胞菌菌株也有活性（MIC50和MIC90分别为1和4微克/毫升）。进一步的临床研究应考虑替加环素在治疗医院获得性和社区获得性严重呼吸道感染中可能发挥的作用。
