In vitro activity of tigecycline against ampicillin-resistant Haemophilus influenzae isolates

Sir, The increasing resistance in Haemophilus influenzae has complicated the choice of antibiotics for empirical treatment of community-acquired respiratory tract infection. Tigecycline, a glycylcycline, is a new semi-synthetic 9-t-butylglycylamido derivative of minocycline with potent in vitro activity against a wide variety of Gram-positive and Gram-negative organisms, including multidrug-resistant strains. Tigecycline overcomes the two major tetracycline resistance mechanisms, efflux and ribosomal protection. Its activity against H. influenzae is not affected by the presence of b-lactamase enzyme. The aim of this study was to evaluate the in vitro activity of tigecycline against ampicillin-resistant H. influenzae isolates. A total of 185 non-duplicate clinical isolates of ampicillinresistant H. influenzae were tested. These strains were obtained as part of a multicentre surveillance of antimicrobial resistance, the VIRA (Vigilancia de la Resistencia a los Antimicrobianos) study, from 40 medical centres throughout Spain (isolation dates in October 2001 and in February 2004). Organisms were identified in each centre using routine methods. At the coordinating laboratory (Clinical Microbiology Laboratory, Hospital Clı́nico San Carlos, Madrid, Spain), the identity of isolates was confirmed by the API NH system (bioMérieux, Marcy l’Étoile, France). MICs of tigecycline were determined by the broth microdilution method following the recommendations of the NCCLS. Microdilution trays were prepared in-house on the day of testing using fresh broth. All but 10 isolates were b-lactamase producers. Most of the isolates were also resistant to other antimicrobial agents. Twenty-two isolates were resistant to tetracycline, 11 showed intermediate resistance to this antibiotic and 23 were resistant to chloramphenicol. Of 62 isolates that were resistant to trimethoprim/sulfamethoxazole, 14 were also resistant to chloramphenicol. Twenty-two isolates were non-susceptible to both tetracycline and chloramphenicol. Serotyping was performed using a slide agglutination procedure (Phadebact Haemophilus Test; Boule Diagnostics AB, Sweden). Six (3.2%) isolates belonged to capsular serotypes a or c–f, four (2.2%) to capsular serotype b and the 175 (94.6%) remaining isolates were non-typeable. Tigecycline inhibited all of the isolates at concentrations of between 0.06 and 2 mg/L (MIC50 1 mg/L and MIC90 2 mg/L). If the provisional susceptibility breakpoint for tigecycline of # 2 mg/L was used, all isolates would be susceptible to this new antibiotic. No difference between tigecycline MICs was detected between tetracyclinesusceptible and -resistant isolates. The increasing antimicrobial resistance in H. influenzae is of clinical concern. The results of this study confirm the absence of cross-resistance between tetracycline and tigecycline and indicate that tigecycline is very active against ampicillin-resistant H. influenzae isolates, including those resistant to other antibiotics such as trimethoprim/sulfamethoxazole, chloramphenicol or tetracycline, as well as multiresistant isolates. The MIC50 and MIC90 values of tigecycline were 1 dilution lower than those reported by Zhanel et al., but 1 dilution higher than those recently reported by Fritsche et al. among b-lactamase-positive isolates. In vivo efficacy of tigecycline has been evaluated in several animal infection models. Pharmacodynamic and pharmacokinetic studies demonstrated a prolonged half-life (t1 2 ), significant postantibiotic effect, and excellent and homogeneous tissue diffusion using the rabbit model of endocarditis. Preliminary pharmacokinetic studies in humans showed that the mean t1 2 was 36 h, making once-daily dosing possible. Its efficacy and tolerability are being investigated in humans. Tigecycline may play an important role as a new alternative for the treatment of communityacquired respiratory tract infections caused by ampicillin-resistant H. influenzae isolates. Further clinical studies are warranted to confirm the efficacy of this new agent.