Symposium section (Tigecycline)Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit
Introduction
Tigecycline is a semisynthetic glycylcycline derived from the minocycline molecule. Tigecycline has documented activity against tetracycline-resistant (tet-R) Gram-positive and Gram-negative pathogens refractory by both efflux and ribosomal protection mechanisms (Bergeron et al., 1996, Nathwani, 2005, Zhanel et al., 2004). This compound has also demonstrated excellent in vitro activity against multidrug-resistant (MDR) pathogens, including oxacillin-resistant (MRSA) and glycopeptide-intermediate Staphylococcus aureus, vancomycin-resistant enterococci (VRE), penicillin-resistant Streptococcus pneumoniae, extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae, and some nonfermentative Gram-negative bacilli such as Acinetobacter spp. and Stenotrophomonas maltophilia (Betriu et al., 2002, Biedenbach et al., 2001, Cercenado et al., 2003, Fritsche and Jones, 2004, Fritsche et al., 2004, Petersen et al., 2002).
Patients hospitalized in the intensive care unit (ICU) are at particular risk for acquiring nosocomial infections. Exposure to various antimicrobial agents may further complicate hospitalization and create conditions that favor resistance selection among host bacterial flora or nosocomially transmitted pathogens. Thus, rates of antimicrobial resistance are generally higher in bacteria isolated from ICU patients compared with patient strains occurring in other hospital wards and outpatient clinics (Fluit et al., 2001, Fridkin and Gaynes, 1999, Fridkin et al., 2002, Streit et al., 2004).
The present study was conducted to evaluate the in vitro activity of tigecycline in comparison to tetracycline and other antimicrobial agents when tested against clinical bacterial isolates collected from patients hospitalized in ICUs worldwide.
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Materials and methods
To assess the spectrum of activity and potency of tigecycline, recent clinical isolates submitted to a reference laboratory (JMI Laboratories, North Liberty, IA) were examined. A total of 9093 Gram-positive and Gram-negative bacterial isolates recovered from patients hospitalized in ICU were analyzed. Consecutively acquired, nonduplicate, patient isolates were submitted from 93 participating medical centers representing 29 countries in the 5 continents of Asia, Australia, Europe, North America,
Results
The most frequently isolated pathogen from ICU patients in the 2000–2004 period was S. aureus (32.1%), followed by Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), and P. aeruginosa (8.4%). These 4 pathogens showed high rates of resistance to commonly used antimicrobial agents and accounted for two thirds (67.2%) of the isolates collected during the study period (Table 1).
Discussion
Although the emergence of antimicrobial resistance occurs in a number of clinical settings, the best documented and most striking examples often occur in the ICU, a unit that appears to operate as both a selector of, and a reservoir for, resistant organisms. A number of factors contribute to this clinical situation, including the severity of patient illness, predisposition to nosocomial infections, and the widespread use of prophylactic and therapeutic antimicrobial agents (Fridkin and Gaynes,
Acknowledgments
The authors express their appreciation to the following individuals who have contributed significant expertise and effort in the preparation of this report: K.L. Meyer, P. Strabala, M.G. Stilwell, and P.R. Rhomberg. This work was funded by an educational/research grant from Wyeth Pharmaceuticals.
Since acceptance of this publication, the US FDA has granted approval of tigecycline (June 15, 2005) for treatment of complicated skin and skin structure infections and for complicated intra-abdominal
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