Symposium section (Tigecycline)
Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit

https://doi.org/10.1016/j.diagmicrobio.2005.05.002Get rights and content

Abstract

The antimicrobial activity of tigecycline and selected antimicrobials was evaluated against bacterial pathogens isolated from patients hospitalized in intensive care units (ICUs) worldwide. A total of 9093 isolates were consecutively collected in >70 medical centers in North America (4157), South America (1830), Europe (3034), and the Asia–Australia (72) areas. The isolates were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft tissue (5.5%), and urinary tract (2.0%) infections in the 2000–2004 period, and susceptibility was tested by reference broth microdilution methods. The most frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens (5665) were inhibited at ≤1 μg/mL of tigecycline. Resistance to oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS, and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of ≤1 μg/mL, except for Serratia spp. (2 μg/mL). Extended-spectrum β-lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme production). These resistance phenotypes did not adversely affect tigecycline activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 μg/mL respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1 μg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline (MIC90, 16 μg/mL). In summary, isolates from ICU patients worldwide showed high rates of antimicrobial resistance. The most alarming problems detected were vancomycin resistance among enterococci, ESBL-mediated β-lactam resistance and fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro activity against most of clinically important pathogenic bacteria (except P. aeruginosa) isolated from ICU patients and may represent an excellent option for the treatment of infections in this clinical environment.

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.

Section snippets

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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