JAC Advance Access originally published online on September 13, 2007
Journal of Antimicrobial Chemotherapy 2007 60(5):1018-1029; doi:10.1093/jac/dkm310
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Antimicrobial susceptibility among organisms from the Asia/Pacific Rim, Europe and Latin and North America collected as part of TEST and the in vitro activity of tigecycline
1 Institute for Medical Microbiology, National Reference Centre for Streptococci, Aachen, Germany 2 Department of Microbiology, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada 3 Microbiology Laboratory, Hospital das Clinicas da Faculdade de Medicina, São Paulo, Brazil 4 Peking Union Medical College Hospital, Beijing, China 5 Department of Microbiology, Sir Gangaram Hospital, New Delhi, India 6 Infectious Disease Group, Wyeth Pharmaceuticals, Collegeville, PA, USA
* Corresponding author. Tel: +49-241-8089946; Fax: +49-241-8082483; E-mail: reinert{at}rwth-aachen.de
Received 25 April 2007; returned 1 June 2007; revised 6 July 2007; accepted 27 July 2007
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Abstract |
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Objectives: To describe antimicrobial susceptibility among bacterial isolates associated with hospital infections collected from 266 centres in Asia/Pacific Rim (n = 1947), North America (n = 24 283), Latin America (n = 1957) and Europe (n = 8796).
Methods: Isolates were collected from blood, respiratory tract, urine, skin, wound, body fluids and other defined sources between January 2004 and August 2006. Only one isolate per patient was accepted. In vitro MICs for the isolates were determined according to the CLSI (formerly NCCLS) guidelines.
Results: Key organisms collected were Acinetobacter baumannii (n = 2902), Enterobacter spp. (n = 5731), Escherichia coli (n = 6504), Klebsiella pneumoniae (n = 4916), Pseudomonas aeruginosa (n = 5128), Serratia marcescens (n = 2313), Enterococcus faecalis (n = 2701), Enterococcus faecium (n = 1035) and Staphylococcus aureus (n = 5753). Rates of methicillin resistance among S. aureus and of vancomycin resistance among enterococci were highest in North America (2016/3809, 52.9% and 571/2544, 22.4%, respectively) and lowest in Europe (337/1340, 25.1% and 36/916, 3.9%, respectively). Tigecycline was the only antimicrobial to maintain activity against all Gram-positive isolates (MIC90 values of 
0.25 mg/L). Overall, tigecycline and imipenem were the most active (>93% susceptibility in all regions) antimicrobials against the Gram-negative species, except for A. baumannii and P. aeruginosa. Piperacillin/tazobactam and amikacin were the most active against P. aeruginosa. Extended-spectrum ß-lactamase producers among K. pneumoniae occurred most frequently in Latin America (124/282, 44.0%).
Conclusions: Tigecycline is a novel broad-spectrum antimicrobial that is active against the common organisms associated with infections.
Keywords: global , hospital infections , surveillance , resistance
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Introduction |
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Significant changes in causative organisms of nosocomial bacterial infections have been observed globally over the past 100 years. In the first half of the 20th century, Gram-positive cocci, particularly Staphylococcus aureus and streptococci, were of primary concern. By the end of the 1970s, Enterobacteriaceae (mainly Escherichia coli, Enterobacter spp. and Klebsiella spp.) and Pseudomonas aeruginosa had gained prominence as nosocomial pathogens; however, methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci had also emerged. More recently, Acinetobacter spp. have become important pathogens in intensive care units (ICUs), with increasing resistance to most antimicrobial agents.1
Widespread inappropriate use of antimicrobial agents in the hospital setting has resulted in the emergence of resistance in nosocomial organisms, and lack of adherence to hygiene practices has facilitated their dissemination.2 Clinical success is much more likely if the pathogen is susceptible to the chosen antimicrobial; however, there are no agents available that are fully effective against all the common pathogens. The key to antimicrobial development has been to design agents that elude the main bacterial resistance mechanisms. One such agent is tigecycline, a tetracycline analogue in the new antimicrobial class of glycylcyclines. Like the tetracyclines, tigecycline binds to the 30S subunit of bacterial ribosomes and inhibits protein synthesis by preventing the incorporation of amino acid residues into elongating peptide chains.3,4 Tigecycline, however, can overcome two major tetracycline resistance mechanisms (ribosomal protection and active efflux), and this is thought to be due to steric hindrance by a large substituent at position 9 of the molecule.5 In addition, tigecycline binds 5-fold more effectively than related compounds to the ribosomal site.6 The activity of tigecycline is also unaffected by other mechanisms such as ß-lactamase production, penicillin-binding protein alterations, macrolide efflux pumps and DNA gyrase mutations. Consequently, tigecycline has a broad spectrum of in vitro activity, including most organisms of importance in nosocomial infections. However, it should be noted that the activity of tigecycline is affected by the intrinsic multidrug pumps of P. aeruginosa, Proteae and some isolates of Acinetobacter spp.7–9
The Tigecycline Evaluation and Surveillance Trial (TEST) is a global multicentre study designed to compare the in vitro activity of tigecycline with established antimicrobial agents against a range of clinically important organisms. In this article, we report the TEST data for a range of common organisms collected between January 2004 and August 2006, from patients with hospital-associated infections in four geographic regions: Asia/Pacific Rim, North America, Latin America and Europe.
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Materials and methods |
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Bacterial isolates
A total of 266 centres, located in Asia/Pacific Rim (15 centres), North America (176), Latin America (13) and Europe (62), participated in TEST (Table 1). Each study centre was required to collect, identify and test the antimicrobial susceptibility of a maximum of 200 consecutive fresh clinically significant isolates (defined by institutional criteria) from patients with documented infections. Isolates from hospital- and community-acquired infections were permitted into the study. A hospital infection was defined as occurring more than 48 h after admission. Isolates, restricted to one per patient, were obtained from blood, respiratory tract, urine (limited to no more than 25% of all isolates), skin, wound, fluids and other defined sources.
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Species requested by the protocol included (number of isolates requested appear in parentheses) Acinetobacter spp. (15), Enterococcus spp. (15), Enterobacter spp. (25), E. coli (25), Klebsiella spp. (25), P. aeruginosa (20), S. aureus (25) and Serratia spp. (10).
Antimicrobial susceptibility testing
MICs were determined at the local laboratory using broth microdilution methodology with either MicroScan® panels (Dade Behring Inc., Sacramento, CA, USA) or Sensititre® plates (TREK Diagnostic Systems, West Sussex, UK), according to guidelines published by the CLSI (formerly NCCLS).10 Antimicrobial agents tested against Gram-negative organisms (with concentrations expressed in mg/L) were: amikacin (0.5–64); amoxicillin/clavulanic acid (0.12/0.06–32/16); ampicillin (0.5–32); cefepime (0.5–32); ceftriaxone (0.06–64); ceftazidime (8–32); imipenem (0.06–16; MicroScan® only); levofloxacin (0.008–8); minocycline (0.5–16); tigecycline (0.008–16); and piperacillin/tazobactam (0.06/4–128/4). Antimicrobial agents tested against Gram-positive organisms (with concentrations expressed in mg/L) were: amoxicillin/clavulanic acid (0.03/0.0015–8/4); ampicillin (0.06–16); penicillin (0.06–8); linezolid (0.5–8); ceftriaxone (0.03–64); imipenem (0.12–16; MicroScan® only); levofloxacin (0.06–32); minocycline (0.25–8); tigecycline (0.008–16); piperacillin/tazobactam (0.25/4–16/4); and vancomycin (0.12–32). MIC breakpoints followed published CLSI guidelines.11 For tigecycline, the US Food and Drug Administration (FDA) breakpoints were applied for S. aureus (susceptible 0.5 mg/L), vancomycin-susceptible Enterococcus faecalis (susceptible 0.25 mg/L) and Enterobacteriaceae (susceptible 2 mg/L), where applicable.12
Broth microdilution panels inoculated with Gram-negative organisms were incubated in ambient air at 35°C for 16–20 h. S. aureus and Enterococcus spp. were incubated in ambient air at 35°C for 20–24 h. Quality control of panels was performed using E. coli ATCC 25922 and 35218, S. aureus ATCC 29213, P. aeruginosa ATCC 27853 and E. faecalis ATCC 29212, when appropriate.
All isolates and data were sent to a central laboratory, International Health Management Associates, Inc. (Schaumburg, IL, USA), for confirmation of identity and inclusion into a centralized database. The data were collected using the proprietary OptiScanTM data collection form. Organism identification was carried out according to the American Society for Microbiology methodology13 and the Remel RapidID system (Remel, Lenexa, KS, USA).
Extended-spectrum ß-lactamase (ESBL) determination
E. coli and Klebsiella spp. were screened and confirmed for ESBL activity, according to CLSI guidelines.11 The discs used were cefotaxime (30 µg), cefotaxime/clavulanic acid (30/10 µg), ceftazidime (30 µg) and ceftazidime/clavulanic acid (30/10 µg). Discs were manufactured by Oxoid, Inc. (Ogdensburg, NY, USA). The Mueller–Hinton agar was used in testing was manufactured by Remel, Inc. Quality control was performed using Klebsiella pneumoniae ATCC 700603 (ESBL-positive) and E. coli ATCC 25922 (ESBL-negative). In addition, P. aeruginosa ATCC 27853 was used for the quality control of the ceftazidime and cefotaxime discs.
Methicillin resistance determination
S. aureus were screened using local methodology to identify isolates that were methicillin-resistant. On receipt at the central laboratory, the cefoxitin disc (30 µg discs; Remel) diffusion method was used to confirm methicillin resistance.
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Results |
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Demographic description
Bacterial isolates were collected between January 2004 and August 2006 and comprised a wide range of aerobic organisms cultured from a variety of sources (mainly respiratory, cardiovascular and genito-urinary). Of the isolates, 65.7% were collected in North America and 74.4% were Gram-negative. Isolates were collected from more male patients than female, typically in the ratio 3:2, with the exception of E. coli (60.2% collected from female patients). Approximately half of the isolates were collected from adult patients aged between 18 and 64 years, whereas <15% of isolates were from paediatric patients. At least 70% of the isolates came from hospitalized patients, mainly from non-ICU wards. Only Latin America contributed more isolates from the ICU than from non-ICU. Specifically, 67.0% of Acinetobacter baumannii from Latin America came from the ICU, 54.9% of P. aeruginosa and 64.3% of vancomycin-resistant Enterococcus faecium.
Overall, the susceptibility results of 9489 Gram-positive isolates are reported. A total of 5753 isolates of S. aureus were collected from the four geographical regions, 1035 E. faecium and 2701 E. faecalis.
The prevalence of MRSA was lowest in Europe (25.1%), while approximately half of the S. aureus isolates from North America were methicillin-resistant (Figure 1). In Europe, Greece and Poland had the highest levels of MRSA (55.6% and 60.9%, respectively), followed by Italy and Portugal (36.4% and 37.5%, respectively). No MRSA isolates were collected from the Czech Republic, Denmark, Finland and the Netherlands, while Latvia and Sweden had low MRSA rates (6%). The MRSA rates varied in North America (Canada, 21.6% and the USA, 53.7%) and the Asia/Pacific Rim region, where Australia, Pakistan, the Philippines and Singapore had the lowest rates (
20%), compared with China (59.1%), India (50%) and Korea (85%). In Latin America, the MRSA rates in Argentina, Brazil and Chile were more consistent, ranging between 43.5% and 51.1%; whereas the rate in Mexico was notably higher (86.4%).
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All isolates of methicillin-susceptible S. aureus and MRSA were susceptible to tigecycline, linezolid and vancomycin (Tables 2 and 3).
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Enterococcus spp
Vancomycin resistance was seen in <5% of E. faecalis isolates: North America 4.6%; Europe 1.5%; Latin America 1.4%; and Asia/Pacific Rim 0%. Vancomycin resistance in E. faecium varied widely among regions: North America 65.6%; Latin America 46.7%; Asia/Pacific Rim 31%; and Europe 12%. In terms of country distribution, only 14 of the 29 countries submitted more that 10 E. faecium isolates and among these, the numbers of vancomycin-resistant isolates were small, except in the USA (n = 477). The USA, Argentina and Korea had the highest percentages of vancomycin-resistant E. faecium (>60%) (Figure 2).
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E. faecalis isolates were largely susceptible to the panel of antimicrobials, with the exception of levofloxacin (56.5% to 77.9% susceptible) and minocycline (30.8% to 47.9% susceptible) (Table 2). All isolates were susceptible to penicillin and ampicillin, and tigecycline was the most active compound. The four regions were comparable in terms of MIC90 values of all antimicrobials.
Irrespective of vancomycin susceptibility, E. faecium isolates showed poor antimicrobial susceptibility, except tigecycline and linezolid (Tables 2 and 3). MIC90s of tigecycline were 0.12 mg/L, irrespective of susceptibility to vancomycin. For linezolid, the MIC90 values were 2 mg/L (>90% susceptible).
Results from 27 494 Gram-negative isolates are presented. In the four regions, 4916 K. pneumoniae, 6504 E. coli, 5731 Enterobacter spp., 2313 Serratia marcescens, 2902 A. baumannii and 5128 P. aeruginosa were submitted.
The occurrence of ESBL producers among K. pneumoniae isolates collected over 3 years was highest in Latin America (44%), compared with Asia/Pacific Rim (22.4%), North America (7.5%) and Europe (13.3%) (Figure 3). By country, the highest ESBL rates occurred in India (72%) and Mexico (71.4%). Also notable were the rates in the other Latin American countries (37.8% to 55.3%), Greece (43.1%) and Poland (37.5%). No ESBL-producing isolates were reported in Austria, Czech Republic, Denmark, Finland, Ireland, Switzerland and the Netherlands.
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Against all K. pneumoniae collected, imipenem was the most active antimicrobial, with >99% susceptibility in each region. This was followed by tigecycline (>94% of isolates susceptible in each region) (Table 4). Imipenem and tigecycline were also the most active agents against the subpopulation of ESBL-producing K. pneumoniae (Table 3). The susceptibility rates for ß-lactams and levofloxacin varied widely among the regions and were markedly lower in Latin America than the other regions in the cases of amoxicillin/clavulanate and piperacillin/tazobactam.
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E. coli
ESBL production among E. coli was variable among the regions; Asia/Pacific Rim and Latin America had the highest rates (12.0% and 13.5%, respectively) and North America had the lowest rate (2.2%). In Europe, 7.6% of E. coli were ESBL producers. E. coli isolates showed 100% susceptibility to tigecycline and imipenem and >90% susceptibility to piperacillin/tazobactam and amikacin in the four regions (Table 4). Overall, antimicrobial susceptibility was comparable in the four regions; however, the MIC90 values varied widely for ceftriaxone (0.25 to 
128 mg/L) and cefepime (0.5–32 mg/L). Ampicillin, amoxicillin/clavulanic acid and levofloxacin showed poor activity against E. coli.
These isolates comprised mostly Enterobacter aerogenes (25.5%) and Enterobacter cloacae (71.2%); both species had similar antimicrobial susceptibility profiles (data not shown). Susceptibilities to tigecycline, imipenem and amikacin ranged between 89.8% and 100% among the Enterobacter spp. isolates in all four regions (Table 4). The Enterobacter spp. were totally or almost totally resistant to ampicillin and amoxicillin/clavulanic acid. Latin America had the lowest susceptibility rates among the regions for the remaining ß-lactams (piperacillin/tazobactam, ceftazidime, ceftriaxone and cefepime), levofloxacin and minocycline.
With the exception of ampicillin and amoxicillin/clavulanic acid, S. marcescens was largely susceptible to the panel of antimicrobials (Table 4). Imipenem was the most active antimicrobial (100% susceptibility), followed by tigecycline (>96% susceptibility across the regions). Levofloxacin and minocycline susceptibility rates were moderately consistent across the regions (87.9% to 95.6% and 88.5% to 90.9%, respectively). For the remaining antimicrobials, however, the susceptibility rates were lower in Latin America than the other regions.
With the exception of minocycline and tigecycline, A. baumannii isolates exhibited relatively poor antimicrobial susceptibility (Table 4). The susceptibility of imipenem and amikacin varied across the regions, from fairly good in North America and Europe (74%) to poor or moderate in Latin America (60.6% and 23.4%, respectively) and Asia/Pacific Rim (69.2% and 59.6%, respectively). Susceptibility rates for those antimicrobials with breakpoints (except minocycline) were markedly lower in Latin America than the other regions.
Among the P. aeruginosa collected, >85% susceptibility to piperacillin/tazobactam was seen for isolates from all regions and to amikacin among isolates from Asia/Pacific Rim, North America and Europe (Table 4). Of the antimicrobials with breakpoints, minocycline had the lowest susceptibility rates (<7%). No breakpoints were available for tigecycline, but the MIC90 value was 32 mg/L in each region. There was a trend for lower susceptibility rates in Latin America than the other regions.
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Discussion |
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These TEST data provide information about the distribution of antimicrobial-resistant organisms in four major geographic regions. They demonstrate the large variation in the percentage of resistant organisms among countries and regions. The clinical importance of antimicrobial resistance, among both Gram-positive and Gram-negative organisms, has been demonstrated in a number of studies.14 MRSA, in particular, is a global problem and as expected, the MRSA isolates collected in the TEST study were largely multiresistant, but remained susceptible to vancomycin and linezolid, as well as tigecycline. Tigecycline is notable as it is the first compound in some time to be licensed that combines activity against MRSA with activity against Gram-negative organisms.
Of the four regions, Europe had the lowest proportion of MRSA among S. aureus isolates over the 3 years; the rate (25%) was in line with the findings of the European Antimicrobial Resistance Surveillance System (EARSS) for 2004 (24%).15 However, large variations in the rates of MRSA within Europe have been reported15 and are supported by the findings of this study. Greece, Italy and Portugal had rates of >35% in both the TEST data and EARSS.15 Interestingly, the UK, although reported to have a high rate of MRSA,16 was not among the countries with the highest rates in TEST. The number of centres participating in TEST is low in most countries, and any deviation from EARSS among the TEST data may reflect the local infection control practices and antimicrobial use associated with the limited number of study centres.
Markedly higher rates of methicillin resistance were seen in the other three regions included in this article, with the highest rates in North and Latin America. For the USA, the rate of 53.7% is comparable with the 2006 value (59.5%) from the National Nosocomial Infections Surveillance system.17 The MRSA rate for Latin America (49.4%) is an appreciable increase from the published rate of 35% for a previous period (1997–99),18 perhaps a reflection of the rapid rise in antimicrobial resistance in this region. Included in this region is Mexico, the country with the highest MRSA rate (86.4%) in this study. This figure is inconsistent with previous estimates of up to 30% and may represent a clonal outbreak at the single Mexican centre.19 The wide variation in MRSA prevalence among the Asia/Pacific Rim countries was similar to that reported for the SENTRY Program during 1998–99 (65%).20
Enterococci are a predominant cause of nosocomial infections and are intrinsically resistant to many antimicrobial agents. As previously reported for Enterococcus spp. by Low et al. for 1997–99,21 the vancomycin resistance rate among E. faecium in the USA was the highest. As seen with MRSA, the rate of vancomycin-resistant E. faecium is highly variable among countries, although it is important to note that rates of vancomycin-resistant Enterococcus have not reached the same levels as seen for MRSA in many parts of the world. Published data are scant for some of the countries involved in TEST. For example, the rate reported here for India is notably higher than local publications, but there are few data available in the wider literature.22 Against both E. faecalis and E. faecium, tigecycline was the most active compound and the MIC90s reported by this study are similar to those reported for isolates collected from Phase III clinical trials23 and other studies.24
The geographical distribution of the ESBL-producing isolates was reflected in the overall antimicrobial susceptibility profile. Latin America had the highest prevalence of Klebsiella ESBL producers (44.0%). Only half of all K. pneumoniae isolates from Latin America were susceptible to the cephalosporins and combinations of ß-lactam/ß-lactamase inhibitor. This is in contrast with the other three regions, in which typically >80% of the isolates were susceptible to these antimicrobials. These results support the findings of Winokur et al.25 The most active agents against K. pneumoniae (and the subgroup of ESBL producers) were imipenem and tigecycline. Carbapenem resistance among K. pneumoniae remained low key until an outbreak in several hospitals in New York City in 2003.26 The K. pneumoniae implicated in this outbreak was multiresistant with the blaKPC gene, and the most consistently susceptible agents were tigecycline and polymyxin B/rifampicin.27 In TEST, imipenem remained >99% active against K. pneumoniae in all regions. Susceptibility to tigecycline ranged between 94.3% and 97.1%. With the FDA-approved breakpoints used in this study, a total of 56 isolates were on the tigecycline resistance breakpoint of 8 mg/L. These were isolated in Europe (10 isolates), Latin America (4) and North America (42). Such isolates have been reported previously28 and the mechanism(s) of resistance warrants further investigation. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) published breakpoints for tigecycline in 2006. For Enterobacteriaceae, they are one doubling dilution lower than those approved by the FDA. Applying the EUCAST breakpoint to the European K. pneumoniae isolates collected in this study gave susceptibility rates of 88.9% for all K. pneumoniae and 75.4% for ESBL-producing isolates.
ESBL production among isolates of E. coli ranged from 2.2% in North America to 13.5% in Latin America. The emergence of strains that produce ESBLs or other ß-lactamases and the general increase in multidrug resistance among Gram-negative organisms represent a major threat that affects patient outcomes, particularly in ICUs, although community-acquired ESBL producers, especially among the E. coli, are becoming more frequent. So far, carbapenem resistance in E. coli remains rare29 and none was seen in the TEST data. Tigecycline, along with imipenem, was the most active against E. coli and all isolates from all four regions were susceptible to these two agents. Applying the EUCAST breakpoints to the collection of isolates from European centres gave a rate of susceptibility of 99.9%, with two isolates on the intermediate breakpoint of 2 mg/L. Isolates with an MIC of 2 mg/L have been reported previously in both European and Global studies.23,30
As seen for K. pneumoniae, the TEST data showed a trend for lower susceptibility rates in Latin America among isolates of A. baumannii and P. aeruginosa. These observations are in agreement with published reports.31,32 Significant increases in antimicrobial resistance, mainly to carbapenems and fluoroquinolones, have also been reported among P. aeruginosa isolated in Latin America between 1997 and 2001.33 However, it is established that antimicrobial resistance rates for most nosocomial organisms are higher among ICU patients than among non-ICU patients.34 One contributing factor to our observations in TEST may well be that a larger proportion of isolates of P. aeruginosa and A. baumannii (as well as vancomycin-resistant E. faecium) originated from ICU than from non-ICU in Latin America when compared with the other regions.
Among the Gram-negative isolates, A. baumannii and P. aeruginosa were the most resistant to the antimicrobials tested. A. baumannii might be considered to be currently the most troublesome nosocomial pathogen, mainly affecting patients in ICUs. These isolates, largely resistant to the commonly used antimicrobials, have now developed resistance to the carbapenems.35,36 Treatment options for carbapenem-resistant A. baumannii infections are limited and agents such as colistin, a drug that was in clinical use in the 1950s but was abandoned when better-tolerated agents became available, are now being reconsidered.37,38 The antimicrobial with the lowest MIC90s for A. baumannii in the TEST panel was tigecycline, and it may be a viable option for the treatment of infections caused by A. baumannii, although clinical data are lacking.
The susceptibility profile for P. aeruginosa in TEST was similar to that reported by Karlowsky et al.,39 piperacillin/tazobactam and amikacin were comparable in activity and the most active, followed by ceftazidime, cefepime and imipenem. Higgins et al.40 described decreased piperacillin/tazobactam susceptibility among imipenem-resistant isolates and linked imipenem resistance in P. aeruginosa with higher rates of resistance to other unrelated antimicrobials. In TEST, imipenem remained fairly active against P. aeruginosa, with higher susceptibility rates (>80%, except in Latin America) than ceftazidime, the antipseudomonal cephalosporin. Tigecycline is not considered active against P. aeruginosa,41 and does not have an indication for the treatment of infection caused by this organism.
Surveillance of antimicrobial resistance is essential to understand trends in resistance so as to develop judicious treatment guidelines and to assess the effectiveness of interventions. There are a number of international surveillance studies currently in operation, perhaps the most widely known being The Surveillance Network (TSN) and SENTRY. TEST covers a large geographic area, involves a wide range of Gram-positive and Gram-negative organisms and with 3 years of operation currently contains more than 35 000 isolates in its database. As seen by the data presented here, a large proportion of the isolates collected are from North America (and the USA in particular); however, with the continuation of this study, the contribution from other regions will increase. A possible bias of this study is that it only collected isolates from teaching hospitals and so the results may be an overrepresentation of resistant organisms in the general population. The study would also benefit from the addition of genotyping analysis. As stated by Bax et al.,42 there is no ‘ideal’ surveillance system, but the data presented by TEST add to the knowledge already available on antimicrobial resistance globally.
Few antimicrobial agents remain that are active against a wide range of organisms. Against Gram-positive organisms, vancomycin and linezolid continue to provide excellent activity, and for Gram-negatives, imipenem is highly active. However, as shown by the data presented here, high rates of resistance have been reported for many antimicrobials, but tigecycline, with its ability to circumvent the common resistance mechanisms and its activity against both Gram-positive and Gram-negative organisms, may make a welcome alternative for the treatment of nosocomial infections.
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The study was funded by Wyeth Pharmaceuticals.
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Transparency declarations |
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R. R. R. received consultancy fees and funds for research from Wyeth. D. E. L. has received research funding and honoraria for presentations from Bayer Healthcare Inc., Sanofi-Aventis and Pfizer Canada Inc. F. R. has received funds for research from Wyeth and for speaking at symposia organized on behalf of Wyeth. X. Z. has received research funds from Wyeth. C. W. received funds on behalf of Sir Ganga Ram Hospital for TEST research from Wyeth. M. J. D. is an employee of Wyeth.
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Acknowledgements |
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We wish to thank all of the investigators who have contributed to this study and the staff of International Health Management Associates, Inc., Schaumburg, IL, USA for their coordination of TEST.
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References |
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