Services on Demand
Print version ISSN 1413-8670
Braz J Infect Dis vol.8 no.1 Salvador Feb. 2004
Helio S. SaderI,II; Ronald N. JonesII; Ana C. GalesI; Juliana B. SilvaI; Antonio C. PignatariI ; the SENTRY Participants Group (Latin America)
ISpecial Laboratory of Clinical Microbiology; Division of Infectious Diseases, Federal University of São Paulo, São Paulo, SP, Brazil
IIThe JONES Group / JMI Laboratories, North Liberty, Iowa, USA
The alarming emergence and spread of antimicrobial resistance among common bacteria threatens the effectiveness of therapy for many infections. Surveillance of antimicrobial resistance is essential to identify the major problems and guide adequate control measures. Several resistance surveillance programs have been implemented in North America and Europe in the last decade; however, very few programs have assessed antimicrobial resistance in Latin American countries. The SENTRY Antimicrobial Surveillance Program was initiated in 1997 and represents the most comprehensive surveillance program in place at the present time worldwide. The SENTRY Program collects consecutive isolates from clinically documented infections in more than 80 medical centers worldwide (10 in Latin America). The isolates are collected according to the type of infection (objectives) and susceptibility tested in a central microbiology laboratory by reference broth microdilution methods according to NCCLS guidelines. The Program also incorporated molecular typing (ribotyping and PFGE) and resistance mechanism analysis of selected isolates. In this report we present a very broad analysis of the data generated by testing almost 20,000 bacterial isolates against more than 30 antimicrobial agents. The susceptibility results (MIC50, MIC90 and % susceptible) are presented in 11 tables according to the organism and site of infection. The data from Brazil, as well as the data from isolates collected in 2001, are analyzed separately. This report allows the evaluation of the activities numerous antimicrobial agents against clinical isolates collected in Latin American countries.
Key Words: SENTRY, antimicrobial resistance, nosocomial infection, surveillance, Latin America.
The importance of antimicrobial resistance among nosocomial and community-acquired pathogens is acknowledged worldwide. Well-designed antimicrobial surveillance programs are essential in the fight against these cases of resistance . These programs provide important information on the trend in microbial occurrence in different geographical regions and antimicrobial resistance patterns in nosocomial and community-acquired infections. Such information has the potential to guide therapeutic approaches for serious infections, pending directions from local susceptibility testing, and may have value in the prevention and control of infection. However, in order to be effective, surveillance data should be analyzed, tabulated and rapidly presented to the medical community and infection control workers.
The SENTRY Antimicrobial Surveillance Program (SENTRY) was initiated in 1997 and was designed to monitor the spectrum of microbial pathogens and antimicrobial resistance trends for both nosocomial and community-acquired infections on a global scale, by using validated reference quality identification and susceptibility testing methods in designated central laboratories [1-4]. Rapid communication and dissemination of information is a guiding principal of the SENTRY Program. This report is a summary of the data collected in the Latin American region during the first five years of the SENTRY Program (1997 through 2001).
Material and Methods
The SENTRY Program was established to monitor the important pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections via a broad network of sentinel hospitals distributed by geographic location and size. The collection of isolates was done according to the site of infection and/or type of patient. The types of infections that are monitored include bloodstream infections or true bacteremia (BSI, objective A), community-acquired respiratory tract infections (CARTI, objective B), lower respiratory tract infections in hospitalized patients (LRTI, objective C), skin and soft tissue infections in hospitalized patients (SSTI, objective D), urinary tract infections in hospitalized patients (UTI, objective E), gastroenteritis (objective G), b-haemolytic streptococci from community-acquired infections (objective H), and assessment of pathogens and resistance patterns among infected patients in the intensive care unit (ICU, objective I). Objectives G, H and I were introduced into the program in 2001.
Each participating center contributed results (organism identification, date of isolation, antimicrobial susceptibility profile, etc.) for the first 20 consecutive episodes of BSI per month from January 1997 to December 2001, 100 consecutive episodes of LRTI and CARTI per year from 1997 to 2001, 50 consecutive isolates from SSTI per year from 1997 to 2000, and 50 consecutive isolates from UTI per year from 1997 to 1999 and in 2001, 25 consecutive isolates of organisms considered producers of diarrheal diseases (gastroenteritis) collected in 2001, 25 consecutive b-haemolytic streptococci isolated from community-acquired infections in 2001, and 50 consecutive and clinically relevant bacterial isolates from patients hospitalized in the ICU in 2001. Just one isolate per patient was included in the study and all isolates were saved on transport swabs and sent to the monitoring center (Iowa, USA) for storage and further characterization by reference identification and susceptibility testing methods. We evaluated all the isolates that were recovered and the data collected from January 1997 to December 2001.
The laboratories were distributed in various cites of six countries: Sao Paulo, Rio de Janeiro, Florianopolis, Porto Alegre, and Brasilia, Brazil; Buenos Aires and San Isidro, Argentina; Santiago (two centers), Chile; Medellin, Colombia; Mexico City, Mexico; and Montevideo, Uruguay. In 1998, the center located in Montevideo was replaced by a center in Caracas, Venezuela; and in 1999 the Brazilian center located in Rio de Janeiro was replaced by another Brazilian center in Porto Alegre, which is also located in the South region of Brazil. In 2001, the center located in Mendellin, Colombia was replaced by a center located in Brasilia, Brazil. The selection of participant centers was based on the principle that they should be representative in their respective geographic region.
All isolates were identified at the participating institution by the routine methodology in use at each laboratory. On receipt at the monitoring center, isolates were subcultured on blood agar to ensure viability and purity. Species identification was confirmed by standardized methods or performed by using the Vitek System (bioMérieux, Hazelwood, MO) or API (bioMérieux, Hazelwood, MO). Isolates were frozen at -70°C until they were processed.
Antimicrobial susceptibility testing of isolates was performed by reference broth microdilution methods, as described by the National Committee for Clinical Laboratory Standards (NCCLS) . Microdilution trays were purchased from TREK Diagnostics (Cleveland, OH), MicroScanâ (West Sacramento, CA), and PML Microbiologicals (Wilsonville, OR). Antimicrobial agents were obtained from their respective manufactures as laboratory grade powder and included cephalosporins (cefepime, cefuroxime, cefotaxime, ceftriaxone, ceftazidime, cefazolin, cefoxitin, cefaclor, and cefixime), penicillins (ampicillin, penicillin, amoxicillin, and oxacillin), b-lactamase inhibitor combinations (amoxicillin-clavulanate, ticarcillin-clavulanate, and piperacillin-tazobactam), carbapenems (imipenem and meropenem), a monobactam (aztreonam), fluoroquinolones (ciprofloxacin, levofloxacin, gatifloxacin, and garenoxacin [formerly BMS 284756]), aminoglycosides (amikacin, gentamicin, and tobramycin), macrolides (erythromycin, azithromycin, and clarithromycin), glycopeptides (vancomycin and teicoplanin), the oxazolidinone linezolid, the streptogramin quinupristin-dalfopristin, and other drugs, such as clindamycin, chloramphenicol, tetracycline, rifampin, and trimethoprim-sulfamethoxazole. Quality control was performed by testing E. coli American Type Culture Collection (ATCC) 25922, Pseudomonas aeruginosa ATCC 27853, and other strains, as recommended by the NCCLS [5,6]. Interpretive criteria for each antimicrobial tested were those published by the NCCLS [5,6].
Almost 20,000 clinical isolates were analyzed during this period, and the frequencies of the different pathogens were investigated (Table 1). The antimicrobial susceptibility data for the year 2001 were analyzed separately (Tables 2-5), while the data for the entire 5-year period was also compiled (Tables 6-11).
In addition, data collected in the participating Brazilian centers were analyzed separately from the data of the entire Latin American region (including Brazil). Minimum antimicrobial concentrations that inhibits 50% and 90% of the organism collection (MIC50 and MIC90, respectively) were presented only for the data of the entire region. Isolates collected from bloodstream infections and from lower respiratory tract infections (mainly pneumonia) in hospitalized patients were also analyzed separately (Tables 3, 5, 7 and 9).
Two groups of pathogens, streptococci and extended-spectrum (ESBL)-producing strains, were analyzed separately due to their importance in community-acquired and nosocomial-acquired infections, respectively. Table 10 presents the antimicrobial susceptibility of streptococcal species, while Table 11 presents the antimicrobial susceptibility of ESBL-producing E. coli and Klebsiella pneumoniae.
We made a comprehensive analysis of the Latin American SENTRY Program data collected during the first five years of this global program. During this period, SENTRY has provided valuable information worldwide [2-4, 7-9]. The rapid publication of regional susceptibility data concerning a large number of antimicrobial agents, indexed by the site of infection, allowed the detection of considerable geographical variation of the in vitro activity of several antimicrobial agents and made evident the emergence of important resistance patterns. These data have been used to guide empirical therapy and the local implementation of control or intervention measures. In addition, SENTRY Program data has guided the implementation of more focused, local surveillance studies, which have been designed based on local resistance problems detected by SENTRY Program results [10,11].
The SENTRY Program has shown that resistance among Gram-negative bacteria seems to be much higher in Latin America when compared to other regions of the world, especially North America and Europe [1,2]. On the other hand, some resistance problems related to Gram-positive cocci, such as glycopeptide-resistance among enterococci, and high-level penicillin-resistance among pneumococci, are less frequently described in Latin America .
The main antimicrobial resistance problems the Latin American countries are presently facing are multidrug resistant (MDR) non-fermentative Gram-negative bacilli (Acinetobacter spp. and P. aeruginosa) and ESBL-prodcing Enterobacteriaceae [1,3,8,9,11-13]. Pseudomonas aeruginosa was the third and the fifth most frequently isolated pathogen in general and from blood stream infections, respectively. In addition, resistance rates were very high for all antimicrobial agents evaluated, except polymyxin B, which was evaluated since January 2001 only (Tables 2, 4, 6, and 8). The prevalence of isolates resistant to all antimicrobial agents except the polymyxins has been increasing continuously since the program started in 1997 . Additionally, P. aeruginosa resistance rates were slightly higher among isolates collected in the Brazilian centers (Tables 2, 4, 6, and 8).
Acinetobacter spp. is much more prevalent and presented higher rates of antimicrobial resistance in Latin America, when compared to other regions evaluated by the SENTRY Program . However, resistance rates to the carbapenems imipenem and meropenem were lower than those presented by P. aeruginosa (Tables 2, 4, 6, and 8). Besides these two carbapenems, other reasonable therapeutic options for empirical therapy of Acinetobacter spp. infections are the polymyxins and sulbactam. The SENTRY Program started evaluating these compounds in 2001 (polymyxin B) and 2002 (sulbactam), and the in vitro activity of these antimicrobial agents will be presented in future publications .
The rates of ESBL-producing Enterobacteriaceae, especially K. pneumoniae and E. coli, are among the highest in the world (Tables 2, 4, 6, 8, and 11)[1,3,8,9,11] In addition to resistance to cephalosporins, broad-spectrum penicillins and monobactam, these isolates have also shown high rates of resistance to most antimicrobial agents, including aminoglycosides and fluoroquinolones. Although the fluoroquinolones remained active against some ESBL-producing K. pneumoniae (61.7% to 87.7% susceptible), the carbapenems meropenem and imipenem remained the most reliable options for empirical therapy of infections due to ESBL-producing strains in the region (Table 11).
Other important resistance problems among Enterobacteriaceae include fluoroquinolone resistance due to altered target among E. coli ; and stably derepressed (AmpC) b-lactamases mediated resistance among Enterobacter cloacae, Citrobacter freundii, and other clinically important species. Ciprofloxacin susceptibility rates were as low as 85.5% among E. coli isolated from blood stream infections and 78.1% among isolates from patients hospitalized with lower respiratory tract infections (Tables 4 and 8).
Chromosomaly-inducible b-lactamases (AmpC or Bush group I) are produced by most Enterobacteriaceae species; however, some species, including E. cloacae, C. freundii, Serratia marcescens and indol-positive Proteus ("SPICE" or "CESP" group), can produce large amounts of these enzymes and have become resistant to third-generation cephalosporins, broad-spectrum penicillins and monobactams. In our study, E. cloacae resistance to ceftazidime, which indicates the production of the AmpC b-lactamase, was as high as 42.9% (Table 4). Cefepime (84.9 96.6% susceptibility) and the carbapenems imipenem and meropenem (92.9 100% susceptibility) remained very active against E. cloacae and these other pathogens in the hospitals evaluated by the SENTRY program (Tables 2, 4, 6, and 8).
Among Gram-positive cocci, oxacillin resistance among staphylococci has remained an important problem in Latin America; however, rates varied significantly from hospital to hospital, even within a specific country. The vast majority of ORSA strains showed cross-resistance to most of the antimicrobial agents evaluated, except vancomycin, teicoplanin, quinupristin/dalfopristin and linezolid. Resistance to these agents was not detected among S. aureus isolates (only a small number of isolates had intermediate-resistance to teicoplain or quinupristin/dalfopristin); however, decreased susceptibility to teicoplanin was relatively common among CoNS (90.3% susceptibility; Table 9).
The prevalence of glycopeptide-resistant enterococci remained low in the Latin American hospitals evaluated by the SENTRY Program (97.5% susceptibility in general) and its occurrence is usually linked to clonal dissemination of unique strains [1,10,16].
The prevalence of penicillin-resistant pneumococci varied significantly among the Latin American countries evaluated, and it was especially low in Brazil (only 4.6% with high-level resistance; Table 10). Macrolide resistance rates were around 10% to 12%, with approximately half of the erythromycin resistant isolates showing cross-resistance to clindamycin (MLSB phenotype). Tetracycline resistance rates were relatively elevated (around 20%), while resistance rates to trimethoprim/sulfamethoxazole were very high, especially in Brazil (49.7% susceptibility; Table 10).
Fluoroquinolone resistance was very rare among pneumococci (99.7% susceptibility to gatifloxacin) and it was not detected among other streptococci species (Table 10). b-hemolytic streptococci remained very susceptible to penicillin and all other b-lactams evaluated. However, macrolide resistance was detected among the isolates of this pathogen (erythromycin susceptibility of 92.8% and 96.6% throughout Latin America and in Brazil, respectively). As expected, viridans group streptococci showed the highest rates of resistance among streptococci, with only 66.1% of the Latin American isolates being considered susceptible to penicillin.
Among the active surveillance systems, the SENTRY Program has incorporated extensive molecular strain typing and resistance genotyping as a means of providing additional information that may be useful for understanding pathogenic microorganisms worldwide [1,17]. In any surveillance program the phenotypic characterization of microorganisms and identification of epidemic clusters of certain species and resistance phenotypes is the primary role of the microbiology laboratory. In this way, the surveillance laboratory serves as an "early warning system", alerting the participating institutions of a potential problem with resistant organisms in a variety of patient populations .
The rapid emergence and dissemination of numerous drug resistances among bacteria has raised the necessity for controlling these pathogens in hospitals on a global scale; and the determination of clonality within a phenotypically identical resistant clusters will have a direct impact on the method of corrective intervention. On a broader scale, identification of resistant clones with extensive geographic range may provide insight into strain virulence and pathogenesis; and also may result in broader public health interventions, such as vaccination and antimicrobial restrictions aimed at limiting the spread of the pathogen and associated resistance problems .
Molecular methods may also be used to detect specific antimicrobial resistance genes (resistance genotyping) in a wide variety of organisms and when coupled with DNA fingerprinting have made substantial contributions to our understanding of the genetics of antimicrobial resistance and the spread of resistance determinants in the SENTRY Program medical centers [7,15,19].
The main purpose of this report was to present a comprehensive tabular analysis of the antimicrobial susceptibility data of bacteria collected in the Latin American medical centers participating in the SENTRY Program. Antimicrobial resistances may vary significantly among Latin American countries and SENTRY Program evaluates only a small number of medical centers. However, the main objective of this program was to detect the most important problems of public health concern within the region and to assist/guide regional intervention programs. The data presented here allow the identification of these principal resistance problems and the comparison of the in vitro activity and spectrum of a large number of antimicrobial agents not often tested in most hospitals. Lastly, we emphasize that empirical therapy should be guided by local susceptibility data when those are available, but in the absence of such information, surveillance data can help with therapeutic choices.
We express our appreciation to all medical technicians who have worked in SENTRY. The SENTRY Latin America Study Group in 1997-2001 includes: Helio S. Sader, Ana C. Gales (São Paulo, Brazil - Latin American Coordinator); Jorge Sampaio (Lâmina Laboratory, Rio de Janeiro, Brazil; Cássia Zoccoli (Santa Lúzia Laboratory, Florianopolis, Brazil); Afonso Barth (Hospital de Clinicas, Porto Alegre, Brazil); Julival Ribeiro (Hospital de Base, Brasília, Brazil); José M. Casellas (Centro de Estudios en Antimicrobianos, San Isidro, Argentina); Jorgelina Smayevsky (Microbiology Laboratory C.E.M.I.C., Buenos Aires, Argentina); Valeria Prado (Faculdad de Medicina de Chile, Santiago, Chile); Elizabeth Palavecino / Patricia Garcia (Universidad Catolica del Chile, Santiago, Chile); Homero Bagnulo (Hospital Maciel, Montivideo, Uruguay); Jaime A. Robledo (Corporation para Investigaciones Biologicas, Medellin, Colombia); Jose Sifuentes-Osornio (Instituto Nacional de la Nutricion, Ciudade del Mexico, Mexico); and Manuel Guzmán-Blanco (Hospital Vargas, Caracas, Venezuela). Soraya Andrade, Rodrigo E. Mendes and Suzane Silbert provided excellent technical support. The SENTRY Antimicrobial Surveillance Program has been sponsored by a research/educational grant from Bristol-Myers Squibb.
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Dr.Helio S. Sader, MD., PhD
The JONES Group / JMI Laboratories
345 Beaver Kreek Centre, Suite A
North Liberty, Iowa 52317
Phone: 1 (319) 665-3370. Fax: 1 (319) 665-3371
Received on 13 July 2003
revised 29 january 2004