Biomedical subjects
Publications and source records attributed to Ana C Gales.
Multidrug-resistant Acinetobacter spp. constitute a serious cause of nosocomial infection in Brazilian hospitals. This manuscript reports the first appearance of an IMP-like metallo-beta-lactamase encountered in a clinical isolate of A. baumannii from a Brazilian teaching hospital.
Enterobacter spp. and Klebsiella spp. are important clinical pathogens that frequently exhibit resistance to third-generation cephalosporins. In Enterobacter spp. strains, resistance is usually due to derepression of the Amp C locus, whereas plasmid-encoded extended-spectrum beta-lactamases (ESBLs) are primarily responsible for resistance in Klebsiella spp. Here we report the results from the SENTRY Antimicrobial Surveillance Program concerning the rates and trends of resistance to extended-spectrum beta-lactams and other antimicrobial agents in Enterobacter spp. and Klebsiella spp. isolated between 1997 and 2000 in participating hospitals in the United States. Among Enterobacter spp., resistance (MIC>or=32 mg/l) to aztreonam, ceftazidime and ceftriaxone ranged from 12.3 to 21.2% over the 4 years, whereas resistance in Klebsiella (MIC>or=2 mg/l) ranged from 5.9 to 6.8%. There was no trend toward increased resistance to these beta-lactam agents over the monitored period. Carbapenems (imipenem, meropenem) and cefepime had excellent activity against both ceftazidime-susceptible and -resistant Enterobacter spp. and Klebsiella spp. (>99% susceptible), although the minimum inhibitory concentration values of cefepime were higher in ceftazidime-resistant isolates compared with ceftazidime-susceptible isolates. Co-resistance to other antimicrobial agents was common in both tested genus groups.
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The frequency of occurrence of ESBL-producing clinical strains varies widely in distinct geographic areas. The objective of this study was to describe the frequency of occurrence, the preferred substrate, and the co-resistance patterns of the ESBL-producing isolates collected from the Asia-Pacific region and South Africa through the SENTRY Antimicrobial Surveillance Program between January 1998 and December 1999. A total of 1,377 Escherichia coli, 678 Klebsiella pneumoniae, and 138 Proteus mirabilis isolates were collected from diverse body sites. Using NCCLS criteria, 139 E. coli (10.1%), 171 K. pneumoniae (25.2%), and 2 P. mirabilis (1.4%) had presumptive ESBL phenotypes; 100, 146 and 1 strain respectively were confirmed to be ESBL producers on clavulanate enhancement testing. The frequency of occurrence of confirmed ESBL-producing E. coli by the medical centers varied from 0-1% for centers located in Australia to 13-35% for mainland Chinese centers. The higher prevalence rates (>20%) of ESBL K. pneumoniae phenotypes were observed in all mainland Chinese centers, one Japanese and one Taiwanese center, and in the Philippine, South African, Singaporean and medical centers. The spread of the presumptive ESBL phenotype to the Enterobacter species was observed in nine medical centers. Overall, ceftriaxone and aztreonam were the best substrates for the detection of the ESBL phenotype between both E. coli isolates and K. pneumoniae ESBL phenotypes; however, there was significant variation between countries in substrate preference. Co-resistances to gentamicin, tobramycin, tetracycline, and trimethoprim-sulfamethoxazole were common throughout isolates collected from most medical centers. Ciprofloxacin resistance rates were very high among isolates collected from Hong Kong, mainland China, Singapore, and the Philippines. The best coverage against ESBL-producing isolates was obtained with imipenem (0% resistance), followed by amikacin (6% resistance).
Urinary tract infections (UTI) are one of the most common infectious diseases diagnosed in outpatients as well as in hospitalized patients. The objective of this study was to report the frequency of occurrence and antimicrobial susceptibility of uropathogens collected in Latin America between 1997 to 2000 through the SENTRY Antimicrobial Surveillance Program. Antimicrobial susceptibility testing was performed and results interpreted using reference broth microdilution methods. In the 4 year period, a total of 1961 urine isolates from hospitalized patients were included. The patients' mean age was 51.3 years and most of the infections occurred among women (65.6%). Esherichia coli was the most frequent pathogen isolated followed by Klebsiella spp., Pseudomonas aeruginosa, and Proteus mirabilis. Among the E. coli isolates, piperacillin/tazobactam, aztreonam, extended-spectrum cephalosporins, carbapenems and amikacin constitute reasonable therapeutic options for treatment of serious UTI in Latin America (91.0-100.0% susceptible). High resistance rates to fluoroquinolones (17.5-18.9%) and trimethoprim/sulfamethoxazole (>45.0%) were observed among the E. coli. In contrast, nitrofurantoin displayed susceptibility rate of > 87.0%. Against Klebsiella spp. infections, the only effective therapeutic option would be the carbapenems due to the high number of isolates (>30.0%) producing extended-spectrum beta-lactamases (ESBL). Even the new fluoroquinolones showed limited activity against Klebsiella spp. (72.1-88.6% susceptible) and the P. aeruginosa isolates showed high resistance rates to most antimicrobial agents tested. The results of this survey endorse the importance of Enterobacteriaceae as cause of UTI in Latin America. Our results also demonstrate that the uropathogens isolated in the Latin American medical centers exhibit high resistance to various classes of antimicrobial agents. Carbapenem-resistant P. aeruginosa, ciprofloxacin-resistant E. coli, ESBL-producing K. pneumoniae constitute serious problem in this geographic region.
In spite of the recent medical advances, lower respiratory tract infections are still the most frequent infectious causes of mortality worldwide. The objective of this study was to determine the frequency of occurrence and antimicrobial susceptibility of bacterial isolates collected from hospitalized patients with pneumonia in Latin American medical centers during the first four years of the SENTRY Program. The five most frequently isolated species were (n/%): Pseudomonas aeruginosa (659/26.3%), Staphylococcus aureus (582/23.3%), Klebsiella pneumoniae (255/10.2%), Acinetobacter spp. (239/9.6%), and Enterobacter spp. (134/5.4%). P. aeruginosa demonstrated high rates of resistance to most of the antimicrobials tested. Against P. aeruginosa, the most active agents were meropenem (MIC(50), 1 microg/ml; 71.6% susceptible), amikacin (MIC(50), 4 microg/ml; 71.0% susceptible), and piperacillin/tazobactam (MIC(50), 16 microg/ml; 70.4% susceptible). Imipenem (MIC(50), 1 microg/ml; 84.1% susceptible) and meropenem (MIC(50), 2 microg/ml; 84.9% susceptible) were the most active agents against Acinetobacter spp. followed by tetracycline (MIC(50), </=4 microg/ml; 52.3% susceptible). Although the broad-spectrum cephalosporins had demonstrated excellent in vitro activity against Klebsiella pneumoniae isolates (MIC(50)s range, </= 0.12 to 0.25 microg/ml), elevated rates of resistance (46.3%-58.5%) were observed. Approximately 44.0% and 29.0% of K. pneumoniae and E. coli isolates were considered ESBL producers based on NCCLS criteria, respectively. Overall, the prevalence of methicillin-resistant S. aureus was 46.2%. The most active drugs against this pathogen were vancomycin, teicoplanin, linezolid and quinupristin/dalfopristin. In summary, the SENTRY Antimicrobial Surveillance Program has detected a high prevalence of methicillin-resistant S. aureus and multidrug resistant non-fermentative Gram-negative bacilli isolated from respiratory tract specimens of hospitalized patients with pneumonia in Latin America. Our results emphasize the importance of local surveillance programs in correctly guiding empiric therapy and local intervention programs in attempt to reduce antimicrobial resistance.
Recent years have seen a dramatic rise in the incidence and severity of cases of human salmonellosis. In addition, multidrug resistant strains have arisen. The objective of this study was to characterize the antimicrobial susceptibility profile of Salmonella spp. clinical isolates collected from Latin American medical centers as part of the SENTRY Antimicrobial Surveillance System. A total of 144 bloodstream Salmonella spp. isolates were collected between 1997 and 2000. The susceptibility to diverse antimicrobial agents was tested by broth microdilution techniques according to the NCCLS recommendations. The Salmonella spp. strains were more frequently collected from adult patients (67.0%; 21-60 years) and isolated from Chile (28.5%) > Brazil (25.0%) > Mexico (18.8%) > Colombia (11.8%). Ampicillin (MIC(50), 1 microg/ml) showed good in vitro activity (92.4% susceptibility). Meropenem (MIC(50), 0.06 microg/ml) and gatifloxacin (MIC(50), 0.03 microg/ml) were the most potent compounds against the Salmonella spp. isolates (100.0% susceptible) followed by piperacillin/tazobactam (99.3%), ceftazidime (98.6%), ceftriaxone (98.6%), and amoxicillin/clavulanic acid (94.4%). The lowest susceptibility rates were observed for tetracycline (87.5%) and trimethoprim/sulfamethoxazole (91.7%). Four of 144 (2.8%) Salmonella spp. isolates demonstrated an ESBL phenotype; however, only two (1.4%) were confirmed as an inhibitable ESBL producer. The results of this study show that multidrug resistance, especially fluoroquinolone resistance, does not represent a serious problem among Salmonella isolates collected from the Latin American medical centers as monitored by the SENTRY Program.
OBJECTIVES: To characterize vancomycin-resistant enterococci (VRE) isolates and to evaluate the mode of dissemination of this pathogen in Brazil. DESIGN: We collected 22 vancomycin-resistant Enterococcus faecium isolates from 6 medical centers in Sao Paulo, Brazil, and 1 isolate from a medical center in Curitiba, Brazil. PARTICIPANTS: All Brazilian hospitals that had identified vancomycin-resistant E. faecium up to the beginning of this study (late 1999) contributed isolates to the study. METHODS: The isolates were susceptibility tested using the broth microdilution method and the E-test. The presence of vancomycin resistance genes (vanA, vanB, vanC1, vanC2-3, and vanD) was evaluated by polymerase chain reaction; molecular typing was performed by pulsed-field gel electrophoresis (PFGE). RESULTS: The vanA gene was demonstrated in all vancomycin-resistant E. faecium, except for 1 isolate. None of the vancomycin resistance genes cited above was detected in the isolate from Curitiba, which was the first vancomycin-resistant E. faecium described in Brazil. All isolates were resistant to ampicillin and teicoplanin. The main clone remains susceptible to doxycycline and chloramphenicol, but intermediate to quinupristin-dalfopristin. PFGE analysis demonstrated 7 major PFGE patterns. A unique PFGE pattern with 4 subtypes was detected in 17 isolates from 4 different hospitals. CONCLUSION: The results of our study indicate the occurrence of intra- and interhospital dissemination of VRE in Sao Paulo, Brazil.
The gene encoding the metallo-beta-lactamase SPM-1 was cloned from a genomic library of Pseudomonas aeruginosa strain 48-1997 A. The insert carrying spm-1 possessed a GC content of 47%, indicating that it is of non-Pseudomonas origin. Upstream of spm-1 there is a small open reading frame (ORF), which is homologous to the LysR family of proteins (69% identity to the LysR protein from Salmonella enterica serovar Typhimurium). Downstream of spm-1 there is the start of an ORF, the product of which shows close homology with the GroEL-type proteins from Xanthomonas campestris. No transmissible element could be identified upstream or downstream of spm-1. The spm-1 gene is carried on a plasmid that can transform both Escherichia coli and P. aeruginosa to ceftazidime resistance. SPM-1 contains the classic metallo-beta-lactamase zinc-binding motif HXHXD and shows the highest identity (35.5%) to IMP-1. SPM-1 is a distinctly different metallo-beta-lactamase from VIM and IMP and, accordingly, represents a new subfamily of mobile metallo-beta-lactamases. The predicted molecular weight of the protein was 27 515 Da, significantly higher than that of IMP (25 041 Da) or VIM (25 322 Da). SPM-1 possesses a unique loop of 23 residues that accounts for the higher molecular mass.
It is not uncommon to see amphotericin B treatment failure in patients with systemic infection caused by Candida lusitaniae. We report a patient with stage IV ovarian carcinoma and C. lusitaniae sepsis whose treatment with amphotericin B failed. The initial blood isolate was susceptible to amphotericin B in vitro; however, the MIC for a blood isolate recovered 7 weeks after treatment began showed a fourfold increase. Direct subculture of two positive blood samples obtained within a week of the patient's death showed the coexistence of two distinct colony color variants on CHROMagar Candida (CAC). One variant was susceptible to amphotericin B, and one was resistant. These results emphasize the importance of repeat amphotericin B susceptibility testing for patients with persistent C. lusitaniae infection. The presence of colony variants on CAC may signal the emergence of amphotericin B resistance in C. lusitaniae and should be investigated.