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HS Sader

Publications and source records attributed to HS Sader.

10 recordsLinked to original sources

Evaluation of the in vitro Activity of Two Fourth-Generation Cephalosporins Against Bacterial Samples Isolated From Patients in Several Brazilian Hospitals.

Cefpirome and cefepime are two fourth-generation cephalosporins recently introduced in Brazil. They have a very similar range of in vitro antimicrobial activity, but some differences have been noticed. The goal of this study was to compare the in vitro activity of cefpirome and cefepime against bacterial samples isolated in Brazilian hospitals. We studied 931 samples taken from hospitalized patients between April and June, 1998. The minimum inhibitory concentration (MIC) was determined by the Etest method. The potency of cefpirome was similar to that of cefepime, except against enterococci and coagulase-negative staphylococci, where cefpirome proved 2-fold more potent. The MIC(90) for cefepime were inferior to cefpirome in response to Klebsiella pneumoniae (MIC(90), 24 and 96µg/mL, respectively), Pseudomonas aeruginosa (MIC(90), 48 and 128µg/mL, respectively), and other Gram-negative organisms (MIC(90), 64 and 256µg/mL, respectively). Despite the fact that cefpirome presented a slightly broader range of action against Gram-positive bacteria (90% sensitive vs. 78% sensitive to cefepime), and that cefepime presented an equally broad range against Gram-negative bacteria (74% sensitive vs. 65% sensitive to cefpirome), these differences were not considered clinically significant because the sensitivity differed in MIC by less than 2 dilutions. Only 16 (1.7%) of the 931 samples tested showed a significant difference in sensitivity. This study suggests that, except for Acinetobacter sp. and P. aeruginosa, laboratories may routinely test only cefpirome and apply the same category result to cefepime. Since category discrepancies are very rare and cefpirome is slightly less active than cefepime against Enterobacteriaceae, isolates susceptible to cefepime will certanly also be susceptible to cefpirome. To optimize the treatment of severely infected patients, especially where species such as Acinetobacter sp and P. aeruginosa are involved, we recommend that both cephalosporins be tested by using the same susceptibility test method to determine the MIC.

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Comparative In Vitro Activities of Moxifloxacin (Bay 12-8039) and Other Antimicrobial Agents Against Respiratory Tract Pathogens in Brazil.

Clinical isolates of respiratory tract pathogens were susceptibility tested against six different antimicrobial agents. The in vitro activity of moxifloxacin was compared with that of levofloxacin, cefaclor, amoxicillin-clavulanate acid, azithromycin and trimethoprim-sulfamethoxazole against 111 isolates, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and other species isolated from respiratory tract infections. All isolates were susceptible to moxifloxacin, except for two isolates of Pseudomonas aeruginosa which showed intermediate-resistance (MIC=6µg/mL), and one isolate of Escherichia coli which showed resistance (MIC>32µg/mL). Only moxifloxacin and amoxicillin-clavulanic acid were active against 100% of S. pneumoniae isolates at the suceptible breakpoint (MIC90, 0.25 µg/mL and 0.064 µg/mL respectively). The rank order of the activity among this group of drugs against S. pneumoniae was as follows (% of susceptibility): moxifloxacin = amoxicillin-clavulanic acid (100%) > levofloxacin (97%) > cefaclor (71%) > trimethoprim-sulfamethoxazole (54%) > azithromycin (53%). Except for trimethoprim-sulfamethoxazole, all antimicrobial agents were 100% active against H. influenzae and M. catarrhalis. The fluoroquinolones, moxifloxacin and levofloxacin, were the most potent compounds against these pathogens (MIC(90) 0.032 0.19 µg/mL). These in vitro susceptibility testing data of moxifloxacin support the view that this fluoroquinolone will have an important therapeutic role in the treatment of respiratory tract diseases.

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Evaluation of the Cephalosporins, Cefepime, Cefpirome and Ceftazidime, against Clinical Isolates of Imipenem-Resistant Pseudomonas aeruginosa.

The level of resistance to imipenem in our institution has increased significantly in recent years, particularly in isolates of Pseudomonas aeruginosa. At present, 30% to 40% of P. aeruginosa isolated in clinical samples are imipenem resistant. The objective of this study was to test therapeutic alternatives within the class of beta-lactam antibiotics in the treatment of infections caused by imipenem-resistant strains of P. aeruginosa (IRPA). We tested 160 isolates of IRPA collected consecutively from in patients at Hospital São Paulo-UNIFESP (Federal University of São Paulo). Using the E-test method, these isolates were tested for cefepime, cefpirome, and ceftadizime susceptibility or resistance. The E-test was also used to confirm the resistance to imipenem. One group of samples was studied epidemiologically using the pulsed-field gel electrophoresis (PFGE) method to determine how this type of resistance spread in our institution. Cefepime was the most active antibiotic (MIC50, 24 µg/mL; MIC(90), 64 µg/mL) and only 57 (35.6%) of the samples showed cross-resistance between imipenem and this fourth-generation cephalosporin. The number of samples that were highly resistant (MIC(90), >256 µg/mL) to cefepime, ceftazidime or cefpirome was 8 (5.0%), 22 (13.8%) and 38 (23.8%), respectively. Molecular typing revealed the presence of 9 molecular profiles among 26 IRPA samples tested, suggesting that selection of resistant mutants occurred in each patient. However, identical molecular profiles were also found in more than one patient. This study showed that cefepime is the most effective cephalosporin against the IRPA samples isolated in our institution. In addition, we conclude that P.areuginosa resistant strains are selected in each patient, but patient to patient transmission also occurs.

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Bacterial Pathogens Isolated from Patients with Bloodstream Infections in Latin America, 1997: Frequency of Occurrence and Antimicrobial Susceptibility Patterns from the SENTRY Antimicrobial Surveillance Program.

We report the antimicrobial susceptibility of 736 organisms isolated from bloodstream infections in 10 Latin American medical centers during the first six months of 1997. The data presented here is from the SENTRY Antimicrobial Surveillance Program, a comprehensive surveillance study involving 72 medical centers worldwide. The isolates ivere tested for in in vitro susceptibility to 35 antimicrobial agents by the broth microdilution method. The five most frequently isolated species were (n/%): Staphylococcus aureus (1 65/22.4%), Escherichia coli(118/16.0%), coagulase-negative staphylococci (CoNS - 115/15.6%), Pseudomonas aeruginosa (51/6.9%), Klebsiella spp. (46/ 6.3%). Susceptibility to oxacillin was 70.9% for S. aureus and only 33.9% for CoNS. Vancomycin was active against all of staphylococci, while teicoplanin was active against 99.4% of S. aureus and only 90.4% of CoNS. The new fluoroquinolones sparfloxacin, gatifloxacin, and trovafloxacin, and the streptogramin, quinupristin/dalfopristin, were very active against these species. Only one vancomycin-resistant enterococcus was detected; however, high-level aminoglycoside resistance rates were common (66.7%). E. coli and Klebsiella spp. showed low susceptibilities for cefotaxime (90.7% and 41.3%) and for cefoxitin (85.6% and 78.3% respectively), indicating a high frequency of isolates that produce ESBL and/or stably derepressed ampC enzymes. These strains, phenotypically consistent with extended-spectrum beta-lactamase (ESBL) production, were typed using ribotyping and pulsed-field gel electrophoresis. The most active compounds (M IC90 in µg/mL /% susceptibility) against P. aeruginosa were meropenem (2 /94.1%), followed by amikacin (>32 / 86.3%), and piperacillin alone or with tazobactam (128/84.3%). Ceftazidime and cefepime showed similar activity (70.6% susceptibility) and levofloxacin was the most active fluoroquinolone (MI C50 &lte; 0.5; 76.5% susceptibility) against this gram-negative species. These results show the unique pattern of bloodstream isolates for Latin America and they demonstrate the present utility of several classes of compounds against emerging antimicrobial-resistant species in this region.

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Results of the 1997 SENTRY Antimicrobial Surveillance Program in Three Brazilian Medical Centers.

The SENTRY Antimicrobial Surveillance Program began in January, 1997, and is designed to monitor nosocomial and selected community acquired infections via a worldwide surveillance network of sentinel hospitals distributed equally by geographic location and size. Three sites in Brazil - Rio de Janeiro, Florianópolis, and São Paulo - participated in the SENTRY Antimicrobial Surveillance Program stet. Rank order of occurrence and antimicrobial susceptibility of pathogenic species causing bloodstream infections, pneumonia, wound or skin and soft tissue infections, and urinary tract infections (UTI) in hospitalized patients were determined by collecting consecutive isolates over a specified period of time. Antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis obtained from outpatients with respiratory tract infections were also evaluated. The isolates for the evaluated infections were: 1) bloodstream - 20 consecutive isolates in each calendar month during a 12-month period; 2) pneumonia - 100 consecutive isolates over a 6 month period; 3) wound or skin and soft tissue - 50 consecutive isolates over a 3 month period; and 4) UTI - 50 consecutive isolates over a 3 month period. Each hospital also contributed, over a 6 month period, consecutive clinically significant outpatient isolates (one isolate per patient) of S. pneumoniae, H. influenzae, and M. catarrhalis that were considered pathogens in respiratory tract infections. Data collected for each isolate included species identification, antimicrobial susceptibility profile, date of isolation, and specimen type. Molecular studies were performed on selected isolates. A total of 1,241 bacterial strains were obtained; the majority were cultured from hospitalized patients, while 139 were fastidious organisms from community acquired respiratory tract infections. Gram-negative bacilli and S. aureus were the predominant pathogens, and Enterobacter spp. was a significant pathogen. The predominance of P. aeruginosa and Acinetobacter spp. and the significant levels of resistance to most agents are of major concern, as is the epidemic rate of ESBL-producing strains of Klebsiella spp. and E. coli in Brazil, which is much higher than rates seen in other areas of the world. Resistance among P. aeruginosa and the Enterobacteriaceae to fluoroquinolones, oxacillin-resistant S. aureus, and penicillin- and trimethoprim-sulfamethoxazole-resistant pneumococci were other significant resistance issues identified in this surveillance study. Vancomycin resistance among the enterococci, S. aureus, and S. pneumoniae was not identified. This benchmark study will serve as comparison for future surveillance studies, including the ongoing SENTRY program, to monitor emerging resistance trends in Brazil. The high rates of resistance observed in this study underscore the need for global surveillance and local action.

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Evaluation of the in vitro Activity of Cefprozil Relative to Other Oral Antimicrobial Agents Against Bacteria in Clinical Specimens from Patients in São Paulo With Respiratory Tract Infections.

Cefprozil is a new oral second generation cephalosporin. Its in vitro antimicrobial activity was evaluated against 371 recent clinical isolates from patients with respiratory infections. We tested the susceptibility of 244 streptococci (96 Streptococcus pneumoniae, 105 group viridans streptococci, 32 Streptococcus agalactiae, and 11 group A beta-hemolitic streptococci) 107 Haemophilus influenzae, and 20 oxacillin-susceptible S.aureus (OSSA). The isolates were susceptibility tested against cefprozil, cefaclor and amoxicillin/clavulanic acid by the E-test method; and against cefadroxil, cefuroxime, cefetamet, erythromycin, and azythromycin by disk diffusion. The methods and the susceptibility categorization followed the National Committee for Clinical Laboratory Standards (NCCLS) procedures. Amoxicillin/clavulanic acid was slightly more active againstH.influenzae (MICs(90) 0.5µg/mL) than cefprozil or cefaclor (MICs(90) 4 and 2µg/mL respectively). Cefprozil demonstrated potent activity against streptococci. Against S.pneumoniae, cefprozil was 2-4 fold more active than cefaclor (MICs(90)0.125 and 0.38µg/mL, respectively). S. pneumoniae susceptibility was 84% to penicillin, 95% to erythromycin and 97% to azithromycin by disk diffusion. Viridans streptococci showed higher MICs for cefprozil and cefaclor (MICs(90) 4µg/mL and 8µg/mL, respectively) and only 50% susceptibility to the macrolides. Cefprozil was four times more active than cefaclor and as active as amoxieillin/clavulanic acid against group A beta-hemolytic streptococci and S.agalactiae. These three compounds showed similar activity against OSSA. In conclusion, cefprozil demonstrated excellent in vitro activity against bacterial species responsible for respiratory infections in São Paulo.

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Vancomycin-Resistant Enterococcus faecium: First Case in Brazil.

We report a fatal case of septicemia due to a vancomycin-resistant Enterococcus faecium in a 9 year old girl with aplastic anemia. The isolate was also resistant to ampicillin, teicoplanin, gentamicin (high level), and streptomycin (high level). We believe that this is the first case of vancomycin-resistant Enterococcus (VRE) reported from a clinical specimen in Brazil.

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Piperacillin/Tazobactam: Evaluation of Its In vitro Activity against Bacteria Isolated in Two Brazilian Hospitals and an Overview of Its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Potential.

Piperacillin/tazobactam is a highly active antibiotic against most clinically important species of Gram-negative and positive bacteria, including anaerobes. It has never been used or tested against bacteria isolated in Brazil. In this article we report the in vitro activity of piperacillin/tazobactam against clinical isolates from two tertiary hospitals in São Paulo and Rio de Janeiro and review the evolving clinical literature. The study was performed before its commercialization in Brazil. Its activity was compared to that of several broad-spectrum antimicrobial agents commercially available in Brazil. Piperacillin/tazobactam was active against 83% of the isolates tested, while imipenem was active against 91%, cefepime 77%, and ciprofloxacin 73%. Against Enterobacteriaceae (n=398), cefepime was more active than piperacillin/tazobactam (92% versus 88%). Klebsiella pneumoniae strains (n=95) presented low susceptibility to piperacillin/tazobactam (79%), ceftazidime (67%), and to cefepime (82%) indicating a high percentage of ESBL-producing strains. The most active compounds against this species were imipenem (100%) and ciprofloxacin (93%). Piperacillin/tazobactam was the most active compound against Gram-positive cocci (n=238; percentage of susceptibility rank order: piperacillin/tazobactam = imipenem > ciprofloxacin > cefepime) and the second most active against nonenteric Gram-negative bacilli (n=250, rank order: imipenem [72%] > piperacillin/tazobactam [60%] > cefepime [56%] > ceftazidime [52%] > gentamicin [45%] > ciprofloxacin = aztreonam [42%]). Cefepime was the most active compound against P. aeruginosa (n=128, only 67%), followed by ceftazidime (64%), piperacillin/tazobactam (63%) and imipenem (59%). Only imipenem (91%) was active against more than 50% of the A. baumannii isolates (n=79) tested. Piperacillin/tazobactam was the second most active compound against A. baumannii (49%) and the most active against B. cepacia (91%). Our results demonstrated a high level of antimicrobial resistance in the hospitals evaluated, especially among nonenteric Gram-negative bacilli; and clonal dissemination of multiresistant strains. Piperacillin/tazobactam may contribute to the treatment of nosocomial infections in Brazil, however, some degree of resistance was detected in some species in the instance of frequent multiresistant bacteria in the tertiary level hospitals where the drug was evaluated.

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Antimicrobial Susceptibility of Klebsiella pneumoniae Producing Extended-Spectrum beta-lactamase (ESBL) Isolated in Hospitals in Brazil.

The prevalence of klebsiella pneumoniae producing extended-spectrum beta-lactamase (ESBL) has been increasing all over the world. Infections caused by ESBL producing isolates are difficult to detect with current susceptibility tests, and are difficult to treat. ESBLs confer resistance to all currently available beta-lactam, except carbapenems. In addition, ESBL production is usually associated with resistance to other classes of antimicrobial agents such as aminoglycosides and quinolones. The objective of this study was to evaluate the in vitro susceptibility patterns of ESBL producing K pneumoniae isolated in Brazil. Seventy-two strains were tested using E test against 30 antimicrobial agents, including carbapenems, second and third generation cephalosporins, aminoglycosides, quinolones, and some new compounds. The most active compounds (i.e. 100% susceptibility) were meropenem (MIC90, 0.125µg/mL), imipenem (MIC90, 0.25µg/mL), and cefotetan (MIC90, 2µg/mL). Ciprofloxacin (MIC90, 1µg/mL, 94% susceptibility) and cefepime (MIC90, 6µg/mL, 92% susceptibility), were also very active against our collection of ESBL producing K pneumoniae. None of the six aminoglycosides showed good activity against these strains (16% to 41% susceptibility) and only 39% of the isolates were susceptible to piperacillin/tazobactam. The results of our study indicated that the carbapenems are the most active compounds against ESBL producing L pneumoniae in Brazil, and ciprofloxacin remains very active against these strains. Cefotetan and cefepime were also very active against ESBL producing K.pneumoniaein Brazil; however, further studies are necessary to evaluate the role of these cephalosporins in the treatment of infections due to ESBL producing strains.

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Comparative in vitro Activity of Meropenem Versus Other Extended-Spectrum Antimicrobial Agents Against 2,085 Clinical Isolates Tested in 13 Brazilian Centers.

Meropenem is a parenteral carbapenem antibacterial agent with a very broad spectrum of antibacterial activity. It is the second agent of its class to become available in Brazil. The in vitro antibacterial activity of meropenem was compared with imipenem and four other antimicrobial agents in a multicenter study. This study involved 13 clinical microbiology laboratories, 10 of which came from 8 Brazilian states. A total of 2,085 clinical isolates consecutively collected between December 1995 and March 1996 were susceptibility tested using the Etest and following the NCCLS procedures. Meropenem inhibited more than 90% of isolates of Enterobacteriaceae at 0.5 µg/mL, except for Citrobacter sp. (1 µg/ml). Generally, meropenem was slightly more active than imipenem against Gram-negative organisms and its spectrum of antimicrobial activity was broader than those of all other drugs tested. Against Pseudomonas aeruginosa, meropenem (MIC50, 0.38 µg/ml) was approximately 8-fold more active than imipenem (MIC 50,3 µg/mL). Imipenem was two-to eight-fold more active than meropenem against some Gram-positive specees oxacillin, including Enterococcus faecalis (MIC 50 of 0.75 µg/mL and 2 µg/mL respectively), oxacillin-susceptible Staphylococcus aureus (MIC 50 of 0.47 &mul;g/mL and 0.094 µg/mL), oxacillin-susceptible Staphylococcus epidermidis (MIC 50 of 0.064 µg/mL and 0.5mg/mL). Against Streptococcus sp. meropenem was slightly more active than imipenem (MIC 50, 0.016 µg/mL). The results of this study may be used to guide empiric therapy in Brazil and indicates that meropenem may have an important role in the treatment of infections caused by multiresistant strains of bacteria.

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