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Helio S Sader

Publications and source records attributed to Helio S Sader.

At least 37 records · Page 2Linked to original sources
PubMed2006

Spectrum and potency of dalbavancin tested against 3322 Gram-positive cocci isolated in the United States Surveillance Program (2004).

Dalbavancin is an injectable, next generation lipoglycopeptide with an extended serum elimination half-life. Once-weekly dosing has been successful for treatment of skin and skin structure (SSSI) and catheter-related bloodstream infections (CR-BSI). Concurrent with clinical trails, dalbavancin resistance surveillance was initiated in 2003, and results are reported here for the 2004 United States (USA) component. A total of 3322 Gram-positive cocci were tested by reference broth microdilution methods. Organism species tested included: Staphylococcus aureus (2102; 49% oxacillin-resistant), coagulase-negative staphylococci (CoNS; 255, 82% oxacillin-resistant), beta-hemolytic streptococci (241), viridans group streptococci (46), and Streptococcus pneumoniae (678). Dalbavancin (MIC90,0.06-0.12 microg/mL) was comparable in spectrum, but superior in potency to vancomycin (MIC90,1-2 microg/mL) against staphylococci. Dalbavancin MIC90 values against the tested streptococci was 0.03 microg/mL. Dalbavancin was more active against tested SSTI pathogens than comparator agents having complete susceptibility rates (100.0%) similar to vancomycin. Vancomycin, (16- to 32-fold), linezolid (8- to 32-fold), daptomycin (4- to 32-fold), and quinupristin/dalfopristin (4- to 32-fold) were less active than dalbavancin. In conclusion, dalbavancin exhibited greater potency than comparison glycopeptides or lipopeptides, streptogramin combinations, and oxazolidinones against Gram-positive pathogens associated with SSSI or CR-BSI. Dalbavancin wild-type MIC distributions remain unchanged compared with prior sampled years (2002-2003) in the USA.

Anti-Bacterial Agents↗
PubMed2006

Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000-2004).

Emergence and dissemination of Enterobacteriaceae isolates harboring carbapenemases in various geographic regions represents a significant threat to the management of nosocomial infections. Enterobacteriaceae isolates from the SENTRY Antimicrobial Surveillance Program (2000-2004) demonstrating decreased susceptibility to imipenem and meropenem (minimum inhibitory concentration [MIC], > or =2 mg/L) were evaluated for the production of metallo-beta-lactamases and serine carbapenemases using disk approximation and polymerase chain reaction (PCR) tests. Carbapenemase-producing strains were epidemiologically typed by automated riboprinting and pulsed-field gel electrophoresis (PFGE) to establish clonality. Among 37,557 Enterobacteriaceae (5 genus groups) evaluated, 119 (0.32%) had increased carbapenem MIC values, and a carbapenemase was identified in 51 (42.9%) of these strains. KPC-2 and KPC-3 were the most frequently occurring carbapenemases (24 isolates, 20.2%) in the United States and were detected in Klebsiella spp, Citrobacter spp., Enterobacter spp., and Serratia marcescens strains isolated in New York, Arkansas, and Virginia. SME-2-producing S. marcescens were isolated in the New York City area, Texas, and Ohio, while NMC-A was found in one E. cloacae strain from New York. In contrast, metallo-beta-lactamases were prevalent in Europe. IMP-1-producing E. cloacae (11 isolates) were detected in Turkey, while VIM-1-producing strains were found in Italy (Enterobacter spp.) and Greece (Klebsiella pneumoniae). Clonal dissemination of carbapenemase-producing strains was observed in several medical centers on both continents. The occurrence of carbapenemases in various Enterobacteriaceae remains rare but appears to be spreading geographically (not in Latin America), mainly with metallo-beta-lactamases being found in Mediterranean Europe and KPC enzymes in the New York City area.

Anti-Bacterial Agents↗
PubMed2006

Activity of retapamulin (SB-275833), a novel pleuromutilin, against selected resistant gram-positive cocci.

Retapamulin (SB-275833), the first pleuromutilin to be developed for human topical use, was tested against a selected population of staphylococci and beta-hemolytic streptococci. The MIC90 results for retapamulin were 0.12 microg/ml for Staphylococcus aureus and < or = 0.03 microg/ml for Streptococcus pyogenes; no cross-resistance was observed for organism subsets resistant to oxacillin, erythromycin, or mupirocin.

Anti-Bacterial Agents↗
PubMed2006

Daptomycin bactericidal activity and correlation between disk and broth microdilution method results in testing of Staphylococcus aureus strains with decreased susceptibility to vancomycin.

A total of 207 Staphylococcus aureus strains, including 105 well-characterized strains with decreased susceptibility to vancomycin (17 vancomycin-intermediate S. aureus [VISA] and 88 heteroresistant VISA [hVISA] strains) and 102 wild-type methicillin-resistant S. aureus (MRSA-WT) strains were tested by reference/standardized broth microdilution and disk diffusion methods, as well as by Etest (AB BIODISK, Solna, Sweden), against daptomycin and vancomycin. The lowest concentration of antimicrobial agent that killed > or = 99.9% of the initial inoculum was defined as the minimum bactericidal concentration (MBC) endpoint, and time-kill curves were performed in selected strains to further evaluate bactericidal activity. All MRSA-WT and hVISA strains were inhibited by < or = 1 microg/ml of daptomycin, while the VISA strains showed slightly higher daptomycin MICs (range, 0.5 to 4 microg/ml). All daptomycin MBC results were at the MIC or twofold higher. In contrast, 14.7% of MRSA-WT, 69.3% of hVISA, and all VISA strains showed a vancomycin MBC/MIC ratio of > or = 32 or an MBC of > or = 16 microg/ml (tolerant). The correlation coefficients between broth microdilution and disk diffusion method results were low for daptomycin (0.07) and vancomycin (0.11). Eight (3.8%) strains (all hVISA or VISA) were "nonsusceptible" to daptomycin by broth microdilution methods but susceptible by the disk diffusion method. For vancomycin, 35 (16.9%) strains were nonsusceptible by broth microdilution methods but susceptible by disk diffusion methods. In conclusion, daptomycin was highly bactericidal against S. aureus strains, and its bactericidal activity was not affected by decreased susceptibility to vancomycin. In contrast, many (one in seven) contemporary MRSA-WT, the majority of hVISA, and all VISA strains showed vancomycin MBC/MIC ratios consistent with tolerance, a predictor of poor clinical response. Disk diffusion tests generally failed to detect strains categorized as nonsusceptible to daptomycin or vancomycin by the reference broth microdilution method or Etest, and reassessment of breakpoints should be immediately attempted for MIC methods suggested as the test of choice.

Anti-Bacterial Agents↗
PubMed2006

Contemporary prevalence of BRO beta-lactamases in Moraxella catarrhalis: report from the SENTRY antimicrobial surveillance program (North America, 1997 to 2004).

A total of 7,860 community-acquired Moraxella catarrhalis isolates (SENTRY Antimicrobial Surveillance Program, 1997 to 2004) were tested by broth microdilution methods, and 399 randomly selected strains from North American sites were tested for BRO-1 and BRO-2 by PCR methods. Several antimicrobials remained very active, including amoxicillin-clavulanate (MIC90s, < or =0.25 microg/ml), azithromycin (MIC90s, < or =0.12 microg/ml), ceftriaxone (MIC90s, 0.5 microg/ml), and levofloxacin (MIC90s, < or =0.03 to 0.06 microg/ml). The BRO-2 incidence rates by year were 3 to 4% overall (96 to 97% for BRO-1) and were the highest in Canada (7.9%), with the incidence in the United States being only 2.0%.

Anti-Bacterial Agents↗
PubMed2006

Selection of a surrogate agent (vancomycin or teicoplanin) for initial susceptibility testing of dalbavancin: results from an international antimicrobial surveillance program.

The immediate lack of market-dominating commercial products (Vitek or MicroScan) for susceptibility testing of the new glycolipopeptide, dalbavancin, requires a surrogate marker agent to assist microbiologists in the correct categorization of potentially indicated species (staphylococci and streptococci). Error-rate analyses for 16,749 isolates using vancomycin or teicoplanin results to categorize dalbavancin susceptibilities demonstrated that both glycopeptide agents were highly predictive of dalbavancin-susceptible results (nearly 100%) with only a rare minor error. Vancomycin test results most reliably predict dalbavancin susceptibility until validated commercial reagents become available for direct testing in clinical practice.

Anti-Bacterial Agents↗
PubMed2006

Accuracy of three automated systems (MicroScan WalkAway, VITEK, and VITEK 2) for susceptibility testing of Pseudomonas aeruginosa against five broad-spectrum beta-lactam agents.

One hundred recent clinical Pseudomonas aeruginosa isolates were used to assess the quantitative (MIC) and qualitative (susceptibility category) accuracies of the MicroScan WalkAway, VITEK, and VITEK 2 automated susceptibility test systems when five-broad spectrum beta-lactams, aztreonam, cefepime, ceftazidime, imipenem, and piperacillin-tazobactam, were tested. Isolates were selected so that the MICs for the isolates overrepresented the MICs near the breakpoints to assess precisely the agreement between the results obtained with the automated systems and the results obtained by the reference tests. The categorical and MIC results from the automated systems were compared to the consensus result of three reference methods: broth microdilution, agar dilution, and disk diffusion. The consensus categorical testing (susceptibility and resistance) rates were 47 and 27%, respectively, for aztreonam; 59 and 14%, respectively, for cefepime; 44 and 43%, respectively, for ceftazidime; 71 and 19%, respectively, for imipenem; and 50 and 50%, respectively, for piperacillin-tazobactam. All systems tested exhibited a high, unacceptable level of very major (false-susceptible) errors for piperacillin-tazobactam (19 to 27%). Major (false-resistant) error rates were generally acceptable (0 to 3%), but minor error rates were elevated (8 to 32%) for cefepime (VITEK 2 and VITEK) and for aztreonam (all three systems), leading to consistent trends toward false resistance. Manufacturer reevaluation of these automated systems for the testing of selected beta-lactams with current clinical isolates of P. aeruginosa that exhibit contemporary resistance mechanisms would be prudent to minimize the potential for serious reporting errors.

Bacteriological Techniques↗
PubMed2006

Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?

Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI) is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI) broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66%), followed by Klebsiella spp. (7%), Proteus mirabilis (6.4%), Enterococcus spp. (5.6%), and Pseudomonas aeruginosa (4.6%). Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6%), TMP/SMX (40.4%), ciprofloxacin (21.6%), and gatifloxacin (17.1%). Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4%, respectively), and P. mirabilis (71.8 and 84.6%, respectively). For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1%, respectively. High-level resistance to gentamicin was detected in 24% of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.

Adult↗
PubMed2005

Oxazolidinone susceptibility patterns in 2004: report from the Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program assessing isolates from 16 nations.

OBJECTIVES: To investigate the activity of linezolid (an oxazolidinone), a potent choice for community- and hospital-acquired infections, via a worldwide surveillance network called the Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program. METHODS: A total of 4098 Gram-positive strains were collected from 42 laboratories located in North America (five sites in Canada), South America (10 sites), Europe (16 sites) and the Far East (11 sites). Each country or site submitted 200 isolates (Canada submitted 200 isolates for each of five sites; total 1000) for confirmation of organism identification and reference MIC processing. Nearly 25 comparator agents were tested along with quality control strains, and interpretative criteria from the CLSI, formerly the NCCLS, M100-S15 were applied. No linezolid resistance was detected in strains from 16 monitored countries in 2004. RESULTS: Linezolid remained highly active against Streptococcus pneumoniae, viridans group and beta-haemolytic streptococci (MIC90, 1 mg/L). Against Staphylococcus aureus, linezolid showed 99.5% of results at 0.5-2 mg/L with only one isolate at 4 mg/L. Oxacillin-resistant S. aureus rates varied between nations and ranged from 1.4% in Sweden to 29.5% in the UK to 65.2% in Mexico. Linezolid MIC values were generally one log2 dilution step lower for coagulase-negative staphylococci (CoNS) when compared with S. aureus. No CoNS strains produced a linezolid result at 4 mg/L. Compared with ZAAPS 2002 and 2003 results for enterococci where seven resistant strains were identified, the 2004 data revealed no resistance and 98.1% of linezolid MIC results were at 1 or 2 mg/L. Vancomycin-resistant enterococci (5.3% overall) varied markedly by country including a high of 47.2% in Korea. CONCLUSIONS: Linezolid continues to be effective in vitro against Gram-positive pathogens from five continents and no oxazolidinone-resistant strains were identified among the 4098 systemically collected strains (2004) or among 20 158 non-United States isolates for the entire ZAAPS Program (2002-04).

Acetamides↗
PubMed2005

Antimicrobial susceptibility patterns of unusual nonfermentative gram-negative bacilli isolated from Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2002).

The antimicrobial susceptibility of 176 unusual non-fermentative gram-negative bacilli (NF-GNB) collected from Latin America region through the SENTRY Program between 1997 and 2002 was evaluated by broth microdilution according to the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. Nearly 74% of the NF-BGN belonged to the following genera/species: Burkholderia spp. (83), Achromobacter spp. (25), Ralstonia pickettii (16), Alcaligenes spp. (12), and Cryseobacterium spp. (12). Generally, trimethoprim/sulfamethoxazole (MIC50, < 0.5 microg/ml) was the most potent drug followed by levofloxacin (MIC50, 0.5 microg/ml), and gatifloxacin (MIC50, 1 microg/ml). The highest susceptibility rates were observed for levofloxacin (78.3%), gatifloxacin (75.6%), and meropenem (72.6%). Ceftazidime (MIC50, 4 microg/ml; 83.1% susceptible) was the most active beta-lactam against B. cepacia. Against Achromobacter spp. isolates, meropenem (MIC50, 0.25 microg/ml; 88% susceptible) was more active than imipenem (MIC50, 2 microg/ml). Cefepime (MIC50, 2 microg/ml; 81.3% susceptible), and imipenem (MIC50, 2 microg/ml; 81.3% susceptible) were more active than ceftazidime (MIC50, >16 microg/ml; 18.8% susceptible) and meropenem (MIC50, 8 microg/ml; 50% susceptible) against Ralstonia pickettii. Since selection of the most appropriate antimicrobial agents for testing and reporting has not been established by the NCCLS for many of NF-GNB species, results from large multicenter studies may help to guide the best empiric therapy.

Anti-Bacterial Agents↗
PubMed2005

Antimicrobial activity of daptomycin tested against clinical strains of indicated species isolated in North American medical centers (2003).

Daptomycin is a cyclic lipopeptide approved for use by the US Food and Drug Administration (FDA) for the treatment of complicated skin and skin structure infections caused by Staphylococcus aureus, groups A and B beta-hemolytic streptococci, and vancomycin-susceptible Enterococcus faecalis. We evaluated the daptomycin spectrum against these pathogens by testing 2759 clinical strains consecutively collected in more than 30 hospitals located across the United States and Canada. The isolates were susceptibility tested against daptomycin and many comparators by the reference broth microdilution method. Daptomycin was very active against indicated species with the highest MIC results being 1, 2, and 0.5 microg/mL for S. aureus, E. faecalis, and beta-hemolytic streptococci, respectively. All isolates tested were considered susceptible to daptomycin, according to Clinical and Laboratory Standards Institute and FDA breakpoints, and daptomycin was the most potent (lowest MIC90) among selected antimicrobials commonly used to treat Gram-positive infections. Resistance to oxacillin or vancomycin did not influence daptomycin activity against S. aureus or E. faecalis.

Academic Medical Centers↗
PubMed2005

Susceptibility patterns for amoxicillin/clavulanate tests mimicking the licensed formulations and pharmacokinetic relationships: do the MIC obtained with 2:1 ratio testing accurately reflect activity against beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis?

Amoxicillin/clavulanate has recently undergone formulation changes (XR and ES-600) that represent 14:1 and 16:1 ratios of amoxicillin/clavulanate. These ratios greatly differ from the 2:1 ratio used in initial formulations and in vitro susceptibility testing. The objective of this study was to determine if the reference method using a 2:1 ratio accurately reflects the susceptibility to the various clinically used amoxicillin/clavulanate formulations and their respective serum concentration ratios. A collection of 330 Haemophilus influenzae strains (300 beta-lactamase-positive and 30 beta-lactamase-negative) and 40 Moraxella catarrhalis strains (30 beta-lactamase-positive and 10 beta-lactamase-negative) were tested by the broth microdilution method against eight amoxicillin/clavulanate combinations (4:1, 5:1, 7:1, 9:1, 14:1, and 16:1 ratios; 0.5 and 2 microg/mL fixed clavulanate concentrations) and the minimum inhibitory concentration (MIC) results were compared with those obtained with the reference 2:1 ratio testing. For the beta-lactamase-negative strains of both genera, there was no demonstrable change in the MIC values obtained for all ratios analyzed (2:1 to 16:1). For the beta-lactamase-positive strains of H. influenzae and M. catarrhalis, at ratios >or=4:1 there was a shift in the central tendency of the MIC scatterplot compared with the results of testing 2:1 ratio. As a result, there was a 2-fold dilution increase in the MIC(50) and MIC(90) values, most evident for H. influenzae and BRO-1-producing M. catarrhalis strains. For beta-lactamase-positive strains of H. influenzae, the shift resulted in a change in the interpretive result for 3 isolates (1.0%) from susceptible using the reference method (2:1 ratio) to resistant (8/4 microg/mL; very major error) at the 16:1 ratio. In addition, the number of isolates with MIC values at or 1 dilution lower than the breakpoint (4/2 microg/mL) increased from 5% at 2:1 ratio to 32-33% for ratios 14:1 and 16:1. Our results indicate that, for the beta-lactamase-positive strains of H. influenzae and M. catarrhalis, the results of the amoxicillin/clavulanate reference 2:1 ratio testing do not accurately represent all the currently licensed formulations. Pharmacokinetic/pharmacodynamic (PK/PD) target attainment might be compromised when higher amoxicillin/clavulanate ratios are used clinically. With a better understanding of PK/PD parameters, reevaluation of the amoxicillin/clavulanate in vitro susceptibility testing should be considered by the standardizing authorities to reflect the licensed formulations and accurately predict clinical outcomes.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2005

Evaluation of PPI-0903M (T91825), a novel cephalosporin: bactericidal activity, effects of modifying in vitro testing parameters and optimization of disc diffusion tests.

OBJECTIVES: To evaluate bactericidal activity of PPI-0903M and in vitro testing parameters for this compound. METHODS: A total of 110 strains were tested to determine MIC and MBC values of PPI-0903M. MIC values were determined by reference broth microdilution whereas MBC was assessed by plating the broth from the MIC well and from those wells above the MIC for each organism onto appropriate drug-free growth media. Seventeen strains were tested by the kill-curve methodology to again evaluate the bactericidal activity of PPI-0903M. Broth microdilution results for 15 strains (in triplicate) were compared with the standard, reference method after modifying several testing parameters. Optimal disc content was assessed by testing seven reference strains with five PPI-0903M disc concentrations (5, 10, 30, 50 and 100 microg). RESULTS: PPI-0903MMBC/MIC ratios were < or = 4 in 90% of strains tested. Kill-curve studies showed >99.9% killing at concentrations < or = 4x MIC within 8 to 24 h against staphylococci and Enterobacteriaceae tested. PPI-0903M MIC results were rarely influenced by the test or medium changes evaluated [high inoculum, low calcium or reduced pH (5.0)]. Human serum had no effect on in vitro antimicrobial activity of PPI-0903M. The 10 microg disc content would be recommended for optimal correlation of MIC breakpoints of < or = 1-4 mg/L. CONCLUSIONS: PPI-0903M was generally bactericidal against tested species, and the MIC results were stable across numerous susceptibility test condition changes.

Anti-Bacterial Agents↗
PubMed2005

Emerging metallo-beta-lactamase-mediated resistances: a summary report from the worldwide SENTRY antimicrobial surveillance program.

The rates of occurrence of metallo-beta-lactamase-mediated resistances in Pseudomonas aeruginosa, Acinetobacter species, and Serratia marcescens, among other gram-negative bacilli, have escalated since 2000, severely limiting treatment options in Asia, Europe, and Latin America to non-beta-lactam antimicrobial classes. Clinical isolates harboring metallo-beta-lactamases have also recently been reported in western Canada and in Texas, signaling the need for development of accurate diagnostic tests by clinical laboratories to detect their presence and for new, and more potent, antimicrobial agents.

Acinetobacter↗
PubMed2005

Susceptibility testing accuracy of a CTX-M-type extended-spectrum beta-lactamase organism-producing population of Enterobacteriaceae: intermethod analysis for 9 beta-lactams.

To assess the wide geographical applicability of the current and proposed susceptibility breakpoint criteria for 9 beta-lactam antimicrobials, the performance characteristics of 2 standardized methods were analyzed by testing a contemporary collection of 354 isolates of Enterobacteriaceae, enriched (76; 21.5%) for extended-spectrum beta-lactamase (ESBL)-producing strains. Molecular characterization of 57 ESBL strains revealed that majority of the strains (94.7%) were CTX-M type, with a predominance (85.2%) of CTX-M-14 and -3 types, those types prevalent in China. Bloodstream isolates constituted 68.6% of the entire collection. The 9 beta-lactam antimicrobials analyzed were aztreonam, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, ceftizoxime, and cefuroxime. Reference broth microdilution minimal inhibitory concentration (MIC) results were compared to those zone diameters obtained by disk diffusion testing. The regression coefficient was acceptable for most antimicrobials, ranging from r = 0.84 (cefotetan) to r = 0.98 (cefotaxime, cefuroxime, and ceftriaxone). Using the current breakpoint criteria, the absolute intermethod categorical agreement was acceptable for 8 of the 9 antimicrobials (not cefoxitin, 85.1%) ranging from 92.6% (cefotaxime) to 97.8% (ceftazidime). Very major (false-susceptible) and major (false-resistant) errors were nil (0.0%) for 5 of the beta-lactams and minor errors ranged from 0.8% (cefotetan) to 14.1% (cefoxitin). The proposed (generally lower) MIC breakpoint criteria also had acceptable intermethod concordance ranging from 91.6% (cefoxitin) to 99.2% (cefotaxime and ceftriaxone). Furthermore, an improvement in the intermethod absolute categorical agreement ranging from +0.8% (ceftazidime) to +6.6% (cefotaxime) was observed for 7 of 9 antimicrobials tested, including the ESBL screening test compounds (aztreonam, ceftazidime, cefotaxime, and ceftriaxone). No modification of the susceptible breakpoint criteria, with removal of the intermediate category, was proposed for cefoxitin and cefuroxime, resulted in a shift of error type from minor to major or very major, but the categorical agreement improved (+ >or=1.2%) for both cephems. In conclusion, our results confirm that both the current and the proposed MIC breakpoint criteria with appropriately selected zone diameter correlates have acceptable intermethod error rates even when tested against an Enterobacteriaceae collection enriched with CTX-M-type ESBL-producing strains that are endemic in locations (China) outside the United States.

Anti-Bacterial Agents↗