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Helio S Sader

Publications and source records attributed to Helio S Sader.

At least 55 records · Page 3Linked to original sources
PubMed2005

Antimicrobial activity of LBM415 (NVP PDF-713) tested against pathogenic Neisseria spp. (Neisseria gonorrhoeae and Neisseria meningitidis).

LBM415 (NVP PDF-713), a novel peptide deformylase inhibitor, was tested by reference methods against 2 collections of pathogenic Neisseria, N. gonorrhoeae (157 strains) and N. meningitidis (100 strains). The collection included strains resistant to penicillin, tetracycline, and fluoroquinolones and were also tested against ceftriaxone, ciprofloxacin, penicillin, and tetracycline. The 50% and 90% minimum inhibitory concentration values for LBM415 were 1 and 2 microg/mL, and 4 and 8 microg/mL for N. meningitidis and N. gonorrhoeae, respectively. All comparison agents were more active than this peptide deformylase inhibitor against this genus.

Anti-Bacterial Agents↗
PubMed2005

Reproducibility of gemifloxacin and comparison fluoroquinolone MIC results using Sensititre commercial dry-form panels.

This study examined the ability of commercial dry-form broth microdilution panels (Sensititre, TREK Diagnostics, Cleveland, OH) to produce accurate minimum inhibitory concentration (MIC) results for gemifloxacin, a new fluoroquinolone. Reproducibility for gemifloxacin was 100.0% for on-scale values within +/-1 log2 dilution for same- and between-day comparisons. Newer comparator fluoroquinolones (sparfloxacin, sitafloxacin, and moxifloxacin) also showed excellent reproducibility (100.0%) for on-scale results analyzed at +/-1 log2 dilution for same- and between-day comparisons. Newer and investigational fluoroquinolone agents, including gemifloxacin, can be tested with confidence using these dry-form MIC panels.

Anti-Bacterial Agents↗
PubMed2005

Reevaluation of the cefepime minimal inhibitory concentrations and disk diffusion test zone diameter relationship for a worldwide collection of Enterobacteriaceae enriched for extended-spectrum beta-lactamase-producing organisms.

To reassess the validity of existing susceptibility breakpoint criteria and to propose alternative breakpoint criteria for disk diffusion testing at lower susceptible MIC breakpoints, we analyzed a contemporary global collection of Enterobacteriaceae isolates (350) strains enriched for extended-spectrum beta-lactamase (ESBL) producers (68 strains, 19.4%). The majority of the isolates (88.3% of the entire collection and 83.8% of the ESBL subset) were from bloodstream infections. Cefepime minimal inhibitory concentrations (MICs) were determined by broth microdilution methods and compared with the results obtained from disk diffusion testing for the entire collection of Enterobacteriaceae and for the ESBL subset alone. The regression coefficient was excellent for both scattergrams (r = 0.92-0.94). The intermethod categorical agreement remained excellent for the current breakpoints (susceptible at < or = 8 microg/mL or > or = 18 mm and resistant at > or = 32 microg/mL or < or = 14 mm) published by the National Committee for Clinical Laboratory Standards at 94.0%. The 2 alternative interpretive criteria considered at lower MIC breakpoints (i.e., susceptible as < or = 4 microg/mL and > or = 21 mm and susceptible as < or = 2 microg/mL and > or = 24 mm) did not compromise the intermethod test categorical accuracy, which remained excellent at 96.9% and 94.0%, respectively. Adopting the existing breakpoint criteria that remain accurate for ESBL-producing strains or any one of the above two alternative sets of breakpoint criteria analyzed would be acceptable, with excellent intermethod concordance between the MIC and disk diffusion results.

Anti-Bacterial Agents↗
PubMed2005

Comparative activity of doripenem and three other carbapenems tested against Gram-negative bacilli with various beta-lactamase resistance mechanisms.

Doripenem (formerly S-4661), a novel carbapenem antimicrobial, was compared with ertapenem, imipenem, and meropenem using reference broth microdilution test methods against wild-type and various resistant microbial subsets (380 strains). Doripenem and meropenem were consistently more potent than ertapenem or imipenem when tested against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. Ertapenem exhibited minimum inhibitory concentration (MIC) elevations for some isolates producing AmpC and extended-spectrum beta-lactamases, in contrast to greater enzyme stability for doripenem and other carbapenems tested. Multiple beta-lactamase (TEM, SHV, CTX-M, OXA, CMY types)-producing Escherichia coli had doripenem MIC values at </=0.016 mug/mL (with higher values for ertapenem). Doripenem appears to be a promising, potent carbapenem for parenteral use against contemporary Gram-negative bacilli producing various beta-lactamases.

Anti-Bacterial Agents↗
PubMed2005

Therapeutic options among broad-spectrum beta-lactams for infections caused by levofloxacin-nonsusceptible Streptococcus pneumoniae.

Streptococcus pneumoniae has consistently become more resistant to primary, orally administered treatment regimens used for community-acquired respiratory tract infections (CARTI; sinusitis, bronchitis, pneumonia). As resistance rates approach 40-50% in the United States and North America for penicillin and macrolides, other agents also have exhibited coresistance rates of 10-20% (tetracycline, clindamycin, trimethoprim/sulfamethoxazole). These facts led to altered clinical treatment guidelines (IDSA) supporting the use of respiratory fluoroquinolones (levofloxacin, gatifloxacin, gemifloxacin, and moxifloxacin). This report from the SENTRY Antimicrobial Surveillance Program lists possible parenterally administered treatment alternatives for the fluoroquinolone (levofloxacin)-nonsusceptible pneumococci. The SENTRY Program isolates from CARTI (1997-2003), totaling 21605 strains from Europe, Asia Pacific, and the Americas, were screened for fluoroquinolone-resistant S. pneumoniae. A total of 157 (0.7%) levofloxacin-nonsusceptible (MIC > or = 4 microg/mL) strains were identified and tested by reference broth microdilution methods against 27 antimicrobials. Quinolone resistance-determining region (QRDR) mutations were determined by PCR amplification and gene sequencing. The entire population of S. pneumoniae had the following antibiogram demographics: penicillin-nonsusceptible (32%), macrolide resistance (24%), tetracycline resistance (21%), clindamycin resistance (11%), trimethoprim/sulfamethoxazole resistance (33%), and 6% of strains were resistant to all 5 drugs. Levofloxacin-resistant strains routinely had 2 or more QRDR mutations most frequently in gyrA at Ser81Phe or Tyr and in parC at Ser79Phe or Tyr and Lys137Asn. Four agents had extremely low rates of resistance when tested against the 157 levofloxacin-nonsusceptible strains (e.g., quinupristin/dalfopristin, 0% resistance; vancomycin, 0%; cefepime, 1%; ceftriaxone, 1%). Levofloxacin-nonsusceptible pneumococcal isolates remain uncommon, but are a growing problem in CARTI (1.4% in 2003), especially in previously fluoroquinolone-treated cases. Parenteral cephalosporins (cefepime or ceftriaxone) continue to be potent and safe for use in hospitalized patients with S. pneumoniae community-acquired pneumonia, used with or without co-drugs according to published guidelines.

Anti-Bacterial Agents↗
PubMed2005

Trends in linezolid susceptibility patterns in 2002: report from the worldwide Zyvox Annual Appraisal of Potency and Spectrum Program.

Oxazolidinones have become reliable clinical and candidate antimicrobial agents to be utilized for infections caused by multidrug-resistant Gram-positive cocci, especially vancomycin-resistant enterococci and methicillin-resistant staphylococci. However, mutational resistance of the ribosomal target has been described for several species. Longitudinal surveillance remains necessary to monitor for this evolving linezolid resistance pattern. A survey of linezolid and several comparison Gram-positive focused agents was initiated in 2002 (7971 strains, >99.0% compliance) for 54 participating sites in the United States, Canada, Europe (6 nations), Latin America (2 nations), and the Asia Pacific (2 nations). The 5 and 25 sites in Canada and the United States, respectively, submitted 200 strains each to a central laboratory for organism identification/confirmation and reference MIC processing. The 10 remaining nations had 200 strain samples from 1 to 4 separate institutions. Linezolid resistance (MIC >/= 8 microg/mL) was confirmed by alternative susceptibility testing methods (Etest, AB BIO Disk, Solna, Sweden; disk diffusion method) and target mutation characterization by PCR and sequence analysis. Linezolid activity against the 6 major organism groups did not vary between geographic areas. A total of 98.1% of linezolid MIC values were between 0.5 and 2 microg/mL, and only 0.5% of results were at 4 microg/mL, which included 32 Staphylococcus aureus (0.9%) and 5 (0.5%) enterococcal isolates. Linezolid resistance was detected in only 4 isolates (0.05%): 1 each Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, and a viridans group Streptococcus. All 4 isolates had a G2576U mutation in the 23S rRNA target. Linezolid activity as outlined by these Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program results demonstrate sustained, near complete activity against contemporary Gram-positive isolates on 4 monitored continents and in centers utilizing oxazolidinones. Rare linezolid-resistant strains were identified in the United States only (0.05% resistance overall).

Acetamides↗
PubMed2005

Potency and spectrum trends for cefepime tested against 65746 clinical bacterial isolates collected in North American medical centers: results from the SENTRY Antimicrobial Surveillance Program (1998-2003).

We evaluated the antimicrobial spectrum and potency of cefepime and selected comparators agents against clinical bacterial strains collected in North America over a 6-year period (1998-2003). Isolates were consecutively collected from bloodstream (44%), respiratory tract (41%), urinary tract (6%), and skin/soft tissue (5%) infections in 48 medical centers. Isolates were susceptibility tested by reference broth microdilution methods in a central laboratory. Oxacillin-resistant staphylococci and enterococci were excluded from the analysis. Imipenem (MIC90 = 1 microg/mL, 99.9% susceptible) was the most active compound tested against Enterobacteriaceae (22860 isolates tested) followed by cefepime (MIC90 = 0.25 microg/mL, 99.5% susceptible) > amikacin (99.4% susceptible) > ceftriaxone (95.6% susceptible) > aztreonam (95.1% susceptible). Among comparators, the lowest susceptibility rate for Enterobacteriaceae was observed with ciprofloxacin (92.8% susceptible). Imipenem was also the most active compound against ESBL-producing Klebsiella spp. and Escherichia coli (99.3% and 100% susceptible, respectively), followed by amikacin (81.4% and 97.2% susceptible, respectively) and cefepime (92.5% and 93.8% susceptible, respectively). Cefepime activity against Pseudomonas aeruginosa (85.2% susceptible) was similar to that of imipenem (86.9% susceptible). Against oxacillin-susceptible Staphylococcus aureus, cefepime (MIC90 = 4 microg/mL, 100.0% susceptible) was 4-fold more active than ceftazidime (MIC90 = 16 microg/mL, 86.4% susceptible) and showed a higher susceptibility rate than ciprofloxacin (93.2% susceptible). Cefepime was the most active compound tested against Streptococcus pneumoniae (MIC90 = 1 microg/mL, 97.4% susceptible), ranked after gatifloxacin and levofloxacin (99.2% susceptible). The activity of cefepime remained stable during the study period evaluated with the susceptibility rates varying from 99.3% to 99.8% among the Enterobacteriaceae and 84.4% to 88.4% among P. aeruginosa isolates. In summary, cefepime has retained broad activity and spectrum against Enterobacteriaceae, P. aeruginosa, and Gram-positive cocci (except oxacillin-resistant staphylococci and enterococci) isolated from North American medical centers in the 1998-2003 period. Continued resistance surveillance is critical to monitor the effectiveness of widely used parenteral antimicrobial agents such as cefepime.

Anti-Bacterial Agents↗
PubMed2005

Dalbavancin activity against selected populations of antimicrobial-resistant Gram-positive pathogens.

Dalbavancin, a dimethylaminepropyl amide derivative of the lipoglycopeptide A40926, was tested against 375 antimicrobial-resistant Gram-positive pathogens collected worldwide during 2001-2003. The isolates were tested by reference and Clinical Laboratory Standards Institute broth microdilution susceptibility methods, and dalbavancin was compared with over 20 other antimicrobials. Vancomycin resistance determinants among enterococci were identified using PCR primer sets for vanA and vanB. Dalbavancin was generally more potent than vancomycin or teicoplanin. Dalbavancin was highly active against penicillin- and ceftriaxone-resistant Streptococcus pneumoniae strains (MIC(90), < or = 0.016 microg/mL). Dalbavancin was also very active against teicoplanin-nonsusceptible coagulase-negative staphylococci (CoNS; MIC range, 0.03-0.25 microg/mL), but dalbavancin MIC results were slightly elevated compared with wild type strains. Dalbavancin inhibited vanB enterococci (MIC range, 0.03-0.12 microg/mL) and was active against other resistant, non-vanA enterococcal species. However, vanA enterococcal strains were not as susceptible to dalbavancin (MIC50, 16 microg/mL). In summary, dalbavancin was very active against a wide spectrum of resistant Gram-positive isolates and demonstrated greater potency than vancomycin or teicoplanin.

Anti-Bacterial Agents↗
PubMed2005

Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit.

The antimicrobial activity of tigecycline and selected antimicrobials was evaluated against bacterial pathogens isolated from patients hospitalized in intensive care units (ICUs) worldwide. A total of 9093 isolates were consecutively collected in >70 medical centers in North America (4157), South America (1830), Europe (3034), and the Asia-Australia (72) areas. The isolates were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft tissue (5.5%), and urinary tract (2.0%) infections in the 2000-2004 period, and susceptibility was tested by reference broth microdilution methods. The most frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens (5665) were inhibited at < or =1 microg/mL of tigecycline. Resistance to oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS, and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of < or =1 microg/mL, except for Serratia spp. (2 microg/mL). Extended-spectrum beta-lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme production). These resistance phenotypes did not adversely affect tigecycline activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 microg/mL respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1 microg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline (MIC90, 16 microg/mL). In summary, isolates from ICU patients worldwide showed high rates of antimicrobial resistance. The most alarming problems detected were vancomycin resistance among enterococci, ESBL-mediated beta-lactam resistance and fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro activity against most of clinically important pathogenic bacteria (except P. aeruginosa) isolated from ICU patients and may represent an excellent option for the treatment of infections in this clinical environment.

Anti-Bacterial Agents↗
PubMed2005

Potency and spectrum of tigecycline tested against an international collection of bacterial pathogens associated with skin and soft tissue infections (2000-2004).

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 5289 bacterial isolates recovered from hospitalized patients with skin and soft tissue infections during 2000-2004. Strains were submitted from >70 medical centers in North America, Latin America, and Europe, and were tested centrally using reference broth microdilution methods. The top 10 ranking pathogens (95% of total) recovered included Staphylococcus aureus (55.2%), Enterococcus spp. (9.6%), Pseudomonas aeruginosa (6.4%), Escherichia coli (5.6%), beta-hemolytic streptococci (5.0%), coagulase-negative staphylococci (4.9%), Enterobacter spp. (2.8%), Klebsiella spp. (2.6%), Proteus mirabilis (1.7%), and indole-positive Proteae (1.2%). All staphylococci (S. aureus and coagulase-negative staphylococci), enterococci, beta-hemolytic streptococci, viridans group streptococci, and E. coli were inhibited by < or =2 microg/mL of tigecycline; in addition, 97% of Klebsiella spp., 95% of Enterobacter spp., and 97% of Acinetobacter spp. were inhibited at this concentration. Only P. aeruginosa and all Proteae (MIC90, 16 microg/mL) displayed elevated MIC values to tigecycline. The broad spectrum of activity exhibited by this glycylcycline included tetracycline-resistant organism subsets, as well as oxacillin-resistant S. aureus, vancomycin-resistant enterococci, and extended-spectrum beta-lactamase-producing enteric bacilli strains. Tigecycline represents a new choice among broad-spectrum parenteral agents for the common Gram-positive and -negative pathogens producing serious infections of skin and soft tissues.

Anti-Bacterial Agents↗
PubMed2005

Antimicrobial activity of tigecycline tested against organisms causing community-acquired respiratory tract infection and nosocomial pneumonia.

Emerging antimicrobial resistance among respiratory tract pathogens has created a critical need for development of new antimicrobial agents that are not affected by the commonly occurring genetic resistance mechanisms. Tigecycline, a novel broad-spectrum parenteral glycylcycline, has been shown to be active against many of Gram-positive, Gram-negative, atypical, and anaerobic organisms, including strains highly resistant to commonly prescribed antimicrobials and was recently approved by the US Food and Drug Administration for treating infections of skin and skin structures, and for intra-abdominal infections. In this study, tigecycline spectrum and potency were evaluated against a global collection of pathogens (2000-2004) recovered from community-acquired respiratory infections (7580 strains) or from hospitalized patients with pneumonia (3183 strains). Among community-acquired infections, the ranking pathogens were Haemophilus influenzae (52.9%; 21% ampicillin-resistant), Streptococcus pneumoniae (39.2%; 23.7% penicillin-nonsusceptible), and Moraxella catarrhalis (7.9%). Tigecycline displayed potent activity by inhibiting 100% of the 3 species at clinically achievable concentrations (2, 1, and 0.5 microg/mL, respectively). The 10 most prevalent pathogens producing 94.3% of pneumonias in hospitalized patients were Staphylococcus aureus (48.5% of strains; 49.4% oxacillin-resistant), Pseudomonas aeruginosa (15.6%), Klebsiella spp. (5.6%), S. pneumoniae (4.6%), Acinetobacter spp. (4.5%), Enterobacter spp. (4.0%), Escherichia coli (3.8%), Serratia marcescens (2.5%), Enterococcus spp. (2.3%), Stenotrophomonas maltophilia (1.8%), and beta-hemolytic streptococci (1.1%). At a concentration of 4 microg/mL, tigecycline inhibited >96% of these pathogens (exception, P. aeruginosa). S. aureus was readily inhibited by tigecycline (MIC50 and MIC90, 0.25 and 0.5 microg/mL, respectively) with all strains inhibited at < or =1 microg/mL. Streptococci recovered from hospitalized patients (beta-hemolytic and S. pneumoniae) were also very susceptible to tigecycline with the highest MIC being 0.12 microg/mL. All E. coli (including 13.3% with an extended-spectrum beta-lactamase [ESBL] phenotype) were inhibited by < or =1 microg/mL, and all Klebsiella (25.8% ESBL phenotype) and Enterobacter spp. plus 97.0% of Serratia spp. were inhibited by < or =4 microg/mL. Tigecycline was also active against Acinetobacter spp. and S. maltophilia strains (MIC50 and MIC90, 1 and 4 microg/mL, respectively). Further clinical studies should consider the role that tigecycline may play in the therapy for severe respiratory tract infections, both of nosocomial and community origin.

Anti-Bacterial Agents↗
PubMed2005

Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents.

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.

Anti-Bacterial Agents↗
PubMed2005

Activity of tigecycline tested against a global collection of Enterobacteriaceae, including tetracycline-resistant isolates.

Steadily increasing resistance among the Enterobacteriaceae to beta-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and trimethoprim/sulfamethoxazole has compromised the utility of these commonly used antimicrobial classes for many community- or hospital-acquired infections. The development of tigecycline, the sentinel representative of a novel class of broad-spectrum agents (the glycylcyclines), represents an important milestone in addressing this critical need. Resistance to tigecycline might be expected to occur via the same mechanisms that produce tetracycline resistance; however, tigecycline remains stable and largely unaffected by the commonly occurring efflux and ribosomal protection resistance mechanisms. In this study, an international collection of Enterobacteriaceae (11327 isolates; 32.8% tetracycline-resistant) from global surveillance studies (2000-2004) were evaluated against tigecycline and other comparator antimicrobials. Although the most active agents were the carbapenems and aminoglycosides (97.5-99.7% susceptible), tigecycline displayed high potency (MIC50 and MIC90, 0.25 and 1 microg/mL) with 95.7% of all strains being inhibited at < or =2 microg/mL. Despite higher MIC values observed with Serratia spp. and Proteae, between 90.5% and 97.5% of isolates were inhibited by < or =4 microg/mL of tigecycline. Tetracycline-resistant populations demonstrated only modest decreases in potency to tigecycline, which appeared to be species-dependent (up to 2-fold only for Escherichia coli, Salmonella spp., Shigella spp., and Panteoa agglomerans; and up to 4-fold for Klebsiella spp., Enterobacter spp., and Citrobacter spp.). Among E. coli (263 isolates) and Klebsiella spp. (356) that meet recognized screening definitions for extended-spectrum beta-lactamase production, 100.0% and 94.4% were inhibited by tigecycline at 2 microg/mL, respectively. These findings confirm that tigecycline exhibits potency, breadth of spectrum, and stability to the commonly occurring resistance mechanisms found in contemporary Enterobacteriaceae isolates, attributes that make this parenteral agent an attractive candidate for use against serious infections produced by these species.

Anti-Bacterial Agents↗
PubMed2005

Cefdinir activity against contemporary North American isolates from community-acquired urinary tract infections.

Cefdinir is an oral cephalosporin approved by the US Food and Drug Administration in 1997 for the treatment of community-acquired (CA) respiratory tract and uncomplicated skin and soft tissue infections. The objective of the present study was to evaluate the in vitro activity of cefdinir against recent clinical isolates collected from CA-urinary tract infections (UTIs), a possible expanded indication. A total of 456 isolates from CA-UTI were collected from medical centres in North America (NA; United States and Canada) in 2003 and susceptibility tested by NCCLS reference broth microdilution methods. Cefdinir and cefpodoxime were the most active compounds tested against Escherichia coli (98.7% susceptibility), followed by nitrofurantoin (97.0%) and ciprofloxacin (95.0%). Cefdinir was 8- to 16-fold more potent than cefuroxime axetil and cefprozil against E. coli, Klebsiella spp. and Staphylococcus saprophyticus. The activity of cefdinir was most similar to that of cefpodoxime against E. coli and Klebsiella spp., but cefpodoxime showed inferior activity against S. saprophyticus. The cefdinir spectrum was significant superior (+3.8 to 16.5%) to that of trimethoprim/sulphamethoxazole against all pathogens evaluated. The cefdinir spectrum and potency were comparable or superior to other orally administered beta-lactams tested against recent (2003) clinical isolates from CA-UTI.

Anti-Infective Agents↗
PubMed2005

Dissemination and diversity of metallo-beta-lactamases in Latin America: report from the SENTRY Antimicrobial Surveillance Program.

Carbapenem resistance among Pseudomonas aeruginosa and Acinetobacter spp. is becoming a critical therapeutic problem worldwide. The SENTRY Antimicrobial Surveillance Program monitors pathogen frequency and antimicrobial resistance patterns of nosocomial and community-acquired infections through sentinel hospitals on five continents. Pseudomonas spp. and Acinetobacter spp. strains resistant to imipenem (MIC, >/=16 mg/l), meropenem (MIC, >/=16 mg/l), and ceftazidime (MIC, >/=32 mg/l) collected from January 2001 to December 2003 were routinely screened for antimicrobial resistance genes. Resistant isolates were initially tested for metallo-beta-lactamase (MbetaL) production by phenotypic tests (disk approximation or MbetaL Etest strip) and then characterization of the MbetaL (hydrolysis assays, PCR for bla(IMP), bla(VIM), bla(SPM), gene sequencing). Eighty-nine isolates (33 Acinetobacter spp., 54 Pseudomonas aeruginosa, and 2 P. fluorescens) had positive phenotypic screening tests. Among those, 34 isolates producing MbetaL were identified, including 7 Acinetobacter spp., 25 P. aeruginosa and 2 P. fluorescens. The MbetaLs identified were IMP-1, VIM-2 and two newly described enzymes: SPM-1 and IMP-16. The greatest concentration of MbetaL strains was in Brazil, where imipenem-resistant P. aeruginosa increased significantly in the time period evaluated by the SENTRY Program. MbetaL-producing P. aeruginosa was detected in São Paulo (SPM-1) and Brasilia (SPM-1 and IMP-16), Brazil and Caracas, Venezuela (VIM-2); while MbetaL-producing Acinetobacter spp. isolates were detected in São Paulo, Brazil (IMP-1). P. fluorescens isolates producing IMP-1 and VIM-2 were detected in São Paulo, Brazil and Santiago, Chile, respectively. The emergence and dissemination of mobile MbetaL-producing isolates represent an alarming factor for increasing resistance to carbapenems in several medical centres evaluated by the SENTRY Program in Latin America.

Acinetobacter↗
PubMed2005

Antimicrobial susceptibility of uncommonly isolated non-enteric Gram-negative bacilli.

The frequency of occurrence and antimicrobial susceptibility patterns of 3059 non-enteric Gram-negative bacilli (NGB), other than Pseudomonas aeruginosa and Acinetobacter spp., consecutively collected as part of the SENTRY Antimicrobial Surveillance Program (1997-2003) were reviewed. During this period, a total of 221,084 bacterial isolates were collected from several clinical specimens worldwide, including 25,305 (11.5%) NGB. Acinetobacter spp. and P. aeruginosa accounted for 82.7% of the NGB isolates and have been excluded from this analysis. The antimicrobial susceptibility results of 3509 strains from 13 species/genera have been analysed in this review. The isolates were tested by reference broth microdilution methods in three central laboratories using common reagents and procedures. More than 30 antimicrobial agents were tested and the results for the 18 most active compounds are reported here. Stenotrophomonas maltophilia (2076 strains; 59.2%) was the most frequently isolated pathogen in this group, followed by Aeromonas spp. (385 strain; 11.0%), Burkholderia cepacia (269 strains; 7.7%), Pseudomonas fluorescens/putida (253 strains; 7.2%) and Alcaligenes spp. (236 strains; 6.7%). All other species/genera accounted for less than 3% of the isolates analysed. The antimicrobial agents with the most consistent activity against the NGB evaluated in the present study were the newer fluoroquinolones gatifloxacin and levofloxacin with 84.1 and 84.9% susceptibility overall. Trimethoprim/sulphamethoxazole was active against 85.3% of the isolates tested, but showed reduced activity against P. fluorescens/putida (22.1% susceptibility). Antimicrobial susceptibility varied significantly between species/genera and the geographical regions evaluated. Thus, proper identification and quantitative susceptibility testing will be required for the treatment of NGB infections. Extensive worldwide surveillance programmes remain extremely important to guide empirical antimicrobial therapy for rarely isolated pathogens and also for pathogens that are not routinely tested due to the lack of standardised susceptibility testing methods.

Anti-Bacterial Agents↗
PubMed2005

Susceptibility patterns of Streptococcus pneumoniae isolates in North America (2002-2003): contemporary in vitro activities of amoxicillin/clavulanate and 15 other antimicrobial agents.

A contemporary (2002-2003) national collection of 2100 strains of Streptococcus pneumoniae obtained from 30 sites in the nine United States (US) census regions were tested to determine the comparative antimicrobial properties of amoxicillin/clavulanate and 15 other antimicrobials. The rank order of antimicrobials with the lowest susceptibility rates was: penicillin (67.9%) or=41.1%), trimethoprim/sulphamethoxazole (38.9%), tetracyclines (22.2%) and clindamycin (10.0%). Geographical variation in the susceptibility patterns among US census zones was present with lowest penicillin and erythromycin susceptibility noted for West South Central and West North Central zones ( or=+0.9%), sinus isolates (+2.7%), middle ear fluid isolates (+5.5%), penicillin-resistant strains (>or=+5.8%) and strains from patients <2 years of age (>or=+2.4%). Local and global surveillance studies of common respiratory pathogens such as S. pneumoniae remain instrumental to guide clinicians in appropriate empirical treatments and to emphasize the need for prudent antimicrobial use.

Adolescent↗