Biomedical subjects

Helio S Sader

Publications and source records attributed to Helio S Sader.

At least 73 records · Page 4Linked to original sources

PubMed2005

Comprehensive in vitro evaluation of cefepime combined with aztreonam or ampicillin/sulbactam against multi-drug resistant Pseudomonas aeruginosa and Acinetobacter spp.

Pseudomonas aeruginosa and Acinetobacter spp. are becoming increasingly resistant to antimicrobial agents, and serious infections caused by these organisms often require combination therapy. Interactions of cefepime with either aztreonam (P. aeruginosa; n=46) or ampicillin/sulbactam (Acinetobacter spp.; n=34) were investigated by the chequerboard synergy method against isolates with various resistance phenotypes, including resistance to imipenem (36 P. aeruginosa and 19 Acinetobacter spp.). Synergy or partial synergy interactions occurred with 56.5% of P. aeruginosa and 88.2% of Acinetobacter spp. strains examined. Among the imipenem-resistant strains, synergy or partial synergy interactions were observed in 47.2% of P. aeruginosa and 84.2% of Acinetobacter spp. strains. In addition, the vast majority of impenem-resistant strains showed MIC values within achievable concentrations in plasma for at least one of the antimicrobials evaluated in the combination. The role of combination antimicrobial therapy in the treatment of severe infections caused by multidrug-resistant P. aeruginosa and Acinetobacter spp. should be further evaluated to maximize favourable clinical outcomes.

Acinetobacter↗

PubMed2005

Trends in linezolid susceptibility patterns: report from the 2002-2003 worldwide Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program.

Linezolid is an important oxazolidinone antimicrobial for the treatment of infections caused by Gram-positive cocci, especially vancomycin-resistant enterococci and oxacillin-resistant Staphylococcus aureus (ORSA). Since its introduction, however, ribosomal mutations have been detected that produce resistance; thus, longitudinal surveillance remains necessary to monitor for emerging resistance in all geographic areas of oxazolidinone use. The 2003 Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program compared linezolid minimum inhibitory concentration (MIC) results with 13-15 comparator antimicrobial agents (8089 isolates) and also with results from an earlier surveillance period (2002). Sampling institutions in the United States of America (USA), Canada, Europe (seven nations), South America (three nations) and the Asia-Pacific (three nations) referred 200 Gram-positive cocci to the central laboratory for MIC processing and identification confirmation. Linezolid resistance (MIC > or = 8 mg/L) was established by alternative susceptibility testing methods as well as by ribosomal target characterisation. Concurrent drug use data were collected. Linezolid activity against the six major organism groups did not vary between years or geographic areas. In contrast, penicillin resistance increased 2% in Streptococcus pneumoniae; macrolide resistance was stable among beta-haemolytic streptococci (19-21%), but increased in S. pneumoniae (+2%); ORSA rates increased 4%; and vancomycin resistance in enterococci was present, but varied markedly by region. Non-clonal linezolid-resistant isolates were detected, each having the same G2576U 23S rRNA target mutation. Furthermore, the first linezolid-resistant, non-USA isolate (S. aureus in Greece) was observed, apparently related to linezolid use. In 2003, near complete activity for linezolid against Gram-positive isolates was again documented (99.93% susceptible) in the ZAAPS Program. Rare linezolid-resistant isolates were identified among enterococci, limited to USA strains. Limited correlations of linezolid resistance to drug use continues, with an average consumption rate of 0.63DDD/100 patient days (a 50% increase since 2002), and indicates the important role of hospital hygiene practice in preventing the dissemination of oxazolidinone resistances, should they be detected.

Acetamides↗

PubMed2005

Comparative antimicrobial characterization of LBM415 (NVP PDF-713), a new peptide deformylase inhibitor of clinical importance.

LBM415 (NVP PDF-713) is the first member of the peptide deformylase (PDF) inhibitor class being developed for clinical trials as a parenteral and oral agent for treatment of community-acquired respiratory tract disease and serious infections caused by antimicrobial-resistant gram-positive cocci. In this study susceptibility testing results from 1,306 recent clinical isolates selected to over-represent resistance trends among the species were summarized. All staphylococci (153 strains; MIC at which 90% of isolates were inhibited [MIC90], 2 microg/ml), Streptococcus pneumoniae (170 strains; MIC90, 1 microg/ml), other streptococci (150 strains; MIC90, 1 microg/ml), enterococci (104 strains; MIC90, 4 microg/ml), Moraxella catarrhalis (103 strains; MIC90, 0.5 microg/ml), and Legionella pneumophila (50 strains; MIC90, 0.12 microg/ml) were inhibited at < or = 8 microg of LBM415/ml, as were 97% of Haemophilus influenzae isolates (300 strains; MIC90, 4 to 8 microg/ml). Among other bacterial groups, 100% of gram-positive and -negative anaerobes, including 22 Bacteroides spp. strains (31 strains total; MIC90, 1 microg/ml), were inhibited by < or = 4 microg/ml, whereas Enterobacteriaceae (112 strains) and most nonfermentative bacilli (107 strains) were not inhibited at readily achievable concentrations. The compound was found to have a dominantly bacteriostatic action, and spontaneous single-step mutational rates occurred at low levels (10(-6) to <10(-8)). Drug interaction studies failed to identify any class-specific synergistic interactions, nor were antagonistic interactions observed. Variations in broth and agar MIC test conditions demonstrated that, whereas the agar-based method trended towards a 1-log2 dilution-higher MIC than the broth method and was inoculum dependent, other variations in incubation environment, medium supplements, pH, or calcium concentration had little influence on LBM415 MIC results. Use of the efflux inhibitor phe-arg-beta-naphthylamide showed an average of 1 log2 dilution decrease in H. influenzae MICs, demonstrating the contribution of efflux pumps in influencing susceptibility to PDF inhibitors. The in vitro activity of LBM415 against targeted bacterial species, including resistant subsets, and other laboratory characteristics of this novel compound demonstrate the potential of PDF inhibitors as a new class of antimicrobial agents.

Amidohydrolases↗

PubMed2005

Antimicrobial activity and spectrum of PPI-0903M (T-91825), a novel cephalosporin, tested against a worldwide collection of clinical strains.

PPI-0903M is a novel N-phosphono-type cephalosporin active against oxacillin-resistant staphylococci and many other gram-positive organisms. This study evaluated the in vitro activity and spectrum of PPI-0903M against 1,478 recent clinical isolates collected from 80 medical centers (22 countries). PPI-0903M demonstrated broader in vitro activity against gram-positive bacteria, particularly against multidrug-resistant staphylococci and streptococci of current clinical concern, than currently available extended-spectrum cephalosporins while maintaining similar activity against gram-negative pathogens.

Anti-Bacterial Agents↗

PubMed2004

Initial results from a longitudinal international surveillance programme for anidulafungin (2003).

OBJECTIVES: This longitudinal study evaluated the in vitro activity of anidulafungin against 880 clinical yeast isolates and 68 mould isolates from 64 medical centres in North America, Latin America and Europe. METHODS: MICs of anidulafungin, amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole and voriconazole were determined using reference method (M27-A2) guidelines. The M38-A reference method was used for the filamentous fungi, including determination of minimum effective concentrations (MECs) of anidulafungin. RESULTS: Anidulafungin was more active when compared with fluconazole and itraconazole for Candida albicans (MIC(90), 0.06 mg/L), Candida tropicalis (MIC(90), 0.06 mg/L), Candida glabrata (MIC(90), 0.12 mg/L), Candida krusei (MIC(90), 0.06 mg/L) and Candida lusitaniae (MIC(90), 1 mg/L) as well as the less-often encountered yeast species. Anidulafungin was less active against Candida parapsilosis, Candida guilliermondii and Candida famata (MIC(50), 1-2 mg/L). Anidulafungin also exhibited excellent activity against all Aspergillus spp. (MEC(90), < or =0.03 mg/L). Anidulafungin was also evaluated comparing two end point reading criteria and two incubation intervals. Data indicate that longer incubation periods do not significantly influence overall MIC ranges. These international surveillance results for anidulafungin confirm the activity observed in studies of smaller numbers of isolates.

Anidulafungin↗

PubMed2004

SENTRY antimicrobial surveillance program report: Latin American and Brazilian results for 1997 through 2001.

The alarming emergence and spread of antimicrobial resistance among common bacteria threatens the effectiveness of therapy for many infections. Surveillance of antimicrobial resistance is essential to identify the major problems and guide adequate control measures. Several resistance surveillance programs have been implemented in North America and Europe in the last decade; however, very few programs have assessed antimicrobial resistance in Latin American countries. The SENTRY Antimicrobial Surveillance Program was initiated in 1997 and represents the most comprehensive surveillance program in place at the present time worldwide. The SENTRY Program collects consecutive isolates from clinically documented infections in more than 80 medical centers worldwide (10 in Latin America). The isolates are collected according to the type of infection (objectives) and susceptibility tested in a central microbiology laboratory by reference broth microdilution methods according to NCCLS guidelines. The Program also incorporated molecular typing (ribotyping and PFGE) and resistance mechanism analysis of selected isolates. In this report we present a very broad analysis of the data generated by testing almost 20,000 bacterial isolates against more than 30 antimicrobial agents. The susceptibility results (MIC(50), MIC(90) and % susceptible) are presented in 11 tables according to the organism and site of infection. The data from Brazil, as well as the data from isolates collected in 2001, are analyzed separately. This report allows the evaluation of the activities numerous antimicrobial agents against clinical isolates collected in Latin American countries.

Anti-Bacterial Agents↗

PubMed2004

Doripenem (S-4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluations.

OBJECTIVES: To investigate the potency of doripenem, a broad-spectrum carbapenem characterized by a wider spectrum of activity combining antimicrobial and bactericidal features of imipenem and meropenem. METHODS: This parenteral compound was studied against recent clinical isolates (2001-2002) from a worldwide organism collection. A total of 902 strains were susceptibility tested by reference methods against doripenem and six to 28 comparators including ertapenem, imipenem and meropenem. The organisms tested included: Enterobacteriaceae (281 strains), Acinetobacter spp. (33), Pseudomonas aeruginosa (35), Stenotrophomonas maltophilia (36), other non-fermenters (22), Haemophilus influenzae (61), Moraxella catarrhalis (33), oxacillin-susceptible staphylococci (39), enterococci (84), streptococci (163), various anaerobes (98), and other Gram-positive species such as Corynebacterium and Bacillus spp. (17). RESULTS: Against Enterobacteriaceae, the average doripenem MIC90 was 0.03 mg/L (range, < or =0.015-0.25 mg/L). Doripenem was two- to 16-fold more potent than imipenem and comparable to ertapenem and meropenem; all doripenem MIC values with enteric bacilli were < or =4 mg/L. Doripenem was active against Aeromonas (MIC50, 0.03 mg/L), Bacillus spp. (MIC50, 0.03 mg/L) and all tested anaerobic species (MIC range, < or =0.015-4 mg/L), but was less active against S. maltophilia (MIC90, >32 mg/L) and Enterococcus faecium (MIC90, >32 mg/L) among the enterococcal species. Time-dependent bactericidal action was observed for doripenem and broth MIC results were slightly greater when compared to agar MIC results. In pilot testing, the optimal doripenem disc concentration was 10 microg, identical to standardized reagents for other clinically available carbapenems. CONCLUSIONS: Doripenem appears to be a potent carbapenem with a spectrum resembling currently marketed antipseudomonal carbapenems, but with greater activity when tested against some non-fermentative bacillary strains. Continued evaluation of doripenem against isolates resistant to other beta-lactams appears to be warranted.

Anti-Bacterial Agents↗

PubMed2004

Potential utility of a peptide deformylase inhibitor (NVP PDF-713) against oxazolidinone-resistant or streptogramin-resistant Gram-positive organism isolates.

OBJECTIVES: To evaluate the potency of a novel peptide deformylase inhibitor, NVP PDF-713, against Gram-positive organisms having resistances to linezolid or quinupristin/dalfopristin. MATERIALS AND METHODS: A total of 45 strains from three genera (six species groups) were tested by reference broth microdilution methods. The mechanism of resistance to the oxazolidinone was determined by sequencing of the gene encoding the ribosomal target. RESULTS: NVP PDF-713 retained activity against linezolid-resistant staphylococci (MIC range 0.25-2 mg/L), Streptococcus oralis (MIC 0.5 mg/L), Enterococcus faecalis (MIC range 2-4 mg/L) and Enterococcus faecium (MIC range 0.5-4 mg/L). Quinupristin/dalfopristin-resistant E. faecium (MIC range 1-2 mg/L) and staphylococci (MIC range 0.12-2 mg/L) were also inhibited by NVP PDF-713. Many (10 of 13 strains) of the linezolid-resistant enterococci were resistant to vancomycin and these clinical strains had a G2576U ribosomal target mutation. CONCLUSIONS: NVP PDF-713 appears to be a promising clinical candidate among the peptide deformylase inhibitors for the treatment of infections caused by Gram-positive organisms that possess resistances to oxazolidinones or streptogramin combinations.

Amidohydrolases↗

PubMed2004

The use of molecular typing to evaluate the dissemination of antimicrobial resistance among Gram-negative rods in Brazilian hospitals.

Antimicrobial resistance has increased rapidly in Brazil and worldwide during the past few years, giving rise to a growing necessity for antimicrobial resistance surveillance programs. These programs have been instituted in order to monitor bacterial resistance in various regions, and to guide empirical antimicrobial therapy. We evaluated the use of molecular typing in multicenter surveillance programs. We also studied the dissemination modes of selected resistance profiles. Antimicrobial susceptibility to various antimicrobial agents was evaluated by the reference broth microdilution method. Bacterial isolates with selected susceptibility patterns were characterized by pulsed field-gel electrophoresis (PFGE). A total of 119 Gram-negative bacteria were molecularly typed, including 22 imipenem-resistant Pseudomonas aeruginosa, 26 ESBL-producing Escherichia coli, 27 cefoxitin-resistant-ESBL-producing Klebsiella pneumoniae, 33 Enterobacter spp., 8 Citrobacter spp., and 3 S. marcescens isolates resistant to ceftazidime. The isolates were from clinically apparent bacteremia of patients hospitalized in medical centers located in 13 cities of 11 Brazilian states. Our molecular typing results revealed a great genetic diversity among isolates of the same species. However, some major PFGE patterns were found in more than one isolate. All repeated PFGE patterns were detected in only 2 isolates, which were isolated within the same institutions or in different medical centers. We conclude that the ability to characterize organisms phenotypically and genotypically is a powerful epidemiologic tool and it provides unique information that is very important for multicenter surveillance programs.

Anti-Bacterial Agents↗

PubMed2004

Daptomycin activity and spectrum: a worldwide sample of 6737 clinical Gram-positive organisms.

BACKGROUND: Increasing antimicrobial resistance among bacterial pathogens has prompted attempts to develop new antimicrobial agents active against multidrug-resistant Gram-positive pathogens. OBJECTIVES: To evaluate the in vitro activity of daptomycin against a worldwide collection of clinical bacterial isolates. METHODS: Daptomycin is a novel cyclic lipopeptide recently approved by the United States Food and Drug Administration. Daptomycin and selected comparators were tested against 6737 clinical Gram-positive strains from more than 70 centres located in Europe, North America and South America. RESULTS: The overall distribution of daptomycin MIC values were in the range < or = 0.12-8 mg/L and 99.4% of all strains were inhibited at < or = 2 mg/L. Despite resistances to other antimicrobial agents, >99.9% of staphylococcal isolates were inhibited at < or = 1 mg/L of daptomycin (MIC90 0.5 mg/L for staphylococci). Streptococcal isolates were very susceptible to daptomycin independent of their susceptibility to penicillin. MIC50/90 values were < or = 0.12 and 0.25 mg/L, respectively. Enterococci showed the highest daptomycin MIC values, but all isolates tested were inhibited at < or = 4 mg/L (except for one Enterococcus faecium isolate which showed a daptomycin MIC of 8 mg/L). CONCLUSIONS: Daptomycin exhibited excellent in vitro activity against a wide spectrum of Gram-positive organisms and may represent a therapeutic option for infections caused by multidrug-resistant pathogens worldwide.

Bacillus↗

PubMed2004

Antimicrobial usage and resistance trend relationships from the MYSTIC Programme in North America (1999-2001).

BACKGROUND: The MYSTIC Programme is a global, longitudinal antimicrobial surveillance network of hospitals that frequently utilize carbapenems. One aspect of the programme is the ability to capture antimicrobial consumption data from participating institutions. The current report evaluates these relationships for Enterobacteriaceae and Pseudomonas aeruginosa over the initial 3 year period of the programme in the USA. METHODS: Between 10 and 15 medical centres participated during 1999-2001, each submitting up to 200 isolates/year (7003 strains overall). Evaluations of the relationship between drug usage and antimicrobial resistance in P. aeruginosa and Enterobacteriaceae for the carbapenems (imipenem and meropenem), cefepime, ceftazidime, ciprofloxacin, gentamicin and piperacillin-tazobactam were determined. Data were analysed based on: (1) aggregate usage results; (2) medical centre-specific usage compared with resistance rates; and (3) medical centre-specific usage results compared with yearly changes in resistance rates (DeltaR). The parameter of drug usage was the defined daily dose (DDD)/100 patient days calculated from total grams administered, using WHO definitions. RESULTS: Resistance (1999-2001) among Enterobacteriaceae did not change significantly for beta-lactams, but tended to increase slightly for gentamicin (+1.1%) and ciprofloxacin (+3.1%). P. aeruginosa resistance rates (1999-2001) for gentamicin (+9.0%) and ciprofloxacin (+10.2%) increased, in contrast to a significantly decreased resistance rate for meropenem (-7.7%). Formulary-use changes were noted: increased meropenem and ciprofloxacin use and decreased consumption for imipenem, aminoglycosides, ceftazidime and cefepime. Aggregate ciprofloxacin DDD/100 days rates were directly related (+3.3 DDD) to Enterobacteriaceae and P. aeruginosa resistance changes, whereas among P. aeruginosa, usage and resistance were inversely correlated for gentamicin (-3.8 DDD; +9.0% resistant). Medical centre-specific antimicrobial usage calculations did not demonstrate a correlation to rates of resistance (r = -0.38 to 0.61) or yearly changes in resistance rates (r = -0.56 to 0.43). CONCLUSIONS: The availability of aggregate USA medical centre antimicrobial usage data enabled us to identify several important trends in the incidence of resistance among P. aeruginosa and Enterobacteriaceae: (1) increased use of ciprofloxacin associated with a higher resistance among Enterobacteriaceae; and (2) a correlation between ciprofloxacin categories of resistance and levels of resistance to other antimicrobial classes in P. aeruginosa. Medical centre-specific antimicrobial usage and resistance did not demonstrate direct statistical relationships, and require a continued search for other monitoring methods that can better identify antimicrobial/environmental factors that lead to resistance.

Anti-Bacterial Agents↗

PubMed2004

Worldwide assessment of dalbavancin activity and spectrum against over 6,000 clinical isolates.

Continuing emergence of new antimicrobial resistance mechanisms and the increased frequency of existing resistances, requires the development of alternative antimicrobial agents. Dalbavancin is an amide glycopeptide derivative with a markedly extended serum elimination half-life. Dalbavancin and selected comparators were tested against 6,339 recent clinical isolates (2002) from the Americas and Europe using reference susceptibility testing methods. The general characteristics of this Gram-positive organism collection were: oxacillin (OXA)-resistant Staphylococcus aureus (ORSA) at 39% of strains; vancomycin-resistant enterococci (VRE) at 10%; and penicillin-nonsusceptible pneumococci at 28%. The overall distribution of dalbavancin minimum inhibitory concentration (MIC) values ranged from < or = 0.015 to > 32 microg/ml, but > 99% of MIC results were at < or =1 microg/ml. S. aureus and coagulase-negative staphylococci were extremely susceptible to dalbavancin (MIC90, 0.06 microg/ml) despite resistance patterns to other agents. Dalbavancin was the most potent compound (by weight) against vancomycin-susceptible Enterococcus faecalis and E. faecium (MIC90, 0.06 and 0.12 microg/ml, respectively); however, VRE strains showed decreased dalbavancin susceptibility (MIC50, 4 or 8 microg/ml). All streptococcal isolates were inhibited at < or =0.25 microg/ml of dalbavancin. This reported dalbavancin activity indicates that the new glycopeptide has significant activity, superior to available agents in the class, and a potency that was uniform across geographically sampled organisms. Some VRE were inhibited by very low dalbavancin concentrations (< or = 1 microg/ml; Van B phenotypes). Further clinical development seems warranted for this once-weekly administered agent.

Anti-Bacterial Agents↗

PubMed2004

Antimicrobial spectrum and activity of NVP PDF-713, a novel peptide deformylase inhibitor, tested against 1,837 recent Gram-positive clinical isolates.

Continued emergence of antimicrobial resistances among gram-positive pathogens requires further development of compounds with novel modes of action. The peptide deformylase inhibitor NVP PDF-713 was tested against 1,837 recent strains of Gram-positive organisms. All NVP PDF-713 MICs were at < or = 4microg/mL except for 6 enterococci (0.3% of strains overall). NVP PDF-713 MIC(90) results were: Staphylococcus aureus, beta-haemolytic and viridans group streptococci and Streptococcus bovis at 1 microg/ml; coagulase-negative staphylococci, Streptococcus pneumoniae, and Listeria spp. at 2 microg/mL; and the enterococci at 4 microg/mL. NVP PDF-713 appears to be a promising new agent worthy of continued in vivo development.

Amidohydrolases↗

PubMed2004

Antimicrobial resistance rates and clonality results from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme: report of year five (2003).

The U.S. Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme in the fifth year continues to monitor the spectrum of activity and potency of meropenem within medical centers where carbapenems are used for the treatment of serious infections. The antimicrobial activity of 11 broad-spectrum agents (including initial comparisons for levofloxacin) was assessed against 2,848 isolates in 2003. The minimum inhibitory concentration (MIC) results demonstrate the continued high potency of meropenem against all monitored pathogens. Against all Gram-negative bacilli tested, the overall rank order of susceptibility was meropenem (96.3%) > imipenem (95.6%) > cefepime (93.7%) > tobramycin (91.9%) > piperacillin/tazobactam (90.2%) > ceftazidime (90.1%) > gentamicin (89.6%) > levofloxacin (82.8%) > ciprofloxacin (82.5%) > aztreonam (81.8%) > ceftriaxone (72.3%). Clonal-based resistances were observed that adversely influenced carbapenem resistance rates, particularly among Klebsiella spp. and Acinetobacter baumannii isolates. Continued surveillance of the carbapenem class and other broad-spectrum agents is warranted to monitor activity against pathogens causing serious infections in hospitalized patients.

Academic Medical Centers↗

PubMed2004

Doxycycline use for community-acquired pneumonia: contemporary in vitro spectrum of activity against Streptococcus pneumoniae (1999-2002).

Because of the limited clinical testing of doxycycline, it has received guarded acceptance as an inexpensive, fluoroquinolone-sparing agent for treatment of community-acquired pneumonia. Examination of in vitro data from 3,902 recent Streptococcus pneumoniae isolates (SENTRY Program, USA) suggests that doxycycline has wider clinical application compared to macrolides, oral cephalosporins (directed by penicillin susceptibility), and trimethoprim-sulfamethoxazole.

Anti-Bacterial Agents↗

PubMed2004

Determination of epidemic clonality among multidrug-resistant strains of Acinetobacter spp. and Pseudomonas aeruginosa in the MYSTIC Programme (USA, 1999-2003).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme was initiated in 1997 (1999 for the United States). This program monitors resistance in participant medical centers where carbapenems are prescribed and drug use data can be obtained. An earlier report found antimicrobial use was not a clear cause of local or aggregate changes in resistance rates. This study addresses the role of dissemination of resistant clones on susceptibility rates for nonfermentors, Acinetobacter spp. (ACB) and Pseudomonas aeruginosa (PSA). Carbapenem (CARB)-multidrug-resistant strains (MDR) from among 236 ACB and 1,111 PSA were tested by reference broth microdilution methods, automated ribotyping, and pulsed field gel electrophoresis to determine possible clonal dissemination. Each strain was also tested for metallo-beta-lactamases (MbetaL) (phenotypic and polymerase chain reaction); and then analyzed by CARB-R rate and defined daily dose (DDD)/100 days use groupings (high, moderate, and low). For the aggregate 15 sites in the MYSTIC Programme each year, the CARB-resistant rate decreased over 5 years; but other drug-resistance rates generally escalated. Changes were not related to antimicrobial use calculations. The discovered clonally spread MDR-PSA strains were more frequent in high- (1.8 clones/site) and moderate-resistance (0.6 clones/site) rate centers (21.7% to 29.5% were clonal), compared with unique strains in low-resistance hospitals. ACB clonality was extreme in one geographic area, with dissemination of 5 different clones (931.7/B, C, or D; 1090.2/A; 167.5/A) in 4 centers (02, 04, 06, and 18). Resistance rates in ACB and PSA were clearly related to clonal occurrence and spread, and one MbetaL (VIM-7) was detected. Decreased CARB resistance rates from 1999 through 2002 were directly attributed to the disappearance of resistance clones in some locations. In conclusion, ACB and PSA CARB and MDR resistance rates in MYSTIC Programme institutions have been greatly influenced by clonal dissemination and less by antimicrobial use patterns. The most serious examples of resistance were the clonality observed among ACB in New York City and the documented endemic nature of VIM-7-producing PSA (0.09% of all PSA isolates). Meropenem remained the most active antimicrobial agent tested in the program, and surveillance networks must implement epidemiologic typing to accurately assess the role of clonal spread on the study results.

Acinetobacter↗

PubMed2004

Bactericidal activity of BAL9141, a novel parenteral cephalosporin against contemporary Gram-positive and Gram-negative isolates.

BAL9141, the active principle of prodrug BAL5788, is a parenteral cephalosporin active against oxacillin-resistant Staphylococcus aureus. Previous studies have reported the cidal action of BAL9141 towards limited numbers of isolates by time-kill methods. We tested >100 staphylococci, streptococci, and Gram-negative isolates by broth microdilution methods to determine the antibacterial activity of BAL9141 and to compare minimum inhibitory concentrations (MICs) with minimum bactericidal concentrations (MBCs). Among the 53 staphylococcal isolates, all but one (98%) had a, MBC:MIC ratio < or =2. Forty-five percent (five strains) of the penicillin-nonsusceptible Streptococcus pneumoniae isolates had an MBC:MIC ratio >4. Among 22 Enterobacteriaceae, 73% of isolates had MBC:MIC ratios of 2 or less; three strains with ratios greater than 4 were Serratia marcescens. BAL9141 displayed a predominant bactericidal activity against the majority of Gram-positive and -negative species, including resistant subsets, making it an attractive candidate for further development.

Cephalosporins↗

PubMed2004

Potency and spectrum reevaluation of cefdinir tested against pathogens causing skin and soft tissue infections: a sample of North American isolates.

Cefdinir is a widely used orally administered cephalosporin for community-acquired respiratory tract infections and skin and soft tissue infections (SSTI). A total of 415 nonduplicate isolates of community-acquired SSTI (CA-SSTI) were collected from medical centers in North America and susceptibility tested against cefdinir and various compounds indicated for the treatment of CA-SSTI. The cefdinir MIC(50/90) in microg/mL/% susceptible for strains of the 7 principal CA-SSTI pathogens were: oxacillin-susceptible Staphylococcus aureus (0.5/0.5/100%), oxacillin-susceptible coagulase-negative staphylococci (0.06/0.12/100%), group A streptococci (< or =0.03/< or =0.03/100%), group B streptococci (< or =0.03/0.06/100%), viridans group streptococci (0.25/2/88%), Klebsiella spp. (0.12/1/95%), and Escherichia coli (0.25/0.5/95%). Cefdinir was the most potent oral cephalosporin tested against staphylococci and the Enterobacteriaceae species, and 8-fold to 64-fold more potent than cephalexin against these pathogens. Beta-Hemolytic streptococci was highly susceptible to cefdinir (MIC(90), < or =0.03-0.06 microg/mL), while viridans group streptococci showed slightly elevated MIC results. Cephalexin MIC values for streptococcal strains (MIC(90), 1-32 microg/mL) were 32-fold to 64-fold higher than those of cefdinir or other oral cephalosporins evaluated. Only 0.5% of all 415 recent CA-SSTI pathogens were resistant to cefdinir (MIC, > or = 4 mg/L). Cefdinir showed a spectrum and potency comparable or superior to other orally administered beta-lactams (cephalexin).

Anti-Infective Agents↗