Potency of anidulafungin compared to nine other antifungal agents tested against Candida spp., Cryptococcus spp., and Aspergillus spp.: results from the global SENTRY Antimicrobial Surveillance Program (2008).

The SENTRY Antimicrobial Surveillance Program regularly monitors global susceptibility rates for a spectrum of both novel and established antifungal agents. Anidulafungin and the other echinocandins displayed sustained, excellent activity against Candida spp. and Aspergillus fumigatus, with >or=98% of MIC results at or=0.5 microg/ml were further analyzed for potential fks hot spot (HS) mutations; three isolates had confirmed mutations in the fks1 HS1 region (S645P), and three exhibited mutations in the fks2 HS1 region (S645F and S645P).

Activity of contemporary antifungal agents, including the novel echinocandin anidulafungin, tested against Candida spp., Cryptococcus spp., and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2006 to 2007).

Results from the SENTRY international fungal surveillance program for 2006 to 2007 are presented. A total of 1,448 Candida sp., 49 Aspergillus fumigatus, and 33 Cryptococcus neoformans isolates were obtained from infected sterile-site sources in patients on five continents. Reference susceptibility was determined for anidulafungin, caspofungin, 5-flucytosine, fluconazole, itraconazole, posaconazole, voriconazole, and amphotericin B by CLSI methods.

Comparative activity of meropenem in US medical centers (2007): initiating the 2nd decade of MYSTIC program surveillance.

Since 1997, the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program has monitored the antimicrobial activity of broad-spectrum agents against pathogens from hospitalized patients. In the United States, 2894 isolates were submitted in 2007 from 15 sites, including 1392 Enterobacteriaceae, 643 nonfermentative Gram-negative bacilli, and 829 Gram-positive cocci. All isolates were tested by broth microdilution methods. Meropenem (MIC(90) range, 0.12-2 microg/mL) exhibited the lowest resistance rates (1.9-2.4%) against Enterobacteriaceae, and fluoroquinolones had the highest rates of resistance (17.3-18.3%). KPC carbapenemases, usually found in Klebsiella pneumoniae, were also detected in Citrobacter freundii, Enterobacter spp., and Escherichia coli. Confirmed extended-spectrum beta-lactamase-producing isolate rates for E. coli, Klebsiella spp., and Proteus mirabilis isolates were 6.0%, 12.0%, and 0.0%, respectively. Meropenem remained active against Gram-positive pathogens such as staphylococci (methicillin-susceptible; MIC(90), 0.12-0.25 microg/mL), Streptococcus pneumoniae (MIC(90), 0.5 microg/mL), and beta-hemolytic and viridans group streptococci (MIC(90) range, 0.06-0.25 microg/mL). These US MYSTIC Program results demonstrate the continued emergence of novel beta-lactamases and multidrug-resistant bacterial phenotypes necessitating monitoring of carbapenem activities against Enterobacteriaceae species as well as nonfermentative bacilli.

Activity of meropenem as serine carbapenemases evolve in US Medical Centers: monitoring report from the MYSTIC Program (2006).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Surveillance Program was designed to monitor the antimicrobial potency and spectrum of meropenem, and selected broad-spectrum comparison agents against pathogens from hospitalized patients. In the 2006 (year 8 of the study) United States sample, a total of 2841 isolates (94.7% compliance) including 641 Escherichia coli, 619 Klebsiella spp., 606 Pseudomonas aeruginosa, 456 oxacillin-susceptible Staphylococcus aureus, 300 streptococci, 149 Enterococcus faecalis, and 70 Gram-positive anaerobic organisms were tested by reference broth microdilution or agar dilution susceptibility methods. The carbapenems, especially meropenem, consistently demonstrated the lowest resistance rates against Enterobacteriaceae strains, and the fluoroquinolones had the highest and increasing resistance rates. The presence of qnr-mediated fluoroquinolone resistance was investigated using polymerase chain reaction methods but was only observed at very low levels (2.1%) and was not clonally associated. Confirmed extended-spectrum beta-lactamase rates for E. coli and Klebsiella spp. were only 4.8% and 5.0%, respectively, with mobile AmpC (CMY-2 and FOX-5) enzymes shown in 13 additional Enterobacteriaceae isolates. Clonally related KPC-type serine carbapenemase production (57 strains, 9.5%) was observed at a rate 2-fold greater than the prior year among Klebsiella spp. isolates, primarily from 1 geographic region (Middle Atlantic States). These MYSTIC Program (2006) results demonstrate the continued need to monitor the carbapenem class potency and spectrum of activity against Enterobacteriaceae as well as P. aeruginosa because of the documented presence of serine carbapenemases and rare incidence of metallo-beta-lactamases that may further compromise their activity and that of other beta-lactam agents.

Development of anidulafungin for disk diffusion susceptibility testing against Candida spp.

A disk diffusion (DD) method has been standardized by the Clinical and Laboratory Standards Institute (M44-A) to test Candida susceptibilities for some azoles (fluconazole and voriconazole). The DD method using anidulafungin, a new echinocandin, was initially developed here using Candida spp. (75 strains) and candidate anidulafungin disk concentrations of 1, 2, 5, and 10 microg with or without dimethyl sulfoxide (DMSO) (0.05-1%) and with or without polysorbate 80 (P-80, 0.002-2%). The 2-microg disks (with 1% DMSO and 0.1% P-80) produced acceptable correlation statistics (r = 0.84-0.85 ) when compared with reference MIC results, and this disk was optimal for testing all Candida spp. Good separation of Candida parapsilosis (least anidulafungin-susceptible species) from the more susceptible yeast species and a potential susceptibility breakpoint near the preferred reproducible zone diameter of > or = 15 mm were achieved for all tested yeast species.

Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients: report from the Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program (North America).

The Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program (CANCER) monitored the susceptibility of pathogens recovered in hematology/oncology centers from 2000 to 2002. A total of 3970 isolates from 32 hospitals (26 United States, 6 Canada) were analyzed at a central location (JMI Laboratories, North Liberty, IA) for trends in pathogen occurrence and reference antimicrobial susceptibility profiles. The top 5 ranking pathogens were Staphylococcus aureus (19.3%), coagulase-negative staphylococci (CoNS) (14.1%), Escherichia coli (13.4%), Enterococcus spp. (10.2%), and Klebsiella spp. (9.5%). A total of 35.5% of S. aureus and 78.8% of CoNS were resistant to oxacillin, whereas 22.0% of Enterococcus spp. were resistant to vancomycin. E. coli and Klebsiella spp. were highly susceptible (>90%) to piperacillin/tazobactam, 3rd-generation cephalosporins, and ciprofloxacin, but 3.9% and 2.4% of these species, respectively, met screening criteria for extended spectrum beta-lactamase production. Enterobacter spp. were less susceptible to piperacillin/tazobactam, ceftazidime, and ceftriaxone (83.7-88.2%) because of Amp C production and were most inhibited by cefepime and imipenem. Amikacin and polymyxin B were very active against Pseudomonas aeruginosa (97.4-97.7% susceptible). Prevalence of S. aureus, E. coli, Enterobacter spp., and Klebsiella spp. increased significantly (+48% to 98%) with age, whereas CoNS and viridans group streptococci decreased markedly (-62% to 69%) with advancing age. The isolation of Gram-positive pathogens declined (55% to 47%) with age (< or =14 to > or =65 years). Fluoroquinolones generally exhibited decreased susceptibility with increased age against nearly all listed pathogens. Oxacillin resistance rates for S. aureus increased with age (6-46%) as did vancomycin resistance rates for enterococci (nil in < or =14 years group to 18-24% in adults). Pathogens infecting neutropenic patients did not reflect greater resistance than those found in the general hospitalized patients. Gram-positive organisms were only slightly more predominant (53.4%), and cited age-related variations in pathogen occurrence and/or susceptibility patterns by species must be considered for empiric regimes for hematology and oncology patients.

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.

In vitro activity of tigecycline (GAR-936) tested against 11,859 recent clinical isolates associated with community-acquired respiratory tract and gram-positive cutaneous infections.

Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has demonstrated activity against a variety of bacterial pathogens, including resistant isolates, during preclinical studies. In vitro activities of tigecycline and comparators were tested against 11,859 recent (2000 and 2002) bacterial strains recovered from patients in 29 countries with community-acquired respiratory tract disease (3,317 gram-positive and -negative strains) and skin and soft tissue infections (8,542 gram-positive strains). All oxacillin-susceptible and -resistant Staphylococcus aureus (5,077 strains; tigecycline MIC(90), 0.5 microg/mL) and coagulase-negative staphylococci (1,432 strains; MIC(90), 0.5 microg/mL), penicillin-susceptible and -resistant Streptococcus pneumoniae (1,585 strains; MIC(90), < or =0.25 microg/mL), viridans group streptococci (212 strains; MIC(90), < or =0.25-0.5 microg/mL), vancomycin-susceptible and -resistant enterococci (1,416 strains; MIC(90), 0.25-0.5 microg/mL), beta-haemolytic streptococci (405 strains; MIC(90), < or =0.25 microg/mL), beta-lactamase positive and negative Haemophilus influenzae (1,220 strains; MIC(90), 1 microg/mL), Moraxella catarrhalis (495 strains; MIC(90), 0.25 microg/mL), and Neisseria meningitidis (17 strains; MIC(90), < or =0.12 microg/mL) were inhibited by 2 microg/mL or less of tigecycline. Whereas potency of tetracycline and doxycycline markedly dropped in various resistant organism subsets, tigecycline was unaffected with an overall MIC(90) of 0.5 microg/mL. These findings confirm that tigecycline maintains a truly broad spectrum like the tetracycline class while enhancing potency. It also incorporates stability to the commonly occurring tetracycline resistance mechanisms, making it an attractive candidate for continued clinical development against pathogens causing serious community-acquired respiratory tract infections, as well as cutaneous infections.

Antimicrobial susceptibility and epidemiology of a worldwide collection of Chryseobacterium spp: report from the SENTRY Antimicrobial Surveillance Program (1997-2001).

Limited data are available on Chryseobacterium spp. leading to an evaluation of the patient demographics and susceptibility patterns for Chryseobacterium spp. collected in the first 5 years of the SENTRY Antimicrobial Surveillance Program (1997 to 2001). Fifty isolates (24 Chryseobacterium meningosepticum, 20 Chryseobacterium indologenes, two Chryseobacterium gleum, and 4 Chryseobacterium spp. isolates) were collected. The highest Chryseobacterium prevalence was detected among the elderly. The most active antimicrobials were the newer quinolones (garenoxacin, gatifloxacin, and levofloxacin, each with a MIC at which 90 percent of the isolates are inhibited [MIC(90)] of 1 micro g/ml and 98.0% susceptibility) followed by rifampin (MIC(90), 2 microg/ml and 85.7% susceptibility). Trimethoprim-sulfamethoxazole, ciprofloxacin, and piperacillin-tazobactam also showed reasonable activity; vancomycin showed poor potency.

CANCER resistance surveillance program: initial results from hematology-oncology centers in North America. Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance.

OBJECTIVE: The CANCER (Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance) surveillance program was initiated to collect culture data on antimicrobial and antifungal agents in hospitals treating neutropenic patients in North America, as a means to monitor the development of microbial resistance. METHODS: A total of 2042 isolates from bloodstream, respiratory, urinary, and cutaneous infections in 2000-2001 were submitted by 33 oncology centers, clinics, and hospitals in North America, sent to a central laboratory, and tested by National Committee for Clinical Laboratory Standards methods against 42 different antimicrobials. RESULTS: Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococci, Enterococcus spp., and Klebsiella spp. represented the most frequently isolated pathogens during the initial benchmark year. The incidence of extended-spectrum beta-lactamase-producing phenotypes ranged from 1.6% to 4.6% among E. coli and Klebsiella spp. Amikacin, tobramycin, polymyxin B, and piperacillin/tazobactam provided the highest susceptibility rates against Pseudomonas aeruginosa isolates. Yeast bloodstream isolates demonstrated complete susceptibility to amphotericin B, but 14% of strains were considered to have high-level fluconazole resistance. CONCLUSIONS: Elevated resistance rates when compared to general hospital strains were not observed in the CANCER program during the baseline year of this novel longitudinal, resistance surveillance program. The prevalence of gram-positive pathogens, although representing more than 50% of all bacterial isolates, was slightly lower than that reported previously by other investigators. Continued evaluation for antimicrobial resistance as well as changes in the prevalence of gram-positive pathogens requires the use of longitudinal surveillance programs such as the CANCER program. Such initiatives allow the development of therapeutic strategies for coping with changes in resistance and pathogen prevalence in this dynamic at-risk patient environment.

Geographic variations in garenoxacin (BMS284756) activity tested against pathogens associated with skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (2000).

The antimicrobial activity of garenoxacin, a des-(6)F quinolone (formally BMS284756 and T-3811), was evaluated against 2,537 skin and soft tissue infection (SSTI) isolates from the SENTRY Antimicrobial Surveillance Program. Strains isolated in 2000 from Europe, North and Latin America were tested at a central laboratory using reference broth microdilution methods. The rank order of the seven most frequent SSTI pathogens was: Staphylococcus aureus (39.9%), Pseudomonas aeruginosa (12.1%), Escherichia coli (9.7%), Enterococcus spp. (7.7%), Klebsiella spp. (5.8%), Enterobacter spp. (5.6%) and coagulase-negative staphylococci (CoNS; 4.2%). Garenoxacin exhibited a four-fold greater activity (MIC(90), 0.06 microg/ml) compared to levofloxacin (MIC(90), 0.25 microg/ml) against oxacillin-susceptible S. aureus; and oxacillin-resistant staphylococci were more susceptible to garenoxacin (>/=90.5%) at Europe > North America). Continued development of garenoxacin as a treatment of pathogens that commonly cause SSTIs appears to be warranted.

Geographic variations in activity of broad-spectrum beta-lactams against Pseudomonas aeruginosa: summary of the worldwide SENTRY Antimicrobial Surveillance Program (1997-2000).

With reports of increasing resistance to antimicrobial agents among Pseudomonas aeruginosa clinical isolates worldwide, the activities of cefepime and eight other broad-spectrum beta-lactams against 6969 isolates collected during 1997-2000 from the four regions of the SENTRY Antimicrobial Surveillance Program. P. aeruginosa isolates were tested by the reference broth microdilution method against nine beta-lactam antimicrobial agents (aztreonam, cefepime, ceftazidime, imipenem, meropenem, piperacillin +/- tazobactam, ticarcillin +/- clavulanate), three aminoglycosides (amikacin, gentamicin, tobramycin), and two fluoroquinolones (ciprofloxacin, levofloxacin). The strains were contributed by more than 100 medical centers. National Committee for Clinical Laboratory Standards criteria were used to identify susceptible and resistant isolates. P. aeruginosa strains from Latin America were generally the most resistant to all classes of antimicrobials, compared with strains from other regions. The beta-lactams exhibited a wide range of potency, with carbapenems most active (meropenem, 80-91% susceptible; imipenem, 76-88% susceptible). Piperacillin/tazobactam was the most active penicillin (77-80% susceptible), and cefepime (67-83% susceptible) had an average 2% (range, 0.7-3.5%) greater susceptibility rate than ceftazidime (66-80% susceptible) across all regions. The rank order of beta-lactam activity according to percent resistant isolates in North American P. aeruginosa strains was: meropenem (4.8% resistant) > cefepime (6.8%) > imipenem (8.6%) > piperacillin/tazobactam (10.3%) > piperacillin (12.9%). Only 2.3% and 6.5% of isolates were resistant to amikacin or tobramycin, respectively, and nearly 16% of P. aeruginosa strains were resistant to ciprofloxacin. Compared with other geographic regions, strains of P. aeruginosa remain most susceptible in North America. In all regions, aminoglycosides in combination with carbapenems, cefepime, or piperacillin/tazobactam would provide more potential antipseudomonal activity than fluoroquinolone combinations for wide-spectrum empiric regimens.