Ceftaroline is a new cephalosporin with broad-spectrum activity against Gram-positive and -negative organisms. The prodrug of ceftaroline, ceftaroline fosamil, combined with the β-lactamase inhibitor avibactam (formerly NXL104), was tested against Enterobacteriaceae strains producing Ambler class A, B, C, and D enzymes, including strains producing multiple enzymes, as well as Pseudomonas aeruginosa, Acinetobacter spp., and methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MRSA) strains. Isolates were collected from 1999 to 2008 from global surveillance programs, and susceptibility testing was performed by reference broth microdilution methods. Ceftaroline-avibactam exhibited potent activity against Enterobacteriaceae producing various β-lactamase types (MIC90, 0.25 to 2 μg/ml, except for metalloenzymes), including 99 strains carrying multiple enzymes (2 to 4 β-lactamases; MIC90, 2 μg/ml). All isolates were inhibited by ceftaroline-avibactam at ≤4 μg/ml. Ceftaroline-avibactam (MIC90, 0.5 to 1 μg/ml) was more active than meropenem (MIC90, >8 μg/ml) and other comparators when tested against KPC-producing strains. S. aureus strains, including MRSA with four staphylococcal cassette chromosome mec (SCCmec) types, were dominantly (99.1%) inhibited by ceftaroline-avibactam at ≤2 μg/ml, and the ceftaroline MIC was not adversely affected by the addition of the β-lactamase inhibitor (MIC50/90, 1 and 2 μg/ml for ceftaroline with and without avibactam). Ceftaroline-avibactam demonstrated limited activity against Acinetobacter spp. and P. aeruginosa (MIC50s, 32 and 16 μg/ml, respectively). These results document that ceftaroline-avibactam has potent activity against Enterobacteriaceae that produce KPC, various ESBL types (CTX-M types), and AmpC (chromosomally derepressed or plasmid-mediated enzymes), as well as against those producing more than one of these β-lactamase types, and its development as a therapeutic option for the treatment of infections caused by multidrug-resistant Enterobacteriaceae as well as MRSA is warranted.

A total of 15,480 Gram-positive pathogens were collected from 89 sites in the United States, Europe, the Asia-Pacific region, and Latin America in 2010. Telavancin was active against indicated Staphylococcus aureus (MIC50/90, 0.12/0.25 μg/ml), vancomycin-susceptible Enterococcus faecalis (MIC50/90, 0.5/0.5 μg/ml), and beta-hemolytic (MIC50/90, 0.06/0.12 μg/ml) and viridans group streptococcus (MIC50/90, 0.03/0.06 μg/ml) isolates. These MIC results showed potency for telavancin equal to or greater than that of comparators. These in vitro data confirm a continued potent activity of telavancin when tested against contemporary Gram-positive clinical isolates.

The Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance program is a sentinel resistance monitoring system designed to track the activity of ceftaroline and comparator agents. In the United States, a total of 8,434 isolates were collected during the 2010 surveillance program from 65 medical centers distributed across the nine census regions (5 to 10 medical centers per region). All organisms were isolated from documented infections, including 3,055 (36.2%) bloodstream infections, 2,282 (27.1%) respiratory tract infections, 1,965 (23.3%) acute bacterial skin and skin structure infections, 665 (7.9%) urinary tract infections, and 467 (5.5%) miscellaneous other infection sites. Ceftaroline was the most potent β-lactam agent tested against staphylococci. The MIC90 values were 1 μg/ml for methicillin-resistant Staphylococcus aureus (MRSA; 98.4% susceptible) and 0.5 μg/ml for methicillin-resistant coagulase-negative staphylococci (CoNS). Ceftaroline was 16- to 32-fold more potent than ceftriaxone against methicillin-susceptible staphylococcal strains. All staphylococcus isolates (S. aureus and CoNS) were inhibited at ceftaroline MIC values of ≤2 μg/ml. Ceftaroline also displayed potent activity against streptococci (MIC90, 0.015 μg/ml for beta-hemolytic streptococci; MIC90, 0.25 μg/ml for penicillin-resistant Streptococcus pneumoniae). Potent activity was also shown against Gram-negative pathogens (Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis). Furthermore, wild-type strains of Enterobacteriaceae (non-extended-spectrum β-lactamase [ESBL]-producing strains and non-AmpC-hyperproducing strains) were often susceptible to ceftaroline. Continued monitoring through surveillance networks will allow for the assessment of the evolution of resistance as this new cephalosporin is used more broadly to provide clinicians with up-to-date information to assist in antibiotic stewardship and therapeutic decision making.

The LEADER Program monitors the in vitro activity of linezolid in sampled U.S. medical centers using reference broth microdilution methods with supporting molecular investigations in a central laboratory design. This report summarizes data obtained in 2009, the 6th consecutive year of this longitudinal study. A total of 6,414 isolates from 56 medical centers in all nine Census regions across the United States participated in 2009. For the six leading species/groups, the following linezolid MIC90 values were observed: Staphylococcus aureus, 2 μg/ml; coagulase-negative staphylococci (CoNS), 1 μg/ml; Enterococcus spp., 2 μg/ml; Streptococcus pneumoniae, 1 μg/ml; viridans group streptococci, 1 μg/ml; and beta-hemolytic streptococci, 1 μg/ml. Linezolid resistance was only 0.34% overall, with no evidence of significant increase in the LEADER Program since 2006. The predominant linezolid resistant mechanism found was a G2576T mutation in the 23S rRNA. L3/L4 riboprotein mutations were also found. The mobile multidrug-resistant cfr gene was found in four strains (two S. aureus strains and one strain each of S. epidermidis and S. capitis) from four different states, suggesting persistence but a lack of dissemination. Linezolid continues to exhibit excellent activity and spectrum, and this study documents the need for continued monitoring of emerging mechanisms of resistance over a wide geographic area.

Reports of an increased clinical incidence of pertussis and the development of resistance by Bordetella pertussis to erythromycin prompted the collection and testing of recent clinical isolates from patients in northern California against a range of antimicrobial agents by the Etest (AB BIODISK, Solna, Sweden) method. All isolates were fully susceptible to all eight agents tested (MIC, ≤0.38 μg/ml), including newer fluoroquinolones, such as gatifloxacin (MIC of which 90% of the isolates tested are inhibited, 0.006 μg/ml), which may be used in cases of adolescent or adult pertussis. Continued surveillance of B. pertussis isolates appears to be a prudent practice.

The antimicrobial activity of BMS 284756, a novel des-F(6)-quinolone, was comparatively evaluated against 257 Streptococcus pneumoniae, 198 Haemophilus influenzae, and 88 Moraxella catarrhalis strains isolated in Latin America between July and September of 1999 as part of the SENTRY Antimicrobial Surveillance Program. Nearly 28.0% of S. pneumoniae strains were nonsusceptible to penicillin. The rank order of quinolone potency versus S. pneumoniae was BMS 284756 (MIC at which 90% of isolates were inhibited [MIC90], 0.12 μg/ml) > trovafloxacin (MIC90, 0.25 μg/ml) > gatifloxacin (MIC90, 0.5 μg/ml) > levofloxacin and ciprofloxacin (MIC90, 1 to 2 μg/ml). All S. pneumoniae strains that were not susceptible to other quinolones were inhibited by BMS 284756 at ≤2 μg/ml. The overall prevalence of β-lactamase production was 15.2% in H. influenzae and 98.9% in M. catarrhalis. BMS 284756 showed excellent potency and spectrum against this group of pathogens, inhibiting all isolates at ≤0.12 μg/ml. BMS 284756 exhibited activity similar to those displayed by the new fluoroquinolones, such as levofloxacin, trovafloxacin, or gatifloxacin, and could be a therapeutic option for empirical treatment of community-acquired respiratory tract infections.

We have previously described the activity of low-dose clindamycin in extended-interval dosing regimens by determination of bactericidal titer in serum. In this study, we used a one-compartment in vitro dynamic infection model to compare the pharmacodynamics of clindamycin in three intravenous-dosing regimens (600 mg every 8 h [q8h], 300 mg q8h, and 300 mg q12h) against three clinical isolates of Staphylococcus aureus and two clinical isolates of Streptococcus pneumoniae. Test organisms were added to the central compartment of the model to yield a starting inoculum of 106 CFU/ml. Clindamycin was injected as a bolus into the central compartment at appropriate times over 48 h to simulate the q8h or q12h dosing regimens. Drug-free culture medium was then pumped through the system to mimic a half-life of 2.4 h. At predetermined time points during the experiment, samples were removed from the central compartments for colony count determination and drug concentration analysis. The rates of killing did not significantly differ among the three clindamycin dosing regimens against either S. aureus or S. pneumoniae (P = 0.88 or 0.998, respectively). Likewise, no significant differences in activities were detected among the three regimens against staphylococci (P = 0.677 and 0.667) or pneumococci (P = 0.88 and 0.99). Against an S. aureus isolate exhibiting inducible macrolide-lincosamide-streptogramin B resistance, none of the three clindamycin regimens prevented regrowth of the resistance phenotype in the model. In this model, clindamycin administered at a low dose in an extended-interval regimen (300 mg q12h) exhibited antibacterial activity equivalent to that of the 300- or 600-mg-q8h regimen.

We report the in vitro activities of broad-spectrum β-lactam antimicrobials tested against 1,128 gram-positive pathogens recently isolated from cancer patients. Cefepime and imipenem were more active than ceftazidime and ceftriaxone against these organisms. Only vancomycin demonstrated reliable activity against oxacillin-resistant staphylococci, Enterococcus spp., and Corynebacterium spp. The spectrum of gram-positive organisms against which cefepime and imipenem have activity provides an advantage over ceftazidime as empiric therapy for cancer patients, potentially reducing the need for the empiric addition of glycopeptides.

Between February and June of 1997, a large number of community-acquired respiratory tract isolates of Haemophilus influenzae (n = 1,077) and Moraxella catarrhalis (n = 503) from 27 U.S. and 7 Canadian medical centers were characterized as part of the SENTRY Antimicrobial Surveillance Program. Overall prevalences of β-lactamase production were 33.5% in H. influenzae and 92.2% in M. catarrhalis with no differences noted between isolates recovered in the United States and those from Canada. Among a total of 21 different antimicrobial agents tested, including six cephalosporins, a β-lactamase inhibitor combination, three macrolides, tetracycline, trimethoprim-sulfamethoxazole (TMP-SMX), rifampin, chloramphenicol, five fluoroquinolones, and quinupristin-dalfopristin, resistance rates of >5% with H. influenzae were observed only with cefaclor (12.8%) and TMP-SMX (16.2%).

The SENTRY Program was established in January 1997 to measure the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections over a broad network of sentinel hospitals in the United States (30 sites), Canada (8 sites), South America (10 sites), and Europe (24 sites). During the first 6-month study period (January to June 1997), a total of 5,058 bloodstream infections (BSI) were reported by North American SENTRY participants (4,119 from the United States and 939 from Canada). In both the United States and Canada, Staphylococcus aureus and Escherichia coli were the most common BSI isolates, followed by coagulase-negative staphylococci and enterococci. Klebsiella spp., Enterobacter spp., Pseudomonas aeruginosa, Streptococcus pneumoniae, and β-hemolytic streptococci were also among the 10 most frequently reported species in both the United States and Canada. Although the rank orders of pathogens in the United States and Canada were similar, distinct differences were noted in the antimicrobial susceptibilities of several pathogens. Overall, U.S. isolates were considerably more resistant than those from Canada. The differences in the proportions of oxacillin-resistant S. aureus isolates (26.2 versus 2.7% for U.S. and Canadian isolates, respectively), vancomycin-resistant enterococcal isolates (17.7 versus 0% for U.S. and Canadian isolates, respectively), and ceftazidime-resistant Enterobacter sp. isolates (30.6 versus 6.2% for U.S. and Canadian isolates, respectively) dramatically emphasize the relative lack of specific antimicrobial resistance genes (mecA, vanA, and vanB) in the Canadian microbial population. Among U.S. isolates, resistance to oxacillin among staphylococci, to vancomycin among enterococci, to penicillin among pneumococci, and to ceftazidime among Enterobacter spp. was observed in both nosocomial and community-acquired pathogens, although in almost every instance the proportion of resistant strains was higher among nosocomial isolates. Antimicrobial resistance continues to increase, and ongoing surveillance of microbial pathogens and resistance profiles is essential on national and international scales.

Oritavancin exhibited potent activity against vancomycin-susceptible (MIC50 and MIC90, 0.015/0.03 μg/ml) and vanB-carrying E. faecalis isolates (MIC50 and MIC90, 0.015 and 0.015 μg/ml). Higher (16- to 32-fold) MIC50s and MIC90s for vanA-harboring E. faecalis were noted (MIC50 and MIC90, 0.25 and 0.5 μg/ml), although oritavancin inhibited all strains at ≤0.5 μg/ml. Vancomycin-susceptible and vanB-carrying E. faecium strains (MIC50 and MIC90, ≤0.008 and ≤0.008 μg/ml for both) were very susceptible to oritavancin, as were VanA-producing isolates (MIC50 and MIC90, 0.03 and 0.06 μg/ml). Oritavancin exhibited good in vitro potency against this collection of organisms, including vancomycin-resistant enterococci.

BC-3781 is a novel semisynthetic pleuromutilin antimicrobial agent developed as an intravenous and oral therapy for acute bacterial skin and skin structure infections (ABSSSI) and respiratory tract infections (RTI). BC-3781 and comparator agents were tested by the broth microdilution method against 1,893 clinical Gram-positive organisms predominantly causing ABSSSI. BC-3781 exhibited potent activity against methicillin-resistant Staphylococcus aureus (MIC50/90, 0.12/0.25 μg/ml), coagulase-negative staphylococci (MIC50/90, 0.06/0.12 μg/ml), β-hemolytic streptococci (MIC50/90, 0.03/0.06 μg/ml), viridans group streptococci (MIC50/90, 0.12/0.5 μg/ml), and Enterococcus faecium (including vancomycin-nonsusceptible strains) (MIC50/90, 0.12/2 μg/ml). Compared with other antibiotics in use for the treatment of ABSSSI, BC-3781 displayed the lowest MICs and only a minimal potential for cross-resistance with other antimicrobial classes.

New broad-spectrum β-lactamases such as KPC enzymes and CTX-M-15 enzymes threaten to markedly reduce the utility of our armamentarium of β-lactam agents, even our most potent drugs, such as carbapenems. NXL104 is a broad-spectrum non-β-lactam β-lactamase inhibitor. In this evaluation, we examined organisms carrying defined β-lactamases and identified doses and schedules of NXL104 in combination with the new cephalosporin ceftaroline, which would maintain good bacterial cell kill and suppress resistance emergence for a clinically relevant period of 10 days in our hollow-fiber infection model. We examined three strains of Klebsiella pneumoniae and one isolate of Enterobacter cloacae. K. pneumoniae 27-908M carried KPC-2, SHV-27, and TEM-1 β-lactamases. Its isogenic mutant, K. pneumoniae 4207J, was “cured” of the plasmid expressing the KPC-2 enzyme. K. pneumoniae 24-1318A carried a CTX-M-15 enzyme, and E. cloacae 2-77C expressed a stably derepressed AmpC chromosomal β-lactamase. Dose-ranging experiments for NXL104 administered as a continuous infusion with ceftaroline at 600 mg every 8 h allowed identification of a 24-h area under the concentration-time curve (AUC) for NXL104 that mediated bactericidal activity and resistance suppression. Dose fractionation experiments identified that “time > threshold” was the pharmacodynamic index linked to cell kill and resistance suppression. Given these results, we conclude that NXL104 combined with ceftaroline on an 8-hourly administration schedule would be optimal for circumstances in which highly resistant pathogens are likely to be encountered. This combination dosing regimen should allow for optimal bacterial cell kill (highest likelihood of successful clinical outcome) and the suppression of resistance emergence.

Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC90 values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC90 was 0.12 μg/ml for S. apiospermum, but 1 to >8 μg/ml for other tested agents. Against S. aurantiacum, the MEC50 for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against S. prolificans, the MEC90 for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.

E1210 is a first-in-class broad-spectrum antifungal that suppresses hyphal growth by inhibiting fungal glycophosphatidylinositol (GPI) biosynthesis. In the present study, we extend these findings by examining the activity of E1210 and comparator antifungal agents against Aspergillus spp. by using the methods of the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to test wild-type (WT) as well as amphotericin B (AMB)-resistant (-R) and azole-R strains (as determined by CLSI methods). Seventy-eight clinical isolates of Aspergillus were tested including 20 isolates of Aspergillus flavus species complex (SC), 22 of A. fumigatus SC, 13 of A. niger SC, and 23 of A. terreus SC. The collection included 15 AMB-R (MIC, ≥2 μg/ml) isolates of A. terreus SC and 10 itraconazole-R (MIC, ≥4 μg/ml) isolates of A. fumigatus SC (7 isolates), A. niger SC (2 isolates), and A. terreus SC (1 isolate). Comparator antifungal agents included anidulafungin, caspofungin, amphotericin B, itraconazole, posaconzole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparators. The essential agreement (EA; ±2 log2 dilution steps) was 100% for all comparisons with the exception of posaconazole versus A. terreus SC (EA = 91.3%). The minimum effective concentration (MEC)/MIC90 values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, and voriconazole, respectively, were as follows for each species: for A. flavus SC, 0.03, ≤0.008, 0.12, 1, 1, and 1; for A. fumigatus SC, 0.06, 0.015, 0.12, >8, 1, and 4; for A. niger SC, 0.015, 0.03, 0.12, 4, 1, and 2; and for A. terreus SC, 0.06, 0.015, 0.12, 1, 0.5, and 1. E1210 was very active against AMB-R strains of A. terreus SC (MEC range, 0.015 to 0.06 μg/ml) and itraconazole-R strains of A. fumigatus SC (MEC range, 0.03 to 0.12 μg/ml), A. niger SC (MEC, 0.008 μg/ml), and A. terreus SC (MEC, 0.015 μg/ml). In conclusion, E1210 was a very potent and broad-spectrum antifungal agent regardless of in vitro method applied, with excellent activity against AMB-R and itraconazole-R strains of Aspergillus spp.

JNJ-Q2 is a broad-spectrum bactericidal fluoroquinolone with potent activity against Gram-positive and -negative pathogens. In this study, the in vitro activity of JNJ-Q2 was evaluated against 511 selected Staphylococcus aureus samples isolated in 2008-2009 from patients with acute bacterial skin and skin structure infections in the United States by using reference methodology. JNJ-Q2 was the most potent fluoroquinolone tested overall (MIC50 and MIC90, 0.12 and 0.5 μg/ml, respectively) and against methicillin- and fluoroquinolone-resistant subgroups in direct comparisons to moxifloxacin, levofloxacin, and ciprofloxacin (each being ≥16-fold less potent than JNJ-Q2).

Two blaOXA-48-like-positive isolates (Klebsiella pneumoniae and Enterobacter cloacae) were recovered in Argentina in 2008 as part of a large-scale survey focused on multidrug resistance in Enterobacteriaceae. In both cases, sequencing identified β-lactamase OXA-163, differing from OXA-48 by a single amino substitution and a 4-amino-acid deletion. OXA-163 hydrolyzed penicillins, ceftazidime, and cefotaxime, whereas OXA-48 did not. However, OXA-163 had a much lower ability to hydrolyze carbapenems than OXA-48, therefore barely being considered a carbapenemase. In both isolates, the blaOXA-163 gene was located on plasmids that differed in structure and size. However, a detailed genetic analysis revealed a similar genetic context in those isolates, with the blaOXA-163 gene being bracketed by novel transposase genes, making this genetic environment different from that reported for the blaOXA-48 gene. This study identified the first class D β-lactamase compromising both extended-spectrum cephalosporin and carbapenem activities.

CXA-101, a novel oxyimino-aminothiazolyl cephalosporin, CXA-201 (CXA-101 combined with tazobactam), and various comparators were susceptibility tested by broth microdilution methods against 1,301 well-characterized clinical strains collected worldwide, including ceftazidime-resistant members of the family Enterobacteriaceae and Klebsiella pneumoniae carbapenemase (KPC)- and extended-spectrum β-lactamase (ESBL)-producing strains of Pseudomonas aeruginosa and Bacteroides fragilis. CXA-201 was 2- to 32-fold more active than ceftazidime and piperacillin-tazobactam against ceftazidime-resistant Enterobacteriaceae species but less active than cefepime for some species. CXA-101 and CXA-201 were very active against P. aeruginosa (MIC50, 1 μg/ml for both compounds), including imipenem-resistant strains.

Rifamycin SV is a broad-spectrum, poorly absorbed antimicrobial agent that, when coupled with MMX technology, is being targeted for the oral treatment of traveler's diarrhea (TD) and Clostridium difficile-associated disease (CDAD). Rifamycin SV was tested for activity against 911 TD-associated enteropathogens and 30 C. difficile isolates collected from several global surveillance studies. Rifamycin SV demonstrated similar antimicrobial activity levels against the Enterobacteriaceae, with MIC50 values ranging from 32 to 128 μg/ml for all but one strain (an enterotoxigenic Escherichia coli at >512 μg/ml). For non-Enterobacteriaceae strains, MIC50 values ranged from 2 to 8 μg/ml, with the exception of Campylobacter spp., for which all strains had MIC values of >512 μg/ml. Rifamycin SV also demonstrated excellent activity (MIC50 of ≤0.03 μg/ml) against most C. difficile strains (including one hypervirulent NAP1 strain), and this activity was even superior to the potency observed for vancomycin, metronidazole, and rifaximin. In mutational passaging studies, rifamycin SV induced stable resistance and showed a mutation frequency in E. coli similar to that of rifampin. This study presents the potency of rifamycin SV for enteropathogens commonly recovered from patients with TD and CDAD. Additional in vitro and in vivo studies appear necessary to determine the utility of rifamycin SV as an oral agent for the prevention and treatment of TD and CDAD.

Among 39 carbapenem-resistant Enterobacteriaceae (2.7% overall; Escherichia coli, Enterobacter cloacae, and Klebsiella pneumoniae strains) isolated in 2006 and 2007 in India, 15 strains carried blaNDM-1 and 10 harbored a gene encoding a variant of the carbapenemase OXA-48, named blaOXA-181. One E. cloacae strain harbored blaVIM-6, and one K. pneumoniae strain carrying blaOXA-181 also possessed blaVIM-5. Multiple pulsed-field gel electrophoresis patterns and clonal dissemination within and among sites were observed. Isolates producing NDM-1 were disseminated in Indian health care facilities as early as 2006.

Community-onset (CO) candidemia, defined as a positive blood culture taken at or within 2 days of hospital admission, represents a distinct clinical entity associated with substantial morbidity and mortality. Reference MIC results from the SENTRY Antimicrobial Surveillance Program (2008-2009) were analyzed to compare the antifungal resistance patterns and species distributions from patients with CO and nosocomial bloodstream infections (BSI) in 79 medical centers. Among 1,354 episodes of BSI, 494 (36.5%) were classified as CO and 860 (63.5%) as nosocomial in origin. More than 95% of the isolates from both BSI types were contributed by Candida albicans (48.4%), C. glabrata (18.2%), C. parapsilosis (17.1%), C. tropicalis (10.6%), and C. krusei (2.0%). C. albicans was more common in CO BSI (51.0%) than nosocomial BSI (46.9%), whereas C. parapsilosis and C. krusei were more common in nosocomial BSIs (18.1 and 2.7%, respectively) than in CO BSIs (15.4 and 0.8%, respectively). C. glabrata and C. tropicalis were comparable in both CO (18.4 and 10.5%, respectively) and nosocomial (18.1 and 10.6%, respectively) episodes. Resistance to azoles (fluconazole, posaconazole, and voriconazole) and echinocandins (anidulafungin, caspofungin, and micafungin) was uncommon (<5%) in CO BSI using recently established Clinical and Laboratory Standards Institute breakpoint criteria. Resistance to echinocandins (anidulafungin [3.8%], caspofungin [5.1%], and micafungin [3.2%]) and azoles (fluconazole [7.7%], posaconazole [5.1%], and voriconazole [6.4%]) was most prevalent among nosocomial BSI isolates of C. glabrata. CO candidemia is not uncommon and appears to be increasing worldwide due to changing health care practices. Although resistance to the azoles and echinocandins remains uncommon among CO isolates, we demonstrate the emergence of nosocomial occurrences of C. glabrata expressing resistance to both monitored classes of antifungal agents.

Among 4,167 Staphylococcus aureus and 790 coagulase-negative Staphylococcus (CoNS; not S. saprophyticus) isolates collected consecutively from North American and Australian hospitals, only 87 (1.7% overall) isolates displayed a fusidic acid (FA; also known as CEM-102) MIC of ≥2 μg/ml (FA resistance). These strains were further evaluated with a multiplex PCR to amplify the acquired resistance genes fusB, fusC, and fusD. Mutations in fusA and fusE were evaluated in all isolates showing an absence of acquired resistance genes and/or showing FA MIC values of ≥64 μg/ml. S. aureus resistance rates were very low in the United States (0.3%) and were higher in Canada and Australia (7.0% for both countries). Among CoNS isolates, FA resistance rates were significantly more elevated than that for S. aureus (7.2 to 20.0%; the highest rates were in Canada). All 52 (41 CoNS) FA-resistant isolates from the United States showed FA MIC results of ≤64 μg/ml, and 7 of 11 S. aureus isolates carried fusC. CoNS strains from the United States carried fusB or fusC. In Canada, fusB and fusC occurrences were similar among S. aureus and CoNS isolates, and modestly elevated FA MIC values were observed (all MIC results were ≤32 μg/ml). Isolates from Australia showed MIC values ranging from 2 to 32 μg/ml, and S. aureus isolates were predominantly fusC positive. fusA mutations were detected in only three S. aureus isolates, conferring FA MIC values of 2 to 8 μg/ml. Target mutations have been considered the primary FA resistance mechanism among Staphylococcus spp.; however, acquired resistance genes appear to have a dominant role in resistance against this older antimicrobial agent. In summary, this study shows that acquired genes are highly prevalent among FA-resistant strains (>90%) in three nations with distinct or absence (United States) of fusidic acid clinical use.

The activity of CEM-101, a fluoroketolide, was compared to those of 11 other antimicrobial agents using the reference broth microdilution method tested against 103 Neisseria meningitidis strains, including ciprofloxacin-nonsusceptible isolates with confirmed gyrA (T91I) mutations. Among the tested isolates, 79.6% were serogroup B or C and all isolates were susceptible to ceftriaxone, azithromycin, minocycline, and rifampin. However, penicillin-nonsusceptible strains were observed (15.5%) and susceptibility to trimethoprim-sulfamethoxazole was only 50.5%. CEM-101 was the most active macrolide-like compound (MIC90, ≤0.015 μg/ml) compared with MIC90s of telithromycin (MIC90, 0.03 μg/ml), azithromycin and clarithromycin (MIC90, 0.12 μg/ml), and erythromycin (MIC90, 0.25 μg/ml). CEM-101 could provide a potent alternative for the prophylaxis of meningococcal disease.