In vitro activity of RP59500, an injectable streptogramin antibiotic, against vancomycin-resistant gram-positive organisms.

The in vitro activity of RP59500, a streptogramin antibiotic, against 146 clinical isolates of vancomycin-resistant gram-positive bacteria was examined. Five strains of the species Enterococcus casseliflavus and Enterococcus gallinarum, for which the MIC of vancomycin was 8 micrograms/ml, were also studied. Twenty-eight vancomycin-susceptible strains of Enterococcus faecalis and Enterococcus faecium were included for comparison. The drug was highly active against Leuconostoc spp., Lactobacillus spp., and Pediococcus spp. (MICs, < or = 2 micrograms/ml). RP59500 was more active against vancomycin-susceptible strains of E. faecium than E. faecalis (MICs for 90% of the strains [MIC90s], 1.0 versus 32 micrograms/ml). Vancomycin-resistant strains of E. faecalis were as resistant to RP59500 as vancomycin-susceptible strains (MIC90, 32 micrograms/ml), but some vancomycin-resistant E. faecium strains were relatively more resistant to the new agent (MIC90, 16; MIC range, 0.5 to 32 micrograms/ml) than were vancomycin-susceptible organisms of this species.     

Analysis by PCR and direct DNA sequencing of gyrA mutations associated with fluoroquinolone resistance in Enterococcus faecalis.

A region of gyrA, the gene encoding subunit A of DNA gyrase, that is known to be associated with resistance was amplified and sequenced from 16 Enterococcus faecalis and Enterococcus faecium isolates. Six ciprofloxacin-resistant clinical isolates (MICs of ciprofloxacin, 32 to 64 micrograms/ml) and one multistep resistant laboratory mutant of E. faecalis (MIC of ciprofloxacin, 128 micrograms/ml) contained a change from serine to arginine or to isoleucine at codon 83 or a change from glutamic acid to lysine or to glycine at codon 87 (Escherichia coli GyrA coordinates); these changes have been associated with fluoroquinolone resistance in other species. No difference in the region studied was found in two ciprofloxacin-resistant E. faecium isolates (MICs, 32 micrograms/ml) or in four laboratory derived, spontaneous ciprofloxacin-resistant mutants of E. faecalis (MICs, 8 to 16 micrograms/ml), suggesting that other mechanisms may be responsible for fluoroquinolone resistance in some enterococci.     

In vitro detection of enterococcal vancomycin resistance.

By using agar dilution as the standard method, we determined the ability of broth microdilution, disk diffusion, and an automated system (AMS Vitek) to detect three different levels of vancomycin resistance among six enterococcal isolates. Enterococcus gallinarum AIB-38 and AIB-39 exhibited low-level resistance (MIC, 16 to 32 micrograms/ml) that was detected only by agar and broth dilution methods. E. faecalis V583, E. faecium AIB-42, and E. faecalis AIB-41 showed moderately high-level resistance (MIC, 128 to 256 micrograms/ml) that was detected by dilution methods but not by disk diffusion unless prolonged incubation or an inoculum 10-fold greater than the standard was used. Similarly, this level of resistance was detected by AMS Vitek only when an inoculum 10-fold larger than recommended was used. The high resistance demonstrated by E. faecium AIB-40 (MIC, 2,048 micrograms/ml) was readily detected by all methods studied. Variation in the ability of different methods to detect vancomycin resistance among enterococci complicates monitoring the incidence of these organisms and could result in very major susceptibility reporting errors.     

Antimicrobial Susceptibility Patterns of Enterococci Causing Infections in Europe

In vitro susceptibilities of 4,208 enterococci (83% Enterococcus faecalis isolates, 13.6% Enterococcus faecium isolates, and 3.4% isolates of other species) from patients in 27 European countries towards 16 antibiotics were determined. High-level resistance to gentamicin varied by country (range, 1 to 49%; mean, 22.6% +/- 12. 3%) and per species (19.7% E. faecalis isolates, 13.6% E. faecium isolates, 3.4% by other species). Vancomycin resistance was detected in 0.06% E. faecalis, 3.8% E. faecium, and 19.1% isolates of other species. All enterococci were susceptible to LY 333328 and everninomicin, and 25% of E. faecalis isolates and 85% of other enterococci were susceptible to quinupristin-dalfopristin. The MIC of moxifloxacin and trovafloxacin for ciprofloxacin-susceptible E. faecalis at which 90% of the isolates were inhibited was 0.25 to 0.5 microg/ml.     

In vitro activity of decaplanin (M86-1410), a new glycopeptide antibiotic.

The in vitro activity of decaplanin (formerly M86-1410), a novel glycopeptide antimicrobial agent, was tested against 169 gram-positive bloodstream isolates from patients at the University of Iowa Hospitals and Clinics and 12 selected vancomycin-resistant strains. Enterococcus faecalis, E. faecium, Staphylococcus aureus, streptococci, bacilli, corynebacteria, and listeria were inhibited by decaplanin (MICs for 90% of the strains tested [MIC90s], 0.12 to 4 micrograms/ml). However, some rarely isolated and selected Enterococcus sp. populations had a MIC90 of 16 micrograms/ml, and S. haemolyticus strains had a MIC90 of 8 micrograms/ml. These in vitro results suggest that decaplanin may be useful against most gram-positive strains, even though some Enterococcus species and coagulase-negative staphylococci were potentially resistant (MICs, greater than or equal to 8 micrograms/ml).     

In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria

The in vitro activities of two new ketolides, HMR 3647 and HMR 3004, were tested by the agar dilution method against 280 strains of gram-positive bacteria with different antibiotic susceptibility profiles, including Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus spp. (group A streptococci, group B streptococci, Streptococcus pneumoniae, and alpha-hemolytic streptococci). Seventeen erythromycin-susceptible (EMs), methicillin-susceptible S. aureus strains were found to have HMR 3647 and HMR 3004 MICs 4- to 16-fold lower than those of erythromycin (MIC at which 50% of isolates were inhibited [MIC50] [HMR 3647 and HMR 3004], 0.03 microgram/ml; range, 0.03 to 0.06 microgram/ml; MIC50 [erythromycin], 0.25 microgram/ml; range, 0.25 to 0.5 microgram/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of > 64 micrograms/ml. The ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC50s of HMR 3647 and HMR 3004 against Ems enterococci (MIC < or = 0.5 microgram/ml) and those enterococcal isolates with erythromycin MICs of 1 to 16 micrograms/ml were 0.015 microgram/ml. E. faecalis strains that had erythromycin MICs of 128 to > 512 micrograms/ml showed HMR 3647 MICs in the range of 0.03 to 16 micrograms/ml and HMR 3004 MICs in the range of 0.03 to 64 micrograms/ml. In the group of E. faecium strains for which MICs of erythromycin were > or = 512 micrograms/ml, MICs of both ketolides were in the range of 1 to 64 micrograms/ml, with almost all isolates showing ketolide MICs of < or = 16 micrograms/ml. The ketolides were also more active than erythromycin against group A streptococci, group B streptococci, S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids. Time-kill studies showed bactericidal activity against one strain of S. aureus among the four strains tested. The increased activity of ketolides against gram-positive bacteria suggests that further study of these agents for possible efficacy against infections caused by these bacteria is warranted.     

Antibacterial oxazolidinones. In vitro activity of a new analogue, E3709.

The oxazolidinone compound E3709, which contains a 4-pyridyl group, was found to be more active in vitro than other members of this series, such as DuP 721. MIC90 for staphylococci(including methicillin-resistant isolates), streptococci (including Enterococcus faecalis), Clostridia, and diphtheroids was less than 0.5 micrograms/ml. Haemophilus influenzae, Moraxella catarrhalis, and Bacteroides fragilis were less susceptible, with an MIC90 between 2 and 8 micrograms/ml. E3709 MICs of Gram-negative species ranged from 100 to greater than 1000 micrograms/ml. At a concentration of 10 micrograms/ml, E3709 was bactericidal for selected Gram-positive species. A postantibiotic effect of 3 hr was observed against staphylococci. Resistance to E3709 was not detected.     

Susceptibility of enterococci to trimethoprim and trimethoprim-sulfamethoxazole.

The in vitro activities of trimethoprim (TMP), alone and in combination with sulfamethoxazole (SMX), against 131 clinical isolates of enterococci, 126 Streptococcus faecalis isolates, and 5 Streptococcus faecium isolates were determined by a broth microdilution method with Mueller-Hinton broth that was substantially free of inhibitory substances. The geometric mean MIC of TMP for strains of S. faecalis was 0.164 micrograms/ml (range, 0.03 to 8 micrograms/ml), with a geometric mean MBC of 0.298 micrograms/ml (range, 0.063 to 8 micrograms/ml). Although all strains were resistant to the sulfonamide alone, the inhibitory and bactericidal activities of TMP against strains of S. faecalis were markedly potentiated when TMP was combined in a fixed ratio of 1:19 with SMX; the geometric mean MIC of TMP was reduced to 0.016 micrograms/ml (range, 0.002 to 0.25 micrograms/ml), with a geometric mean MBC of 0.031 micrograms/ml (range, 0.004 to 0.25 micrograms/ml). The combination had no synergistic effect against strains of S. faecium; the geometric mean MICs and MBCs of both agents were ca. 0.06 micrograms/ml. The MBC/MIC ratios for TMP and TMP-SMX were less than or equal to 16 for all 131 strains. MICs and MBCs for TMP-SMX were unchanged, and for TMP they decreased when performed in broth supplemented with 50% heat-inactivated pooled human serum. For TMP and TMP-SMX, the susceptibilities of isolates with high-level resistance to gentamicin or streptomycin were the same as those of isolates susceptible to less than or equal to 2,000 micrograms of aminoglycoside per ml. These results suggest that TMP-SMX and TMP alone could prove useful in the treatment of serious enterococcal infections, including infections by strains with high-level resistance to aminoglycosides.     

Glycopeptide susceptibility among Danish Enterococcus faecium and Enterococcus faecalis isolates of animal and human origin and PCR identification of genes within the VanA cluster.

The MICs of vancomycin and avoparcin were determined for isolates of Enterococcus faecium and isolates of Enterococcus faecalis recovered from the feces of humans and animals in Denmark. Two hundred twenty-one of 376 (59%) isolates of E. faecium and 2 of 133 (1.5%) isolates of E. faecalis were resistant to vancomycin (MICs, 128 to > or = 256 micrograms/ml), and all vancomycin-resistant isolates were resistant to avoparcin (MICs, 64 to > or = 256 micrograms/ml). All vancomycin-resistant isolates examined carried the vanA, vanX, and vanR genes, suggesting that a gene cluster similar to that of the transposon Tn1546 was responsible for the resistance.     

In vitro activity of moxifloxacin, a new 8-methoxyquinolone, against gram-positive bacteria

The in vitro activity of moxifloxacin, formerly BAY 12-8039, against gram-positive bacteria was tested by the agar dilution method. A total of 189 isolates that included Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, streptococci, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids were tested. Moxifloxacin showed greater potency than ciprofloxacin against S. aureus, streptococci, and enterococci, having Minimal Inhibitory Concentrations (MICs) lower than those of ciprofloxacin by 2- to 64-fold. This improved activity was most prominent for S. aureus. Moxifloxacin was active against Leuconostoc and Rhodococcus species. Time-kill studies using moxifloxacin at a concentration of 3 micrograms/mL against one isolate each of methicillin-resistant S. aureus (MSSA) (MIC, 0.031 microgram/mL), MRSA (MIC, 1 microgram/mL), two isolates of E. faecalis (MICs, 0.25 and 2 micrograms/mL), and two isolates of vancomycin-resistant E. faecium (MICs, 0.25 and 2 micrograms/mL) revealed an average decrease in colony forming unit (CFU) by 3.8, 0.4, 4.0, 2.0, 4.2, and 1.8 log10 CFU/mL at 24 h, respectively. Moxifloxacin is a new 8-methoxyquinolone with improved in vitro activity against gram-positive bacteria. Further studies of the in vivo activity of this compound appear warranted.     

Increasing resistance to beta-lactam antibiotics among clinical isolates of Enterococcus faecium: a 22-year review at one institution.

To identify any change in the antibiotic resistance of Enterococcus faecium, we examined the antibiotic susceptibilities of clinical strains (n = 84) isolated at one institution during the 22 years since 1968. A significant increase in resistance to penicillin was observed during the study period: the MICs of penicillin for 50 and 90% of isolates tested were 16 and 64 micrograms/ml, respectively, from 1969 to 1988 (n = 48; geometric mean MIC, 14 micrograms/ml) , whereas they were 256 and 512 micrograms/ml, respectively, from 1989 to 1990 (n = 36; geometric mean MIC, 123 micrograms/ml) (P less than 0.001). A comparable increase in resistance to ampicillin was also noted (P less than 0.001). No strains produced detectable beta-lactamase. In contrast, susceptibilities to vancomycin, teicoplanin, and ciprofloxacin remained stable. High-level resistance to gentamicin was observed in none of 48 isolates from 1969 to 1988, but was present in 22 of 36 strains (61%) from 1989 to 1990 (P less than 0.001) and was significantly associated with resistance (MIC, greater than or equal to 128 micrograms/ml) to penicillin (P less than 0.001). To assess the potential evolution of antibiotic resistance in this species, clinical isolates (n = 24) were compared with strains isolated in 1968 from a human population in the Solomon Islands that was never exposed to antibiotics. Solomon Island isolates were significantly more susceptible than all clinical strains to penicillin, ampicillin, and vancomycin (P less than 0.001 for each), but they exhibited no differences in susceptibility to teicoplanin or ciprofloxacin. The penicillin-binding affinity of penicillin-binding protein 5 (PBP 5) in penicillin-resistant clinical strains (MIC, 512 micrograms/ml) was notably lower than that in strains with more typical susceptibilities, suggesting an alteration in this PBP as a possible mechanism for increased penicillin resistance. Solomon Island strains most susceptible to penicillin demonstrated a prominent PBP 5* and the absence of PBP 5. These changes in the antibiotic resistance of E. faecium emphasize the importance of identifying this species in patients with serious enterococcal infections and the necessity of assessing its susceptibility to both beta-lactams and aminoglycosides if effective therapy is to be identified.     

The activity of metal compounds against aerobic and anaerobic bacteria.

We evaluated the antimicrobial activity of two metal compounds, JM-1397 (OsO2[xylyl]2) and JM-2469 (AuCl[S2CPEt3]). Both inhibited methicillin-susceptible and methicillin-resistant Staphylococcus aureus at concentrations of 0.5-2 micrograms/ml, with a minimum inhibitory concentration (MIC90) of 1 microgram/ml for JM-1397 and 0.5 microgram/ml for JM-2469. Similar concentrations inhibited methicillin-susceptible and -resistant coagulase-negative staphylococci (S. epidermidis, S. haemolyticus, and S. saprophyticus). JM-2469 inhibited group A, B, C, F, and G beta-hemolytic streptococci and viridans group streptococci at 1-8 micrograms/ml (MIC90 4 micrograms/ml) but Enterococcus faecalis and E. faecium had MICs of 8-16 micrograms/ml. JM-1397 had MICs for these organisms of greater than 64 micrograms/ml. Bacteroides fragilis, other Bacteroides, and Clostridium species were inhibited by less than or equal to 0.12-4 micrograms/ml (MIC90, 0.5 microgram/ml). MICs of both compounds for Enterobacteriaceae and Pseudomonas spp. were greater than 64 micrograms/ml. These studies show that osmium and gold compounds have potential as topical agents against Gram-positive and anaerobic species.     

In vitro activity of linezolid against key gram-positive organisms isolated in the united states: results of the LEADER 2004 surveillance program

Since the approval of linezolid in 2000, sporadic reports of resistance have been given and a greater understanding of the underlying mechanisms of resistance has been gained. However, since these developments, an updated status of the in vitro activity of linezolid against gram-positive organisms from the United States has not been reported. The LEADER 2004 surveillance initiative was undertaken to obtain current and representative data on the activity of linezolid against key species, including isolates with significant resistance phenotypes. Organisms were isolated during 2004 and included 2,872 Staphylococcus aureus, 496 coagulase-negative staphylococcus (CNS), 428 Enterococcus faecalis, 196 Enterococcus faecium, and 422 Streptococcus pneumoniae isolates. All S. aureus isolates (54.2% oxacillin resistant) were susceptible to linezolid (MIC90 = 2 microg/ml); MIC distributions were consistent, regardless of oxacillin or multidrug resistance status. For CNS, one nonsusceptible isolate was encountered (Staphylococcus epidermidis; MIC = 32 microg/ml), but overall, the MIC(90) (1 microg/ml) was lower than that obtained with S. aureus. For E. faecalis and E. faecium, 99.5% and 96.4% of isolates, respectively, were linezolid susceptible. Both species had an MIC90 of 2 microg/ml, and MIC distributions did not vary with the vancomycin susceptibility status of the populations analyzed. Linezolid nonsusceptibility was not encountered among the S. pneumoniae isolates. These findings indicate that linezolid nonsusceptibility has remained rare among staphylococci and uncommon and sporadic among enterococci. Nonetheless, careful and ongoing monitoring of the in vitro effectiveness of linezolid will be needed so that any changes to the current status may be detected as soon as possible.     

An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin-dalfopristin

Enterococcus faecalis isolates are resistant to clindamycin (CLI) and quinupristin-dalfopristin (Q-D), and this is thought to be a species characteristic. Disruption of a gene (abc-23, now designated lsa, for "lincosamide and streptogramin A resistance") of E. faecalis was associated with a > or =40-fold decrease in MICs of Q-D (to 0.75 microg/ml), CLI (to 0.12 to 0.5 microg/ml), and dalfopristin (DAL) (to 4 to 8 microg/ml) for the wild-type E. faecalis parental strain (Q-D MIC, 32 microg/ml; CLI MIC, 32 to 48 microg/ml; DAL MIC, 512 microg/ml). Complementation of the disruption mutant with lsa on a shuttle plasmid resulted in restoration of the MICs of CLI, Q-D, and DAL to wild-type levels. Under high-stringency conditions, lsa was found in 180 of 180 isolates of E. faecalis but in none of 189 other enterococci. Among 19 erm(B)-lacking Enterococcus faecium strains, 9 (47%) were highly susceptible to CLI (MIC, 0.06 to 0.25 microg/ml) and had DAL MICs of 4 to 16 microg/ml; for the remaining erm(B)-lacking E. faecium strains, the CLI and DAL MICs were 4 to > 256 and 2 to > 128 microg/ml, respectively. In contrast, none of 32 erm(B)-lacking E. faecalis strains were susceptible (CLI MIC range, 16 to 32 microg/ml; DAL MIC range, > or =32 microg/ml). When lsa was introduced into an E. faecium strain initially susceptible to CLI, the MICs of CLI and DAL increased > or =60-fold and that of Q-D increased 6-fold (to 3 to 6 microg/ml). Introduction of lsa into two DAL-resistant (MICs, > 128 microg/ml), Q-D-susceptible (MICs, 0.5 and 1.5 microg/ml) E. faecium strains (CLI MICs, 12 and >256 microg/ml) resulted in an increase in the Q-D MICs from 3- to 10-fold (to 8 and >32 microg/ml), respectively. Although efflux was not studied, the similarity (41 to 64%) of the predicted Lsa protein to ABC proteins such as Vga(A), Vga(B), and Msr(A) of Staphylococcus aureus and YjcA of Lactococcus lactis and the presence of Walker A and B ATP-binding motifs suggest that this resistance may be related to efflux of these antibiotics. In conclusion, lsa appears to be an intrinsic gene of E. faecalis that explains the characteristic resistance of this species to CLI and Q-D.     

In vitro activity of Ro 13-9904, a new beta-lactamase-stable cephalosporin.

The minimal inhibitory concentration (MIC) of Ro 13-9904 against 245 clinical isolates was determined by an agar dilution method. The activity of Ro 13-9904 against most Enterobacteriaceae was similar to that of cefotaxime; it was slightly more active than cefotaxime against Proteus mirabilis, Providencia species, and Serratia marcescens, but slightly less active against Klebsiella species. Ro 13-9904 was twofold more active than cefotaxime and threefold more active than ticarcillin against ticarcillin-susceptible Pseudomonas aeruginosa, with a mean MIC of 7.2 micrograms/ml; isolates highly resistant to ticarcillin were inhibited by a mean MIC of 17.2 micrograms/ml. Ro 13-9904 was fourfold more active than ampicillin against susceptible Haemophilus influenzae and was equally active against beta-lactamase-producing isolates. Ro 13-9904 was highly active against pneumococci and moderately active (MIC, 4 micrograms/ml) against Staphylococcus aureus isolates, whether they were susceptible or resistant to penicillin G. Oxacillin-resistant S. aureus and Streptococcus faecalis were completely resistant to Ro 13-9904 (MIC, greater than 128 micrograms/ml).     

In vitro activities of sparfloxacin, tosufloxacin, ciprofloxacin, and fleroxacin.

The in vitro activity of sparfloxacin was compared with those of tosufloxacin, ciprofloxacin, and fleroxacin against 730 bacterial isolates representing 49 different species. Sparfloxacin and ciprofloxacin had similar spectra of activity, but sparfloxacin was less active against Pseudomonas aeruginosa and more active against many gram-positive cocci and anaerobic bacteria. Tosufloxacin MICs were generally 8- to 16-fold lower than those for sparfloxacin or ciprofloxacin. All four fluoroquinolones were active against nalidixic acid-susceptible strains of the family Enterobacteriaceae (MIC for 90% of the isolates [MIC90], less than or equal to 0.25 micrograms/ml) but nalidixic acid-resistant strains were less susceptible (MIC90, greater than or equal to 4.0 micrograms/ml). Against Pseudomonas aeruginosa isolates, MIC90s were 1.0 micrograms/ml for tosufloxacin, 2.0 micrograms/ml for ciprofloxacin, and 4.0 micrograms/ml for sparfloxacin. Against Enterococcus faecalis, sparfloxacin and ciprofloxacin MIC90s were 1.0 and 2.0 micrograms/ml, respectively. MIC90s for ciprofloxacin-susceptible Staphylococcus aureus were 0.016 micrograms/ml for tosufloxacin, 0.06 micrograms/ml for sparfloxacin, and 0.5 micrograms/ml for both ciprofloxacin and fleroxacin. With four species of gram-negative bacilli, mutants resistant to two to four times the sparfloxacin MIC occurred spontaneously at frequencies of 10(-7) to 10(-9): single-step high-level resistance was not observed. In vitro-selected sparfloxacin-resistant mutants displayed cross-resistance to other quinolones, as did clinical isolates of ciprofloxacin-resistant S. aureus. Tosufloxacin MICs with broth microdilution methods were four- to eightfold greater than those obtained with agar dilution methods. The two procedures gave comparable results when sparfloxacin or ciprofloxacin was being tested.     

儿童患者中肠球菌属临床分离株耐药特征分析

目的了解儿童患者临床分离肠球菌属的耐药特征，指导临床合理用药。方法测定11种抗菌药物对158株肠球菌的MIC，Nithocefin纸片法检测B内酰胺酶，数据用WHONET5．3软件分析处理。结果158株儿童临床分离肠球菌中，粪肠球菌、屎肠球菌、坚韧肠球菌、鸟肠球菌和海氏肠球菌分别占56．3％、39．9％、1．3％、1．3％和1．3％；屎肠球菌对氨苄西林、阿莫西林-克拉维酸和环丙沙星的耐药率分别为96．8％，95，2％和84．1％，粪肠球菌对上述3种抗菌药的耐药率分别为23．6％，18％和49，4％，屎肠球菌的耐药率明显高于粪肠球菌（P〈20，001）；粪肠球菌出现2株万古霉素MIC为8mg／L的耐药菌，粪肠球菌和屎肠球菌对替考拉宁全部敏感。儿童患者中多重耐药肠球菌属菌株占88．6％。结论儿童患者肠球菌属的耐药状况十分严重，尤其屎肠球菌对B内酰胺类、氨基糖苷类和氟喹诺酮类抗菌药耐药率很高。     

In vitro activities of quinolones against enterococci resistant to penicillin-aminoglycoside synergy.

The MICs and MBCs of CI-934, ciprofloxacin, difloxacin (A-56619), A-56620, norfloxacin, enoxacin, amifloxacin, and coumermycin were determined for 43 clinical isolates of Enterococcus faecalis known to be resistant to penicillin-aminoglycoside synergy. Results were compared with those obtained for 37 synergy-susceptible E. faecalis and 22 Enterococcus faecium strains. Although no substantial differences in quinolone activities were observed between synergy-resistant and -susceptible E. faecalis strains, CI-934 and ciprofloxacin were the drugs that demonstrated the greatest bactericidal activity against both types of E. faecalis. The MBCs of the other quinolones were generally within a single twofold dilution of the MICs, but their antienterococcal activity did not approach that of CI-934 or ciprofloxacin. The MBCs for 90% of the isolates of CI-934 for synergy-resistant and -susceptible E. faecalis strains were 1 and less than or equal to 0.5 microgram/ml, respectively. The ciprofloxacin MBC for 90% of the E. faecalis strains tested was 1 microgram/ml. For E. faecium isolates the CI-934 and ciprofloxacin MBCs for 90% of the isolates were 8 and 4 micrograms/ml, respectively. Time-kill assays performed with synergy-susceptible enterococcal strains showed that the bactericidal activities of both CI-934 and ciprofloxacin were less than those of the penicillin-aminoglycoside combinations tested. However, against synergy-resistant isolates the activities of these two quinolones were comparable with and sometimes greater than those of penicillin-aminoglycoside combinations.     

Vancomycin-resistant enterococci (VRE) colonization of high-risk patients in tertiary care Canadian hospitals. Canadian VRE Surveillance Group.

We isolated 1487 Enterococcus species from 1200 stool specimens collected from high-risk patients in 12 Canadian tertiary care hospitals between October 1995 and November 1996. The composition of the 1487 isolates was 601 vancomycin-sensitive Enterococcus faecalis (40.4%), 667 vancomycin-sensitive Enterococcus faecium (44.9%), 18 vancomycin-resistant (nine isolates MIC 8-16 micrograms/mL; nine isolates MIC > or = 32 micrograms/mL) E. faecium (VREF) (1.2%), 95 vancomycin-sensitive Enterococcus gallinarum (6.4%), 29 vancomycin-resistant (all MICs 8-16 micrograms/mL) E. gallinarum (2.0%), and 77 vancomycin-sensitive Enterococcus casseliflavus (5.2%). Nine of the 18 VREF isolates collected possessed the vanA genotype and were from three patients at one hospital. Two other VREF isolates, of the vanB genotype, were from a single patient at a second hospital, and the remaining seven isolates, also all of the vanB genotype, were from five patients at a third hospital. All VREF were ampicillin resistant (MIC > or = 16 micrograms/mL), streptomycin resistant (MIC > 1000 micrograms/mL), and ciprofloxacin resistant (MIC > or = 4 micrograms/mL). Ten of the 18 VREF were also resistant to gentamicin (MIC > 500 micrograms/mL), while all 18 isolates had quinupristin/dalfopristin MICs < or = 0.5 microgram/mL. In conclusion, high-risk patients in tertiary care Canadian hospitals are rarely colonized (9/1200 patients, 0.75%) with VREF in their lower gastrointestinal tract. These findings correlate well with the lack of reported VREF infection in high-risk patients in Canadian hospitals. Quinupristin/dalfopristin demonstrated excellent in vitro activity against VREF and other non-faecalis species of Enterococcus, many of which also possessed high-level ampicillin, and/or high-level aminoglycoside, and/or ciprofloxacin resistance.     

In vitro activity of LY264826, a new glycopeptide antibiotic, against gram-positive bacteria isolated from patients with cancer.

The in vitro activity of LY264826, a novel glycopeptide antibiotic produced by Amycolatopsis orientalis, was compared with those of vancomycin, teicoplanin, and oxacillin against 311 gram-positive clinical isolates from patients with cancer, LY264826 had lower MICs for 90% of isolates (MIC90) than vancomycin for all species tested. It was active against oxacillin-resistant isolates including Staphylococcus aureus (MIC90, 0.5 micrograms/ml), Staphylococcus haemolyticus (MIC90, 2.0 micrograms/ml), Enterococcus spp. (MIC90, 0.5 micrograms/ml), Bacillus cereus (MIC90, 0.25 micrograms/ml), and Corynebacterium jeikeium (MIC90, 0.12 micrograms/ml). For S. aureus, including oxacillin-resistant isolates, the MICs of LY264826 were similar to those of teicoplanin. For coagulase-negative staphylococci, however, LY264826 had MICs that were 4- to 32-fold lower than those of teicoplanin. Against most streptococcal species the activities of LY264826 and teicoplanin were similar. Bactericidal activity against Staphylococcus spp. and most Streptococcus pyogenes isolates was less than or equal to 1 dilution of the MIC. One isolate of S. pyogenes and all Enterococcus faecalis strains tested were tolerant of LY264826, with MBCs greater than or equal to 32-fold greater than the MICs. The addition of 50% human serum resulted in a significant increase in activity only against Staphylococcus epidermidis. Variations in pH from 6.4 to 8.4 and in inoculum from 10(3) to 10(7) CFU/ml did not significantly affect the activity of LY264826.