In vitro activity of LY264826 compared to other glycopeptides and daptomycin.

LY264826 a new naturally occurring glycopeptide inhibited 90% of methicillin-susceptible and -resistant Staphylococcus aureus at 1 micrograms/ml. LY264826 had similar activity against methicillin-susceptible and -resistant coagulase-negative staphylococci. The LY264826 MIC90 for Streptococcus pyogenes was 0.25 microgram/ml, twofold more active than vancomycin and twofold less active than teicoplanin. LY264826 was eightfold more active than vancomycin and twofold more active than teicoplanin against enterococci. LY264826 inhibited Streptococcus pneumoniae at 0.25 microgram/ml and Listeria monocytogenes at 0.5 microgram/ml. Clostridium were inhibited by less than or equal to 0.25 microgram/ml of LY264826 and peptococci, peptostreptococci, and Fusobacterium were inhibited by less than 0.5 microgram/ml. Bacteroides species were LY284826 -resistant as were all Enterobacteriaceae, Flavobacterium, and Neisseria spp. Minimum bactericidal and inhibitory concentrations (MBCs and MICs) were within a dilution for S. aureus, S. pyogenes, and S. pneumoniae, but greater than or equal to 32-fold greater for enterococci.     

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.     

Activity of glycopeptides against vancomycin-resistant gram-positive bacteria.

Gram-positive bacteria resistant to vancomycin are rare; but they include members of the genera Leuconostoc, Lactobacillus, and Pediococcus, as well as recently emerging vancomycin-resistant strains of Enterococcus faecium and Enterococcus faecalis. Vancomycin, teicoplanin, and several vancomycin derivatives were tested for their activities against vancomycin-resistant gram-positive bacteria. Vancomycin-resistant E. faecium and E. faecalis were generally cross-resistant to other glycopeptides, but some N-substituted vancomycin derivatives were active against the resistant strains, with MICs of 2 to 32 micrograms/ml. These vancomycin derivatives also had significant levels of activity against intrinsically vancomycin-resistant organisms such as Leuconostoc sp. While vancomycin resistance in E. faecium and E. faecalis was inducible, resistance in members of the genera Leuconostoc, Lactobacillus, and Pediococcus appeared to be expressed constitutively. Antibody to a vancomycin-induced membrane protein found in membranes of resistant enterococci did not detect a cross-reacting protein in other vancomycin-resistant species.     

Comparison of LY264826-gentamicin with vancomycin-gentamicin against enterococci from blood cultures.

The combination of the new glycopeptide LY264826 and gentamicin was compared with the combination of vancomycin and gentamicin against 30 strains of enterococci, comprising 20 strains of Enterococcus faecalis, five strains of Enterococcus faecium and five strains of Enterococcus avium, isolated from blood cultures. LY264826 plus gentamicin was synergic against E. faecalis and E. faecium, but not against E. avium.     

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.     

Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium.

Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the combination of a glycopeptide antibiotic plus gentamicin was effective against experimental infection due to E. faecium with low-level resistance to vancomycin.     

In vitro antibacterial activity of LY333328, a new semisynthetic glycopeptide.

LY333328 is a semisynthetic N-alkyl derivative of LY264826, a naturally occurring structural analog of vancomycin. LY333328 was evaluated for its in vitro inhibitory and bactericidal activities in comparison with those of the two currently available glycopeptides (vancomycin and teicoplanin). Glycopeptide-susceptible test strains included a total of 311 isolates (most of clinical origin) from the genera Staphylococcus, Enterococcus, Streptococcus, Aerococcus, Gemella, Lactococcus, Listeria, Corynebacterium, and Clostridium. Test strains resistant or intermediate to vancomycin and/or teicoplanin included 56 clinical isolates of Enterococcus (of the VanA, VanB, and VanC phenotypes) and 32 clinical isolates of Staphylococcus (S. haemolyticus, S. epidermidis, and S. aureus), 31 strains of gram-positive genera outside the spectrum of activity of vancomycin (Leuconostoc, Pediococcus, Lactobacillus, and Erysipelothrix), and laboratory-derived organisms obtained after exposure of susceptible Staphylococcus isolates to teicoplanin (6 strains) or laboratory-derived organisms with resistance determinants received from VanA enterococci (2 Enterococcus and 25 Listeria transconjugants). LY333328 was highly active against staphylococci, enterococci, and listeriae (whether they were clinical or laboratory-derived strains) resistant to the currently available glycopeptides. In particular, the MICs of LY333328 did not vary substantially between teicoplanin-susceptible and teicoplanin-resistant staphylococci and between vancomycin-susceptible and vancomycin-resistant enterococci. LY333328 demonstrated fairly good inhibitory activity even against most strains of Leuconostoc, Pediococcus, and Erysipelothrix (MIC range, 1 to 8 microg/ml), whereas it proved less active (although much more active than vancomycin or teicoplanin) against Lactobacillus strains. In minimal bactericidal concentration (MBC) and time-kill studies, LY333328 demonstrated excellent bactericidal activity; enterococci, in particular, which were largely tolerant of vancomycin and teicoplanin, were uniformly killed by LY333328, with MBC-to-MIC ratios of 4 to 8 for most vancomycin-susceptible and vancomycin-resistant strains. In attempts to select for resistant clones, no survivors stably growing in the presence of 10 microg of LY333328 per ml were obtained from the Staphylococcus and Enterococcus test strains exposed to the drug.     

In vitro activity of the trinem sanfetrinem (GV104326) against gram-positive organisms.

The in vitro activity of the trinem sanfetrinem (formerly GV104326) (GV) was compared with that of vancomycin, ampicillin, and/or nafcillin against 287 gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and multiresistant enterococci, by the agar and microbroth dilution methods. GV demonstrated 2 to 16 times more activity than ampicillin and nafcillin against the majority of these organisms. The MIC range of GV was 16 to 64 micrograms/ml for 19 Enterococcus faecium strains that were highly resistant to ampicillin (ampicillin MIC range, 64 to 512 micrograms/ml) and vancomycin resistant and 0.25 to 32 micrograms/ml for resistant Rhodococcus spp. Similar activities (+/-1 dilution) were observed by either the agar or the broth microdilution method. GV demonstrated bactericidal activity against a beta-lactamase-producing Enterococcus faecalis strain and against two methicillin-susceptible Staphylococcus aureus strains in 10(5)-CFU/ml inocula. Synergy between GV and gentamicin was observed against an E. faecalis strain that lacked high-level gentamicin resistance. The activity of GV suggests this compound warrants further study.     

Susceptibility of gram-positive cocci from 25 UK hospitals to antimicrobial agents including linezolid. The Linezolid Study Group

The prevalence of antibiotic resistance amongst Gram-positive cocci from 25 UK hospitals was studied over an 8 month period in 1999. A total of 3770 isolates were tested by the sentinel laboratories using the Etest; these bacteria comprised 1000 pneumococci, 1005 Staphylococcus aureus, 769 coagulase-negative staphylococci (CNS) and 996 enterococci. To ensure quality, 10% of the isolates were retested centrally, as were any found to express unusual resistance patterns. The prevalence of penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci and methicillin-resistant S. aureus (MRSA) varied widely amongst the sentinel laboratories. The resistance rates to methicillin among S. aureus and CNS were 19.2 and 38.9%, respectively, with MRSA rates in individual sentinel sites ranging from 0 to 43%. No glycopeptide resistance was seen in S. aureus, but 6.5% of CNS isolates were teicoplanin resistant and 0.5% were vancomycin resistant. Vancomycin resistance was much more frequent among Enterococcus faecium (24.1%) than E. faecalis (0.5%) (P<0.05), with most resistant isolates carrying vanA. The rate of penicillin resistance in pneumococci was 8.9%, and this resistance was predominantly intermediate (7.9%), with only six hospitals reporting isolates with high level resistance. The prevalence of erythromycin resistance among pneumococci was 12.3%, with the majority of resistant isolates having the macrolide efflux mechanism mediated by mefE. All the organisms tested were susceptible to linezolid with MICs in the range 0.12-4 mg/L. The modal MICs of linezolid were 1 mg/L for CNS and pneumococci, and 2 mg/L for S. aureus and enterococci. Linezolid was the most potent agent tested against Gram-positive cocci, including multiresistant strains, and as such may prove a valuable therapeutic option for the management of Gram-positive infections in hospitals.     

革兰阳性球菌耐药性监测

目的监测和探讨从感染患者中分离出的革兰阳性球菌的耐药情况。方法收集2007年1～12月分离的非重复阳性球菌420株，采用国际标准琼脂稀释法测定最小抑菌浓度。结果耐甲氧西林金黄色葡萄球菌（MRSA）和耐甲氧西林表皮葡萄球菌（MRSE）分别占40％（24／60）和70％（49／70）。未发现MRSA或MRSE对万古霉素和替考拉宁耐药菌株。耐青霉素肺炎链球菌的总耐药率为32．5％（耐药2．5％，中敏30％）。肠球菌40株，耐青霉素粪肠球菌占40％，而屎肠球菌对青霉素100％耐药。粪肠球菌和屎肠球菌对高浓度庆大霉素耐药率分别为55％（30％～86％）和78％（50％～100％）。未发现对万古霉素、替考拉宁耐药的肠球菌。结论大部分抗菌药物耐药率与国内报道一致，替考拉宁和万古霉素对革兰阳性球菌仍然保持很高的抗菌活性。     

2010年中国12所教学医院革兰阳性球菌耐药性研究

目的调查2010年我国12所教学医院临床分离的革兰阳性球菌的耐药性。方法收集2010年6-12月9个城市12所教学医院临床分离的1 181株非重复革兰阳性球菌。采用琼脂稀释法测定抗菌药物的最低抑菌浓度(MIC)值,计算不同病原菌对常用临床抗菌药物的耐药率。结果金葡菌和凝固酶阴性葡萄球菌中耐苯唑西林菌株分别占40.6%(191/470)和79.6%(187/236);不同标本苯唑西林耐药金葡菌(MRSA)检出率为22.2%～72.7%。在ICU患者中,MRSA的检出率为71.4%,高于MRSA在住院患者中的比率。未发现对替考拉宁、万古霉素和利奈唑胺耐药的金葡菌;替加环素对金葡菌的MIC值范围为0.032～0.5 mg/L。在肠球菌属中发现10株屎肠球菌和2株粪肠球菌对万古霉素耐药。粪肠球菌和屎肠球菌对替加环素的敏感率均为100%,对利奈唑胺的敏感率分别为98.3%和100%。按青霉素非脑膜炎株折点判读,肺炎链球菌中青霉素耐药株(PRSP)的比率为6.0%(14/232),其中5岁以下儿童中PRSP的比率为13.8%(9/65),65岁以上的老人中PRSP的发生率为5.1%(3/59);未发现对替考拉宁、万古霉素、利奈唑胺、替加环素耐药的肺炎链球菌。结论葡萄球菌中MRSA检出率在ICU患者中较门诊和住院患者高,MRSA主要分离自呼吸道标本和各种分泌物和脓液标本。万古霉素耐药的肠球菌在我国发生率低。PRSP在5岁以下儿童中的比率明显高于其他年龄组。替考拉宁、万古霉素、利奈唑胺、替加环素对葡萄球菌、粪肠球菌、屎肠球菌和肺炎链球菌具有很好的抗菌活性。     

Activities of the semisynthetic glycopeptide LY191145 against vancomycin-resistant enterococci and other gram-positive bacteria.

LY191145 is the prototype of a series of compounds with activities against vancomycin-resistant enterococci derived by modification of the glycopeptide antibiotic LY264826. LY191145 had MICs for vancomycin- and teicoplanin-resistant enterococci of < or = 4 micrograms/ml for 50% of isolates and < or = 16 micrograms/ml for 90% of isolates. Its MICs for vancomycin-resistant, teicoplanin-susceptible enterococci were 1 to 8 micrograms/ml. LY191145 retains the potent activities of its parent compound against staphylococci and streptococci. In vivo studies in a mouse infection model confirmed these activities. This compound indicates the potential of semisynthetic glycopeptides as agents against antibiotic-resistant gram-positive bacteria.     

In vitro activity of RP 59500, a semisynthetic injectable pristinamycin, against staphylococci, streptococci, and enterococci.

The in vitro activity of RP 59500, a semisynthetic pristinamycin, was compared with the activities of vancomycin, oxacillin, ampicillin, gentamicin, ciprofloxacin, and rifampin against five Staphylococcus species, five Streptococcus species, and four Enterococcus species. For staphylococci, MICs were 0.13 to 1 microgram/ml and the MICs for 90% of the strains tested (MIC90s) were 0.13 to 0.5 microgram/ml; there were no differences between oxacillin-susceptible and -resistant strains. For streptococci, MICs were 0.03 to 4 micrograms/ml and MIC90s were 0.25 to 2 micrograms/ml; viridans group streptococci were the least susceptible streptococci. For enterococci, MICs were 0.25 to 32 micrograms/ml and MIC90s were 2 to 4 micrograms/ml; Enterococcus faecalis was the least susceptible. Vancomycin was the only comparative drug with consistent activity against all species of gram-positive cocci. With RP 59500, raising the inoculum 100-fold, lowering the pH of cation-adjusted Mueller-Hinton broth to 5.5, or omitting cation supplementation had little effect on MICs, but 50% serum increased MICs 2 to 4 dilution steps. The differences between MBCs and MICs were greater for staphylococci and enterococci than for streptococci. Time-kill studies with 24 strains indicated that RP 59500 concentrations 2-, 4-, and 16-fold greater than the MICs usually killed bacteria of each species at similar rates; reductions in CFU per milliliter were less than those observed with oxacillin or vancomycin against staphylococci and less than those observed with ampicillin against enterococci. RP 59500 antagonized the bactericidal activities of oxacillin and gentamicin against Staphylococcus aureus ATCC 29213 and that of ampicillin against E. faecalis ATCC 29212. Against the latter, combination with gentamicin was indifferent. RP 59500 has a broad spectrum of in vitro activity against gram-positive cocci; combining it with other drugs is not advantageous.     

In vitro activity of LY333328, an investigational glycopeptide antibiotic, against enterococci and staphylococci.

The in vitro activities of LY333328 were compared with those of vancomycin, teicoplanin, and quinupristin-dalfopristin (Synercid) against 219 strains of enterococci and staphylococci, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. MICs and MBCs were determined by a microtiter dilution protocol. LY333328 demonstrated superior activity against vancomycin-resistant enterococci and was the only antibiotic which was bactericidal. Its potency was comparable or superior to those of other antibiotics tested against methicillin-resistant staphylococci.     

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.     

In vitro activities of LY333328 and comparative agents against nosocomial gram-positive pathogens collected in a 1997 global surveillance study

The in vitro activity of LY333328 was evaluated for 1,479 nosocomial gram-positive pathogens isolated in 12 countries during 1997. LY333328 MICs at which 90% of the isolates tested were inhibited for Enterococcus faecalis (n = 351), Enterococcus faecium (n = 100), Staphylococcus aureus (n = 593), coagulase-negative Staphylococcus species (n = 325), and Streptococcus pneumoniae (n = 110) were 1, 1, 2, 2, and 0.015 microg/ml, respectively. LY333328 demonstrated potent activity against isolates of vancomycin-resistant enterococci, oxacillin-resistant staphylococci, and penicillin-resistant pneumococci.     

In vitro susceptibility studies of vancomycin-resistant Enterococcus faecalis.

Vancomycin resistance exhibited by Enterococcus faecalis isolates V583, V586, and V587 is described. The vancomycin MICs ranged from 32 to 64 micrograms/ml. Although resistant to vancomycin, the isolates were susceptible to teicoplanin (MIC, less than or equal to 0.5 micrograms/ml). Such a glycopeptide susceptibility profile has not been previously described for E. faecalis. Time kill studies showed that vancomycin resistance adversely affected the synergistic activity that vancomycin and aminoglycoside combinations usually demonstrate against enterococci. However, the ability to detect vancomycin resistance varied with the susceptibility testing method used. Whereas broth microdilution, broth macrodilution, and agar dilution methods detected resistance, disk-agar diffusion and the AutoMicrobic system Gram-Positive GPS-A susceptibility card (Vitek Systems Inc., Hazelwood, Mo.) did not. To detect vancomycin resistance reliably and establish the incidence of such E. faecalis isolates, adjustments in some susceptibility testing methods may be necessary.     

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.     

Effects of combinations of beta-lactams, daptomycin, gentamicin, and glycopeptides against glycopeptide-resistant enterococci.

Activities of combinations of beta-lactams, daptomycin, gentamicin, teicoplanin, and vancomycin against 11 clinical isolates of Enterococcus faecium highly resistant to glycopeptides, three plasmid-cured derivatives, eight E. faecalis and E. faecium transconjugants, and two susceptible recipient strains were tested. A marked synergy between penicillins or imipenem and glycopeptides against the glycopeptide-resistant strains but not against the glycopeptide-susceptible strains was observed by the double-disk agar diffusion assay. The synergy of combinations of amoxicillin, imipenem, penicillin G, or piperacillin with vancomycin or teicoplanin against resistant strains was confirmed by the checkerboard technique. The fractional inhibitory concentration indexes were generally below 0.25, except for one strain of E. faecium resistant to high levels of penicillin G. However, the combinations were not bactericidal as tested by time-killing experiments, and high concentrations (64 micrograms/ml) of amoxicillin, penicillin G, or piperacillin combined with 8 micrograms of vancomycin or teicoplanin per ml tended to be antagonistic. Addition of 4 micrograms of gentamicin per ml to these combinations enhanced their bactericidal effect, but they occasionally remained slightly less effective than beta-lactams associated with gentamicin. The combination of 10 micrograms of daptomycin per ml with gentamicin was bactericidal after 6 h against 11 glycopeptide-resistant strains.     

Quinupristin-dalfopristin resistance among gram-positive bacteria in Taiwan

To understand quinupristin-dalfopristin resistance among clinical isolates of gram-positive bacteria in Taiwan, where this agent is not yet available for clinical use, we evaluated 1,287 nonduplicate isolates recovered from January 1996 to December 1999 for in vitro susceptibility to quinupristin-dalfopristin and other newer antimicrobial agents. All methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to quinupristin-dalfopristin. High rates of nonsusceptibility to quinupristin-dalfopristin (MICs, >/=2 microg/ml) were demonstrated for the following organisms: methicillin-resistant S. aureus (MRSA) (31%), coagulase-negative staphylococci (CoNS) (16%), Streptococcus pneumoniae (8%), viridans group streptococci (51%), vancomycin-susceptible enterococci (85%), vancomycin-resistant Enterococcus faecalis (100%), vancomycin-resistant Enterococcus faecium (66%), Leuconostoc spp. (100%), Lactobacillus spp. (50%), and Pediococcus spp. (87%). All isolates of MSSA, MRSA, S. pneumoniae, and viridans group streptococci were susceptible to vancomycin and teicoplanin. The rates of nonsusceptibility to vancomycin and teicoplanin were 5 and 7%, respectively, for CoNS, ranging from 12 and 18% for S. simulans to 0 and 0% for S. cohnii and S. auricularis. Moxifloxacin and trovafloxacin had good activities against these isolates except for ciprofloxacin-resistant vancomycin-resistant enterococci and methicillin-resistant staphylococci. In Taiwan, virginiamycin has been used in animal husbandry for more than 20 years, which may contribute to the high rates of quinupristin-dalfopristin resistance.