In vitro activity of various antimicrobial agents against Staphylococcus aureus isolates including fluoroquinolone- and oxacillin-resistant strains.

To determine susceptibility to 31 old and new antimicrobials, 44 strains of Staphylococcus aureus, most resistant to oxacillin and ciprofloxacin and isolated in a community hospital, were tested in vitro. For the peptide/peptide-derivative compounds, with the exception of mersacidin, all strains were inhibited by less than or equal to 2 micrograms/ml. Minimum inhibitory concentration (MIC)90 values indicated mupirocin, teicoplanin, and MDL 62211 to be fourfold more active than vancomycin, ramoplanin, and decaplanin. For fluoroquinolones, ciprofloxacin-resistant S. aureus exhibited high-level cross-resistance to ofloxacin, norfloxacin, fleroxacin, enoxacin, and Ro 23-9424. WIN 57253, a new fluorinated naphthyridine, showed good activity against these strains. Among the beta-lactams, the penem-derivative compounds (imipenem, meropenem, FCE 22101, and HRE 664) had the greatest activity, although resistance to each compound was detected among oxacillin-resistant S. aureus. The presence of tazobactam reduced the piperacillin MIC90 fourfold. Oxacillin-susceptible strains were susceptible to cephalosporins/cephamycins, whereas most oxacillin-resistant strains exhibited resistance. This study has shown that certain old and new quinolones and peptide-derivative compounds have good in vitro activity against multiply resistant strains of S. aureus.     

阿莫西林-双氯西林的体外抗菌作用研究

目的评价阿莫西林-双氯西林对常见感染临床分离菌的体外抗菌作用.方法收集临床分离菌按CLSI/NCCLS推荐的琼脂对倍稀释法测定阿莫西林-双氯西林的最低抑菌浓度（MIC）,并与相关抗菌药物进行比较.结果收集临床分离菌共513株,其中需氧革兰阳性菌248株,需氧革兰阴性菌265株.阿莫西林-双氯西林对受试的需氧革兰阳性球菌,包括肺炎链球菌、化脓性链球菌等链球菌属、甲氧西林敏感葡萄球菌、粪肠球菌具有高度抗菌活性,大多与阿莫西林-克拉维酸相仿,亦优于其他受试药,该药对卡他莫拉菌、流感嗜血杆菌抗菌作用强,其中对流感嗜血杆菌的产酶株作用略差;对伤寒沙门菌具有良好抗菌作用,对大肠埃希菌、肺炎克雷伯菌、奇异变形杆菌和志贺菌的抗菌作用较差.结论阿莫西林-双氯西林对社区获得的上、下呼吸道感染和单纯性皮肤软组织感染的常见病原菌具有良好抗菌作用,对伤寒沙门菌作用亦强,提示该药为治疗上述感染的适宜选用药物之一.     

In vitro activity of pristinamycin against methicillin-resistant Staphylococcus aureus

An agar dilution technique was used to determine the MIC of pristinamycin for 124 clinical isolates of methicillin-resistant Staphylococcus aureus. All were inhibited by less than or equal to 0.5 mg/1, quite similar to the sensitivity of a number of methicillin-sensitive strains. MICs obtained using a microdilution method were also comparable. Antagonism was seen with the combination of pristinamycin and erythromycin.     

In vitro activity of TD-6424 against Staphylococcus aureus

TD-6424, a rapidly bactericidal agent with multiple mechanisms of action, is more potent in vitro and more rapidly bactericidal than currently available agents against methicillin-susceptible and methicillin-resistant Staphylococcus aureus. TD-6424 produces a postantibiotic effect with a duration of 4 to 6 h against these organisms. The results suggest potential efficacy against susceptible and resistant strains of S. aureus.     

In vitro activity of recombinant lysostaphin against Staphylococcus aureus isolates from anterior nares and blood

The in vitro activity of recombinant lysostaphin was tested against a collection of well-characterized clinical Staphylococcus aureus isolates by disk diffusion (429 isolates) and minimum bactericidal concentration (10 isolates) assays. Minimum bactericidal concentrations of 0.16 microg/ml and zones of inhibition ranging between 15 and 21 mm in diameter demonstrate that lysostaphin was highly active against all isolates tested.     

In vitro activity of ceftobiprole, linezolid, tigecycline, and 23 other antimicrobial agents against Staphylococcus aureus isolates in China

We investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in China and determined the susceptibility of S. aureus to 26 antimicrobial agents, including ceftobiprole, linezolid, and tigecycline. A total of 798 isolates were collected and tested by agar dilution. The mean prevalence of MRSA was 50.4%, the highest in Shanghai (80.3%), followed by those in Beijing (55.5%) and Shenyang (50.0%). Only 4.2% to 12.6% of MRSA were susceptible to erythromycin, fluoroquinolones, gentamicin, and tetracycline. All isolates were susceptible to teicoplanin, vancomycin, linezolid, tigecycline, and ceftobiprole.     

In vitro activity of novel rifamycins against rifamycin-resistant Staphylococcus aureus

We describe novel rifamycin derivatives (new chemical entities [NCEs]) that retain significant activity against a comprehensive collection of Staphylococcus aureus strains that are resistant to rifamycins. This collection of resistant strains contains 21 of the 26 known single-amino-acid alterations in RpoB, the target of rifamycins. Some NCEs also demonstrated a lower frequency of resistance development than rifampin and rifalazil in S. aureus as measured in a resistance emergence test. When assayed for activity against the strongest rifamycin-resistant mutants, several NCEs had MICs of 2 microg/ml, in contrast to MICs of rifampin and rifalazil, which were 512 microg/ml for the same strains. The properties of these NCEs therefore demonstrate a significant improvement over those of earlier rifamycins, which have been limited primarily to combination therapy due to resistance development, and suggest a potential use of these NCEs for monotherapy in several clinical indications.     

In vitro activity of multiple antimicrobial combinations against Pseudomonas cepacia isolates

For 16 isolates of Pseudomonas cepacia from patients with cystic fibrosis, synergism was determined by the killing curve method, utilizing various combinations of antibiotics [ticarcillin (Ti), rifampin (Ri), tobramycin (To), imipenem (Im), ofloxacin (Of), polymyxin B (PB), and trimethoprim/sulfamethoxazole (S x T)]. All 16 isolates were resistant to Ti, To, Ri, and PB; 11 were sensitive to S x T, 13 were sensitive to Im, and 2 were sensitive to Of. The combination of Im/Ri was synergistic for 8 isolates. Several combinations (Ti/Ri/Im), (Ti/Im/To), (Ri/Im/To) also demonstrated synergism for these 8 isolates. The Im/Ri combination did not demonstrate synergism against the other 8 isolates. The Ti/Im/To combination was synergistic for 6 of these. The Ri/Im/To combination was synergistic for 5 and the Ti/Im/Ri combination was synergistic for 3. Synergism could also be demonstrated with several 4-drug combinations. This study suggests that multi-drug combinations may have a role in the treatment of P. cepacia infections if proven in clinical studies.     

An antibiotic that inhibits a late step in wall teichoic acid biosynthesis induces the cell wall stress stimulon in Staphylococcus aureus

Wall teichoic acids (WTAs) are phosphate-rich, sugar-based polymers attached to the cell walls of most Gram-positive bacteria. In Staphylococcus aureus, these anionic polymers regulate cell division, protect cells from osmotic stress, mediate host colonization, and mask enzymatically susceptible peptidoglycan bonds. Although WTAs are not required for survival in vitro, blocking the pathway at a late stage of synthesis is lethal. We recently discovered a novel antibiotic, targocil, that inhibits a late acting step in the WTA pathway. Its target is TarG, the transmembrane component of the ABC transporter (TarGH) that exports WTAs to the cell surface. We examined here the effects of targocil on S. aureus using transmission electron microscopy and gene expression profiling. We report that targocil treatment leads to multicellular clusters containing swollen cells displaying evidence of osmotic stress, strongly induces the cell wall stress stimulon, and reduces the expression of key virulence genes, including dltABCD and capsule genes. We conclude that WTA inhibitors that act at a late stage of the biosynthetic pathway may be useful as antibiotics, and we present evidence that they could be particularly useful in combination with beta-lactams.     

In vitro activities of 28 antimicrobial agents against Staphylococcus aureus isolates from tertiary-care hospitals in Korea: a nationwide survey

Staphylococcus aureus, one of the most frequently isolated pathogens in both hospitals and the community, has been particularly efficient at developing resistance to antimicrobial agents. As methicillin-resistant S. aureus (MRSA) has prevailed and, furthermore, as S. aureus with reduced susceptibility to vancomycin has emerged, the therapeutic options for the treatment of S. aureus infections have become limited. To update the current status of antibiotic resistance, clinical S. aureus isolates were collected from eight university-affiliated hospitals from June 1999 to January 2001. Susceptibility tests with 28 antibiotics were performed by the disk diffusion method. Among a total of 682 isolates, the methicillin resistance rate was 64% (439 of 682), and most of the MRSA isolates were resistant to multiple classes of antibiotics. Although a constitutive macrolide-lincosamide-streptogramin B resistance phenotype was common, no isolates were resistant to quinupristin-dalfopristin or linezolid. Rifampin, fusidic acid, trimethoprim-sulfamethoxazole, and arbekacin showed superior in vitro activity compared with the other antibiotics against the MRSA isolates. No isolates showed reduced susceptibility to vancomycin.     

In vitro activity of linezolid against Staphylococcus aureus: a population study

In our study, we aim to determine the existence of microorganisms that are heteroresistant to linezolid among Staphylococcus aureus clinical isolates in our setting between 1996 and 2002; during this period, linezolid was not used in clinical practice. There was no resistant subpopulation to 4 mg/l of linezolid in 99.4% of the strains. On the other hand, 16.46% of the strains exhibited resistant subpopulations to 4 microg/ml of vancomycin. However, the emergence of strains resistant to this drug has been described and the emergence of resistant strains should be monitored.     

耐甲氧西林葡萄球菌对夫西地酸的体外敏感性分析

目的：了解夫西地酸(FA)对耐甲氧西林的葡萄球菌(MRS)的体外抗菌活性。方法：用纸片琼脂扩散(K-B法)试验检测FA对MRS的体外抗菌活性，并与其他常用抗生素比较。结果：筛选出耐甲氧西林金黄色葡萄球菌(MRSA)57株，占71．3％；耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)59株，占71．1％。共人选MRS116株．本组中未发现对万古霉素敏感性下降的菌株。MRSA和MRCNS对FA的耐药率分别为1．7％和3．3％，略高于万古霉素，明显低于其他常用的抗生素(14％～100％)。结论：FA对MRS有较高的体外抗菌活性。     

In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus.

The effects of combinations of beta-lactams with two beta-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 micrograms/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the beta-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the beta-lactams against methicillin-susceptible S. aureus strains. At 42 degrees C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35 degrees C, and no synergy between these beta-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42 degrees C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of beta-lactamase produced were not related to the decreases in the MICs of the beta-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger beta-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the beta-lactams, except for penicillin G, may not be due to beta-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors.     

In-vitro activity of methicillin against clinical isolates of Staphylococcus aureus

Methicillin activity against 149 penicillin-resistant, methicillin-susceptible Staphylococcus aureus strains from bacteraemia cases with endocarditis (n = 89) or without endocarditis (n = 60), from the years 1976-1981, was studied with broth dilution and agar dilution. While no differences in methicillin susceptibility were found in relation to the origin of the strains, Staph. aureus of the phage type complex 94,96 showed significantly higher MIC and IC50 by agar dilution than strains of other phage groups/complexes. This difference probably has no clinical importance but is of epidemiological interest. Broth dilution MIC was generally one dilution higher than agar dilution MIC, possibly explained by methodological factors. The MBC/MIC ratios never exceeded two in any of the strains, indicating a lack of tolerance in these clinically important isolates.