In vitro interaction between rifampin and clindamycin against pathogenic coagulase-negative staphylococci.

The MICs and MBCs for 90% of strains tested (MIC90 and MBC90, respectively) of rifampin for 75 clinical isolates of pathogenic coagulase-negative staphylococci (PCNS) were 0.03 and 0.25 microgram/ml, respectively, while the MIC90 and MBC90 of clindamycin were both greater than 25 micrograms/ml. Although no synergy between rifampicin and clindamycin was found among the 15 strains studied by the checkerboard method, 6 of 12 selected strains showed synergy by the kill-curve method. No antagonism was observed by either method. All 30 strains rapidly developed resistance to rifampin in vitro, and this could be prevented by the simultaneous presence of 1.0 microgram of clindamycin per ml in the 24 methicillin-susceptible PCNS strains. The synergy between rifampin and clindamycin observed in vitro for some strains of PCNS, together with the prevention of emergence of resistance to rifampin by clindamycin, suggests that this antibiotic combination may be useful for the treatment of infections caused by methicillin-susceptible PCNS.     

In vitro bactericidal activity of daptomycin against staphylococci

MICs and minimum bactericidal concentrations (MBCs) of daptomycin, vancomycin, linezolid and quinupristin-dalfopristin (Q-D) were determined for 108 staphylococcal isolates. All strains were susceptible (MICs) to daptomycin (< or =2.0 mg/L) and Q-D (< or =1.0 mg/L). All but three isolates were susceptible to vancomycin (< or =4.0 mg/L) and all but one methicillin-resistant Staphylococcus aureus strain were susceptible to linezolid (< or =4.0 mg/L). Q-D had the lowest geometric mean MIC (0.29 mg/L) and daptomycin had the lowest geometric mean MBC (0.57 mg/L). Time-kill tests were performed on 25 isolates. Bactericidal activity (>99.9% kill) was observed with daptomycin at 2 mg/L and at 2 x MBC for 92% of strains tested. In comparison, the bactericidal rates for the other drugs at breakpoint concentrations and at 2 x MBC were 72% and 70% for vancomycin, 46% and 60% for Q-D, and 7% and 14% for linezolid. Of the four drugs tested, daptomycin was bactericidal against the most strains and had the most rapid cidal activity.     

In vitro activity of l-ofloxacin against norfloxacin-resistant coagulase-negative staphylococci.

The in vitro activity of l-ofloxacin was determined against coagulase-negative staphylococci that were induced to norfloxacin resistance. l-Ofloxacin was the most active agent tested with an MIC90 of 4 micrograms/ml compared with greater than 128, 32, and 128 micrograms/ml for norfloxacin, ciprofloxacin, and enoxacin, respectively. Rifampin-resistant, coagulase-negative staphylococci were not cross-resistant to the quinolones tested. Among the rifampin-resistant organisms tested, l-ofloxacin was also the most active agent with an MIC90 of 0.25 micrograms/ml.     

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。     

Effect of mixing on rifampin bactericidal activity against staphylococci.

Minimal bactericidal concentrations of rifampin were significantly increased, and serum bactericidal activity from volunteers receiving this drug was significantly decreased by vigorous mixing of microtiter plates before sampling when tested against Staphylococcus aureus and Staphylococcus epidermidis at 10(5) and 10(6) colony-forming units per ml. These results suggest that microtiter estimates of the bactericidal activity of rifampin against staphylococci should be performed after vigorous shaking.     

In vitro activity of the new quinolone WCK 771 against staphylococci

The activity of WCK 771, an experimental quinolone developed to overcome quinolone resistance in staphylococci and other bacteria, was determined against quinolone-susceptible and -resistant Staphylococcus aureus and S. epidermidis. WCK 771 MICs for 50 and 90% of the strains tested (MIC(50) and MIC(90), respectively) were 0.008 and 0.015 microg/ml for S. aureus (n = 43) and 0.015 and 0.03 microg/ml for S. epidermidis (n = 44) for quinolone-susceptible isolates, compared to ciprofloxacin values of 0.12 and 0.25 microg/ml and 0.25 and 0.5 microg/ml, respectively. Values for levofloxacin were 0.12 and 0.25 microg/ml and 0.12 and 0.25 microg/ml, those for clinafloxacin were 0.015 and 0.03 microg/ml and 0.015 and 0.03 microg/ml, those for moxifloxacin were 0.03 and 0.06 microg/ml and 0.06 and 0.12 microg/ml, and those for gatifloxacin were 0.06 and 0.12 microg/ml and 0.12 and 0.25 microg/ml, respectively. The WCK 771 MIC(50) and MIC(90), respectively, were 0.5 and 1 microg/ml for both species of staphylococci (n = 73 for S. aureus, n = 70 for S. epidermidis) for isolates highly resistant to ciprofloxacin (MIC(50) and MIC(90), >32 and >32 microg/ml, respectively). Values for levofloxacin were 8 and 32 microg/ml and 8 and 32 microg/ml, those for clinafloxacin were 1 and 2 microg/ml and 0.5 and 2 microg/ml, those for moxifloxacin 4 and >4 microg/ml and 4 and >4 microg/ml, and those for gatifloxacin were 4 and >4 microg/ml and 2 and >4 microg/ml, respectively. WCK 771 and clinafloxacin demonstrated MICs of 1 microg/ml against three vancomycin-intermediate strains. WCK 771 showed concentration-independent killing for up to 24 h at 2, 4, and 8 times the MICs against quinolone-resistant staphylococci and was also bactericidal after 8 h for high-density inocula (10(8) CFU/ml) of quinolone-resistant strains at 5 microg/ml, whereas moxifloxacin at 7.5 microg/ml was bacteriostatic. WCK 771 was not a substrate of the NorA efflux pump as evident from the similar MICs against both an efflux-positive and an efflux-negative strain. Overall, WCK 771 was the most potent quinolone tested against the staphylococci tested, regardless of quinolone susceptibility.     

In vitro activity of imipenem against enterococci and staphylococci and evidence for high rates of synergism with teicoplanin, fosfomycin, and rifampin.

The in vitro activities of imipenem alone and in combination with teicoplanin, fosfomycin, and rifampin were tested against clinical isolates of enterococci and staphylococci. In both groups of organisms, the three combinations demonstrated high rates of synergism in both checkerboard and time-kill studies.     

In vitro activity of rifampin in combination with oxacillin against Staphylococcus aureus.

The in vitro activity of rifampin alone and in combination with oxacillin was determined for 75 Staphylococcus aureus strains (64 susceptible and 11 resistant to oxacillin). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined by broth microdilution; antibiotic combinations were evaluated by microdilution checkerboard and time-kill studies. The 90% MIC of rifampin was less than or equal to 0.015 micrograms/ml after both 24 and 48 h of incubation. The 90% MBC of rifampin was less than or equal to 2.0 micrograms/ml on subculture at 24 h of incubation and less than or equal to 0.5 micrograms/ml on subculture at 48 h. MIC checkerboards with oxacillin-susceptible strains revealed an additive or indifferent effect in 35 strains (55%) and antagonism in 29 strains (45%). MBC checkerboards performed by subculture at 24 h demonstrated antagonism for all but one of the oxacillin-susceptible strains, with sub-MBCs of rifampin impairing the bactericidal activity of oxacillin. MBC checkerboards performed by 48-h subculture revealed antagonism with 37 strains (58%); in 26 additional strains (40%), a synergistic, additive, or indifferent effect was observed at low antibiotic concentrations, but antagonism was seen at higher concentrations. Time-kill studies tended to show indifference rather than antagonism with oxacillin plus rifampin. In checkerboards performed with oxacillin-resistant strains, the addition of rifampin did not improve oxacillin inhibitory or bactericidal activity to a clinically significant extent; however, the addition of oxacillin improved the bactericidal activity of rifampin at easily achievable serum concentrations.     

In vitro activity of novobiocin and rifampin alone and in combination against oxacillin-resistant Staphylococcus aureus

Rifampin and novobiocin both have excellent activity against oxacillin-resistant Staphylococcus aureus, but their single use may be associated with the development of resistance. To help predict their clinical value in our institution, 60 recent clinical isolates of oxacillin-resistant S. aureus were studied for in vitro susceptibility to the two agents. Ten isolates with increased MICs to both agents or to rifampin alone were also studied by modified checkerboard and kill-curve methods. Indifference was consistently demonstrated by the checkerboard method and generally found in kill-curve studies. Prevention of development of resistance was demonstrated with the antimicrobial combinations for some isolates. Isolates with increased MICs for the two agents fell into two distinctive groups, with prevention of the development of rifampin resistance occurring in one group but not in the other, suggesting that different strains of oxacillin-resistant S. aureus may have different capacities for development of rifampin resistance.     

In vitro activity of LY146032 against staphylococci, streptococci, and enterococci.

The in vitro activities of LY146032 and seven comparative antimicrobial agents against 14 species of staphylococci, streptococci, and enterococci were studied. MICs of LY146032 were less than or equal to 0.5 microgram/ml for all staphylococci, including oxacillin-resistant strains; less than or equal to 0.25 microgram/ml for all streptococci (except viridans group streptococci); and less than or equal to 4 micrograms/ml for all viridans group streptococci and enterococci. MICs were minimally affected by variations in inoculum size, and LY146032 was bactericidal against all species tested.     

Comparative in vitro activity of faropenem against staphylococci

The anti-staphylococcal activity of faropenem, a novel beta-lactam, was examined and compared with that of amoxicillin, cefuroxime, clindamycin and vancomycin using the agar dilution method. A total of 234 staphylococci, including a large number of clonally different methicillin-resistant strains and a representative number of Staphylococcus aureus small colony variants, were tested. While the activity of faropenem was independent of the staphylococcal phenotype, the novel penem was up to eight times more active against methicillin-susceptible strains compared with the other agents tested. In addition, faropenem was active against many methicillin-resistant strains of S. aureus and coagulase-negative staphylococci.     

In vitro activity of the oxazolidinone RWJ-416457 against linezolid-resistant and -susceptible staphylococci and enterococci

RWJ-416457, a novel oxazolidinone, had modal MICs of 0.5 to 1 microg/ml for linezolid-susceptible staphylococci and enterococci, versus linezolid MICs for these organisms of 1 or 2 microg/ml. RWJ-416457 MICs for mutants with 23S rRNA mutations were 2 to 32 microg/ml, versus linezolid MICs of 8 to 64 microg/ml; actual values reflected the proportion of gene copies mutated.     

In vitro synergism between cefotaxime and minocycline against Vibrio vulnificus.

We conducted time-kill studies to evaluate the inhibitory activities of either cefotaxime or minocycline alone and the two drugs in combination against a clinical strain of Vibrio vulnificus. The MICs of cefotaxime and minocycline were 0.03 and 0.06 microg/ml, respectively. When approximately 5 x 10(5) CFU of V. vulnificus per ml was incubated with cefotaxime at 0.03 or 0.05 microg/ml, the bacterial growth was inhibited during the initial 2 and 8 h, respectively. Thereafter, V. vulnificus regrew and the level of growth reached that of the control. Within the dose range of less than five times the MIC, the duration of the inhibitory effect of cefotaxime was proportional to its concentration. When minocycline at 0.015, 0.03, 0.045, and 0.06 microg/ml was used to evaluate the inhibitory effect, a similar trend was observed. Either antibiotic at a concentration of five times the MIC or greater prevented the regrowth of V. vulnificus for at least 48 h. When cefotaxime at 0.05 microg/ml and minocycline at 0.045 microg/ml were combined in the same culture, the inhibitory effect against V. vulnificus persisted for more than 48 h, with no regrowth noted. The use of a combination of these two antibiotics resulted in the reduction of growth by 6 orders of magnitude compared to the use of either of the two antibiotics alone, and the number of surviving organisms in the presence of the antibiotics combined was approximately 3 orders of magnitude less than that in the starting inoculum. We conclude that cefotaxime and minocycline acted synergistically in inhibiting V. vulnificus in vitro.     

In vitro activity of telavancin and comparator antimicrobial agents against a panel of genetically defined staphylococci

The in vitro activity of telavancin was determined for 94 diverse Staphylococcus spp. Telavancin had MIC(90) values of 0.5 μg/mL for methicillin-susceptible, methicillin-resistant, and vancomycin-susceptible Staphylococcus aureus, and coagulase-negative staphylococci isolates. Telavancin MICs were 0.5-1 μg/mL for vancomycin-intermediate S. aureus isolates and 2-4 μg/mL for vancomycin-resistant S. aureus strains.     

In vitro activity of S-3578, a new broad-spectrum cephalosporin active against methicillin-resistant staphylococci

The in vitro antibacterial activity of S-3578, a new parenteral cephalosporin, against clinical isolates was evaluated. The MICs of the drug at which 90% of the isolates were inhibited were 4 micro g/ml for methicillin-resistant Staphylococcus aureus (MRSA) and 2 micro g/ml for methicillin-resistant Staphylococcus epidermidis, which were fourfold higher than and equal to those of vancomycin, respectively. The anti-MRSA activity of S-3578 was considered to be due to its high affinity for penicillin-binding protein 2a (50% inhibitory concentration, 4.5 micro g/ml). In time-kill studies with 10 strains each of MRSA and methicillin-susceptible S. aureus, S-3578 caused more than a 4-log(10) decrease of viable cells on the average at twice the MIC after 24 h of exposure, indicating that it had potent bactericidal activity. Furthermore, in population analysis of MRSA strains with heterogeneous or homogeneous resistance to imipenem, no colonies emerged from about 10(9) cells on agar plates containing twice the MIC of S-3578, suggesting the low frequency of emergence of S-3578-resistant strains from MRSA. S-3578 was also highly active against penicillin-resistant Streptococcus pneumoniae (PRSP), with a MIC(90) of 1 micro g/ml, which was comparable to that of ceftriaxone. S-3578 also had antibacterial activity against a variety of gram-negative bacteria including Pseudomonas aeruginosa, though its activity was not superior to that of cefepime. In conclusion, S-3578 exhibited a broad antibacterial spectrum and, particularly, had excellent activity against gram-positive bacteria including methicillin-resistant staphylococci and PRSP. Thus, S-3578 was considered to be worthy of further evaluation.     

Update on minocycline in vitro activity against odontogenic bacteria

Periodontitis, which is a chronic inflammation caused by biofilm from numerous gram-negative and -positive oral bacterial species between gingiva and tooth, is known to have a poor prognosis.Susceptibility of standard strains (19 strains) and clinical isolates (90 strains) of aerobic and anaerobic oral bacteria, including a recently recovered as novel pathogens for periodontitis called Filifactor alocis, was tested to minocycline (MINO) by using the agar dilution method according to the Clinical and Laboratory Standards Institute.MINO is a well-used therapeutic antibiotic for periodontits. In this study, minimum inhibitory concentrations (MICs) of MINO against Aggregatibacter actinomycetemcomitans (n = 1), Porphyromonas gingivalis (n = 5), Prevotella intermedia (n = 1), Tannerella forsythia (n = 1) and F. alocis (n = 1), were 0.12, ≤0.016–0.03, ≤0.016, 0.03, and 2 μg/mL, respectively. MICs range of MINO against clinical isolates (10 isolates each) Streptococcus intermedius, P. gingivalis, P. intermedia, Fusobacterum nucleatum, Parvimonas micra were 0.06–16, ≤0.016–0.03, ≤0.016–1, ≤0.016–0.12, and ≤0.016–0.25 μg/mL, respectively.These results showed that MINO has superior in vitro activities against to known and recent recovered oral bacteria. Moreover, low prevalence in non-susceptible bacteria was observed to MINO.     

米诺环素、替加环素对多重耐药菌的体外抗菌活性比较

目的评价米诺环素、替加环素对多重耐药的耐甲氧西林金葡菌(MRSA)、肠球菌和鲍曼不动杆菌的体外抗菌活性。方法采用微量肉汤稀释法测定临床分离的多重耐药细菌对米诺环素、替加环素的敏感性。结果多重耐药的1 55株鲍曼不动杆菌,99株(63.9%)对米诺环素敏感,39株(25.2%)对米诺环素耐药,17株(11.0%)对米诺环素中介。75株多重耐药MRSA,50株(66.7%)对米诺环素敏感,20株(26.7%)对米诺环素中介,5株(6.7%)为耐药株。93株多重耐药屎肠球菌中36株(38.7%)对米诺环素敏感,57株(61.3%)对米诺环素耐药。39株粪肠球菌中25株(64.1%)对米诺环素敏感。75株MRSA对替加环素100%敏感,132株肠球菌100%敏感。5株耐万古霉素屎肠球菌和4株产新德里金属β内酰胺酶不动杆菌全部对替加环素敏感,MRSA和肠球菌对替加环素敏感性为100%。结论替加环素对米诺环素耐药的肠球菌和MRSA有很好的体外抗菌活性,替加环素对米诺环素耐药的鲍曼不动杆菌的抗菌活性也不理想。