In vitro susceptibilities of four species of coagulase-negative staphylococci.

The in vitro susceptibilities of 260 strains of coagulase-negative staphylococci to penicillin G, oxacillin, nafcillin, methicillin, cephalothin, and seven non-beta-lactam antimicrobial agents were determined and compared with the susceptibilities of 54 strains of Staphylococcus aureus with known patterns of susceptibility. Penicillin G susceptibility for S. aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis was readily determined by using beta-lactamase tests with induced cells and with a standardized microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to the coagulase-negative species. Percentages of organisms susceptible were as follows: S. epidermidis, 7%; S. haemolyticus, 5%; and S. hominis, 47%. Oxacillin susceptibility for these four species was readily determined by using a modification of the microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to S. haemolyticus and S. hominis, but alternate criteria were necessary for S. epidermidis. Percentages of organisms susceptible were as follows: S. epidermidis, 29%; S. haemolyticus, 36%; and S. hominis, 97%. Staphylococcus saprophyticus differed from the other staphylococcal species; all strains were beta-lactamase negative and were penicillin susceptible but had higher penicillin G MICs than did susceptible strains of the other species. There was total cross resistance among the penicillinase-resistant penicillins and cephalothin for the coagulase-negative staphylococci as well as for S. aureus; oxacillin MICs were more reliable than MICs of the other drugs or a standardized disk diffusion test for distinguishing resistant from susceptible strains. Vancomycin, rifampin, and ciprofloxacin were consistently active against all staphylococci. Erythromycin, clindamycin, gentamicin, and trimethoprim-sulfamethoxazole were more active against oxacillin-susceptible staphylococci than against oxacillin-resistant staphylococci.     

Development of in-vitro resistance to glycopeptide antibiotics: assessment in staphylococci of different species.

Forty-two clinical isolates belonging to ten species of staphylococci were studied for their ability to develop single-step resistance, in vitro, to glycopeptide antibiotics. Selection was attempted through separate exposure to four glycopeptides (vancomycin, teicoplanin, and two investigational semisynthetic derivatives of the latter, TD-A3 and CTA-A1) on agar containing 10 mg/l of the test drug. No survivors from any test strain were recovered after exposure to TD-A3 or CTA-A1. After exposure to vancomycin or teicoplanin, surviving clones were only recovered from strains of three species, Staphylococcus aureus, S. epidermidis, and S. haemolyticus. Emergence of resistant clones was easier to observe from strains of S. haemolyticus exposed to teicoplanin. When tested for susceptibility, many survivors exhibited vancomycin and teicoplanin MICs below the drug concentration used for in-vitro selection, probably due to an inoculum effect in the plating procedure. In particular, the vancomycin MICs did not exceed 8 mg/l for S. aureus and S. epidermidis clones, and reached 16 mg/l for some clones from a S. haemolyticus strain. Teicoplanin MICs did not exceed 8 mg/l for S. aureus clones, but reached 64 mg/l for some clones of S. epidermidis, and were particularly high (64 to greater than or equal to 128 mg/l) for most clones of S. haemolyticus. In contrast, against all clones selected from all three species, the MICs of TD-A3 and CTA-A1 did not exceed 2 and 4 mg/l, respectively. Morphological investigations indicated that the colonies of a highly resistant S. haemolyticus clone were smaller and more butyraceous in consistency than those of the parent strain. In transmission and scanning electron microscopy studies, this same S. haemolyticus clone showed a more irregular cell wall than the parent strain.     

In-vitro microbiological activities of DuP 105 and DuP 721, novel synthetic oxazolidinones

DuP 105 and 721, synthetic antibiotics belonging to a totally novel chemical class (oxazolidinones), have been found to be active in vitro against a wide range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. DuP 721 had geometric mean MICs ranging from 1.1 to 16 mg/l against 167 strains of Staph. aureus, Staph. epidermidis, Staph. saprophyticus, streptococci of Groups A, B and D and diphtheroids. DuP 105 was between 1.5 and eight-fold less active. Bacteroides fragilis strains were also susceptible to the DuP compounds (mean MICs being 8.3 and 14.9 mg/l for DuP 721 and 105, respectively), but other Gram-negative species and yeasts were not inhibited by concentrations in excess of 100 mg/l. Both compounds had a predominantly bacteriostatic action. No primary resistance was found, and the incidence of resistant variants in 105 strains tested was less than 1 per 10(8) bacteria.     

Activity of clindamycin against Staphylococcus aureus and Staphylococcus epidermidis from four UK centres.

MICs of penicillin, methicillin, clindamycin, erythromycin, sodium fusidate and gentamicin were determined by an agar dilution method for 300 current isolates of Staphylococcus aureus and 100 of S. epidermidis, collected from four centres, and 38 stock strains of methicillin-resistant S. aureus (MRSA). All but one of the 300 current isolates of S. aureus were sensitive to clindamycin (MIC less than 0.5 mg/l), with an MIC90 of 0.12 mg/l. Of a total of 39 MRSA strains, 11 (28.2%) were resistant to clindamycin (MIC greater than 32 mg/l); all of these strains were also resistant to erythromycin. Ten of the 100 strains of S. epidermidis were resistant to clindamycin; they came from a reasonably equal geographical distribution and were also resistant to erythromycin. The results suggest that clindamycin might still be useful as a second-line agent for infections caused by S. aureus and S. epidermidis, although its activity against MRSA was limited to approximately two-thirds of the MRSA strains tested in this study.     

In vitro activity of daptomycin against 297 staphylococcal isolates

The in vitro activity of daptomycin against 297 clinical isolates of Staphylococcus aureus and S. epidermidis sensu strictu was compared with the activities of cephalothin, dicloxacillin, tobramycin, and vancomycin. Minimal inhibitory concentrations (MICs) were determined by an agar dilution method. Cephalothin and dicloxacillin showed the highest activity against S. aureus on a weight-for-weight basis, all isolates being inhibited by 0.5 mg/l or less of either agent. Cephalothin was somewhat more active against S. epidermidis than was dicloxacillin. Daptomycin and vancomycin exhibited high and similar activity against both S. aureus and S. epidermidis (MIC90% = 1 and 2 mg/l, respectively). Tobramycin was highly active against S. aureus, but the activity against S. epidermidis was greatly variable (MIC range less than or equal to 0.03 - greater than or equal to 16 mg/l). The activity of daptomycin was markedly influenced by the test medium; the MICs were generally 32 times higher when the isolates were tested on Iso-Sensitest agar than on Mueller-Hinton agar. Supplementation of Iso-Sensitest agar with increasing concentrations of calcium potentiated the activity of daptomycin substantially, the results obtained on Iso-Sensitest agar supplemented with 20 mg Ca2+/l being similar to those obtained on Mueller-Hinton agar.     

In vitro antibacterial activity of men 10700, a new penem antibiotic

We report here the antibacterial activity of the new penem antibiotic Men 10700 against a total of 740 gram-positive and gram-negative clinical isolates, in comparison to imipenem, meropenem, cefotaxime, ceftriaxone, ciprofloxacin and gentamicin. Men 10700 has shown a wide spectrum of antibacterial activity, with a potent activity both against gram-positive species (with the exception of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis) as indicated by minimal inhibitory concentration (MIC(90)) values < or =0.5 mg/l, and gram-negative species, with MIC(90) values generally < or =2 mg/l. Men 10700 was the most potent antibiotic against methicillin-susceptible S. aureus and S. epidermidis, while the overall spectrum of activity resembled that of imipenem; meropenem was more active against most gram-negative species. In comparison with third-generation cephalosporins, Men 10700 demonstrated superior activity against methicillin-susceptible S. aureus and S. epidermidis and some gram-negative species such as Morganella morganii, Serratia spp. and Enterobacter cloacae; moreover, in contrast to third-generation cephalosporins, Men 10700 showed moderate activity against Enterococcus spp. The activity of Men 10700 against penicillin-resistant Streptococcus pneumoniae (10 strains) and some gram-negative strains selected for their resistance to cefotaxime (20 strains) was particularly interesting. Copyright Copyright 1999 S. Karger AG, Basel.     

HR 810 and BMY-28142, two new cephalosporins with broad-spectrum activity: an in-vitro comparison with other beta-lactam antibiotics

The in-vitro activity of the new parenteral cephalosporins, HR 810 (HR) and BMY-28142 (BMY), was compared with that of other beta-lactam antibiotics, including cefotaxime, against a total of 315 recent clinical isolates and characterized beta-lactamase producers. An agar dilution procedure was used to determine MICs and two inocula (10(4) and 10(6) cfu) were used throughout. Against all species of the Enterobacteriaceae tested, both HR and BMY were as active as, or slightly more active than, cefotaxime. HR differed from cefotaxime mainly in being eight-fold more active against Pseudomonas aeruginosa and two-fold more active against Staphylococcus aureus. BMY was also eight-fold more active than cefotaxime against Ps. aeruginosa but was two-fold less active than the latter against Staph. aureus. Both new compounds had good activity against Haemophilus influenzae, including the beta-lactamase producing strains of that species, and both had poor activity against the Bacteroides fragilis group (MIC90 greater than 128 mg/l).     

Temafloxacin: in vitro comparison with five other antibacterial agents

The in vitro activity of the new fluorinated quinolone temafloxacin was compared with the activities of ciprofloxacin, fleroxacin, ofloxacin, ceftazidime and tobramycin. A total of 662 recent clinical isolates were included in the study, representing a variety of gram-negative and gram-positive bacteria. An agar dilution method was employed for the determination of minimal inhibitory concentrations (MICs). Ciprofloxacin showed the highest potency against the Enterobacteriaceae, 90% of the isolates being inhibited by 0.06 mg/l or less. The other quinolones were also highly active (MIC90 = 0.25-0.5 mg/l). Ciprofloxacin and tobramycin were the most active agents against the Pseudomonas isolates (MIC90 = 0.25 and 0.5 mg/l, respectively), whereas the activities of temafloxacin, fleroxacin and ofloxacin were more variable. All the quinolones had relatively high and similar activity against Staphylococcus aureus and S. epidermidis, but S. saprophyticus was markedly less susceptible to fleroxacin than to the other quinolones. The activity of temafloxacin against Streptococcus pneumoniae was somewhat higher than those of the other quinolones tested. Temafloxacin showed variable activity against Bacteroides fragilis isolates but was generally more potent against these isolates than were the other quinolones. The MICs of temafloxacin were slightly lower at pH 7.3 compared with those obtained at pHs 5.8 or 8.8.     

Staphylococcus saprophyticus beta-lactamase production and disk diffusion susceptibility testing for three beta-lactam antimicrobial agents.

beta-Lactamase production and MIC determinations for penicillin, methicillin, and cephalothin were assessed for 67 strains of Staphylococcus saprophyticus and correlated with results of disk diffusion susceptibility testing. Fifty-five (82%) of the 67 strains produced beta-lactamase, and 40 (77%) of these beta-lactamase-producing strains were susceptible (zone size, greater than 29 mm) by disk diffusion techniques. Although the range of zone sizes for beta-lactamase producers was broad (26 to 36 mm), all 38 strains with a zone size of less than 31 mm by disk diffusion testing were beta-lactamase producers compared with 17 (59%) of 29 with larger zone sizes (P = 0.0000008). The median penicillin MIC for 12 S. saprophyticus strains was 0.25 micrograms/ml and was not related to beta-lactamase production. Although the methicillin MICs for 15 strains were in the susceptible range (4.0 micrograms/ml), interpretation of disk diffusion testing for oxacillin varied greatly among laboratories using identically prepared media and standardized techniques. Criteria presently used to define susceptibility of Staphylococcus aureus to penicillin and oxacillin by disk diffusion are inappropriate for S. saprophyticus. The clinical significance of the beta-lactamase produced by these strains needs further evaluation.     

Comparative in vitro activity of ceftriaxone against clinical bacterial isolates in Nigeria

The in vitro activity of ceftriaxone, a cephalosporin derivative, recently introduced in Nigeria was compared with the activities of other related beta-lactam antibiotics such as cefotaxime, cefuroxime, cephaloridine, cloxacillin/ampicillin and ampicillin against 530 local clinical isolates of gram-negative and gram-positive bacteria. The spectra of activity and potency of ceftriaxone and cefotaxime were generally similar against the Enterobacteriaceae, Pseudomonas aeruginosa, Serratia spp., Streptococcus spp. and Neisseria gonorrhoeae, but less active against Staphylococcus aureus and Staphylococcus epidermidis when compared to cefotaxime. All the other beta-lactam antibiotics tested were less active than ceftriaxone. The action of ceftriaxone was bactericidal and the minimum inhibitory concentration values observed with R-plasmid beta-lactamase mediated resistant Escherichia coli, Klebsiella spp., Proteus spp. and N. gonorrhoeae strains did not exceed the maximum value obtained with the beta-lactamase-negative strains.     

Antistaphylococcal activities of sparfloxacin (CI-978; AT-4140), ofloxacin, and ciprofloxacin.

The activity of sparfloxacin (CI-978; AT-4140) was compared with those of ofloxacin and ciprofloxacin against clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis. All 10 ciprofloxacin-resistant staphylococci had reduced susceptibility to sparfloxacin and ofloxacin. Against 105 ciprofloxacin-susceptible strains of S. aureus, the sparfloxacin MIC for 90% of strains tested was at least fourfold lower than those of ciprofloxacin and ofloxacin, while against 104 ciprofloxacin-susceptible strains of S. epidermidis, the MIC of sparfloxacin for 90% of strains tested was twofold lower than that of ciprofloxacin and fourfold lower than that of ofloxacin. MBCs of sparfloxacin were less than or equal to 4 x MICs. The effects of inoculum size and pH variations, as well as the presence of serum, on the MICs of sparfloxacin were minimal. Subinhibitory concentrations of sparfloxacin did reduce adherence of S. epidermidis.     

A rapid test to detect the most clinically significant Staphylococcus species

A new two-hour test system (RAPIDEC staph) to detect the main staphylococci was evaluated. Of 124 reference strains tested, 83 represented species most often found in clinical specimens, the remaining 41 strains representing five species primarily of animal origin. RAPIDEC staph detected all Staph, aureus, Staph. epidermidis and seven of eight Staph. saprophyticus strains. Of the animal species, all Staphylococcus intermedius strains were assigned to the correct category, the remainder were misidentified as Staph. epidermidis. With 121 catalase-positive Gram-positive cocci isolated from urines the test system correctly detected all Staph. aureus strains, 39 of 41 Staph. epidermidis, and 34 of 36 Staph. saprophyticus. Of 25 atypical Staph. aureus strains which were either slide or tube coagulase negative the test system correctly detected all 17 slide coagulase negative strains but failed to detect eight which were tube coagulase negative. There were no false positives. RAPIDEC staph is a rapid, accurate system for the detection of the three main clinically important species of staphylococci.     

In-vitro activity of BMY 28142, a new aminothiazolyl cephalosporin

The in-vitro activity of BMY 28142, a new alpha-methoxyimino aminothiazolyl cephalosporin, was determined by microdilution broth techniques. The agent demonstrated excellent activity against recent clinical Enterobacteriaceae isolates with a 90% minimum inhibitory concentration (MIC90) of 0.25 mg/l or less for all but one species tested. BMY 28142 inhibited all Pseudomonas aeruginosa strains tested (MIC90 = 8.0 mg/l) as well as most other non-fermentative bacteria studied. Methicillin-susceptible Staphylococcus aureus were susceptible to BMY 28142 with MIC90 = 4.0 mg/l, while methicillin-resistant strains were generally resistant (MIC range 8- greater than 32 mg/l).     

Comparative in vitro inhibitory and killing activity of cefpirome, ceftazidime, and cefotaxime against Pseudomonas aeruginosa, enterococci, Staphylococcus epidermidis, and methicillin-susceptible and -resistant and tolerant and nontolerant Staphylococcus aureus.

With a macrotube dilution method, MICs and MBCs were determined for three aminothiazolyl cephalosporins, cefpirome (HR 810), ceftazidime, and cefotaxime, against Pseudomonas aeruginosa, enterococci, Staphylococcus epidermidis, and methicillin-resistant, -susceptible, and -tolerant strains of Staphylococcus aureus. Comparatively, cefpirome was the most active agent against all gram-positive cocci, including enterococci and methicillin-resistant S. aureus, and was as active as ceftazidime against P. aeruginosa. MBCs of cefpirome were within two dilutions of the MICs for 91% of P. aeruginosa and 90% of gram-positive cocci strains tested, except methicillin-resistant S. aureus, for which the MBCs were within three dilutions for 90% of strains.     

In-vitro susceptibility of gram-positive cocci to LY146032 teicoplanin, sodium fusidate, vancomycin, and rifampicin

LY146032, a new antimicrobial agent with activity against Gram-positive cocci, was tested against methicillin-susceptible and methicillin-resistant Staphylococcus aureus, methicillin-susceptible and methicillin-resistant Staph. epidermidis, Staph. saprophyticus, and Streptococcus faecalis. MIC90s in cation-supplemented Mueller Hinton broth by the microdilution broth method were less than 1.0 mg/l for all organisms tested. Increasing or decreasing the inoculum size did not appreciably effect the MIC50 or MIC90 for any organism group nor did decreasing the incubation temperature. The addition of sodium chloride to the test system did not appreciably effect the susceptibility of methicillin-resistant Staph. aureus to LY146032. All organisms were 4 to 32 times more susceptible to LY146032 than to vancomycin. The Staph. aureus had LY146032 susceptibility patterns which were similar to those of teicoplanin and sodium fusidate. LY146032 was 4-16 times more active than teicoplanin against Staph. saprophyticus and Staph. epidermidis while teicoplanin was 8-16 times more active than LY146032 against Str. faecalis.     

RWJ-54428 (MC-02,479), a new cephalosporin with high affinity for penicillin-binding proteins,including PBP 2a,and stability to staphylococcal beta-lactamases

RWJ-54428 (MC-02,479) is a new cephalosporin active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The potency of this new cephalosporin against MRSA is related to a high affinity for penicillin-binding protein 2a (PBP 2a), as assessed in a competition assay using biotinylated ampicillin as the reporter molecule. RWJ-54428 had high activity against MRSA strains COL and 67-0 (MIC of 1 micro g/ml) and also showed affinity for PBP 2a, with a 50% inhibitory concentration (IC(50)) of 0.7 micro g/ml. RWJ-54428 also displayed excellent affinity for PBP 5 from Enterococcus hirae R40, with an IC(50) of 0.8 micro g/ml and a MIC of 0.5 micro g/ml. The affinity of RWJ-54428 for PBPs of beta-lactam-susceptible S. aureus (MSSA), enterococci (E. hirae), and Streptococcus pneumoniae showed that the good affinity of RWJ-54428 for MRSA PBP 2a and E. hirae PBP 5 does not compromise its binding to susceptible PBPs. RWJ-54428 showed stability to hydrolysis by purified type A beta-lactamase isolated from S. aureus PC1. In addition, RWJ-54428 displayed low MICs against strains of S. aureus bearing the four classes of staphylococcal beta-lactamases, including beta-lactamase hyperproducers. The frequency of isolation of resistant mutants to RWJ-54428 from MRSA strains was very low. In summary, RWJ-54428 has high affinity to multiple PBPs and is stable to beta-lactamase, properties that may explain our inability to find resistance by standard methods. These data are consistent with its excellent activity against beta-lactam-resistant gram-positive bacteria.     

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.     

Activity of gatifloxacin compared to those of seven agents against bacteria recovered from outpatients with respiratory tract infection

The in vitro activity of gatifloxacin and levofloxacin, ciprofloxacin, penicillin, ampicillin, ampicillin-sulbactam, ceftriaxone and clarithromycin was evaluated against 173 S. pneumoniae strains (128, penicillin-susceptible strains; 32, intermediate penicillin- resistant strains and 13, penicillin-resistant strains), 163 H. influenzae strains (128, beta-lactamase non-producer; 35, beta-lactamase producers), 111 M. catarrhalis (9, beta-lactamase non-producer; 102, beta-lactamase producers), 95 Streptococcus pyogenes and 116 S. aureus strains (96, methicillin-susceptible; 20, methicillin-resistant) recovered from outpatients with respiratory tract infection.Based upon the MICs at which 50% and 90% of the isolates were inhibited we concluded that gatifloxacin proved to be the most active antibiotic against respiratory pathogens, including all the penicillin-resistant pneumococci and H. influenzae or M. catarrhalis producing beta-lactamase. Furthermore, their MICs against S. pneumoniae and methicillin-resistant S. aureus were lower than those of levofloxacin and ciprofloxacin.Therefore, this new fluoroquinolone displayed in vitro features that make it suitable for treating community-acquired respiratory tract infections.     

MEN 10700, a new penem antibiotic: in vitro antibacterial activity on clinical isolates

MEN 10700 is a new broad-spectrum penem, currently in preclinical development. In the present study, the activity of MEN 10700 was compared to that of imipenem, meropenem, cefotaxime, ampicillin/sulbactam, amikacin and ciprofloxacin against 619 gram-positive and gram-negative bacterial strains, and to that of imipenem, meropenem, cefotaxime, ceftriaxone, ceftazidime, cefepime and ampicillin/sulbactam against 38 strains of ciprofloxacin-resistant Escherichia coli, and against 19 extended-spectrum-beta-lactamase (ESBL)-producing strains of the KES group. MEN 10700 was highly active against most gram-positive and gram-negative strains, and overall demonstrated comparable activity to imipenem and meropenem. Methicillin-susceptible Staphylococcus aureus and methicillin-susceptible Staphylococcus epidermidis were highly susceptible to MEN 10700, which was the most potent among the antibiotics tested. MEN 10700 was less potent than the carbapenem antibiotics on Morganella morganii, Serratia marcescens and Acinetobacter spp. Ciprofloxacin-resistant E. coli were uniformly susceptible to MEN 10700, imipenem and meropenem, with MIC90 values in the range of < or = 0.12-0.25 mg/l, while showing much lower susceptibility to the other antibiotics tested, including the fourth-generation cephalosporin cefepime. This feature was even more evident in ESBL-producing strains of the KES group, with an MIC90 of 1- 2 mg/l for MEN 10700, imipenem and meropenem, and a MIC90 of 16-64 mg/l for the other antibiotics tested, including cefepime.     

Mechanisms of action of quinolones against staphylococci and relationship with their in vitro bactericidal activity

Ciprofloxacin and norfloxacin exhibited mechanism A (requires cell division as well as bacterial protein and RNA synthesis to kill bacteria) and C (active against nondividing bacteria but requires protein and RNA synthesis) against the reference strain Staphylococcus aureus ATCC 25923, yet only mechanism A was exhibited by these fluoroquinolones when tested against three clinical isolates: S. aureus Sa-215, Staphylococcus epidermidis Se-81 and Staphylococcus haemolyticus Sx-1. On the contrary, fleroxacin exerted mechanism A and C against the three clinical isolates but only mechanism A against the reference strain. Ofloxacin displayed mechanism A against S. epidermidis Se-81, mechanism A and C against S. haemolyticus and mechanism A and B (active against nondividing bacteria and does not require protein and RNA synthesis) against the two S. aureus tested. Sparfloxacin showed mechanism A and C against the four Staphylococcus species studied, and temafloxacin was the only fluoroquinolone tested that exhibited mechanism A and B against the four bacterial strains assayed. No correlation was found between the in vitro bactericidal activity (expressed as minimum inhibitory concentration and optimal bactericidal concentration) and the mechanisms of action exhibited by these fluoroquinolones.