Antimicrobial activity and a comparison of published pharmacodynamics of gemifloxacin and eight fluoroquinolones against Streptococcus pneumoniae

Gemifloxacin was evaluated for its in vitro activity and was compared with eight fluoroquinolones. Pharmacodynamic comparisons were made based on published pharmacokinetic information. Gemifloxacin demonstrated excellent in vitro activity (minimum inhibitory concentration necessary to inhibit 90% of the strains tested, MIC90 = 0.03 mg/L (range 0.0019-0.03 mg/L)) against 199 strains of Streptococcus pneumoniae. Its activity was not influenced by penicillin or ciprofloxacin non-susceptibility. Gemifloxacin demonstrated excellent pharmacodynamic parameters, with a Cmax/MIC90 of 67 (where Cmax is the peak serum level) and an AUC/MIC90 of 297 (where AUC is the area under the curve). Compared with the other eight fluoroquinolones tested, gemifloxacin demonstrated the best in vitro activity and Cmax/MIC90.     

In vitro activity of older and newer fluoroquinolones against efflux-mediated high-level ciprofloxacin-resistant Streptococcus pneumoniae

The effect of high-level efflux activity on the MICs of fluoroquinolones against Streptococcus pneumoniae in the absence of topoisomerase mutations leading to fluoroquinolones resistance was investigated. A S. pneumoniae ATCC 46619-derived strain with high-level efflux activity was obtained (SP-25A). Both the parent and obtained strains were tested against efflux substrates acriflavine (Acr) and ethidium bromide (EtBr), and against norfloxacin (NFX), ciprofloxacin (CFX), levofloxacin (LFX), moxifloxacin (MFX), trovafloxacin (TVX) and sitafloxacin (SFX), in presence and absence of the efflux pump inhibitor reserpine. gyrA, gyrB, parC and parE QRDR genes were amplified by PCR and sequenced. MICs of NFX and CFX against SP-25A were 64-fold higher than parent strain MICs (256 mg/L versus 4 mg/L and 64 mg/L versus 1mg/L, respectively). MIC of LFX increased from 1 to 4 mg/L and MICs of MFX, TVX and SFX remained virtually unchanged (0.1-0.2 mg/L). MICs of Acr and EtBr against SP-25A were 8- and 16-fold higher than against parent strains. In both cases, reserpine reverted MICs to the parent strain values (1 and 0.2 mg/L). Only parE showed two mutations leading to a Pro(454) --> Ser and Glu(443) changes, which have previously been shown not to lead to significant fluoroquinolones MIC increases. SP-25A showed a significant increase of MICs of the hydrophilic fluoroquinolones, apparently derived only from efflux activity. Efflux activity, at these high levels, can lead to high-level resistance to older hydrophilic fluoroquinolones, but does affect newer fluoroquinolones such as moxifloxacin, trovafloxacin and sitafloxacin.     

In vitro activity and pharmacodynamics of oral beta-lactam antibiotics against Streptococcus pneumoniae from southeast Missouri.

STUDY OBJECTIVES: To determine the frequency of reduced susceptibility to penicillin, and to compare the in vitro activity and pharmacodynamics of oral beta-lactam antibiotics against clinical isolates of Streptococcus pneumoniae from southeast Missouri. SETTING: Cape Girardeau, Missouri (population 35,500). Interventions. Minimum inhibitory concentrations (MICs) were determined for penicillin, amoxicillin, amoxicillin-clavulanic acid, cefprozil, cefuroxime, cefpodoxime, cefaclor, and loracarbef by E test for 108 isolates of S. pneumoniae. The MIC50, MIC90, and percentage susceptibility were calculated for each agent. Pharmacokinetic variables were obtained from the literature, and serum concentration-time profiles were simulated for a 25-kg child taking pediatric dosages commonly administered to treat otitis media. The average time above MIC (T > MIC) was calculated as percentage of the dosing interval using free concentrations and the MIC for each individual isolate. Analysis of variance (Scheffe post hoc test) was used to determine differences among agents for in vitro activity and T > MIC (level of significance, p<0.05). MEASUREMENTS AND MAIN RESULTS: The frequency of penicillin-nonsusceptible S. pneumoniae was 28.7% (31/108). For 25 penicillin-intermediate isolates, amoxicillin and amoxicillin-clavulanic acid were significantly more active than cefprozil, cefaclor, and loracarbef. The T > MIC for amoxicillin and amoxicillin-clavulanic acid, simulated at 13.3 mg/kg every 8 hours, was significantly longer than that for all other beta-lactams. CONCLUSION: Amoxicillin and amoxicillin-clavulanic acid have superior in vitro activity and longer T > MIC for penicillin-intermediate isolates than the other oral beta-lactams.     

In vitro activity of garenoxacin against recent clinical isolates of Chlamydia pneumoniae

The in vitro activities of garenoxacin, a novel des-F (6)-quinolone, levofloxacin, moxifloxacin and clarithromycin were tested against 30 recent clinical isolates of Chlamydia pneumoniae. The minimal inhibitory concentration (MIC) at which 90% of the isolates were inhibited and the minimal bactericidal concentration (MBC) at which 90% of the isolates were killed by garenoxacin for C. pneumoniae was 0.03 mg/l (range 0.015–0.03 mg/l).     

Comparative in vitro activity of ciprofloxacin and five other quinoline derivatives against gram-negative isolates

A total of 375 Gram-negative bacterial strains were isolated from midstream urine specimens of the same number of patients affected by urinary tract infections. All bacteria were identified by standard bacteriological methods and their susceptibility to six quinoline derivatives (ciprofloxacin, cinoxacin, norfloxacin, oxolinic acid, pipemidic acid, nalidixic acid) was studied by determining the MICs and MBCs for each compound using a miniaturized dilution broth method in microtitre plates and twofold dilutions of each drug from 256 to 0.12 mcg/ml. Ciprofloxacin, a new quinoline carboxylic acid compound structurally related to nalidixic acid, showed a much higher antibacterial activity against all bacterial strains under examination, including Pseudomonas, than the other compounds, except for norfloxacin. The MIC90 and MBC90 of ciprofloxacin never exceeded 1 mcg/ml with any of the bacterial species; and MBC/MIC ratios were very low, which represents an important clinical advantage. Only norfloxacin showed comparable effectiveness. No bacterial strain showed resistance to the drug and the MIC90 and MBC90 never exceeded 8 mcg/ml.     

In vitro activity of telithromycin compared with macrolides and fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis

The in vitro activity of telithromycin was compared with erythromycin A, azithromycin, clarithromycin, moxifloxacin, gemifloxacin, levofloxacin, ciprofloxacin, penicillin G, ampicillin, cefuroxime and ceftriaxone against 336 consecutive strains (83 Streptococcus pneumoniae, 168 Haemophilus influenzae and 85 Moraxella catarrhalis) isolated from patients with community-acquired respiratory tract infections. Telithromycin (MIC(90), 0.008 mg/l) was the most active drug against S. pneumoniae. Telithromycin was also highly active against M. catarrhalis (MIC(90), 0.06 mg/l), but less active against H. influenzae (MIC(90), 4 mg/l).     

Comparative in-vitro activity of penicillin alone and combined with gentamicin against clinical isolates of Streptococcus pneumoniae with decreased susceptibility to penicillin

The worldwide emergence of Streptococcus pneumoniae with decreased susceptibility to penicillin has led to the suggestion that drug combinations might be used. The aim of this study was to determine possible synergy using a combination of penicillin with sub-inhibitory doses of gentamicin against 26 clinical isolates of S. pneumoniae with decreased susceptibility to penicillin, using half-chequerboards and killing curves. Synergy was demonstrated for ten of the 26 isolates with the combination of penicillin with gentamicin at 1 mg/l and for 22 isolates with penicillin and gentamicin at 2 mg/l. Killing curves on three isolates showed synergy and confirmed the chequerboard results. Further synergy studies using penicillin or cefotaxime/ceftriaxone, plus low dose gentamicin against penicillin-resistant pneumococci are indicated.     

In vitro activity of sitafloxacin compared with several fluoroquinolones against Streptococcus anginosus and Streptococcus constellatus

The in vitro activities of sitafloxacin and seven other fluoroquinolones a (ciprofloxacin, tosufloxacin, sparfloxacin, levofloxacin, T-3811ME, moxifloxacin and trovafloxacin) were examined by the microdilution method against 79 clinically isolated 'Streptococcus milleri' group (SMG) microorganisms. No statistically significant differences were found between the minimum inhibitory concentrations (MIC(50) and MIC(90)) against Streptococcus anginosus and Streptococcus constellatus. Sitafloxacin was the most active agent of the eight fluoroquinolones tested against SMG, with a MIC(90) of 0.06 microg/mL, which was 8 times more active than ciprofloxacin and 16 times more active than levofloxacin. Although none of the SMG strains showed high resistance to any of the fluoroquinolones tested, three agents (trovafloxacin, sitafloxacin and T-3811ME) had low MICs against 23 SMG strains against which levofloxacin had a MIC> 1 microg/mL. In conclusion, several fluoroquinolones have low MICs against SMG, but sitafloxacin has the lowest.     

Comparative in vitro activity of ciprofloxacin against aerobic and anaerobic bacteria from clinical isolates

1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazin-1- ylquinoline-3-carboxylic acid (ciprofloxacin, Bay o 9867, Ciprobay) is a broad spectrum antibiotic of the 4-quinolone group. It possesses a bactericidal effect attributable to the property of DNA-gyrase inhibition. The antimicrobial action comprises all grampositive strains (including Streptococcus faecalis) and gramnegative strains (including Pseudomonas aeruginosa and Serratia spp.), as well as Bacteroides fragilis and other Bacteroides species. In this comparative study the antimicrobial effect of ciprofloxacin was tested against 665 gramnegative, 412 grampositive and 274 anaerobic strains from fresh clinical isolates and compared with that of other frequently used antibiotics. The minimum inhibitory concentrations (MIC) were determined by means of a serial dilution test with micro standard plates. Within the group of gramnegative strains, ciprofloxacin was the most active antibiotic with an MIC90 of 0.12 mg/l to 0.5 mg/l for most isolates. Ciprofloxacin shows a broad spectrum of activity against gramnegative pathogenic bacteria including Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Serratia spp. and Acinetobacter spp., and also covers resistant strains of Pseudomonas aeruginosa and Alcaligenes faecalis. Ciprofloxacin also shows a high inhibiting activity against grampositive strains (Staphylococci, Enterococci) and anaerobic pathogens.     

甲磺酸左氧氟沙星对耐青霉素肺炎链球菌的体外抗菌活性

目的 观察甲磺酸左氧氮沙星对耐青霉素肺炎链球菌(PRSP)的药敏及疗效。方法 对6株临床分离的耐青霉素肺炎链球菌，采用E—test方法，测定甲磺酸左氧氮沙星等6种抗生素的抗菌活性。同时观察甲磺酸左氧氮沙星单药治疗取SP临床疗效及不良反应。结果6株取SP均为低耐药菌株，对甲磺酸左氧氮沙星敏感。6例患者经治疗后，5例痊愈，l例显效，无明显副反应发生。结论 甲磺酸左氧氮沙星可有效治疗耐青霉素肺炎链球菌性肺炎。     

Measurement of the bactericidal activity of fluoroquinolones against Streptococcus pneumoniae using the bactericidal index method

Kill curve analysis alone showed trovafloxacin to be more bactericidal than levofloxacin, grepafloxacin and moxifloxacin against four isolates of Streptococcus pneumoniae. However, using the bactericidal index (BI) method, levofloxacin was the most bactericidal fluoroquinolone using serum or lung biopsy concentration levels against the ofloxacin-susceptible strains and trovafloxacin was the most bactericidal against the ofloxacin-intermediate strain. None of the fluoroquinolones was bactericidal against the ofloxacin-resistant strain. With BIs using epithelial lining fluid or alveolar macrophage concentration levels, trovafloxacin or grepafloxacin was most bactericidal, respectively. These data illustrate that simple analysis of traditional kill curves may not be adequate in the evaluation of fluoroquinolone bactericidal activity. The results of this study suggest a need for further investigation to assess the role of tissue concentration and bactericidal activity in antimicrobial efficacy.     

In vitro activity of four fluoroquinolones against clinical isolates of Pseudomonas aeruginosa determined by the E test

Ciprofloxacin, levofloxacin, ofloxacin, and trovafloxacin were tested by the E-test against 100 clinical isolates of Pseudomonas aeruginosa. Ciprofloxacin was the most active of the tested agents with 82% of isolates having a MIC 8). Levofloxacin and trovafloxacin had nearly identical potency: 75% and 76% of the isolates were inhibited by 8 for levofloxacin; 0.19->8 for trovafloxacin). Ofloxacin was the least active of the four quinolones, with 43% of the isolates having a MIC >2 mg/l. All isolates resistant to ciprofloxacin were also resistant to the other agents, i.e. resistance to ciprofloxacin predicted resistance to all the quinolones tested in every case. This data demonstrates that fluoroquinolones are active agents against P. aeruginosa. In vitro susceptibility testing, however, is crucial to assess the resistance pattern in any specific location and for each individual agent.     

Comparative in vitro activity of gemifloxacin to other fluoroquinolones and non-quinolone agents against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in the United States in 1999-2000

This study was undertaken to assess the in vitro activity of gemifloxacin, five other fluoroquinolone antimicrobial agents (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin and ofloxacin) and other non-quinolone comparator agents (ampicillin, erythromycin, clindamycin, doxycycline, penicillin and trimethoprim/sulphamethoxazole) against Streptococcus pneumoniae collected in the United States. Susceptibility testing of 550 S. pneumoniae, 290 Haemophilus influenzae and 205 Moraxella catarrhalis showed that 38.2% of pneumococci were penicillin nonsusceptible, while 26.2 and 95.6% of H. influenzae and M. catarrhalis, respectively, produced beta-lactamase. Overall new fluoroquinolones were the most active agents. The in vitro activity (based on MIC90 in mg/l) of the six fluoroquinolones was gemifloxacin>moxifloxacin>gatifloxacin>levofloxacin>ciprofloxacin and ofloxacin.     

帕珠沙星对临床分离致病菌的体外抗菌活性研究

目的评价帕珠沙星的体外抗菌活性。方法采用琼脂二倍稀释法，测定帕珠沙星与左氧氟沙星对342株临床分离菌株的最低抑菌浓度（MIC）。结果帕珠沙星对革兰阴性菌和革兰阳性菌的MIC90分别为0．06～4和1～16μg／ml。对大肠埃希菌、阴沟肠杆菌、变形菌、铜绿假单胞菌、不动杆菌和链球菌的MIC90为0．06～4μg／ml，是左氧氟沙星的1／2～1／8;对肺炎克雷伯菌、金葡菌和表葡菌与左氧氟沙星抗菌作用相当，MIC90分别为0．5、1、1μg／ml；对流感嗜血杆菌、黏膜炎莫拉菌和粪肠球菌的MIC90为0．5、1、16μg／ml，高于左氧氟沙星（0．25、0．5、8μg／ml）。结论帕珠沙星对革兰阴性菌和革兰阳性菌均具有广谱的抗菌作用，对革兰阴性菌的抗菌活性优于革兰阳性菌。     

In vitro activity of sitafloxacin against clinical isolates in 2009

In vitro activity of sitafloxacin (STFX) and various oral antimicrobial agents against bacterial isolates recovered from clinical specimens between January and December 2009, at different healthcare facilities in Japan was evaluated. A total of 1,620 isolates including aerobic and anaerobic organisms was available for the susceptibility testing using the microbroth dilution methods recommended by Clinical Laboratory Standard Institute. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) was 0.06 microg/mL for methicillin-susceptible Staphylococcus aureus and was equal to that of garenoxacin (GRNX), 2 times lower than that of moxifloxacin (MFLX), and 8 times lower than that of levofloxacin (LVFX). STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90s of STFX ranged from 0.03 to 0.06 microg/mL and were 1 to 2 times lower than those of GRNX, 2 to 4 times lower than those of MFLX, and 16 to 32 times lower than those of LVFX. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL and was 2 times lower than that of GRNX, 4 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX was 0.25 microg/mL for Enterococcus faecalis, and was 2 times lower than those of GRNX and MFLX, and 8 times lower than that of LVFX. The MIC90 of STFX for E. coli was 2 microg/mL, and the MIC90s of other 10 species of Enterobacteriaceae which were the lowest values of the quinolones tested ranged from 0.03 to 1 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 8 microg/mL and was 16 times lower than those of GRNX, MFLX and LVFX. The MIC90 of STFX for P aeruginosa isolates recovered from respiratory infections was 2 microg/mL and was 32 times lower than those of GRNX and MFLX, and 16 times lower than that of LVFX. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less, and was 2 to 4 times lower than those of GRNX, 8 times lower than those of MFLX, and 4 times lower than those of LVFX. The MIC90 of STFX was 0.008 microg/mL for Moraxella catarrhalis, and was 2 times lower than that of GRNX, 8 times lower than those of MFLX and LVFX. The MIC90s of STFX ranged from 0.015 to 0.12 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested. In conclusion, the activity of STFX against Gram-positive cocci was comparable or superior to those of GRNX, MFLX and LVFX. STFX showed the most potent activity against Gram-negative bacteria and anaerobic bacteria of all the antimicrobial agents tested in this study.     

Comparative pharmacodynamics of the new fluoroquinolone ABT492 and levofloxacin with Streptococcus pneumoniae in an in vitro dynamic model

The kinetics of killing of Streptococcus pneumoniae exposed to ABT492 or levofloxacin were compared. S. pneumoniae ATCC 49619 and four ciprofloxacin-resistant clinical isolates, S. pneumoniae 1149, 391, 79 and 804, were exposed to ABT492 and levofloxacin as a single dose in a dynamic model that simulates human pharmacokinetics of the quinolones. With S. pneumoniae ATCC 49619 eight-fold ranging AUC/MIC ratios (60-500 h) were simulated for each quinolone. In addition, two larger AUC/MICs, i.e., 1080 and 2150 h for ABT492 and 1460 and 3660 h for levofloxacin which correspond to 100 and 200 mg doses of ABT492 and 200 and 500 mg doses of levofloxacin, respectively, were mimicked. Each ciprofloxacin-resistant organism was exposed to the clinical doses of ABT492 (400 mg) and levofloxacin (500 mg); the respective AUC/MIC ratios were from 580 to 3470 h and from 28 to 110 h. At comparable AUC/MICs (from 60 to 500 h), regrowth of S. pneumoniae ATCC 49619 followed initial killing, and the times to regrowth were longer with levofloxacin than ABT492. However, no regrowth of S. pneumoniae ATCC 49619 occurred at the higher AUC/MICs of ABT492 (1080 and 2150 h) and levofloxacin (1460 and 3660 h). Killing of S. pneumoniae 1149, 391 and 79 without bacterial regrowth, was provided by ABT492 (AUC/MIC 3470, 2310 and 1160 h, respectively) but not levofloxacin (AUC/MIC 55, 110 and 28 h, respectively). Regrowth of S. pneumoniae 804 was observed with both ABT492 and levofloxacin (AUC/MIC 580 and 55 h, respectively). Areas between the control growth curve and the time-kill curve (ABBCs) for ABT492 against S. pneumoniae 1149, 391 and 79 were 2.6-4.2 times larger than the respective ABBCs for levofloxacin, whereas similar ABBCs were found with S. pneumoniae 804 exposed to both quinolones. These findings predict significantly greater efficacy of ABT492 than levofloxacin at clinically achievable AUC/MIC ratios against ciprofloxacin-resistant S. pneumoniae and similar efficacies of the two quinolones against susceptible organisms.     

Ciclopiroxolamine: in vitro antifungal activity against clinical yeast isolates

The in vitro susceptibility of 225 clinical isolates of yeasts to ciclopiroxolamine (CPO) was compared with that of clotrimazole, econazole, ketoconazole, miconazole, tioconazole, fluconazole, itraconazole and nystatin using a standardized agar diffusion method (NeoSensitabs). Two hundred and eight strains of yeasts comprising 16 species of Candida and 22 strains belonging to other yeast genera were tested. One strain (0.4%) was resistant, four strains (1.8%) of intermediate susceptibility and 220 strains (97.3%) susceptible to CPO. More strains were susceptible to CPO than to the other antifungals studied. Susceptibility patterns of antifungal agents were not linked to species. The in vitro antifungal susceptibility profile of CPO was better than topical azole derivatives or fluconazole and itraconazole against a wide variety of clinically important yeasts.