In vitro susceptibility of 4903 bacterial isolates to gemifloxacin--an advanced fluoroquinolone

The in vitro activity of gemifloxacin against over 4900 bacterial isolates was determined by microbroth dilution with interpretation in accordance with NCCLS guidelines. Susceptibility results were compared with those for ciprofloxacin, gatifloxacin, levofloxacin and moxifloxacin. Gemifloxacin and the other fluoroquinolones were not affected by either beta-lactamase production or penicillin-resistance in Streptococcus pneumoniae. The MIC90 values for gemifloxacin were: S. pneumoniae 0.063 mg/l; Haemophilus influenzae 0.016 mg/l; Moraxella catarrhalis 0.008 mg/l, methicillin-susceptible Staphylococcus aureus 0.063 mg/l; methicillin-susceptible Streptococcus pyogenes 0.031 mg/l; Enterobacteriaceae 0.031-0.16 mg/l; Pseudomonas aeruginosa 4 mg/l; Neisseria meningitidis 0.008 mg/l. The MIC90 for gemifloxacin was lower than those for the other quinolones tested against S. pneumoniae (ciprofloxacin 2-4 mg/l, gatifloxacin 0.5 mg/l, levofloxacin 1-2 mg/l, moxifloxacin 0.25 mg/l). This study confirms the enhanced potent activity of gemifloxacin against Gram-positive pathogens, its broad-spectrum, Gram-negative activity and indicates that gemifloxacin is likely to have an important role in treating patients with Gram-positive and/or Gram-negative infections.     

Comparison of minimal inhibitory and mutant prevention drug concentrations of 4 fluoroquinolones against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus

Staphylococcus aureus remains an important human pathogen affecting both outpatients and those hospitalized. Increasing antimicrobial resistance is global but prevalence rates are variable for different geographical areas. Fluoroquinolones have been used to treat S. aureus infections and the newer quinolones have enhanced in vitro activity against this organism. The mutant prevention concentration (MPC) defines the antimicrobial drug concentration threshold that would require an organism to simultaneously possess two mutations for growth in the presence of the drug. We tested clinical isolates of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) S. aureus by minimum inhibitory concentration (MIC) and MPC against gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin. For MSSA strains, the rank order of potency based on MIC(90) values were gemifloxacin (0.063 mg/l) = moxifloxacin (0.063 mg/l) > gatifloxacin (0.05 mg/l) = levofloxacin (0.25 mg/l) and by MPC values moxifloxacin (0.25 mg/l) > gemifloxacin (0.5 mg/l) > gatifloxacin (1 mg/l) = levofloxacin (1mg/l). For 87% of the isolates the MPC value was 0.5 mg/l for gatifloxacin. The rank order of potency based on the time the serum drug concentration exceeded the MPC(90), was as follows: moxifloxacin (>24 h) > levofloxacin (>18 h) > gatifloxacin (12 h) > gemifloxacin (9 h). Serum drug concentration remained in excess of the MPC(87) for 24 h for gatifloxacin. Both MIC(90) and MPC(90) values were higher against MRSA strains and the time above the MPC(90) was significantly shorter for all agents.     

In vitro activity of gatifloxacin compared with gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin against uropathogens cultured from patients with complicated urinary tract infections

Minimum inhibitory concentrations (MICs) of gatifloxacin were compared with those of gemifloxacin, moxifloxacin, trovafloxacin, ciprofloxacin and ofloxacin using an agar dilution method for 400 uropathogens cultured from the urine of urological patients with complicated and/or hospital-acquired urinary tract infections (UTI). The collection of strains was made up of Enterobacteriaceae (34.5%), enterococci (31.5%), staphylococci (21.2%) and non-fermenting bacteria (12.8%). The antibacterial activity of the three newer fluoroquinolones, gatifloxacin, gemifloxacin, and moxifloxacin, were similar, but showed some drug specific differences. Gemifloxacin was most active against Escherichia coli, but less so against Proteus mirabilis. In this series all isolates of E. coli were inhibited at a MIC of 0.25 mg/l gatifloxacin and moxifloxacin and by 0.125 mg/l gemifloxacin. The MIC distribution of all fluoroquinolones showed a bimodal distribution for staphylococci, enterococci and Pseudomonas aeruginosa. The two modes for P. aeruginosa were 1 and 64 mg/l for gemifloxacin and moxifloxacin and 0.5 and 64 mg/l for gatifloxacin. For staphylococci the two modes were 0.125 and 2 mg/l for gatifloxacin, 0.03 and 4 mg/l for gemifloxacin, and 0.03 and 2 mg/l for moxifloxacin; for enterococci, 0.25 and 16 mg/l for gatifloxacin, 0.06 and 2 mg/l for gemifloxacin, and 0.25 and 8 mg/l for moxifloxacin. Compared with trovafloxacin the MICs were similar, but the newer fluoroquinolones were more active than ciprofloxacin and ofloxacin against Gram-positive bacteria. Of the newer fluoroquinolones gatifloxacin had the highest rate of renal excretion and could be considered a promising alternative fluoroquinolone agent for the treatment of UTI.     

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.     

Susceptibility of Canadian isolates of Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae to oral antimicrobial agents

We measured the susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several currently approved antimicrobial agents by two different methods. We also measured the susceptibility of isolates to seven fluoroquinolones. Beta-lactamase was produced by 123/566 (21.7%) of H. influenzae isolates compared with 178/200 (89%) of M. catarrhalis isolates. For S. pneumoniae 83/374 (22.2%) isolates were penicillin resistant and of these 2.1% (8/374) showed high level resistance (MIC≥2 mg/l). Regardless of methodology, all fluoroquinolones were highly active against H. influenzae (MIC₉₀ ≤0.031 mg/l) and M. catarrhalis (MIC₉₀ ≤0.064 mg/l) isolates. Susceptibility of H. influenzae to cefuroxime and amoxycillin/clavulanic acid was 99–100% whereas 84–85.5% were susceptible to cefaclor and cefprozil. Azithromycin susceptibility ranged from 82.6 to 99.2% depending on the method. M. catarrhalis isolates were uniformly susceptible to all agents tested except amoxycillin. Cross-resistance in S. pneumoniae to all non-quinolone agents was concurrent with increasing penicillin resistance as shown by increasing MIC₉₀ values. For the fluoroquinolones tested, the rank order of potency based on MIC₉₀ values was as follows: gemifloxacin (0.031–0.063 mg/l), trovafloxacin (0.125 mg/l), moxifloxacin (0.125–0.25 mg/l), grepafloxacin (0.125–0.25 mg/l), gatifloxacin (0.5 mg/l), levofloxacin (1 mg/l) and ciprofloxacin (2 mg/l). Our study confirms either a high or increasing prevalence of antimicrobial resistant respiratory pathogens in Canada and also compares the new and old fluoroquinolones and their potential role as therapy for community-acquired infections. The prevalence of β-lactamase positive H. influenzae may have decreased from levels reported in previous studies.     

In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point

A dose-decreasing immunocompetent sepsis mouse model was used to evaluate the in vivo effect of levofloxacin, moxifloxacin and gemifloxacin, using a ciprofloxacin/levofloxacin susceptible serotype 6B strain (ciprofloxacin MIC: 1 mg/l) and two resistant serotype 14 and 19F strains with gyrA and parC point mutations (ciprofloxacin MICs of 32 and 64 mg/l, respectively). Significant higher in vivo activity was found for moxifloxacin and gemifloxacin than for levofloxacin against strains 1 and 2, and for gemifloxacin versus moxifloxacin or levofloxacin against strain 3. Gemifloxacin treatment resulted in 100% survival against strains 1 and 2(AUC0-24 h/MIC of 30 and 62) but against strain 3, survival was 60-80% (AUC0-24 h/MIC of 93). Similar AUC0-24 h/MIC values produced different therapeutic results suggesting that in vitro parameters other than the MIC could influence efficacy predictions based on in vitro susceptibility tests (MICs) or pharmacodynamic parameters (AUC0-24 h/MIC).     

Susceptibility of bacterial isolates to gatifloxacin and ciprofloxacin from clinical trials 1997-1998

MICs of gatifloxacin and ciprofloxacin against 3482 pre-treatment, clinical trial isolates collected during 1997–1998 are reported. These data suggested that gatifloxacin was four- to eight-fold more active than ciprofloxacin against Gram-positive bacteria, with gatifloxacin MIC₉₀s≤0.33 mg/l against Staphylococcus aureus and Streptococcus pneumoniae, and ≤1.0 mg/l versus viridans streptococci and Enterococcus faecalis. Both quinolones had similar MIC₉₀s versus Enterobacteriaceae (generally ≤0.38 mg/l, except 0.7–0.8 mg/l for Citrobacter freundii) and Pseudomonas aeruginosa (8 mg/l). A total of 78% P. aeruginosa had gatifloxacin MICs ≤2 mg/l. Gatifloxacin was more active than ciprofloxacin against Acinetobacter species and non-P. aeruginosa pseudomonads. Both had exceptional activity versus Haemophilus spp, Moraxella catarrhalis and Neisseria gonorrhoeae. In summary, compared to ciprofloxacin, gatifloxacin had improved activity against Gram-positive bacteria and comparable activity against Gram-negative bacteria.     

舒巴坦联合9种抗菌药物对耐碳青霉烯类鲍曼不动杆菌体外抗菌活性研究

目的：评价舒巴坦与9种临床常用抗菌药物联合用药对耐碳青霉烯类鲍曼不动杆菌（CRAB）的体外抗菌效应。方法：从临床分离得到24株CRAB。采取微量肉汤稀释法测定10种抗菌药物单一用药对CRAB的最低抑菌浓度（MIC）。采用棋盘法设计,微量肉汤稀释法测定舒巴坦分别联合9种抗菌药物对CRAB的MIC,并计算部分抑菌浓度指数（FIC）判定联合效应。结果：9种抗菌药物联用舒巴坦后的MIC均比单用时降低;联用后替加环素、多西环素、环丙沙星、左氧氟沙星的MIC₅₀均低于对应单药敏感折点,替加环素的MIC₉₀达到单药的敏感折点。舒巴坦与9组联合用药均未出现拮抗作用;舒巴坦联合阿米卡星的协同作用最强,其次为美罗培南、帕尼培南、亚胺培南、多西环素、替加环素。结论：与单药相比,9种药物联用舒巴坦对CRAB的体外抑菌作用均有增强效果。9种抗菌药物联合舒巴坦有效地降低MIC值,其中多西环素、替加环素、环丙沙星和左氧氟沙星,可使其MIC值降至敏感范围内。     

In vitro activities of mutant prevention concentration-targeted concentrations of fluoroquinolones against Staphylococcus aureus in a pharmacodynamic model

To test the validity of the mutant selection window, we simulated mutant prevention concentration-targeted fluoroquinolone concentrations using an in vitro model with infected fibrin clots. Therapeutic ciprofloxacin (peak 5 microg/mL; t(1/2) 4 h), gatifloxacin (3.5 microg/mL; 8h), gemifloxacin (1.25 microg/mL; 8 h), levofloxacin (6 microg/mL; 6 h) and moxifloxacin (4.5 microg/mL; 12 h) were tested against methicillin-susceptible and -resistant Staphylococcus aureus, as were mutant prevention concentration (MPC)-targeted regimens achieving a trough of 1/4x or 2x MPC. MIC/MPC for MSSA K553 were 0.125/2, 0.03/0.125, 0.03/0.063, 0.125/1 and 0.015/0.25 microg/mL for ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin, respectively. Corresponding values for MRSA 494 were 0.125/1, 0.063/0.125, 0.03/0.063, 0.125/0.5 and 0.063/0.125 microg/mL. All regimens produced efflux mutants of MSSA K553. For MRSA 494, therapeutic and 1/4x MPC levofloxacin regimens produced resistance, whereas only 1/4x MPC regimens of gatifloxacin, gemifloxacin, and moxifloxacin produced resistance. All ciprofloxacin regimens produced resistance. Ciprofloxacin 1/4x MPC and therapeutic levofloxacin caused outgrowth of GrlA mutants (S80Y amino acid substitution); efflux mutants were isolated in all other cases. Overall, gatifloxacin, gemifloxacin, and moxifloxacin displayed a lesser propensity to select resistant isolates of S. aureus than ciprofloxacin and levofloxacin. The mutant selection window premise appeared valid for MRSA only. Additional studies are necessary to define the applicability of the MPC.     

In vitro activities of fourteen antimicrobial agents against obligately anaerobic bacteria

The in vitro activities of fourteen antimicrobial agents were tested against 292 clinical isolates of obligately anaerobic bacteria using the broth microdilution technique. Taking all strains as a group the MIC(50/90) (mg/l) values were metronidazole and imipenem 0.25/1, meropenem 0.25/0.5, trovafloxacin 0.25/1, gatifloxacin and moxifloxacin 0.5/2, levofloxacin 2/16, ciprofloxacin 4/32, clindamycin 0.5/8, amoxycillin/clavulanate 1/4, doxycycline and chloramphenicol 2/4, erythromycin 4/>32 and penicillin G 16/>32.     

甲磺酸加替沙星与其他4种氟喹诺酮类药物对临床分离菌的体外抗菌活性比较

目的 :比较甲磺酸加替沙星与氧氟沙星、左氧沙星、环丙沙星、司帕沙星对 182株临床分离菌的体外抗菌活性。方法 :采用琼脂平板二倍稀释法测定加替沙星等 5种氟喹诺酮类药物对 182株临床试验分离菌株的最低抑菌浓度 (MIC)。结果 :加替沙星对葡萄球菌属的MIC90 比其他 4种氟喹诺酮类药物低。葡萄球菌属对加替沙星的敏感率显著高于其他4种氟喹诺酮类药物 ;对其他G 球菌的MICR 也较其他氟喹诺酮类药物低。G-杆菌中埃希菌属、肠杆菌属对加替沙星的敏感率明显高于其他 4种氟喹诺酮类药物 ,加替沙星对埃希菌属、肠杆菌属的MIC90比左氧沙星低 2倍 ,比其他 3种抗菌药物低 8倍 ;假单胞菌属、克雷伯菌属和其他G-杆菌对加替沙星的敏感率与左氧沙星的差异无统计学意义 ,与其他 3种氟喹诺酮类药物的差异有统计学意义。结论 :甲磺酸加替沙星具有广谱而强大的体外抗菌活性。     

Antimicrobial susceptibilities of 40 isolates of Bacillus anthracis isolated in Turkey

Forty clinical isolates of Bacillus anthracis were studied. The MIC(90) values of penicillin G, doxycycline, ciprofloxacin, gatifloxacin, and levofloxacin were 0.016, 0.03, 0.06, 0.06 and 0.12 mg/l, respectively. Susceptibilities suggest that the quinolones may also be considered as an alternative therapy for anthrax.     

In vitro activity of moxifloxacin,levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis

The in vitro activity of moxifloxacin, gatifloxacin, levofloxacin and linezolid was evaluated against 234 strains of Mycobacterium tuberculosis isolated in the Southeast of Spain. All drugs tested showed good activity, with an MIC₉₀ of less than 1 mg/l, and were active against isociacide and rifampicin resistant strains. Three strains were resistant to isoniazid and to the fluoroquinolones, which suggested the existence of mechanisms of resistance not yet described. These new compounds may prove to be therapeutic alternatives for treatment of multi-resistant tuberculosis and further studies should be done to demonstrate their true usefulness.     

氟喹诺酮类药物浓度对预防肺炎链球菌耐药的影响研究

目的检测氟喹诺酮类药物对肺炎链球菌临床耐药的预防作用,并比较防突变浓度（MPC）与最低抑菌浓度（MIC）间的关系,为临床合理用药提供依据。方法采用琼脂二倍稀释法检测5种抗菌药物的MIC值,计算MIC50和MIC90值;采用新鲜制备的1010 CFU/mL菌液测定MPC值,测定MPC值,接种细菌浓度〉1010,计算MPC50和MPC90值,并比较MPC/MIC。结果在5种药物中,莫西沙星的MPC50和MPC90值最低,分别为1mg/L和2mg/L,环丙沙星最高,为16mg/L和32mg/L;测定菌株对莫西沙星、左氧沙星的MPC/MIC范围主要在8～16,对加替沙星、司巴沙星的MPC/MIC范围主要在16～32,对环丙沙星的MPC/MIC范围主要在32～64。结论莫西沙星、左氧沙星抗菌谱广,而且MPC值较低,并可以防止肺炎链球菌突变的发生。     

In vitro activity of linezolid,synercid and telithromycin against genetically defined high level fluoroquinolone-resistant methicillin-resistant Staphylococcus aureus

The in vitro activity of levofloxacin, moxifloxacin, gatifloxacin, erythromycin, telithromycin, linezolid, synercid and vancomycin was measured against 36 genetically defined, gyrA/grlA double mutant MRSA clinical strains with an MIC to ciprofloxacin > or = 8 mg/l. The three newer fluoroquinolones tested were more active than ciprofloxacin. Resistance rates for levofloxacin and gatifloxacin were high (44.5 and 36.1%, respectively). All the strains were moxifloxacin-susceptible, though most of them had MICs close to the break point. All the strains were intermediate or resistant to erythromycin and most were also resistant to telithromycin. No strains were resistant to linezolid, synercid or vancomycin (MIC(90): 2, 1 and 2 mg/l, respectively).     

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).     

Activity of moxifloxacin and other quinolones against pneumococci resistant to first-line agents, or with high-level ciprofloxacin resistance

The activity of moxifloxacin and other quinolones was assessed against 288 epidemiologically diverse isolates of Streptococcus pneumoniae, many of them resistant to one or more first-line agents and/or with increased ciprofloxacin resistance (minimum inhibitory concentrations, MICs 16- > 64 mg/l compared with 1-2 mg/l for most isolates). Moxifloxacin and grepafloxacin were the most active quinolone analogues, inhibiting about 90% of the isolates at < or = 1 mg/l, whereas levofloxacin inhibited 64% of isolates at < = 1 mg/l and ciprofloxacin inhibited 42%. Moxifloxacin also was the most active agent against isolates with elevated ciprofloxacin resistance (MIC 16- > 64 mg/l): moxifloxacin MICs of around 4 mg/l were seen for most such isolates, compared with 16-32 mg for levofloxacin and grepafloxacin. The activity of moxifloxacin against pneumococci resistant to one or more first-line agent suggests it will have a useful therapeutic role, although its activity against highly ciprofloxacin resistant isolates seems marginal.     

A critical review of the fluoroquinolones: focus on respiratory infections.

The new fluoroquinolones (clinafloxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin) offer excellent activity against Gram-negative bacilli and improved Gram-positive activity (e.g. against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin. Ciprofloxacin still maintains the best in vitro activity against Pseudomonas aeruginosa. Clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (e.g. Bacteroides fragilis) versus ciprofloxacin. All of the new fluoroquinolones display excellent bioavailability and have longer serum half-lives than ciprofloxacin allowing for once daily dose administration. Clinical trials comparing the new fluoroquinolones to each other or to standard therapy have demonstrated good efficacy in a variety of community-acquired respiratory infections (e.g. pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis). Limited data suggest that the new fluoroquinolones as a class may lead to better outcomes in community-acquired pneumonia and acute exacerbations of chronic bronchitis versus comparators. Several of these agents have either been withdrawn from the market, had their use severely restricted because of adverse effects (clinafloxacin because of phototoxicity and hypoglycaemia; grepafloxacin because of prolongation of the QTc and resultant torsades de pointes; sparfloxacin because of phototoxicity; and trovafloxacin because of hepatotoxicity), or were discontinued during developmental phases. The remaining fluoroquinolones such as gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin have adverse effect profiles similar to ciprofloxacin. Extensive post-marketing safety surveillance data (as are available with ciprofloxacin and levofloxacin) are required for all new fluoroquinolones before safety can be definitively established. Drug interactions are limited; however, all fluoroquinolones interact with metal ion containing drugs (eg. antacids). The new fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin) offer several advantages over ciprofloxacin and are emerging as important therapeutic agents in the treatment of community-acquired respiratory infections. Their broad spectrum of activity which includes respiratory pathogens such as penicillin and macrolide resistant S. pneumoniae, favourable pharmacokinetic parameters, good bacteriological and clinical efficacy will lead to growing use of these agents in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis. These agents may result in cost savings especially in situations where, because of their potent broad-spectrum activity and excellent bioavailability, they may be used orally in place of intravenous antibacterials. Prudent use of the new fluoroquinolones will be required to minimise the development of resistance to these agents.     

A comparative study of the fluoroquinolone antibacterial agents on the action potential duration in guinea pig ventricular myocardia

We examined the effects of ten fluoroquinolone antibacterial agents, levofloxacin, sitafloxacin, trovafloxacin, ciprofloxacin, gemifloxacin, tosufloxacin, gatifloxacin, grepafloxacin, moxifloxacin and sparfloxacin, on action potentials recorded from guinea pig ventricular myocardia. Sparfloxacin prolonged action potential duration (APD) by about 8% at 10 microM and 41% at 100 microM. Gatifloxacin, grepafloxacin and moxifloxacin also prolonged APD at 100 microM by about 13%, 24% and 25%, respectively. In contrast, levofloxacin, sitafloxacin, trovafloxacin, ciprofloxacin, gemifloxacin and tosufloxacin had little or no APD-prolonging effect at concentrations as high as 100 microM. These findings suggest that there are differences in potency to prolong QT interval among the fluoroquinolones.     

In vitro activity of gemifloxacin and contemporary oral antimicrobial agents against 27247 Gram-positive and Gram-negative aerobic isolates: a global surveillance study

This study was a multi-centre, multi-country surveillance of 27247 Gram-positive and Gram-negative isolates collected from 131 study centres in 44 countries from 1997 to 2000. MICs of gemifloxacin were compared with penicillin, amoxicillin-clavulanic acid, cefuroxime, azithromycin, clarithromycin, trimethoprim-sulphamethoxazole, ciprofloxacin, grepafloxacin and levofloxacin by broth microdilution. Penicillin resistance in Streptococcus pneumoniae was extremely high in the Middle East (65.6%), Africa (64.0%) and Asia (60.4%) and lower in North America (40.3%), Europe (36.9%) and the South Pacific (31.8%). Macrolide resistance in S. pneumoniae was highest in Asia (51.7%) but varied widely between laboratories in Europe (26.0%), North America (21.6%), the Middle East (13.7%), the South Pacific (10.6%) and Africa (10.0%). All the study quinolones were highly active against penicillin-resistant and macrolide-resistant S. pneumoniae. Overall, gemifloxacin had the lowest MIC(90) at 0.06 mg/l with MICs 4-64-fold lower than ciprofloxacin, levofloxacin and grepafloxacin against S. pneumoniae. Gemifloxacin MICs were more potent than grepafloxacin > levoflaxacin > ciproflaxin against the Gram-positive aerobes and shared comparable Gram-negative activity with ciprofloxacin and levofloxacin.