In vitro activity of linezolid against Gram-positive uropathogens of hospitalized patients with complicated urinary tract infections.

The antimicrobial activity of linezolid, a recently developed antibiotic agent active against Gram-positive bacteria, was tested against pathogens from three different collections. (1) Uropathogens from hospitalized urological patients (1990/1991) with complicated and/or hospital-acquired UTIs; Urologic Clinic, Hospital St. Elisabeth, Straubing. (2) Uropathogens from a multi-centre study (1995/1996) comprising 37 urological centres throughout Germany. (3) MRSA isolates of patients and staff (1999/2000) within the Hospital St. Elisabeth, Straubing. Genotyping of the latter isolates was performed by pulsed-field-electrophoresis. The minimal inhibitory concentrations (MIC) of linezolid determined by an agar (Isosensitest) dilution method using a multipoint inoculator and an inoculum of 10(4) cfu per point ranged for methicillin susceptible Staphylococcus aureus (MSSA) (n=27) between 2 and 4 mg/l, for methicillin resistant S. aureus (MRSA) (n=35) between 1 and 2 mg/l, for methicillin susceptible coagulase-negative staphylococci (CNS) (MSSE) (n=67) between 0.5 and 4 mg/l, for methicillin resistant CNS (MRSE) (n=19) between 0.25 and 2 mg/l, for Enterococcus. faecalis (n=184) between 0.5 and 4 mg/l, for E. faecium (n=3) 2 mg/l and for Streptococcus spp. (n=4) between 0.25 and 1 mg/l, indicating that all strains were susceptible. According to the in vitro activity, linezolid may be considered a promising antibacterial agent for the treatment of complicated UTI caused by Gram-positive uropathogens. Thus, linezolid should be evaluated in a clinical study.     

In vitro antibacterial activity of various cephems against clinical isolates from complicated urinary tract infections

In vitro antibacterial activity of several cephems (CEZ as the first generation (group A); CTM and CMZ as the second generation (group B); CMX, CPZ, LMOX, CTX and CZX as the third generation (group C)) against 8 species, each of 54 strains, of Gram-negative clinical isolates from complicated urinary tract infection was compared by determination of the MICs. The following results were obtained: The most sensitive drugs against each species in MIC80; CTX (MIC80 0.20 microgram/ml) against E. coli, CMX (1.56 microgram/ml) against K. pneumoniae, LMOX (0.39 microgram/ml) against P. mirabilis, LMOX (0.78 microgram/ml) against Indole (+) Proteus, CMX and CPZ (50 micrograms/ml) against E. cloacae, CMX and LMOX (50 micrograms/ml) against C. freundii, CMX (3.13 micrograms/ml) against S. marcescens and CPZ (25 micrograms/ml) against P. aeruginosa The most sensitive drugs against each species in MICS100; CMX (MIC100 3.13 micrograms/ml) against E. coli, CMX (6.25 micrograms/ml) against K. pneumoniae, CTX (0.78 microgram/ml) against P. mirabilis, LMOX (1.56 microgram/ml) against Indole (+) Proteus, CPZ (100 micrograms/ml) against E. cloacae, CMX (100 micrograms/ml) against C. freundii, CMX (12.5 microgram/ml) against S. marcescens and CPZ (50 micrograms/ml) against P. aeruginosa. In each species, the group C were most sensitive followed by those of the group B. Many isolates were highly resistant to the group A (especially in C. freundii, S. marcescens and P. aeruginosa).     

In vitro drug interaction studies of atorvastatin with ciprofloxacin, gatifloxacin, and ofloxacin

We describe the in vitro availability of atorvastatin, a potent HMG-CoA reductase inhibitor, in presence of ciprofloxacin, gatifloxacin, and ofloxacin, all with a wide antibacterial spectrum. These studies were performed at 37°C, 48°C, and 60°C in different pH environments, simulating human body compartments. The reactions were studied by UV spectroscopy, and the availability of both the drugs in presence of each other was determined by deriving a simultaneous equation for two component system through modification of Beer’s law. It has been observed that due to interaction, the availability of both atorvastatin and quinolones increased considerably in nearly all pH mediums, which are attributed to the formation of charge-transfer complexes. The results were further confirmed by IR, HNMR, and mass spectrometric studies.     

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.     

Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms

Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin are fluoroquinolones with enhanced Gram-positive activity while retaining broad-spectrum activity against Gram-negative pathogens. Levofloxacin and ciprofloxacin are older quinolones with broad activity against Gram-negative pathogens and borderline activity against some Gram-positive organisms. We compared the in vitro activity of these compounds against 4151 Gram-negative and -positive organisms. Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin were highly active against penicillin sensitive and resistant Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae. Ciprofloxacin and levofloxacin were active but less potent. All compounds were highly active (overall) against Gram-negative pathogens with ciprofloxacin being the most active agent against Pseudomonas aeruginosa. Our data indicate that the advanced fluoroquinolones will be important compounds for treating infections caused by Gram-positive and Gram-negative pathogens.     

Antianaerobic activity of moxifloxacin compared with that of ofloxacin,ciprofloxacin, clindamycin,metronidazole and beta-lactams

Minimal inhibitory concentrations of moxifloxacin were compared with those of ofloxacin, ciprofloxacin, clindamycin, metronidazole and six beta-lactams for 159 anaerobes isolated from human clinical samples. Unlike other fluoroquinolones, moxifloxacin demonstrated high activity against the 76 strains of the Bacteroides fragilis group as the minimal inhibitory concentration(50) was 0.5 mg/l. Porphyromonas, Prevotella, Fusobacterium and Gram-positive anaerobic cocci were inhibited by 1 mg/l or less of moxifloxacin. It inhibited 93.7, 94.9 and 98% of the 159 strains investigated at concentrations of 1, 2 and 4 mg/l, respectively. Moxifloxacin was more potent than ofloxacin and ciprofloxacin against Gram-positive rods and anaerobic cocci. Its broad anaerobic spectrum in vitro is promising for the treatment of intra-abdominal and respiratory infections.     

Antimicrobial activity of imipenem against isolates from complicated urinary tract infections

Antimicrobial activity of imipenem was measured using 4725 strains isolated from patients with complicated urinary tract infections (CUTIs) between 1988 and 2000. Imipenem was inactive against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, Enterococcus faecium and some non-fermenting Gram-negative rods. Resistant strains (MIC>16 mg/l) were observed in Staphylococcus haemolyticus (22%), Enterococcus faecalis (4%), Enterococcus avium (8%), Serratia marcescens (5%) and Pseudomonas aeruginosa (7%). Although the prevalence of imipenem-resistant strains of S. aureus, S. epidermidis and P. aeruginosa was sporadically high in some years, no steady increase was seen over the period. Resistant strains were rare in other major uropathogenic species. These results suggest that imipenem is still one of the most reliable antimicrobial drugs.     

In vivo activity of ciprofloxacin, ofloxacin, norfloxacin and pipemidic acid against Escherichia coli infections in mice

The therapeutic efficacy of four quinolones, i.e. ciprofloxacin, ofloxacin, norfloxacin and pipemidic acid, was investigated in experimental infections in mice caused by pipemidic acid-susceptible and -resistant E. coli. For intraperitoneal infections caused by E. coli strain 444 and 23, the efficacy of ciprofloxacin, ofloxacin and norfloxacin was superior to that of pipemidic acid. Furthermore, ciprofloxacin and ofloxacin had higher activity than norfloxacin and pipemidic acid in urinary tract and uterine infections. Serum and uterus levels of ciprofloxacin and ofloxacin in normal mice were higher and more durable than those of norfloxacin.     

In vitro antibacterial activity and pharmacokinetics of ofloxacin in chronic respiratory tract infections

Serum and sputum levels of ofloxacin (OFLX) were measured in 5 patients with chronic respiratory tract infections and were compared with antibacterial activity in vitro. Sputum OFLX levels higher than the MIC's against H. influenzae and K. pneumoniae were maintained during the period when daily oral administrations were continued. The MIC70 of OFLX against S. aureus was under 0.78 microgram/ml and the MIC70 of OFLX against P. aeruginosa was 1.56 micrograms/ml. The maximum OFLX levels in sputum were higher than these MIC's during the period when 200-300 mg X 2 times/day oral administrations were maintained. From these results, OFLX was considered to be effective and useful for the treatment of patients with chronic respiratory tract infections.     

In vitro activity of aztreonam, cefuroxime and ceftazidime against gram-negative rods isolated from hospital patients with urinary tract infection

The in vitro activity of aztreonam, cefuroxime and ceftazidime was determined against 2,372 Gram-negative rods (including Pseudomonas spp.) isolated from hospital patients with urinary tract infections during 1985. Minimum inhibitory concentrations (MICs) were determined using an agar incorporation technique in Mueller-Hinton agar. The inoculum used was approximately 10(5) colony forming units (cfu) contained in 10 microliter Mueller-Hinton broth, which was applied to the surface of the agar plates using a multipoint inoculator. Following inoculation plates were incubated aerobically at 37 degrees C for 18 h. The MIC of each antimicrobial for each organism examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentration required to inhibit the growth of 90% (MIC90) of the bacterial isolates in each genus or species examined was also determined. In general the antibacterial spectrum of aztreonam was comparable to that of ceftazidime and superior to that of cefuroxime. Against Escherichia coli, which accounted for 72% of the isolates examined, aztreonam (MIC90 less than or equal to 0.25 microgram/ml) was slightly more active than ceftazidime (MIC90 0.5 microgram/ml) and considerably more active than cefuroxime (MIC90 8 micrograms/ml). Aztreonam was active against Pseudomonas spp. (MIC90 16 micrograms/ml), although somewhat less so than ceftazidime (MIC90 4 micrograms/ml). Cefuroxime showed low activity against this genus (MIC90 greater than 128 micrograms/ml).     

Spectrum and antibiotic resistance of uropathogens from hospitalized patients with urinary tract infections: 1994-2000

During the period 1994–2000 all uropathogens cultured from urine of hospitalized urological patients were identified and susceptibility was tested against 11 antibacterials. Duplicated isolates were eliminated. There was no general trend of increased of resistance apart from E. coli to ciprofloxacin (10.4% in 2000). Vancomycin-resistant staphylococci or enterococci was not significant. The lowest overall rates of resistance were found with piperacillin/tazobactam followed by ciprofloxacin and trimethoprim/sulphamethoxazole. Ciprofloxacin was the best oral antibiotic for the empirical treatment of urinary tract infection (UTI) due to Gram-negative rods and ampicillin/sulbactam for the treatment of UTI with Gram-positive cocci.     

Spectrum and antibiotic resistance of uropathogens from hospitalised patients with urinary tract infections: 1994-2005

From 1994-2005, all uropathogens cultured from the urine of hospitalised urological patients were identified and their sensitivity was tested against the most important antibiotics for the treatment of urinary tract infection (UTI). Duplicate isolates were eliminated. The following results were obtained: (i) there was no general trend of increase in resistance; (ii) certain uropathogens developed resistance to some antibiotics; (iii) vancomycin- or linezolid-resistant staphylococci or enterococci did not play a role; (iv) the lowest overall rates of resistance were found with piperacillin/tazobactam; and (v) ciprofloxacin and trimethoprim/sulfamethoxazole showed the next favourable overall activity. Adequate initial antibiotic therapy is critical in the treatment of severe UTI. Therefore, ongoing surveillance of antibiotic resistance must be performed in every institution. Additionally, it reflects antibiotic and hospital infection policies in a defined department or institution.     

In vitro activity of prulifloxacin against Escherichia coli isolated from urinary tract infections and the biological cost of prulifloxacin resistance

Minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of prulifloxacin against 30 strains of Escherichia coli isolated from urinary tract infections as well as the ‘biological cost’ related to acquisition of resistance to the same drug in 10 uropathogenic E. coli were assessed. In terms of MIC₉₀, prulifloxacin was more potent than ciprofloxacin and levofloxacin. Prulifloxacin produced lower or equal MPC values than the other two fluoroquinolones (93.3% and 73.3% compared with levofloxacin and ciprofloxacin, respectively). Compared with susceptible strains, prulifloxacin-resistant mutants showed a reduced rate of growth (ranging from 20.0% to 98.0% in different culture media and incubation conditions) and a decreased fitness index (ranging from 0.959 to 0.999). They were also impaired in their ability to adhere to uroepithelial cells and urinary catheters (11.7–66.4% and 16.3–78.3% reduction, respectively) and showed a lower surface hydrophobicity (51.2–76.0%). They were more susceptible to ultraviolet irradiation (30.6–93.8% excess mortality), showed increased resistance to colicins and diminished transfer of plasmids (<1–8.5 × 10⁻⁸ vs. 3.3 × 10⁻⁷–2.4 × 10⁻⁴). Synthesis of haemolysin and type I fimbriae and production of flagella were also adversely affected. This study demonstrates a strict relationship between acquisition of prulifloxacin resistance and loss of important virulence traits. In this transition, E. coli pays a severe biological cost that entails a general reduction of fitness, thus compromising competition with susceptible wild-type strains in the absence of the drug.     

Lomefloxacin versus norfloxacin versus ciprofloxacin in the treatment of complicated urinary tract infections

The safety and efficacy of lomefloxacin 400 mg once daily in the treatment of complicated urinary tract infections (UTIs) were assessed in one open, non-comparative study (n = 101) and three comparative, multicenter studies - two versus norfloxacin 400 mg b.i.d. (n = 326) and one versus ciprofloxacin 500 mg b.i.d. (n = 150). The antibiotics were administered orally for 7-14 days. Safety was assessed by physical examination, laboratory tests and questioning of patients. Patients had initial counts of - 10(5) colony-forming units/ml (CFU/ml) of pathogens which were susceptible to the study drugs. Clinical and bacteriologic outcome were assessed 5-9 days post-treatment. Success (cure or improvement of presenting signs and symptoms) was achieved in approximately 90% of the patients, irrespective of the drug therapy used. Eradication of baseline pathogens was achieved with lomefloxacin in 79.4% (50 63 ) of evaluable patients in the open study, in 91.3% (84 92 ) of patients in the norfloxacin comparative studies and in 97.2% (70 72 ) of evaluable patients in the ciprofloxacin comparative study. Eradication was achieved in 78.4% (76 97 ) of norfloxacin-treated evaluable patients and in 95.7% (67 70 ) of evaluable patiens treated with ciprofloxacin. The results obtained with lomefloxacin were statistically significantly better than those obtained with norfloxacin (p = 0.015), but equivalent to those with ciprofloxacin (p = 0.626). Superinfections occurred in 5.3% (12 227 ) of evaluable patients treated with lomefloxacin and in 9.3% (9 97 ) treated with norfloxacin. There were no superinfections in the 70 evaluable patients treated with ciprofloxacin. Adverse events (mainly gastrointestinal) which were probably drug-related occurred in 6.7% (23 341 ) of patients treated with lomefloxacin, in 3.1% (5 160 ) pateints treated with norfloxacin and in 6.7% (5 75 ) of patients treated with ciprofloxacin. A once-daily regimen of lomefloxacin 400 mg was found to be safe and produced superior or equivalent eradication rates of norfloxacin and ciprofloxacin, respectively.     

Treatment of murine pneumonic Francisella tularensis infection with gatifloxacin, moxifloxacin or ciprofloxacin

The efficacies of gatifloxacin and moxifloxacin were assessed in a BALB/c mouse model of pneumonic tularemia and compared with the efficacy of ciprofloxacin. The rate of relapse following dexamethasone treatment was also investigated. Mice were given 100 mg/kg of the antibiotic by oral administration twice daily for 14 days following an aerosol challenge. All three fluoroquinolones prevented disease during the treatment period, but significant failure rates occurred after the cessation of therapy. Both gatifloxacin and moxifloxacin were more effective than ciprofloxacin at reducing late mortality. Fluoroquinolones may therefore be considered useful candidates for the treatment of pneumonic tularemia.     

加替沙星对金黄色葡萄球菌的体外抗菌活性

考察加替沙星对金黄色葡萄球菌的体外抗菌活性以及抗MRSA的能力。采用药敏纸片法（K－B法），从129株临床分离的金黄色葡萄球菌筛选对甲氧西林和氟喹诺酮类药物的耐药菌株，用琼脂二倍稀释法对交叉耐药菌进行MIC测试，比较了加替沙星与环丙沙星等第二代氟喹诺酮类药物的耐药菌株，用琼脂二倍稀释法对交叉耐药菌进行MIC测试，比较了加替沙星与环丙沙星等第二代氟喹诺酮类药物的抗菌活性。用苯唑西林筛选三代自发突变株，比较环丙沙星、加替沙星对MRSA的抗菌活性。实验表明，苯唑西林、环丙沙星、氧氟沙星、左氧氟沙星对129株金黄色葡萄球菌的耐药率相似。体外活性表明，加替沙星比环丙沙星等第二代氟喹诺酮类药物的抗菌活性强，抗MRSA菌株的活性较强；敏感金黄色葡萄球菌发生加替沙星耐药的突变频率在所试药物中也是最低的。说明加替沙星比环丙沙星等第二代氟喹诺酮类药物的抗菌活性得到明显提高。     

In vitro synergism of beta-lactams with ciprofloxacin and moxifloxacin against genetically distinct multidrug-resistant isolates of Pseudomonas aeruginosa

In vitro combinations of beta-lactams with fluoroquinolones against multidrug-resistant (MDR) Pseudomonas aeruginosa were tested. From a total of 200 isolates, 24 genetically distinct isolates defined by pulsed-field gel electrophoresis (PFGE) were selected. The isolates were exposed over time to imipenem, meropenem and ceftazidime as well as to their combinations with ciprofloxacin and moxifloxacin. All isolates were resistant to all agents tested at concentrations equal to their average serum level. Synergy of any of the tested combinations was found in 10 isolates (41.7%). This was shown after 4h and 6h of exposure accompanied by re-growth after 24h. Not all the tested combinations were active against the same isolates. The combinations of imipenem+ciprofloxacin, ceftazidime+ciprofloxacin and imipenem+moxifloxacin were the most active. When time-kill assays were repeated for the latter isolates at antimicrobial concentrations equal to their maximum serum levels, synergy was prolonged to 24h. The present findings should be interpreted with caution for the management of infections by MDR P. aeruginosa. They underscore the potential interest of reporting synergism between beta-lactams and fluoroquinolones in the nosocomial setting when a MDR isolate emerges.     

莫西沙星对224株凝固酶阴性葡萄球菌的体外抗菌活性观察

目的观察莫西沙星对224株表皮葡萄球菌、溶血葡萄球菌和里昂葡萄球菌等凝固酶阴性葡萄球菌（CNS）的体外抗菌活性。方法用二倍琼脂稀释法测定其最低抑菌浓度（MIC）。结果莫西沙星对表皮葡萄球菌、溶血葡萄球菌等CNS的抑菌效果较好，对124株表皮葡萄球菌的MIC50和MIC90分别为≥0．063和0．25μg／ml；对42株溶血葡萄球菌和14株里昂葡萄球菌的MIC90分别为2和0．5μg／ml。结论莫西沙星对表皮葡萄球菌、溶血葡萄球菌、里昂葡萄球菌和人葡萄球菌的抗菌效果好，敏感率分别为96．77％、85．71％、100％和100％；对35株耳葡萄球菌等的敏感率为100％。