zithromax and trovafloxacin

This review describes clinical results of gastrointestinal intubation studies of eight controlled release (CR) candidates under development during the 1990s and offers suggestions for determining why, when and how to conduct human intubation studies.. Experience with the administration of the following eight compounds to various regions of the gastrointestinal tract is described: CJ-13,610, CP-195,543, CP-331,684, CP-409,092, CP-424,391, azithromycin, sertraline, and trovafloxacin. Also included are human pharmacokinetic studies with prototype CR dosage forms for CJ-13,610 and CP-424,391.. Intubation studies, while appearing invasive, are safe and not unpleasant procedures that have been found to be valuable in the development of CR formulations.. The following recommendations are made regarding intubation studies: (i) no intubation study is recommended for compounds with high permeability, since these compounds are likely to be well absorbed from the colon; (ii) compounds with moderate permeability may require an intubation study if the dog colon and in silico models predict a marginally acceptable CR concentration-time profile; (iii) use a dose that approximates 1 h of the intended CR delivery rate; (iv) use the smallest volume possible; (v) define and record tubing placement; (vi) use a thermodynamically stable solution or/and suspension.

Topics: Animals; Azithromycin; Colon; Delayed-Action Preparations; Dogs; Fluoroquinolones; Humans; Imidazoles; Intestinal Absorption; Intubation, Gastrointestinal; Naphthyridines; Permeability; Sertraline; Solubility; Sulfides

The prophylactic potential of the azalide azithromycin as well as the fluoroquinolones trovafloxacin and grepafloxacin was assessed for the control of infection with Brucella melitensis in an experimental mouse model, determined by reduction in splenic bacterial burden. Trovafloxacin showed limited protective efficacy when administered 2h following a low-dose B. melitensis challenge, whereas grepafloxacin was ineffective. In comparison, azithromycin provided significant control of infection both following low- and high-dose challenges. Overall, the data confirm the potential utility of azithromycin in the prophylaxis of brucellosis and suggest that neither trovafloxacin nor grepafloxacin would likely be valuable for post-exposure prophylaxis of Brucella infection.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Brucella melitensis; Brucellosis; Colony Count, Microbial; Disease Models, Animal; Female; Fluoroquinolones; Humans; Mice; Mice, Inbred BALB C; Naphthyridines; Piperazines; Spleen

The efficacies of the azalide azithromycin and the fluoroquinolones trovafloxacin and grepafloxacin for pre- and post-exposure prophylaxis of infection with high or low challenge doses of Burkholderia pseudomallei strain 576 were assessed in an experimental mouse model. Trovafloxacin and grepafloxacin afforded significant levels of protection, whereas azithromycin was ineffective and potentially detrimental. Overall, the data suggest that some fluoroquinolones may have potential utility in prophylaxis of melioidosis and suggest that azithromycin would not be effective in prophylaxis of B. pseudomallei infection.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Burkholderia pseudomallei; Disease Models, Animal; Female; Fluoroquinolones; Humans; Melioidosis; Mice; Mice, Inbred BALB C; Naphthyridines; Piperazines; Survival Analysis

A rat model was used to study the effects of cirrhosis on antibiotic therapy of pneumococcal pneumonia. Cirrhotic and control male Sprague-Dawley rats were infected transtracheally with type 3 Streptococcus pneumoniae. Treatment began 18 h later with phosphate-buffered saline (PBS), azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic concentrations were measured by high-performance liquid chromatography. Azithromycin, trovafloxacin, and ceftriaxone were all equally effective at preventing mortality in both cirrhotic and normal rats. Free fraction area under the curve to minimum inhibitory concentration ratio (AUC/MIC) and maximum calculated serum concentration to MIC ratio (C(max)/MIC) and percent time that the serum concentration exceeded the MIC (%T > MIC) were greater for ceftriaxone compared with azithromycin or trovafloxacin. Azithromycin achieved higher concentrations in bronchoalveolar lavage fluid (BALF), epithelial lining fluid (ELF), and BAL white blood cells than ceftriaxone or trovafloxacin in cirrhotic rats. Macrolide, beta-lactam, or fluoroquinolone antibiotic efficacy in a pneumococcal pneumonia model does not appear to be affected by hepatic cirrhosis.

Topics: Animals; Azithromycin; Biological Availability; Blood Chemical Analysis; Bronchoalveolar Lavage Fluid; Ceftriaxone; Disease Models, Animal; Drug Therapy, Combination; Fluoroquinolones; Injections, Subcutaneous; Liver Cirrhosis; Male; Naphthyridines; Pneumonia, Pneumococcal; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Risk Assessment; Sensitivity and Specificity; Survival Rate

Pneumococci can enter and survive inside human lung alveolar carcinoma cells. We examined the activity of azithromycin, gentamicin, levofloxacin, moxifloxacin, penicillin G, rifampin, telithromycin, and trovafloxacin against pneumococci inside and outside cells. We found that moxifloxacin, trovafloxacin, and telithromycin were the most active, but only telithromycin killed all intracellular organisms.

Topics: Anti-Bacterial Agents; Aza Compounds; Azithromycin; Fluoroquinolones; Gentamicins; Humans; Ketolides; Levofloxacin; Macrolides; Microbial Sensitivity Tests; Moxifloxacin; Naphthyridines; Ofloxacin; Penicillin G; Quinolines; Rifampin; Streptococcus pneumoniae; Tumor Cells, Cultured

Dogs were experimentally inoculated with Rickettsia rickettsii (canine origin) in order to compare the efficacies of azithromycin and trovafloxacin to that of the current antibiotic standard, doxycycline, for the treatment of Rocky Mountain spotted fever. Clinicopathologic parameters, isolation of rickettsiae in tissue culture, and PCR amplification of rickettsial DNA were used to evaluate the response to therapy or duration of illness (untreated infection control group) in the four groups. Concentrations of the three antibiotics in plasma and blood cells were measured by high-performance liquid chromatography. Doxycycline and trovafloxacin treatments resulted in more-rapid defervescence, whereas all three antibiotics caused rapid improvement in attitudinal scores, blood platelet numbers, and the albumin/total-protein ratio. Based upon detection of retinal vascular lesions by fluorescein angiography, trovafloxacin and doxycycline substantially decreased rickettsia-induced vascular injury to the eye, whereas the number of ocular lesions in the azithromycin group did not differ from that in the infection control group. As assessed by tissue culture isolation, doxycycline resulted in the earliest apparent clearance of viable circulating rickettsiae; however, rickettsial DNA could still be detected in the blood of some dogs from all four groups on day 21 postinfection, despite our inability to isolate viable rickettsiae at that point. As administered in this study, trovafloxacin was as efficacious as doxycycline but azithromycin proved less efficacious, possibly due to the short duration of administration.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Capillary Permeability; DNA, Bacterial; Dogs; Doxycycline; Female; Fluoroquinolones; Guinea Pigs; Male; Naphthyridines; Polymerase Chain Reaction; Rickettsia rickettsii; Rocky Mountain Spotted Fever; Treatment Outcome

Oral Fusobacterium nucleatum populations from 20 young, healthy children were examined for beta-lactamase production. Ten children (50%) harbored, altogether, 25 beta-lactamase-positive F. nucleatum isolates that were identified as F. nucleatum subsp. polymorphum, F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii (J. L. Dzink, M. T. Sheenan, and S. S. Socransky, Int. J. Syst. Bacteriol. 40:74-78, 1990). In vitro susceptibility of these beta-lactamase-producing and 26 non-beta-lactamase-producing F. nucleatum isolates was tested with penicillin G, amoxicillin-clavulanic acid, tetracycline hydrochloride, metronidazole, trovafloxacin, and azithromycin. Except for penicillin G, the antimicrobials exhibited good activity against all F. nucleatum isolates.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Child, Preschool; Female; Fluoroquinolones; Fusobacterium nucleatum; Humans; Male; Metronidazole; Microbial Sensitivity Tests; Naphthyridines; Penicillin G; Tetracycline

A rat model of ethanol feeding was used to study the effects of ethanol on antibiotic therapy of pneumococcal pneumonia. Male Sprague-Dawley rats (150 g) received a liquid diet containing 36% of total calories as ethanol. Controls were pair-fed a liquid diet without ethanol or received rat chow. Diets began 7 days pre- and continued postinfection. Rats were infected transtracheally with type 3 Streptococcus pneumoniae and then treated with azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic levels in serum, lung cells, and lavage fluid were measured by HPLC. Ethanol- and pair-fed rats had depressed baseline peripheral neutrophil counts but were able to generate adequate numbers of peripheral and pulmonary polymorphonuclear leukocytes early in the course of their infection. Ethanol feeding did not alter the pharmacokinetics of azithromycin, trovafloxacin, or ceftriaxone. All three antibiotics were equally effective in curing experimental pneumococcal pneumonia, and survival rates were similar in treated ethanol-fed and control rats.

Topics: Animals; Anti-Infective Agents; Azithromycin; Bronchoalveolar Lavage Fluid; Ceftriaxone; Disease Models, Animal; Ethanol; Feeding Behavior; Fluoroquinolones; Leukocyte Count; Male; Naphthyridines; Neutrophils; Pneumonia, Pneumococcal; Rats; Rats, Sprague-Dawley

The activity of trovafloxacin and five other oral agents against 250 aerobic and 137 anaerobic strains isolated from human and animal bite wounds was determined by an agar dilution method. Trovafloxacin was active against all aerobic and fastidious facultative isolates at < or = 0.5 mg/L and all anaerobes at < or = 2 mg/L (Bacteroides tectum, Porphyromonas salivosa and Prevotella heparinolytica, < or = 0.25 mg/L; Porphyromonas spp., < or = 0.5 mg/L; Prevotella spp. and peptostreptococci, < or = 2.0 mg/L), except Fusobacterium nucleatum and other fusobacteria (MIC90 < or = 4 mg/L). Levofloxacin was generally one to two dilutions more active than ofloxacin, while ciprofloxacin was active against aerobes (MIC < or = 1 mg/L) but less active against anaerobic strains (MIC90 < or = 16 mg/L).

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Bites and Stings; Bites, Human; Ciprofloxacin; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Drug Resistance, Multiple; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Species Specificity; Wound Infection

As part of the Artemis project, 11500 isolates (3000 from patients with respiratory tract infections) were collected throughout six European countries between 1994 and 1996. Twenty-seven hospitals or laboratories participated in this first phase of the study. The activities of three classes of antimicrobial agents (fluoroquinolones, beta-lactam agents, macrolides) are presented for the six most frequently isolated pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Klebsiella pneumoniae). Overall, trovafloxacin and ciprofloxacin activities were similar for Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae isolates. Of the Streptococcus pneumoniae isolates, 6% were resistant to penicillin. Trovafloxacin had the highest activity against the Streptococcus pneumoniae isolates, with a minimum inhibitory concentration of 0.25 mg/l for 90% of isolates (MIC90); all strains tested were susceptible to trovafloxacin. The MIC90 of ciprofloxacin for Streptococcus pneumoniae was 3 mg/l, and overall 52% of the strains were susceptible; 9% were resistant. Azithromycin and clarithromycin exhibited similar activity against all collected pathogens, except Haemophilus influenzae. All strains of Haemophilus influenzae were susceptible to azithromycin compared with 79% for clarithromycin, with respective MIC90s of 2 and 16 mg/l. The data presented demonstrate differences in the susceptibility patterns of six major respiratory tract pathogens in Europe.

Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ciprofloxacin; Clarithromycin; Drug Resistance, Microbial; Europe; Fluoroquinolones; Gram-Negative Bacteria; Gram-Positive Cocci; Haemophilus influenzae; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Moraxella catarrhalis; Naphthyridines; Pseudomonas aeruginosa; Respiratory System; Staphylococcus aureus; Streptococcus pneumoniae

Topics: Anti-Infective Agents; Azithromycin; Cephalosporins; Drug Therapy, Combination; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Naphthyridines; Pseudomonas aeruginosa; Xanthomonas

The in-vitro activity of CG 5501 against a wide range of recent clinical isolates was compared with that of three fluoroquinolones. CG 5501 inhibited 90% of the species of the family Enterobacteriaceae at 0.5 mg/L or less, exceptions being Enterobacter spp. (MIC90 2 mg/L) and Serratia spp. (MIC90 4 mg/L). Ninety per cent of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter spp. were inhibited by 16, 4 and 1 mg/L respectively. CG 5501 had high activity against Gram-positive cocci, 90% of staphylococci being inhibited at 2 mg/L. Methicillin-resistant Staphylococcus aureus strains were generally ciprofloxacin-resistant yet were all susceptible to 4 mg/L or less of CG 5501. Isolates of Streptococcus pneumoniae were eight-fold more susceptible to CG 5501 (MIC90 0.5 mg/L) than to ciprofloxacin (MIC90 4 mg/L) and the former had a similar activity to that of trovafloxacin and sparfloxacin. Enterococcus faecalis was generally two- to four-fold more susceptible to CG 5501 or trovafloxacin than to ciprofloxacin. CG 5501 and trovafloxacin had high activity against Bacteroides fragilis (MIC90 0.25 mg/L). Five strains of Chlamydia spp. were inhibited by < or =0.12 mg/L of CG 5501; sensitive and multiresistant strains of Mycobacterium tuberculosis were inhibited by < or =0.5 mg/L of CG 5501. The high activity and breadth of its antibacterial spectrum suggests that CG 5501 should be useful in a wide range of clinical infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacteroides fragilis; Chlamydia; Ciprofloxacin; Clarithromycin; Doxycycline; Enterobacter; Erythromycin; Fluoroquinolones; Gatifloxacin; Gram-Positive Bacteria; Haemophilus influenzae; Microbial Sensitivity Tests; Naphthyridines; Piperazines; Pseudomonas aeruginosa; Quinolones; Streptococcus pneumoniae

The in vitro susceptibilities of 12 strains of Chlamydia pneumoniae to a new quinolone, trovafloxacin, and ofloxacin, doxycycline, erythromycin, and azithromycin were determined. The activity of trovafloxacin was similar to that of ofloxacin, with a MIC at which 90% of the isolates are inhibited and a minimal concentration at which 90% of the isolates are killed of 1.0 microg/ml, but trovafloxacin was less active than doxycycline, erythromycin, and azithromycin.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Chlamydophila pneumoniae; Doxycycline; Erythromycin; Fluoroquinolones; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin

Quality control guidelines for standardized antimicrobial susceptibility test methods are critical to the continuing accuracy of the tests. In this report, quality control limits were proposed for 22 organism-antimicrobial combinations with minimum inhibitory concentration (MIC) ranges of three or four log2 dilution steps. Disk diffusion zone diameter ranges were proposed for azithromycin compared with Neisseria gonorrhoeae ATCC 49226 and ticarcillin with and without clavulanic acid tested against Staphylococcus aureus ATCC 25923. The data from five or six participating laboratories produced > or = 94.7% of results within proposed MIC limits, and 94.3%-99.0% of zones were found within suggested zone guidelines. These proposed quality control ranges should be validated by in-use results from clinical laboratories.

Topics: Acetamides; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Infective Agents; Azithromycin; Clavulanic Acids; Fluoroquinolones; Humans; Linezolid; Microbial Sensitivity Tests; Naphthyridines; Oxazoles; Oxazolidinones; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Quality Control; Roxithromycin; Ticarcillin

The in-vitro activities of CP-99, 219, ciprofloxacin, pefloxacin, azithromycin and penicillin was tested against 114 Neisseria gonorrhoeae strains. The MIC90s were: 0.008 mg/L (MIC range 0.001-0.06 mg/L) for CP-99, 219, 0.008 mg/L (MIC range 0.001-0.25 mg/L) for ciprofloxacin, 0.12 mg/L (MIC range 0.008-4 mg/L) for pefloxacin, 0.25 mg/L (MIC range 0.03-1 mg/L) for azithromycin and 16 mg/L (MIC range 0.015-16 mg/L) for penicillin. The activity of CP-99,219 against various N. gonorrhoeae isolates was comparable to ciprofloxacin.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ciprofloxacin; Fluoroquinolones; Gonorrhea; Humans; Microbial Sensitivity Tests; Naphthyridines; Neisseria gonorrhoeae; Pefloxacin; Penicillins