zithromax and sparfloxacin

Comparative in vitro activities of several antimicrobial agents against Helicobacter pylori were evaluated. Minimum inhibitory concentrations against 41 strains of H. pylori were determined by using E test. All 41 strains were isolated from gastric mucosa of patients suspected to have gastric ulcer. The ranges of MIC of amoxicillin was from 0.016 microgram/ml and less to 0.064 microgram/ml. The ranges of MIC of clarithromycin, erythromycin, and azithromycin were from 0.016 microgram/ml and less to 64 micrograms/ml, from 0.016 microgram/ml and less to more than 256 micrograms/ml, from 0.064 to more than 256 micrograms/ml, respectively. The ranges of MIC of ciprofloxacin, sparfloxacin, levofloxacin, norfloxacin were from 0.016 microgram/ml and less to 32 micrograms/ml, from 0.002 microgram/ml and less to more than 32 micrograms/ml, from 0.002 microgram/ml and less to more than 32 micrograms/ml, from 0.064 to more than 32 micrograms/ml, respectively.

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ciprofloxacin; Clarithromycin; Drug Resistance, Bacterial; Erythromycin; Fluoroquinolones; Gastric Mucosa; Helicobacter pylori; Humans; Levofloxacin; Microbial Sensitivity Tests; Norfloxacin; Ofloxacin; Penicillins; Stomach Ulcer

We examined the cost-effectiveness of sparfloxacin compared with other selected oral antimicrobials in outpatient treatment of community-acquired pneumonia (CAP) using clinical pathway-based decision analysis. Cost estimates were obtained from medical claims databases and Medicare reimbursement schedules. Probability estimates were derived from published clinical trials, the medical literature, and clinical expert opinion. Overall adjusted efficacy rates were 89% for sparfloxacin, 79.4% for azithromycin, 77.8% for clarithromycin, 73% for cefaclor, 70.8% for amoxicillin-clavulanic acid, and 69% for erythromycin. The expected total cost/CAP episode of treatment with sparfloxacin was $216.07 compared with $258.97, $297.08, $345.75, $389.80, and $395.93 for azithromycin, clarithromycin, erythromycin, amoxicillin-clavulanic acid, and cefaclor, respectively. Therapy with sparfloxacin for managing CAP is cost effective-relative to other commonly prescribed antibiotics, resulting in net cost savings.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Antitubercular Agents; Azithromycin; Cefaclor; Clarithromycin; Community-Acquired Infections; Cost-Benefit Analysis; Erythromycin; Fluoroquinolones; Humans; Models, Economic; Outpatients; Pneumonia; Treatment Outcome

Listeria monocytogenes, a facultative intracellular pathogen, readily enters cells and multiplies in the cytosol after escaping from phagosomal vacuoles. Macrophages exposed to gamma interferon, one of the main cellular host defenses against Listeria, become nonpermissive for bacterial growth while containing Listeria in the phagosomes. Using the human myelomonocytic cell line THP-1, we show that the combination of L-monomethyl arginine and catalase restores bacterial growth without affecting the phagosomal containment of Listeria. A previous report (B. Scorneaux, Y. Ouadrhiri, G. Anzalone, and P. M. Tulkens, Antimicrob. Agents Chemother. 40:1225-1230, 1996) showed that intracellular Listeria was almost equally sensitive to ampicillin, azithromycin, and sparfloxacin in control cells but became insensitive to ampicillin and more sensitive to azithromycin and sparfloxacin in gamma interferon-treated cells. We show here that these modulations of antibiotic activity are largely counteracted by L-monomethyl arginine and catalase. In parallel, we show that gamma interferon enhances the cellular accumulation of azithromycin and sparfloxacin, an effect which is not reversed by addition of L-monomethyl arginine and catalase and which therefore cannot account for the increased activity of these antibiotics in gamma interferon-treated cells. We conclude that (i) the control exerted by gamma interferon on intracellular multiplication of Listeria in THP-1 macrophages is dependent on the production of nitric oxide and hydrogen peroxide; (ii) intracellular Listeria may become insensitive to ampicillin in macrophages exposed to gamma interferon because the increase in reactive oxygen and nitrogen intermediates already controls bacterial growth; and (iii) azithromycin and still more sparfloxacin cooperate efficiently with gamma interferon, one of the main cellular host defenses in Listeria infection.

Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Antitubercular Agents; Azithromycin; Cell Death; Cell Line; Drug Interactions; Drug Resistance, Microbial; Fluoroquinolones; Humans; Hydrogen Peroxide; Interferon-gamma; Listeria monocytogenes; Listeriosis; Macrophage Activation; Macrophages; Male; Nitric Oxide

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

Most antibiotics are known to be incapable of killing nongrowing or slowly growing bacteria with few exceptions. Bacterial cell division is inhibited during the postantibiotic phase (PA phase) after short exposure to antibiotics. Only scarce and conflicting data are available concerning the ability of antibiotics to kill bacteria in the PA phase. The aim of the present study was to investigate the killing effect of four different antibiotics on bacteria in the PA phase. A postantibiotic effect (PAE) was induced by exposing Streptococcus pyogenes and Haemophilus influenzae to 10x MICs of benzylpenicillin, cefuroxime, sparfloxacin, and azithromycin. The bacteria were thereafter reexposed to a 10x MIC of the same antibiotic used for the induction of the PAE at the beginning of and after 2 and 4 h in the PA phase. Due to a very long PAE, the bacteria in PA phase induced by azithromycin were also exposed to 10x MICs after 6 and 8 h. A previously unexposed culture exposed to a 10x MIC was used as a control. The results seem to be dependent on both the antibiotic used and the bacterial species. The antibiotics exhibiting a fork bactericidal action gave significantly reduced killing of the bacteria in PA phase (cefuroxime with S. pyogenes, P < 0.01, and sparfloxacin with H. influenzae, P < 0.001), which was restored at 4 h for cefuroxime with S. pyogenes. There was a tendency to restoration of the bactericidal activity also with sparfloxacin and H. influenzae, but there was still a significant difference in killing between the control and the test bacteria in PA phase at 4 h. However, in the combinations with a lesser bactericidal effect (benzylpenicillin with S. pyogenes and sparfloxacin with S. pyogenes), there was no difference in killing between the control and the test bacteria in PA phase. Azithromycin induced long PAEs in both S. pyogenes and H. influenzae and exhibited a slower bactericidal action on both the control and the bacteria in PA phase especially at the end of the PAE, when the killing was almost bacteriostatic. Our findings in this study support the concept that a long interval (> 12 h) between doses of azithromycin, restoring full bactericidal action, may be beneficial to optimize efficacy of this drug but is not necessary for the other antibiotics evaluated, since the bactericidal effect seems to be restored already at 4 h.

Topics: Anti-Bacterial Agents; Azithromycin; Cefuroxime; Drug Administration Schedule; Drug Resistance, Microbial; Fluoroquinolones; Haemophilus influenzae; Kinetics; Microbial Sensitivity Tests; Penicillin G; Quinolones; Streptococcus pyogenes

Listeria monocytogenes is a facultative intracellular pathogen which enters cells by endocytosis and reaches phagolysosomes from where it escapes and multiplies in the cytosol of untreated cells. Exposure of macrophages to gamma interferon (IFN-gamma) restricts L. monocytogenes to phagosomes and prevents its intracellular multiplication. We have tested whether IFN-gamma also modulates the susceptibility of L. monocytogenes to antibiotics. We selected drugs from three different classes displaying marked properties concerning their cellular accumulation and subcellular distribution, namely, ampicillin (not accumulated by cells but present in cytosol), azithromycin (largely accumulated by cells but mostly restricted to lysosomes), and sparfloxacin (accumulated to a fair extent but detected only in cytosol). We used a continuous line of myelomonocytic cells (THP-1 macrophages), which display specific surface receptors for IFN-gamma, and examined the activity of these antibiotics against L. monocytogenes Hly+ (virulent variant) and L. monocytogenes Hly- (a nonvirulent variant defective in hemolysin production). Untreated THP-1 and phorbol myristate acetate-differentiated THP-1 were permissive for infection and multiplication of intracellular L. monocytogenes Hly+ (virulent variant). All three antibiotics tested were bactericidal against this Listeria strain when added to an extracellular concentration of 10x their MIC. After preexposure of THP-1 to IFN-gamma, L. monocytogenes Hly+ was still phagocytosed but no longer grew intracellularly. The activity of ampicillin became almost undetectable (antagonistic effect), and that of azithromycin was unchanged (additive effect with that of IFN-gamma), whereas that of sparfloxacin was markedly enhanced (synergy). A similar behavior (lack of bacterial growth, associated with a loss of activity of ampicillin, an enhanced activity of sparfloxacin, and unchanged activity of azithromycin) was observed in cells infected with L. monocytogenes Hly-. This modulation of antibiotic activity, which we ascribe to the change of subcellular localization of L. monocytogenes caused by IFN-gamma or by the lack of virulence factor, could result from a change in bacterial responsiveness to antibiotics, a modification of the drug activity, or differences in drug bioavailabilities between cytosol and phagosomes.

Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cell Line; Fluoroquinolones; Humans; Interferon-gamma; Listeria monocytogenes; Macrophage Activation; Macrophages; Quinolones; Recombinant Proteins; Tetradecanoylphorbol Acetate; Virulence

The activities of sparfloxacin, levofloxacin, Bay y 3118, azithromycin, cefprozil, loracarbef, and nine other oral antimicrobial agents against 194 aerobic and anaerobic clinical bite wound isolates were determined by the agar dilution method. Sparfloxacin, levofloxacin, and Bay y 3118 were active against all aerobic isolates (MICs at which 90% of the isolates are inhibited [MIC90], < or = 1.0 microgram/ml for sparfloxacin and levofloxacin and 0.1 microgram/ml for Bay y 3118) and many anaerobic isolates, with the exception of the fusobacteria. Azithromycin was more active than erythromycin by 1 to 2 dilutions against many aerobes, including Pasteurella multocida and Eikenella corrodens, and by 2 to 4 dilutions against anaerobic isolates. Cefprozil was more active (MIC90, < or = 1 microgram/ml) than loracarbef (MIC90, < or = 4 micrograms/ml) against aerobic gram-positive isolates, but both had poor activity (MIC90, > or = 16 micrograms/ml) against peptostreptococci. Both cefprozil and loracarbef had MIC90s of < or = 0.5 micrograms/ml against P. multocida.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacteria, Aerobic; Bacteria, Anaerobic; Bites and Stings; Bites, Human; Fluoroquinolones; Humans; Levofloxacin; Microbial Sensitivity Tests; Ofloxacin; Quinolones; Wound Infection

Organisms of the Mycobacterium avium complex (MAC) cause disseminated disease in patients with AIDS, and evidence points to the gastrointestinal tract as the major route of infection. Since MAC can bind to and invade intestinal mucosal cells, we examined whether subinhibitory concentrations of antibiotics which have anti-MAC activity in vitro affect the interaction between MAC and HT-29 intestinal mucosal cells. MAC isolates were exposed to subinhibitory concentrations of rifabutin (MIC, 2.6 micrograms/ml), sparfloxacin (MIC, 8.4 micrograms/ml), or azithromycin (MIC, 32 micrograms/ml) for 30 to 120 min, washed, and incubated with HT-29 cell monolayers for 2 h at 4 degrees C. HT-29 cell monolayers were then washed to remove unbound bacteria and were subsequently lysed. The number of MAC isolates that bound to the HT-29 cells was determined by plating the cell lysate onto 7H10 agar. Preincubation of the MAC isolates with rifabutin at concentrations of 1 and 2 micrograms/ml reduced MAC binding to HT-29 cells by 80 to 90%, while MAC exposed to sparfloxacin at 1 and 7 micrograms/ml inhibited binding by 77 to 93%. Azithromycin at concentrations of 2, 10, and 30 micrograms/ml had no effect on MAC binding to HT-29 cells. Inhibition of MAC binding to the gastrointestinal mucosa may be one underlying mechanism for the prophylactic effects of rifabutin and quinolones.

Topics: Anti-Infective Agents; Azithromycin; Bacterial Adhesion; Fluoroquinolones; Humans; Intestinal Mucosa; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Quinolones; Rifabutin; Tumor Cells, Cultured

The in vitro activities of azithromycin, clarithromycin and sparfloxacin were evaluated by studying inhibition of in vitro Chlamydia trachomatis propagation in McCoy cells, comparatively with erythromycin, ofloxacin and tetracycline. Fifteen clinical isolates of C. trachomatis were tested with an inoculum of 5.10(3) inclusion--forming units in a 96--well microtiter plate. Minimal inhibitory concentration (MIC) ranges were as follows: azithromycin, 0.06 to 0.125 microgram/ml; clarithromycin, 0.008 microgram/ml; erythromycin, 0.06 to 0.125 microgram/ml; ofloxacin 0.5 to 1 microgram/mg; sparfloxacin, 0.03 to 0.06 microgram/ml; and tetracycline 0.125 to 0.25 microgram/ml. Minimal bactericidal concentration (MBC) ranges, calculated from passage into antibiotic--free medium, were as follows: azithromycin 0.25 to 0.5 microgram/ml; clarithromycin, 0.03 to 0.125 microgram/ml; erythromycin, 0.25 to 2 micrograms/ml; ofloxacin, 0.5 to 1 microgram ml; sparfloxacin, 0.03-0.06 microgram/ml; and tetracycline, 1 to 4 micrograms/ml. Clarithromycin and sparfloxacin showed the greatest activity and clinical studies of these agents in C. trachomatis infections are therefore indicated.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Chlamydia trachomatis; Clarithromycin; Dose-Response Relationship, Drug; Fluoroquinolones; Humans; In Vitro Techniques; Quinolones