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Ofloxacin is highly active against Gram-negative aerobic bacilli, but moderately active against Gram-positive cocci. The minimal inhibitory concentrations (MICs) against Streptococcus pneumoniae range between 1 and 2 mg/L. MICs of roxithromycin (RU 28965) against S. pneumoniae range between 0.004 and 0.03 mg/L, but Gram-negative bacilli are resistant. The bactericidal activities of ofloxacin and roxithromycin were evaluated against 15 strains of S. pneumoniae, which were isolated recently from clinical specimens. Killing activity was evaluated under conditions simulating serum pharmacokinetic parameters. Initial concentrations were 10 mg/L for roxithromycin and 2 mg/L for ofloxacin, and the half-life was 6 hours for both compounds. Under these conditions, roxithromycin was rapidly bactericidal. The speed at which pneumococci were killed was faster with roxithromycin than with ofloxacin. No regrowth was seen with roxithromycin, but regrowth occurred in 8 of 15 strains with ofloxacin.
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We describe the obstetric consequences of Q fever diagnosed during pregnancy from a series of cases. When an antenatal diagnosis was made, antibiotic therapy with roxithromycin (Rulid(®)) was started until delivery.
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The study involved 412 strains of Gram-positive cocci isolated from throat, sputum, urine and stool of patients prepared for bone marrow transplantation at Department of Hematology. Determination of drug susceptibility was performed by disc diffusion method applying discs with roxithromycin, erythromycin, lincomycin, clindamycin and augmentin. Among strains of S. aureus, S. epidermidis and Micrococcus susceptible strains comprised respectively 48, 48 and 45%; among group A, B, C and G streptococci respectively 92 and 52%. Among 108 strains of group D Streptococci only 24% were susceptible to roxithromycin. Comparison of susceptibility of tested strains to roxithromycin and other antibiotics revealed similar susceptibility of staphylococci and streptococci to roxithromycin and erythromycin, while among staphylococci higher percentage of strains and among streptococci lower percentage was susceptible to lincomycin than to roxithromycin.
A two-compartment model with saturable absorption described the data (n = 63); changes in free drug exposure were simulated using a saturable protein binding model. Simulations indicated that a 300 mg daily regimen achieves a 37% and 53% lower total or free AUC (fAUC), respectively, compared with 150 mg twice daily. These pharmacokinetic differences translated to significantly lower target attainment (fAUC/MIC ratio >20) with a 300 mg daily regimen at MICs of 0.5 and 1 mg/L (51% and 7%) compared with patients receiving 150 mg twice daily (82% and 54%).
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The antimicrobial susceptibilities of 1385 clinical isolates of Streptococcus pneumoniae obtained from 25 laboratories across Austria between December 1994 and January 1996 were tested. Minimal inhibitory concentration (MIC) values were determined in tests with penicillin, amoxycillin, amoxycillin/clavulanate, ceftriaxone, cefodizime, cefpirome, cefotaxime, cefpodoxime, cefadroxile, azithromycin, clarithromycin, josamycin and roxithromycin by the agar-dilution method. A total of 40 isolates (2.9%) demonstrated intermediate resistance (MIC 0.125-1 microg/ml) and 28 isolates (2.0%) had high-level resistance (MIC > or = 2 microg/ml) to penicillin. Excepting cefadroxil, with an MIC90 of 2 microg/ml, all other tested beta-lactams had MIC90s of 0.03-0.06 microg/ml. Penicillin-resistant strains were much more likely to be also resistant to the other beta-lactams. The macrolides proved to be very active compounds against pneumococci with MIC90s of 0.06 microg/ml (clarithromycin) and 0.25 microg/ml (all other macrolides). Regional differences within Austria with regard to antimicrobial resistance were not observed.
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Our study probed the effects of the beta-2 adrenergic agonist, formoterol and the macrolide antibiotic, roxithromycin, on muscle wasting in a well-characterized animal model of cancer cachexia. Female Wistar rats were inoculated with Yoshida AH130 ascites hepatoma (AH) cells to induce rapid and severe cachexia as demonstrated by wet weight determinations of the hearts, gastrocnemius muscles and carcasses. The control animals received saline (vehicle) inoculations. The AH-inoculated rats were treated once daily for four days by i.p. injection with a vehicle control, 1 mg/kg formoterol, 5 and 50 mg/kg roxithromycin or 1 mg/kg formoterol plus 5, 25, 40 and 50 mg/kg roxithromycin. The saline-inoculated animals were treated by i.p. injection with vehicle control, 1 mg/kg formoterol, 5 and 40 mg/kg roxithromycin. As a result, formoterol alone reduced the loss of muscle mass in the AH-inoculated rats by approximately one-half, consistent with literature reports. Roxithromycin alone at 5 mg/kg did not affect muscle mass in the AH-inoculated rats. Roxithromycin given alone at 50 mg/kg reduced the loss of muscle mass in AH-inoculated animals by approximately one-half. With respect to the antagonizing muscle loss, formoterol combined with either 5 or 25 mg/kg roxithromycin did not reach statistical significance versus formoterol alone, while formoterol plus either 40 or 50 mg/kg roxithromycin enhanced protection against muscle loss versus formoterol alone. The gastrocnemius weights in the AH-inoculated rats treated with formoterol combined with 40 mg/kg roxithromycin were not significantly different from the muscle weights in the saline-inoculated controls. To sum up, formoterol and roxithromycin apparently exert anti-cachectic effects in an additive fashion and may offer the potential for combination therapy in cachexia.
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For H. pylori eradication, the combination of lansoprazole, roxithromycin and metronidazole proved to be as safe as other current triple therapy regimens, while a comparison of efficacy rates yet remains to be assessed in prospective controlled trials. The metronidazole-resistant H. pylori is not rare in Germany and, in the present study, has strongly influenced treatment success.
464 physicians treated 904 patients with moxifloxacin and 846 patients with one of the macrolides. Age, sex and body mass index were well matched between the two treatment groups. However, more moxifloxacin than macrolide patients presented with a generally bad condition (62.8% vs 48.6%). About 42% of patients in both groups had had chronic bronchitis for 1-5 years, and about 27% for 5-10 years. The mean number of AECBs in the previous 12 months was 2.7 and 2.6, respectively. Moxifloxacin was administered to most patients for 5 (43.8%) or 7 days (42.4%). Patients in the macrolide group were treated in most cases with clarithromycin 500 mg for 4-7 days, roxithromycin 300 mg for 6-7 days or azithromycin 500 mg for 3 days. Physicians assessed overall efficacy and tolerability as 'very good' or 'good' in 96.1% and 98.1%, respectively, of moxifloxacin-treated patients and in 67.5% and 91.7%, respectively, of macrolide-treated patients. The mean duration until improvement and cure of AECB was 3.2 days (+/- SD 1.5) and 6.2 days (+/- 2.6) in moxifloxacin-treated patients compared with 4.5 days (+/- 1.8) and 7.5 days (+/- 3.0) in macrolide-treated patients (p < 0.0001).
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RP 59,500 (Quinupristin-Dalfopristin) is the first semisynthetic injectable streptogramin antimicrobial agent, which is a combination of quinupristin and dalfopristin in a 30:70 ratio. The components of RP 59,500 act synergically to provide bactericidal activity through action at different sites on bacterial ribosomes. In the present study, the antimicrobial activity of RP 59,500 was compared with those of four macrolides (erythromycin, clarithromycin, azithromycin, roxithromycin). Susceptibility testing was carried out by microdilution method on 303 strains of 10 species, especially antibiotic-resistant Gram-positive cocci. RP 59,500 was active against a wide range of Gram-positive cocci including methicillin-resistant Staphylococci and penicillin-resistant Streptococcus pneumoniae. The MICs90 of RP 59,500 against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis were both 0.25 microgram/ml, although those of four macrolides were higher than 32 micrograms/ml. The MICs90 of RP 59,500 against penicillin-sensitive, -intermediate and -resistant S. pneumoniae were all 0.5 microgram/ml, although those of four macrolides against penicillin-resistant S. pneumoniae were higher than 32 micrograms/ml. RP 59,500 also exhibited equivalent activities to the four macrolides against strains of Streptococcus pyogenes. Streptococcus agalactiae and Moraxella catarrhalis. RP 59,500 exhibited the highest activities against Enterococcus faecalis, Enterococcus faecium and Enterococcus avium strains which are intrinsically resistant to most antimicrobial agents. No cross-resistance was observed between RP 59,500 and the four macrolides, which will merit attention in future clinical trials of the agent. The effect of human serum on the MIC of RP 59,500 was studied with strains of S. aureus, S. epidermidis and E. faecalis. The presence of 20% (V/V) serum had little or no effect on the MIC, although 50% (V/V) serum increased MICs by 4-8 folds. Laboratory-induced resistance to RP 59,500 occurred in a stepwise fashion in broth cultures of S. aureus, S. epidermidis and E. facalis strains and the induction rate was slow and no more than four fold increases were observed. Population analysis was performed on RP 59,500 and the reference macrolides against S. aureus ATCC 25,923 strain. Although low frequencies (less than 0.01%) of resistant sub-population were detected with EM, CAM, AZM and RXM, no RP 59,500-resistant sub-population was detected in this study.
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Prescribing patterns were similar for the control and active groups in the predetailing period. For both groups, there were significant (P<0.03) increases (45% for control and 40% for active) in total number of antibiotic prescriptions in the post compared with the predetailing period. This trend was anticipated on the basis of the winter seasonal increase in respiratory infections. In line with the chart recommendations for first-line treatment, doctors in the active group prescribed significantly more amoxycillin (P<0.02) and doxycycline (P<0.001) in the post vs predetailing periods. By contrast, doctors in the control group prescribed significantly more cefaclor (P<0.03) and roxithromycin (P<0.03), drugs that were not recommended. The total cost of antibiotics prescribed by doctors in the control group increased by 48% ($37 150) from the preto postdetailing periods. In the same time period, the costs for the active group increased by only 35% ($21 020).
We report four cases of rhabdomyolysis and severe, disabling myopathy associated with HMG CoA reductase-inhibitor therapy. Patient developed symptoms following the addition of roxithromycin to combination lipid-lowering therapy with simvastatin and gemfibrozil. Patients 2 and 3 became symptomatic after developing acute on chronic renal impairment while taking simvastatin. The muscle biopsy of patient 3 revealed a necrotizing myopathy and the presence of inclusion bodies. Patient 4 developed symptoms within 4 weeks of starting cerivastatin monotherapy. The four cases illustrate the importance of considering the potential for drug interactions and making appropriate dosage adjustments for renal insufficiency in patients receiving HMG CoA reductase therapy.
The objective of the present study was to investigate the uptake, depuration, and bioconcentration of two pharmaceuticals, roxithromycin (ROX) and propranolol (PRP), in Daphnia magna via aqueous exposure. Additionally, dietary and pH effects on the bioconcentration of two pharmaceuticals in daphnia were studied. During the 24-h uptake phase followed by the 24-h depuration phase, the uptake rate constants (k(u)) of ROX for daphnia were 9.21 and 2.77 L kg(-1) h(-1), corresponding to the exposure concentrations of 5 and 100 μg L(-1), respectively; For PRP at the nominal concentrations of 5 and 100 μg L(-1), k(u) were 2.29 and 0.99 L kg(-1) h(-1), respectively. The depuration rate constants (k(d)) of ROX in daphnia, at the exposure concentrations of 5 and 100 μg L(-1), were 0.0985 and 0.207 h(-1), respectively; while those of PRP were 0.0276 and 0.0539 h(-1) for the nominal concentrations of 5 and 100 μg L(-1), respectively. With the decreasing exposure concentrations, the bioconcentration factors (BCFs) in daphnia ranged from 13.4 to 93.5 L kg(-1) for ROX, and 18.4 to 83.0 L kg(-1) for PRP, revealing the considerable accumulation potential of these two pharmaceuticals. Moreover, after 6h exposure, the body burdens of ROX and PRP in dead daphnia were 4.98-6.14 and 7.42-12.9 times higher than those in living daphnia, respectively, implying that body surface sorption dominates the bioconcentration of the two pharmaceuticals in daphnia. In addition, the presence of algal food in the media could significantly elevate the kd values for both ROX and PRP, thereby restraining their bioconcentration in daphnia. A pH-dependent bioconcentration study revealed that the bioconcentration of the two pharmaceuticals in daphnia increased with increasing pH levels, which ranged from 7 to 9. Finally, a model was developed to estimate the relationships between pH and the BCFs of the two pharmaceuticals in zooplankton. The predicted values based on this model were highly consistent with wildlife monitoring data, implying that this model will be useful in identifying the bioaccumulation risks that pharmaceuticals pose to zooplankton.
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New, clean water wells were drilled under local supervision for each of 26 identified villages. All people living in villages near the wells were screened for trachoma and then treated with antibiotic if required. Education on personal and environmental hygiene was provided by trained volunteers. Patients affected by trichiasis and corneal scarring received surgery, locally if possible. Attempts to control fly populations by cleaning villages, penning livestock, and digging latrines were undertaken. This was performed under advisement and consultation with local villagers and government officials. Data was collected on variables normally associated with trachoma and others relating to demographics, water quality, environment and hygiene.
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To assess the impact of two interventions on computer-generated prescriptions for antibiotics--(i) an educational intervention to reduce automatic computerised ordering of repeat antibiotic prescriptions, and (ii) a legislative change prohibiting the "no brand substitution" box being checked as a default setting in prescribing software--and to compare these findings with those of a similar survey we conducted in 2000.
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We report the case of a 61-year-old man who presented with coughing fits followed by sinus pauses and syncope. Cardiac and neurological diagnostic work-up was negative and the patient was considered to have cough syncope. As this occurred within the context of febrile pneumonia, an infectious disease was suspected but diagnostic work-up only revealed an increase of antibodies against Chlamydia pneumoniae. The responsibility of this agent is discussed. Clinical recovery was obtained with the prescription of antitussive medication.
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Recently we found that certain antibiotics which are markedly concentrated by human polymorphonuclear leukocytes (PMN) failed to kill susceptible, intraphagocytic Staphylococcus aureus, even though cellular drug levels were quite high. The possibility that specific antibiotics might adversely affect phagocyte antibacterial function was considered. Thus, we studied the effects of multiple antibiotics and adenosine, a known modulator of the PMN respiratory burst response, on neutrophil antibacterial function. At nontoxic concentrations, these drugs had no effect on degranulation in stimulated PMN. Adenosine was a potent inhibitor of formyl-methionyl-leucyl-phenylalanine (FMPL)-stimulated superoxide and hydrogen peroxide generation in PMN but produced less inhibition of microbial particle-induced respiratory burst activity. Three of the tested antibiotics, all of which reach high concentrations in phagocytic cells, had a marked modulatory effect on the PMN respiratory burst. Clindamycin, which enters phagocytes by the cell membrane adenosine (nucleoside) transport system, had only a modest effect on FMLP-mediated superoxide production but inhibited the microbial particle-induced response by approximately 50%. Roxithromycin and trimethoprim were efficient inhibitors of PMN superoxide generation stimulated by FMLP and concanavalin A (also inhibited by erythromycin) but had less effect on zymosan-mediated respiratory burst activity. Antibiotics which entered phagocytes less readily had no effect on the respiratory burst response in PMN. These results, as well as those of experiments with inhibitors of cell membrane nucleoside receptors, indicated that the antibiotic effect is mediated through intraphagocytic pathways. The possibility that antibiotic-associated inhibition of the PMN respiratory burst response might alter leukocyte antimicrobial and inflammatory function deserves further evaluation.
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Measurement of killing kinetics of azithromycin against strains of Streptococcus pneumoniae and Klebsiella pneumoniae in vitro showed that it had a limited bactericidal activity (greater than 90% kill) for the first eight hours of incubation, but developed complete bactericidal activity (greater than 99.9% kill) by 24 h incubation. Since high and sustained tissue levels of azithromycin occur in animals and humans, it was proposed that it might produce a bactericidal effect in vivo. This was demonstrated in a lung infection model in mice, designed to mimic the in-vitro killing studies. A 25 mg/kg dose of azithromycin given 24 h before intranasal challenge reduced the recoverable Str. pneumoniae population by greater than 99.9%, in comparison with untreated controls. Erythromycin did not produce a bactericidal effect at 100 mg/kg, and roxithromycin only reduced the viable count by 96%, at a dose of 50 mg/kg. Against a K. pneumoniae lung infection, a 50 mg/kg dose of azithromycin reduced the bacterial count by 99%. The bactericidal effect was correlated with lung tissue concentrations of azithromycin. In a proliferating Escherichia coli paper disc infection model, extravascular fluid concentrations of azithromycin were correlated with a 99.9% reduction in bacterial count, while corresponding serum concentrations were always less than the MIC. Dosing with azithromycin eradicated Haemophilus influenzae from the bulla (middle ear) of gerbils, as was not the case with erythromycin and roxithromycin. This effect was correlated with the antibiotic concentration in bulla lavage.
This study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause.
Multicenter, double-blind, randomized study.
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Treatment of prurigo nodularis (PN) is often very difficult even with strong corticosteroid dressing and other available means. Macrolide roxithromycin (RXM) is used in consideration of its immunosuppressive effects in treating several skin disorders. Tranilast (N-(3,4-dimethoxycinnamoyl) is useful for treating atopic disorders and hypertrophic scars as well, suggesting its capacity to inhibit fibroblast proliferation. More adequate and effective therapy for this disorder has been requested. We report 3 cases of uncontrollable PN treated with 300 mg/day roxithromycin and 200 mg/day tranilast. Complete and/or remarkable regression of PN was observed on treatment with roxithromycin and tranilast in combination within 4 to 6 months. The 2 agents in combination can be used effectively for the treatment of uncontrollable PN.