ru-66647 and Acute-Disease

A case of mild hepatocellular injury associated with the administration of telithromycin in a patient with no risk factors for hepatotoxicity is presented.. A 44-year-old man with no significant past medical history arrived at the emergency room after six days of high fever, chills, headache, neck stiffness, and back pain. Five days earlier, he visited a family medicine clinic for his symptoms and oral telithromycin 800 mg daily was prescribed for a suspected upper-respiratory-tract infection. The patient stopped taking the drug after three days due to persistent symptoms. On admission, the patient's laboratory tests revealed an aspartate transaminase (AST) concentration of 68 units/L, an alanine transaminase (ALT) value of 155 units/L, and an erythrocyte sedimentation rate of 40 mm/hr. The patient was not taking any long-term medications, had taken only aspirin for his fever, and denied the use of alcohol and illegal drugs. The patient was admitted to the general medical unit with a diagnosis of possible viral hepatitis. His urine culture was negative, and serology tests later revealed no evidence of hepatitis A, B, or C. Ibuprofen, pantoprazole, and enoxaparin were prescribed. On hospital day 2, the patient's AST and ALT concentrations had decreased to 50 and 110 units/L, respectively. By day 3, the patient's symptoms had improved and he remained afebrile. His AST and ALT values had further decreased to 41 and 105 units/L, respectively. He was then diagnosed with acute viral upper-respiratory-tract infection with mild hepatotoxicity associated with telithromycin and was discharged home with orders for follow-up at the family medicine clinic.. A patient without risk factors for hepatotoxicity developed mild elevations in hepatic transaminases after receiving telithromycin for the treatment of a suspected upper-respiratory-tract infection.

Topics: Acute Disease; Adult; Alanine Transaminase; Anti-Bacterial Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Humans; Ketolides; Liver; Male; Respiratory Tract Infections

To compare the efficacy and tolerability of a 5-day course of telithromycin (800 mg once daily) with a 10-day course of telithromycin or standard comparators (amoxicillin-clavulanate 500/125 mg three times daily or cefuroxime axetil 250 mg twice daily) in patients with acute maxillary sinusitis (AMS).. Data from three randomised double blind studies were pooled. The studies included patients with clinical symptoms of AMS and sinus X-ray findings of total opacity, air-fluid levels or mucosal thickening.. Pooled analysis of results for 5-day telithromycin revealed overall clinical cure rates of 83.6% (383/458 patients) at post-therapy (days 17-24) and 78.9% (330/418 patients) at late post-therapy (days 31-45) in the per-protocol population. Clinical cure rates at post-therapy were equivalent to those observed with 10-day telithromycin (82.5% vs 81.7%) or comparator treatment (80.9% vs 77.4%). Moreover, clinical cure rates exceeded 80% in subgroups of patients of interest, including those with severe infection and those fulfilling more stringent criteria for bacterial AMS. A satisfactory bacteriological outcome was achieved in 87.6% of patients. The 5-day telithromycin regimen was well tolerated.. Telithromycin once daily for 5 days offers effective treatment for AMS and is comparable to 10-day courses of standard treatments.

Topics: Acute Disease; Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefuroxime; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged

Telithromycin, the first approved ketolide antibiotic, was developed to treat community-acquired respiratory tract infections, including acute bacterial maxillary sinusitis (ABMS). A previously published study showed that a 5-day course of 800 mg telithromycin once daily is as effective as a 10-day course in the treatment of ABMS.. Data were pooled from two controlled, multinational, prospective, randomized, double-blinded ABMS trials comparing 5-day telithromycin (800 mg once daily) with 10-day amoxicillin-clavulanate (500/125 mg 3 times daily) and cefuroxime axetil (250 mg twice daily). Clinical cure and bacteriologic eradication rates were compared by means of descriptive statistics.. The clinical cure rate for telithromycin was 80.9% versus 77.4% for comparators; bacteriologic eradication rate for telithromycin was 84.9% versus 81.7% for comparators. Most adverse events were mild to moderate in intensity and, most commonly, gastrointestinal in nature.. These results support the conclusion that 5 days of treatment with telithromycin is as safe and effective in patients with ABMS as a 10-day course of treatment with amoxicillin-clavulanate or cefuroxime axetil.

Topics: Acute Disease; Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Cefuroxime; Double-Blind Method; Drug Administration Schedule; Female; Haemophilus influenzae; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged; Moraxella catarrhalis; Prospective Studies; Randomized Controlled Trials as Topic; Staphylococcus aureus; Streptococcus pneumoniae

Telithromycin, a ketolide antibiotic used for the treatment of community-acquired respiratory infections, is widely prescribed in primary care practice. Treatment-related adverse events are mainly of gastrointestinal origin and generally mild in intensity. The authors report the first case of telithromycin-induced severe acute interstitial nephritis. Practitioners should be aware of the possibility that telithromycin therapy could result in this form of drug-induced acute renal failure.

Topics: Acute Disease; Adolescent; Humans; Ketolides; Kidney; Male; Methylprednisolone; Nephritis, Interstitial; Respiratory Tract Infections

This study compared the clinical efficacy, time to symptom resolution, and tolerability of a 5-day regimen of telithromycin with a 10-day regimen of high-dose amoxicillin-clavulanate in acute bacterial sinusitis (ABS).. In this multinational (41 centers in Canada, Germany, Greece, Portugal, and Turkey), open-label, noninferiority study, patients >/=18 years old (n=298) with a clinical (>7 days' symptoms) and radiological (air/fluid level, total opacification, mucosal thickening >/=10 mm) diagnosis of ABS were randomized to receive telithromycin 800 mg once daily for 5 days or amoxicillin-clavulanate 875/125 mg twice daily for 10 days. Clinical efficacy and tolerability were assessed at the test-of-cure visit (days 17-21). Time to symptom resolution was based on patients' daily diary assessment of individual symptoms.. The per-protocol clinical success rate (primary endpoint) with telithromycin (88.6% (109/123)) was noninferior to that with amoxicillin-clavulanate (88.8% (111/125)) (95% confidence interval: -8.9 to 8.5). In the modified intention-to-treat (mITT) population, the median time for 50% reduction of total symptom scores was significantly shorter for telithromycin (4 days) vs. amoxicillin-clavulanate (5 days; p=0.044); median times for 75% reduction of total symptom scores were: telithromycin, 7 days; amoxicillin-clavulanate, 8 days (p=0.115). The median time for reduction of total symptom scores to the absent/very mild category (mITT population) was 6 days for telithromycin vs. 8 days for amoxicillin-clavulanate (p=0.04). All treatment-emergent adverse events (TEAEs) were mostly gastrointestinal and occurred in 20.7% (30/145) of telithromycin-treated patients vs. 31.8% (47/148) of amoxicillin-clavulanate-treated patients (p=0.034). One serious AE was reported in the telithromycin group, but it was considered not to be related to treatment.. This open-label, randomized study demonstrated that treatment of ABS with telithromycin resulted in comparable clinical efficacy, shorter times to symptom resolution, and fewer total TEAEs than treatment with amoxicillin-clavulanate.

Topics: Acute Disease; Adult; Amoxicillin; Anti-Bacterial Agents; Bacterial Infections; beta-Lactam Resistance; Drug Administration Schedule; Female; Haemophilus influenzae; Humans; Ketolides; Male; Middle Aged; Outcome Assessment, Health Care; Quality of Life; Sinusitis; Streptococcus pneumoniae; Surveys and Questionnaires

Clarithromycin is commonly dosed for 7 or more days in patients with acute bacterial exacerbation of chronic bronchitis (ABECB). Studies with other antibiotics have shown equivalent efficacy, reduced/similar frequency of adverse events, improved adherence and patient satisfaction, and lower treatment costs with a shorter treatment course.. The study population was derived from two multicenter, randomized, double-blind (North America)/single-blind (France) comparative trials in which outpatients at least 35 years old with a presumptive diagnosis of obstructive ABECB were randomized to receive clarithromycin extended-release (ER) 1000 mg once daily for 5 days or a comparator agent--clarithromycin immediate-release (IR) 500 mg twice daily for 7 days (in North America) or telithromycin 800 mg once daily for 5 days (in France).. A total of 818 patients were randomized (411 to clarithromycin ER and 407 to a comparator agent). The clinical cure rate in clinically evaluable patients at the follow-up visit was 90% each for the clarithromycin ER group (318/353) and the comparator group (318/355). The patient bacteriological cure rate and the overall target pathogen eradication rate in clinically and bacteriologically evaluable patients were each 92% for the clarithromycin ER group (155/168 and 189/205, respectively) and 93% for the comparator group (147/158 and 183/197, respectively) at the follow-up visit. The study drugs were generally well tolerated, with < 2% of patients discontinuing their treatment prematurely due to a drug-related adverse event. The incidence of drug-related adverse events was 18% (73/411) in the clarithromycin ER group and 24% (97/407) in the comparator group. Clarithromycin ER-treated patients reported statistically significantly fewer episodes of abdominal pain than did patients treated with a comparator agent (0.2% vs. 1.7%, respectively; p = 0.037). This combined analysis is limited by differing blinding methods, comparator agents, and their duration of administration. Furthermore, many patients were excluded from the clinically and bacteriologically evaluable group due to lack of a pretreatment target pathogen.. A once daily, 5-day clarithromycin ER regimen appears to be a suitable choice for treating patients with ABECB.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Bronchitis; Clarithromycin; Delayed-Action Preparations; Disease Progression; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Ketolides; Male; Middle Aged; Research Design; Severity of Illness Index; Sputum; Treatment Outcome

We conducted a double-blind, randomized, placebo-controlled study to evaluate the efficacy of telithromycin in patients with acute exacerbations of asthma.. A total of 278 adults with diagnosed asthma were enrolled within 24 hours after an acute exacerbation of asthma requiring short-term medical care. The patients were randomly assigned to receive 10 days of oral treatment with telithromycin (at a dose of 800 mg daily) or placebo in addition to usual care. Primary efficacy end points were a change from baseline over the treatment period in symptoms (as recorded by patients in a diary card) and in the peak expiratory flow in the morning at home. The presence of Chlamydophila pneumoniae or Mycoplasma pneumoniae was ascertained by serologic analysis, polymerase chain reaction, and culture.. Of the two prespecified primary outcomes, only asthma symptoms showed a significantly greater reduction among patients receiving telithromycin than among those receiving placebo. Mean (+/-SD) scores on a test of asthma symptoms (on a 7-point scale, with 0 denoting no symptoms and 6 denoting severe symptoms) were 3.0+/-1.4 at baseline and 1.7+/-1.1 at the end of treatment for the telithromycin group and 2.8+/-1.3 at baseline and 2.0+/-1.0 at the end of treatment for the placebo group. The mean decrease in symptom scores during the treatment period was 1.3 for telithromycin and 1.0 for placebo (mean difference, -0.3; 95 percent confidence interval, -0.5 to -0.1; P=0.004). There was no significant treatment effect on the other primary outcome measure, a change in morning peak expiratory flow. Nausea was more common among patients in the telithromycin group than in the placebo group (P=0.01). Although 61 percent of patients had evidence of infection with C. pneumoniae, M. pneumoniae, or both, there was no relationship between bacteriologic status and the response to asthma treatment.. This study provides evidence of the benefit of telithromycin in patients with acute exacerbations of asthma; the mechanisms of benefit remain unclear. (ClinicalTrials.gov number, NCT00273520.).

Topics: Acute Disease; Administration, Oral; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Bacterial Agents; Asthma; Chlamydophila Infections; Chlamydophila pneumoniae; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Ketolides; Male; Middle Aged; Mycoplasma pneumoniae; Peak Expiratory Flow Rate; Pneumonia, Mycoplasma; Treatment Outcome

To explore the efficacy of the ketolide telithromycin compared with azithromycin in eradicating S pneumoniae from the nasopharynx of adults with acute maxillary sinusitis. The growing resistance of Streptococcus pneumoniae to penicillin and macrolides brought about the development of a new class of antibiotics-the ketolides-that are effective against resistant pneumococci.. Otolaryngology clinic.. One-hundred five patients with acute maxillary sinusitis.. Nasopharyngeal cultures were obtained before therapy and 10 to 12 days after initiation of treatment. Fifty-nine patients were treated with 500 mg of azithromycin daily for 3 days and 46 were treated with 800 mg of telithromycin daily for 5 days.. Sixty-seven potential pathogens were recovered prior to initiation of therapy in 57 patients, 32 treated with telithromycin and 25 treated with azithromycin: S pneumoniae (31 isolates), Haemophilus influenzae (non-type b) (13), Staphylococcus aureus (8), Streptococcus pyogenes (8), and Moraxella catarrhalis (7). The distribution of the pathogens was similar in both groups. The number of S pneumoniae isolates in the azithromycin group was reduced following treatment from 14 to 8 (43% reduction), and 5 of these 8 isolates were resistant to azithromycin. In contrast, the number of S pneumoniae isolates in the telithromycin group was reduced following treatment from 17 to 1 (94% reduction) (P < .01). This isolate was susceptible to azithromycin and telithromycin. No differences were noted in the eradication rate of all of the other potential pathogens, which were all susceptible to both azithromycin and telithromycin. Development of resistance to the antimicrobial agents used (defined as increase in the minimal inhibitory concentration by at least 2 tubes) was found only in 5 isolates (4 S pneumoniae and 1 H influenzae) recovered only from patients who received azithromycin (P < .05).. These data illustrate the superiority of telithromycin to azithromycin in the eradication of S pneumoniae from the nasopharynx.

Topics: Acute Disease; Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Female; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged; Pneumococcal Infections; Streptococcus pneumoniae

The aim of this study was to evaluate the efficacy and tolerance of 5 days of telithromycin (800 mg once a day) in the treatment of bacteriologically proven acute maxillary sinusitis (AMS).. Two hundred and sixty-three patients with a clinically diagnosed AMS and purulent rhinorrhea were included in this prospective, multicenter, non-comparative open-labeled French study. Pus was sampled from the middle meatus before inclusion. The bacterial origin of the infection was confirmed by a scientific committee (presence of leucocytes/bacteria on direct microscopic examination of pus, and positive culture).. Seven to 14 days after the end of the treatment the clinical success rate (cure and improvement) was 91% (63/69 patients) in the per protocol bacteriologically documented (PPb) population and 90% (231/257 patients) in the modified intent-to-treat population. The main strains identified in the 69 patients of PPb population were Streptococcus pneumoniae (47.8%, of which 15 strains with reduced susceptibility to penicillin and 15 erythromycin resistant strains), Haemophilus influenzae (14.5%), Branhamella catarrhalis (8.7%) and Streptococcus aureus (29.0%). Drug tolerance was assessed on 263 patients as satisfactory with mainly gastro-intestinal disorders considered to be related to the treatment in 7.6% of patients. No serious adverse event related to the study drug was reported.. The efficacy of telithromycin 800 mg once daily for 5 days is confirmed in the treatment of AMS, even for those due to S. Pneumoniae.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Bacterial Infections; Female; France; Humans; Ketolides; Male; Maxillary Sinusitis; Recurrence; Reproducibility of Results; Safety

To demonstrate equivalence in the clinical efficacy of telithromycin vs clarithromycin treatment of outpatients with acute exacerbations of chronic bronchitis (AECB), and to compare the tolerability and respiratory-related health-care resource utilization associated with these treatment regimens.. A randomized, double-blind, multicenter, clinical study was conducted at 105 centers in 14 countries. Adult outpatients (age > or = 30 years) received oral telithromycin, 800 mg qd for 5 days (n = 270), or oral clarithromycin, 500 mg bid for 10 days (n = 282), for the treatment of AECB. Clinical and bacteriologic outcomes were assessed at the posttherapy/test-of-cure (TOC) visit (days 17 to 24; per-protocol population). Health-care resource utilization data were collected for each patient by investigators blinded to study medication up to the late posttherapy visit (days 31 to 36).. Clinical cure rates at the posttherapy/TOC visit were comparable between the groups (telithromycin, 193 of 225 patients [85.8%]; clarithromycin, 206 of 231 patients [89.2%]); bacteriologic outcome was satisfactory for 59 of 72 telithromycin-treated patients (81.9%) vs 63 of 76 clarithromycin-treated patients (82.9%). Health-care resource utilization assessed up to the late posttherapy visit was lower in the telithromycin treatment group than the clarithromycin treatment group, with significantly fewer hospitalizations for respiratory-related causes (one hospitalization vs eight hospitalizations for a total of 4 inpatient days vs 39 inpatient days, respectively), significantly fewer AECB-related emergency department visits (0 vs 8), and fewer unscheduled outpatient visits (11 vs 18). Fewer telithromycin-treated patients reported days lost from work (21 of 91 patients [23.1%]; 133 days) compared with those receiving clarithromycin (30 of 98 patients [30.6%]; 141 days). Telithromycin was well tolerated; adverse events considered possibly related to study medication were reported by 61 of 269 patients (22.7%) and 100 of 280 patients (35.7%) receiving telithromycin and clarithromycin, respectively.. In this study, 5-day telithromycin treatment was as effective and well tolerated as 10-day clarithromycin treatment for patients with AECB, and was associated with a reduced utilization of health-care resources.

Topics: Acute Disease; Adult; Aged; Bronchitis; Chronic Disease; Clarithromycin; Disease Progression; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Health Care Rationing; Humans; Ketolides; Male; Middle Aged; Single-Blind Method; Smoking; Vital Capacity

The aim of this study was to evaluate the clinical efficacy of telithromycin administered for 5 days at a dosage of 800 mg/day, in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) presenting with at least 2 of Anthonisen's criteria including the increase of purulence.. During this multicenter (211 private lung specialists), prospective, non-comparative, open-labeled French study, 365 patients were included between April 2002 and March 2003. Clinical efficacy was assessed on D12-D19 by the rate of clinical success as defined by recovery or clinical improvement (main endpoint) according to the number of exacerbation episodes during the previous year.. On D12-D19 clinical success rate in the per protocol global population was 88.0% and respectively 87.9% in patients with or=4 episodes in the previous year. These success rates were similar to those in the intent-to-treat population. Safety, assessed on 359 patients, was satisfactory, with mainly digestive disorders related to the treatment in 3.9% of the patients. No treatment-related serious adverse events were observed.. This study, conducted among private practitioners in France according to COPD classification as defined by official recommendations, validates the results obtained in previous studies. Our results confirm the place attributed to telithromycin in the treatment of patients presenting with AECOPD without chronic respiratory failure, according to ongoing official recommendations.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Female; France; Humans; Ketolides; Male; Middle Aged; Patient Selection; Private Practice; Pulmonary Disease, Chronic Obstructive; Risk Factors; Treatment Outcome

To compare the clinical and bacteriologic efficacy and safety of short-duration treatment with telithromycin given for 5 days with moxifloxacin given for 10 days in adults with acute bacterial rhinosinusitis (ABRS).. In this prospective, double-blind, parallel-group, randomized, multicenter study, adult patients (N = 349) with ABRS were randomized to oral telithromycin (800 mg once daily for 5 days) or to oral moxifloxacin (400 mg once daily for 10 days) and followed for 31 to 36 days. Clinical outcome was determined by the investigator at the posttherapy/test of cure (TOC) visit. Bacteriologic outcome was determined by comparing cultures taken at the pretreatment visit with cultures obtained at the posttherapy/TOC visit. The primary objective was to demonstrate equivalence of clinical cure rates in the per-protocol population between treatment groups at the posttherapy/TOC visit.. Clinical success at TOC (primary endpoint) was achieved in 87.4% of patients in the telithromycin group compared with 86.9% for moxifloxacin (per-protocol patients; 0.5% difference between treatment groups; 95% confidence interval [CI], -8.1, 9.2; P = 0.8930). The bacteriologic success rates were 94.1% and 93.9%, respectively (0.2% difference between treatment groups; 95% CI, -14.2, 14.5; P = 0.9734). Overall treatment-emergent adverse events for both drugs (mostly gastrointestinal) were mild to moderate in intensity.. The clinical and bacteriologic efficacy of telithromycin 800 mg once daily for 5 days was equivalent to that of moxifloxacin 400 mg once daily for 10 days, establishing telithromycin as an important treatment option for ABRS.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Aza Compounds; Bacterial Infections; Double-Blind Method; Drug Administration Schedule; Female; Fluoroquinolones; Humans; Ketolides; Macrolides; Male; Middle Aged; Moxifloxacin; Prospective Studies; Quinolines; Rhinitis; Sinusitis; Time Factors

The efficacy and tolerability of oral telithromycin 800 mg once daily for 5 vs. 10 days were assessed in patients with acute maxillary sinusitis (AMS).. Adults (n = 341) with confirmed AMS diagnosed on clinical signs and symptoms and sinus X-ray showing total opacity or air-fluid level were randomized to receive oral telithromycin for 5 days (followed by placebo for 5 days; n = 170) or 10 days (n = 171). Causative pathogens were isolated by pretreatment sinus puncture (day 1). Clinical and bacteriologic outcomes, and safety and tolerability endpoints were assessed.. Clinical cure rates post-therapy (per-protocol; days 17-21) were comparable (91.1% in the 5-day group, n = 123; 91.0% in the 10-day group, n = 133). Bacteriologic eradication rates (per-protocol) were also similar (90.7 vs. 91.3%). Both regimens were well tolerated.. A 5-day course of telithromycin 800 mg once daily is an effective, well-tolerated treatment for adults with AMS, comparable to a 10-day regimen.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Double-Blind Method; Drug Administration Schedule; Female; Humans; Ketolides; Macrolides; Male; Maxillary Sinusitis; Middle Aged; Treatment Outcome

Quantitative methods have been proposed to assess and compare the benefit-risk balance of treatments. Among them, multicriteria decision analysis (MCDA) is a popular decision tool as it permits to summarise the benefits and the risks of a drug in a single utility score, accounting for the preferences of the decision-makers. However, the utility score is often derived using a linear model which might lead to counter-intuitive conclusions; for example, drugs with no benefit or extreme risk could be recommended. Moreover, it assumes that the relative importance of benefits against risks is constant for all levels of benefit or risk, which might not hold for all drugs. We propose Scale Loss Score (SLoS) as a new tool for the benefit-risk assessment, which offers the same advantages as the linear multicriteria decision analysis utility score but has, in addition, desirable properties permitting to avoid recommendations of non-effective or extremely unsafe treatments, and to tolerate larger increases in risk for a given increase in benefit when the amount of benefit is small than when it is high. We present an application to a real case study on telithromycin in Community Acquired Pneumonia and Acute Bacterial Sinusitis, and we investigated the patterns of behaviour of Scale Loss Score, as compared to the linear multicriteria decision analysis, in a comprehensive simulation study.

Topics: Acute Disease; Anti-Bacterial Agents; Community-Acquired Infections; Computer Simulation; Decision Support Techniques; Humans; Ketolides; Pneumonia; Risk Assessment; Sinusitis

Topics: Acute Disease; Anti-Bacterial Agents; Bronchitis, Chronic; Community-Acquired Infections; Drug Approval; Drug Labeling; Humans; Ketolides; Patient Education as Topic; Pneumonia, Bacterial; Sinusitis; United States; United States Food and Drug Administration

Topics: Acute Disease; Anti-Bacterial Agents; Bacterial Infections; Conflict of Interest; Drug Industry; Humans; Ketolides; Periodicals as Topic; Practice Guidelines as Topic; Rhinitis; Sinusitis; United States

Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious.. A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of "acute hepatitis of unknown origin," that occurred after telithromycin usage. Both incidents occurred within a year.. Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time.. Here we report a case of acute hepatitis probably associated with the administration of telithromycin.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Humans; Ketolides; Male; Respiratory Tract Infections

Since the late 1990s, the prevalence of erythromycin-resistant Streptococcus pyogenes has significantly increased in several European countries. Between January 1999 and December 2002, 1,577 isolates of S. pyogenes were recovered from children with tonsillopharyngitis living in various areas of Western Greece. Erythromycin resistance was observed in 379 (24%) of the 1,577 isolates. All erythromycin-resistant strains along with 153 randomly selected erythromycin-susceptible S. pyogenes isolates were tested for their antimicrobial susceptibility, resistance phenotypes, and genotypes. Representative isolates underwent emm gene sequence typing. Isolates with reduced susceptibility to telithromycin (MIC, > or = 2 microg/ml) were studied for multilocus sequence type, L22, L4, and 23S rRNA mutations. Of the total 379 erythromycin-resistant isolates, 193 (50.9%) harbored the mef(A) gene, 163 (43%) erm(A), 1 (0.3%) mef(A) plus erm(A), and 22 (5.8%) the erm(B) gene. Among the erythromycin-susceptible isolates, emm 1 (25%), emm 2 (12.5%), and emm 77 (12.5%) predominated. Furthermore, among the erythromycin-resistant isolates, emm 4 (30.6%), emm 28 (22.2%), and emm 77 (12.5%) prevailed. Resistance to telithromycin was observed in 22 (5.8%) of the erythromycin-resistant isolates. Sixteen (72.7%) of the 22 isolates appeared to be clonally related, since all of them belonged to emm type 28 and multilocus sequence type 52. One of the well-known mutations (T2166C) in 23S rRNA, as well as a new one (T2136C), was detected in erythromycin- and telithromycin-resistant isolates. High incidence of macrolide resistance and clonal spread of telithromycin resistance were the characteristics of the Greek S. pyogenes isolates obtained from 1999 to 2002.

Topics: Acute Disease; Child; Child, Preschool; Drug Resistance, Bacterial; Erythromycin; Genotype; Greece; Humans; Ketolides; Pharyngitis; Phenotype; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis

A 58-year-old woman who had been taking digoxin 0.25 mg/day for more than 35 years for heart palpitations after mitral valve repair was prescribed a 5-day course of telithromycin for acute bronchitis. On the sixth day of therapy, she came to the emergency department complaining of general malaise and having experienced three episodes of syncope over the previous 2 days. Laboratory analysis revealed elevated digoxin plasma levels, and electrocardiography showed several nonspecific repolarization anomalies. Telithromycin is known to increase digoxin plasma levels; however, the clinical significance of this interaction is not known. To our knowledge, this is the first report of elevated plasma digoxin levels associated with signs and symptoms of toxicity. This drug interaction-determined as probable according to the Naranjo adverse drug reaction probability scale-may be mediated by P-glycoprotein. By inhibiting the transport of digoxin by P-glycoprotein, telithromycin may have decreased digoxin elimination in the intestinal lumen and its renal tubular excretion, resulting in elevated plasma levels and drug toxicity. Clinicians should be aware of possible digoxin toxicity after concomitant administration with telithromycin, especially in patients who are at risk, such as those with electrolyte abnormalities and decreased renal function.

Topics: Acute Disease; Bronchitis; Digoxin; Drug Interactions; Electrocardiography; Female; Heart; Humans; Ketolides; Middle Aged

Topics: Acute Disease; Adrenal Cortex Hormones; Anti-Bacterial Agents; Asthma; Forced Expiratory Volume; Health Services Misuse; Humans; Ketolides

Topics: Acute Disease; Anti-Bacterial Agents; Asthma; Gastroesophageal Reflux; Humans; Ketolides

The ketolide telithromycin represents a new subclass of 14-membered semisynthetic macrolides. Because there is evidence that traditional macrolides such as roxithromycin exert anti-inflammatory activity, we investigated the anti-inflammatory action of telithromycin against lipopolysaccharide (LPS)-induced acute systemic inflammation in mice in comparison with roxithromycin.. CD-1 mice were injected intraperitoneally with LPS (1 mg/kg), and the effects of pretreatment with a single intraperitoneal dose of telithromycin (150 mg/kg) or roxithromycin (50 mg/kg) for 2 h on the expression and formation of tumour necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta), interferon gamma (IFNgamma) and inducible nitric oxide synthase (NOS-II) as well as nitric oxide (NO) were analysed at different time points after LPS-treatment. Cytokine and NOS-II mRNA abundance was examined using real-time RT-PCR. Tissue cytokine levels were determined by enzyme-linked immunosorbent assay kits (ELISA); NO levels were measured by colorimetric assay kits.. Pretreatment of mice with telithromycin as well as roxithromycin similarly attenuated the LPS-induced expression and formation of TNFalpha, IL-1beta and IFNgamma. Furthermore, the LPS-induced increase of NOS-II mRNA and the formation of NO were clearly diminished.. These results suggest that the ketolide telithromycin has anti-inflammatory properties like conventional macrolides due to inhibition of the production of proinflammatory cytokines, which leads to a decreased formation of NO in LPS-treated mice. Our data indicate that ketolides may have beneficial therapeutic effects independent of their antibacterial activity.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Ketolides; Lipopolysaccharides; Male; Mice; Mice, Inbred Strains; Nitric Oxide; Organ Specificity; Roxithromycin; Systemic Inflammatory Response Syndrome; Time Factors

The effect on the nasopharyngeal flora of 7 days of amoxicillin-clavulanate or 5 days of 800 mg once a day was studied in 50 adults with acute sinusitis. The numbers of potential pathogens and interfering alpha-hemolytic streptococci were equally reduced after both therapies. However, the number of interfering Prevotella spp. declined more significantly after amoxicillin-clavulanate treatment.

Topics: Acute Disease; Adolescent; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria; Female; Haemophilus influenzae; Humans; Ketolides; Male; Maxillary Sinusitis; Middle Aged; Moraxella catarrhalis; Nasopharynx; Prevotella; Streptococcus pneumoniae

The efficacy of telithromycin, a new ketolide antibiotic, was investigated in the treatment of acute Chlamydia pneumoniae infection in a mouse model.. C57BL/6J mice were inoculated intranasally, and the effects of three different doses of telithromycin (25, 50 and 100 mg/kg) were assessed after 5 and 10 days of treatment. Lungs for culture, PCR, histopathology, and blood for serum samples were collected immediately after each treatment period and at 3 weeks post-inoculation. C. pneumoniae-specific antibodies were analysed, and the effect of treatment was assessed by culture, detection of C. pneumoniae DNA and determination of histopathological inflammatory changes in mouse lungs.. Culture negativity in the lungs was achieved with the higher doses, 50 and 100 mg/kg, after 10 days of treatment. C. pneumoniae DNA was not totally eradicated with the treatments, but the groups treated with 50 and 100 mg/kg doses for 10 days had the lowest DNA positivity rates (10%) 3 weeks after the inoculation. In lung histopathology, the efficacy of telithromycin on inflammatory changes was also dose-dependent: higher doses were more effective in reducing the inflammatory reaction. Overall, the 25 mg/kg dose had a weaker effect compared with the others.. Telithromycin had both time- and dose-dependent effects on the eradication of chlamydia and on reducing infection-induced inflammatory changes in mouse lungs.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Chlamydia Infections; Chlamydophila pneumoniae; DNA, Bacterial; Dose-Response Relationship, Drug; Female; Immunoglobulin G; Inflammation; Ketolides; Lung; Macrolides; Mice; Mice, Inbred C57BL; Pneumonia, Bacterial; Reverse Transcriptase Polymerase Chain Reaction

To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with telithromycin in respiratory tract infections.. The activity of telithromycin was determined by in vitro susceptibility testing of key respiratory tract pathogens isolated from patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating the clinical efficacy of telithromycin.. In this pooled analysis, telithromycin mode minimum inhibitory concentration (MIC) and MIC90, respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626); 0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789), respectively.. High levels of in vitro susceptibility to telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.

Topics: Acute Disease; Adolescent; Adult; Bacteria; Bronchitis; Chronic Disease; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Community-Acquired Infections; Female; Humans; In Vitro Techniques; Ketolides; Macrolides; Male; Microbial Sensitivity Tests; Pneumonia; Randomized Controlled Trials as Topic; Sinusitis

A pharmacoeconomic analysis was done to compare the efficiency of two treatments in the acute exacerbation of chronic bronchitis: telithromycin and cefuroxime-axetil.. Restrospective analysis, modeled through a decision tree. The effectiveness of the treatments was estimated through a randomized and double-blind clinical trial in which 800 mg/day (5 days) of telithromycin were compared with 1,000 mg/day (10 days) of cefuroxime-axetil in patients with acute exacerbation of chronic bronchitis (140 and 142 patients, respectively). Resources use was estimated from clinical trial and from Spanish data, and the unit costs through a health costs dabatase. The model was validated by a panel of Spanish clinical experts.. Since the clinical trial was designed to demonstrate equivalence, there were no significant differences of effectiveness among both treatments (with a rate of clinical cure of 86.4% and 83.1%, respectively) which means that an analysis of costs minimization was done. In the average case, the average cost of the disease by patient was 174.83 Euros with telithromycin and 194.68 Euros with cefuroxime-axetil (a difference of 19.85 Euros). The results were maintained in the analysis of sensitivity, with favorable differences for telithromycin that ranged between 18.04 Euros and 22.25 Euros.. With telithromycin up to 22 Euros by patient with acute exacerbation of chronic bronchitis could be saved, in comparison with cefuroxime-axetil.

Topics: Acute Disease; Algorithms; Anti-Bacterial Agents; Bronchitis, Chronic; Cefuroxime; Cost-Benefit Analysis; Drug Administration Schedule; Humans; Ketolides

Topics: Acute Disease; Anti-Bacterial Agents; Bronchitis; Chronic Disease; Community-Acquired Infections; Emergency Treatment; Hospitalization; Humans; Ketolides; Macrolides; Patient Selection; Pneumonia, Bacterial

Thirteen multinational, Phase III studies were conducted to establish the efficacy of telithromycin 800 mg once daily in the treatment of community-acquired respiratory tract infections (RTIs).. Data were analyzed from 4,743 adult patients participating across four indications: community-acquired pneumonia (CAP) of mild to moderate severity, acute exacerbations of chronic bronchitis (AECB), acute maxillary sinusitis (AMS) and tonsillitis/pharyngitis.. Treatment with telithromycin for either 5 days (AECB, AMS and tonsillitis/pharyngitis) or 7-10 days (CAP and AMS) provided high rates of clinical and bacteriologic cure (5-day, 87.0% and 86.0%, respectively; 7 to 10-days, 90.3% and 90.5%, respectively) that were equivalent to those of a 10-day course of comparator antibacterials (86.5% and 86.5%, respectively). The clinical efficacy of telithromycin extended to high-risk CAP and AECB patients and to all key respiratory pathogens, including Streptococcus pneumoniae strains resistant to penicillin or erythromycin and atypical/intracellular pathogens. Telithromycin was generally well-tolerated across patient groups.. These findings support the use of telithromycin as an effective therapy for the treatment of community-acquired RTIs.

Topics: Acute Disease; Adolescent; Adult; Aged; Bacterial Infections; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Ketolides; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Retrospective Studies; Risk Assessment; Treatment Outcome

Topics: Acute Disease; Anti-Bacterial Agents; Chronic Disease; Clinical Trials as Topic; Coronary Disease; Diabetes Complications; Drug Interactions; Humans; Ketolides; Macrolides; Respiratory Tract Infections; Risk Factors; Time Factors

The increasing antimicrobial resistance amongst bacterial pathogens causing community-acquired respiratory tract infections (CARTIs) necessitates surveillance at the local, regional, national and international levels to provide information to guide empiric antimicrobial therapy. PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a longitudinal, global, multicenter surveillance study designed to monitor the worldwide development of antimicrobial resistance and disseminate up-to-date information via the internet to assist in the choice of empiric therapy at the local level. In this paper, the results for the first year of PROTEKT are presented from a global perspective. Streptococcus pneumoniae, followed by Haemophilus influenzae and Moraxella catarrhalis, are the principal organisms responsible for the majority of CARTIs. The global prevalence of penicillin G resistance in S. pneumoniae has risen to an alarming 36.3% (high-level resistance 22.1%, intermediate-level 14.2%) with the highest prevalence found in Asia (68%). In all regions, macrolide resistance is greater than penicillin G resistance with a global prevalence rate of 31.2%. High resistance rates were also found for tetracycline (30.5%) and co-trimoxazole (43.9%), and multiresistance was found between penicillin G, macrolides, tetracycline and co-trimoxazole. The prevalence of beta-lactamase-producing H. influenzae and M. catarrhalis was found to be similar to previous reports. Macrolide resistance in S. pyogenes was 0.3% overall. Telithromycin demonstrated excellent in vitro activity against all organisms and is a potential new candidate for the empiric therapy of CARTIs. The first year of PROTEKT has provided valuable information on the prevalence of antimicrobial resistance of bacterial agents causing CARTIs that can be used for guiding empiric therapy and policies. The rapidly developing and geographically varying resistance observed in this study further emphasizes the need for accurate up-to-date surveillance data.

Topics: Acute Disease; Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Bacterial; Gram-Negative Bacterial Infections; Humans; Information Dissemination; International Cooperation; Internet; Ketolides; Longitudinal Studies; Macrolides; Microbial Sensitivity Tests; Population Surveillance; Prospective Studies; Respiratory Tract Infections; Streptococcal Infections

Topics: Acute Disease; Anti-Bacterial Agents; Community-Acquired Infections; Emergencies; France; Humans; Ketolides; Macrolides; Pneumonia, Bacterial