ru-66647 and Pneumonia--Bacterial

Drug options for treatment of infections are increasingly limited. The pharmaceutical industry has found it difficult to discover new antimicrobial agents, and only two novel classes of antibiotics, the oxazolidinones and the cyclic lipopeptides, have entered the market since the late 1960s. Few new agents have reached the market in the last decade with potential interest for community-acquired pneumonia (CAP) treatment, including linezolid (the first oxazolidinone in clinical use), new fluoroquinolones, cefditoren, ertapenem, and telithromycin. Agents currently in clinical development include other novel quinolones and ketolides, broad-spectrum cephalosporin derivatives, faropenem, several glycopeptides, and iclaprim. Other molecules are considered to be promising candidates for the future. In addition to the foregoing agents, alternative treatment approaches have also been introduced into clinical practice, which include the administration of the appropriate antimicrobials in a timely manner and the consideration of the pharmacokinetic-pharmacodynamic properties of the agent(s).

Topics: Acetamides; Anti-Infective Agents; beta-Lactams; Cephalosporins; Community-Acquired Infections; Drug Design; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Ertapenem; Fluoroquinolones; Humans; Ketolides; Linezolid; Lipopeptides; Oxazolidinones; Pneumonia, Bacterial; Practice Guidelines as Topic

The purpose of this review is to assess the benefits and risks associated with the use of the ketolide antibacterial telithromycin, currently licensed for the treatment of adults with mild to moderate community-acquired pneumonia (CAP). Telithromycin is active against both the major (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) and atypical/intracellular (Chlamydophila pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae) CAP pathogens. It is associated with a low potential to select for resistance and has maintained its in vitro activity against isolates of respiratory pathogens in countries where it has been in clinical use for several years. In randomized clinical trials, telithromycin has demonstrated efficacy comparable to the established antibacterial classes (macrolides, fluoroquinolones and beta-lactams) in the treatment of CAP.The safety profile of telithromycin is broadly similar to that of other antibacterials used to treat CAP. The most common adverse events are gastrointestinal adverse effects and headache; these are generally mild to moderate in severity and reversible. Telithromycin appears to be well tolerated by adult patients in all age groups, including those with co-morbid conditions. In common with other antibacterials, telithromycin has the potential to affect the corrected QT interval; the concomitant use of cisapride or pimozide with telithromycin is contraindicated, while telithromycin should be avoided in patients receiving Class IA or Class III antiarrhythmic drugs. Visual disturbances (usually transient) have occurred in a small proportion of patients treated with telithromycin; it is recommended that activities such as driving are minimized during treatment. Telithromycin is contraindicated in patients with myasthenia gravis. Hepatic dysfunction may occur in some patients taking telithromycin; rare cases of acute hepatic failure and severe liver injury, including deaths, have been reported. As telithromycin is an inhibitor of the cytochrome P450 (CYP) 3A4 system, coadministration of telithromycin with drugs metabolized by this pathway may require dose adjustments (e.g. with benzodiazepines) or a temporary hiatus in the use of the coadministered drug (e.g. HMG-CoA reductase inhibitors) metabolized by CYP3A4. Telithromycin may potentiate the effects of oral anticoagulants; careful monitoring is recommended in patients receiving telithromycin and oral anticoagulants simultaneously.Although s

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Drug Interactions; Humans; Ketolides; Pneumonia, Bacterial; Risk Assessment

This retrospective analysis was performed to determine the clinical and bacteriologic efficacy of the ketolide antibacterial telithromycin in patients with community-acquired pneumonia (CAP) with pneumococcal bacteremia. Patients 13 years old with radiologically confirmed CAP and a positive blood culture for Streptococcus pneumoniae at screening were analyzed from eight multicenter Phase III/IV clinical trials. In four open-label, non-comparative studies, patients received telithromycin 800 mg once daily for 7-10 days. In four randomized, controlled, double-blind, comparative studies, patients received telithromycin 800 mg once daily for 5-10 days or a comparator antimicrobial (amoxicillin 1000 mg three times daily, clarithromycin 500 mg twice daily, or trovafloxacin 200 mg once daily) for 7-10 days. In total, 118 patients (telithromycin, 94/1061 [8.9%]; comparator, 24/244 [9.8%]) had documented pneumococcal bacteremia. Those who were treated with telithromycin achieved a clinical cure rate of 90.2% (74/82, per-protocol population); S. pneumoniae was eradicated in 77/82 (93.9%) bacteremic patients who received telithromycin and 15/19 (78.9%) comparator-treated patients. Clinical cure was also observed among telithromycin-treated bacteremic patients who were infected with penicillin- or erythromycin-resistant strains of S. pneumoniae (5/7 and 8/10, respectively). In conclusion, telithromycin achieves high clinical and bacteriologic cure rates in CAP patients with pneumococcal bacteremia.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Clinical Trials, Phase IV as Topic; Community-Acquired Infections; Female; Humans; Ketolides; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Retrospective Studies

This review discusses the clinicoradiological findings of community-acquired respiratory infections and the treatment strategy for respiratory infections. To make a differential diagnosis between bacterial pneumonia, pneumonia caused by atypical pathogens, and mycobacterial infections, it is very important to analyze the radiological findings of inflammatory lung diseases based on normal antomical structures. If clinicoradiological anlyses could make these differentiations, the appropriate treatment strategy for respiratory infections could be established. To accomplish this, exact orientations of pulmonary lobulus, acinus, and respiratory bronchioles is very important. Then, through analyzing chest CT findings and distribution patterns based on normal anatomical structures, estimation of causative pathogens could be possible. Especially, whether inflammatory exudates could pass Kohn's pores as well as Lambert's channel or not is very important factor to affect radiological findings of several pneumonia (as traditionally called "segmental" and "nonsegmental" distribution). To differentiate infections caused by Mycobacterium tuberculosis from nontuberculous mycobacteria, several important criteria have been demonstrated. Briefly, it has been suggested that Mycobacterium avium complex (MAC) respiratory infection is increasing especially in elderly women without underlying diseases. In MAC respiratory infection, right middle lobe and left lingula are frequently involved and centrilobular nodules and diffuse bronchiectases are characteristic radiological findings. Finally, the role of telithromycin in the treatment of respiratory infections is discussed.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Diagnosis, Differential; Humans; Ketolides; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Pneumonia, Bacterial; Radiography, Thoracic; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Bronchitis; Clinical Trials as Topic; Humans; Ketolides; Macrolides; Pharyngitis; Pneumonia, Bacterial; Respiratory Tract Infections; Sinusitis; Tonsillitis

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Community-Acquired Infections; Gram-Positive Bacteria; Humans; Ketolides; Macrolides; Pneumonia, Bacterial; Streptococcus pneumoniae

The efficacy of telithromycin has been assessed in six Phase III studies involving adults with mild to moderate community-acquired pneumonia (CAP) with a degree of severity compatible with oral therapy. Patients received telithromycin 800 mg once daily for 7-10 days in three open-label studies (n=870) and three randomized, double-blind, comparator-controlled studies (n=503). Comparator antibacterials were amoxicillin 1000 mg three-times daily, clarithromycin 500 mg twice daily and trovafloxacin 200 mg once daily. Clinical and bacteriological outcomes were assessed 7-14 days post-therapy. Among telithromycin-treated patients, per-protocol clinical cure rates were 93.1 and 91.0% for the open-label and comparative studies, respectively. Telithromycin treatment was as effective as the comparator agents. High eradication and clinical cure rates were observed for infections caused by key pathogens: Streptococcus pneumoniae including isolates resistant to penicillin G and/or erythromycin A (95.4%), Haemophilus influenzae (89.5%) and Moraxella catarrhalis (90%). Telithromycin was also highly effective in patients with infections caused by atypical and/or intracellular pathogens and those at increased risk of morbidity. Telithromycin was generally well tolerated. Telithromycin 800 mg once daily for 7-10 days offers a convenient and well-tolerated first-line oral therapy for the empirical treatment of mild to moderate CAP.

Topics: Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Infective Agents; Clarithromycin; Clinical Trials, Phase III as Topic; Community-Acquired Infections; Double-Blind Method; Fluoroquinolones; Humans; Ketolides; Macrolides; Naphthyridines; Penicillins; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Treatment Outcome

Community-acquired pneumonia (CAP) is a common disorder that has been the focus of a major international research effort to define its epidemiology, etiology and management. The microbial etiology of CAP is complex and severity assessment is important in identifying at-risk populations as well as defining therapeutic strategies. Laboratory investigations rarely influence initial therapy, which remains empirical. Guidelines have been developed in many countries in response to the need to optimize management and outcomes. However, many of these guidelines have been based on expert opinion rather than robust evidence. New evidence-based guidelines have been developed that take into account disease severity, the local distribution of pathogens and their likely susceptibility to antimicrobials, and that include newer treatment options. Macrolide and fluoroquinolone antimicrobials feature heavily in these new treatment recommendations. Promising new therapies continue to emerge that may offer advantages over fluoroquinolones and macrolides, in particular with regard to the problem of resistance. Of these, the ketolides are of special interest. Telithromycin, the first ketolide antibacterial, has been evaluated in the treatment of > 700 patients with CAP. A once-daily oral dose of telithromycin 800 mg for 7-10 days produces clinical and bacteriological success rates > 90% and equivalent to standard comparator agents, whilst maintaining efficacy against resistant pathogens.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Community-Acquired Infections; Female; Fluoroquinolones; Humans; Ketolides; Macrolides; Male; Middle Aged; Pneumonia, Bacterial; Practice Guidelines as Topic

The pharmacodynamics of telithromycin, a new ketolide antibacterial, was examined in 115 patients with community-acquired pneumonia (CAP). Patients received telithromycin 800 mg qd for 7-10 days. Pharmacokinetic parameters were determined, and exposure was linked to microbiological outcome using logistic regression analysis. A breakpoint for increased probability of microbiological eradication was developed and was found to be the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) of 3.375. The final logistic regression model of microbiological outcome included body weight and AUC/MIC ratio breakpoint. This model was found in analyses of the entire population and when Streptococcus pneumoniae and Haemophilus influenzae were examined separately. The AUC/MIC ratio target attainment rate is expected to be >99.9% for S. pneumoniae and Moraxella catarrhalis and 93.1% for H. influenzae. This study demonstrated a relationship between telithromycin drug exposure and microbiological outcome. Telithromycin is expected to achieve the drug exposure breakpoint for the majority of isolates causing CAP.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Haemophilus influenzae; Humans; Ketolides; Microbial Sensitivity Tests; Moraxella catarrhalis; Pneumonia, Bacterial; Streptococcus pneumoniae; Treatment Outcome

Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality throughout the world. Telithromycin (a new ketolide) has shown good in vitro activity against the key causative pathogens of CAP, including S pneumoniae resistant to penicillin and/or macrolides.. The efficacy and safety of telithromycin 800 mg orally once daily for 7 days in the treatment of CAP were assessed in an open-label, multicenter study of 442 adults.. Of 149 microbiologically evaluable patients, 57 (9 bacteremic) had Streptococcus pneumoniae. Of the 57 S pneumoniae pathogens isolated in these patients, 9 (2 bacteremic) were penicillin- or erythromycin-resistant; all 57 were susceptible to telithromycin and were eradicated. Other pathogens and their eradication rates were: Haemophilus influenzae (96%), Moraxella catarrhalis (100%), Staphylococcus aureus (80%), and Legionella spp. (100%). The overall bacteriologic eradication rate was 91.9%. Of the 357 clinically evaluable patients, clinical cure was achieved in 332 (93%). In the 430 patients evaluable for safety, the most common drug-related adverse events were diarrhea (8.1%) and nausea (5.8%).. Telithromycin 800 mg once daily for 7 days is an effective and well-tolerated oral monotherapy and offers a new treatment option for CAP patients, including those with resistant S pneumoniae.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Community-Acquired Infections; Female; Humans; Ketolides; Male; Middle Aged; Pneumonia, Bacterial; Time Factors

To compare hospitalization rates among patients with community-acquired pneumonia (CAP) treated with oral telithromycin and clarithromycin, based on pooled data from two randomized, double-blind, multinational clinical trials.. Adult patients with CAP eligible for oral therapy (Study 1, n = 448; Study 2, n = 575) received telithromycin 800 mg once daily for 10 (Study 1, 2-arms), 5 or 7 (Study 2, 3-arms) days, or clarithromycin 500 mg twice daily for 10 days. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use, as well as CAP-related length of hospital stay and hospitalization costs, were compared by treatment group (intent to treat populations) up until the late post-therapy visit (Days 31-36). Study investigators blinded to treatment regimen assessed whether hospital admissions were CAP related.. Despite equivalent clinical efficacy for telithromycin vs clarithromycin in the clinically evaluable per-protocol populations (n = 784) (88.8% [428/482] vs 90.1% [272/302]--difference: -1.3%; 95% CI: -6.0, 3.4), telithromycin treatment for 5, 7, or 10 days was associated with significantly fewer CAP-related hospitalizations (p = 0.023) and CAP-related hospital days (p = 0.025) vs clarithromycin (reduction of 2.3 hospitalizations and 23.4 hospital days per 100 patients). Accordingly, estimated CAP-related hospitalization costs were significantly lower (p = 0.025) for telithromycin recipients (30,231 US dollars less per 100 patients). CAP-related hospitalizations, duration of hospital stay, and hospitalization costs for 7- to 10-day telithromycin--the approved dosing regimen for CAP--were significantly lower (p = 0.023, 0.025, and 0.025, respectively) than for clarithromycin.. Data from this study indicate that telithromycin 800 mg once daily for 5, 7, or 10 days provides an effective therapy for patients with CAP, and may be associated with fewer CAP-related hospitalizations and hospital days than clarithromycin 500 mg twice daily for 10 days. Treatment with telithromycin could, therefore, potentially translate into cost savings in the management of CAP.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clarithromycin; Community-Acquired Infections; Double-Blind Method; Female; Hospitalization; Humans; Ketolides; Macrolides; Male; Middle Aged; Pneumonia, Bacterial

This randomized, double-blind study compared the efficacy and tolerability of the new ketolide antimicrobial telithromycin with that of high-dose amoxicillin in the treatment of community-acquired pneumonia (CAP).. Adult patients (n = 404), with signs and symptoms of CAP and radiologic confirmation were randomized to receive telithromycin 800 mg once daily (n = 199) or amoxicillin 1,000 mg three times a day (n = 205) for 10 days. Clinical and bacteriologic outcomes were assessed at post-therapy test-of-cure (days 17-24) and late post therapy (days 31-36).. The clinical cure rate for telithromycin-treated patients (per protocol) pst therapy (days 17-24) was 141/149 (94.6%) and compared well with that for amoxicillin (137/152 (90.1%)). Subset analysis of patients (per protocol) showed high clinical cure rates for patients aged >/= 65 years (telithromycin 21/24, 87.5%; amoxicillin 22/29, 75.9%); those with documented pneumococcal bacteremia (telithromycin 10/10, 100%; amoxicillin 7/9, 77.8%); and patients with a Fine score >/= III (telithromycin 31/34, 91.2%; amoxicillin 38/47, 80.9%). Bacterial eradication rates were comparable between treatments (telithromycin 42/48, 87.5%; amoxicillin 39/45, 86.7%), with 22/23 vs 18/21 Streptococcus pneumoniae strains 9/12 vs 11/13 Haemophilus influenzae strains and all Moraxella catarrhalis isolates (five and three patients, respectively) eradicated at the test-of-cure visit. Both treatments were generally well tolerated.. Telithromycin 800 mg once daily is a convenient, optimal-spectrum, first-line treatment for CAP in adults, at least as effective and well tolerated as high-dose amoxicillin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Community-Acquired Infections; Double-Blind Method; Drug Administration Schedule; Female; Humans; Ketolides; Macrolides; Male; Middle Aged; Pneumonia, Bacterial

Telithromycin, the first ketolide antibacterial, was developed for the treatment of community-acquired respiratory tract infections. This multicenter, open-label, uncontrolled study assessed the efficacy and safety of 800 mg, once-daily telithromycin in adults with community-acquired pneumonia (CAP). Based on bacteriologic eradication rates, telithromycin was shown to be effective for the treatment of CAP. Telithromycin was generally well tolerated, with gastro-intestinal adverse events observed most frequently (diarrhea 4/218 [1.8%], nausea 4/218 [1.8%], vomiting 5/218 [2.3%]). These results were consistent with those observed in randomized, active-controlled studies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Community-Acquired Infections; Female; Humans; Ketolides; Macrolides; Male; Middle Aged; Pneumonia, Bacterial; Treatment Outcome

We present here the novel ketolide RBx 14255, a semisynthetic macrolide derivative obtained by the derivatization of clarithromycin, for its in vitro and in vivo activities against sensitive and macrolide-resistant Streptococcus pneumoniae. RBx 14255 showed excellent in vitro activity against macrolide-resistant S. pneumoniae, including an in-house-generated telithromycin-resistant strain (S. pneumoniae 3390 NDDR). RBx 14255 also showed potent protein synthesis inhibition against telithromycin-resistant S. pneumoniae 3390 NDDR. The binding affinity of RBx 14255 toward ribosomes was found to be more than that for other tested drugs. The in vivo efficacy of RBx 14255 was determined in murine pulmonary infection induced by intranasal inoculation of S. pneumoniae ATCC 6303 and systemic infection with S. pneumoniae 3390 NDDR strains. The 50% effective dose (ED50) of RBx 14255 against S. pneumoniae ATCC 6303 in a murine pulmonary infection model was 3.12 mg/kg of body weight. In addition, RBx 14255 resulted in 100% survival of mice with systemic infection caused by macrolide-resistant S. pneumoniae 3390 NDDR at 100 mg/kg four times daily (QID) and at 50 mg/kg QID. RBx 14255 showed favorable pharmacokinetic properties that were comparable to those of telithromycin.

Topics: Animals; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Bacterial; Ketolides; Male; Mice; Microbial Sensitivity Tests; Pneumonia, Bacterial; Protein Synthesis Inhibitors; Ribosomes; Sepsis; Streptococcus pneumoniae; Survival Analysis

A case of Salmonella paratyphi A infection was diagnosed late in a patient treated for febrile pneumonia after his returning from India. This case was remarkable in two aspects: first, it illustrated the reemergence of S.paratyphi A infections in people having traveled to India, with increasing fluoroquinolone resistance, and second the difficulty of diagnosing this disease, since the patient was initially treated for pneumonia and flu-like syndrome. Salmonella typhi or paratyphi infections should be evoked in case of persistent fever in patients having traveled to endemic areas, even if digestive signs are absent. Furthermore, choosing an empiric antibiotic treatment with fluoroquinolones could lead to treatment failure if the patient traveled in a country where fluoroquinolone resistance is high, as in Asia and especially in India.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bangladesh; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Endemic Diseases; Fluoroquinolones; Humans; India; Ketolides; Male; Paratyphoid Fever; Pneumonia, Bacterial; Salmonella paratyphi A; Travel

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

Telithromycin (Ketek) was approved in April 2004 for the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB), bacterial sinusitis, and community-acquired pneumonia. The approval of telithromycin was controversial due to trial irregularities, noninferiority study designs, and use of foreign safety data. Safety concerns involving hepatotoxicity, myasthenia gravis exacerbation, and visual disturbances were increasingly documented in the literature after approval. On February 12, 2007, the U.S. Food and Drug Administration (FDA) removed the bacterial sinusitis and ABECB indications and strengthened safety warnings for telithromycin.. To (1) assess the prevalence and distribution of on-label telithromycin utilization before and after the revisions of the product label and (2) assess the association of pivotal events in the life cycle of telithromycin with its use as reflected in pharmacy and medical claims.. Using retrospective administrative medical and pharmacy claims from a large midwestern commercial insurer with an eligible membership of 1.8 million members, individuals with a telithromycin claim during January 1, 2007, through April 13, 2007, were identified. Their medical claims within 30 days prior to or on the initial telithromycin claim were analyzed for the presence of an on-label diagnosis code. Monthly telithromycin and clarithromycin claim totals per million members from January 2004 through March 2007 were calculated. Claim totals were plotted to identify utilization trends in relation to the FDA health advisory for telithromycin on January 20, 2006, and the telithromycin label changes on February 12, 2007.. The medical diagnosis analysis consisted of 507 members with 1 or more medical claims with dates of service within 30 days of at least 1 pharmacy claim for telithromycin. Using the original approved telithromycin indications, 52.3% (256 of 507) of telithromycin use was on-label. The most common on-label diagnoses were sinusitis (33.9%) and bronchitis (14.4%). A diagnosis of pneumonia was present for 3.9% of telithromycin utilizers. After the February 12, 2007, label change limiting telithromycin to community-acquired pneumonia, on-label use was 6.7% (12 of 179) of utilizers. Telithromycin claims were first detected in August 2004 and overtook the clarithromycin rate of 729 claims per million members in January 2005, reaching a peak rate of 940 claims per million members in January 2006. Telithromycin monthly claims remained higher than clarithromycin until April 2006, 3 months after the liver toxicity health advisory. In comparison with January 2006, the January 2007 telithromycin claims were 186 claims per million members, a decrease of 80%.. Despite revised FDA indications and safety warnings, fewer than 1 in 15 active telithromycin users have a medical claim consistent with the only currently approved indication (pneumonia). Pharmacy claims for telithromycin dropped substantially following reports of severe hepatotoxicity and strengthened safety warnings. The high prevalence of telithromycin off-label use despite hepatotoxicity and other safety risks is cause for continued concern.

Topics: Anti-Bacterial Agents; Bronchitis, Chronic; Community-Acquired Infections; Drug Approval; Drug Labeling; Drug Utilization Review; Humans; Insurance Claim Reporting; Ketolides; Pneumonia, Bacterial; Retrospective Studies; Risk Assessment; Sinusitis; United States; United States Food and Drug Administration

Topics: Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Community-Acquired Infections; Drug Labeling; Humans; Insurance Claim Reporting; Ketolides; Liver Failure; Patient Care Team; Pneumonia, Bacterial; United States; United States Food and Drug Administration

Legionella species have been widely recognized as among the important causative organisms of community-acquired pneumonia in Japan. A delay in the start of adequate treatment has a negative influence on the outcome of the disease. Telithromycin, the first oral ketolide antibacterial, was developed for the treatment of community-acquired pneumonia, including Legionella pneumonia. However, few reports have indicated the efficacy of telithromycin in community-acquired pneumonia caused by Legionella species. We report three cases of Legionella pneumonia, that were improved by early telithromycin therapy. The first patient (67-year-old man) had bronchiectasis as an underlying disease, and the second patient (73-year-old man) had diabetes mellitus and chronic renal failure. The third patient (62-year-old man) developed pneumonia after a spa tour. The diagnosis of Legionella pneumonia was made on the basis of the presence of a single IgG titer of 1/256 in case 1 and positive antigenuria in cases 2 and 3. The patients were classified into a mild group (case 1) and a moderate group (cases 2 and 3) based on the severity of the community-acquired pneumonia according to the 2005 Japanese Respiratory Society Guidelines. The results support the efficacy of telithromycin in mild to moderate Legionella pneumonia.

Topics: Aged; Anti-Bacterial Agents; Humans; Ketolides; Legionnaires' Disease; Male; Middle Aged; Pneumonia, Bacterial

Topics: Aged; Anti-Bacterial Agents; Community Health Nursing; Community-Acquired Infections; Drug Interactions; Female; Humans; Ketolides; Nurse's Role; Nursing Assessment; Pneumonia, Bacterial

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

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

This open, multinational study examined the efficacy and tolerability of telithromycin (HMR 3647), the first ketolide antibacterial agent, at an oral dose of 800 mg once daily for seven to ten days (further validated using pharmacokinetic analysis) as an empiric therapy in adults with mild to moderate community-acquired pneumonia (CAP).. A total of 240 patients (aged 18-79 years; median 40 years) with clinical signs and symptoms of CAP (radiologically confirmed) were enrolled in the study and received at least one dose of study medication. Sputum and blood samples for bacteriologic documentation were collected within 48 h prior to enrollment. Clinical and bacteriological outcomes were assessed 17-21 days (test of cure visit) and 31-36 days (late post-therapy visit) after treatment initiation. Adverse events were assessed by spontaneous reporting and investigator observation.. At the test of cure visit, 92.9% (95% CI: 88.4-96.1; n= 197) of patients achieved clinical cure in the per-protocol (PP) population. In the modified intent-to-treat (mITT) population, the cure rate was 79.6% (95% CI: 73.9-84.5; n= 240), including 12.5% of undetermined cases categorized as failures. Clinical cure (PP population) remained high in patients >/=65 years (85.7%), and in patients with a Fine score >/=III (92.1%). Among those patients for whom bacteriologic data were available, the majority had a satisfactory outcome (88.9% in the bacteriologic PP; n= 45). Bacterial eradication rates were similarly high (85.5% and 82.7% for the mITT and PP populations, respectively). All patients with infections as a result of atypical/intracellular pathogens Chlamydophila (Chlamydia) pneumoniae, Mycoplasma pneumoniae or Legionella pneumophila had a clinical outcome of cure. Treatment was well tolerated. Adverse events were mainly gastrointestinal in origin and mild in intensity.. An oral dose of telithromycin 800 mg once daily for seven to ten days is an effective and well-tolerated first-line treatment for mild to moderate CAP in adults.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Dose-Response Relationship, Drug; Female; Humans; Ketolides; Macrolides; Male; Middle Aged; Pneumonia, Bacterial

We studied the efficacy of telithromycin in Haemophilus influenzae pneumoniae in three different age groups of mice. Pneumonia was produced by endotracheal instillation of 1 x 10(4) CFU/ml of bacteria and treatment was initiated with saline for control and compared with two different doses, 50 and 100 mg/kg per BID telithromycin twice a day for 1 week. For comparison, we used erythromycin (ERY) and clarithromycin (CLA), both given twice a day at 50 mg/kg per BID. Some animals were euthanized on the third or 7th day of therapy and their lung tissue was cultured for bacteria. Presence of bacteria was considered a failure and a sterile lung was considered cured. As expected, about one half of middle-aged animals (8-10 months) were cured on saline. In contrast, almost none of the young (2-3 weeks) and old animals (18-20 months) were cured without antibiotic therapy. Among the young, the cure rates with telithromycin, ERY and CLA were 81, 50 and 33%, respectively. Of the senescent mice, the cure rate with ERY was 50% whereas the rates with CLA and telithromycin (50 mg/kg) were 62 and 75%, respectively. In conclusion, telithromycin is effective against H. influenzae at both extremes of life.

Topics: Aging; Animals; Animals, Suckling; Anti-Bacterial Agents; Area Under Curve; Clarithromycin; Drug Administration Schedule; Drug Evaluation, Preclinical; Erythromycin; Haemophilus influenzae; Ketolides; Lung; Macrolides; Mice; Pneumonia, Bacterial; Tissue Distribution

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

Telithromycin is the first member of a new family of the macrolide-lincosamide-streptogramin-B (MLS(B)) class of antimicrobials, the ketolides. It has a good spectrum of activity against respiratory pathogens, including penicillin- and erythromycin-resistant pneumococci, as well as intracellular and atypical bacteria. Furthermore, it has a low potential to select for resistance or induce cross-resistance among other MLS(B) antimicrobials. At the recommended dosage of 800 mg orally once daily, telithromycin reaches maximal plasma concentrations of about 2 mg/L. It penetrates rapidly into bronchopulmonary, tonsillar, sinus and middle ear tissues and/or fluids and achieves high concentrations at sites of infection. It also concentrates within polymorphonuclear neutrophils. In clinical trials in patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) or pharyngitis/tonsillitis caused by group A beta-haemolytic streptococci, telithromycin 800 mg once daily achieved clinical cure rates of 86 to 95%. In acute maxillary sinusitis (AMS), cure rates were 73 to 91%. A 7- to 10-day regimen of telithromycin was as effective as a 10-day course of amoxicillin 1000 mg 3 times daily, clarithromycin 500 mg twice daily or a 7- to 10-day course of trovafloxacin 200 mg once daily for treating CAP. A 5-day regimen of telithromycin was as effective as a 10-day regimen of cefuroxime axetil 500 mg twice daily or amoxicillin/clavulanic acid 500/125 mg 3 times daily in AECB. A 5-day regimen of telithromycin was as effective as a 10-day regimen of clarithromycin 250 mg twice daily or phenoxymethylpenicillin 500 mg 3 times daily in pharyngitis/tonsillitis, or a 10-day regimen of amoxicillin/clavulanic acid 500/125 mg 3 times daily in patients with AMS. Telithromycin was well tolerated across all patient populations. Adverse events associated with telithromycin were generally mild to moderate in intensity and seldom led to treatment discontinuation. The most frequent adverse events were diarrhoea (13.3%) and nausea (8.1%). Other adverse events included dizziness and vomiting.

Topics: Anti-Bacterial Agents; Bronchitis; Clinical Trials as Topic; Drug Interactions; Humans; Ketolides; Macrolides; Maxillary Sinusitis; Pharyngitis; Pneumonia, Bacterial

The MICs of HMR 3004 and HMR 3647 at which 90% of beta-lactamase-producing Haemophilus influenzae isolates were inhibited were 4 and 2 micrograms/ml, respectively. Both HMR 3004 and HMR 3647 were active against beta-lactamase-producing H. influenzae in a murine model of experimental pneumonia. As assessed by pulmonary clearance of H. influenzae, HMR 3004 was more effective (P < 0.05) than was azithromycin, ciprofloxacin, clarithromycin, erythromycin A, pristinamycin, or HMR 3647 in this model.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Colony Count, Microbial; Drug Resistance, Microbial; Haemophilus Infections; Haemophilus influenzae; Humans; Ketolides; Macrolides; Mice; Mice, Inbred C57BL; Pneumonia, Bacterial