Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023241 (Legionella)
6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selection of therapy for legionella infections originated with the clinical observation after the 1976 Philadelphia outbreak that patients treated with erythromycin or tetracycline did better than those who received cephalosporins or aminoglycosides. Early in vitro antibiotic susceptibility studies suggested that rifampin and erythromycin were both active against Legionella pneumophila. However, subsequent in vitro susceptibility studies to other antibiotics have produced variable results, depending on the medium and methodology used. Antibiotic studies within polymorphonuclear leukocytes and alveolar macrophages indicate that those actively concentrated within these cells are predictive of successful therapy. These include erythromycin, rifampin, and certain quinolones. On the other hand, beta-lactam antibiotics such as penicillin, cefoxitin, and imipenem are less likely to be successful because of their lack of concentration within phagocytes. These observations have been confirmed in animal model studies where erythromycin, rifampin, and quinolones have demonstrated efficacy. The addition of rifampin to erythromycin or to doxycycline may be more effective than therapeutic results with either antibiotic alone. Although erythromycin is presently the treatment of choice for legionellosis, the addition of rifampin is recommended, particularly in immunocompromised patients. Doxycycline has served as an appropriate alternative agent, the newer quinolones may be useful and are deserving of carefully designed clinical trials.
...
PMID:Therapeutic considerations in the treatment of Legionella infections. 332 98

The activities of tetracycline, doxycycline and minocycline against Legionella pneumophila strain Philadelphia-1 were compared in vitro, in peritoneal macrophages and in-vivo experiments in guinea-pigs. Minocycline was the most effective in in-vitro minimum inhibitory concentration assays. In the assay measuring inhibitory effects of drugs on intracellular bacterial multiplication, minocycline and doxycycline were equally effective and tetracycline was the least effective of the three. In-vivo experiments were carried out using guinea-pigs infected intraperitoneally. From the analysis of cumulative survival rates, only minocycline had statistically significant effects. Doxycycline, however, did significantly prolong the infected animals' survival days. These data lend some support to the case reports showing that tetracycline derivatives are effective in the treatment of Legionnaires' disease.
...
PMID:Effects of tetracyclines on experimental Legionella pneumophila infection in guinea-pigs. 406 57

The chemistry, mode of action, antimicrobial activity, pharmacokinetics, and therapeutic efficacy of doxycycline are reviewed. Doxycycline displays excellent activity against gram-positive and gram-negative aerobic and anaerobic pathogens. The oral absorption of doxycycline is rapid and virtually complete and is not significantly decreased by food. Moreover, serum concentrations of doxycycline following oral and intravenous (i.v.) administration are comparable. Because of the prolonged half-life of doxycycline, once daily administration is possible. Tissue penetration of doxycycline is excellent. Levels within the therapeutic range have been found in most organs and tissues, including kidney, lung, gallbladder, prostate, intestinal tract, myocardium, sinus secretions, tonsil, aqueous humor, and female reproductive tissue. Doxycycline does not accumulate in patients with renal insufficiency and is not removed from the blood to any great extent during hemodialysis. Extensive clinical investigation has shown doxycycline to be highly effective in infections of the respiratory tract, including atypical pneumonias; skin and soft tissue; genitourinary infection including gonorrhea, syphilis, nonspecific urethritis, and prostatitis; intraabdominal infection due to trauma, sepsis, or surgery; and cholera. Evidence also suggests that doxycycline will prove effective in the treatment of Legionnaires' disease. In addition, placebo-controlled clinical trials suggest doxycycline is effective in the prevention of traveler's diarrhea.
...
PMID:Doxycycline. 704 45

Pneumonias caused by atypical organisms usually have extra-pulmonary features. Chlamydial pneumonia often starts with hoarseness and fever, and respiratory tract symptoms may not appear for days. Mycoplasmal pneumonia may manifest with ear pain and a nonproductive cough. Legionnaires' disease presents with high fevers and central nervous system and gastrointestinal abnormalities. Diagnosis of chlamydial infection is accomplished with serologic testing. Patients are unresponsive to erythromycin treatment and should be started on empirical doxycycline (Doryx, Vibramycin) therapy. The presence of cold agglutinins in the appropriate clinical setting permits a presumptive diagnosis of mycoplasmal infection. Clinical diagnosis of Legionella pneumonia may be made in patients with pneumonia who also have relative bradycardia with elevated serum transaminases or hypophosphatemia with gastrointestinal or central nervous system symptoms. Erythromycin is the mainstay of treatment of legionnaires' disease, but treatment failures have been reported. Doxycycline is less expensive, has a better safety profile, and is better tolerated than erythromycin.
...
PMID:Atypical pneumonias. Clinical and extrapulmonary features of Chlamydia, Mycoplasma, and Legionella infections. 849 98

Erythromycin has been the most commonly used drug for the treatment of legionnaires' disease; however, failures have occurred and adverse effects are common. Doxycycline intravenously is preferred and is less expensive. The newer macrolides/azalides, clarithromycin and azithromycin, have excellent in vitro activity against Legionella and fewer adverse effects than erythromycin. The fluoroquinolones, particularly levofloxacin, are the most active anti-Legionella antibiotics available. Other agents with activity against Legionella pneumophila include minocycline, rifampin, and trimethoprim-sulfamethoxazole. The preferred therapy of legionellosis in immunocompromised patients are quinolone/macrolide combinations, eg, levofloxacin plus azithromycin.
...
PMID:Treatment of legionnaires' disease. 964 92

Atypical organisms such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila are implicated in up to 40 percent of cases of community-acquired pneumonia. Antibiotic treatment is empiric and includes coverage for both typical and atypical organisms. Doxycycline, a fluoroquinolone with enhanced activity against Streptococcus pneumoniae, or a macrolide is appropriate for outpatient treatment of immunocompetent adult patients. Hospitalized adults should be treated with cefotaxime or ceftriaxone plus a macrolide, or with a fluoroquinolone alone. The same agents can be used in adult patients in intensive care units, although fluoroquinolone monotherapy is not recommended; ampicillin-sulbactam or piperacillin-tazobactam can be used instead of cefotaxime or ceftriaxone. Outpatient treatment of children two months to five years of age consists of high-dose amoxicillin given for seven to 10 days. A single dose of ceftriaxone can be used in infants when the first dose of antibiotic is likely to be delayed or not absorbed. Older children can be treated with a macrolide. Hospitalized children should be treated with a macrolide plus a beta-lactam inhibitor. In a bioterrorist attack, pulmonary illness may result from the organisms that cause anthrax, plague, or tularemia. Sudden acute respiratory syndrome begins with a flu-like illness, followed two to seven days later by cough, dyspnea and, in some instances, acute respiratory distress.
...
PMID:Atypical pathogens and challenges in community-acquired pneumonia. 1508 42