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

Macrolide antibiotics have been available and used clinically since 1952. The class of drugs originated from a soil sample obtained from the City of Ilo-Ilo on the Island of Paray in the Philippines. Erythromycin has been the most widely used agent of this class called 'macrolides' because they possess the macrocyclic lactone nucleus. Many esters of erythromycin are well established as agents to treat a variety of respiratory and cutaneous infections, particularly in children. There has been a resurgence of interest in macrolides as a result of the recognition of pathogens such as Legionella, Chlamydia and Campylobacter spp. A number of new 14-membered macrolides have been synthesised in recent years with the goal of overcoming some of the problems of the older erythromycin agents. There has been variable activity of erythromycin against Haemophilus influenzae; there has been gastrointestinal irritation, particularly in adults; and the older agents are administered four times a day. Clarithromycin has increased activity against Legionella, and Branhamella spp., and Pasteurella multocida, and, with its 14-OH metabolite, inhibits Haemophilus spp. It is also more active against chlamydia and against anaerobic species while retaining excellent activity against streptococci including Streptococcus pneumoniae. It has increased plasma peak levels and a sufficiently long half-life for twice daily administration. Furthermore, it is well tolerated. Thus clarithromycin offers potential for use in those areas in which a safe, well tolerated macrolide will be used, namely respiratory, skin structure and selected diarrhoeal and genital infections.
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PMID:The development of macrolides: clarithromycin in perspective. 182 94

Analogs of 9-deoxo-12-deoxy-9,12-epoxyerythromycin A with an epimeric hydroxy, amino, or ketone substitution at the 11 position of the macrolide ring and an amino or epimeric hydroxy substitution at the 4" position of the cladinose sugar were synthesized in an attempt to produce acid-stable derivatives of erythromycin with improved bioavailability and activity against gram-negative bacteria. These modifications produced compounds with in vitro activities which were generally similar to that of erythromycin. In mice, however, selected analogs were more active than was erythromycin against staphylococci, streptococci, Haemophilus influenzae, and Legionella pneumophila. In mice, the 11-keto (A-63881), 11-epiamino (A-69334), 11-epiamino-4"-amino (A-71671), and 11-epiamino-4"-epiamino (A-73020) analogs achieved peak concentrations in serum and lung, serum half-lives, and/or areas under the serum curve which were greater than those of erythromycin. Improved pharmacokinetics, as compared with those of erythromycin, may explain the increased in vivo antibacterial activities of these compounds.
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PMID:In vitro activity and in vivo efficacy of a new series of 9-deoxo-12-deoxy-9,12-epoxyerythromycin A derivatives. 185 73

A genomic library of Legionella pneumophila, the causative agent of Legionnaires disease in humans, was constructed in Escherichia coli K-12, and the recombinant clones were screened by immuno-colony blots with an antiserum raised against heat-killed L. pneumophila. Twenty-three clones coding for a Legionella-specific protein of 19 kDa were isolated. The 19-kDa protein, which represents an outer membrane protein, was found to be associated with the peptidoglycan layer both in L. pneumophila and in the recombinant E. coli clones. This was shown by electrophoresis and Western immunoblot analysis of bacterial cell membrane fractions with a monospecific polyclonal 19-kDa protein-specific antiserum. The protein was termed peptidoglycan-associated protein of L. pneumophila (Ppl). The corresponding genetic determinant, ppl, was subcloned on a 1.8-kb ClaI fragment. DNA sequence studies revealed that two open reading frames, pplA and pplB, coding for putative proteins of 18.9 and 16.8 kDa, respectively, were located on the ClaI fragment. Exonuclease III digestion studies confirmed that pplA is the gene coding for the peptidoglycan-associated 19-kDa protein of L. pneumophila. The amino acid sequence of PplA exhibits a high degree of homology to the sequences of the Pal lipoproteins of E. coli K-12 and Haemophilus influenzae.
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PMID:Cloning, genetic analysis, and nucleotide sequence of a determinant coding for a 19-kilodalton peptidoglycan-associated protein (Ppl) of Legionella pneumophila. 185 72

Community-acquired pneumonia (CAP) is the sixth most common cause of death in the United States. Despite its frequency and mortality, specific etiologic diagnosis remains a major clinical challenge. The organisms most commonly implicated in CAP are Streptococcus pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila, Haemophilus influenzae, Chlamydia pneumoniae (TWAR), and viruses. Clinical and radiographic criteria have proven to be of little value in determining the etiology of CAP. Laboratory studies, including Gram's stain and culture of sputum, have also been shown to be of severely limited value to the clinician faced with the patient with CAP. Antibiotic therapy must, therefore, generally be empiric. Regimens including erythromycin either as a single agent or coupled with an aminoglycoside or cephalosporin appear to be most efficacious.
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PMID:Community-acquired pneumonia: the clinical dilemma. 186 Dec 71

A 10 month prospective study of all adults admitted to Waikato Hospital with community acquired pneumonia was performed to assess aetiology, mortality, hospital stay, and the value of a prognostic index based on that obtained from a British Thoracic Society study. The 92 patients in the survey had a mean age of 56 (range 13-97) years. A microbiological diagnosis was established in 72%; Streptococcus pneumoniae (33%), Mycoplasma pneumoniae (18%), and influenza A virus (8%) were the most common microorganisms. Other causative organisms were Legionella pneumophila (4 cases), Staphylococcus aureus (3), Klebsiella pneumoniae (2), Haemophilus influenzae (2), Nocardia brasiliensis (1), and Acinetobacter calcoaceticus (1). Chlamydia sp, influenza B virus and adenovirus were each found in one case; all were cultured on nasopharygeal aspirates. Aspiration was considered to be the underlying cause in five patients, two with epilepsy and one with pseudobulbar palsy. Five of the six deaths that occurred were in patients over 75 years of age and the other was 69. In four of the six the established causative organisms were Chlamydia sp (1), K pneumoniae (1), and S aureus (2). Patients had a 16 fold increased risk of death if they had two or more of the following on admission: a respiratory rate of 30/minute or more, diastolic blood pressure of 60 mm Hg or less, and either confusion or a plasma urea concentration greater than 7.0 mmol/l.
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PMID:Community acquired pneumonia: aetiology and prognostic index evaluation. 190 34

A prospective study of community acquired lower respiratory tract infection in the elderly was carried out over a 15-month period. During this time 127 consecutive admissions to two acute geriatric medical wards were studied. An aetiology was established in 77 (61%) of cases. Streptococcus pneumoniae was identified in 37% of patients. Haemophilus influenzae in 18% and Branhamella catarrhalis in 10%. Infection with Mycoplasma pneumoniae was found in only one episode and no cases of Legionella pneumophilia were diagnosed. A significant number of patients had multiple bacterial pathogens isolated: 18% of all bacterial pathogens isolated were ampicillin resistant. Fourteen patients died (11%). Lower respiratory tract infection is a frequent cause of hospital admission for those aged over 65 and is often regarded as a preterminal event. Adequately treated however, mortality is no higher than in the general population. Knowledge of the likely pathogens allows early and appropriate antibiotic therapy for these patients whether at home or on admission to hospital.
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PMID:Prospective hospital study of community acquired lower respiratory tract infection in the elderly. 190 44

The activity of the quinolone temafloxacin against respiratory pathogens was compared with those of ciprofloxacin and ofloxacin. MICs for 90% of strains tested indicated that temafloxacin was at least two- to fourfold more potent than the other two quinolones against Staphylococcus aureus, Streptococcus pneumoniae, and Legionella pneumophila. Temafloxacin had potency equal to that of ciprofloxacin and was twofold more active than ofloxacin against Streptococcus pyogenes. Moraxella catarrhalis, and Bordetella pertussis. Against Haemophilus influenzae and Klebsiella pneumoniae, temafloxacin was four- and twofold less potent than ciprofloxacin, respectively. When administered orally in mouse protection tests against S. aureus, S. pneumoniae, and S. pyogenes, temafloxacin was at least eight times more potent than ciprofloxacin and was two to four times more active than ofloxacin. Against H. influenzae, temafloxacin was as active as ofloxacin and was two times less active than ciprofloxacin following oral administration in mice. In treating L. pneumophila in guinea pigs and H. influenzae otitis media in gerbils, temafloxacin and ofloxacin were more effective than ciprofloxacin. Against S. pneumoniae otitis media in gerbils, temafloxacin and ciprofloxacin were more active than ofloxacin. Following subcutaneous administration in mice, temafloxacin achieved higher lung levels than ciprofloxacin or ofloxacin did.
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PMID:Activity of temafloxacin against respiratory pathogens. 203 92

Approximately 4% of recipients of solid organ transplants in the United States develop bacterial pneumonia in the posttransplant period, often in the first 3 months following transplantation. The incidence of bacterial pneumonia is highest in recipients of heartlung (22%) and liver transplants (17%), intermediate in recipients of heart transplants (5%), and lowest in renal transplant patients (1 to 2%). The crude mortality of bacterial pneumonia in solid organ transplantation has exceeded 40% in most series. Beyond those risk factors identified for nosocomial pneumonia, the occurrence of primary cytomegalovirus (CMV) infection, graft rejection, maintenance antirejection therapy with prednisone, azathioprine, and antilymphocyte globulin, antirejection therapy with high-dose corticosteroids or OKT3 and splenectomy have been associated with a significantly increased risk of bacterial pneumonia in these patients. In the first 3 months posttransplant, gram-negative bacilli, Staphylococcus aureus and Legionella predominate and mortality is very high, in excess of 60%. Thereafter, bacterial pneumonias are caused primarily by Streptococcus pneumoniae and Hemophilus influenzae, with considerably lower mortality. Bacterial pneumonia must be suspected in any transplant patient presenting with fever and cough, especially associated with dyspnea or infiltrates on chest radiograph. If large numbers of bacteria and polymorphonuclear leukocytes are not visualized in respiratory secretions the work-up should proceed directly to fiberoptic bronchoscopy with bronchoalveolar lavage and/or protected brush specimen to establish the microbiologic diagnosis as accurately as possible. For presumptive gram-negative bacillary pneumonia, the initial regimen must be effective against Pseudomonas aeruginosa. Prevention of bacterial pneumonia in transplant patients must begin with immunization against S pneumoniae and Influenza A, and include precautions taken to prevent nosocomial pneumonia. It further may include measures to prevent CMV infection and the use of trimethoprim/sulfamethoxazole prophylaxis during the first year posttransplantation. Ultimately, novel technologies such as selective antimicrobial decontamination and/or protective isolation during the early postoperative period may prove effective.
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PMID:Bacterial pneumonia in solid organ transplantation. 218 17

Three hundred fifty-nine consecutive patients with community-acquired pneumonia admitted to university, community, and VA hospitals underwent a standardized evaluation, including specialized tests for Legionella spp. and Chlamydia pneumoniae (TWAR). The most common underlying illnesses were immunosuppression (36.3%), chronic obstructive pulmonary disease (32.4%), and malignancy (28.4%). The most frequent etiologic agents were Streptococcus pneumoniae (15.3%) and Hemophilus influenzae (10.9%). Surprisingly, Legionella spp. and C. pneumoniae were the third and fourth most frequent etiologies at 6.7% and 6.1%, respectively. Aerobic gram-negative pneumonias were relatively uncommon causes of pneumonia despite the fact that empiric broad-spectrum combination antibiotic therapy is so often directed at this subgroup. In 32.9%, the etiology was undetermined. Antibiotic administration before admission was significantly associated with undetermined etiology (p = 0.0003). There were no distinctive clinical features found to be diagnostic for any etiologic agent, although high fever occurred more frequently in Legionnaires' disease. Clinical manifestations for C. pneumoniae were generally mild, although 38% of patients had mental status changes. Mortality was highest for Staphylococcus aureus (50%) and lowest for C. pneumoniae (4.5%) and Mycoplasma pneumoniae (0%). We document that specialized laboratory testing for C. pneumoniae and Legionella spp. should be more widely used rather than reserved for cases not responding to standard therapy. Furthermore, realization that C. pneumoniae and Legionella spp. are common etiologies for community-acquired pneumonia should affect empiric antibiotic prescription.
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PMID:New and emerging etiologies for community-acquired pneumonia with implications for therapy. A prospective multicenter study of 359 cases. 220 84

The efficacy of intravenous ofloxacin therapy (200 mg 12-hourly) followed, when appropriate, by oral administration of the same dose was evaluated in an open multicentre trial involving 185 patients in 31 French hospitals. Dosage adjustment was made for patients in renal failure. Infection was hospital-acquired in 35 cases, 53 patients required admission to an intensive care unit. The infections comprised septicaemia (n = 56), pneumonia (n = 18), bronchitis (n = 10), urinary tract (n = 78), female pelvis (n = 8), bone and joint (n = 5), skin and soft tissues (n = 10). The causative pathogens were: Staphylococcus spp. (n = 23), Streptococcus spp. (n = 11), Escherichia coli (n = 85), Haemophilus influenzae (n = 9), Klebsiella, Enterobacter or Serratia spp. (n = 21), Salmonella spp. (n = 22), Chlamydia spp. (n = 3), Legionella spp. (n = 1), Mycoplasma pneumoniae (n = 1) and miscellaneous Gram-negative bacilli (n = 17). All were ofloxacin-susceptible. Mean duration of therapy was 8.06 ( +/- 2.6) days for the i.v. and 14.8 ( +/- 14.39) days for the oral preparation. Clinical cure was achieved in 173 patients (93.5%). It is concluded that iv ofloxacin is an effective treatment for a range of infections due to susceptible organisms.
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PMID:Efficacy of intravenous ofloxacin: a French multicentre trial in 185 patients. 228 86


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