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Quinolones are a class of antibiotics structurally related to nalidixic acid. They exhibit bactericidal activity primarily by inhibiting bacterial DNA gyrase. The early quinolones had a limited spectrum of activity, low potency, high frequency of spontaneous bacterial resistance, low serum drug concentrations and short half-lives, which virtually restricted their use to urinary tract infection. The new fluorinated quinolones differ from their predecessors in their broad antibacterial spectrum, including both Gram-negative and Gram-positive aerobic, and facultative anaerobic bacteria as well as many Mycobacterium spp., Chlamydia spp., Legionella spp. and Mycoplasma spp., in addition to many strains of bacteria that are multiresistant to beta-lactam antibiotics and aminoglycosides. They also exhibit high potency, a low incidence of resistance, high oral bioavailability, extensive tissue penetration, low protein binding and long elimination half-lives. They are generally well tolerated apart from some gastrointestinal disturbance and rashes, including photosensitive eruptions and a propensity to cause central nervous system excitation. Clinically important interactions include those with antacids, theophylline, fenbufen and warfarin. Potential toxic effects include cartilage damage, ocular toxicity, teratogenicity and impairment of spermatogenesis. The role of fluoroquinolones continues to widen, encompassing infections of the urinary tract, respiratory tract, skin and soft tissues, bone and joints, infections in immunocompromised patients, sexually transmitted diseases, infectious diarrhoea, gynaecological infections and surgical prophylaxis. The convenience of oral therapy is an added advantage of the new fluoroquinolones.
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PMID:Quinolone antibacterials. An update of their pharmacology and therapeutic use. 752 29

The fluoroquinolones are characterised by a broad spectrum of antibacterial activity that includes many Mycobacterium, Chlamydia, Legionella, and Mycoplasma species as well as many multiply-resistant bacterial strains, good oral bioavailability, extensive tissue penetration, low protein binding and long elimination half-lives. Numerous clinical trials have shown that these compounds are effective and well tolerated in the treatment of adult patients with various infections, including urinary tract, respiratory tract, skin and soft tissue, bone and joint, and gynaecological infections, sexually transmitted diseases, infectious diarrhoea, infections in immunocompromised patients, and in surgical prophylaxis. Thus, there is increasing pressure to use this class of drugs in paediatric patients. However, concerns regarding adverse effects, particularly cartilage toxicity, have restricted development of the fluoroquinolone compounds for use in this population. Potential indications include Pseudomonas infections (mainly exacerbations of cystic fibrosis), urinary tract, gastrointestinal and central nervous system infections, infections in immunocompromised patients, certain otorhinolaryngological infections and infections caused by multiply-resistant pathogens. To date, clinical experience gained with fluoroquinolones in paediatric infections, which has been mainly on a compassionate-use basis, indicates that well-designed formal studies should be conducted to fully assess the efficacy and tolerability of these agents in specific indications in children.
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PMID:Fluoroquinolones in paediatrics--1995. 854 23

This study was undertaken to examine quantitatively the risks to human health posed by heterotrophic plate count (HPC) bacteria found naturally in ambient and potable waters. There is no clear-cut evidence that the HPC bacteria as a whole pose a public health risk. Only certain members are opportunistic pathogens. Using the four-tiered approach for risk assessment from the National Academy of Sciences, hazard identification, dose-response modeling, and exposure through ingestion of drinking water were evaluated to develop a risk characterization, which estimates the probability of infection for individuals consuming various levels of specific HPC bacteria. HPC bacteria in drinking water often include isolates from the following genera: Pseudomonas, Acinetobacter, Moraxella, Aeromonas, and Xanthomonas. Other bacteria that are commonly found are Legionella and Mycobacterium. All these genera contain species that are opportunistic pathogens which may cause serious diseases. For example, the three nonfermentative gram-negative rods most frequently isolated in the clinical laboratory are (1) Pseudomonas aeruginosa, (2) Acinetobacter, and (3) Xanthomonas maltophilia. P. aeruginosa is a major cause of hospital-acquired infections with a high mortality rate. Aeromonas is sometimes associated with wound infections and suspected to be a causative agent of diarrhea. Legionella pneumophila causes 4%-20% of cases of community-acquired pneumonia and has been ranked as the second or third most frequent cause of pneumonia requiring hospitalization. The number of cases of pulmonary disease associated with Mycobacterium avian is rapidly increasing and is approaching the incidence of M. tuberculosis in some areas. Moraxella can cause infections of the eye and upper respiratory tract. The oral infectious doses are as follows in animal and human test subjects: P. aeruginosa, 10(8)-10(9); A, hydrophila, > 10(10); M. avium, 10(4)-10(7); and X. maltophilia, 10(6)-10(9). The infectious dose for an opportunistic pathogen is lower for immunocompromised subjects or those on antibiotic treatment. These bacteria have been found in drinking water at the following frequencies: P. aeruginosa, < 1%-24%; Acinetobacter, 5%-38%; X. maltophilia, < 1%-2%; Aeromonas, 1%-27%; Moraxella, 10%-80%; M. avium, < 1%-50%; and L. pneumophila, 3%-33%. These data suggest that drinking water could be a source of infection for some of these bacteria. The risk characterization showed that risks of infection from oral ingestion ranged from a low of 7.3 x 10(-9) (7.3/billion) for low exposures to Aeromonas to higher risks predicted at high levels of exposure to Pseudomonas of 9 x 10(-2) (98/100). This higher risk was only predicted for individuals on antibiotics. Overall, the evidence suggests that specific members of HPC bacteria found in drinking water may be causative agents of both hospital- and community-acquired infections. However, the case numbers may be very low and the risks represent levels generally less than 1/10,000 for a single exposure to the bacterial agent. Future research needs include (1) determining the seasonal concentrations of these bacteria in drinking water, (2) conducting adequate dose-response studies in animal subjects or human volunteers, (3) determining the health risks for an individual with multiple exposures to the opportunistic pathogens, and (4) evaluating the increase in host susceptibility conferred by antibiotic use or immunosuppression.
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PMID:Risk assessment of opportunistic bacterial pathogens in drinking water. 929 85

The aim of this study was to compare the clinical, biological, and radiologic features of presentation in the emergency ward of community-acquired pneumonia (CAP) by Legionella pneumophila (LP) and other community-acquired bacterial pneumonias to help in early diagnosis of CAP by LP. Three hundred ninety-two patients with CAP were studied prospectively in the emergency department of a 600-bed university hospital. Univariate and multivariate analyses were performed to compare epidemiologic and demographic data and clinical, analytical, and radiologic features of presentation in 48 patients with CAP by LP and 125 patients with CAP by other bacterial etiology (68 by Streptococcus pneumoniae, 41 by Chlamydia pneumoniae, 5 by Mycoplasma pneumoniae, 4 by Coxiella burnetii, 3 by Pseudomonas aeruginosa, 2 by Haemophilus influenzae, and 2 by Nocardia species. Univariate analysis showed that CAP by LP was more frequent in middle-aged, male healthy (but alcohol drinking) patients than CAP by other etiology. Moreover, the lack of response to previous beta-lactamic drugs, headache, diarrhea, severe hyponatremia, and elevation in serum creatine kinase (CK) levels on presentation were more frequent in CAP by LP, while cough, expectoration, and thoracic pain were more frequent in CAP by other bacterial etiology. However, multivariate analysis only confirmed these differences with respect to lack of underlying disease, diarrhea, and elevation in the CK level. We conclude that detailed analysis of features of presentation of CAP allows suspicion of Legionnaire's disease in the emergency department. The initiation of antibiotic treatment, including a macrolide, and the performance of rapid diagnostic techniques are mandatory in these cases.
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PMID:Comparative study of the clinical presentation of Legionella pneumonia and other community-acquired pneumonias. 959 85

Legionella have a predilection for infecting immunocompromised patients, and transplant recipients have the highest risk. Legionella spp have been the most common cause of nosocomial pneumonia among transplant recipients at selected medical centers. Diagnosis is dependent on the ability of the clinical microbiology laboratory to isolate the organism by culture; therefore, the disease is easily overlooked. The mode of transmission of Legionella pneumophila is likely aspiration in transplant recipients. Clinical manifestations are similar to that of other bacterial pneumonias, although diarrhea is often prominent. The quinolone antibiotics (especially ciprofloxacin) are the antibiotics of choice because, unlike the macrolides or rifampin, they do not interact with the immunosuppressive agents used to counter rejection. Prevention of nosocomial legionellosis involves disinfection of the hospital's potable water system. Effective disinfection methods include superheat and flush or copper-silver ionization; hyperchlorination is no longer recommended. Routine culture surveillance directed at the hospital water supply for Legionella is mandatory in hospitals caring for transplant patients.
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PMID:Legionella: a major opportunistic pathogen in transplant recipients. 964 91

A fatal pneumonia due to Legionella pneumophila was diagnosed in a young calf reared in a dairy herd located in northern Italy. Clinical symptoms consisted of watery diarrhea, hyperthermia, anorexia, and severe dyspnea. The pathological and histological findings were very similar to those observed in human legionellosis. Legionella pneumophila serogroup 1 (SG1) and SG10 were isolated from the calfs lung, and L. pneumophila SG1 was isolated from the calfs liver. L. pneumophila SG1 was also demonstrated in the lung tissue by immunofluorescence and immunohistochemical examinations. Nine of 10 L. pneumophila SG1 isolates belonged to the Olda subtype, and 1 belonged to the Camperdown subtype. A very low prevalence of antibodies to Legionella was detected in cows and calves reared in the same herd. Cultures of aqueous sediment of an old electric water heater which supplied hot water for the feeding of the calves yielded L. pneumophila SG1. Four of the colonies tested belonged to the Olda subtype. Ten clinical and four environmental isolates were examined for the presence of plasmids. Nine of them were also examined by pulsed-field gel electrophoresis assay, and the same patterns were found for L. pneumophila SG1 Olda strains isolated from the calf and from the electric heater. This is the first report of a documented case of a naturally occurring Legionella pneumonia in an animal. Cattle probably act as accidental hosts for legionellae, much the same as humans.
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PMID:Epidemiological and environmental investigations of Legionella pneumophila infection in cattle and case report of fatal pneumonia in a calf. 965 Sep 41

Digestive disorders in Legionella pneumophila pneumonia such as nausea, vomiting, diarrhoea, are common; they are clinical arguments to suspect this bacteria to be responsible for this pneumonia. In this case-report, a patient with pneumonia due to Legionella pneumophila serogroup I presented in the follow-up with signs of enteritis with ascites. We looked ahead in literature who made us discover the multiple organ involvement that may happen in Legionnaires' disease. Diagnostic procedures consist in simple tests as ultrasonography, abdominal computerised tomography, that show inflammatory disease signs and sometimes ascites. Exceptionally, Legionella pneumophila has been demonstrated with direct immunofluorescent microscopic study, in inflammatory colitis pieces with haemorrhagic necrosis in different stage processes. Pathogenesis could be explained by the systemic spread of the organism and formation at distance of necrotising enteritis focus. It is initiated by necrotising factors of bacterial origin and hypersensitivity reactions (type I and III).
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PMID:[Digestive disorders and Legionnaires' lung disease. Accompanying signs or visceral location?]. 1085 68

Telithromycin is a new ketolide antimicrobial, specifically developed for the treatment of community-acquired respiratory tract infections. It has a wide spectrum of antibacterial activity against common respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. It also has activity against atypical pathogens, such as Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae. Telithromycin maintains activity against beta-lactam and macrolide-resistant respiratory tract pathogens and does not appear to induce cross-resistance to other members of the macrolide-lincosamide-streptogramin (MLS) group of antimicrobials. It demonstrates bactericidal activity against S. pneumoniae and H. influenzae and has a prolonged concentration-dependent post-antibiotic effect (PAE) in vitro. The drug has favourable pharmacokinetics following oral administration. It is well absorbed, achieves good plasma levels and is highly concentrated in pulmonary tissues and white blood cells. In clinical trials, telithromycin given orally at a dose of 800 mg once daily for 5 - 10 days was as effective as comparator antimicrobials for the treatment of adults with community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute maxillary sinusitis and group A-beta-haemolytic streptococcal pharyngitis or tonsillitis. The adverse events and safety profile were similar to comparator antimicrobials. The most common adverse events were diarrhoea, nausea, headache and dizziness. Telithromycin should provide an effective, convenient and well-tolerated once-daily oral therapy for treatment of respiratory infections.
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PMID:Telithromycin: a new ketolide antimicrobial for treatment of respiratory tract infections. 1117 47

A 54-year-old man was admitted to our hospital complaining of a high fever and watery diarrhea. The chest radiograph on admission revealed a homogeneous consolidation of the left upper lobe. Laboratory findings included proteinuria, oligouria, hematuria, myoglobinuria, hyponatremia, and serum CPK elevation. On the basis of these findings, a tentative diagnosis of Legionella pneumonia was made. He was treated with sulbactam/cefoperazon and erythromycin, but his high fever remained and the consolidation shadow deteriorated. He was therefore given both erythromycin and ciprofloxacin intravenously. After several days the fever had returned to normal, the appearance of the chest radiograph had improved, and his symptoms were quickly relieved. This case suggests that intravenous administration of ciprofloxacin and erythromycin can be an effective treatment against Legionella pneumonia.
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PMID:[A case of Legionella pneumonia successfully treated intravenously with both erythromycin and ciprofloxacin]. 1187 14

M. pneumoniae infection occurs world-wide and is the most common cause of community-acquired pneumonia (CAP) in the 5 to 20 year-old age group. The most reliable diagnostic test is enzyme immunoassay that allows immunoglobulin (Ig)G and IgM titration and presents 92% sensitivity and 95% specificity on paired samples. Potentially active drugs are tetracyclines, macrolides, ketolides, lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. The incidence of Legionella infection, in spite of its world-wide diffusion, is highly variable in different studies, ranging from 1% to 27% of CAP. The most likely mode of transmission is direct inhalation from Legionella-contaminated water-supply systems. Extrapulmonary manifestations are relatively common but nonspecific. However, some signs and symptoms may raise the suspicion of Legionella infection: a sputum Gram stain with a high number of neutrophils without any organism, hyponatremia, and diarrhea in a critically ill patient. Urinary radioimmunoassay (RIA) antigen detection is the method of choice for L. pneumophila serogroup 1. The best treatment regimen is a full three-week treatment with a macrolide (erythromycin, clarithromycin, azithromycin). An alternative treatment regimen may be the association of second generation fluoroquinolones with tetracyclines. A notable improvement in most of the new fluoroquinolones is their activity against Legionella, so that their use as single agent may be hypothesised even if clinical data are still insufficient for a definitive indication. Chlamydia pneumoniae account for 6-20% of CAP depending on several factors such as setting of the studied population, age group examined, and diagnostic methods used. The current gold standard for serological diagnosis of acute infection is microimmunofluorescence testing. Tetracyclines and erythromycin show good in vitro activity and so far have been the most commonly employed drugs in the treatment of C. pneumoniae infection. New macrolides, ketolides, and new fluoroquinolones are other potentially effective drugs.
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PMID:Community-acquired pneumonia: role of atypical organisms. 1198 Feb 85


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