USA and Australia showed case–fatality rates of 14% for nosocomial infections and 5–10% for community-acquired infections (Benin et al., 2002;Howden et al., 2003). In Europe, the overall case–fatality rate is about 12%

Previously healthy and no risk factors for drug-resistantS. pneumoniae(DRSP) infection:A. A macrolide (azithromycin, clarithromycin, orerythromycin) (strong recommendation; level Ievidence)

Interruption of gyrase activity by quinolones

zithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal

FeoB is required for efficient killing of macrophages and full virulence in a mouse model of Legionnaires’ disease.

Finally, secreted phospholipases connect Legionella virulence to host lipid

Virulence Properties of the Legionella Pneumophila Cell Envelope

egionellagrows bestin warm water that is not moving or that does not have enough disinfectant to kill germs.

asons external to the building itself, like nearby constructio

Current or former smokers and people with a chronic lung disease, such as emphysem

commercially available radioimmunoassay for bacterial antigen in urine is satisfactory, but is available only for serogroup 1 of L pneumophila

possesses pili (fimbriae), and most species are motile by means of a single polar flagellum

nother factor that favors the survival of Legionella in natural or treated waters is its relative resistance to the effects of chlorine and heat; Legionella can find refuge in relatively inhospitable environments such as hot-water tanks.

may appear that we are defenseless against Legionella infection, because the most effective type of host defense shows only very modest bactericidal abilities in vitro. In fact most infections are subclinical, and mortality is low in patients who are not immunocompromised. Similarly, even susceptible experimental animals survive infection unless moderately large doses of bacteria are given. The defense mechanisms probably function better in vivo than in vitro. The action of host defenses may also be additive in vivo. One can construct a scenario by which bacteria are increasingly phagocytosed by cells that do not permit bacterial growth. The net result is a decreasing number of extracellular bacteria and hence a decreased source of infection for a decreasing population of permissive cells. Obsolescent inflammatory cells in the lungs are removed by the mucociliary escalator and expectorated as sputum. Therefore, the infection may begin with a bang, but it ends in most cases with a whimper.

erythromycin and rifampin inhibit the growth of Legionella organisms in infected macrophages, but do not kill the bacteria

tibiotics used to treat the Pennsylvania legionnaires suggests that erythromycin was the most effective agen

The preferred drug for symptomatic Legionella infections is erythromycin. If the patient is seriously ill, it is important to deliver the antibiotic intravenously at first; subsequently, oral therapy may be used. Rifampin is sometimes added as a second antibiotic in seriously ill patients

his medium contains yeast extract, iron, L-cysteine, and α-ketoglutarate for bacterial growth; activated charcoal to inactivate toxic peroxides that develop in the media; and buffer with a pK at pH 6.9, the optimum for growth of Legionella organisms. Addition of albumin to the media may further facilitate growth of species other than L pneumophila. For contaminated specimens such as sputum, antibiotics should be added. Morphologically distinctive bacterial colonies can usually be detected within 3 to 5 days and identified presumptively as Legionella species if the isolated bacteria depend on cysteine for growth. The identification can be confirmed by specific immunologic typing of the isolated bacteria or, in problematic cases, by molecular analysis.

Direct detection of bacterial antigen in clinical specimens is potentially much faster than culturing

Serologic diagnosis

charcoal-yeast extract - α-ketoglutarate medium.

poradic or epidemic, community acquired or nosocomial. There is great geographic variation in the frequency of infection even within communities

air-cooling equipment that generates aerosols.

Aerosols are produced in numerous ways in our environment, from taking a shower to flushing the toilet.

The only documented source of Legionella species is water, particularly the surface waters of rivers and lakes and drinking water.

The classic pathway of the complement system is activated by L pneumophila, enhancing phagocytosis still furthe

Virulence appears to be multifactorial. An outer membrane protein that functions as a metalloprotease and a cytoplasmic membrane heat-shock protein elicit protective immune responses, but are not essential for expression of virulence. A gene that encodes a 29 Kd protein and plays a role in cellular infection has been identified. Mutations of the gene are associated with decreased virulence.

ymptoms of Legionella infection undoubtedly result from a combination of physical interference with oxygenation of blood, ventilation-perfusion imbalance in the remaining lung tissue, and release of toxic products from bacteria and inflammatory cells. Bacterial factors include a protease that may be responsible for tissue damage. Cellular factors include interleukin-1, which produces fever after it is released from monocytes, and tumor necrosis factor, which may be responsible for some of the systemic symptoms.

Leaky capillaries allow the transudation of serum and deposition of fibrin in the alveoli. The result is a destructive pneumonia that obliterates the air spaces and compromises respiratory function

The bacteria bind to alveolar macrophages via the complement receptors and are engulfed into a phagosomal vacuole. However, by an unknown mechanism, the bacteria block the fusion of lysosomes with the phagosome, preventing the normal acidification of the phagolysosome and keeping the toxic myeloperoxidase system segregated from the susceptible bacteria. The bacilli multiply within the phagosome. Thus, a cellular compartment that should be a death trap instead becomes a nursery. Eventually, the cell is destroyed, releasing a new generation of microbes to infect other cells.

Person-to-person transmission has never been demonstrated, and Legionella is not a member of the bacterial flora of humans.

Important antigens include outer membrane proteins, some of which are species specific antigens, and the lipopolysaccharide that is the major serogroup specific antigen.

rimary growth factor required is L-cysteine, a nutrient that is also essential for Francisella tularensis. Ferric iron is also essential, and other compounds are necessary for optimal growth. Energy is derived from amino acids rather than carbohydrates.

fastidious only in regard to the media commonly used in laboratories

Gram-negative bacilli

Bacteremia occurs during Legionella pneumonia, and symptomatic infection outside the lungs occasionally develops

acute pneumonia, which varies in severity from mild illness that does not require hospitalization (walking pneumonia) to fatal multilobar pneumonia. Typically, patients have high, unremitting fever and cough but do not produce much sputum. Extrapulmonary symptoms, such as headache, confusion, muscle aches, and gastrointestinal disturbances, are common. Most patients respond promptly to appropriate antimicrobial therapy, but convalescence is often prolonged (lasting many weeks or even months).

infections are primarily respirator

drug of choice is erythromycin

method is culturing on special charcoal-containing agar.

Disease may be sporadic or epidemic and may occur in the community or in hospitals. People with compromised host defenses are at increased risk.

most common presentation of Legionella pneumophila is acute pneumonia

) through target-site modification by methylation or mutation that prevents the binding of the antibiotic to its ribosomal target, (2) through efflux of the antibiotic, and (3) by drug inactiva

L. pneumophila8 (14%)00017 (30%)39 (70%)

Rifampin specifically inhibits bacterial RNA polymerase, the enzyme responsible for DNA transcription, by forming a stable drug-enzyme complex with a binding constant of 10(-9) M at 37 C. T

binding inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Erythromycin may be bacteriostatic or bactericidal depending on the organism and drug concentration.

macrolide antibiotic

erythromycin [ĕ-rith″ro-mi´sin] a broad-spectrum antibiotic produced by a strain

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irect fluorescent antibody (DFA) testing has the ability to provide results in a time frame able to influence clinical management and has a specificity of close to 100% (5). However, DFA is technically demanding and insensitive. As with sputum culture, DFA has limited usefulness when patients cannot produce sputum.

L pneumophila by urinary antigen testing (LPUAT) is a rapid tool for early diagnosis of Legionella infection (6-14). An enzyme immunoassay (EIA) for detecting L pneumophila serogroup 1, which accounts for between 50% and 70% of cases of Legionella p

Sputum culture is favoured by many because it has the ability to detect all species and subgroups of Legionella and has a specificity of 100%

Legionella pneumophila is responsible for 1% to 4% of cases of community-acquired pneumonia requiring hospitalization

under UV light. Incubated aerobically for 72 hours at 35ºC.

On BCYE and BCYE Selective Agars, colonies of Legionella pneumophila appear white-gray to blue-gray and fluoresce yellow-green under long-wave UV light.

Incubate plates at 35 +/- 2ºC. for a minimum of 3 days. Growth is typically visible after 3-4 days, but may take up to 2 weeks.

L. pneumophila is divided into 15 serogroups, among which serogroup 1 is the most prevalent disease-causing variant

Since the organism was first identified in 1976 during an outbreak at an American Legion Convention in Philadelphia, Legionella has been recognized as a relatively common cause of both community-acquired [1,2] and hospital-acquired pneumonia

emperatures of 20 to 50 degrees Celsius (optimal 35 degrees Celsius

s illnesses have occurred after short exposures and 3 or more km from the source of outbreaks

Legionella pneumophila and related species are commonly found in lakes, rivers, creeks, hot springs and other bodies of wate

Cough — 41 to 92 percentChills — 42 to 77 percentFever >38.8ºC — 88 to 90 percent