Gram Negative Bacilli Outside GIT PDF

GRAM NEGATIVE BACILLI OUTSIDE THE ENTERIC TRACT KLEBSIELLA–ENTEROBACTER–SERRATIA GROUP Diseases: Opportunistic pathogens that cause nosocomial infections, especially pneumonia and urinary tract infections. Klebsiella pneumoniae is an important respiratory tract pathogen outside hospitals as well. I...

GRAM NEGATIVE BACILLI OUTSIDE THE ENTERIC TRACT KLEBSIELLA–ENTEROBACTER–SERRATIA GROUP Diseases: Opportunistic pathogens that cause nosocomial infections, especially pneumonia and urinary tract infections. Klebsiella pneumoniae is an important respiratory tract pathogen outside hospitals as well. Important Properties Klebsiella pneumoniae, Enterobacter cloacae, and Serratia marcescens are the species found in the large intestine but are also present in soil and water. Klebsiella pneumoniae has a very large polysaccharide capsule, which gives its colonies a mucoid appearance. Serratia marcescens produces red-pigmented prodigiosin colonies on nutrient agar. Prodigiosin is known to be produced as a response to stressful stimuli. Pathogenesis & Epidemiology Of the three organisms, K. pneumoniae is most likely to be a primary, non-opportunistic pathogen; this property is related to its antiphagocytic capsule. Although this organism is a primary pathogen, patients with K. pneumonia infections frequently have predisposing conditions such as advanced age, chronic respiratory disease, diabetes, or alcoholism. The organism is carried in the respiratory tract of about 10% of healthy people, who are prone to pneumonia if host defenses are lowered. Enterobacter and Serratia infections are related to hospitalization like invasive procedures such as intravenous catheterization, respiratory intubation, and urinary tract manipulations. In addition, outbreaks of Serratia pneumonia have been associated with contamination of the water in respiratory therapy devices. E.g. S. marcescens. Serratia also causes endocarditis in injection drug users. As with many other gram-negative rods, the pathogenesis of septic shock is due to endotoxins in their cell walls. Clinical Findings Urinary tract infections, pneumonia, bacteremia and secondary spread to meninges and liver occur. It is difficult to distinguish infections caused by these organisms on clinical grounds, with the exception of pneumonia caused by Klebsiella, which produces a thick, mucoid, bloody sputum (“currant-jelly” sputum) and can progress to necrosis and abscess formation. Klebsiella ozaenae causes atrophic rhinitis, and Klebsiella rhinoscleromatis causes a destructive granuloma of the nose and pharynx. Laboratory Diagnosis All produce lactose-fermenting (colored/pink) colonies on differential agar such as MacConkey’s or EMB, although Serratia, which is a late/slow lactose fermenter, can produce a negative reaction. Klebsiella colonies are extremely mucoid on nutrient agar and will tend to drip into the lid of the plate while incubating in an inverted position. These organisms are differentiated by biochemical tests. Treatment Carbapenem-resistant strains are an important cause of hospital-acquired infections and are resistant to almost all known antibiotics. An aminoglycoside (e.g., gentamicin) and a cephalosporin (e.g., cefotaxime) are used instead. In severe Enterobacter infections, a combination of imipenem and gentamicin is used. Prevention - Changing the site of intravenous catheters, - removing urinary catheters when no longer needed, - taking proper care of respiratory therapy devices. There is no vaccine. PROTEUS–PROVIDENCIA–MORGANELLA GROUP Diseases: cause urinary tract infections, both community- and hospital-acquired. Important Properties These are distinguished from other members of the Enterobacteriaceae by their ability to produce the enzyme phenylalanine deaminase and urease, which cleaves urea to form NH3 (Ammonia) and CO2. Certain species are very motile and produce a swarming effect on blood agar, characterized by expanding rings (waves) of organisms over the surface of the agar. The cell wall O antigens of certain strains of Proteus, such as OX-2, OX-19, and OX-K, cross-react with antigens of rickettsiae. These Proteus antigens can be used in laboratory tests to detect the presence of antibodies against certain rickettsiae in patients’ serum. This test, called the Weil-Felix reaction. Two Species have been renamed: Proteus morganii is now Morganella morganii, and Proteus rettgeri is now Providencia rettgeri. In the clinical laboratory, these organisms are distinguished from Proteus vulgaris and Proteus mirabilis on the basis of biochemical tests. Both P. mirabilis and P. vulgaris can also cause acute pyelonephritis and septicaemia. Pathogenesis & Epidemiology The organisms are present in the human colon, soil and water. Their tendency to cause urinary tract infections is due to their presence in the colon which lead to the colonization of the urethra, especially in women. The vigorous motility of Proteus organisms may contribute to their ability to invade the urinary tract. Production of the enzyme urease is an important feature of the pathogenesis of urinary tract infections by this group. Urease hydrolyzes the urea in urine to form ammonia, which raises the pH, producing an alkaline urine which encourages the formation of stones (calculi) called “struvite” composed of magnesium ammonium phosphate. Struvite stones appear as staghorn calculi in the renal pelvis. They obstruct urine flow, damage urinary epithelium, and serve as an area for recurrent infection by trapping bacteria within the stone. Because alkaline urine also favors growth of the organisms and more extensive renal damage, treatment involves keeping the urine at a low pH. Clinical Findings Proteus species can also cause pneumonia, wound infections, and septicemia. Proteus mirabilis causes most community- and hospital-acquired infections, but P. rettgeri is now emerging. Laboratory Diagnosis Highly motile (peritrichous) and produce a “swarming” overgrowth on blood agar. Growth on blood agar containing phenylethyl alcohol inhibits swarming, thus allowing isolated colonies of Proteus and others to grow. They produce non–lactose-fermenting (colorless) colonies on MacConkey’s or EMB agar. Proteus vulgaris and P. mirabilis produce H2S, which blackens the butt of TSI agar, whereas M. morganii or P. rettgeri does not. Proteus mirabilis is indole negative, whereas the other three species are indole positive—a distinction that can be used clinically to guide the choice of antibiotics. These four medically important species are urease-positive. Difference between Proteus mirabilis and Proteus vulgaris 1. Prevalence: P. mirabilis is more common than P. vulgaris in human urinary tract infections. 2. Indole production: P. mirabilis is indole negative, while P. vulgaris is indole positive. 3. Antibiotic sensitivity: P. mirabilis is usually sensitive to ampicillin and other β-lactam antibiotics, while P. vulgaris is usually resistant to penicillins and many cephalosporins. 4. Swarming: P. mirabilis can switch between swimming and swarming forms. 5. Fermentation: P. vulgaris ferments glucose and amygdalin, but does not ferment mannitol or lactose. Treatment Most strains are sensitive to aminoglycosides and trimethoprim-sulfamethoxazole. Proteus mirabilis is the species most sensitive to ampicillin. The indole-positive species (P. vulgaris, M. morganii, and P. rettgeri) are more resistant to antibiotics than is P. mirabilis, which is indole-negative. For the indole-positive species is cephalosporin (e.g., cefotaxime). Proteus rettgeri is resistant to multiple antibiotics. Prevention Prompt removal of urinary catheters. PSEUDOMONAS Diseases: causes sepsis, pneumonia, and urinary tract infections primarily in patients with lowered host defenses. It also causes chronic lower respiratory tract infections in patients with cystic fibrosis, wound infections (cellulitis) in burn patients, and malignant otitis externa in diabetic patients. It is the most common cause of ventilator- associated pneumonia. Important Properties Pseudomonads gram negative rods that are strict aerobes (i.e., they derive their energy only by oxidation of sugars rather than by fermentation). Because they do not ferment glucose, they are called non-fermenters, in contrast to the members of the Enterobacteriaceae, which do ferment glucose. Oxidation involves electron transport by cytochrome c (i.e., they are oxidase-positive). Pseudomonads are able to grow in: water containing only traces of nutrients (e.g., tap water), withstand disinfectants, hexachlorophene-containing soap solutions, in antiseptics, in detergents. - And these all favor their persistence in the hospital environment. Pseudomonas aeruginosa produces two pigments useful in clinical and laboratory diagnosis: 1. Pyocyanin, which can color the pus in a wound blue, and 2. Pyoverdin (fluorescein), a yellow-green pigment that fluoresces under ultraviolet light, a property that can be used in the early detection of skin infection in burn patients. In the laboratory, these pigments diffuse into the agar, forming a blue-green color that is useful in identification. Pseudomonas aeruginosa is the only species of Pseudomonas that synthesizes pyocyanin. Strains of P. aeruginosa isolated from cystic fibrosis patients have a prominent slime layer (glycocalyx), which gives their colonies a very mucoid appearance. The slime layer mediates adherence to mucous membranes of the respiratory tract and prevents antibody from binding to the organism. Pathogenesis & Epidemiology Pseudomonas aeruginosa is found in soil and water, although 10% of people carry it in the normal flora of the colon. It is found on the skin in moist areas and can colonize the upper respiratory tract of hospitalized patients. Its ability to grow in simple aqueous solutions has resulted in contamination of respiratory therapy and anesthesia equipment, intravenous fluids, and even distilled water. Pathogenesis is based on multiple virulence factors: endotoxin, exotoxins, and enzymes. - Its endotoxin, causes sepsis and septic shock. - Exotoxin A, which causes tissue necrosis. It inhibits eukaryotic protein synthesis by the same mechanism as diphtheria exotoxin, namely, ADP-ribosylation of elongation factor-2. - It also produces enzymes, such as elastase and proteases that are histotoxic and facilitate invasion of the organism into the bloodstream. - Pyocyanin damages the cilia and mucosal cells of the respiratory tract. Strains of P. aeruginosa that have a “type III secretion system” are more virulent than those that do not. This secretion system transfers the exotoxin from the bacterium directly into the adjacent human cell, which allows the toxin to avoid neutralizing antibody. Type III secretion systems are mediated by transport pumps in the bacterial cell membrane. Of the four exoenzymes known to be transported by this secretion system, Exo S is the one most clearly associated with virulence as it causes ADP ribosylation of a Ras protein, leading to damage to the cytoskeleton. Clinical Findings Pseudomonas aeruginosa is an opportunistic pathogen that causes infections: 1. in hospitalized patients (e.g., those with extensive burns), 2. whom the skin host defenses are destroyed; 3. in those with chronic respiratory disease (e.g., cystic fibrosis), 4. whom the normal clearance mechanisms are impaired; 5. in those who are immunosuppressed; in those with neutrophil counts of less than 500/μL; 6. Those with indwelling catheters. 7. It causes 10% to 20% of hospital-acquired; most common cause of gram-negative nosocomial pneumonia, especially ventilator-associated pneumonia. - The bacteria can spread to the skin, where they cause black, necrotic lesions called ecthyma gangrenosum. - P. aeruginosa sepsis have a mortality rate of greater than 50%. Severe external otitis (malignant otitis externa) other skin lesions (e.g., folliculitis) occur in users of swimming pools and hot tubs (hot tub folliculitis) in which the chlorination is inadequate. - Pseudomonas aeruginosa is the most common cause of osteomyelitis of the foot in those who sustain puncture wounds through the soles of gym shoes. - Corneal infections caused by P. aeruginosa are seen in contact lens users. Laboratory Diagnosis - Non–lactose-fermenting, flat, colorless colonies on MacConkey’s or EMB agar. - It is oxidase, catalase and citrate-positive. - A typical metallic sheen of the growth on TSI agar, with the blue-green pigment on ordinary nutrient agar, and a fruity aroma are sufficient to make a presumptive diagnosis. - They are non-spore forming and monotrichous motility. They have a very strict aerobic respiratory metabolism with oxygen but in some cases, nitrate has been used as an alternative that allows anaerobic growth. Identification for epidemiologic purposes is done by bacteriophage or pyocin typing. A pyocin is a type of bacteriocin produced by P. aeruginosa. Treatment - Antipseudomonal penicillin (e.g., piperacillin/tazobactam or ticarcillin/clavulanate) plus an aminoglycoside (e.g., gentamicin or amikacin). Ceftazidime is also effective. - Highly resistant strains: Colistin (Polymyxin E) is useful. - Urinary tract infections is ciprofloxacin. Prevention - Keeping neutrophil counts above 500/ml - Removing indwelling catheters promptly - Taking special care of burned skin