Infectious Disease- Pathogenic Enterobacteriaceae Part 2 (class 5)

Infectious Disease- Pathogenic Enterobacteriaceae Part 2 (Class 5) Tuesday, November 03, 2009 9:03 PM

Proteus: Background: ○ Proteus species are part of the Enterobacteriaceae family of gram-negative bacilli ○ They are commonly found in the human intestinal tract as normal human intestinal flora (along with E. coli and Klebsiella). ○ Proteus is also found in multiple habitats such as long-term care facilities and hospitals ○ Infection primarily occurs when these bacilli colonize the skin and oral mucosa ○ They are NOT the most common cause of nosocomial infections ○ Proteus mirabilis causes 90% of Proteus infections and can be considered a community-acquired infection

Pathophysiology: ○ Proteus has an extracytoplasmic outer membrane ( a feature of all gram-negative bacteria) ○ The outer membrane contains a lipid bilayer, lipoproteins, polysaccharides, and lipopolysaccharides ○ Fimbriae facilitate adherence of the microbe to the host tissue and enhance the capacity of the organism to produce disease ○ Chemicals located on the tips of the pilli enable organisms to attach to certain host tissues (i.e. urinary tract endothelium) ○ Proteus organisms induce apoptosis and epithelial cell desquamation ○ Bacterial production of urease (degrades urea) has been shown to increase the risk of pyelonephritis ○ Urease production, along with the presence of bacterial motility and fimbriae, may favor the production of UTIs by organisms such as Proteus ○ ** The ability of Proteus to produce urease and alkalinize the urine by hydrolyzing urea to ammonia makes it effective in producing an environment in which it can survive. ○ This leads to precipitation of organic and inorganic compounds, which leads to struvite stone formation (which shows that presence of Proteus species in the urine may indicate that the patient may have renal calculi or a tumor because these organisms grow in an alkaline environment). ○ Urease metabolizes urea into ammonia and carbon dioxide. ○ Since Proteus species are common in the male preprutial flora, a finding of Proteus in a urine sample of an uncircumcised man or young boy could indicate contamination

Clinical Manifestations: ○ Symptoms associated with stone formation are uncommon ○ More often, women present with UTI, flank pain, or hematuria and have a persistently alkaline urine pH

Treatment: ○ Uncomplicated UTIs in women can be treated with an oral quinolone or trimethoprim/sulfamethoxazole for 3 days ○ If a renal calculus is found, it must be removed Pseudomonads: Background: ○ The Pseudomonas-related group of organisms are gram-negative rods (including the most commonly encountered pathogen in this group, Pseudomonas aeruginosa) ○ More than half of all clinical isolates produce the blue-green pigment pyocyanin ○ Pseudomonas has a characteristic sweet odor ○ In clinical medicine, P. aeruginosa is primarily encountered as a nosocomial pathogen (in particular, moist environments). ○ It has also become an important cause of infection, especially in immunocompromised patients (in particular, cystic fibrosis)

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○ particular, cystic fibrosis) ○ The organism is able to survive in environments that have only minimal nutritional components; it has been isolated from the axilla, ear, and perineum and other moist environments such as water in sinks, drains, toilets, and showers Pathophysiology: ○ Virtually all major classes of bacterial virulence systems are found in this organism:  Exotoxins, endotoxins, type III secreted toxins, pili, flagella, proteases, phospholipases, iron -binding proteins, exopolysaccharides, the ability to form biofilms, and elaboration of toxic small molecules such as pyocyanins  One major toxin is exotoxin A, an adenosine diphosphate-ribosylating toxin with activity similar to the diphtheria toxin ○ The organism has bacterial factors produced to counter host defenses, allowing the organism to advance the infectious process ○ Pseudomonas aeruginosa is an opportunistic pathogen. ○ It rarely causes disease in health people unless a physical barrier to infection is lost (i.e. skin, mucous membrane) or an immune deficiency is present ○ Pseudomonas species are both invasive and toxigenic. The three stages of disease are: 1) Bacterial attachment and colonization 2) Local infection 3) Bloodstream dissemination and systemic disease ○ The importance of colonization and adherence is most important when in the context of respiratory tract infection in patients with cystic fibrosis ○ Production of extracellular proteases adds to the organism's virulence by assisting in bacterial adherence and invasion ○ Pseudomonas is also found in contact lens-associated keratitis and in burn and wound infections

Clinical Manifestations: ○ Bacteremia:  Patients are usually febrile, but more severe patients in shock may be hypothermic  The difference between Pseudomonas from other causes of bacteremia are distinctive skin lesions known as ecthyma gangrenosum, which occur in neutropenic patients. These lesions are small, painful, reddish, maculopapular, well-circumscribed lesions that have a geographic margin and begin pink, darken to purple, and finally become black and necrotic  Histopathology indicates that the lesions are caused by vascular invasion after bacteremia and are teeming with bacteria ○ Acute Pneumonia  The respiratory tract is the most frequent site of infection by P. aeruginosa  P aeruginosa plays a major role in ventilator-assisted pneumonia based on results of cultures of endotracheal tube aspirates ○ Chronic Respiratory Tract Infections  P aeruginosa is responsible for chronic infections of the airways associated predominantly Cystic Fibrosis  There is also a chronic relapsing infection by P. aeruginosa that is characterized by increased sputum production, fever, and focal lung infiltrates  Strains from this chronic relapsing infection undergo the same type of mucoid conversion as stains from CF, which reflects the overproduction of a clear pathogenic factor in chronic lung disease ○ Bone and Joint Infections  P aeruginosa is not a frequent cause of bone or joint infections ○ CNS Infections  Primary CNS infections by P. aeruginosa are relatively rare.  Involvement is usually secondary to head trauma or a surgical procedure and found to be noted after bacteremia ○ Eye Infections  Eye infections from P. aeruginosa occur from direct innoculation into tissue as a result of trauma or surface injury caused by contact lenses Keratitis is the most frequent type of disease seen and should be considered a medical emergency MS 114.1 Internal Medicine I Page 2

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surface injury caused by contact lenses  Keratitis is the most frequent type of disease seen and should be considered a medical emergency because of the rapidity in which it can progress and lead to loss of sight Ear Infections  P aeruginosa ear infections vary from the mild swimmer's ear to chronic draining ears, to serious life threatening conditions  Swimmer's ear is commonly seen in children and results from infection of moist macerated skin of the external ear canal  The source of the organism is likely to be the swimming pool if unchlorinated  Also causes chronic suppurative otitis media Urinary Tract Infections  Generally occurs as a complication of the presence of a foreign body such as a stone, stent, or catheter in the urinary tract or an obstruction within the genitourinary system  Paraplegic patients are at high risk  Frequently serves as the nidus, or origin, for P. aeruginosa bacteremia by ascending infection Skin and Soft Tissue, Including Burns  P aeruginosa causes ecythema gangrenosum in neutropenic patients  Secondary infection of chronic skin ulcers or burns can also occur  Maceration of normal skin, such as from soaking in a hot tub, can lead to superficial infection □ Multiple outbreaks linked to whirlpools, spas, and swimming pools  Folliculitis and other lesions (dermatitis) are also caused by P. aeruginosa  Can also be found in burn wound sepsis, but not as frequent. □ Previously, when prevalent, had formation of a black necrotic eschar and sepsis, with or without bacteremia  Diagnosis made by blood culture or by clinical picture of expanding burn lesion caused by infection with P. aeruginosa Endovascular Infections  P aeruginosa may cause endovascular infections, such as endocarditis  In intravenous drug abusers, source is generally paraphernalia or illicit drugs  Organism has also been reported to cause prosthetic valve endocarditis □ Outbreaks on native heart valves have been described in IVDAs Infections in Febrile Neutropenia  Although not as common as it once was, emperic treatment must include coverage against P. aeruginosa for febrile neutropenia  In some parts of the world, P. aeruginosa continues to be a significant problem for neutropenic patients in that it is responsible for the largest proportion of infections caused by a single organism  The clinical syndromes in these patients were bacteremia, pneumonia, and soft tissue infections (manly ecthyma gangrenosum). Uncommon Infections  Noma neonatorum (necrotizing mucosal and perianal infection of newborns)  Toe web infections  "Green nail syndrome" (result of frequent submersion of hands in water). The green discoloration results from diffusion of pyocyanin into the nail bed

Treatment: ○ Treatment of Bacteremia:  Standard of care = β-lactam antibiotic combined with an aminoglycoside □ High failure rates when aminoglycosides are used alone  Adult nonazotemic (azotemia = excess of urea and other nitrogenous wastes in the blood) patients may be given ceftazadime, cefepime, or meropenem.  Patients with serious β-lactam allergy can be given aztreonam ○ Treatment of Pneumonia  Similar treatment as for bacteremia (β-lactam antibiotic combined with an aminoglycoside)  Macrolides can be used, but they have no antibacterial activity against P. aeruginosa; they are thought to suppress the immune response and perhaps suppress production of P. aeruginosa virulence factors □ Most common: clarithromycin and azithromycin (Z-pak) ○ Treatment of Other Infections Most other infections will be treated with β-lactam antibiotic or ciprofloxacin (although bacterial MS 114.1 Internal Medicine I Page 3

 Most other infections will be treated with β-lactam antibiotic or ciprofloxacin (although bacterial resistance of cipro has been documented)

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