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PATHOLOGY OF BACTERIAL INFECTIONS GRAM POSITIVE BACTERIAL INFECTIONS Common gram-positive pathogens include: Staphylococcus, Streptococcus, Enterococcus, Less common diseases caused by gram-positive rod-shaped organisms: diphtheria, listeriosis, anthrax, and nocardiosis. Clostridia, which are gram-positive, are discussed with the anaerobes. All these infections are diagnosed by culture and some special tests mentioned below. Staphylococcal Infections Staphylococcus aureus are pyogenic gram-positive cocci that form clusters like bunches of grapes. These bacteria cause a myriad of skin lesions (boils, carbuncles, impetigo, and scalded-skin syndrome) as well as abscesses, sepsis, osteomyelitis, pneumonia, endocarditis, food poisoning, and toxic shock syndrome (TSS) Staphylococcal Infections S. epidermidis, a species that is related to S. aureus, causes opportunistic infections in catheterized patients, patients with prosthetic cardiac valves, and drug addicts. S. saprophyticus is a common cause of urinary tract infections in young women. Staphylococcal Infections S. aureus possess a multitude of virulence factors, which include surface proteins involved in adherence, secreted enzymes that degrade proteins, and secreted toxins that damage host cells Staphylococcal Infections A furuncle, or boil, is a focal suppurative inflammation of the skin and subcutaneous tissue, either solitary or multiple or recurrent in successive crops. Furuncles are most frequent in moist, hairy areas, such as the face, axillae, groin, legs, and submammary folds. Staphylococcal Infections Beginning in a single hair follicle, a boil develops into a growing and deepening abscess that eventually "comes to a head" by thinning and rupturing the overlying skin. Staphylococcal Infections A carbuncle is a deeper suppurative infection that spreads laterally beneath the deep subcutaneous fascia and then burrows superficially to erupt in multiple adjacent skin sinuses. Carbuncles typically appear beneath the skin of the upper back and posterior neck, where fascial planes favor their spread. Staphylococcal Infections Hidradenitis is a chronic suppurative infection of apocrine glands, most often in the axilla. Infections of the nail bed (paronychia) or on the palmar side of the fingertips (felons) are exquisitely painful. They may follow trauma or embedded splinters and, if deep enough, destroy the bone of the terminal phalanx or detach the fingernail. S. aureus lung infections usually occur in people with a hematogenous source, such as an infected thrombus, or a predisposing condition such as influenza. Staphylococcal scalded-skin syndrome, also called Ritter disease, most frequently occurs in children with staphylococcal infections of the nasopharynx or skin. There is a sunburn-like rash that spreads over the entire body and evolves into fragile bullae that lead to partial or total skin loss. The desquamation of the epidermis in staphylococcal scalded-skin syndrome occurs at the level of the granulosa layer, distinguishing it from toxic epidermal necrolysis, or Lyell's disease, which is secondary to drug hypersensitivity and causes desquamation at the level of the epidermal-dermal junction. Streptococcal Infections Streptococci are gram-positive cocci that grow in pairs or chains and cause a myriad of suppurative infections of the skin, oropharynx, lungs, and heart valves.. S. pyogenes (group A) causes pharyngitis, scarlet fever, erysipelas, impetigo, rheumatic fever, TSS, and glomerulonephritis S. agalactiae (group B) colonizes the female genital tract and causes sepsis and meningitis in neonates and chorioamnionitis in pregnancy. S. pneumoniae, the most important αhemolytic streptococcus, is a common cause of community-acquired pneumonia and meningitis in adults. The viridans group streptococci include several species of α-hemolytic and nonhemolytic streptococci that are normal oral flora and are also a common cause of endocarditis. S. mutans is the major cause of dental caries. Streptococcal infections are diagnosed by culture, and the rapid antigen test for pharyngitis. Streptococcal infections are characterized by diffuse interstitial neutrophilic infiltrates with minimal destruction of host tissues. The skin lesions caused by streptococci (furuncles, carbuncles, and impetigo) resemble those of staphylococci . Erysipelas is most common among middle-aged persons in warm climates and is caused by exotoxins from superficial infection with S. pyogenes. It is characterized by rapidly spreading erythematous cutaneous swelling that may begin on the face or, less frequently, on the body or an extremity. The rash has a sharp, well-demarcated, serpiginous border and may form a "butterfly" distribution on the face On histologic examination there is a diffuse, edematous, neutrophilic inflammatory reaction in the dermis and epidermis extending into the subcutaneous tissues. Microabscesses may be formed, but tissue necrosis is usually minor. Streptococcal pharyngitis, which is the major antecedent of poststreptococcal glomerulonephritis is marked by edema, epiglottic swelling, and punctate abscesses of the tonsillar crypts, sometimes accompanied by cervical lymphadenopathy. Swelling associated with severe pharyngeal infection may encroach on the airways, especially if there is peritonsillar or retropharyngeal Scarlet fever, associated with pharyngitis caused by S. pyogenes, is most common between the ages of 3 and 15 years. It is manifested by a punctate erythematous rash that is most prominent over the trunk and inner aspects of the arms and legs. The face is also involved, but usually a small area about the mouth remains relatively unaffected to produce a circumoral pallor. The inflammation of the skin usually leads to hyperkeratosis and scaling during defervescence. S. pneumoniae is an important cause of lobar pneumonia Enterococcal Infections Enterococci are also gram-positive cocci that grow in chains. Enterococci are often resistant to commonly used antibiotics and are a significant cause of endocarditis and urinary tract infections. Enterococci are also gram-positive cocci that grow in chains. Enterococci are often resistant to commonly used antibiotics and are a significant cause of endocarditis and urinary tract infections Diphtheria Diphtheria is caused by Corynebacterium diphtheriae, a slender gram-positive rod with clubbed ends, that is passed from person to person through aerosols or skin exudate. C. diphtheriae may be carried asymptomatically or cause illnesses ranging from skin lesions in neglected wounds of combat troops in the tropics, and a life-threatening syndrome that includes formation of a tough pharyngeal membrane and toxin-mediated damage to the heart, nerves, and other organs Listeriosis Listeria monocytogenes is a gram-positive, facultative intracellular bacillus that causes severe food-borne infections In acute human infections, L. monocytogenes evokes an exudative pattern of inflamma-tion with numerous neutrophils. The meningitis it causes is macroscopically and microscopically indistinguishable from that caused by other pyogenic bacteria The finding of gram-positive, mostly intracellular, bacilli in the CSF is virtually diagnostic. More varied lesions may be encountered in neonates and immunosuppressed adults. Focal abscesses alternate with grayish or yellow nodules representing necrotic amorphous basophilic tissue debris. These can occur in any organ, including the lung, liver, spleen, and lymph nodes. In infections of longer duration, macrophages appear in large numbers, but granulomas are rare Infants born with L. monocytogenes sepsis often have a papular red rash over the extremities, and listerial abscesses can be seen in the placenta. A smear of the meconium will disclose the grampositive organisms. Anthrax Bacillus anthracis is a large, spore-forming gram-positive rod-shaped bacterium. These bacteria are common pathogens in farm and wild animals that have contact with soil contaminated with B. anthracis spores. Anthrax spores can be ground to a fine powder, making a potent biologic weapon. B. anthracis is typically acquired through exposure to animals or animal products such as wool or hides. There are three major anthrax syndromes. Cutaneous anthrax, which makes up 95% of naturally occurring infections, begins as a painless, pruritic papule that develops into a vesicle within 2 days. As the vesicle enlarges, striking edema may form around it, and regional lymphadenopathy develops. After the vesicle ruptures, the remaining ulcer becomes covered with a characteristic black eschar, which dries and falls off as the person recovers. Bacteremia is rare with cutaneous anthrax. Inhalational anthrax occurs when spores are inhaled. The organism is carried by phagocytes to lymph nodes where the spores germinate, and the release of toxins causes hemorrhagic mediastinitis. After a prodromal illness of 1 to 6 days characterized by fever, cough, and chest or abdominal pain, there is abrupt onset of increased fever, hypoxia, and sweating. Frequently, anthrax meningitis develops from bacteremia. Inhalational anthrax rapidly leads to shock and frequently death within 1 to 2 days. Gastrointestinal anthrax is an uncommon form of this infection that is usually contracted by eating undercooked meat contaminated with B. anthracis. Initially, the person has nausea, abdominal pain, and vomiting, followed by severe, bloody diarrhea. Mortality is over 50%. Anthrax lesions at any site are typified by necrosis and exudative inflammation with infiltration of neutrophils and macrophages. The presence of large, boxcar-shaped grampositive extracellular bacteria in chains, seen histopathologically or recovered in culture, should suggest the diagnosis. Inhalational anthrax causes numerous foci of hemorrhage in the mediastinum with hemorrhagic, enlarged hilar and peribronchial lymph nodes. Microscopic examination of the lungs typically shows a perihilar interstitial pneumonia with infiltration of macrophages and neutrophils and pulmonary vasculitis. Hemorrhagic lesions associated with vasculitis are also present in about half of cases. Mediastinal lymph nodes show lymphocytosis, macrophages with phagocytosed apoptotic lymphocytes, and a fibrin-rich edema B. anthracis is present predominantly in the alveolar capillaries and venules and, to a lesser degree, within the alveolar space. In fatal cases, B. anthracis is evident in multiple organs (spleen, liver, intestines, kidneys, adrenal glands, and meninges). GRAM-NEGATIVE BACTERIAL INFECTIONS Neisserial Infections Neisseria are gram-negative diplococci that are flattened on the adjoining sides, giving the pair the shape of a coffee bean These aerobic bacteria have stringent nutritional requirements and grow best on enriched media such as lysed sheep's blood agar ("chocolate" agar). The two clinically significant Neisseria are N. meningitidis and N. gonorrhoeae. N. meningitidis is a significant cause of bacterial meningitis, particularly among children younger than 2 years of age. The organism is a common colonizer of the oropharynx and is spread by the respiratory route. Approximately 10% of the population is colonized at any one time, and each episode of colonization lasts, on average, for several months. N. gonorrhoeae is an important cause of sexually transmitted disease (STD) It is second only to C. trachomatis as a bacterial causative agent of STDs. Infection in men causes urethritis. In women, N. gonorrhoeae infection is often asymptomatic and so may go unnoticed. Untreated infection can lead to pelvic inflammatory disease, which can cause infertility or ectopic pregnancy Infection is diagnosed by PCR tests, in addition to culture. Whooping Cough Whooping cough, caused by the gram-negative coccobacillus Bordetella pertussis, characterized by paroxysms of violent coughing followed by a loud inspiratory "whoop." B. pertussis vaccination, whether with killed bacteria or the newer acellular vaccine, has been effective in preventing whooping cough. The diagnosis is best made by PCR, because culture is less sensitive. Bordetella bacteria cause a laryngotracheobronchitis that in severe cases features bronchial mucosal erosion, hyperemia, and copious mucopurulent exudate Unless superinfected, the lung alveoli remain open and intact. In parallel with a striking peripheral lymphocytosis (up to 90%), there is hypercellularity and enlargement of the mucosal lymph follicles and peribronchial lymph nodes. Pseudomonas Infection Pseudomonas aeruginosa is an opportunistic aerobic gram-negative bacillus that is a frequent, deadly pathogen of people with cystic fibrosis, severe burns, or neutropenia.93 Many people with cystic fibrosis die of pulmonary failure secondary to chronic infection with P. aeruginosa. P. aeruginosa can be very resistant to antibiotics, making these infections difficult to treat. P. aeruginosa Pseudomonas causes a necrotizing pneumonia that is distributed through the terminal airways in a fleur-de-lis pattern, with striking pale necrotic centers and red, hemorrhagic peripheral areas. On microscopic examination, masses of organisms cloud the tissue with a bluish haze, concentrating in the walls of blood vessels, where host cells undergo coagulative necrosis This picture of gram-negative vasculitis accompanied by thrombosis and hemorrhage, although not pathognomonic, is highly suggestive of P. aeruginosa infection. In skin burns, P. aeruginosa proliferates penetrating deeply into the veins and spreading hematogenously. Well-demarcated necrotic and hemorrhagic oval skin lesions, called ecthyma gangrenosum Disseminated intravascular coagulation (DIC) is a frequent complication of bacteremia. Plague Yersinia pestis is a gram-negative facultative intracellular bacterium that is transmitted from rodents to humans by fleabites or, less often, from one human to another by aerosols Yersinia pestis causes lymph node enlargement (buboes), pneumonia, or sepsis with a striking neutrophilia. The distinctive histologic features (1) massive proliferation of the organisms, (2) early appearance of protein-rich and polysacchariderich effusions with few inflammatory cells but with marked tissue swelling, (3) necrosis of tissues and blood vessels with hemorrhage and thrombosis, (4) neutrophilic infiltrates that accumulate adjacent to necrotic areas as healing begins. In bubonic plague the infected fleabite is usually on the legs and is marked by a small pustule or ulcer. The draining lymph nodes enlarge dramatically within a few days and become soft, pulpy, and plum colored, and may infarct or rupture through the skin In pneumonic plague there is a severe, confluent, hemorrhagic and necrotizing bronchopneumonia, often with fibrinous pleuritis. In septicemic plague lymph nodes throughout the body as well as organs rich in mononuclear phagocytes develop foci of necrosis. Fulminant bacteremias also induce DIC with widespread hemorrhages and thrombi. Chancroid (Soft Chancre) Chancroid is an acute, sexually transmitted, ulcerative infection caused by Hemophilus ducreyi. The disease is most common in tropical and subtropical areas among lower socioeconomic groups and men who have regular contact with prostitutes. Chancroid is one of the most common causes of genital ulcers in Four to seven days after inoculation the person develops a tender, erythematous papule involving the external genitalia. In males the primary lesion is usually on the penis; in females most lesions occur in the vagina or the periurethral area. Over the course of several days the surface of the primary lesion erodes to produce an irregular ulcer, which is more apt to be painful in males than in females In contrast to the primary chancre of syphilis, the ulcer of chancroid is not indurated, and multiple lesions may be present. The base of the ulcer is covered by shaggy, yellow-gray exudate. The regional lymph nodes, particularly in the inguinal region, become enlarged and tender in about 50% of cases within 1 to 2 weeks of the primary inoculation. In untreated cases the inflamed and enlarged nodes (buboes) may erode the overlying skin to produce chronic, draining ulcers Microscopically, the ulcer of chancroid contains a superficial zone of neutrophilic debris and fibrin, with an underlying zone of granulation tissue containing areas of necrosis and thrombosed vessels. A dense, lymphoplasmacytic inflammatory infiltrate is present beneath the layer of granulation tissue. Coccobacilli are sometimes demonstrable in Gram or silver stains, but they are often obscured by other bacteria that colonize the ulcer base. Granuloma Inguinale Granuloma inguinale, or donovanosis, is a chronic inflammatory disease caused by Klebsiella granulomatis (formerly called Calymmatobacterium donovani), a minute, encapsulated, coccobacillus. The organism is sexually transmitted Granuloma inguinale begins as a raised, papular lesion on the moist, stratified squamous epithelium of the genitalia or, rarely, the oral mucosa or pharynx. The lesion eventually ulcerates and develops abundant granulation tissue, which is manifested grossly as a protuberant, soft, painless mass. As the lesion enlarges, its borders become raised and indurated. Disfiguring scars may develop in untreated cases and are sometimes associated with urethral, vulvar, or anal strictures. Regional lymph nodes typically are spared or show only nonspecific reactive changes, in contrast to chancroid. Microscopic examination of active lesions reveals marked epithelial hyperplasia at the borders of the ulcer, sometimes mimicking carcinoma (pseudoepitheliomatous hyperplasia). A mixture of neutrophils and mononuclear inflammatory cells is present at the base of the ulcer and beneath the surrounding epithelium. The organisms are demonstrable in Giemsa-stained smears of the exudate as minute, encapsulated coccobacilli (Donovan bodies) in macrophages. Silver stains (e.g., the Warthin-Starry stain) may also be used to demonstrate the organism. CHLAMYDIAL DISEASES Chlamydiae are obligate intracellular organisms, larger than viruses. The host response is neutrophilic. Chlamydiae are passively taken up into phagocytic vacuoles of host cells in which they multiply; they are best visualized by immunofluorescence or Giemsa-stained cell smears. Cytoplasmic chlamydial inclusions, important in microscopic diagnosis, consist of aggregates of these bodies in their vacuoles. C. trachomatis – the most common cause of sexually transmitted diseases, in men: nongonococcal urethritis and epididymitis; – in women: cervicitis, urethritis, and pelvic inflammatory – Reiter's syndrome; – neonatal conjunctivitis and pneumonia acquired through maternal transmission. – C. trachomatis has been implicated in 20% of adults with pharyngitis. C. psittaci – infects many animals, – but human infection is closely related to contact with birds. C. pneumoniae – a serotype of C. psittaci, – can cause pneumonia, especially in children and young adults. – It may be clinically indistinguishable from pneumonia caused by Mycoplasma pneumoniae. – The organism has been found in atheromatous lesions, and infection is associated with increased risk of coronary artery disease. Chlamydial infection Tissue response Inclusion body conjunctivitis Acute Ornithosis Acute Trachoma Chronic, including granulomas Veneral disease Chronic, including granulomas Ornithosis (Psittacosis, parrot fever) Ornithosis is caused by Chlamydia psittaci, transmitted to man by inhalation of dusts containing infected-bird excreta. Most any kind of bird can do it; the classic is parrots. Inhalation of the agent may lead to an asymptomatic infection (a flu like illness), or a serious, even fatal neutrophilic pneumonia. In severe cases there is edema, alveolar damage, consodalition, and bacterial superinfection. Histologically, there is edema and mononuclear leukocytic infiltration within the alveolar septa. Seroproteinaceous fluid or fibrin may accumulate within the alveoli. Alveolar septal cells may contain intracytoplasmic chlamydial inclusions (Giemsa or immunofluorescence stain shows inclusion bodies in the cytoplasm). Lethal generalized disease is marked by focal necrosis in the liver and spleen and by diffuse mononuclear leukocytic infiltration in the kidneys, heart, and brain. Recovery is the rule after a few weeks. The infection may remain latent, and may recur. Trachoma Trachoma is a chronic suppurative eye disease follicular keratoconjunctivitis caused by Chlamydia trachomatis . A disease of the poor nations, and the world's most important cause of preventable blindness. Infection of the surface of the eye with an aggressive strain (A-C) of Chlamydia trachomatis, a micro-organism which flourishes in arid and sandy countries Chlamydia reaches the eyes by means of fingers, contaminated particles, or flies. The resulting inflammation produces proliferation of the conjunctival surface tissue. Infection can be either self-limiting or progressive. In a progressive infection, there is a suppuration with lymphoplasmacytic infiltration and formation of lymphoid cell follicles. Lymphoid follicles and epithelial hyperplasia help establish the diagnosis. Soon, the conjunctiva ulcerates, and penetration into the cornea leads to pannus (inflammatory membrane) formation with scarring granulation tissue. With enough scarring, the eyelids fail to close properly. Many of these people are also vitamin A deficient. With no access to antibiotics (or any medical care) blindness will result. Inclusion conjunctivitis Inclusion conjunctivitis is a benign, self-limited, suppurative conjunctivitis that occurs in babies of mothers having Chlamydia trachomatis birth canal infection. Or caught from people with genital chlamydia (fingers, un-halogenated swimming pools). The latter produces "swimming pool conjunctivitis". It is characterized by conjunctival hyperemia, edema and monocyte-rich purulent exudate infiltration. The pannus and corneal scarring seen in trachoma do not occur. Lymphogranuloma venereum (LGV) Infection of the anogenital region with aggressive Chlamydia trachomatis (serotypes L-1, -2, or -3). Fortunately rare, this disease is encountered primarily in the tropics; non-tropical cases have mostly been in gay men. Stages of the disease: Stage I. The disease begins with a small vesicle that promptly bursts and ulcerates with abundant neutrophilic exudation at the site of inoculation (genital, labial, anorectal, buccopharyngeal, digital). Later, granulomas may form at the ulcer base, and clamydial inclusions can be seen by specific immunofluorescence technique. Stage II. It spreads to the axillary or inguinal lymph nodes, which suppurate (buboes; there is a granulomatous admixture; stellate microabscesses rimmed by granulomas are typical). In heterosexual males, inguinal lymphadenopathy is rule; in females, spread is to the deep pelvic and perirectal lymph nodes. The disease does not become systemic. Stage III. The end stage is rectal strictures and/or elephantiasis due to dense fibrosis, and chronic inflammatory infiltration with abundant plasma cells. Chlamydial urethritis and cervicitis Very common sexually transmitted diseases, usually caused by less virulent strains of Chlamydia trachomatis than cause LGV. This organism is our most important cause of nongonococcal urethritis and nongonococcal cervicitis. This is an important cause of fallopian tube infections ("pelvic inflammatory disease"), and it can be transmitted to the baby during birth. Look for DNA probes as the future's preferred way of making the diagnosis of chlamydial genital infections. Rapid enzyme immunoassay to screen a man's urine to see if he has chlamydia on board. Chlamydia pneumoniae is an important cause of wheezy adult lung infections and very likely a major player in much chronic asthma. RICKETTSIAL DISEASES - Rickettsiae are obligate intracellular bacteria that cannot grow except within cells. - They are inhabit ticks, mites fleas or lice. - Infection is contracted either by an arthropod bite or by contact of arthropod excreta with abraded skin. - Rickettsiae never part of the "normal flora", and always indicate disease. Typhus fever (epidemic typhus) A dread disease caused by Rickettsia prowazekii, transmitted by louse feces. Epidemics occur during wartime, famine, and natural disaster. Death is not uncommon in untreated cases. It results from brain, heart, and lung involvement. Patients have generalized skin rash, headache, fever, mental changes, and even gangrene (from vasculitis). The essential pathology is swelling and necrosis of the endothelial cells in many parts of the body. Endothelial proliferation and swelling in the capillaries, arterioles, and venules may narrow the lumina of these vessels. In milder cases, the macroscopic changes are limited to the skin rash and small hemorrhages. In severe cases there may be areas of necrosis of the skin with gangrene of the tips of fingers, nose, ear lobes, scrotum, penis, and vulva. In such cases, irregular ecchymotic hemorrhages may be found internally, principally in the brain, heart muscle, testes, serosal membrane, lung, and kidneys. In the brain of untreated patients, reactive glia mixed with inflammatory cells produce characteristic typhus nodules. Mononuclear cell meningitis, and ring hemorrhages about the small vessels may occur. Typically, there is also nonspesific lymphadenitis and splenitis. Foci resembling the typhus nodules of the brain may appear in the heart, kidney, testes, and liver. Rocky Mountain spotted fever of Americans is caused by Rickettsia rickettsi. It is a tick-borne rickettsia which invades both endothelial and vascular smooth muscle cells. Hemorrhages (spots) from necrosis of the skin arterioles are present everywhere, including on the palms and soles, also the scrotum/vulva. Patients are systemically sick, and the vasculitis and hemostatic chaos can be fatal if untreated. Scrub typhus (tsutsugamushi fever) is caused by Orientia tsutsugamushi, carried by a mite, endemic throughout the Far East and Pacific rim. Q-fever is a pneumonitis caused by Coxiella burnetti. The "Q" comes from Queensland, Australia, but this infection is found worldwide. The disease is common among sheep, and can be transmitted by ticks or by droplets. Coxiella can tolerate drying, unlike the other rickettsia. Bacillary angiomatosis is an opportunistic infections (AIDS patients) caused by either Bartonella henselae (the cat-scratch fever organism) or Bartonella (Rochalimaea) quintana (the trench fever organism). Dilated vessels in the liver, spleen, and elsewhere are typical. Bacteria can accumulate in masses dense enough to appear as granular hyaline. The disease responds to antibiotics. MYCOPLASMAL DISEASES Mycoplasmas are also called pleuropneumonia-like organisms (PPLO's) or Eaton agent. They are little (0.3-0.8 ) bacteria without cell walls. Mycoplasma genitalium and Ureaplasma urealyticum are causes purulent, acute, nongonococcal urethritis as well as chronic pelvic inflammatory disease. Mycoplasma pneumoniae is probably the commonest cause of a chest cold (primary atypical pneumonia), generally with an upper respiratory infection. It behaves as an extracellular human parasite, and incites epithelial damage in the airways. The pulmonary involvement mimics to viral pneumonia. The epidemics are mostly seen in closed institutions (e.g., military recruits, prisons). Death is rare. ACTINOMYCETES Nocardiosis Actinomycosis NOCARDIOSIS Infection with "Nocardia", a lowvirulence, filamentous, gram-positive, weakly acid-fast bacterium An acute or chronic, often disseminated, granulomatous-suppurative infectious disease usually caused by the aerobic gram-positive bacillus Nocardia asteroides, a soil saprophyte. N. asteroides usually enters the body via the lungs and rarely via the GI tract or skin. Immunosuppressed patients develop lung infections with Nocardia asteroides. Nocardia typically cause single or multipl, chronic, necrotizing, walled-off abscesses without granuloma formation. Predisposing factors: – – – – – – – Lymphoreticular malignancies, organ transplantation, high-dose corticosteroid immunosuppressive therapy, HIV, underlying pulmonary disease. About half the patients have no preexisting disease. Primary skin lesions are necrotizing or purulent, or both. "Immunologically normal" people can develop Nocardia brasiliensis skin infections ("mycetomas", a generic name for hard-to-treat, nodular "fungal" skin infections, especially common on the feet in countries where shoes are a luxury). – The problem is common in Latin America. An acute or chronic, often disseminated, granulomatous-suppurative infectious disease usually caused by the aerobic gram-positive bacillus Nocardia asteroides, a soil saprophyte. N. asteroides usually enters the body via the lungs and rarely via the GI tract or skin. Disseminated nocardiosis usually begins as a pulmonary infection that may resemble actinomycosis, N. asteroides is more likely to disseminate hematogenously with abscess formation in the brain, kidneys or in multiple organs. Skin or subcutaneous abscesses occur frequently, sometimes as a primary site of localized infection. Lung lesions are nonspecific and resemble those of TB or suppurative pneumonia. Pleural effusion also may occur. Metastatic brain abscesses may occur in as many as 1/3 of cases. Nocardia asteroides ACTINOMYCOSIS Chronic fibrosing, pus-producing infections with multiple draining sinuses due to an anaerobic "Actinomyces" bacterium, usually Actinomyces israelii. The causative anaerobic, gram-positive microorganisms, species of Actinomyces or Propionobacterium (most commonly A. israelii), are often present comensally on the gums, tonsils, and teeth. The characteristic lesion is an indurated area of multiple, small, communicating abscesses surrounded by granulation tissue. Tissue lesions tend to form sinus tracts that communicate to the skin and drain a purulent discharge containing yellow sulfur granules. The classic form is cervicofacial actinomycosis, with running sores in the mouth, and on the face and neck. At first the gingivae and adjacent soft tissues become swollen and indurated. In course of time, a large, woody swelling develops,characteristically over the angle of the jaw. The inflammation often extends to the skin to perforate and form multiple sinuses. Periostitis and osteomyelitis with extensive destruction of bone are common accompaniments. In the cervicofacial (lumpy jaw) form, the most common portal of entry is decayed teeth – The cheek, tongue, pharynx, salivary glands, cranial bones, meninges, or brain may be affected, usually by direct extension. Lung abscesses (thoracic actinomycosis) – pulmonary disease results from aspiration of oral secretions. The peritoneal cavity may become involved after rupture of the gut (abdominal actinomycosis) – a break in the mucosa of a diverticulum, the appendix, or during trauma. In a localized pelvic form, actinomycosis is a complication of certain types of intrauterine device (IUD) contraceptives. Abdominal actinomycosis arises from invasion of the intestinal mucosa, most commonly of the appendix or colon. – Bowel lesions produce localized peritoneal abscess, sometimes with the formation of draining external sinuses. Thoracic actinomycosis: lung abscesses may cause pulmonopleural fistulas, and empyeme. – Further spread may erode the ribs and the anterior chest wall or extends into the vertebral column and pericardium. Smears of actinomycosis pus show naked-eye "sulfur granules" (large yellow actinomyces colonies). The histologic features: – central suppuration surrounded by granulation tissue – intense fibrosis – bacterial colony consisting of intertwined radiating flaments (rays), capped by eosinophilic material (sunburst pattern). Spread from primary sites occurs rarely, presumably by hematogenous spread from primary sites of infection In the generalized form, infection spreads hematogenously to the skin, vertebral bodies, brain, liver, kidney, ureter, and (in women) pelvic organs. Actinomycosis of other sites follows bites or punch injuries. Pelvic actinomycosis was a complication of the oldfashioned intra-uterine devices. The radially-oriented bacteria at their edges earned the actinomyces the unfortunate name "ray fungi". Actinomyces israelii