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Chapter 20

Chapter 20. The Gram-Negative Bacilli of Medical Importance. Aerobic Gram-Negative Nonenteric Bacilli. Common characteristics Gram negative bacilli

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Chapter 20

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  1. Chapter 20 The Gram-Negative Bacilli of Medical Importance

  2. Aerobic Gram-Negative Nonenteric Bacilli • Common characteristics • Gram negative bacilli • Ubiquitous - many can be recovered from environment, especially wet environments in hospitals (respiratory therapy equipment, sinks, water baths) and contaminate medications, sterile solutions & other fluids used on patients • Infections usually require compromised individual (opportunistic); Nosocomial infections common • Often resistant to disinfectants or antimicrobial agents - even thrive in their presence • Most are non-fermentative (oxidative or non-saccharolytic)

  3. Pseudomonadaceae • Major NFGB to cause human infections; major cause of nosocomial infections; infections may be exogenous or endogenous (from GI or respiratory tract)

  4. Pseudomonas aeruginosa • Burn wound infections • Respiratory disease - pneumonia; associated with chronic lung disease in persons with cystic fibrosis (most isolates are quite mucoid) • Otitis externa (swimmer’s ear) - one of Pseudomonas infections occurring in healthy people • Folliculitis - associated primarily with persons using whirl-pool baths and swimming pools • Other - meningitis, urinary tract infections, endocarditis & osteomyelitis

  5. Pseudomonas aeruginosa • Folliculitis - associated primarily with persons using whirl-pool baths and swimming pools

  6. Pseudomonas aeruginosa • Pseudomonas aeruginosa produces a blue to green pigment and is resistant to many types of antibiotics

  7. Burkholderia cepacia Isolated in nosocomial outbreaks of pneumonia, septicemia, urinary tract infections & wound infections • Infections usually traced to use of contaminated disinfectants

  8. Burkholderia pseudomallei • Etiologic agent of malioidosis; a glanders-like disease of humans; manifests as septicemia; high mortality • Seen primarily in Southeast Asia; seen in US among military returned from Southeast Asia, especially Vietnam • Soil organism; acquired through abrasions or wounds contaminted with soil

  9. Stenotrophomonas maltophilia • May cause wide spectrum of nosocomial infections including endocarditis, meningitis, pneumonia & UTI • Infections require compromised host

  10. Epidemiology - Pseudomonas • Natural habitat - most are environmental (soil & water) or part of normal flora (respiratory or intestinal tract) of humans or animals • Transmission • Endogenous • Exogenous • Inhalation - droplet infection; often associated with respiratory therapy equipment • Contamination of wounds with soil, water, or disinfectants containing organisms

  11. Epidemiology - Pseudomonas • Control & prevention • Vaccines - vaccines to Pseudomonas aeruginosa may be used for patients with burns, cystic fibrosis or immunosuppression • Treatment • Antimicrobial therapy based on antibiogram • Supportive therapy - fluid replacement, analgesics to lower fever

  12. Brucella • Brucella abortus - cattle • Brucella suis - pigs • Clinical manifestations - Brucellosis (also known as undulant fever, Malta fever)

  13. Pathogenesis - Brucella • Pathogenesis (all species produce similar diseases) • Penetrate break in skin or mucous membranes • Organisms carried within PMN’s to regional lymph nodes & thoracic duct • Virulent organisms enter macrophages; multiply in RES (liver, spleen, BM) = facultative intracellular parasite • Organisms killed by T-cell response or infection progresses to systemic granulomas; bacteremic episodes accompanied by chills & fever (undulant fever)

  14. Brucellosis • Begins 7-21 days after infection with malaise, chills & fever • Afternoon or evening drenching sweats common – may continue for years (chronic) • Body aches, headache, & anorexia with weight loss may occur with prolonged illness; splenomegaly, lymphadenopathy & hepatomegaly occur • Osteomyelitis = most frequent complication

  15. Epidemiology - Brucella • Natural habitat - sheep, cattle, pigs; disease mild or asymptomatic in animal hosts • Transmission - direct or indirect contact of mucus membranes with infected animal tissue of body fluids (blood or milk); occupational disease of farmers, abattoir workers, & vets • Prevention and control (fewer that 200 cases/yr. in US) • Prevent disease in livestock with vaccines • Minimize exposure (protective clothing) • Pasteurize milk products • Treatment - tetracycline combine with streptomycin or gentamicin drugs of choice; often unsuccessful because of intracellular nature of organisms

  16. Francisella tularensis and Tularemia • Clinical manifestations - tularemia (also called glandular fever, rabbit fever, tick fever or deerfly fever) • Primarily intracellular parasite of macrophages in RES • Incubation period = 3-5 days; symptoms begin abruptly; fever, chills, malaise & fatigue • Systemic infections - may follow any form; lesions produced in multiple sites • Mortality rate = 5-30% without treatment

  17. Forms of Tularemia - based on entry site of organism • Ulceroglandular - most common form; follows skin contact; ulcers at site of exposure become necrotic & ulcerative, regional lymph node become swollen (lymphadenopathy) & painful; rarely fatal • Glandular - follows skin contact; lymphadenopathy major symptom • Typhoidal - follows ingestion; abdominal manifestations & prolonged fever = symptoms • Oculoglanular - follows conjunctival entry; purulent, painful conjunctivitis accompanied by lymphadenopathy • Pneumonic - follows inhalation or seeding of lungs from another body site after bacteremia; can spread person to person

  18. Epidemiology of Tularemia • Natural habitat • Wild animals, esp. rabbits, squirrels, muskrats, beaver & deer; usually asymptomatic • Reservoir probably wood tick; passed trans-ovarianly • Routes of transmission • Direct contact with animal = most common • Occasionally associated with bite or scratch of dog or cat after they have ingested diseased animal • May be transmitted by ticks (more common in US) or deer flies

  19. Epidemiology of Tularemia • Prevention and control - difficult because of large reservoir • Protective clothing & eye wear when skinning animals • Prompt removal of ticks • Thorough cooking of suspect meats • Vaccines available for those unable to avoid contact • Treatment - streptomycin for prolonged periods (intracellular existence)

  20. Bordetella • Classification • B. pertussis • B. parapertussis • Clinical Manifestations • B. pertussis (strict human pathogen) = whooping cough • Pathogenesis - exposure; selective tropism (ciliated epithelium) with immobilization & destruction of epithelium; local inflammation • Incubation = 7-10 days • Stages: • Catarrhal – rhinorrhea or nasal drainage; 1-2 weeks; highly communicable • Paroxysmal – hacking cough; lymphocytosis (40,000/mm3); 2-4 weeks • Convalescent - decrease in symptoms; 3-4 weeks • Complications - most commonly involves lung; others = convulsions, hemorrhage & hernias • B. parapertussis - milder form of B. pertussis

  21. Epidemiology of Bordetella • Natural habitat - strict human pathogens • Transmission - droplet (close contact) • Prevention and control - vaccine = inactivated whole cell suspension = original & more purified forms now available; combined with diphtheria & tetanus toxoid = DPT • Treatment - antimicrobics (erythromycin) early; later = supportive

  22. Legionella • Species most commonly isolated in clinical lab - Legionella pneumophila • Pathogenesis • Organisms enter via mucus membranes of respiratory tract or through breaks in skin • Taken up by macrophages (facultative intracellular parasite); shielded from antibody; elicit cell-mediated response • Inflammatory response occurs in lungs or skin - organisms can spread to other body sites via blood

  23. Clinical manifestations of Legionella - large spectrum of diseases • Legionnaires’ disease (legionellosis) - acute pneumonia • Opportunistic - risk factors = immunosuppression, cigarette smoking, chronic pulmonary disease, alcohol consumption, endotracheal intubation • Multisystem disease but primarily pneumonia - cough, chest pains, abnormal chest sounds • May be fatal - rarely seen in children; males predominate

  24. Clinical manifestations of Legionella - large spectrum of diseases • Pontiac fever - acute, self-limited, nonpneumonic, febrile illness • Resembles allergic response rather than infection • Pneumonia does not occur • Self-limiting & non-fatal; fever, headache, dizziness & muscle pain • Other infections = cutaneous abscesses, post-op. wound infections, hepatic abscesses, pericarditis, myocarditis, & bacteremia

  25. Epidemiology of Legionella • Habitat - primarily aquatic; may also be in soil • Transmission - aerosols; person to person not known • Control - difficult to impossible; requires disinfection of water (air-conditioner water towers, etc.); organisms resistant to chlorine; removed by heating to 60 C • Treatment - erythromycin

  26. Enterobacteriaceae • Enterobacteriaceae - now over 25 genera & more than 100 species • Classification of major groups of medically important genera • Escherichiae - Escherichia and Shigella • Edwardsielleae - Edwardsiella • Salmonellae - Salmonella, Arizona, and Citrobacter • Klebsielleae - Klebsiella, Enterobacter, Serratia • Proteeae - Proteus, Morganella, Providencia • Yersineae - Yersinia

  27. Common characteristics of Enterobacteriaceae • Gram negative, rod-shaped, non-sporogenous • Facultative anaerobes • Do not produce indophenol oxidase (oxidase negative) • Peritrichous flagellation when motile - 2 pathogenic genera characteristically non-motile = Klebsiella & Shigella • Reduce nitrates to nitrites • Possess pili or fimbriae • Most = normal in GI tract - exceptions include Salmonella & Shigella, Yersinia & certain strains of Escherichia which cause disease when present in intestine

  28. Common characteristics of Enterobacteriaceae • Fermentation of glucose (dextrose) • Fermentative utilization of carbohydrates • Classification based on growth & production of acids in O-F • Fermenters - produce gas and/or large amounts strong acids under anaerobic conditions • Non-fermenters - for not produce acids under anaerobic conditions • Oxidizers - produce smal amounts of weakacids under aerobic conditions • Nonsaccharolytic - unable to utilize carbohydrates as energy source

  29. O-F medium contains small amounts peptones, large amounts carbohydrates (usually glu) & pH indicator thatdetects small amounts of acid

  30. Anatomical or cell products that serve as virulence factors for Enterobacteriaceae • Toxins • Endotoxin • Part of LPS layer of G(-) cell wall • Released on cell death • Causes fever, DIC & depression of RES • Exotoxins/enterotoxins • Proteins secreted as organisms grow • Generally associated with G(+) but may be produced by G(-) • Specific in activity (neurotoxins, cytotoxins, etc) • Most are heat labile - enterotoxins = heat stable • Antigenic - vaccines possible • Hemolysins • Capsules (esp. Klebsiella) • Pili

  31. Antigenic characteristics for Enterobacteriaceae • O antigens = somatic CW antigens • H antigens = flagella • K antigens = capsular • Identification of O and H antigens = serotyping; used esp. with Salmonella & Shigella and sometimes E. coli

  32. Escherichia coli - Intestinal Manifestations • Enteropathogenic (EPEC) • Primary disease = diarrhea in infants & children under 2 years • Belong to limited number of O antigenic groups • Mechanism of pathogenicity poorly understood; produce adhesion factor (EAF) causing tight adherence to mucosa & destroy microvilli

  33. Escherichia coli - Intestinal Manifestations • Enterotoxigenic (ETEC) • Secretory diarrhea - watery stools (Traveler’s diarrhea) • Mechanism of pathogenicity = 2 toxins (LT = heat stable; antigenic; Ab’s protective; similar to cholera toxin; and ST = heat stable toxin; non-antigenic) & surface antigen that enables organisms to attach to intestinal epithelial cells • Toxins cause enterocytes to lose water & electrolytes - increases adenyl (LT) or guanyl (ST) cyclase that increase levels of cAMP or cGMP in cells

  34. Escherichia coli - Intestinal Manifestations • Enteroinvasive (EIEC) • Dysentery-like illness similar to Shigella – invade mucosal cells causing destruction of colonic epithelium • Mechanism of invasiveness unknown - appear to produce low levels of Shiga-like toxin • Stool contains blood & mucus

  35. Escherichia coli - Intestinal Manifestations • Enterohemorrhagic (EHEC) • Hemorrhagic colitis & hemolytic uremic syndrome (can result in acute renal failure with microangiopathic hemolytic anemia & thrombocytopenia) • Mechanism - production of one or both Shiga-likeor Vero-toxins (SLT-I and/or SLT-II); destroy epithelial lining of intestine • Early isolates belonged to serotype O157:H7 but other EHEC strains now recognized • Outbreaks traced to contaminated food, esp. hamburger meat • Symptoms - severe abdominal cramping & copious bloody diarrhea

  36. Escherichia coli - Extraintestinal Manifestations • Urinary tract infections • Caused most commonly by E. coli; esp. cystitis • Pili main virulence factor; mediates adherence • May become systemic (bacteremia; septicemia) • Meningitis - common cause in newborns; assoc. with encapsulated strains • Sepsis - frequent cause; shock and death occur from endotoxemia • Pneumonia • Nosocomial infections (hospital acquired)

  37. Enterobacter, Klebsiella, and Serratia • All are normal in intestine - not known to produce intestinal disease; Klebsiella also normal in upper respiratory tract; Enterobacter found normally on plants • Considered opportunistic pathogens (compromised host required) • Primary cause of sepsis resulting from contaminated fluids • Most common infections = urinary tract infections & pneumonia • Klebsiella rhinoscleromatis = rhinoscleroma (granuloma of nose & pharynx)

  38. Enterobacter, Klebsiella, and Serratia • Capsule commonly present in highly virulent strains

  39. Enterobacter, Klebsiella, and Serratia • Serratia marcescens produces an intense red pigment when grown at room temperature • Capable of producing pneumonia in compromised host

  40. Proteus, Morganella & Provedencia • Opportunistic infections including bacteremia & septicemia • Proteus commonly associated with urinary tract and wound infections - urease critical for colonization & disease by forming ammonia from urea which may directly damage urinary epithelium and increase pH to facilitate deposition of calcium, magnesium & ammonium-magnesium phosphates to form stones; may also produce pneumonia & septicemia • Providencia a significant cause of burn infections

  41. Shigella (Sh. flexneri, Sh. sonnei, Sh. boydii and Sh. dysenteriae) - all etiologic agents of bacillary dysentery (bloody diarrhea) • Effects attributed to Shiga toxin; kills cells resulting in inhibition of absorption of fluids • Toxic products cause inflammatory response involving PMN’s & macrophages resulting in bloody, mucopurulent diarrhea • Organisms remain localized in colonic epithelium • Humans only hosts - transmitted person to person via fecal/oral route • Severest form = Sh. dysenteriae; thought to produce greater amounts Shiga toxin • Most prevalent in US = Sh. sonnei; also mildest form

  42. Salmonella (Sal. typhi, Sal. choleraesuis & Sal. enteritidis) • Originally over 1700 species recognized; naming changed over years; current practice uses 3 species (above) further subdivided into types by O & H antigens • Cause infection in man & animals (animals may serve as reservoir; esp. fowl) - acquired by ingestion of contaminated food or drink

  43. Types of infection for Salmonella • Enterocolitis (gastroenteritis) - organisms multiply in epithelial lining of small & large intestine causing inflammatory response; most common form of Sal. infection • Remains localized in intestine • Caused by many of Salmonella sp. • Symptoms begin 8-48 hrs. after ingestion = nausea, headache, vomitting, profuse diarrhea; lasts 2-7 days • Effects attributed to secretion of cholera - like toxin (heat stable enterotoxin) & low levels of cytotoxin

  44. Types of infection for Salmonella • Enteric fevers ( typhoid, paratyphoid & nontyphoidal) • Begins as inflammation of sm. intestine; regional lymph nodes invaded - lymphatic system - blood -organs & tissues (esp. liver, kidneys, spleen, BM, gall bladder & sometimes heart); reinvade intestine from biliary tract; multiplication in skin = rose spots • Symptoms = splenomegaly, headache, loss of appetite, abdominal pain, weakness, stupor & continued fever • Most often detect when reinvade GI • Sal. typhi has ability to grow intracellularly in monocytes where protected from Ab & complement

  45. Types of infection for Salmonella • Septicemia (bacteremia) • Fulminating blood infection with or without intestinal involvement • Suppurating lesions found throughout body • Most commonly caused by Sal. choleraesuis • May result in metastatic infections (bones, joints, meninges or cardiovascular)

  46. Types of infection for Salmonella • Carrier state • Follows enteric fever or septicemic forms • Organisms become lodged in biliary (liver) tract, esp. gall bladder (organisms are resistant to bile) • May be no symptoms - excrete organisms for months to years; prolonged state may require surgical removal of gall bladder

  47. Yersinia • Y. pestis (formerly called Pasteurella pestis) • Etiologic agent (causes) plague • Zoonosis of rats - man infected by rat flea (vector) bite • Nature of virulence factors unknown • Forms - depend on mode of acquisition • Bubonic - bite of rat flea; organisms travel from site via lymphatics to regional lymph nodes; cause inflammation = bubo (swelling) • Pneumonic - inhalation from another human case • Sometimes called black death - organisms cause localized hemorrhages or trigger DIC (endotoxemia)

  48. The Infection Cycle of Yersinia pestis

  49. Yersinia • Y. enterocolitica • Acquired via oral/fecal route - esp. contaminated milk • Cause enterocolitis with swelling of mesenteric lymph nodes & abdominal pain - may mimic appendicitis or dysentery • Septicemic form resembling typhoid fever rare; metastatic lesions possible esp. compromised persons • Major cause of enteric illness in Europe, Canada & northern US - not commonly found here • Nature of virulence factors unknown

  50. Epidemiology of Enterobacteriaceae • Natural Habitat • Most are normal in GI tract of man & animals; E. coli only found in GI - used as indicator of fecal contamination if found elsewhere • Other members widely distributed in nature (soil & plants) • Salmonella, Shigella, Yersinia & some strains of E. coli not normal in GI or elsewhere & considered intestinal pathogens • Man only known host for Shigella • Salmonella common in fowl

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