*Medically Important Gram-Positive BacilliCan be subdivided into three general groups, based on presence or absence of endospores and acid-fastnessThree general groups:Endospore-formersNon-endospore-formersIrregular shaped and staining properties

*

*Spore-Forming BacilliGenus BacillusGenus ClostridiumGenus Sporolactobacillus

*General Characteristics of the Genus Bacillus Gram-positive, endospore-forming, motile rodsMostly saprobicAerobic and catalase positiveVersatile in degrading complex macromoleculesSource of antibioticsPrimary habitat is soil2 species of medical importance:Bacillus anthracisBacillus cereus

*Bacillus AnthracisLarge, block-shaped rodsCentral spores that develop under all conditions except in the living bodyVirulence factors polypeptide capsule and exotoxins3 types of anthrax:Cutaneous spores enter through skin, black sore- eschar; least dangerousPulmonary inhalation of sporesGastrointestinal ingested spores

Cutaneous anthrax*

*Control and TreatmentTreated with penicillin, tetracycline, or ciprofloxacinVaccines Live spores and toxoid to protect livestockPurified toxoid; for high risk occupations and military personnel; toxoid 6 inoculations over 1.5 years; annual boosters

*Bacillus anthracis

*Bacillus CereusCommon airborne and dustborne; usual methods of disinfection and antisepsis are ineffectiveGrows in foods, spores survive cooking and reheatingIngestion of toxin-containing food causes nausea, vomiting, abdominal cramps, and diarrhea; 24-hour durationNo treatmentIncreasingly reported in immunosuppressed

*The Genus ClostridiumGram-positive, spore-forming rodsAnaerobic and catalase negative120 speciesOval or spherical spores produced only under anaerobic conditionsSynthesize organic acids, alcohols, and exotoxinsCause wound infections, tissue infections, and food intoxications

*

*Gas GangreneClostridium perfringens most frequent clostridia involved in soft tissue and wound infections myonecrosisSpores found in soil, human skin, intestine, and vaginaPredisposing factors surgical incisions, compound fractures, diabetic ulcers, septic abortions, puncture wounds, gunshot wounds

*Virulence FactorsVirulence factorsToxinsAlpha toxin causes RBC rupture, edema, and tissue destructionCollagenaseHyaluronidaseDNase

Growth of Clostridium perfringens*

*PathologyNot highly invasive; requires damaged and dead tissue and anaerobic conditionsConditions stimulate spore germination, vegetative growth and release of exotoxins, and other virulence factorsFermentation of muscle carbohydrates results in the formation of gas and further destruction of tissue

Myonecrosis*

*Treatment and PreventionImmediate cleansing of dirty wounds, deep wounds, compound fractures, and infected incisionsDebridement of disease tissueLarge doses of cephalosporin or penicillinHyperbaric oxygen therapy No vaccines available

*Clostridium Difficile-Associated Disease (CDAD)Normal resident of colon, in low numbersCauses antibiotic-associated colitis Relatively non-invasive; treatment with broad-spectrum antibiotics kills the other bacteria, allowing C. difficile to overgrowProduces enterotoxins that damage intestinesMajor cause of diarrhea in hospitalsIncreasingly more common in community-acquired diarrhea

*Treatment and PreventionMild uncomplicated cases respond to fluid and electrolyte replacement and withdrawal of antimicrobialsSevere infections treated with oral vancomycin or metronidazole and replacement culturesIncreased precautions to prevent spread

Antibiotic-associated colitis*

*Tetanus Clostridium tetaniCommon resident of soil and GI tracts of animals Causes tetanus or lockjaw, a neuromuscular diseaseMost commonly among geriatric patients and IV drug abusers; neonates in developing countries

*PathologySpores usually enter through accidental puncture wounds, burns, umbilical stumps, frostbite, and crushed body partsAnaerobic environment is required for vegetative cells to grow and release toxinTetanospasmin neurotoxin causes paralysis by binding to motor nerve endings; blocking the release of neurotransmitter for muscular contraction inhibition; muscles contract uncontrollably Death most often due to paralysis of respiratory muscles

The events in tetanus*

Neonatal tetanus*

*Treatment and PreventionTreatment aimed at deterring degree of toxemia and infection and maintaining homeostasisAntitoxin therapy with human tetanus immune globulin; inactivates circulating toxin but does not counteract that which is already boundControl infection with penicillin or tetracycline; and muscle relaxantsVaccine available; booster needed every 10 years

*Clostridial Food PoisoningClostridium botulinum rare but severe intoxication usually from home canned foodClostridium perfringens mild intestinal illness; second most common form of food poisoning worldwide

*Botulinum Food PoisoningBotulism intoxication associated with inadequate food preservationClostridium botulinum spore-forming anaerobe; commonly inhabits soil and water

*PathogenesisSpores are present on food when gathered and processedIf reliable temperature and pressure are not achieved air will be evacuated but spores will remainAnaerobic conditions favor spore germination and vegetative growthPotent toxin, botulin, is releasedToxin is carried to neuromuscular junctions and blocks the release of acetylcholine, necessary for muscle contraction to occurDouble or blurred vision, difficulty swallowing, neuromuscular symptoms

Physiological effects of botulism toxin*

*Infant and Wound BotulismInfant botulism caused by ingested spores that germinate and release toxin; flaccid paralysisWound botulism spores enter wound and cause food poisoning symptoms

*Treatment and PreventionDetermine presence of toxin in food, intestinal contents or fecesAdminister antitoxin; cardiac and respiratory supportInfectious botulism treated with penicillinPractice proper methods of preserving and handling canned foods; addition of preservatives

*Clostridial GastroenteritisClostrium perfringensSpores contaminate food that has not been cooked thoroughly enough to destroy sporesSpores germinate and multiply (especially if unrefrigerated)When consumed, toxin is produced in the intestine; acts on epithelial cells, acute abdominal pain, diarrhea, and nauseaRapid recovery

*

*Gram-Positive Regular Non-Spore-Forming BacilliRegular: stain uniformly and do not assume pleomorphic shapesMedically important:Listeria monocytogenesErysipelothrix rhusiopathiae

*Listeria MonocytogenesNon-spore-forming gram-positive Ranging from coccobacilli to long filaments1-4 flagellaNo capsulesResistant to cold, heat, salt, pH extremes, and bileVirulence attributed to ability to replicate in the cytoplasm of cells after inducing phagocytosis; avoids humoral immune system

*Multiplication cycle of Listeria monocytogenes

*Epidemiology and PathologyPrimary reservoir is soil and water; animal intestinesCan contaminate foods and grow during refrigerationListeriosis most cases associated with dairy products, poultry, and meat Often mild or subclinical in normal adults Immunocompromised patients, fetuses, and neonates; affects brain and meninges20% death rate

*Diagnosis and ControlCulture requires lengthy cold enrichment processRapid diagnostic tests using ELISA, immunofluorescence, and DNA analysisAmpicillin and trimethoprim/ sulfamethoxazolePrevention pasteurization and cooking

*Gram-Positive Irregular Non-Spore-Forming BacilliIrregular: pleomorphic, stain unevenlyMedically important genera:CorynebacteriumPropionibacteriumMycobacteriumActinomycesNocardia

*20 genera; Corynebacterium, Mycobacterium, and Nocardia greatest clinical significanceAll produce catalase, possess mycolic acids, and a unique type of peptidoglycan

*Corynebacterium DiptheriaeGram-positive irregular bacilli

*EpidemiologyReservoir of healthy carriers; potential for diphtheria is always presentMost cases occur in non-immunized children living in crowded, unsanitary conditionsAcquired via respiratory droplets from carriers or actively infected individuals

*Incidence and case fatality of diphtheria

*Pathology2 stages of disease: Local infection upper respiratory tract inflammation Sore throat, nausea, vomiting, swollen lymph nodes; pseudomembrane formation can cause asphyxiation Diptherotoxin production and toxemia Target organs primarily heart and nerves

The Iditirod

*Diagnostic MethodsPseudomembrane and swelling indicativeStainsConditions, historySerological assay

Diagnosing diphtheria*

*Treatment and PreventionAntitoxinPenicillin or erythromycinPrevented by toxoid vaccine series and boosters

*Genus PropionibacteriumPropionibacterium acnes most commonGram-positive rodsAerotolerant or anaerobicNontoxigenicCommon resident of pilosebaceous glandsCauses acne

*Mycobacteria: Acid-Fast BacilliGram-positive irregular bacilliAcid-fast stainingStrict aerobes Produce catalasePossess mycolic acids and a unique type of peptidoglycanDo not form capsules, flagella, or sporesGrow slowly

*

Microscopic morphology of mycobacteria*

*Mycobacterium TuberculosisTubercle bacillusProduces no exotoxins or enzymes that contribute to infectiousnessVirulence factors contain complex waxes and cord factor that prevent destruction by lysosomes or macrophages

*Epidemiology of Tuberculosis Predisposing factors include: inadequate nutrition, debilitation of the immune system, poor access to medical care, lung damage, and geneticsEstimate 1/3rd of world population and 15 million in U.S. carry tubercle bacillus; highest rate in U.S. occurring in recent immigrantsBacillus very resistant; transmitted by airborne respiratory droplets

*Course of Infection and Disease5% to 10% of infected people develop clinical diseaseUntreated, the disease progresses slowly; majority of TB cases contained in lungsClinical tuberculosis divided into:Primary tuberculosisSecondary tuberculosis (reactivation or reinfection)Disseminated (extrapulmonary) tuberculosis

Staging of tuberculosis*

*Primary TBInfectious dose 10 cellsPhagocytosed by alveolar macrophages and multiply intracellularlyAfter 3-4 weeks immune system attacks, forming tubercles, granulomas consisting of a central core containing bacilli surrounded by WBCs tubercleIf center of tubercle breaks down into necrotic caseous lesions, they gradually heal by calcification

Section of a tubercle*

*Secondary TBIf patient doesnt recover from primary tuberculosis, reactivation of bacilli can occurTubercles expand and drain into the bronchial tubes and upper respiratory tractGradually the patient experiences more severe symptomsViolent coughing, greenish or bloody sputum, fever, anorexia, weight loss, fatigueUntreated, 60% mortality rate

*Extrapulmonary TBDuring secondary TB, bacilli disseminate to regional lymph nodes, kidneys, long bones, genital tract, brain, and meningesThese complications are grave

*Diagnosis In vivo or tuberculin testingMantoux test local intradermal injection of purified protein derivative (PPD); look for red wheal to form in 48-72 hours induration; established guidelines to indicate interpretation of result based on size of wheal and specific population factorsX-raysDirect identification of acid-fast bacilli in specimenCultural isolation and biochemical testing

*Skin testing for tuberculosis

X-ray of secondary tubercular infection*

Fluorescent acid-fast stain of Mycobacterium tuberculosis*

*Management and Prevention of TB6-24 months of at least 2 drugs from a list of 11One pill regimen called Rifater (isoniazid, rifampin, pyrazinamide)Vaccine based on attenuated bacilli Calmet-Guerin strain of M. bovis used in other countries

*Mycobacterium Leprae: The Leprosy Bacillus Hansens bacillus/Hansens DiseaseStrict parasite has not been grown on artificial media or tissue cultureSlowest growing of all speciesMultiplies within host cells in large packets called globiCauses leprosy, a chronic disease that begins in the skin and mucous membranes and progresses into nerves

*Epidemiology and Transmission of LeprosyEndemic regions throughout the worldMechanism of transmission is not fully verifiedNot highly virulent; appears that health and living conditions influence susceptibility and the course of the diseaseMay be associated with specific genetic marker

Leprosy lesions*

*Course of Infection and DiseaseMacrophages phagocytize the bacilli, but a weakened macrophage or slow T cell response may not kill bacillusIncubation from 2-5 years; if untreated, bacilli grow slowly in the skin macrophages and Schwann cells of peripheral nerves2 forms possible:Tuberculoid asymmetrical, shallow lesions, damage nerves results in local loss of pain receptionLepromatous a deeply nodular infection that causes severe disfigurement of the face and extremities, widespread dissemination

*

*DiagnosingCombination of symptomology, microscopic examination of lesions, and patient historyNumbness in hands and feet, loss of heat and cold sensitivity, muscle weakness, thickened earlobes, chronic stuffy noseDetection of acid-fast bacilli in skin lesions, nasal discharges, and tissue samples

Feather test for leprosy*

*Treatment and PreventionTreatment by long-term combined therapyPrevention requires constant surveillance of high-risk populationsWHO sponsoring a trial vaccine

*Infections by Non-Tuberculosis Mycobacteria (NTM)M. avium complex third most common cause of death in AIDS patientsM. kansaii pulmonary infections in adult white males with emphysema or bronchitisM. marinum water inhabitant; lesions develop after scraping on swimming pool concreteM. scrofulaceum infects cervical lymph nodesM. paratuberculosis raw cows milk; recovered from 65% of individuals diagnosed with Crohns disease

Chronic swimming pool granuloma*

*

*Actinomycetes: Filamentous BacilliGenera Actinomyces & Nocardia are nonmotile filamentous bacteria related to mycobacteriaMay cause chronic infection of skin and soft tissuesActinomyces israelii responsible for diseases of the oral cavity, thoracic or intestines actinomycosesNocardia brasiliensis causes pulmonary disease similar to TB

Symptoms and signs of actinomycosis*

Nocardiosis*

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