JOSEPH ONGRÁDIINSTITUTE OF MEDICAL MICROBIOLOGY

SEMMELWEIS UNIVERSITYBudapest 2013

GRAM POSITIVE SPORE-FORMING

RODS

NON-SPORE FORMING OBLIGATE

ANAEROBIC BACTERIA AND

ASSOCIATED INFECTIONS

ALLOCATED IN SEVERAL TAXONOMIC UNITSHERE: FUNCTIONAL GROUPINGS

GRAM POSITIVE SPORE-FORMING RODS

CLOSTRIDIUM GENUSONLY!!!

NON-SPORE FORMINGANAEROBIC BACTERIAGram + cocci and

rodsGram – cocci and

rods

COMMON CHARASTERISTICS

CATABOLISM: ANAEROBIC (fermentation)lack of the cytochrom system, superoxide dismutase,catalase and peroxidase enzymes

TOXIC END PRODUCTS OF OXYGEN METABOLISM

OBLIGATE ANAEROBIC --------- AEROTOLERANT

SPECIMEN COLLECTION: transport media without O2

CULTIVATION: removal of O2 (GasPack, etc.)

DISTINCT CHARACTERISTICS

GRAM POSITIVESPORE-FORMING RODS

Exogenous infections1 species = 1 diseaseSmall number of species ���� more clinical entitiesVaried pathomechanisms,

but molecularly wellcharacterized

Diagnosis: unambigousTreatment: unambigousPrevention: unambigous

NON-SPORE FORMING ANAEROBIC BACTERIA

Endogenous infectionsMany species Mixed infections: (polymicrobial)

more aerobic + anaerobic species

����

similar clinical entities

Diagnosis: complicatedTreatment: difficultPrevention: difficult

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ENDOSPORE: ENSURES SURVIVALPRODUCED IN THE ENVIRONMENT (SOIL, WATER, AIR)EXTREME RESISTANCE(PARAMETERS AND BIOLOGICAL MONITORING OF STERILIZATION PROCEDURES)

Bacillus genus

AerobicSpore Ø < bacterium ØB. anthracis (flagella-, capsule+) B. cereus (flagella+, capsule-) enterotoxins: (food poisoning) heat stabile: emeticheat labile: diarrhoeaeye, wound infections, IVDA

B. subtilis: contaminant ,bioterrorism model

B. megaterium: contaminantB. mesentericus: contaminantB. stearothermophilus, B. pumilis:

monitoring sterilization proceduresB. globigii: modelling bioterrorismsOther Bacilii: insecticides

Clostridium genus

Obligate anaerobicSpore Ø > bacterium ØPeritrichous flagella(capsule: C. perfringens)Exogenous infectionsEndogenous: C. perfringens

C. difficile Intensive metabolism,

gas production +/-Neurotoxic (exotoxin): C. tetani (non- invasive) C. botulinum (toxicosis) Histotoxic (invasive):C. perfringens + C. septicum +C. novyi + otherEnteral (nosocomial): C. difficile (dysbacteriosis) 4

MORPHOLOGY: 5-10 μm x 1 μmSquare endsCapsule (in host), central spore(in nature)

CULTIVATION:agar/bloodagar: medusa headlecithinase (weak)

PATHOGENIESIS: cattle, sheep> feces/carcasses>soil>saprophytic > spores persist for decades in dry earth> human infection

Capsule+exotoxin (protective antigen, edema factor, lethal factor)

CLINICAL FINDINGS:

Skin anthrax:animal products , scratch,wound, > 12-24 h latency> gelation edema>

malignant pustule>necrotic ulcer>bacteremia>sepsis

Inhalation anthrax: hemorrhagic lobular pneumonia,edema>meningitis, sepsis, shock „woolsorter's disease”biological warfare (bioterrorism)

Intestinal anthrax: abdominal pain, bloody diarrhea, vomiting, ascites

Cutaneous anthrax

Respitarory anthrax

Intestinalanthrax

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DIAGNOSIS:Specimens: fluid or pus from pustules

blood, sputum, fecesstaining, immunofluorescent stainingcultivation on blood agar(no hemolysis, no swarming)

Serology: precipitation, hemagglutinationto detect animal or human antibodiesAscoli test: immune serum + tissue extractAnimal infection: guinea pig andmouse – sensitive, rat – resistant

PREVENTION: public health control measuresdeep burial in lime-pitsautoclaving animal productsprotective clothing

Vaccination: live attenuated vaccine for animalshumans (occupational risk): cell-free vaccine

TREATMENT: as early as possible!penicillin (except in inhalation anthrax)tetracyclin, erythromycin, clindamycin

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WHAT IS BIOTERRORISM?A BIOTERRORIST ATTACK IS

THE DELIBERATE RELEASE OF BACTERIA, VIRUSES, OTHER GERMSOR TOXINS TO CAUSE ILLNESS, DEATH, DISRUPTION OR FEARIN HUMANS, LIVESTOCK, FOOD CROPS AND ENVIRONMENTAL RESOURCES

39 MAJOR MICROORGANISMS AND BIOLOGICALS TO BE USED (NATO categorization)

RECENT DEVELOPMENT:corrosive microbes to destroy electric appliances, health care products,

gaskets

THE MOST LIKELY, PREDICTED METHOD OF NEXT BIOLOGICAL ATTACKS: AEROSOLIZED AGENTS

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CHARACTERISTICS OF BIOTERRORIST ATTACKS

SUDDEN AND UNEXPECTED ONSETLARGE NUMBER OF CASESTYPICAL, ATYPICAL OR UNKNOWN CLINICAL ENTITIESTHE EFFECT: DEADLY (SMALLPOX)

INCAPACITIVE, TEMPORARY (Q-FEVER)SPREAD: CONTAGIOUS (PLAGUE)

NON-CONTAGIOUS (TOXINS)THE FATE OF AFFECTED PERSONS: CURABLE (ANTHRAX)

INCURABLE (EBOLA)SPREAD OF THE AGENT: aerosol (<5 micrometer droplets)

ventillation systems, water supply, food, public transportinfected humans, animals, vectors, contaminated objects

THE TERRORIST: strongly motivated, fanatic, well educated,good financial support minority groups, governmental support: global terrorism

(BIOLOGICAL CRIMES: THREATENING USE OF MICROBES FOR COMMON CRIMES)

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BIOTERRORISM AGENT CATEGORIZATION

CATEGORIZATION

HOW EASILY THEY ARE TO OBTAIN, WEAPONIZE,

DISSEMINATE

HOW MUCH DEATH, THE SEVERITY OF ILLNESS

HOW MUCH DAMAGE, DISRUPTION OR FEAR THEY

MIGHT CAUSE

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CATEGORY AHigh priority agents (organisms, toxins) that pose the highest risk to the public security:easy spread or transmitted from person to personhigh death rate, major public health impactcause public panic, social disruptionrequire special action for public health preparedness

Variola majorBacillus anthracisClostridium botulinum (toxin)Yersinia pestisFrancisella tularensisFILOVIRUSES (Ebola, Marburg viruses)ARENAVIRUSES (Lassa, Junin, Machupo)BUNYAVIRUSES (Crimean-fever, Rift-valley fever)

2010 SU Dept. Public Health 12

THE MOST IMPORTANT MICROORGANISMS FOR BIOTERRORISM (II)

CATEGORY BTHE SECOND HIGHEST PRIORITYMODERATELY EASY TO SPREADMODERATE ILLNESS RATES, LOW DEATH RATESREQUIRE SPECIFIC ENHANCEMENTS OF LABORATORY CAPACITY

Brucella spp.Burkholderia malleiBurkholderia pseudomalleiRickettsia prowazekiiCoxiella burnettiChlamydia psittaciAlphaviruses (Venezuelan horse encephalitis)Staphylococcus aureus (enterotoxin B)Salmonella spp.Escherichia coli O57:H7Vibrio cholerae Shigella spp.Cryptosporidium parvum

2010 SU Dept. Public Health 13

THE MOST IMPORTANT MICROORGANISMS FOR BIOTERRORISM (III)

CATEGORY C EMERGING PATHOGENS THAT COULD BE ENGINEERED FOR THE FUTURE

EASILY AVAILABLEEASILY PRODUCED AND SPREADATYPICAL OR NEW DISEASESPOTENTIAL HIGH MORBIDITY AND MORTALITY RATESMAJOR HEALTH IMPACT

NIPAH VIRUS, HANTA VIRUSRECOMBINANT MICROBES (bacteria, viruses, fungi)THE FUTUREADAPTING ANIMAL VIRUSES TO HUMANS (Iraq: camel smallpox virus)ENHANCED PATHOGENICITY OF KNOWN MICROBES

insertion of IL-4 gene into mouse pox virus to inhibit immune functions(Australia)Clostridium botulinum: to spread from person to person (Soviet Union)Bacillus anthracis: insertion of more virulence genes to circumvent vaccination(Soviet Union)recombination of Ebola and HIV (Soviet Union)insertion of antibiotic resistance genes to produce polyresistant bacteria (SU)

RISK OF ANTHRAX INFECTION

U.S. Postal Service distribution clerk Sheila Dickson-Ongrady uses gloves as shesorts mail in Hamilton Township, N.J., facility Tuesday. An employee of thefacility is believed to have contracted inhalation anthrax (Laredo MorningTimes).

Saprophyte in the soil

MORPHOLOGY: flagella +, capsule –

CULTIVATION: swarming, hemolysis on blood agar

PATHOGENESIS:1. Enterotoxin>food poisoning, intoxication

Emetic type (spores: soiI>rice, pasta) Diarrheal type (meat)2. Other: eye infections (trauma, foreign body>

keratitis, end-, panophthalmitis) endocarditis, meningitis, osteomyelitis, pneumonia, IVDA

OTHER BACILLIParasites of insects < commercial insecticidesFood poisoning?

DIFFERENTIAL DIAGNOSIS: biochemistry, phage typization

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Tetanus (1888)

MORPHOLOGY: 2-5 μm x 1-2 μm, flagella (specific antigen), terminal spore

CULTIVATION: obligate anaerobic ββββ-hemolysis on blood agar

PATHOGENESIS: 1884EXOTOXIN=tetanospasmin (151 kD, A-B-C chains)Released by bacteriolysis. Minimal wound>necroparasite>non invasivegermination and toxin production is aided by associated pyogenic infection, calcium salts reducing oxidation-reduction potentialToxin absorption in neurons>retrograde axonal transport to CNS >circulation>fixed to gangliosides> postsynaptic inhibition of acetylcholineinhibitory factor>generalized muscular spasms, hyperreflexia, seizures =TOXEMIA (tetanolysin=exotoxin, non pathogenic)

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Opisthotonus

Trismus

Risus sardonicus Neonatal tetanus

TETANUS

CLINICAL FINDINGS:

5-7 days of latency>spasms> convulsive tonic contraction of voluntary muscles> lockjaw, hydrophobia, opisthotonus, interference with

mechanics of respiration>death. Fully conscious!

INFECTION: soil, horse stool (occupational disease),spores in air

wounds, uterus, umbilical stump (90% in developing countries), abortion, burns

iatrogenic: surgery, ointments, catgut, injections mortality: 50-60%, 1 M cases/year worldwide

DIFFERENTIAL DIAGNOSIS: rabies, strychnin poisoning

TREATMENT:1.Symptomatic: proper care of wounds, surgical debridement (no hyperbaric oxygen) muscle relactants, sedation (external stimuli precipitate tetanic seizures), assisted ventilation2.Toxoid recall injectiontoxoid + antitoxin iv. (earlier horse serum,recently human serum: tetanus immunoglobulin, HTIG) 3. Antitoxin: before toxin becomes fixed onto nerves4.Antibiotics (penicillin, tetracyclin to stop toxin production)

treatment of associated pyogenic infection

PREVENTION: toxoid - active immunizationDPT combination (childhood)recall injections in every 10 years (toxoid 0.5 ml)totally preventable, immunization is mandatory

Booster shot in the elderly population would be ideal!

SAPROPHYTE BACTERIA (SOIL, INTESTINAL TRACT, DUNG)

MORPHOLOGY: 7-8 μm x 1-2 μm, Gram+spore Ø > bacterium ØGermination into bacterium > sporulationC. perfringens: capsulePeritrichous flagella: C. novyi, C. septicum,

C. histiolyticum, C. sporogenes, C. tertium, C. bifermentans, C. fallax, C. sordelli, etc.(90 species/20 human pathogens)

CULTIVATION: anaerobic, gas production(aerotolerants: milk stormy fermentation, clot torn)

ANTIGENS: 12 types

BIOCHEMISTRY: 1. Toxins: α, β, …,τ(αααα=lecithinase, LD50=50 ng, hemolysing, cell lysing, cardiotoxicinhibition by antitoxin: Nagler-reaction)toxinogenic strains: A-E 2. Enzymes: collagenase, hyaluronidase, proteinase, DNase, etc.

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PATHOGENESIS: normal habitat in the gut (skin, vagina) flora

Pathogenical local effects = tissue necrosis:1. >endogenous infections: Colon surgery, colon-carcinoma,appendicitis>perforation,uterus <instrumental abortus, puerperal infections,abscess in pelvis (female),brain abscess +/- meningitis, empyema, pneumonia, biliary tract inflammations (male, diabetes)

2. Exogenous infection: soil, feces> war, trauma, iatrogenicfoul-smelling discharge, edema malignum,gas-phlegmone.myositis: edema,myonecrosis,exsudate,rapid progression, crepitation (acetylene, H2, etc), cellulitis

General effects = toxic: malaise, hypotonia, fever, vomiting, nervousity, toxemia, shock, death.

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GAS GANGRENE

3. Bacteremia (10-15%): death

4. C. perfr. "A" (C,D): food poisoning, meat dishes high protein content protects bacteria form strong acidic pHincubation: 9-15 hsymptomps: abdominal cramps, diarrhea<enterotoxin (through sporulation, spore coat) ileum, jejunum

(w/o adenylyl/guanylyl cyclase) self limited, no treatment is needed (but: infusion application)

5. C. perfringens "C": enteritis necrotisans (pigbel) contaminated pork,New Guinea

<ββββ toxinhighly fatal in childrenprevention: immunization with type C toxoid

6. C. septicum: enterocolitis + neutropenianatural: leukemia, congenital neutropeniaiatrogenic: cytotoxic drugs

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DIAGNOSIS: microscopy, cultivation (chopped meat-glucose medium, egg yolk medium), biochemistry, gas chromatography, toxin-neutralization (VERO-cells) phage typization, DNA-probes

TREATMENT:1. ANTITOXIN

(polyvalent: C. perfringens, C. septicum, C. novyi)to detoxity patients rapidly

2. Antibiotics (penicillin, chloramphenicol, erythromycin, tetracyclin). Metronidazol

3. Symptomatic carepromt and extensive surgical debridement, hyperbaric oxygen early amputation

PREVENTION: Cleansing of contaminated wounds

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Pseudomembranous colitisIatrogenic: antibiotic-associated diarrhea MORPHOLOGY: spores CULTIVATION: obligate anaerobic. Resistant. PATHOGENESIS: in normal flora (3% of adults)colonization: in newbornsin adults during hospitalization from the hand ofpersonnel, endoscopes, devices NON INVASIVE (yes: newborns, neutropenia) TOXEMIA (plasmid, phage, regulation?)toxin A: 440-500 kD enterotoxin (watery diarrhea)toxin B: 360-470 kD cytotoxic (colon wall destruction)Binding to gut wall: gradual > microabscesses >contraction > bleeding>necrosis>inflammation>protein loss>watery/bloody diarrhea PROLONGED TREATMENT WITH ANTIBIOTICS(aminoglycosid, clindamycin) > dysbacteriosis > selectionof resistant mutants > 4-9 days of incubation, abdominalpain > diarrhea, fever, elevated number of WBC(rarely: perforation, peritonitis, acute arthritis)

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CLINICAL DIAGNOSIS: endoscopy MICROBIOLOGICAL DIAGNOSIS:1. Cultivation

(cycloserin, cefoxitin, fructose-agar, CCFA)2. Phage typization3. Toxin detection

toxin B on VERO cells (24h CPE) and neutralisationtoxin A detection: latex agglutination toxin A+B: ELISAPCR

TREATMENT:1. Discontinuing administration of offending antibiotic2. Antibiotics: vancomycin, metronidazol, bacitracin3. Symptomatic: cholestyramin

(=toxin B binding, but: binds vancomycin) 4. Surgical (in case of perforation)PREVENTION: vancomycin in case of carriers and hospitalized patientsmedical personneldisinfection of medical devices, endoscopes:glutaraldehyde, Na-hypochlorite, iodine (sporocidal)wearing gloves during physical examinations by health care personnel

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MORPHOLOGY: 3-8 μm x 1-2 μm, flagella, sporeCULTIVATION: blood agar, anaerobicANTIGENS: common "O", type specific "H" EXOTOXINS: A-H (A, B, E /F/ human pathogenic) 150-165 kD, 2 chains, disulfide bonds. Phage control. Heavy chain: binding to motor nerve endplates, internalization, light chain blocks acetylcholine releaseExtremely toxic: 1-2 µg lethal doseHeat labile: 100 oC, 20 min

PATHOGENESIS: J. Kerner, 18201.Botulism (botulus = sausage), food poisoning spore > food (canned,vacuum packed,smoked, spiced alkaline products, home canned vegetables) > germination >eaten w/o cooking/baking (20', 100C) > toxin absorption from gut (INTOXICATION)2.Spore > honey > colonization in infants>toxin production and absorption > poor feeding, weakness, floppy baby > sudden infant death syndrome (1976)

Complete recovery3.Wound infection > toxin absorption (1943)EXOTOXIN in circulation > nerve endings > flaccid paralysis

Saprophyte, ubiquiter in nature, (soil, dung ����vegetables, meat products)

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CLINICAL FINDINGS: 1-2h—1-2 days of latency, speech difficulty, double vision, inability to swallow, muscular weakness, +/- gastroenteritis, respiratory paralysis, cardiac arrest>no fever>deathFully conscious. High mortality (65>25%)Recovery without antitoxins in serum

DIAGNOSIS: toxin detection: leftover food, vomiting, stool (infants), approx. for 1 month toxin-neutralization: mouse injection, ELISA from sera: passive HA, RIA

TREATMENT: 1. Polyvalent (A,B,E) antitoxin80.000 U horse serum: promtly administered

2.Symptomatic: adequate ventilation (for 100 days!)3.Infants, wound infections: antibiotics (penicillin 10-20 MU/day)

Contraindicated: tetracyclin, aminoglycosid (due to nerve toxicity)PREVENTION:1. strict regulation of commercial canning food hygiene2. home canning: boiling food for >20 min before consumption

toxic food (beans, corn, peas, fish, vacuum-packed fish in plastic bags)spoiled, rancid, cans „swell”, innocuous appearance

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GENUS Species Biochemistry Residence

Gram positive cocci

Peptostreptococci 13 Protein hydrolysis/utilization

Mouth, vaginaPeptococci 1 Mouth, respiratory tract,

vagina, skinAnaerob streptococci 3

Gram positive rodsAcids

Propionibacteria 4 Propionic Skin, mouth, vaginaBifidobacteria 8 Acetic/lactic Gut, mouth, vaginaLactobacilli 56 Lactic Gut, mouth, vaginaActinomyces 20 +/- fermentation Gut, mouth, vaginaEubacteria 45 Butyric Gut, mouth, vaginaMobiluncus 2 Hydrolysis Vagina, rectum

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GENUS Species Biochemistry/characteristc

Residence

Gram negative cocci

Veilonella 3 Lactic acid Mouth, vagina

Acidaminococci 1 Acetic/lactic acid Gut

Megasphera 1 Capronic acid Gut

Gram negative rods

Bacteriodes 18 Capsule Mouth, gut, vagina

Prevotella 16 Pigment Mouth, vagina

Porphyromonas 8 Pigment Mouth

Fusobacterium 4 Polymorph Mouth, gut, vagina

Leptotrichia 2 Elongated Mouth

CONTINOUSLY CHANGING TAXONOMY: genera, number of species, new characteristics 31

>40 species pathogenic in human

MICROBIOLOGYObligate anaerobic ---------- microaerophilModerate biochemical activityProtein hydrolisisStarch and carbohydrate fermentation:

CO2, foul-smelling gases

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Anaerobic streptococci:S. hanseniiS. pleomorphusS. parvulus

Residence:mainly respiratory tract (particularly the pharynx)

Cultivation:non-hemolytic or alpha-hemolytic

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Peptostreptococcus microsresident in the normal mouth flora

Produced diseases: periodontitis,abscesses around tooth implants(24%)hematogenic spread ���� brain abscesschronic sinusitis in children, nasopharyngitis, otitis mediaretropharyngeal abscess, pulmonary abscess, erythema

Peptostreptococcus anaerobiusresident in normal mouth flora

Produced diseases: as P. microsperitonitis appendicitis, diverticulitis, after abdominal surgery

postpartum endometritis, septic abortion

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Peptococcus nigerProduced diseases: postpartum endometritis,

tuboovarial abscessseptic abortion

CoprococcusRuminococcus

Residents in the normal flora of human and animal

Sarcina ventriculiMostly in the gut flora of vegetarian peopleUnusual high number in the stomach: cancer

GaffkyaResident in the normal gut flora

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Pathomechanism:~ 15%- of normal floraPredominantly in dental plaques and periodontal pocketsContinously changing resident flora in the mouth and gutDepending on age and nutrition (food habits)

Polymicrobial (mixed) aerobic +anaerobic infection

1. aerobic bacteria growth ����

2. lack of normal oxygenization in tissues����3. tissue destruction/necrosis, anaerobic conditions����4. vast proliferation of anaerobic bacteria����5. abscess formation, suppuration, gangrene, gas production

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Specimen collection:aspiration, punction

Laboratory process:smears, staining

Cultivation:usually small, grey colonies or other dark pigmentsno ideal selective media are availableother microbes overgrow gram positive anaerobic cocci

Identification at species level:no concensus protocol or scheme, uncertaincarbohydrate fermentation, gas productionenzyme reaction (urease, phosphatase, etc.)gas- liquid chromatography (GLC)

Common end products: acetate, butyrate, capronic acid

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Penicillin resistance(due to the mutations of penicllin binding proteins)

Resistance to metronidazole(mainly the microaerophilic species)

Effective antibiotics:clindamycin (depending on geographical location)amoxicillin + clavulic acid4th generation quinolones (e.g. trova- and clinafloxacin)

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BACTEROIDES GENUSintensive sugar fermentationstrictly anaerobic, very pleomorphic, non-motilepolysaccharide capsule: B. fragilisno lipopolysaccharide endotoxincolonization: fimbriae

Normal inhabitants of the upper respiratory tract, intestinaland female genital tract1011 organism/g stool(B. caccae, B. merdae, etc.)

Produced anaerobic infections:abdominal, brain, lung abcesses, empyema, PIDsurgical infections, peritonitis (pus: foul smelling)bacteremia ���� endocarditis

Taxonomical changes: Bacteroides melaninogenicus ����Porphyromonas gingivalis, Prevotella melaninogenica

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PORPHYROMONAS GENUSPorphyromonas gingivalisOxygen tolerant, small black colonies

on chocolate agarno carbohydrate fermentation,

but proteolytic

Porphyromonas endodontalis, P. asaccharolytica

Residents of the normal mouth floraProduced diseases: soft tissue infection followinghuman bites

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PREVOTELLA GENUSmoderate carbohydrate fermentationglucose fermentation ���� acid productionsaccharose fermentation!proteolysispigment production

P. intermedia, P. melaninogenica (B. melaninogenicus), P. denticola, P. loeschii

residents in the normal mouth floraendogenous infections, inflammationsperiodontitis, surgical wound infection

and abscesses

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FUSOBACTERIUM GENUSPleomorphic rods, produce butyric acidConvert threonine to propionic acidCystein, methionin: H2S productionF. nucleatum**, F. alocis, F. sulci, F. necrophorum, F. periodonticum*

** and * in the normal mouth flora, others in the gut** Prevotella/Porphyromonas coinfection

Fusospirochetosis: nomaOccassionally: Fusobacterium the only species

in an infection (e.g. osteomyelitis)LEPTOTRICHIA GENUS

Pleomorphic rodsFirst isolation: anaerobic,subcultures: elevate CO2 level requirementL. buccalis: resident in the normal mouth florain immunocompromised individuals: ulcerative gingivitisFrequent coinfection with Treponema, Porphyromonas,

Fusobacterium species 42

Metronidazole (Klion)

Amoxicillin + clavulic acid (Augmentin)

Imipenem

Chloramphenicol(severe side effects)

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Acne (carbunculus,phegmone,sepsis): Propionibacterium

Skin (carbunculus): Eubacterium

Chronic sinusitis: Peptostreptococcus, Eubacterium

Post-maxillo-facial or periodontal surgery: Bacteroides, Fusobacterium, Porphyromonas, Prevotella, Actinomyces, Peptostreptococcus, Veilonella, Propionibacterium

Gingivitis ulcerans: Leptotrichia, Porphyromonas, Fusobacterium (+Treponema)

Peritonsillar abscess: Fusobacterium

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Brain abscess: Peptostreptococcus

Pulmonary abscess, empyema: Bacteroides, Porphyromonas, Prevotella, Peptostreptococcus

Thoracal infection: Actinomyces

Hepatic- and perihepatic abscesses : Bacteroides

Peritoneal infections, peritonitis, bowel rupture, post-surgicalinfection, war injury: Bacteroides fragilis, Gram+ anaerobic cocci,

Actinomyces

IUD in women, abscess, criminal (instrumental) abortus, salpyngitis, uterus abscess: Bacteroides, Fusobacterium,

Peptostreptococcus, Mobiluncus

Bacterial vaginosis: Mobiluncus, Porphyromonas, Prevotella, Gram+ anaerobic cocci (G.vaginalis)

Perirectal abscess, fistule: Bacteroides, Fusobacterium45

Necrotising cellulitis in the limbs: gas gangrene clostridia

Joint infections: Gram+ anaerobic cocci

Leg ulcers: mixed infection (but: Clostridium)

Bacteremia, septicemia, endocarditis:Bacteroides fragilis, Propionibacterium, Clostridium, Mobiluncus

Infections in immunocompromised: Bifidobacterium, Lactobacillus

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LOCAL FACTORS

ENDOGENOUS INFECTIONSdermal and mucosal woundsdiminished tissue oxygenization(diabetes mellitus, angiopathy)surgery (oral, abdominal, gynecological)

EXOGENOUS INFECTIONShuman or animal bites

SYMPTOMSfoul-smelling pus, exsudate < fatty acids(diagnosis: gas chromatography)abscess formation, necrosis, gas production(differential diagnosis!)

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NEWBORN: sterile, colonization in few days

SMALL CHILDREN: mixed flora (cocci, bacilli)FROM PUBERTY:1. Aerobic and anaerobic Lactobacilli (Döderlein)

estrogen > glycogen fermentation of epithelial cells > lactic acid production > pH 4-4.5

(~ treatment: 0.5% lactic acid)

2. Resident flora: Bacteroides, Mobiluncus, Gram+ cocci, αααα-hemolysing streptococci, enterococci, Gardnerella , Mycoplasma, Ureaplasma, staphylococci, Mobiluncus, Candida species etc.

3. Transient flora: Enterobacter, staphylococci, streptococci, clostridia

Critical pH (preventing harmful microbes): 6.0-6.5Anaerobic : aerobic ratio: 2-5:1Sexual activity: individual and continously changing flora

MODEL: VAGINA

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BACTERIAL VAGINOSISAlterations in the ratio of the normal flora = dysbacteriosis >

inflammation

1. Decreased ratio of Lactobacilli in the flora2. Activation of endogenous bacteria = endogenous infection >

increasing ratio > massive infection3. Promoting factors

hormonal changes (age, menses, gravidity, oral contraception)chemical effects: antibiotics, chemotherapymechanical effects: contraceptive barriers, IUD

4. Consequences: pH increase (alkaline) > increasing ratio of all anaerobic bacteria (1000:1)>genital discharge> „amin vaginosis”>recurrent vaginal and urinary tract infections(109/ml Mobiluncus, Prevotella, Porphyromonas, Gram+anaerob cocci, Myco-, Ureaplasma, Gardnerella, etc.)infection of the sexual partners (non-gonorrhoic urethritis)or the newborn at time of delivery

DIAGNOSIS: clue cells, presence of PMNL, amin-test49

In the majority of cases: mixed (aerobic + anaerobic) infection

Surgical debridement, excision of all devitalized tissues

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THERAPY ANAEROBESGram positive Gram negative

Recommendedwithout sensitivity test

ββββ-lactam + ββββ-lactamase inhibitors:e.g. Augmentin

imipenemchloramphenicol

clindamycin metronidazole

Recommended as determined

by sensitivity tests

tetracyclineserythromycins

clindamycincefoxitin

moxalactamother β-lactams

penicillinesclindamycin metronidazole

Notrecommended

(resistant)

aminoglycosidesfluoroquinolones

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www.bact.wisc.edu/Bact330/lectureanthrax

www.cdc.gov

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