Agents of Sepsis: Lecture for 3rd-year students

1. Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno Miroslav Votava Agents of sepsis Lecture for 3rd-year students 30th November, 2012

2. Infections with skin symptoms– revision • primary skin infections • secondary infections of already diseased skin • skin symptoms of systemic infections Etiology: bacterial viral fungal parasitic

3. Primary acute bacterial skin infections I – revision acne vulgaris –Propionibacterium acnes carbunculusnuchae – Staphylococcus aureus ecthymagangraenosum – Pseudom. aeruginosa erysipelas – Streptococcus pyogenes erysipeloid – Erysipelothrix rhusiopathiae erythrasma – Corynebacterium minutissimum folliculitis – Staph. aureus, P. aeruginosa furunculosis (boil) – Staphylococcus aureus

4. Primary acute bacterial skin infections II – revision hidradenitissuppurativa – Staph. aureus hordeolum (stye) – Staph. aureus impetigo – Staph. aureus, Str. pyogenes lymphangoitis – Streptococcus pyogenes panaritium – Staphylococcus aureus paronychium – Staphylococcus aureus sycosisbarbae – Staphylococcus aureus

5. Primary chronic bacterial skin infections – revision actinomycosis – Actinomyces israelii chronicsubcutaneous abscesses – A. israelii, Nocardia asteroides, Rhodococcus equi skingranulomas – Mycobacterium marinum, M. haemophilum, M. chelonae leprosy – Mycobacterium leprae lupusvulgaris – Mycob. tuberculosis scrophuloderma – M. tuberculosis, M. bovis

6. Secondary infections of skin lesions – revision decubitus (bedsore), trophic ulcer –neighbouring and endogenous flora (staphylococci, streptococci, enterococci, enteric bacteria, pseudomonads and other Gram-negative non-fermenting rods, anaerobes, yeasts) infected atheroma – S. aureus, Propion. acnes infected intertrigo (raw) – S. aureus, P. acnes sec. infected dermatomycoses –S. pyogenes infected wounds – discussed in previous lecture (esp. staphylococci, streptococci & clostridia)

7. Skin symptoms of systemic bacterial infections – revision roseola (rash in typhoid fever)– Salmonella Typhi disseminated gonorrhoea – Neisseria gonorrhoeae erythemamigrans – Borrelia burgdorferi infectiveendocarditis – to be dealt with by sepsis meningococcemia – Neisseria meningitidis scarlatina (scarlet fever) – Streptococcus pyogenes SSSS (staphylococcal scalded skin syndrome) – Staphylococcus aureus toxic shock syndrome – S. aureus, S. pyogenes syphilis(branded as a „great imitator“) – Treponema pallidum

8. Etiology of skin fungal infections– revision Etiology differs in • superficialmycoses, like pityriasisversicolor – Malassezia furfur (prev. Pityrosporum ovale) • mucocutaneousmycoses – Candida albicans and other species of candidae • cutaneous mycoses – typical dermatophytes • subcutaneous mycoses • opportuneskin mycoses in immunodeficites

9. Etiology of cutaneous mycoses I – revision Three genera of dermatophytes: Trichophyton e.g. Trichophyton rubrum • Microsporum e.g. Microsporum canis • Epidermophyton only Epidermophyton floccosum

10. Etiology of cutaneous mycoses II – revision tinea pedis – Trichophyton rubrum, Trich. mentagrophytes var. interdigitale, Epidermophyton floccosum onychomycosis– Trich. rubrum, Epid. floccosum tinea corporis– Trich. rubrum, Microsporum canis, Micr. gypseum, Trich. mentagrophytes var. mentagrophytes, Epid. floccosum tinea capitis, type ectothrix – M. gypseum, Micr. canis, Micr. audouinii, T. mentagrophytes var. mentagrophytes, Trich. verrucosum type endothrix – Trich. tonsurans favus– Trichophyton schoenleinii

11. Etiology of subcutaneous mycoses– revision pheohyphomycosis (lesions with pigmentedhyphae) – genera Alternaria, Aureobasidium, Cladosporium, Culvularia, Exophiala, Phaeoannelomyces, Phoma, Wangiella & others chromoblastomycosis (warty nodules with scleroticbodies) – Cladophialophora, Fonsecaea, Phialophora mycetoma eumycoticum (swollen lesion with draining tractscontaining small grains) – Acremonium, Exophiala, Madurella, Pseudoallescheria (= Scedosporium) sporotrichosis– Sporothrix schenckii(dimorphic fungus)

12. Etiology of opportune skin mycoses in immunodeficites – revision Fusarium solani, Fusarium oxysporum, Fusarium verticillioides Pseudoallescheriaboydii (= teleomorf, sexual phase of anamorf Scedosporium apiospermum) Penicilliummarneffei (systemic infection with skin manifestations – in AIDS) Scopulariopsis brevicaulis

13. Skin symptoms in viral diseases I – revision Macular (spotted) exanthem: measles – morbilli virus (Morbillivirus genus) rubella– rubella virus (Rubivirus genus) erythemainfectiosum (the fifth disease) – parvovirus B19 (Erythrovirus genus) exanthemasubitum (roseola infantum, the sixth disease) – human herpesvirus 6 (HHV 6, Roseolovirus genus) some echovirus infections – ›30 serotypes (Enterovirus genus)

14. Skin symptoms in viral diseases II – revision Umbiliform papulae: molluscumcontagiosum – molluscum contagiosum virus (Molluscipoxvirus genus)

15. Skin symptoms in viral diseases III– revision Vesicles: herpessimplex (cold sore) – herpes simplex virus type 1 (HSV 1, Simplexvirus genus) herpesgenitalis – HSV 2 (Simplexvirus genus) varicella (chicken pox) – primary infection by varicella-zoster virus (VZV, Varicellovirus genus) herpeszoster (shingles) – activation of latent infection by varicella-zoster virus variolavera (smallpox, now eradicated) – variola virus (genusOrthopoxvirus) (continued)

16. Skin symptoms in viral diseases IV– revision Vesicles – cont.: vaccinia – vaccinia virus (for vaccination against variola, Orthopoxvirus genus) cowpox, monkey pox – cowpox and monkey pox viruses(Orthopoxvirus genus) tubera mulgentium (milkers´ nodules) – milker´s nodule virus (Parapoxvirus genus) aphthae epizooticae (foot and mouth disease) – foot-and-mouth disease virus (FMDV,Aphthovirus genus) hand, foot and mouth disease – coxsackievirus A16 (Enterovirus genus)

17. Skin symptoms in viral diseases V– revision Petechiae: hemorrhagic fevers – Ebola fever, Ebola virus (Ebolavirus genus) Marburg disease, Marburg virus (genusMarburgvirus) Lassa fever, Lassa virus (Arenavirus genus) generalizedcongenitalcytomegalic disease – cytomegalovirus (CMV, Cytomegalovirus genus)

18. Skin symptoms in parasitosesI– revision Domestic (native) parasitoses: scabies – itch mite (Sarcoptes scabiei) demodicosis – human follicle mites (members of Demodex genus) pediculosis capitis – head louse (Pediculus capitis) pediculosis corporis – body louse (Pediculus humanus, syn. Pediculus corporis) pediculosis pubis (phthiriasis) – pubic (crab) louse (Phthirus pubis) dermatitis cercariosa – cercariae of avian and mammalian schistosomae non-pathogenic for man

19. Skin symptoms in parasitoses II– revision Infestation by native ectoparasites: cimicosis, urticaria cimicosa – bites by bedbug Cimex lectularius pulicosis – bites by human flea Pulex irritans, dog flea Ctenocephalides canis, cat flea Ctenocephalides felis, chicken flea Ceratophyllus gallinae ixodosis – bite by hard tick Ixodes ricinus culicosis – bites by common mosquitoes, e.g.Culex pipiens trombiculosis, trombidiosis – bites by Neotrombicula autumnalislarvae

20. Skin symptoms in parasitoses III– revision Tropical parasitoses: ulcus humidum (humid ulcer) – countryside in Near and Middle East, northern and western Africa; Leishmania major ulcus siccum (dry ulcer, oriental sore) – cities in Near and Middle East, seats in northern and eastern Africa; Leishmania tropica espundia (severe, even fatal disease) – South America; Leishmania braziliensis tungosis (sore caused by skin-burrowed female of chigoe or sand flea) – subtropical and tropical America and Africa; Tunga penetrans dracunculosis (Guinea worm disease, „the fiery serpent“) – now in Africa only; Dracunculus medinensis Loa loa filariosis(loiasis, Calabar swellings) – West Africa (Cameroon); filariae Loa loa onchocerciasis (river blindness; various skin signs, e.g. „leopard skin“) – Africa, Middle and South America; filariae Onchocerca volvulus and their endosymbiont Wolbachia pipientis …

21. Bacteremia versus sepsis – I Bacteremia= mere presence of bacteria in blood But: bacteria = starting mechanism of sepsis Interaction of microbial products with macrophages releases a lot of cytokines →systemic inflammatory response syndrome(SIRS); symtoms of SIRS = • elevated temperature • accelerated pulse and breathing • leukocytosis

22. Bacteremia versus sepsis – II Sepsis= suspect or proved infection +systemic inflammatory response syndrome (SIRS) Severe sepsis= sepsis + organ dysfunction (hypotension, hypoxemia, oliguria, metabolic acidosis, thrombocytopenia, confusion) Septic shock= severe sepsis + hypotension despite adequate supply of fluids

23. Characterization of sepsis Clinic: fever or hypothermia ↑↓ Temperature tachycardia  Pulse tachypnoe ↑ Breathing lowered blood pressure ↓ BP confusion Laboratory: leukocytes ↑↓ Leu serum bicarbonate ↓ HCO3- bacteremia – may not be already demonstrable

24. Types of bacteremia – I Intermitentbacteremia – in localizedinfections: pneumonia (pneumococci) meningitis (meningococci) pyelonephritis (Escherichia coli) osteomyelitis (Staphylococcus aureus) septic arthritis (S. aureus, gonococci) cholecystitis (enteric bacteria, enterococci) peritonitis (mixed anaerobic and facultatively anaerobic flora) wound infections (Staph. aureus, Str. pyogenes) bedsores (mixed skin and intestinal flora)

25. Types of bacteremia – II Continual bacteremia– in generalinfections: typhoid fever (Salmonella Typhi) brucellosis (Brucella melitensis) plague (Yersinia pestis)

26. Types of bacteremia – III Bacteremiainbloodstreaminfections: thrombophlebitis (Staph. aureus, Str. pyogenes) acute endocarditis (S. aureus, S. pyogenes, Str. pneumoniae, Neisseria gonorrhoeae) subacute bacterial endocarditis = sepsis lenta (α-hemolytic streptococci, enterococci, HACEK group = Haemophilus aphrophilus,Actinobacillus actinomycetemcomitans,Cardiobacterium hominis,Eikenella corrodens,Kingella kingae) „culture-negative“ endocarditis (bartonellae, coxiellae, legionellae)

27. Types of bacteremia – IV & V Bacteremia in some malignities: colonic carcinoma(Streptococcus bovis) leukemia (aeromonads, Bacillus cereus, Bacillus subtilis, Clostridium septicum) Bacteremia inintravenous drug users: skin flora (staphylococci, corynebacteria) mouth flora (neisseriae, eikenellae, even nasopharyngeal pathogens) bacteria from the environment (clostridia, bacilli)

28. Types of bacteremia – VI Bacteremia in iatrogenicinfections: tooth extraction (α-streptococci, prevotellae) bronchoscopy (nasopharyngeal flora including pathogens) bladder catheterization (Escherichia coli) infusions (skin flora, G– non-fermenting rods) vascularcatheters (coagulase-negative staphylococci, yeasts) invasive devices and implants (coagulase-negative staphylococci, micrococci, corynebacteria, nocardiae) febrile neutropenia (antibiotic-resistant staphs, enterococci, G– rods, yeasts, moulds)

29. Clinical types of sepsis • wound-originated sepsis • urosepsis • abdominalsepsis • fulminantsepsis • nosocomial(hospital-acquired) sepsis

30. Wound-originated sepsis Staphylococcus aureus Streptococcus pyogenes beta-hemolytic streptococci groupsG, F, C Pseudomonas aeruginosa (burns) Clostridium septicum

31. Urosepsis Escherichia coli Proteus mirabilis other enteric bacteria

32. Abdominal sepsis Polymicrobial etiology anaerobes: Bacteroides fragilis Peptostreptococcus micros Peptostr. anaerobius & facultative anaerobes: Escherichia coli Proteus mirabilis

33. Fulminant sepsis Neisseria meningitidis († in 24 hours!) Streptococcus pyogenes Yersinia pestis

34. Nosocomial sepsis Staphylococci, coagulase-negative (intravenous catheter-associated sepsis, infections of plastic devices in situ, febrile neutropenia) Staphylococcus aureus(infected surgical wounds) E. coli & other enterobacteria(catheter-associated infections of the urinary tract) Gram-negative non-fermenting rods (contaminated infusion fluids) yeasts(catheter-associated sepsis, febrile neutropenia) many other microbes(see above the agents of iatrogenic bacteremia)

35. Treatment of sepsis At intensive care units (ICU) only • Control of infection • antibiotics – initially broad spectrum ones, then oriented on the isolated microbe • removal of all infected tissues or devices) • Support of breathing and hemodynamics • artificial ventilation • oxygen • fluids • vasopressors etc. …

36. Homework 10Francisco José de Goya y Lucientes (1746–1828):Goya Attended by Dr. Arietta

37. Homework 9 Successful homework 9 solver: Filippos-Paschalis Rorris Congratulations!

38. Homework 11Please give the name of the author and of the painting

39. Answer and questions The solution of the homework and possible questions please mail to the address mvotava@med.muni.cz Thank you for your attention