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 9th December, 2011 9th December, 2011

2. Infections with skin symptoms – revision 1.primary skin infections 2.secondary infections of already diseased skin 3.skin symptoms of systemic infections Etiology: bacterial viral viral fungal fungal parasitic parasitic

3. Primary acute bacterial skin infections I – revision acne vulgaris – Propionibacterium acnes carbunculus nuchae – Staphylococcus aureus ecthyma gangraenosum – 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 hidradenitis suppurativa – Staph. aureus hordeolum (stye) – Staph. aureus impetigo – Staph. aureus, Str. pyogenes lymphangoitis – Streptococcus pyogenes panaritium – Staphylococcus aureus paronychium – Staphylococcus aureus sycosis barbae – Staphylococcus aureus

5. Primary chronic bacterial skin infections – revision actinomycosis – Actinomyces israelii chronic subcutaneous abscesses – A. israelii, Nocardia asteroides, Rhodococcus equi skin granulomas – Mycobacterium marinum, M. haemophilum, M. chelonae leprosy – Mycobacterium leprae lupus vulgaris – 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 erythema migrans – Borrelia burgdorferi infective endocarditis – 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 superficial mycoses, like pityriasis versicolor – Malassezia furfur (prev. Pityrosporum ovale)superficial mycoses, like pityriasis versicolor – Malassezia furfur (prev. Pityrosporum ovale) mucocutaneous mycoses – Candida albicans and other species of candidaemucocutaneous mycoses – Candida albicans and other species of candidae cutaneous mycoses – typical dermatophytescutaneous mycoses – typical dermatophytes subcutaneous mycosessubcutaneous mycoses opportune skin mycoses in immunodeficitesopportune skin mycoses in immunodeficites

9. Etiology of cutaneous mycoses I – revision Three genera of dermatophytes: Trichophyton e.g. Trichophyton rubrum 2.Microsporum e.g. Microsporum canis 3.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 type endothrix – Trich. tonsurans favus – Trichophyton schoenleinii

11. Etiology of subcutaneous mycoses – revision pheohyphomycosis (lesions with pigmented hyphae) – genera Alternaria, Aureobasidium, Cladosporium, Culvularia, Exophiala, Phaeoannelomyces, Phoma, Wangiella & others chromoblastomycosis (warty nodules with sclerotic bodies) – Cladophialophora, Fonsecaea, Phialophora mycetoma eumycoticum (swollen lesion with draining tracts containing 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 Pseudoallescheria boydii (= teleomorf, sexual phase of anamorf Scedosporium apiospermum) Penicillium marneffei (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) erythema infectiosum (the fifth disease) – parvovirus B19 (Erythrovirus genus) exanthema subitum (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: molluscum contagiosum – molluscum contagiosum virus (Molluscipoxvirus genus)

15. Skin symptoms in viral diseases III – revision Vesicles: herpes simplex (cold sore) – herpes simplex virus type 1 (HSV 1, Simplexvirus genus) herpes genitalis – HSV 2 (Simplexvirus genus) varicella (chicken pox) – primary infection by varicella-zoster virus (VZV, Varicellovirus genus) herpes zoster (shingles) – activation of latent infection by varicella-zoster virus variola vera (smallpox, now eradicated) – variola virus (genus Orthopoxvirus) (continued) (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) Ebola fever, Ebola virus (Ebolavirus genus) Marburg disease, Marburg virus (genus Marburgvirus) Marburg disease, Marburg virus (genus Marburgvirus) Lassa fever, Lassa virus (Arenavirus genus) Lassa fever, Lassa virus (Arenavirus genus) generalized congenital cytomegalic disease – cytomegalovirus (CMV, Cytomegalovirus genus) cytomegalovirus (CMV, Cytomegalovirus genus)

18. Skin symptoms in parasitoses I – 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 autumnalis larvae

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 temperatureelevated temperature accelerated pulse and breathingaccelerated pulse and breathing leukocytosisleukocytosis

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 ↓ HCO 3 - bacteremia – may not be already demonstrable bacteremia – may not be already demonstrable

24. Types of bacteremia – I Intermitent bacteremia – in localized infections: 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 general infections: typhoid fever (Salmonella Typhi) brucellosis (Brucella melitensis) plague (Yersinia pestis)

26. Types of bacteremia – III Bacteremia in bloodstream infections: 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 in intravenous 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 iatrogenic infections: tooth extraction (α-streptococci, prevotellae) bronchoscopy (nasopharyngeal flora including pathogens) bladder catheterization (Escherichia coli) infusions (skin flora, G– non-fermenting rods) vascular catheters (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 sepsiswound-originated sepsis urosepsisurosepsis abdominal sepsisabdominal sepsis fulminant sepsisfulminant sepsis nosocomial (hospital-acquired) sepsisnosocomial (hospital-acquired) sepsis

30. Wound-originated sepsis Staphylococcus aureus Streptococcus pyogenes beta-hemolytic streptococci groups G, 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 Peptostreptococcus micros Peptostr. anaerobius Peptostr. anaerobius& facultative anaerobes: Escherichia coli Proteus mirabilis 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 infectionControl of infection –antibiotics – initially broad spectrum ones, then oriented on the isolated microbe –removal of all infected tissues or devices) Support of breathing and hemodynamicsSupport of breathing and hemodynamics –artificial ventilation –oxygen –fluids –vasopressors etc. …

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

37. Homework 10 Successful homework 10 solvers: Mavis Araba Koufie Congratulations!

38. Homework 11 Please 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