1. Lecture for 3rd-year students
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
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)
mucocutaneous mycoses – Candida albicans and other species of candidae
cutaneous mycoses – typical dermatophytes
subcutaneous mycoses
opportune skin 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 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)

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 (genus Marburgvirus)
Lassa fever, Lassa virus (Arenavirus genus)
generalized congenital cytomegalic disease –
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 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. Intermitent bacteremia – in localized infections:
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 sepsis
urosepsis
abdominal sepsis
fulminant sepsis
nosocomial (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
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. At intensive care units (ICU) only
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 10 Francisco José de Goya y Lucientes (1746–1828): Goya Attended by Dr. Arietta

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

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

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