PYOGENIC INFECTIONS Dr. Kenéz Éva - Anna Division of Infectious Diseases 2015.11.10
KEY POINTS The virulence factors of streptococcus and staphylococcus Disease caused by streptococcus and staphylococcus Antistaphylococcal antibiotics, antistreptococcal penicillin
Case presentation 1. A 32 year old women became ill 4 days after the onset of her menstrual period. She presented in the ED with fever, elevated WBC count, and an erythematous, sunburn-like rash on her trunk and extremities. She complained of fatigue, vomiting and diarrhea. She had recently eaten at a fast-food restaurant, but otherwise had prepared all her meals at home. The patient described most likely has: A) Staph food poisoning B) scaled skin syndrome C) infection with Staph. saprophyticus D) rubella E) toxic shock syndrome
Case presentation 2. A 57 year old man arrives at the ED complaining of weakness, fatigue, and intermittent fever that has recurred for several weeks. The patient had a cardiac valvular prosthesis implanted 5 years earlier. Physical examination reveals petechiae on the chest. Blood cultures grew catalase positive, coagulase negative cocci. The gram pos. organisms failed to ferment mannitol, and their growth was inhibited by novobiocin. What is the most likely infectious agent? A) staph aureus B) staph epidermidis D) strep pneumoniae E) strep agalactiae
Case presentation 3. A 8 o th old hild as rought the pediatri ia s office with what appeared to be a sunburn, although the parents denied that the child had been overexposed to the sun. The parents did recall seeing a area of red ess a d s all listers o the hild s ar the night before. Which of the following virulence factors is critical to this disease manifestation? A) toxic shock syndrome toxin B) Panton-Valentine leukocidine C) Protein A D) capsule E) exfoliatin
Staphylococcus Gram +, round, nonmotile, grape-like clusters Do not form spores Cultured on enriched media Yellow, hemolytic colonies Aerobic/facultatively anaerobic Catalase, coagulase, mannitol + Resistant to heat and drying
Staphylococcus Aureus Most virulent Major cause of morbidity and mortality Pluripotent pathogen toxin-mediated non toxin-mediated mechanism Nosocomial and CA infections Mild soft tissue infection to life-threatening systemic infections
EPIDEMIOLOGY SA is part of the human flora: 25-50% of healthy persons may be persistently or transiently colonized (nares, oropharynx, axilla, vagina, perineum) conditions that increase the risk of colonization conditions that increase the risk of infection Leading cause of nosocomial infections (MRSA, VISA, VRSA) CA-MRSA
PATHOGENESIS Opportunistic pathogen For infection the following steps are needed: contamination and colonization of tissue surfaces establishment of a localized infection invasion evasion of host response metastatic spread The most important virulence factors are: structural components enzymes toxins
LEVELS OF INFECTION Colonization Skin infections Metastatic Infections Toxinoses
CLINICAL SYNDROMES - range from localized to systemic Skin and soft tissue infections: invade skin throught wounds, follicles or glands Folliculitis: superficial inflammation of the hair follicule, usually resolves without complication, but can progress. Furuncle: boil, often form around foreign bodies, respond well to local therapy. Carbuncle: larger, deeper, multiloculated skin infection, that can lead to bacteremia, require antibiotic and debridment. Impetigo: localized, superficial, crusty skin lesion generally seen in children, commonly caused by streptococcus pyogenes. Mastitis Hidradenitis suppurativa Surgical wound infections
CLINICAL SYNDROMES Musculoskeletal infections: resulting from hematogenous dissemination and contiguous spread from a soft tissue site. Osteomyelitis Septic arthritis Pyomiositis Respiratory tract infections: CA respiratory tract infections follow viral infections Nosocomial respiratoty tract infections Empyema
CLINICAL SYNDROMES Bacteremia: may be complicated by sepsis, endocarditis, vasculitis and metastatic seeding. The frequency of metastatic seeding is 30% (bones, joints, kidney, lung). Infective endocarditis: Staph. Au is the leading cause, responsible for the 25-30% of cases. Injection drug use associated Native- valve Prosthetic-valve Nosocomial Prosthetic device-related infections Intravascular catheters, prosthetic joints
TOXIN-MEDIATED DISEASE a)staphylococcal gastroenteritis: - heat- stabile enterotoxin a) SSSS: - exfoliative toxin - superficial bullae - affects newborns and children c) TSS: - toxic shock syndrome toxin - highly absorbent tampon
Staphylococcal scalded skin syndrome - Pemphigus neonatorum - most often occurs in infants - low mortality rate - excellent prognosis - complete resolution in 10 days - DD: toxic epydermal necrolysis
Staphylococcal Toxic Shock Syndrome Asso iated ith ta po use i early 8 s - ignored for a while but is re-emerging Colonization with a TSST-producing strain Fever > 38.9 C Hypotension Diffuse macular erythematous rash with desquamation 1-2 weeks after onset Multisystem involvement Hepatic (bilirubin/got,gpt > 2 times normal) Hematologic (platelet count < 100.000/ul) Muscular (myalgia, CK> 2 times) CNS (disorientation) Mucous membranes (vaginal, oropharyngeal, conjunctival hyperaemia) Gastrointestinal (vomiting, diarrhoea)
PREVENTION In hospital settings involve hand washing and appropriate isolation procedures. Elimination of nasal carriage-use of topical antimicrobial agents (mupirocin, chlorhexidine) No available immunization strategy
Antibiotic resistance in S. aureus 1944 -lactamase 1940 Penicillin 1960 Methicillin/ Oxacillin 1970 s meca 1996-VISA 2002 VanA Vancomycin 2000 s Daptomycin
ORAL THERAPY FOR SKIN AND SOFT TISSUE INFECTIONS Aggressive treatment: incision, drainage and antibiotic MSSA: Dicloxacillin 500 mg qid Cephalexin 500 mg qid Minocycline/doxycycline 100 mg q 12 h TMP-SMX 1-2 ds tablets bid Clindamycin 300-450 mg tid MRSA: Minocycline/doxycycline 100 mg q 12 h TMP-SMX 1-2 1-2 ds tablets bid Clindamycin 300-450 mg tid
PARENTERAL THERAPY FOR SERIOUS INFECTIONS Sensitive to penicillin: Penicillin G 4 MU q 4h Nafcillin, oxacillin 2g q 4h Cefazolin 2g q8h Vancomycin 1g q 12 h MSSA: Nafcillin, oxacillin 2g q 4h Cefazolin 2g q8h Vancomycin 1g q 12 h
PARENTERAL THERAPY FOR SERIOUS INFECTIONS MRSA: Vancomycin 15-20 mg/kg q8-12h Daptomycin 6 mg/kg q 24 h Linezolid 600 mg q 12 h Qiunapristin/dalfopristin Empirical therapy Vancomycin 15-20 mg/kg q8-12h
Other Staphylococci Coagulase-negative staphylococcus; frequently involved in nosocomial and opportunistic infections S. epidermidis lives on skin and mucous membranes, produces an extracellular polysaccharide material sli e cause infections of intravenous catheters & prosthetic implants, vascular grafts. S. lugdunensis, S. schleiferi native-valve endocarditis, osteomyelitis S. saprophyticus infrequently lives on skin, intestine, vagina associated with UTI 26
Case presentation 4. 3 y old child presents with fever, generalized sa dpaper rash, o iti g a d s olle ly ph nodes. On physical examination enlarge papillae and coated tongue are remarcable. Which of the following virulence factors is critical to this disease manifestation? a) pyrogenic toxin b) erytrogenic toxin c) Streptolysin O d) Streptodornase
Streptococcus - G+, non-motile - Ovoid/spherical, arranged in chains - Complex nutritional requirements - Facultative/obligate anaerobe - Catalase negative - Does not survive well in the environment
Classification Antigenic structure - polysaccharide antigens (C Ag) * group-specific antigen * 20 groups (A-H, K-V) * group A main human pathogens - surface protein antigens (M Ag) * type-specific antigen * group A>80 serotypes
Classification based on hemolysis on blood agar Hemolysis alpha beta gamma
Human streptococcal pathogens S. pyogenes S. agalactiae S. viridans S. pneumoniae Enterococci
CLINICAL MANIFESTATIONS Necrotizing fasciitis Infection of the superficial muscle, fascia and adjacent subcutaneous tissue GAS is implicated in 60% of cases Acute onset Severe pain, malaise, fever, chills, toxic appearance Progress in several hours Early surgical exploration is diagnostically and therapeutically Debridement is required!
CLINICAL MANIFESTATIONS Scarlet fever Pharygitis accompanied by rash mi ute papules gi i g a sa dpaper fell to the ski, circumoral palor desquamation of palms and soles follows the rash tra erry to gue, Pastia s line Erythrogenic toxin
CLINICAL MANIFESTATIONS Streptococcal toxic shock syndrome Isolation of GAS from sterile/nonsterile site Hypotension + 2 of the following: Renal impairment Coagulopathy Liver function impairment Adult respiratory distress syndrome Generalized erythematous macular rash that may desquamate Soft tissue necrosis
CLINICAL MANIFESTATIONS AND TREATMENT REGIMENS Localised infections Pharyngitis Treatment: Benzatin penicillin G 1.2 mu IM/penicillin V 250 mg PO tid/ 500 mg PO bid X 10 days, macrolides Scarlet fever Treatment: the same as in pharyngitis Impetigo Treatment: the same as in pharyngitis Cellulitis Treatment: Penicillin G 1-2 mu IV q4h Necrotizing fasciitis: Treatment: debridement + Penicillin G 2-4 mu IV q4h + Clindamycin 600-900 mg q8h+iv Ig 2g/kg
CLINICAL MANIFESTATIONS AND TREATMENT REGIMENS Systemic infections Streptococcal toxic shock syndome Treatment: Penicillin G 2-4 mu IV q4h + Clindamycin 600-900 mg q8h+iv Ig 2g/kg Pneumonia/empyema Treatment: Penicillin G 2-4 mu IV q4h + drainage Bacteremia Puerperal sepsis