IP4 test 2 (warning: created while half asleep)

List the bacteria that are normal flora on human's skin.
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Terms in this set (196)
- Superficial skin infection
- face is a common site
- common in children
- highly communicable
- common in hot, humid regions
- Common causes: Streptococcus pyogenes, staphylococcus aureus

- Often spontaneous resolves without treatment
- Topical therapy: Mupirocin ointment bid, Retapamulin ointment bid
- Systemic therapy only for severe cases: patients with numerous lesions, during outbreaks
When empirically covering for S. aureus, you must remember to cover for what?MRSA (cultures help with antibiotic de-escalationWhat is the treatment for empiric therapy for moderate purulent SSTI treatment or moderate purulent SSTI with defined MRSA?- bactrim PO - Doxycycline PO - treatment length is 5 daysWhat is the treatment for empiric therapy for severe purulent SSTI treatment or severe purulent SSTI with defined MRSA?- Vancomycin IV - Daptomycin IV - linezolid IV - telavancin IV - ceftaroline IV - treatment length is 10 daysWhat is the treatment for empiric therapy for moderate purulent SSTI with defined MSSA?- Dicloxacillin PO - Cephalexin PO - treatment length is 5 daysWhat is the treatment for empiric therapy for severe purulent SSTI with defined MSSA?- Nafcillin IV - Cefazolin IV - Clindamycin IV ( Clindamycin does not cover MSSA well, and it is the number one cause of C. Diff. It has a lot of side effects and it is not an amazing drug.) - treatment length is 10 daysCellulitis- Diffuse, superficial, spreading skin infection - Pathogens: Group A streptococcus (Streptococcus pyogenes) - Erythema (redness), swelling, tenderness, warmth, more common in lower extremities - Recommend against getting cultures unless: severe infection; pt is immunocompromisedLymphangitis- infection of lymphatic channels - Secondary to: puncture wounds, infected blisters, other skin lesions - Common cause: Group A streptococcus (S. pyogenes) - Symptoms: fever and chills, malaise, red streaks along lymphatic pathsWhat is the treatment for a mild, non-purulent skin infection?- Penicillin VK PO - Cephalexin PO - Dicloxacillin PO - Clindamycin PO - duration of therapy: 5 days; managed as an outpatientWhat is the treatment for a moderate, non-purulent skin infection?- Penicillin G IV - Ceftriaxone IV - Cefazolin IV - Clindamycin IV - duration of therapy: 5 days; give 1-2 days of IV antibiotics as an inpatient and discharged on oral medsWhat is the treatment for a severe, non-purulent skin infection?- need to start large then we can narrow - Vancomycin IV + piperacillin/tazobactam - Duration of therapy: 7-14 daysnecrotizing fasciitis- involve fascial and/or muscle - rapidly progressing - Bacterial toxin plays a vital role (cause major tissue destruction) - More common in lower limbs - Mortality ranges from 30-70% - Direct visual examination: swollen and dull gray appearance; skin tissue can be easily punctured with finger or proble - CT scan: gas seen inside tissue Symptoms: - Severe pain, disproportionate to findings‚Äč - Failure to respond to antibiotics‚Äč - Symptoms extending beyond area of skin involvement:‚ÄčHard, wooden feel of subcutaneous tissue; Edema and tenderness‚Äč - Systemic toxicity‚Äč - Bullous lesions‚Äč - Skin necrosisWhat is the treatment for necrotizing fasciitis?- Surgical debridement is definitive therapy‚Äč Must physically remove dead tissue‚Äč ‚Äč- Source control is vital‚Äč ‚Äč- Antibiotics must also be given until:‚Äč + Further debridement is not needed ‚Äč- May require multiple surgeries‚Äč ‚Äč+ Patient has improved clinically‚Äč ‚Äč+ Fever has been absent for 48-72 hours Secondly, you need broad spectrum coverage (chose one of each of the following): - Gram negatives (including Pseudomonas): Pip/tazo, Cefepime - Gram positives (including MRSA): Vancomycin, Linezolid - Anaerobes: Pip/tazo, Metronidazole - Anti-toxin effects: Clindamycin, LinezolidClostridial gas gangrene and myonecrosis- Pathogens: Clostridium perfringens (most commonly); Streptococcus pyogenes (rarely) - Cause: secondary to trauma; toxin mediated - Signs and symptoms: Rapidly progression (symptoms within 24 hrs), Gas in the tissue seen on imaging, crepitus (sound of someone eating potato chips) Treatment: - Surgical debridement - Empiric antibiotics: Clindamycin; penicillinDog and cat bite infections- Usually polymicrobial: + Aerobes: Streptococcus spp., S. aureus + Anaerobes: Eikenella, corrodes, Fusobacterium, Peptococcus, Prevotella spp. + Pasteurella multocida (esp in cats) Treatment: amoxicillin/clavulanateHuman bite infection- Usually polymicrobial: + Aerobes: Streptococcus spp., S. aureus + Anaerobes: Eikenella, corrodes, Fusobacterium, Peptococcus, Prevotella spp. Treatment: amoxicillin/clavulanateDecubitus ulcer (Bed sore and pressure sores)- Common problem among chronically debilitated (>70 yo; pts w/ spinal cord injuries) - May progress to osteomyelitis (pt have no feeling, therefore wound progresses) - Often polymicrobial:‚Äč Gram-positives: Staphylococcus aureus, Enterococcus faecalis‚Äč Gram-negatives: Escherchia coli, Proteus mirabilis‚Äč Anaerobes: Bacteriodes fragilis‚Äč ‚Äč- Difficult to differentiate between causative pathogen and colonizing bacteria‚Äč ‚Äč- Require surgical debridement‚Äč ‚Äč- Clean with normal saline Empiric therapy should cover:‚Äč - MRSA: Vancomycin‚Äč ‚Äč- Gram-negative bacilli: Ceftriaxone‚Äč ‚Äč- Anaerobes: MetronidazoleOsteomyelitisRelatively uncommon infection‚Äč ‚Äč Infection of the bone caused by:‚Äč - Hematogenous spread‚Äč ‚Äč- Contiguous spread‚Äč ‚Äč- Direct inoculation‚Äč ‚Äč - Most cases are caused by Staphylococcus species ‚Äč- >50% of all osteomyelitis cases‚Äč ‚Äč- 80% of hematogenous cases in childrenHematogenous osteomyelitis- Cause: Staphylococcus aureus (mono microbial) - ~20% of cases‚Äč - Blood slows in arterioles‚Äč: Allows bacteria to settle ‚Äč ‚Äč Settled bacteria causes:‚Äč - Inflammation‚Äč - Occlusion of vessels ‚Äč - Necrosis Most common in:‚Äč - Long bones of children <1 year of age‚Äč - Vertebrae of adults ‚Äč>50 years of age (less common) - children: S. aureus - neonates: Group B streptococci; Escherichia coli - Adults: Mostly S.aureus; Urinary pathogens common (E.coli, Proteus spp.) - Adults w/ IVDU: >80% gram-negativescontiguous osteomyelitis- Cause: Staphylococcus aureus (polymicrobial - depends on site of wound) - bacterial spread from adjacent soft tissue + Decubitus ulcers +SSTIs + Sinus infection + Diabetic foot ulcer - Occurs mostly in individuals >50 yo - Skin infection that probes to boneDirect inoculation osteomyelitis- Cause: Staphylococcus aureus; Pseudomonas aeruginosa - Caused by penetrating wounds and open fracturesWhat is the clinical presentation of osteomyelitis?- Signs: Tenderness, pain, swelling, fever, chills, decreased motion, malaise, can probe wound down to bone - Lab test: Elevated WBC, ESR, and C-reactive protein; cultures - Radiography: MRI is more useful than X ray (changes in X ray noted in 10-14 days while in MRS it is 3-5 days)treatment of osteomyelitis - Surgery- Depends on the site: can amputate a toe with contiguous osteomyelitis; cannot amputate a child's entire arm with hematogenous osteomyelitis - If surgery is planed, stop abx 48-72 hrs prior to surgery (Do not stop antibiotics if patient is emergently ill; antibiotic use will decrease chance of growth on intra-operative cultures)MSSA osteomyelitisFirst line: Naficillin or oxacillin IV; Cefazolin IV Alternative: Vancomycin IVMRSA osteomyelitisFirst line: Vancomycin IV Alternative: Daptomycin IV; linezolid IV/POStreptococci osteomyelitisFirst line: Penicillin IV; Ampicillin IV ; may add aminoglycoside Alternative: vancomycin IVGram negative osteomyelitisFirst line: Ceftriaxone IV , Ceftazidime IV; cefepime IV Alternative: Ciprofloxacin IV/PO; Levofloxacin IV/POosteomylelitis outcome- High dose abx for long duration (4-6 wks) - start with IV abx; may transition to Po antibiotics if pt is responding well Monitor: - symptoms - WBC weekly - ESR weekly - CRP weeklyWhat is the H antigen of Enterobacteriaceae?flagella antigenWhat is the O antigen of Enterobacteriaceae?Cell wall lipopolysaccharide - major cause of sickness leading to food born illness - allow them to invade M cells, but they do not invade deeplyWhat is the K antigen of Enterobacteriaceae?polysaccharide capsule antigen - Klebsiella - large and regular capsule - E. coli - sometimes has capsule - Salmonella -sometimes has capsuleWhat kind of diseases are common among enterbacteriaceae?- Infectious diarrhea‚Äč - Urinary tract infection‚Äč - Community-acquired pneumonia‚Äč(K. pneumoniae‚Äč) - Bacteremia/sepsis‚Äč - Peritonitis (primary/secondary; tertiary)What are the morphological traits of Klebsiella pneumoniae?- GNRs that are non-motile with a large capsle - CAP (community acquired pneumonia) - Beta-lactamase producing (good susceptibility to a few antibiotics) - can cause bacteremia/septicemia and primary peritonitis - MDR Klebsiella - you need to reach for special products - capsule, non-motile, no flagellaWhat are the morphological traits of Escherichia coli?- Gram negative rod‚Äč - Facultative anaerobe‚Äč - Grow as single cells, no tendency to form groups‚Äč - Flagellae‚Äč - Ferments a wide range of carbohydrates‚Äč + Extensive regulation over carbon metabolism.‚Äč + Lac operon enables lactose metabolism when glucose is not available.‚Äč - Positive indole test. - Most common cause of UTIs - Capsule (sometimes) - Fermenters of glucose, do not oxidize glucose‚Äč - Catalase positive, oxidase negative‚Äč - Oxidase negative = lacks cytochrome C oxidaseWhat are the morphological traits of Salmonella spp?- Capsule, motile, flagellae - S. enterica, S. bongori - Can cause enteric fever: + S. Paratyphi A (Serogroup A)‚Äč + S. Paratyphi B (Serogroup B)‚Äč + S. Choleraesuis (Serogroup C1) ‚Äč + S. Typhi (serogroup D) - Can cause enterocolitis: + typhimurium and enteritidis - Fermenters of glucose, do not oxidize glucose‚Äč - Catalase positive, oxidase negative‚Äč - Oxidase negative = lacks cytochrome C oxidaseDescribe enterocolitis in Salmonella.- all bacteria is in GI tract - Typhimurium and Enteritidis (in US)‚Äč - No bacteremia‚Äč - Inflammatory lesions in intestines‚Äč - Onset 8-48 hours (soon)‚Äč - Nausea‚Äč - Headache‚Äč - Vomiting‚Äč - Diarrhea‚Äč - White blood cells in stoolDescribe enteric fever in Salmonella.- Other four serotypes‚Äč + S. Paratyphi A (Serogroup A)‚Äč + S. Paratyphi B (Serogroup B)‚Äč + S. Choleraesuis (Serogroup C1) ‚Äč + S. Typhi (serogroup D) - Bacteremia ‚Äč - Lesions in lymph tissue‚Äč - Onset relatively late (10-14 days)‚Äč - Fever‚Äč - Malaise‚Äč - Headache‚Äč - Constipation‚Äč - WBC count is low/normal - spreads to adjacent cellsWhat are the morphological traits of Proteus mirabilis?- Proteus mirabilis = >90% of all Proteus infection.‚Äč - Urinary tract infections (community/nosocomial)‚Äč - Common in burn patients‚Äč( Bacteremia/septicemia/pneumoniae‚Äč) - Beta-lactamase production‚Äč - Luckily, P. mirabilis is susceptible to most antimicrobial classes. - Fermenters of glucose, do not oxidize glucose‚Äč - Catalase positive, oxidase negative‚Äč - Oxidase negative = lacks cytochrome C oxidaseWhat are the morphological traits of shigella?- No capsule, non-motile - beta-lactamase producing - limited susceptibility to many antibiotics - Dysentery (watery + blood diarrhea) - Many serotypes based on O antigen - Fermenters of glucose, do not oxidize glucose‚Äč - Catalase positive, oxidase negative‚Äč - Oxidase negative = lacks cytochrome C oxidase - spread via person to person contact - Their lipopolysaccharides (O antigens) allow them to invade M cells, but they do not invade deeply - produces shiga toxinWhat are the morphological traits of Enterobacter spp?- GNR - hyper secretes beta lactamase; resistant to beta lactams mostly (ampC) - penicillins, 1st and some 2nd gen cephs - E. cloacae and aerogenes - Motile with a small capsule - we require 3rd generations cephs and up with these - limited susceptibility to few antibiotics - produce capsules - increasing associated with nosocomial infection (UTI, hospital acquired pneumonia, device contracted infection) - Fermenters of glucose, do not oxidize glucose‚Äč - Catalase positive, oxidase negative‚Äč - Oxidase negative = lacks cytochrome C oxidaseshiga toxin- Shigella, and E. coli O157:H7 (enterhemorrphagic e.coli - worst of all) - stx2 cleaves an adenine from host cell's 28S rRNA, irreversibly inhibiting eukaryotic ribosome function (more important in the development of hemolytic uremic syndrome) - Stx1 inactivates Bcl2 and induces apoptosis - Shiga toxin binds to cell surface receptor. It gets internalized by induced cell endocytosis. The shiga toxin will bind to the ribosome (to the terminal adenine of ribosome that is involved in assembling peptides) This will cleave the terminal adenine and cleaving the ribosomal machinery halts ribosome function. The ribosome can no longer make proteins. This leads to necrosis. The cell dies a violent death. This results in bloody stool. Because of the violent nature of the shiga toxin poison, you often time will get the release of a lot of cellular constituents into the body. The kidney will eventually fail trying to filter all of these out. So, the second thing that occurs is hemolytic uremic syndrome. This is the failure of the kidneys to filter out the blood products as a result of this violent cell killing. This can be fatalWhat is primary peritonitis?- Idiopathic; no apparent source of contamination - Associated with ascites, hepatitisWhat is secondary peritonitis?- Results from spillage of an intraabdominal abcess - involves a mix of anaerobic GNRs from colon - usually due to gram negative rods - wound spillage into GT tract to cause polymicrobial stateWhat is tertiary peritonitis?Persistence/recurrence after 48 hrs of apparent resolution of primary or secondary peritonitisDescribe the pathophysiology of EHEC (enterohemorrhagic).- caused by Enterohemorrhagic E.coli and shiga toxin producing (EHEC/STEC) bacteria e.g. E. coli O157:H7 - mainly characterized by hemorrhagic colitis and hemolytic uremic syndrome - shiga toxins bind to membrane associated glycolipids on host cells - grossly bloody diarrhea - significant pain, fecal leukocytes are common - shigella toxin can then be deposited in endothelial tissues that line the brain and kidney - comes from ground beef during processing - manure, runoff, other produce can also contaminate water systemsDescribe the pathophysiology of ETEC (enterotoxigenic).- important cause of traveler's diarrhea in infants - ETEC colonization factors result in attachment to enterocytes in the small bowel - A heat labile exotoxin attaches to membrane of enterocytes. Subunit A enters the cell stimulates adenylyl cyclase. cAMP levels go up. Hypersecretion of water and Cl-; inhibition of sodium reabsorption. - The gut is distended with fluid, hyper motility results. Several days' worth of diarrhea. - hallmark trait is plasmid-encoded enterotoxins - cooking raw foods is highly recommended to prevent traveler's diarrhea - Antibiotic txt can reduce duration of infectionDescribe the pathophysiology of EIEC (enterinvasive).- disease similar to shigellosis - common among travelers and children in developing countries - relatively uncommon cause of diarrhea - non-motile and non lactose fermenters - invade intestinal mucosal epithelial cells only at large inoculum sizes after long onset of 1-3 days - Toxins inflame the small bowels, colonization occur and cell to cell spreading - inflammatory colitis, fever, abdominal pain - usually self limitedDescribe the pathophysiology of EPEC (enteropathogenic).- important cause of diarrhea in infants - EPEC attach to the mucosal cells of the small bowel - two important pathogenic factors: + bundle forming pilus encoded by plasmid- EPEC adherence factor (EAF)‚Äč - mediates attachment to mucosal cells and aggregation + Chromosomal locus of enterocyte effacement- (LEE); - mediates tight adherence and removal of microvilli. - EPEC forms small cuplike structure that sometimes allow EPEC to invade mucosal cells (lesions evident on small bowel biopsy) - infants: leads to severe, watery diarrhea, vomiting, and fever - limited to O antigen (most damaging) and some H antigen E.coli - effectively limited by antibiotic treatmentWhat are the major drug resistance traits for Proteus?beta-lactamase productionWhat are drug resistance traits for E.Coli?E. coli strains can become resistant to beta lactam antibiotics by producing extended spectrum beta lactamaseWhat are the drug resistance traits of Shigella?beta lactamase producing - decrease in cellular permeability, extrusion of drugs by active efflux pumps, and overexpression of drug-modifying and -inactivating enzymes or target modification by mutation - O antigensWhat are the major drug resistance traits of Klebsiella?- Beta lactamase producing - NDM-1 gene: the most extended spectrum beta lactamase to date - through the production of enzymes such as Extended Spectrum ő≤-Lactamase (ESBLs) and CarbapenemaseWhat are the major drug resistance traits of Enterobacter?- hyper secretes beta lactamase; resistant to beta lactams mostly - AmpC - induced at different levels by different beta lactam drugs. The rate-limiting factor is how much enzyme is made; Chromosomal copies of ampC are often induced to a lower extent than plasmid-borne copies due to gene dosage.‚ÄčList the SPACE bugsSerratia Pseudomonas Acinetobacter Citrobacter EnterobacterWhat are the hallmark features of SPACE bacteria?- multidrug resistant, gram negatives, many of which are associated with beta lactamaseWhich of the SPACE bacteria produce extended spectrum beta lactamases?- Enterbacter Cloacae, Enterbacter aerogenes (AmpC) - Some isolates of Serratia (ampC) - Klebsiella (NDM-1 gene)AmpC- is induced at different levels by different beta lactam drugs. The rate-limiting factor is how much enzyme is made.‚Äč Chromosomal copies of ampC are often induced to a lower extent than plasmid-borne copies due to gene dosage. - Most frequently harbored by Enterobacter cloacae, Enterobacter aerogenes‚Äč - Some isolates of Serratia‚Äč Substrates: - Penicillins‚Äč - Cephalosporins (1st, 2nd, 3rd, 4th)‚Äč - Beta lactamase inhibitor combinations (Unasyn, etc.)NDM-1- New Delhi metallo-beta-lactamase 1 is the most extended-spectrum beta lactamase to date.‚Äč - Isolated from Klebsiella pneumoniae.‚Äč - Substrate beta lactam antibiotics:‚Äč + Penicillins‚Äč + Cephalosporins (1st, 2nd, 3rd, 4th)‚Äč _ Beta lactamase inhibitor combinations (Unasyn, etc.)‚Äč - **Carbapenems**Serratia morphology, site of infection, types of infections- Enteric, gram negative rod bacteria - Lactose/indole negative - has AmpC beta lactamase gene (ESBL) - red pigmentation from prodigiosin - resistant to penicillins and aminoglycosides (3rd gen cephalosporins are effective) - Dwell in colon of infected persons - hospital acquired infection - Infection/bacteremia:‚Äč + Respiratory tract infection‚Äč + Genitourinary tract‚Äč + Intravascular devices‚Äč + Surgical wounds‚Äč + Soft tissue infections and infusion-related (IV, etc.)‚Äč (Rarely causative for endocarditis)Acinetobacter morphology, site of infection, types of infections- Aerobic, gram negative bacteria, oxidase negative - also found in hospitals environment - They also have very impermeable membranes‚Äč - Porins (Proteins 1 and 2) of the outer membrane are very small channels that are very exclusive to uptake of antibiotics. - usually involved in device associated infection - bacteremia usually due to intravenous catherization - Usually MDR - colistin is last resort against infectionCitrobacter morphology, site of infection, types of infections- Gram negative, coliform bacteria.‚Äč - Facultative anaerobe - C. freundii is indole negative, C. koseri is indole positive.‚Äč - 100% of isolates are oxidase negative. - happen in hospital - part of normal fecal flora of humans - 40-50% of all infections occur in urinary tract, soft tissue, device associated infections all possible. - Citrobacter possesses AmpC beta lactamase; derepression of this may result in sudden beta lactam resistance. (most strains are susceptible to amikacin, cefepime, tigecycline, carbapenems, etc)Pseudomonas morphology, site of infection, types of infections- motile, flagellated gram negative.‚Äč - Pseudomonads are widely distributed in soil and water.‚Äč - Pseudomonas aeruginosa is the most clinically-important ‚Äč - oxidase positive, which is consistent with it being an aerobe. - P. aeruginosa has a green fluorescent appearance due to pigments that diffuse into agar. - P. aeruginosa infects wounds or burns and gives rise to blue-green pus; when the wound is a puncture during neurosurgery, gives rise to meningitis.; When exposed to catheters, it gives rise to UTI. Contaminated respirators leads to respiratory disease. - people most at risk are burn pts and pts with cystic fibrosisWhat are the mechanisms of resistance for Pseudomonas?- Intrinsic resistance (Outer membrane impermeability‚Äč) - The outer membrane of P. aeruginosa is a hydrophobic, impermeable barrier to antibiotics. - Efflux pumps - OprE is a water-filled porin for antibiotics; Small, bad architecture for entry. - OprD is a dipeptide channel open only to zwitterionic carbapenems. - When drugs enter the cell, especially at concentrations < MIC, efflux pumps pump them out. - ‚Äč MexA, MexB, and OprM proteins all pump out drugs.What are the mechanisms of resistance for Acinetobacter?- impermeable membranes - Porins (Proteins 1 and 2) of the outer membrane are very small channels that are very exclusive to uptake of antibiotics.What is ecthyma gangrenosum?- Hemorrhagic necrosis of the skin - Ecthyma gangrenosum is particular to P. aeruginosa.‚Äč - Ecthyma gangrenosum is remarkable (and different from anaerobic foot ulcers) because it lacks pus.What is exotoxin A?is responsible for tissue necrosis in P.aeruginosaPrebiotics- Substances that are fermented in the colon and support enteric microbiota‚Äč - Must selectively stimulate growth or activity of health promoting bacteria in the colon - found in asparagus, bananas, artichoke, leak, onions, and soy - eaten by probiotics?Probiotics- Nonpathogenic, living microorganisms with beneficial effect on host when consumed in adequate amounts - dont permanently colonize the GI tract and must injected enough regularly to maintain - Fresh: corn, cabbage, beans, yogurt - Fermented: brined olives, kimchi, miso, sauerkraut, tempehMOA of probiotics- Stronger GI barrier‚Äč - Epitheal cell regeneration‚Äč - Maintenance of tight junctions‚Äč - Inhibit apoptosis - Antimicrobial action ‚Äč - Competition for space and nutrients‚Äč - Produce lactic acid lowering pHProbiotics counseling points- Administration: separate from antibiotic dose; continue duration of antibiotic course; follow manufacturer direction - side effects: mild gi discomfort - Avoid: immunocompromised; severely illProbiotics ebmIf you see Corynebacterium spp., ‚ÄčNon-anthracis Bacillus spp., and Propionibacterium acnes, how likely is it a culture contamination in the blood? (bacteremia)- It is very likely. This is common skin flora that do not cause infections in humans normally.If you see Coagulase-negative Staphylococcus ‚Äč(CoNS), how likely is it a culture contamination in the blood? (bacteremia)It is possible. - If 1 out of 2 blood cultures are positive for CoNS, is likely a contaminant. If 2 out of 2 blood cultures are positive for CoNS, is likely a real infection.If you see staphlococcus aureus, how likely is it a culture contamination in the blood? (bacteremia)NeverWhat do we use in empiric treatment of bacteremia?Vancomycin‚Äč Daptomycin if allergic to vancomycinMSSA bacteria targeted treatment or ‚Äč Methicillin-susceptible coagulase-negative staphylococcus Bacteremia treatmentNafcillin IV Oxacillin IV Cefazolin IVMRSA bacteria target treatment or Methicillin resistant coagulase negative staphylococcus Bacteremia treatment- vanco IV - Dapto (avoid if cause is pneumonia)When s. aureus is present in blood what should you do?- NEVER considered a contaminant when in blood‚Äč ‚Äč - Evaluation for endocarditis via echocardiogram ‚Äč - Transthoracic echocardiogram (TTE)‚Äč - If TTE is negative: ‚Äč Obtain a transesophageal echocardiogram (TEE)‚Äč ‚Äč - Blood cultures drawn daily until 1 is negative‚Äč "Serial blood cultures"How many days of treatment should a patient with S. aureus bacteremia get?"14 days" of treatment with IV antibiotics‚Äč ‚Äč "Day 1" is day of first negative blood cultureEndocarditis MicrobiologyHACEK organisms‚Äč - Haemophilus spp.‚Äč - Aggregatibacter actinomycetemcomitans‚Äč - Cardibacterium hominis‚Äč - Eikenella corrodens‚Äč - Kingella kingae‚Äč ‚Äč - Mouth flora that frequently cause endocarditis‚Äč ‚Äč - Bacteremia with any of these could mean endocarditisWhat are the signs and symptoms of endocardititis?Fever in >90% of cases‚Äč ‚Äč Heart murmur in 85%(New or changed‚Äč) ‚Äč Continuous bacteremia- Remaining positive after several days of appropriate antibiotics‚Äč ‚Äč Splenomegaly if subacute‚Äč ‚Äč Laboratory abnormalities‚Äč (Anemia, thrombocytopenia, leukocytosis)What is the treatment for endocardititis prophylaxis?Oral amoxicillin 2 g PO x1 ‚Äč(Take 30-60 minutes prior to dental procedures‚Äč) ‚Äč Recommended for highest risk patients‚Äč: - Presence of prosthetic valve or prosthetic other prosthetic cardiac material‚Äč - Prior history of infective endocarditis‚Äč - Congenital heart disease (CHD)What are the diagnostic criteria for a patient to have SIRs?Temperature: ‚Č• 38‚ĄÉ (100.4‚ĄČ) or <36‚ĄÉ (98.8‚ĄČ) Heart: > 90 beats/min Respiratory rate (RR) OR PaCO‚āā: >20 breaths/min OR <32 mmHg WBC: > 12,000 (12.0 x 10¬≥) cell/mm¬≥ or < 4,000 (4.0 x 10¬≥) cells/mm¬≥ OR bands: >10%How do you diagnose sepsis?SIRS + active infectionHow do you diagnose septic shock?- MAP <65 or serum lactate >2 mmol/L AFTER FLUID BOLUS - These patients require vasopressors to maintain MAPs ‚Č• 65 mmHgWhat is the formula for Mean Arterial Pressure (MAP)?Infection Sites & Pathogens of sepsis/ septic shock?Gram negative bacteria - 53.8%‚Äč Commonly: E. coli, Klebsiella, Pseudomonas‚Äč ‚Äč Gram positive bacteria - 46%‚Äč Commonly: S. pneumoniae, S. aureus, Enterococcus‚Äč ‚Äč Anaerobic Bacteria - 6.1%‚Äč B. fragilis, Clostridium spp.‚Äč If involved, not likely the primary/sole pathogen‚Äč ‚Äč Organism dependent on source of infection!!Surviving Sepsis Campaign ‚ÄčTreatment Recommendations- Measure lactate level‚Äč Remeasure if elevated (> 2 mmol/L)‚Äč ‚Äč - Obtain blood cultures before administering antibiotics‚Äč ‚Äč - Administer antibiotics‚Äč ‚Äč - Administer fluid bolus if hypotensive or lactate > 2 ‚Äč(30 mL/kg of "balanced" crystalloid fluid‚Äč) ‚Äč - Apply vasopressors if hypotensive after fluid bolus‚Äč (Goal: maintain MAPs of > 65 mmHg‚Äč)How do we restore blood flow to vital organs during septic shock?Hemodynamic stabilization: ‚Äč Step 1: Fluid resuscitation‚Äč: Rehydrates patient, increasing BP‚Äč. If hypotension resolves, do not proceed to step 2‚Äč. Give in the first hour. ‚Äč Step 2: Vasopressor administration‚Äč: For patients with septic shock‚Äč- Increases vasoconstriction, increasing BPWhat are the fluid resuscitation option for septic shock?Classic Crystalloids‚Äč: - Normal saline (NS), ¬Ĺ NS, hypertonic saline (3% NaCl)‚Äč - 5% dextrose in water (D5W), 10% dextrose in water‚Äč ‚Äč "Balanced" Crystalloids:‚Äč **preferred** - Lactated Ringers - mixture of sodium, lactate, KCl, and CaCl‚Äč - Plasma-Lyte A - mixture of Na+, K+, Mg2+, Cl-, acetate, and gluconate‚Äč ‚Äč Colloids‚Äč: - Albumin‚Äč - Hexastarch‚Äč - Modified Gelatin‚Äč - DextranVasopressor crash course- Norepinephrine - increases vasoconstriction and heart contractility‚Äč ‚Äč - Dopamine - increases stroke volume and heart rate‚Äč Decreased survival and increased ADRs compared to norepinephrine‚Äč ‚Äč - Epinephrine - increases vasoconstriction in large doses‚Äč. Adverse effects of splanchnic circulation and produces hyperlactatemia‚Äč. No difference in mortality compared to norepinephrine‚Äč. ‚Äč Vasopressin - increases vasoconstriction. Effective in patient is refractory to other vasopressors (add-on therapy)‚Äč. High dose associated with cardiac and splanchnic ischemia.Septic shock vasopressor recommendationsVasopressors if MAP < 65 after fluid boluses‚Äč - Norepinephrine is the recommended 1st line vasopressor‚Äč. 8-12 mcg/min titrated to MAP > 65 mmHg‚Äč. ‚Äč - If MAP still <65 after norepinephrine drip:‚Äč Initiate vasopressin drip.‚Äč ‚Äč - If MAP still <65 after norepinephrine and vasopressin drip:‚Äč Initiate epinephrine drip.What is the empiric treatment for sepsis?Empirically cover normal pathogens for inciting infectionWhat is the empiric treatment for septic shock?- Empirically cover broad spectrum gram-negative and gram-positive organisms‚Äč( If patient isn't improving, consider fungal pathogens‚Äč. Treat fungal pathogens with echinocandins or fluconazole‚Äč.) ‚Äč - De-escalate antibiotics once stabilized or if cultures are growing a specific pathogen‚Äč ‚Äč - Duration of therapy is 7-10 days if patient is improving (doesn't have to be IV entire time) THEN: - Obtain cultures then start antibiotics targeting most likely pathogens‚Äč - Administer 30 mL/kg balanced crystalloid fluid bolus if hypotensiveSeptic shock empiric treatment for gram positive bacteriaTargeted pathogens: MRSA, Enterococcus, Streptococcus spp., Possibly VRE (only a concern when patient has a past medical history significant for these organisms) Antibiotic options: Vancomycin, Linezolid (if VRE concern), Daptomycin (if VRE concern)Septic shock empiric treatment for gram negative bacteriaTargeted pathogens: Pseudomonas aeruginosa, E. coli, Klebsiella spp., Possibly ESBLs (only a concern when patient has a past medical history significant for these organisms) Antibiotic options: Piperacillin/tazobactam, Cefepime, Carbapenems (If ESBL is a concern)Septic shock empiric treatment for anaerobe bacteriaTargeted pathogens: Bacteroides fragilis Antibiotic options: Metronidazole, piperacillin/tazobactam, carbapenemsWhich anaerobes are above the diaphragm?- Peptostreptococcus (gram positive) - Peptococcus (gram positive) - Prevotella melaninogenica (gram negative)What anaerobes are below the diaphragm?- Clostridium perfringens (gram positives) - Bacteroides fragilis (gram negative) - Clostridium difficile (UTI)What are obligate anaerobes?- bacteria that cannot use O2 for the ETC. High O2 concentrations are poisonous. - These are cells that prefer low or negative reduction (Eh) potential growth conditions by NOT using electron acceptors that are likely to get reduced. - release less energy - Anaerobes have become more creative with respect to carbon source utilization‚ÄčWhat are facultative anaerobes?- bacteria that can use O2 for the terminal electron acceptor of the ETC. In low O2 conditions, can also use fermentation. - Facultative anaerobes can be active at high reduction (Eh) potential, and at low reduction potential (Eh) in the presence of oxygen-bearing inorganic compounds, such as nitrates and sulfates.What are obligate aerobe bacteria?- bacteria that require O2 as the terminal electron acceptor of the electron transport chain. - These are cells that prefer high or positive reduction (Eh) potential growth conditions - have highest reduction potential and highest amount of energy released electron transportWhat is the central metabolic pathway for anaerobes?fermentation (2 atp)What is the central metabolic pathway fro aerobes?oxidative phosphorylation (38 atp) Aerobes have 3 metabolic systems that anaerobes do no: 1. Aerobes have cytochrome systems that can metabolize O2.‚Äč 2. Aerobes have superoxide dismutase (SOD) that can catalyze the reaction:‚Äč O2- + O2- ‚Üí H2O2+ O2‚Äč 3. Aerobes have catalase, which catalyzes the following reaction:‚Äč 2 H2O2 ‚Üí 2 H2O + O2 (gas bubbles)What is redox potential?the tendency of a molecule to acquire electronsHow do aerobes detoxify reactive oxygen species?O2 goes through metabolism. It produces toxic by products. These byproducts go through detoxifying pathways to form H2O and O2. These are very safe byproducts.How do anaerobes detoxify reactive oxygen species?O2 goes through metabolism. It produces toxic byproducts. There's no detoxifying pathway, and the anaerobes dies. Anaerobds will not be found in tissues where oxygen is high. They will often be found in wounds with puss involved. Pus is a nice layer of fluid to block out O2. They could be found with other bacteria as a kind of polymicrobial infection.Describe the polymicrobial nature of anaerobic infections.- Anaerobes are synergistic. In rat model of intraabdominal infection, there is a biphasic infectious process. This means There is a high mortality rate and isolation of E.coli from blood. Once O2 levels drop aka when a late abcess is formed, B. frag and Fusobacterium barium can be seen. The anaerobes will take over later on. - Bacteria are often team players.‚ÄčHow are bacteria team players in polymicrobial infections?- Facultative anaerobes (E. coli) consume the O2 in the wound (early phase)‚Äč - Obligate anaerobes, B. fragilis then colonize the low O2 environment (late phase).‚Äč - This often necessitates the use of combination therapy or empiric therapy that covers gram negative bacteria and anaerobes.What are the microbiological traits for bactericides fragilis?- Major GNR infection - bile resistant bugs that resemble coccobacilli. - Normally inhibit the gut - very high in stool - **Mostly implicated in intraabdominal infections**‚Äč (Due to perforations during surgery, diverticulitis, trauma, etc).‚Äč - You have to cover gram negative anaerobes as empiric therapy for intraabdominal infection.‚Äč - Cefotetan/cefoxitan - Also found in pelvic inflammatory disease and ovarian abscesses.What are the pathogenic traits for bactericides fragilis?- Produces suite of enzymes that strip cell membranes and cause hemolysis of erythrocytes‚Äč - Cytolysins, proteases, neuraminidases. - Bacteroides has a capsular polysaccharide that can cause abscesses by itself.‚Äč - Purified B. frag capsular polysaccharide causes abscess in rat model‚Äč - B. frag produces low levels of SOD ‚Äč - B. frag also produces lipopolysaccharides that are less toxic than other GNRs.‚Äč - Sepsis (shock/fever) are NOT due to the LPS, but due to secondary inflammation that results!‚Äč ‚Äč- associate capsular polysaccharide with b. fragWhat are the microbiological and pathogenetic traits for Prevotella melaninogenica?- Coccoid shaped GNRs‚Äč - Associated with upper respiratory tract‚Äč - Found in lung/brain abscesses - Brain abscess revealed on CT scanWhat are the microbiological traits for Clostridium perfringens?- Gram positive, anaerobic, rod‚Äč - Causative organism of gas gangrene.‚Äč - Gas gangrene makes a sound like "potato chips crumpling"‚Äč - Crepitus‚Äč - This is release of gas from the gangrene.‚Äč Uses nitrate instead of oxygen as electron acceptor.What of the many, many, many, many toxins of clostridium perfringens which is the most important to know?Epilson toxin. It is the most lethal toxin and cause hemorrhaging of heart, kidney, spinal cord, and brain. It has a potential use as a bioweapon.What are the pathogenetic traits of clostridium perfringens?- C. perfringens, simply put, terminates human tissues.‚Äč - The necrotizing effect can spread as much as 2 cm h-1‚Äč - Gas is produced from glucose fermentation. - C. perfringens is highly O2 tolerant because it forms endospores which C.dif dose as well. Endospores is a metabolically inactive state that the cell lives in. If you are trying to treat it with drugs like daptomycin or vancomycin, they require RNA polymerase doing things like transcriptions. Endospores are doing nothing. One of the most common ways drugs fail against Clostridium is because of the formation of endospores.Why does c. perfringes have a strong, foul odor?- C. perfringens has no genes for TCA cycle or respiratory chain.‚Äč - C. perfringens is completely dependent on fermentation‚Äč - It is an energy hog.‚Äč - It has several resulting fermentation products that give rise to a foul odorWhat are the microbiological traits for Fusobacterium necrophorum?- Pleomorphic, round, long gram negative rod with round ends.‚Äč - NOT a healthy component of the oral cavity - Very bad obligate anaerobe. If someone has this, they will need to undergo drug treatment immediately. - It is the causative agent of Lemierre's disease.What are the pathogenetic traits of Fusobacterium necrophorum?- Acute oropharyngeal infection is results in tonsular abscess‚Äč (it starts out as an infection in the tonsils) - This is quickly followed by secondary septic thrombophlebitis of the jugular vein‚Äč - This leads to metastatic infection of the lungs and joints. Infectious metastasis, not cancerous.‚Äč (metastatic means establishing site and moving to other tissues) - The bacteria form lesions in the lungs with pleural effusion.‚Äč (starts out making pus) - Also called necrobacillosis‚Äč (can be fatal)What is the immunologic bases behind immunizations?- Following exposure to an antigen the body develops an immune response to protect itself.‚Äč Immune responses are divided into:‚Äč - Innate immune responses‚Äč - Adaptive immune responsesWhat are innate immune responses?- Rapid and nonspecific‚Äč - First line of defense‚Äč Mediated by:‚Äč - Natural killer cells: Recognize and kill virally infected cells‚Äč - Complement‚Äč: Activated by components of bacteria‚Äč - Phagocytes: Macrophages and dendritic cells‚Äč; Ingest foreign particlesWhat are adaptive immune responses?- Specific ‚Äč - Develops over days‚Äč - Long-term immune memory‚Äč Stimulated through immunization‚Äč Mediated by:‚Äč - T lymphocytes‚Äč - B lymphocytesT lymphocytes- Subtype of white blood cell‚Äč - Part of cell-mediated immunity‚Äč - T helper cells: help other WBC in immunologic process (CD4+ T cells)‚Äč - Th1 cells: lead to cell-mediated responses‚Äč - Th2 cells: produce IL-4 and IL-5 which cause B cells to differentiate into antibody-secreting plasma cells‚Äč - Cytotoxic cells: destroy virus-infected and tumor cells (CD8+ T cells)‚Äč - Memory T cells: long-lived and can quickly respond to a stimulusB lymphocytes- Subtype of white blood cell‚Äč - Part of humoral-mediated immunity‚Äč - Plasma cells: Long-lived, non-proliferating antibody secreting cells‚Äč - Memory B cells: circulate throughout the body and initiate a stronger, more rapid antibody response if they detect the antigen that had activated their parent B cellAntibodies- Y-shaped protein produced by plasma cells‚Äč - Recognize antigens and bind to pathogen to tag it for attack by the immune system or neutralize the target by blocking invasion or impacting survival‚Äč - Also called immunoglobulins (Ig)‚Äč - IgM: Secreted in the early stages of a immune response‚Äč - IgG: Provides the majority of antibody based immunityexposures to vaccines- On first exposure to a vaccine, a primary response is induced and circulating antibodies will appear in 7-10 days. - IgM appear early and have low affinity ‚Äč - IgG appear later and have high affinity‚Äč - Antibody titers peak in 2-6 weeks and then decline - After a second exposure to a vaccine, a heightened humoral or cell-mediated response is observed.‚Äč Typically occur within 4-5 daysDeterminants of Immunogenicity‚Äč- Characteristics of the antigen‚Äč - Genetic characteristics of the recipient‚Äč - Physiologic state of the recipient‚Äč- age, nutritional status, sex, pregnancy status, stress, infections, immune status‚Äč - Manner in which the antigen is presented‚Äč- Route of administration, number of doses, timing of doses, presence of adjuvants, conjugationSerologic response to vaccine- Response to vaccines, seroconversion, gauged by measuring the appearance and concentration of antibodies.‚Äč- Only assesses humoral immunity‚Äč - Duration of immunity is assessed by persistence of antibodies.‚Äč May not be reliable‚Äč - Opsonophagocytic activity is used to assess functional antibodies.Response to vaccines - clinical protection - vaccine effectiveness- Calculate the risk of disease among vaccinated and unvaccinated persons and determine reduction in risk. - Recommended vaccine effectiveness for universal use of a vaccine in children is defined as > 80% following a primary series.Adjuvant- is a substance used in combination with an antigen to produce a more robust immune response.‚Äč - Depot effect‚Äč - Up-regulation of cytokines and chemokines‚Äč - Cellular recruitment at injection site‚Äč - Increased antigen uptake and presentation of antigen presenting cells (APC) which express pattern recognition receptors (PRR)‚Äč - Activation of inflammasomes‚ÄčAlum- Results in a depot effect and activates antigen presenting cells (APC)‚Äč - Provoke strong Th2 (humoral) response‚Äč - Poor modulation of Th1 (cellular) responseEmulsions- Results in a depot effect and induces major histocompatibility complex (MHC) response‚Äč - Provoke strong Th2 response‚Äč - Mixed Th1 responsePattern Recognition Receptor (PRR) Ligands‚Äč Pattern recognition receptors- Expressed by cells of the innate immune system : Dendritic cells, macrophages, monocytes, and neutrophils‚Äč - Detect molecules, pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens.‚Äč - Mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines.‚Äč - Examples:‚Äč + Membrane bound: Toll-like receptors (TLR), C-type lectin receptors (CLR)‚Äč + Cytoplasmic: NOD-like receptors (NLR), RIG-I-like receptors (RLR)Pattern Recognition Receptor (PRR) Ligands- Facilitate antigen binding to PRR.‚Äč - Induce innate immunity by targeting antigen presenting cells (APC) and subsequently influencing adaptive immunity.‚Äč - Stimulate Th1 and Th2 responses.B cell response to acapsular polysaccharide is T cell independent, meaning that B cells can produce antibodies without T cell stimulation. - Polysaccharides cannot be loaded onto the MHC complex of antigen presenting cells (APC) because MHC can only bind peptides.Conjugates- A highly antigenic protein that is attached to a poor antigen like a capsular polysaccharide.‚Äč - A conjugated vaccine is able to be presented on the MHC molecule and the T cell can be activated. ‚Äč- Stimulates a more vigorous immune response and promotes a more rapid and long-lasting immunologic memory.Examples of conjugated vaccines- Pneumococcal‚Äč - Haemophilus influenzae type b‚Äč - MeningococcalLive Attenuated Vaccines- Contained live but weakened bacteria or virus‚Äč - Risk of causing disease ‚Äč - Stimulate an immune response similar to the actual disease‚Äč - Durable immunity - Made by passing the pathogen through a series of cell cultures to diminish the pathogenicity. - e.g: Measles, mumps, rubella‚Äč Rotavirus‚Äč Small pox‚Äč Varicella‚Äč Yellow fever‚Äč Zoster (Zostavax)Inactivated vaccines- Contain killed whole microbes, toxoids, or antigenic subunits‚Äč - Cannot cause active disease‚Äč - Immunity tends to wane - Made exposing the pathogen to heat or chemicals such as formaldehyde or formalin.‚Äč - Destroys the ability to replicate but keeps it intact to stimulate the immune system. - E.g Hepatitis A‚Äč Polio‚Äč RabiesToxoid Vaccines‚Äč- Inactivating the toxin with heat or chemicals such as formaldehyde or formalin.‚Äč - Destroys the ability to cause symptoms but keeps it intact to stimulate the immune system.‚Äč Examples:‚Äč Diphtheria‚Äč TetanusSubunit Vaccines‚Äč- Contain fractions of the pathogen that provoke a response from the immune system.‚Äč Examples:‚Äč Haemophilus influenzae type b‚Äč Hepatitis B‚Äč Human papillomavirus‚Äč Meningococcal‚Äč Pertussis‚Äč PneumococcalVaccine Components- Antigen‚Äč - Suspending fluid‚Äč - Preservatives, stabilizers, and antibiotics‚Äč: Inhibit or prevent bacterial growth‚Äč + Thiomerosal is a mercury-based preservative. Now removed from most childhood vaccines.‚Äč + Stabilize the antigen‚Äč - AdjuvantsGeneral rule for administration of vaccinesexception: - Do not administer conjugated pneumococcal vaccine with the conjugated meningococcal vaccine to asplenic patients. Results in decreased response to the pneumococcal vaccine. Recommendation is to administer the pneumococcal vaccine followed by the meningococcal vaccine 4-weeks later.‚Äč - Do not administer the different pneumococcal vaccines (PCV13 and PPSV) together. There is a better immune response when PCV13 is administered first. - Oral typhoid and rotavirus vaccines may be administered with or at any interval before or after any other inactivated or live injectable vaccines.Routes of Vaccine Administration‚Äč- Intramuscular and subcutaneous administration results in primarily an IgG response.‚Äč - Intradermal administration may be more efficient and require less antigen to be administered. Possibly related to direct antigen delivery to the draining lymph nodes.‚Äč - Oral and nasal delivery produce a local IgA and general IgG response.Precautions with Administering Vaccines‚Äč- Allergic reaction to antigens or other vaccine components.‚Äč - Immunocompromised patients‚Äč: Poor response; Possibility of not controlling replication (live)‚Äč - Coadministration with antibiotics, antivirals, or immunoglobulins (live) ‚Äč - PregnancyVaccine Side Effects‚Äč- Vaccines stimulate an immune response‚Äč: Fever and aches are common‚Äč - Vary with vaccine‚Äč - Range from mild injection site reactions to death‚Äč - Vaccines with highest risk of severe adverse reactions:‚Äč Small pox, Yellow fever‚Äč - Guillain-Barre Syndrome‚Äč: Rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system.What is the mechanism of action of the COVID-19 vaccines?- The nucleoside-modified mRNA in the Moderna COVID-19 Vaccine is formulated in lipid particles, which enable delivery of the nucleoside-modified mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19. - The nucleoside-modified mRNA in COMIRNATY is formulated in lipid particles, which enable delivery of the mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.What is the mechanism of action of the streptococcal vaccine conjugate?Prevnar 13, comprised of pneumococcal polysaccharides conjugated to a carrier protein (CRM197), elicits a T-cell dependent immune response. Protein carrier-specific T-cells provide the signals needed for maturation of the B-cell response.What is the mechanism of action of the LIAV vaccine?The nasal-spray flu vaccine contains three different live (but weakened) influenza viruses. When the viruses are sprayed into the nose, they stimulate the body's immune system to develop protective antibodies that will prevent infection by naturally occurring influenza viruses.??Describe the role of adjuvants in stability and immunogenicity for the COVID-19 vaccines.Adjuvanted contains the SARS-CoV-2 spike protein and Matrix-M adjuvant.Describe the role of adjuvants in stability and immunogenicity for the streptococcal vaccine conjugate.Conjugate vaccines have been developed to induce a robust immune response against bacterial capsular polysaccharides (CPSs)What are the drug classes that cover anaerobic bacteria?1. Fluoroquinolone - moxifloxacin (only fluoroquinolone that does) 2. 2nd generation cephalosporins - Cefotetan/Cefoxitin 3. Piperacillin/tazobactam 4. Clindamycin, metronidazole, tetracyclines, tigecyclineMoxifloxacin- Flouroquinolone - Broad spectrum antibiotic - gram negative anaerobes - enteric gram negatives/aerobes e.g. Haemophilus influenzae or E.coli - atypical - streptococcus pneumoniae (also levofloxacin, gemifloxacin) - MOA: Flouroquinolone inhibit DNA topoismerases, enzymes that are involved in winding and unwinding the DNA; the action of the fluoroquinolones can lead to breaks in the DNA and death of the cellcefoxitin, cefotetan- 2nd gen cephalosporins - cover easy gram negatives e.g. E.coli, P. mirabilis - gram negative anaerobes e.g. B. Fragilis - You get MSSA and streptococcus - MOA: all beta lactams inhibit cross linking of peptidoglycan in the cll wall, leading to autolysis and cell death.Piperacillin/Tazobactam- BL/BLI - empiric coverage - oral anaerobes (Penicillin VK gets these) e.g. peptostreptococcus - T. pallidum - Enterococcus, streptococcus, AMP resistant H. influenza - Klebsiella, E.coli, SPACE - MSSA (beta lactamase bugs - B. Fragilis MOA: all beta lactams inhibit cross linking of peptidoglycan in the cll wall, leading to autolysis and cell death. - Ampicillin/sulbactam + Amoxicillin/Clavulanate are on his objectives, but we didn't go over in class ???Tetracyline/tigecycline- Tetracycline: formerly broad spectrum (resistance has somewhat blunted this) - Tigecycline: broader spectrum than tetracycline due to resistance forming against tetracycline Covers (tetracycline + tigecycline): - Rickettsiae - Atypicals - Fusobacterim (oral anaerobes) Tigecycline alone: - MRSA - B.fragilis (tigecycline has a little stronger anaerobic coverage than tetracycline)What is the mechanism of action of tetracycline/tigecycline?- It binds to the 30S subunit, preventing aminoacyl-tRNA from binding to it - bind to the bacterial ribosome at 30s subunit, preventing the docking transfer RNA carrying new amino acids for addition to the elongating protein chain.Metronidazole- Nitroimidazole - It broadly covers anaerobic bacteria (broadly) e.g. B. fragilis, Fusobacterium, clostridium (mild to moderate c.diff) - also covers parasites/ protozoans (Trichomonas, Amoeba) - does not cover aerobes (only anaerobes can actives this drug due to the redox state of anaerobic bacteria) - Disulfiram like reaction with alcohol, etc.(because of the inhibition of aldehyde dehydrogenase; it causes abdominal pain through the formation of acid aldehyde) - Interaction with warfarin: anticoagulation properties are significantly potentiated by inhibition of warfarin metabolism (inhibition of vitamin K2,3-oxidoreductase). Careful monitoring is required, and warfarin dose reduction is likely to be necessary. (hypoprothrombinemia)What is the mechanism of action of metronidazole/Tinidazole?- The key here is the nitro group. The nitro group is reduced by Ferredoxin (enzyme is only present in anaerobes for fermentation). Beforehand, Ferredoxin is reduced by pyruvate:ferredoxin oxidreductase. - Anaerobic bacteria and protozoa activate a part of the nitrimidazole molecule that forms free radicals, which are thought to damage DNA and lead to cell death.Tinidazole- Nitroimidazole - approval for parasitic infections only: protozoans, trichomonads, amoebas, Giardia, etc - Disulfiram like reaction with alcohol, etc.(because of the inhibition of aldehyde dehydrogenase) - Interaction with warfarin: anticoagulation properties are significantly potentiated by inhibition of warfarin metabolism (inhibition of vitamin K2,3-oxidoreductase). Careful monitoring is required, and warfarin dose reduction is likely to be necessary. (hypoprothrombinemia)Clindamycin- has activity against gram positive anaerobes - definitive anaerobe drug - some antistaphylococal activity (D test) - higher level of resistance than metronidazole with B. Fragilis or C.diff, for exampleWhat is the mechanism of action of clindamycin?- Binds to 5OS ribosomal subunit to inhibit translocation of peptidyl-tRNA from acceptor to donor site, thereby inhibiting bacterial protein synthesis - inhibits the transfer of peptides from the A site to the P site.Fidaxomicin- Macrolide - narrow gram positive coverage - only approved for CDI - selective eradication of pathogenic C. diff with minimal disruption to multiple species that make up normal, healthy GI tract - minimal absorption - non-inferior to vanco - $$$What is the mechanism of action of Fidaxomicin?- it binds to the "switch region" of bacterial RNA polymerase and inhibits RNA transcription intiation and synthesis - It depletes uracil during RNA transcription and inhibits cell growth when added to cultures of bacillus subtilisBezlotoxumab and actoxumab- C. diff infections causes damage through toxin A (cytotoxin) and Toxin B (enterotoxin) - Actoxumab binds to C. difficile toxin A via binding to host cells . - Bezlotoxumab binds to and neutralizes C. difficile toxin B via binding to host cells. - two double blind, randomized, placebo controlled studies showed: + Actoxumab had a higher rate of recurrent infection and adverse events when used to treat C. difficile when given adjunct standard of care antibiotics. The recurrent rates were identical with placebo as well. + Bezlotoxumab had a significantly lower C. difficile recurrence rate than placebo. When given with Actoxumab, there was a significantly lower C. difficile recurrence rate as well (showing that Bezlotoxumab accounts for all of the beneficial bacterial activities.)D-zone test- just took this from previous quizlet - If S. aureus is susceptible to clindamycin, there will be a halo effect around the clindamycin disk. - If it has inducible resistance genes (erm genes - resistance to clindamycin and erythromycin), the erythromycin will induce the expression of the erm genes on the left side of the plate give rise to the formation of a D shape. Meaning: do not use clindamycin.septic arthiritisSeptic arthritis:‚Äč Invasion of a joint by an infectious agent‚Äč ‚Äč Synovial fluid:‚Äč Fluid found in the joints to reduce frictionGout synovial fluid reading- crystals: needle like crystals - culture/gram stain: negative - color: yellow - WBC: ~20,000 - leukocytes: >50% - glucose: normal - lactate: normalPseudogout synovial fluid reading- crystals: rhomboid crystals - culture/gram stain: negative - color: yellow - WBC: ~20,000 - leukocytes: >50% - glucose: normal - lactate: normalSeptic joint- crystals: none - culture/gram stain: Postive - color: yellow - WBC: >20,000 - leukocytes: ‚Č•75% - glucose: low - lactate: highSeptic Arthritis Microbiology‚ÄčGram-positive pathogens:‚Äč Staphylococcus aureus; Streptococcus spp.‚Äč ‚Äč Gram-negative pathogens:‚Äč; Escherichia coli ‚Äč; Pseudomonas aeruginosa ‚Äč(Primarily in IV drug users (IVDU) or immunosuppressed patients)Gram positive cocci septic arthritis- Streptococcus, MSSA, MRSA - Empiric coverage: vancomycinGram negative bacilli septic arthritis- E. Coli - Empiric coverage: ceftriaxoneGram stain reported as negative + immunocompetent + no risk factors (Infectious Arthritis)- Streptococcus, MSSA, MRSA - Empiric coverage: VancomycinGram stain reported as negative + Traumatic bacterial arthritis- Streptococcus, MSSA, MRSA, E. Coli - Empiric coverage: Ceftriaxone + vancomycinGram stain reported as negative + Immunocompromised or IVDU- MRSA, Pseudomonas - Empiric coverage: Cefepime or pip/tazo + vancoEarly onset prosthetic joint infectionOnset of infection: < 3 month after surgery - origin of infection: implantaion - Symptoms: wound drainage, implant site erythema, joint pain, fever organism: S. aureus, GNB, anaerobes, polymicrobialDelayed onset prosthetic joint infectiononset of infection: 3-12 months after surgery origin of infection: implantation symptoms: persistent joint pain; fever organisms: cutibacterium, CoNS, enterococcilate onset prosthetic joint infectiononset: >12 months after surgery origin of infection: caused by seeding by another infection symptoms: acute onset of infection in previously well functioning joit organism: s.aureus, beta hemolytic strep, GNBResection arthroplasty with reimplantation- Indication: Delayed-onset‚Äč or‚Äč Late-onset - Two stage: removal of prosthetic followed by 4-6 weeks of IV antibiotics followed by reimplantation‚Äč‚Äč One stage: prosthesis resection, debridement of soft tissue and bone, and reimplantation of new prosthesis during same surgery followed by 4-6 weeks of IV antibioticsDebridement and retention of prosthesis- Early onset - Debridement of surgical site followed by 4-6 weeks of IV antibioticsMSSA prosthetic infection treatmentNafcillin, oxacillin or cefazolin allergic: vancoMRSA prosthetic infection treatmentVancomycin or daptoGroup A Streptococcus prosthetic infection treatmentAmpicillin or ceftriaxone allergic: Vancomycin or clindamycinEnterococcus prosthetic infection treatmentAmpicillin or vancomycin allergic: Vancomycin or daptomycin‚ÄčCutibacterium acnes prosthetic infection treatmentpenicillin G or certriaxone allergic :vancomycin or clindamycinGNB prosthetic infection treatmentCefepime, ceftazidime allergic: Ciprofloxacin or meropenemRifampin prosthetic infectionsMechanism of action: Inhibits bacterial RNA synthesis‚Äč ‚Äč Very effective at penetrating biofilms‚Äč Used in most situations with prosthetic material‚Äč ‚Äč Resistance develops very quickly ‚Äč Should never be given as monotherapy‚Äč ‚Äč Adverse effects:‚Äč Is hepatoxic - avoid in patients with hepatic insufficiency‚Äč ‚Äč Has many drug-drug interactions (strong CYP3A4 inducer)‚Äč ‚Äč Changes urine color to red/orange Rifampin is added for increased biofilm penetration