First Pass Miss - Micro Exam 2 Flashcards
What are the symptoms of the toxic shock syndrome exerted by LPS, and what induces similar physiologic responses?
Hypotension, fever, and disseminated intravascular coagulation (blood clotting / thromboses) mostly mediated via IL-1 / TNFalpha
Staphylococcal / streptococcal superantigens have a similar effect
What are three types of cis-acting regulatory regions?
- Promoter - DNA sequence recognized via RNA polymerase
- Operator - near promotor, binds repressor protein and reduces transcription when bound (i.e. lac repressor)
- Activator - near promotor, binds activator protein to increase transcription (i.e. CRP protein)
What is an attenuator?
mRNA secondary structure which modulates transcription (i.e. hairpin loop)
Would lacI be cis-acting or trans-acting?
Trans-acting since it creates the protein which binds the cis-acting lacO
What is an R factor and their two subunits?
R(esistance) factor is a conjugative episome which encodes for Abx resistance
- RTF - resistance transfer factor, coding autonomous replication and conjugal transfer
- Resistance determinant - composed of 1+ transposons, which carries the antibiotic resistance gene
What is the inducer of the lac operon?
Allolactose (indicates lactose presence), binds lac repressor to inactivate it, increasing transcription
What is lysogenic conversion, and what are some examples?
Change in bacterial phenotype after phage infection (bacterial virulence factors carried by specialized transduction)
Examples:
Diphtheria toxin, botulinum toxin, cholera toxin, exotoxin A (S. pyogenes), Shigatoxin
What penicillin class has the highest chance of kidney damage, and what symptoms are associated?
an be seen with all penicillins, but methicillin most common. Cause:
Acute interstitial nephritis
Triad: Fever, Rash, Eosinophilia which can lead to renal failure
What is the first line empiric treatment for bacterial meningitis?
3rd generation cephalosporins like ceftriaxone and ceftazidime which penetrate the BBB well, then if it’s like listeria you can switch to ampicillin
Why do we worry about SPICE organisms when treatment with 3rd generation cephalosporins? What should we do instead?
All have a beta lactamase which can be selected for during therapy, so against these it is best to use cefepime or carbapenems for invasive / critically ill infections
What does Avibactam do?
It is a non-betalactam b-lactamase inhibitor which can restore ceftazidime activity against organisms which produce b-lactamases and carbapenemases
What is the only monobactam and what is its claim to fame?
Aztreonam (beta-lactam with no side chain)
Used for empiric nosocomial gram negative coverage in patient with penicillin allergy (zero cross-reactivity)
Covers P. aeruginosa but NO ESBL (not quite carbapenem)
What are the only Beta-lactams which are not renally cleared and thus you don’t have to think about dosing?
- Ceftriaxone
- Penicillinase-resistant penicillins - i.e. Nafcillin
Have a major contribution of biliary secretion
Explains why ceftriaxone can’t be used in infants / neonates - biliary sludging
What is changed about the gram + and gram - activity of 3rd gen cephalosporins?
Gram + - Enhanced S. pneumoniae activity (good against Community-acquired pneumonia and bacterial meningitis), but worse MSSA activity (use first class)
Gram - - Good against nosocomial gram negative (PEK), but no Pseudomonas coverage
What is Streptolysin O analogous to in S. aureus?
It is a cytolysin which forms pores in RBCs, analogous to alpha toxin of S. aureus
What is TSST analogous to in S. pyogenes?
SpeA-E, inducing fever, rash, and hypotension. They are Streptococcal pyrogenic exotoxins
What do hydrolytic enzymes like streptokinase cause?
They dissolve fibrin to facilitate spread of bacteria, and are responsible for runny, thin pus. (pyoderma / streptococcal impetigo)
Can be used therapeutically to dissolve blood clots
When does erysipelas occur and what does it progress to? What are the associated symptoms?
Occurs on face, especially following strept throat. Can rapidly spread infection to deeper layers and cause necrosis + septicemia.
Associated with edema, fever, and lymphadenopathy
What limits the spread of tinea infections? What do chronic infections mean?
Rapid shedding of keratinized layers due to advanced skin growth which is induced by infection.
Cell mediated immunity is important and delayed-type (Type 4) hypersensitivity will result
Chronic infections: impaired T cell and lack of DTH reaction
What is the purpose of M protein? What is it responsible for?
Antiphagocytic, does molecular mimicry with antigen variation via N terminus (>80 serotypes)
Mediates binding to epidermis
Responsible for post-streptococcal sequelae, including acute glomerulonephritis, rheumatic heart disease
What are complications of roseola?
High fever, aseptic meningitis, hepatitis, mononucleosis-like syndrome
What is the structure of papillomaviruses?
Non-enveloped icosahedral
Circular dsDNA with 8-10 genes
What is the structure of Picornaviruses and what is one example?
Small, non-enveloped viruses with ssRNA (+) genomes
example: Coxsackieviruses (especially A)
What are two diseases caused by picornaviruses?
- Hand, Foot, and Mouth Disease - blisters / ulcers on all these areas, typical in Asia
- Herpangina - includes only the mouth lesions
What is one difference between HFM disease and when the lesions clear vs Roseola?
Typically, Roseola lesions do not actually appear until the fever is actually gone.
HFM lesions appear immediately and are gone in 1-5 days
What are levofloxacin and moxifloxacin also called and why?
Respiratory fluoroquinones -> good against all streptococcus, and all CAP organisms
Should not be relied on vs Staph / Enterococcus due to easy mutation
What is B. fragilis and what fluoroquinone is good against it?
An anaerobe commonly targeted in therapies
Only moxifloxacin
Unfortunately, it lacks anti-pseudomonal activity, also it’s not good versus UTI’s because it’s not renally cleared
What are the common fluoroquinolone side effects?
CNS toxicity - headaches, seizures, neuropathies
Tendon ruptures due to cartilage damage
Dysglycemia
Cardiac arrythmias / prolonged QT, especially moxifloxacin
What are daptomycin’s issues and when is it absolutely contraindicated?
Causes CPK elevations and rhabdomyolysis (muscle breakdown)
Irreversibly binds pulmonary surfactant, avoid in pneumonia
What is the clinical application of Linezolids?
VRE infections - but keep in mind it’s only static
MRSA - pneumonia (when vanco-resistant, dapto can’t be used)
What are VRE and what is the most common species for it? How is it typically treated?
Vancomycin-resistant enterococcus
Common in Enterococcus faecium
Treated via Linezolid / Daptomycin usually
What are the macrolides mostly active against?
Respiratory pathogens, including pneumococcus, Hemophilus, mycobacterium
Also: Chlamydia / gonorrhea
Mycobacterium avium complex seen in HIV
What is Azithromycin used for? Why is it chosen most often?
Chlymadia, gonorrhea, non-TB mycobacteria, and 1st line for CAP
It has a long half life, allowing for shorter drug course, has fewest CYP3A4 interactions, causes diarrhea least in class
What are doxycycline / minocycline typically used for?
Respiratory tract infections, including CAP
Skin infections, especially when CA-MRSA is a concern
Good against animal bites / lyme disease
What is minocycline emerging as good for?
Carbapenem-resistant A. baumannii
treated with Sulbactam or Imipenem/doripenem/meropenem before with little else
What are the two big problems with tigecycline?
- Highly lipophilic - poor for treating blood, lung, and urine infections
- Causes nausea/vomiting in 20% of patients
What is the spectrum of tigecycline activity? When is it used clinically?
Very broad in both gram positive and negative, just misses PP = pseudomonas and proteus
Used as last line for resistant gram-negative like Acetinobacter and Klebsiella
Used often in POLYMICROBIAL WOUNDS including MRSA or VRE
TPP = tigecycline misses pseudomonas and proteus
What should be done if something is found to be erythromycin resistant but clindamycin susceptible?
Special “D test”, since resistance may be latent and inducible - bacteria likely has the erm gene
What is the major clinical role for TMP/SMX?
Outpatient UTIs, good against MRSA but poor for Strept (not good for skin infections)
Also PJP pneumonia and S. maltophilia pneumonia
What can Trimethoprim cause? Sulfa?
Hyperkalemia -> blocks K+ excretion, so beware with K+ sparing diuretics
Also anemia, leukopenia, and granulocytopenia
Increased bleeding when given with warfarin
Sulfa: Hypersensitivity mostly, + rise in plasma creatinine although just by blocking secretion (unlike daptomycin which causes muscle breakdown and increased CPK)
What are three main uses of metronidazole?
- Empiric anaerobic coverage for intra-abdominal infections
- Drug of choice for mild-moderate C. difficile
- Trichomonas vaginalis coverage
What is the major side effect of metronidazole?
Peripheral neuropathy if given cumulatively
Also warfarin reaction (increase) + disulfiram-like reaction with alcohol consumption
What is Rifampin’s spectrum of activity?
Good against all gram +, including MRSA, but not used as a monotherapy
Ineffective against gram negative unless in combination
Excellent against TB
Give two reasons why Rifampin is not typically used
- Hepatotoxicity
- Induces multiple Cytochrome P450 enzymes, including CYP3A4. Contraindicated in many HIV meds because it causes subtherapeutic levels of the drugs (quicker metabolism)
How does Polymyxin B work and why did it stop being used?
Cationic detergent which destroys outer cell membrane LPS by displacing divalent cations
Stopped being used due to nephrotoxicity, only works against gram negative but works great
Why is polymyxin used clinically?
Last line treatment against multi-drug resistant gram negative:
P. aeruginosa, A. baumanii, K. pneumoniae, E. coli
What is nitrofurantoin used for, and its main contraindication?
Urinary tract organisms (gram negative, narrow spectrum)
Contraindicated if GFR < 60 mL/min (compromised kidney function)
Can be used in place of TMP/SMX or Keflex or Cipro
What is the mechanism of action of dapsone and when is it used?
antagonist of PABA
Used in prevention and treatment of pneumocystic pneumonia when patient has sulfa allergy (can’t used TMP/SMX)
causes Hemolysis worse with G6PDH deficiency
What is the primary virulence factor of Group D Streptococcus / Enterococcus?
Multiple, high-level resistances to a wide variety of antibiotics
Includes VRE
What is used for malaria prophylaxis?
Atovaquone / Proguanil = Malarone
How is Aspergillus identified in culture?
Branched, septate hyphae (mold form). Blood cultures will be negative, biopsy of infected tissue is necessary (unlike Candida).
What are the symptoms of babesiosis? How does it resolve?
Fever, not periodic
Myalgia, anemia, hepatosplenomegaly, renal dysfunction
Resolves spontaneously within a few week, but very dangerous in asplenic individuals
What is one major CNS complication of IE? One more? hehe
Mycotic aneurysm formation in arterial wall (abscess formation of vasovasorum)
Will be silent until rupture occurs causing subarachnoid hemorrhage
Also fibrin plates can break off and cause cerebral emboli
What are three main causes of osteomyelitis?
Recent trauma (hematologic spread) - common in young people
Surgery (local spread)
Diabetes - poor vasculature / insufficiency / necrosis
What time scale defines chronic osteomyelitis, and what is the main difference from acute?
> 3 months duration, often following acute OM
Main difference: chronic can be polymicrobial (acute is usually monomicrobial)
What are the major risk factors for septic arthritis?
Poor health indicators (low SES, diabetes, IDU)
rheumatoid arthritis
joint prostheses / history of steroid injections to joints
What joints are commonly affected in septic arthritis vs reactive arthritis? What disease processes do they follow?
Septic arthritis - usually monoarticular of knees or ankles, follows UTI
Reactive arthritis - usually four or fewer joints, asymmetrical, of back or lower limb, follows UG or GI infection
What are some extra-articular manifestions of reactive arthritis?
Anterior uveitis, conjunctivitis, keratoderm blennorrhagicum (psoriasis-like, often on feet)
What are involucrum and sequestrum?
Sequestrum - necrotic bone in osteomyelitis
Involucrum - ectopic bone overgrowth
What is the first line treatment for aspergillus? What azole is not active against it?
Voriconazole
Only fluconazole is not active against it
What is the clinical application of itraconazole?
Non-life threatening cases of endemic mycoses
What are posaconazole / isuvaconazole used for?
Mucormycoses, with isuvaconazole’s niche to be determined
What organisms are echinocandins good against?
All candida species, considered first line for all, except maybe C. parapsilosis
Aspergillus - used in combination therapy if patient is intolerant to voriconazole or amphotericin
When would you know to use echinocandins vs fluconazole for yeast infection?
If patient is not critically ill and this is new, use fluconazole
If recent azole exposure, known colonizer with C. glabrata, or critically ill, use echinocandins
What is the spectrum for cidofovir and when is it used?
HSV, VZV, CMV
Used for CMV when CMV is resistant to ganciclovir / foscarnet
When is foscarnet used and what are its big side effects?
Only for CMV when ganciclovir is not available
Side effects: Nephrotoxicity, CNS effects, potential chelator of divalent cations in blood (hypokalemia - bananas, hypocalcemia - milk, hypomagnesia - magnets)
What are the major neuraminidase inhibitors and what is one side effect?
Zanamivir (IV), oseltamivir (PO)
Zanamivir can exacerbate COPD if inhaled
What are the side effects of flucytosine?
Dose-dependent bone marrow suppression
What is the mainstay of therapy for animal bites?
Beta-lactam / beta-lactamase inhibitors which hit both gram positive and gram negative infections -> i.e. augmentin
Can still use doxycycline / ceftriaxone though
What drug of the cephalosporin class is good against S. pneumoniae?
1st generation cephalosporins are not good against it (all other streptococci they are fine against)
ceftriaxone is the drug of choice for CAP because of this coverage
What is a common saying for Clindamycin / Metronidazole?
Clindamycin above the diaphragm, metronidazole below
Clindamycin is good at treating Bacteriodetes and anaerobic species from mouth anaerobes leading to aspiration pneumonia
Metronidazole is good at treating anaerobic species in the gut and pelvis (C. difficile, Trichomonas)
What is the drug of choice for enterococccal endocarditis?
Ampicillin 4 weeks, gentamacin can be added
If amp-resistant, 6 weeks Vanco
Do at least 8 weeks if VRE (use daptomycin)
What is the empiric therapy for infected diabetic foot ulcers?
Initially IV therapy with vancomycin +/- ceftriaxone to cover gram negative in case of deep tissue infiltration
DONT WAIT FOR ULCER TO FULLY HEAL TO STOP
What are three major virulence factors of S. pneumoniae?
- Polysaccharide capsule - primary, avoids complement-mediated phagocytosis and lysis
- Pneumolysin, a membrane-damaging cytolysin related to SLO of S. pyogenes
- Cell wall teichoic acid / peptidoglycan promote inflammation
What are two other names for S. pneumoniae?
Pneumococcus or diplococcus (gram positive diplococci)
Same morphology as group B strep
What are the three primary virulence factors of P. aeruginosa?
- Exotoxin A
- Elastase
- Adhesin
What does elastase do? How does it relate to eye pathology?
Cleaves elastin and human Igs, collagen, and complement
It is the primary cause of corneal perforation in eye infection
What is the Quellung reaction?
One of the biochemical tests (other than capsular serotyping and P disk susceptibility testing) to test for P. pneumoniae
It checks if there is capsular swelling on addition of anti-capsule antibodies
What biochemical test is diagnosis of P. aeruginosa?
High levels of cytochrome oxidase -> positive oxidase test
What are the two stages of Chlamydia trachomatis?
- Elementary body - infectious, expresses adhesins
2. Reticulate body - replicative, intracellular
What is inclusion conjunctivitis?
Chlamydia eye infection of the neonate from direct contact with cervical secretions during delivery. (perinatal)
Marked by acute, mucopurulent discharge ~7 days post-partum
What is chronic follicular conjuncitivitis also called and who does it typically affect?
Trachoma - typically chronically infects people in the developing world of lower SES
Can cause blindness if complicated by trichiasis
What is seen on retinoscopy for Candida enophthalmitis?
Following injury, a white cotton ball expanding on retina or floating in vitreous humor
How are humans typically infected via histoplasma?
Inhalation of infectious conidia while handling bird (i.e.. chicken) or bat droppings
What are the two forms of Acanthamoeba species?
- Trophozoites - free-living and tissue-invading
2. Cysts - infectious stage, often get in following mild corneal trauma and improper contact lens sterilization
What is the primary virulence factor of GBS and how does it work? How does it create pneumonia?
Polysaccharide capsule with sialic acid moiety on terminal sugar, limiting C3b deposition and decreasing phagocytosis
Has a beta-hemolysin as well which injures lung epithelial cells and helps it penetrate BBB (E. coli K1 uses invasins)
How is E. coli K1 meningitis contracted?
Via low BW and pre-term babies (GBS meningitis contracted via same group + in moms with no IgG against GBS capsule)
What will Listeria most likely cause if contracted perinatally?
Septicemia + meningitis (third leading cause as a neonate)
Treat with IV Ampicillin
What do infants born with T. gondii often show? (if not aborted or stillbirthed)
Microcephaly, hydrocephaly, psychomotor disturbances, and convulsions (CNS involvement)
What forms are the Hep A and Hep B vaccines?
Hep A - inactivated, given around 12 months
Hep B - given to all high risk adults as recombinant surface antigen (subcellular)
What is Pneumovax?
Prevnar13?
Pneumococcal vaccine, conjugated vaccine covering 23 pneumococcal capsular types
Recommended in adults >65 yo and high risk individuals >2 yo
Prevnar13: 13 types, recommended in all children <5
What does Rotavirus cause? When should you get the vaccine?
Severe acute gastroenteritis
Recommended between ages 2-6 months
What is the meningococcal vaccine?
Vaccine with capsular polysaccharides A, C, Y, and W-135. B was not immunized previously (due to sialic acid autoimmune risk) but is now
