Are penicillin antibiotics bactericidal or bacteriostatic?
Bactericidal for gram + cocci/rods, gram - cocci and spirochetes.
What must penicillin antibiotics be able to do to be effective antibiotics?
1) Penetrate the cell layer in gram negative organisms 2) Maintain the beta-lactam ring 3) Bind transpeptidase and other penicillin binding proteins
How do gram negative organisms specifically alter themselves to become resistant to beta-lactam antibiotics?
Alter their porins and prevent beta-lactam passage through the outer membrane to the inner cell wall.
How do gram positive and gram negatives gain resistance to penicillins?
Gram positive organisms secrete beta-lactamases and gram-negative organisms have beta-lactamases bound to their cytoplasm. Both types of organisms can also alter the structure of their transpeptidase and prevent binding of the beta-lactams.
Common adverse reactions associated with penicillin antibiotics
1) IgE-mediated anaphylaxis 2) Delayed rash that appears days to weeks later 3) GI symptoms from destruction of normal flora
5 types of penicillins?
1) Penicillin 2) Aminopenicillin 3) Penicillinase-resistant penicillin 4) Anti-Pseudomonal Penicillin 5) Cephalosporin
Route of administration for penicillin G and V? Common uses for both?
G = IM/IV (sometimes used for s. aureus pneumonia). V = oral (sometimes used for group A strep pharyngitis).
Common penicillin antibiotics used for bronchitis, UTIs and sinusitis caused by gram-negative bacteria?
Aminopenicillins (ampicillin and amoxicillin). They penetrate gram-negative outer membranes better and thus cover more gram-negative organisms like E. coli, Proteus, Salmonella, Shigella (enterics), H. influenzae and L. monocytogenes. They are also one of the few drugs that work against gram-positive enterococci. Note that they are still susceptible to beta-lactamase.
When would you consider using the “Amp-gent” combo in the hospital?
Combining ampicillin (an aminopenicillin) with gentamycin (an aminoglycoside) provides broad spectrum coverage against gram-negative enteric organisms that cause UTIs. This is useful while you are waiting for cultures to tell you the exact organism.
Penicillin antibiotics that are the drugs of choice for serious s. aureus infections that cause cellulitis, endocarditis and sepsis.
IV penicillinase-resistant penicillins, nafcillin, oxacillin, methicillin (unless it is MRSA). You can also give oral cloxacillin and dicloxacillin.
What organisms are not well controlled by penicillinase-resistant penicillins?
Penicillin antibiotics that are used for pneumonia and sepsis caused by Pseudomonas aeruginosa and gram - rods.
Anti-pseudomonal penicillins. These include the carboxypenicillins: ticarcillin/carbenicillin and the ureidopenicillins: piperacillin/mezlocillin. These are often combined with aminoglycosides as “Pip-gent” and “Ticar-gent” for synergism against pseudomonas.
What organisms are not well controlled by anti-pseudomonal penicillins?
S. aureus. These antibiotics are susceptible to penicillinases.
What can you add to a beta-lactam that extends coverage to beta-lactamase producing gram-positives (S. aureus), gram-negatives (H. influenza) and anaerobes (Bacteroides)?
The beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam
What advantages do the cephalosporin antibiotics have over the beta-lactams? Organisms typically not covered by cephalosporins?
1) More resistant to beta-lactamases 2) Increased variability in coverage. Listeria, Atypicals (chlamydia/mycoplasma), MRSA and Enterococci are typically not covered (except ceftaroline).
How does coverage change as you go from first, to second, to third and fourth generation cephalosporins?
Increased control of gram-negative organisms and decreased control of gram-positive organisms. Note that the 4th generation has good coverage of BOTH gram negative and gram positive organisms.
Why are MRSA and enterococci resistant to all cephalosporins?
These organisms have changed the structure of their penicillin-binding proteins.
What cephalosporins are commonly used in patients with Proteus, E. coli, Klebsiella, Staph/strep infections that are allergic to penicillin AND/OR in patients having surgery for prophylaxis against skin infections (S. aureus)?
1st generations. Most start with “ceph” (like cephalexin). Just remember that cefazolin and cefadroxil are the exception to this rule and are also 1st generation cephalosporins.
What cephalosporins are commonly used in patients infected by gram + cocci, H. influenzae, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella and Serratia?
2nd generations. They have “fam, fa, fur, fox and te” in their names. (ceFAMandole, ceFAclor, ceFURoxime, ceFOXitin, cefoTEtan). The exceptions are cefmetazole, cefonicid, cefprozil and loracarbef.
What cephalosporins are commonly used in patients with nosocomial pneumonia, meningitis, sepsis, gonorrhea and UTIs caused by multi-drug resistant aerobic gram-negative organisms?
3rd generations. Most have “t” in the name (cefTriaxone, cefTazidime, etc.). The exceptions are cefixime, cefoperazone, cefpodoxin. Note that cefoTetan has a “t” but it is a second generation.
What cephalosporins have increased activity against pseudomonas and gram + organisms?
4th generation: Cefepime
Common adverse reactions associated with cephalosporins
10% cross-reactivity w/penicillin: 1) IgE-mediated anaphylaxis 2) Delayed rash.
What cephalosporin is commonly used in patient’s with community-acquired bacterial pneumonia before you know what the causative organism is? What other condition is this commonly used to treat?
Second-generation cefuroxime has good coverage against S. pneumoniae and H. influenzae. It is also used for sinusitis and otitis media caused by H. influenzae and B. catarrhalis.
What cephalosporins provide good coverage of anaerobic bacteria like Bacteroides and are consequently used for intra-abdominal infections, aspiration pneumonia and colorectal surgery prophylaxis?
Second generation: cefotetan, cefoxitin and cefmetazole.
3rd generation cephalosporin most often used for hospital-acquired meningitis caused by MDR gram-negative organisms? What other organism is it 1st line therapy treatment for?
Ceftriaxone has the best CNS penetration of the 3rd generation cephalosporins and is the 1st line drug for meningitis in neonates, children and adults. It is also 1st line for N. gonorrhoeae.
What are the only cephalosporins that are effective for treating pseudomonas?
Ceftazidime (3rd), cefoperazone (3rd) and cefepime (4th).
4 classes of beta-lactam antibiotics
1) Penicillin family 2) Cephalosporins 3) Carbapenems 4) Monobactams
What antibiotics have the broadest antibacterial activity of any of the antibiotics known? What is its Achilles heel?
Imipenem, ertapenem, meropenem, doripenem (from the carbapenem beta-lactam family). It is small (can pass through all sorts of porin channels) and beta-lactamase resistant. It covers gram - rods, gram + cocci and anaerobes (including pseudomonas and enterococcus). Its Achilles heel is MRSA, some pseudomonas and mycoplasma.
Why is cilastin given with imipenem and not meropenem?
Cilastin inhibits renal dihydropeptidase, the enzyme that breaks down imipenem. Meropenem is stable against dihydropeptidase.
Common adverse reactions associated with imipenem and meropenem
Cross-reactivity w/penicillin 1) IgE-mediated anaphylaxis and 2) Delayed rash. It also lowers the seizure threshold (fewer seizures w/meropenem).
What beta-lactam antibiotic is commonly used for nosocomial, MDR, gram-negative bacteria like Pseudomonas with little penicillin cross-reactivity?
Aztreonam (a monobactam beta-lactam antibiotic). Note that aztreonam only binds to gram - transpeptidase and is completely ineffective against gram + or anaerobes. Note that aztreonam can be combined with vancomycin or clindamycin for powerful broad-spectrum coverage.
Targets of the anti-ribosomal antibiotics
Bacterial 50S and 30S subunits of the 70S bacterial ribosome.
Drugs that fall into the anti-ribosomal antibiotics? What part of the ribosome do they affect?
1) Chloramphenicol (50S) 2) Clindamycin (50S) 3) Linezolid (50S) 4) Erythromycin (50S) 5) Tetracycline/Doxycyline (30S) 6) Aminoglycosides (30S)
What antibiotic is good for most clinically important bacteria (gram +, gram - and anaerobes like Bacteroides) in under-developed countries? When is it used in developed countries?
Chloramphenicol. Although it is cheap, it has side effects of aplastic anemia and gray baby syndrome. It is indicated in developed countries for meningitis (excellent CNS penetration) when the organism is unknown and the patient is allergic to penicillins and cephalosporins. It is also indicated in young children or pregnant women with Rocky Mountain Spotted Fever due to adverse effects of tetracycline in these populations.
Why does chloramphenicol cause gray baby syndrome?
Neonates cannot fully conjugate chloramphenicol and it reaches toxic levels in the blood. This results in vasomotor collapse and cyanosis that gives the baby an ashen gray color.
What antibiotic do surgeons like to use for prophylaxis against anaerobes (like bacteroides and clostridium) when their patient has a penetrating abdominal wound? What other conditions is this antibiotic used for?
Clindamycin. It covers gram + organisms and anaerobes *above the diaphragm*. It is often combined with an aminoglycoside to cover gram - enteric organisms and prevents the majority of intra-abdominal infections. It is also used in aspiration pneumonia, lung abscesses, oral infection, invasive group A strep, septic abortions, as an alternative to metronidazole in bacterial vaginosis, acne vulgaris and rosacea.
Common adverse reaction in patients taking clindamycin? How do you manage this condition?
Pseudomembranous colitis (C. difficile). Oral vancomycin or metronidazole are used to treat C. difficile.
What newer antibiotic is commonly used to treat resistant gram + infections like vancomycin-resistant enterococcus?
What are the drugs of choice in patients with community-acquired pneumonia that do not require hospitalization? What other conditions are they used for?
Macrolides (erythromycin, azithromycin, clarithromycin and roxithromycin). They cover Strep. pneumoniae, Staph, H. influenzae, Mycoplasma pneumoniae, Mycobacterium avium-intracellulare and C. trachomatis. They are also used for group A strep pharyngitis and staph cellulitis in patients who are allergic to penicillin. They are the drugs of choice for Legionnaires’ disease.
What antibiotic is effective against most gram + bacteria, Mycoplasma, and gram - Legionella and Chlamydia? Why is it more effective against the gram +?
Erythromycin. Gram + organisms absorb erythromycin 100x better than gram - organisms do.
Although erythromycin is one of the safest antibiotics, what are some of the adverse effects to look out for?
1) GI irritation from stimulation of peristalsis 2) Cholestatic hepatitis 3) Arrhythmias 4) Rash 5) Eosinophilia 6) Increase serum [coumadin/theophylline]
Which macrolide is often used as an alternative to doxycyline in patients with chlamydia?
Azithromycin, single dose!
Why is doxycycline typically more effective than tetracycline?
Tetracycline chelates cations (prominent in dairy products) and is not absorbed when chelated. Doxycycline chelates cations poorly and is better absorbed.
What antibiotics are commonly used for chlamydia, mycoplasma pneumoniae walking pneumoniae (as an alternative to macrolides), tick-borne infections (Brucella/Rickettsia/Borrelia) and acne?
Adverse effects associated with doxycycline and tetracycline?
1) GI irritation 2) Phototoxic dermatitis 3) Renal/Hepatic toxicity in pregnant women when given IV 4) Discolored teeth 5) Depressed bone growth
Why is it practical to always combine aminoglycosides with beta-lactam antibiotics?
Aminoglycosides must diffuse across the bacterial membrane to be effective and beta-lactam antibiotics help break down that membrane.
What drugs fall into the aminoglycosides? What organisms are generally covered by these drugs?
1) Streptomycin 2) Gentamicin 3) Tobramycin (good against pseudomonas) 4) Amikacin (broadest spectrum, great for MDR nosocomial infections) 5) Neomycin (broad coverage but toxic, only used in skin infections) 6) Netilmicin (GI surgery prophylaxis). Generally they cover aerobic gram - enterics like E. coli and pseudomonas.
Adverse effects of aminoglycosides
CN toxicity (irreversible hearing loss & vertigo), reversible renal damage (always monitor BUN/sCr), curare-like neuromuscular blockade. Note that these drugs are generally safe at steady-state levels.
What antibiotic can be used against N. gonorrhoeae as an alternative to penicillin and doxycycline if resistance has developed (this drug inhibits the 30S subunit)? What other drugs can also be used?
Spectinomycin, note that even though this inhibits the 30S subunit, it is NOT an aminoglycoside. Ceftriaxone (3rd gen. cephalosporin), azithromycin (macrolide) and fluoroquinolones (ciprofloxacin/ofloxacin) can also be used for penicillinase-producing and tetracycline-resistant N. gonorrhoeae.
Adverse effects of spectinomycin
Rare, note that it does not cause the vestibulocochlear or renal toxicity like the aminoglycosides do.
Adverse effects of treating a patient with rifampin
Red body fluids, hepatitis, induces P450 (drug-drug interactions w/coumadin, OCPs, oral hypoglycemics, corticosteroids and phenytoin).
How do the fluoroquinolones work in gram + organisms and gram - rods of the urinary/GI tracts (to include pseudomonas and neisseria)?
Bactericidal: Inhibit bacterial DNA gyrase in gram negatives and DNA topoisomerase in gram positives. It is mostly effective against gram negatives.
Adverse effects of fluoroquinolones?
GI irritability, cartilage damage in fetuses and children (tendon rupture, leg cramps), Stevens-Johnson syndrome, photosensitivity, long QT and increased theophyline levels.
What antibiotic is used for coverage of all gram + organisms to include MRSA, enterococcus, pseudomembranous colitis (C. difficile) and endocarditis caused by step and staph? How does it work?
Vancomycin. It complexes with D-Ala-D-Ala to inhibit transpeptidation in cell wall synthesis.
What drugs are options for gram positive organisms that have become resistant to vancomycin?
Synercid (quinopristin/dalfopristin) and linezolid.
How do trimethoprim and sulfamethoxazole work to cover many gram + and gram - bacterial infections, nocardia, chlamydia, shigella, salmonella, pneumocystis jirovecii and toxoplasmosis prophylaxis?
TMP-looks like bacterial dihydrofolate reductase and competitively inhibits the reduction of TH2 to TH4 for purine synthesis. SMX-competitively inhibits dihydropteroate synthase. These act synergistically to inhibit TH4 production and purine synthesis. Note that they are bacteriostatic alone but bactericidal when used together.
Why is TMP-SMX good for UTIs?
It is concentrated and excreted in the urine
Adverse effects of TMP-SMX?
GI symptoms, skin rash/marrow suppression (especially in AIDS patients), hemolysis in G6PD, megaloblastic anemia, tubulointerstitial nephritis, kernicterus in infants, and increased bleeding risk when taken with warfarin (increases warfarin levels).
What infections are controlled by TMP-SMX?
Wide range of gram + and gram - (no anaerobes thought). Remember “TMP-S”. 1) respiratory TREE: strep pneumoniae, H. influenzae otitis media, sinusitis, bronchitis and pneumonia. 2) MOUTH: GI gram - diarrhea (salmonella, shigella, E. coli). 3) PEE: urinary tract, prostatitis and urethritis from enterics like E. coli. 4) SYNDROME: AIDS pneumocystis carinii pneumonia, toxoplasmosis and isospora belli prophylaxis
Which cephalosporins have broad gram + AND gram - coverage that includes MRSA but excludes pseudomonas?
5th generation: ceftaroline
Adverse effects associated with vancomycin
Nephrotoxicity, Ototoxicity, Thrombophlebitis and Red Man Syndrome (causes direct mast cell degranulation and can be managed with slow infusion/anti-histamines)
How do bacteria become vancomycin resistant?
D-ala-D-ala modification to D-ala-D-lac
How do aminoglycosides work?
Bactericidal: inhibiting formation of the initiation complex by binding 30S, cause mRNA misreading and block translocation.
How do organisms become resistant to aminoglycosides?
Enzymatic inactivation of the drugs by acetylation, phosphorylation or adenylation.
How do tetracyclines work?
Bacteriostatic: bind 30S and prevent attachment of aminoacyl-tRNA
Why can doxycycline be used in patients with renal failure?
It is renally eliminated
How do organisms become resistant to tetracyclines
Decreased uptake or increased efflux pumps encoded by plasmids
How do macrolides work?
Bacteriostatic: Inhibit translocation by binding 23S rRNA of 50S subunit
How do organisms become resistant to macrolides?
23S rRNA binding site methylation
How does chloramphenicol work?
Bacteriostatic: Blocks peptidyltranferase at 50S subunit.
How do organisms become resistant to chloramphenicol?
Plasmid acetyltransferases inactive the drug
How does clindamycin work?
Bacteriostatic: Blocks translocation of peptides at 50S.
How do organisms become resistant to sulfonamides?
Altered dihydropteroate synthase, decreased drug uptake or increased PABA synthesis.
How do organisms become resistant to fluoroquinolones?
Efflux pumps and mutation in DNA gyrase gene
How does metronidazole work when treating giardia, entamoeba, trichomonas, gardneralla vaginalis, anaerobes like bacteroides and C. difficile and in triple combination with PPI/clarithromycin?
Bactericidal: forms free radicals in bacteria and protozoa.
How do the rifamycins rifampin and rifabutin work in patients with mycobacterial and Hib infections?
Inhibition of DNA-dependent RNA polymerase
Endocarditis prophylaxis? Gonorrhea prophylaxis? Recurrent UTI prophylaxis? Meningococcal prophylaxis? GBS prophylaxis? Venereal neonatal conjunctivitis prophylaxis? Postsurgical S. aureus prophylaxis? Strep pharyngitis prophylaxis in child with previous rheumatic fever? Syphilis prophylaxis?
Endocarditis: PCNs. Gonorrhea: Ceftriaxone. Recurrent UTIs: TMP-SMX. Meningococcal: Ciprofloxacin, rifampin for kids. GBS: Amp. Venereal neonatal conjunctivitis: Erythromycin ointment. Postsurgical S. aureus: Cefazolin. Strep pharyngitis prophylaxis in child with previous rheumatic fever: Oral PCN. Syphilis: Benzathine PCN G.
Pneumocystis pneumonia prophylaxis in HIV
CD4 < 200 w/TMP-SMX
Toxoplasmosis prophylaxis in HIV
CD4 < 100 w/TMP-SMX
Mycobacterium avium complex prophylaxis in HIV
CD4 < 50 w/Azithromycin
What guanosine analog is used in an aerosol form for treating severe respiratory syncytial virus bronchopneumonia in children?
Ribavirin is a nucleoside with structural similarities with guanosine and interferes with viral nucleic acid synthesis. Mechanisms of actions of ribavirin that interfere with viral replication include the following: 1) Inhibits inosine monophosphate dehydrogenase and depletes cellular stores of guanine. 2) Interferes with guanylation and methylation of the nucleic acid base and blocks the synthesis of mRNA 5’ cap. 3) Inhibits RNA polymerase.
What antiviral agent is a guanosine analog that is effective in the treatment of CMV retinitis in AIDS patients?
CMV encodes an enzyme that phosphorylates ganciclovir to monophosphate. Cellular kinase further phosphorylates monophosphate to triphosphate, which inhibits viral DNA polymerase.
What type of infections are well controlled by the antibiotic that blocks RNA chain initiation by binding to the DNA-dependent RNA polymerase?
Rifampin is effective against gram positive bacteria and mycobacterial infections. It is also used for meningococcal meningitis prophylaxis.
Which vaccines should not be given to people with allergies to eggs?
Influenza, measles, mumps, and yellow fever vaccines - are grown in chick embryos.
A pregnant woman of 36 weeks gestation presented at the obstetric clinic for her monthly follow up. Her anorectal and vaginal cultures were screened for Group B hemolytic streptococcus (GBS). The cultures grew GBS. Routine susceptibility test results of the isolate showed sensitivity to penicillin, ampicillin, cefazolin, clindamycin, vancomycin, and levofloxacin. It was resistant to erythromycin. The patient had history of anaphylactic reaction to penicillin. To prevent GBS infection of her newborn, what antibiotic should be administered to this patient as the intrapartum prophylactic agent?
In persons with penicillin allergy other than anaphylaxis or urticaria, cefazolin is the antibiotic preferred and recommended, as this antibiotic achieves effective intra-amniotic concentrations. But GBS-positive women who are at high risk of anaphylaxis should not receive cephalosporins because of the risk of cross reactivity. Such individuals can be treated with erythromycin or clindamycin if the colonizing strain is susceptible. Erythromycin is less preferred because of its high resistance rates and poor placental transfer. The strain isolated from the above patient is resistant to erythromycin and hence cannot be used. Resistance to erythromycin is often, though not always, associated with resistance to clindamycin. Therefore, it is preferable not to use clindamycin for this patient, and the drug of choice is Vancomycin.
Drug used to treat leprosy
A 42-year-old sexually active G1P1 female presents with a greenish vaginal discharge. Motile, flagellated organisms are seen on wet prep. She is allergic to penicillin and has a history of anaphylactic reactions. Her current medications include warfarin, lisinopril, hydrochlorothiazide, and atenolol. She prefers oral therapy. What is the most likely outcome of the drug interaction with a therapy of choice for her condition?
Increased INR: Trichomonas infection, is treated with metronidazole. Metronidazole is a potent inhibitor of CYP 2C9 systems and it may affect warfarin metabolism.
A 12-year-old girl does not want to eat and appears to have a fever. She has an inflamed throat, and you decide to treat her with 7 days of penicillin, but her mother tells you that her daughter is allergic to penicillin. What antibiotic should you prescribe to this child?
Tetracyclic antibiotics, such as doxycycline or tetracycline, would be the antibiotics of choice for a patient allergic to penicillin. Tetracyclics reversibly bind to the ribosome and inhibit protein synthesis. Doxycycline is contraindicated in children less than 8 years of age, pregnant women, and breastfeeding women. The major classes of antibiotics used today include penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines. A patient who is allergic to 1 type of penicillin (ampicillin, amoxicillin) is allergic to all types. Often, these patients are also allergic to the cephalosporins (cephalexin, cefaclor).
Most serious side effects of gentamycin
Ototoxicity and nephrotoxicity are common with aminoglycosides
A 30-year-old man with HIV is being treated with anti-viral agents. 4 weeks after initiating therapy, he presents with weakness and fatigue. Laboratory studies reveal anemia, leukopenia and thrombocytopenia indicating bone marrow suppression. What anti-viral agent is most likely the cause of his symptoms?
The primary toxic side effect of ZDV is bone marrow suppression leading to anemia and neutropenia, which may require transfusions.
A 32-year-old male presents to your clinic after receiving a vasectomy at an outpatient clinic. He has subsequently developed orchitis, even though he was given first generation cephalosporins as a prophylactic measure. Which of the following organisms is least likely to be sensitive to first-generation cephalosporins? A) Group A strep B) S. aureus C) Serratia D) E. coli E) Klebsiella
1st generation cephalosporins are effective against gram positive organisms like staph and strep. They also work against E. coli, Klebsiella and Proteus. They have no activity against serratia, enterobacter and pseudomonas.
A 6 year old boy presents with pharyngitis. Physical exam reveals pseudomembranes in the throat and severe lymphadenopathy. Culture on cystine-tellurite agar is positive for gram positive rods with metachromatic granules. How does this organism cause damage?
When infected by beta-prophage, corynebacterium diphtheriae secretes diphtheria toxin that inactivates EF-2, inhibits protein synthesis and causes cell death.
A 30 year old man presents with a black eschar on his neck surrounded by an edematous border. He has flu-like symptoms and a fever. He works as a farmer. Gram stain is shown below. What is causing his condition?
Note the gram-positive rods. Bacillus anthracis secretes the exotoxin edema factor, which mimics adenylate cyclase, increases cAMP and causes edema. There are 2 presentations of anthrax: cutaneous and pulmonary. He has both, with pulmonary anthrax being the most concerning because it can lead to pulmonary hemorrhage, mediastinhtis and shock.
A 4 year old boy presents with coughs and whoops on inspiration. His mom has had a cough for 100 days. What is causing their condition?
Bordetella pertussis secretes pertussis toxin, disables Gi, overactivates adenylate cyclase and impairs phagocytosis.
A 16 year old boy steps on a nail at a construction site. Shortly thereafter he cannot open his mouth and experiences spastic paralysis. Physical exam reveals spasticity and risus sardonicus. What is causing his condition?
Clostridium tetani releases the extolling tetanospasmin, which cleaves SNARE proteins in inhibitory neurons, preventing the release of GABA and Gly from Renshaw cells in the spinal cord.
A 60 year old man presents with diarrhea. He has a history of hospitalization 2 weeks ago for an infection. He has been taking clindamycin and ampicillin since discharge. Toxins A and B are detected in his stool. What is causing his condition and how do you treat him?
C. difficile infection produces toxin A, which binds to the brush border of the gut, and toxin B, which causes cytoskeletal disruption, actin depolymerization, pseudomembranous colitis and diarrhea secondary to antibiotics clearing out normal flora. Tx: metronidazole, oral vancomycin, fecal transplant.
A 35 year old man presents to the clinic complaining of a chronic cough, fatigue, night sweats, weight loss and a low-grade fever. He has been coughing up blood for about a week now and complains of low back pain. He has HIV. CXR showed cavitations and a central coin lesion. Biopsy and stain are shown below. What is the pathway this condition has followed as it has progressed?
Note the caseating granuloma with acid-fast bacilli indicative of Tb. Tb usually forms a Ghon complex and heals by fibrosis in primary infection in an immunocompetent host. Primary infection can lead to progressive lung disease and death in immunocompromised. Primary infections can become bacteremic, causing miliary Tb and death. Primary Tb can also become dormant in several organs. This patient most likely has secondary Tb, evidenced by the cavitary lung lesions and back pain (Pott disease). Secondary Tb can also affect the CNS (tuberculoma or meningitis), lymph nodes (adenitis), kindneys, GI and adrenals.
A 35 year old man presents to the clinic complaining of a chronic cough, fatigue, night sweats, weight loss and a low-grade fever. He has been coughing up blood for about a week now and complains of low back pain. He has HIV. CXR showed cavitations and a central coin lesion. What makes this microbe virulent?
Cord factor inhibits macrophage maturation and induces release of TNF-alpha. Sulfatides on the mycobacterium’s surface inhibit fusion of the phagolysosome.
A 40 year old woman with AIDS comes in with fever, diarrhea, weight loss and night sweats. Her CD4 is < 100. Stool has acid-fast bacilli, Hgb 7, Hct 25, WBC 1.5, pot 89k, alk phos 850, ALT 130, AST 80 and hyperbilirubinemia. Physical exam reveals hepatosplenomegaly. After ruling out lymphoma, what is your most likely diagnosis? How do you prophylax against this infection in other patients?
Mycobacterium Avium-Intracellulare presents with GI symptoms and marrow suppression in the immunosuppressed patient. Prophylaxis is done with azithromycin.
What is responsible for the 2 very different presentations of infection by mycobacterium leprae: 1) communicable disease with leonine facies and diffuse skin involvement 2) minimal hypoesthetic and hairless skin plaques?
Lepromatous leprosy is characterized by low cell-mediated immunity with a Th2 humoral response. Tuberculoid leprosy is characterized by a high cell-mediated immunity with a Th1 immune response.
How do you treat a patient who has been affected by mycobacterium leprae?
LEPROMATOUS: Dapsone, rifampin and clofazimine 2-5 years. TUBERCULOID: dapsone and rifampin 6 months.
Who are the lactose fermenting bacteria on MacConkey agar?
Citrobacter, Klebsiella, E. coli, Enterobacter and Serratia.
A 70 year old man presents with severe pneumonia, respiratory distress and diarrhea. Labs reveal a poorly staining gram-negative rod that showed up better with a silver stain. It was grown on charcoal yeast extract and cultured with iron and cysteine. Rapid urine antigen test is positive. What is causing his condition and how do you treat him?
Legionella pneumophilia is transmitted from environmental water sources and causes Legionnaires’ disease. Treat with macrolide or quinolone.
A patient presents with infection caused by a non-lactose fermenting oxidase positive gram-negative rod. The organism is shown below and has a grape-like odor. What conditions can be caused by this bug?
Pseudomonas aeruginosa is associated with burn infections, Pneumonia, Sepsis, External otitis, UTI, Drug abuse, Diabetic osteomyelitis and hot tub folliculitis. It can cause rapidly progressive necrotic skin lesions when bacteremic in immunocompromised patients (Ecthyma gangrenosum shown below).
Tx for pseudomonal infections
Aminoglycoside + extended-spectrum penicillin (piperacillin, ticarcillin, cefepime, imipenem, meropenem)
A 75 year old man presents with fever, cough and rusty colored sputum. Sputum stain reveals a lancet-shaped gram-positive catalase negative, alpha-hemolytic diplococci. It is optichin sensitive. What conditions can this microbe cause?
“MOPS”: Meningitis, Otitis media, Pneumonia and Sinusitis.
A 23 year old college student presents with meningitis. Labs reveal gram-negative diplococci that ferment glucose and maltose. What is causing his condition? How do you treat him?
Neisseria meningitides. Give him ceftriaxone or penicillin G. Give his contacts rifampin, ciprofloxacin or ceftriaxone for prophylaxis.
A 5 year old boy from Mexico presents with pneumonia, fever and nuchal rigidity. Labs show a gram-negative rod grown on chocolate agar with factors V (NAD) and X (hematin). How do you treat him?
He has H. influenzae B infection, treat mucosal infections with augmentin and meningitis with ceftriaxone. If he had meningitis give close contacts rifampin for prophylaxis.
Local vs. systemic tx for mycoses
Local: fluconazole or itraconazole. Systemic: amphoB.
This patient from the Mississippi and Ohio River valleys has a pneumonia, low-grade fevers, cough, hepatosplenomegaly a tongue ulcer and coin lesions on CXR. He was in contact with bird and bat droppings and is HIV+. What is the offending organism?
Histoplasmosis, note the macrophage filled with oval yeast histoplasma capsulatum (typically seen when HIV patients’ CD4 count is
This patient from central america presents with inflammatory lung disease and granulomas in his skin and bone. What is the offending organism?
Blastomycosis, note the broad-base budding.
A patient from the SW United States presents with pneumonia and meningitis after an earthquake. He also has bumps on the skin and arthralgia. What is the offending organism?
Coccidioidomycosis: note the spherules filled with endospores.
What does this patient from South America have?
Paracoccidioidomycosis, note the budding yeast with “captain’s wheel” formation.
A 40 year old patient with AIDS presents with pain on swallowing food, itchy groin and a white tongue. Physical exam reveals a heart murmur. Lab results are shown below. How do you treat this patient?
He has candida albicans infection. Note the pseudohyphae (left), budding yeasts (left) and germ tubes (right). Oral candidiasis will pop up in HIV patients when CD4
A 20 year old patient undergoing chemotherapy presents with chronic asthma that has not been helped by albuterol or fluticasone. He has a history of Tb and has new pleuritic chest pain and hemoptysis; however, CXR shows nothing. Labs are shown below. What type of cancer is he at risk for?
Aspergillus fumigatus is a mold that common affects neutropenic patients and sometimes produce aflatoxins associated with hepatocellular CA. Note the septate hyphae that branch at 45 degree angles. Aspergillus can cause allergic bronchopulmonary aspergillosis (ABPA) which presents like asthma but has associated bronchiectasis and scarring. Patients with prior cavitations from Tb or abscesses are at increased risk for formation of an aspergilloma.
A 35 year old patient with AIDS presents with headache, fever and neck stiffness. He is homeless and lives by all of the pigeons in the park. Culture on Sabouraud’s agar with india ink stain is shown below. Latex agglutination test was positive. What is causing his condition?
Cryptococcus neoformans stains well with india ink because it is heavily encapsulated. Note the “soap bubble” lesions and that the latex agglutination test is more specific than culture w/india ink. Note that this typically presents when CD4
A diabetic patient presents in ketosis. He has rhinocerebral and frontal lob abscesses, a headache, facial pain, black eschar on his face and cranial nerve palsies. Labs are shown below. How do you treat him?
Note the irregular, broad, nonseptate hyphae that branch at wide angles. Mucor is common in diabetic and leukemic patients because fungi proliferate in blood vessel walls when there is excess ketone and glucose. They can penetrate the brain via the cribriform plate and cause ischemia and necrosis of tissue. Tx with amphoB.
A 40 year old AIDS patient presents with pneumonia. CXR shows diffuse, bilateral interstitial infiltrates (ground glass appearance). Brochoalveolar lavage is shown below. How do you treat and when should you prophylax?
Note the disc-shaped yet forms with methenamine silver stain indicating pneumocystis jirovecii. Tx with TMP-SMX or pentamidine. You can also prophylax with dapsone or atovaquone when CD4 count 200 pneumonia is typically due to S. pneumoniae.
A patient with AIDS presents with severe diarrhea. Labs show oocysts on acid-fast stain. What is causing his condition?
Water was not filtered properly and this patient contracted cryptosporidium. Note that this is typically seen when CD4 < 200.
An HIV patient presents with focal neurologic deficits and headache. CT and MRI show several ring-enhancing lesions. Biopsy is shown below. How do you treat this patient and what do you advise to prevent future recurrence?
Note the tachyzoite indicating toxoplasma gondii. Tx with sulfadiazine + pyrimethamine. Prevent by avoiding undercooked meat and cat feces. Note that this typically appears when CD4
What are the live-attenuated vaccines?
Smallpox, yellow fever, chickenpox, Sabin polio virus, MMR and intranasal influenza.
What are the killed vaccines?
Rabies, IM influenza, Salk polio and HAV.
What vaccines are recombinants?
HBV (HGsAg) and HPV (6,11,16,18)
A 20 year old man presents with vesicular oral lesions around the time of midterms. Labs show a linear dsDNA enveloped virus. What viruses are in this family and what conditions do they cause?
HSV1: oral lesions, temporal lobe encephalitis and keratoconjunctivitis. HSV2: genital lesions. VZV: chickenpox and shingles. EBV: mononucleosis, Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal CA. CMV: retinitis, mononucleosis, pneumonia. HHV-6 and HHV-8: roseola. HHV-8: Kaposi sarcoma.
A patient with sickle cell disease presents with aplastic anemia. She was pregnant but delivered a stillborn hydrops fetus. She also complained of arthralgias shortly after her child had erythema infectiosum. What is causing her condition?
ssDNA virus: parvovirus B19.
Where does HSV-1 lie latent? How do you detect it?
Trigeminal ganglia. You can find it with a viral culture or CSF PCR for herpes encephalitis.
Where does HSV-2 lie latent? How do you detect it?
Sacral ganglia. Detect with smear of open skin vesicle (Tzanck smear) looking for multinucleate giant cells and intranuclear Cowdry A inclusions.
Where does VZV lie latent?
Trigeminal dorsal root ganglia.
Where does EBV lie latent? How can you detect it?
B-cells. It can be detected by atypical lymphocytes on peripheral blood smear (reactive cytotoxic T-cells). It can also be detected by the monospot test where heterophile antibodies agglutinate to horse/sheep RBCs.
Where does CMV lie latent? When does it typically present in AIDS patients?
Mononuclear cells. It will present in AIDS patients when CD4 < 50.
A 4 year old child from Mexico presents with high fevers for several days followed by seizures. He has a maculopapular rash. What herpesvirus could be causing his condition?
HHV-6, this is roseola.
A 34 year old HIV patient presents with dark and violaceous flat nodular skin lesions. He has recently had abdominal pain and a chronic cough. What is causing his condition?
HHV-8: Kaposi sarcoma causes proliferation of endothelial cells. This can affect the skin, lungs and GI tract.
Why family of viruses does rubella fall in?
What -ssRNA segmented virus replicates in the nucleus?
What -ssRNA nonsegmented virus causes croup, bronchiolitis, measles and mumps? How do you treat these infections?
Paramyxoviruses: parainfluenza = croup. RSV = bronchiolitis in babies. Tx with ribavirin.
What is the basis behind the drug palivizumab?
It is a monoclonal antibody to F protein that prevents RSV pneumonia by preventing epithelium fusion.
How factors help influenza viruses infect host cells?
Hemagglutinin and neuraminidase.
A 3 year old presents with cough, coryza and conjunctivitis. Physical exam reveals Koplik spots and maculopapular rash. What are serious complications of this child’s condition?
Subacute sclerosing panencephalitis can occur years later, giant cell pneumonia occurs in immunosuppressed and encephalitis can occur rarely withe measles infection.
A child presents withs swollen parotid glands and testis. His neck is also stiff. What is likely causing his infection if he was never vaccinated?
Physical characteristics of HIV
2 RNA. env gene: gp120 and gp41 form from cleavage of gp160. gag gene: p24 capsid protein. pol: reverse transcriptase, aspartate protease and integrase enzymes.
What people are immune to HIV infection? Who are slow progressors?
Homozygous CCR5 mutants are immune. Heterozygous CCR5 mutants are slow progressors.
When is the ELISA (rule out 1st)/Western Blot (rule in 2nd) test for HIV falsely negative? When is it falsely positive?
Falsely negative in 1st 1-2 months of HIV infection because IgG has not yet built up. Falsely positive in babies born to infected mothers because anti-gp120 crosses the placenta.
What are the 4 stages of untreated HIV infection?
1) Flu-like illness 2) Feels fine 3) Falling CD4 count 4) Final crisis
A patient with HIV presents with white lesions on the lateral tongue that cannot be scraped off. What agent causes this?
EBV causes hairy leukoplakia
A patient with HIV presents with superficial vascular proliferation. How do you make a definitive diagnosis in this patient?
Biopsy. Bartonella henselae causes bacillary angiomatosis and will show neutrophilic inflammation. HHV-8 causes Kaposi sarcoma and reveals lymphocytic inflammation.
A patient with HIV presents with focal neurologic symptoms. CT/MRI show demyelination of white matter tracts. What is causing this condition
JC virus reactivation can cause PML in AIDS patients when CD4 < 200.
Common cancer seen in patients with AIDS? Why?
Non-Hodgkin lymphoma (large cell type, esp. in oropharynx as Waldeyer ring) associated with EBV. Primary CNS lymphoma (associated with EBV). Squamous cell cervical and anal carcinoma (HPV). Kaposi sarcoma (HHV8)
A patient presents with facial abscesses that drain via the sinus tracts. Further examination reveals yellow sulfur granules and branching rods. What is your diagnosis and how do you treat it?
Actinomyces israelii, tx with penicillin G.
What antibiotics act on each bacterial region shown below?
1) Topoisomerase: fluoroquinolones 2) DNA: metronidazole 3) RNA polymerase: rifampin 4) 50S ribosomes: chloramphenicol, clindamycin, linezolid, macrolides, streptogramins 5) 30S ribosomes: aminoglycosides and tetracyclines 6) Cell wall: penicillinase-sensitive PCNs, penicillinase-resistant PCNs, antipseudomonal PCNs, cephalosporins, carbapenems and monobactams. 7) Peptidoglycan synthesis: glycopeptides vancomycin & bacitracin 8) Folic acid synthesis: sulfonamides and trimethoprim.
What antivirals act on each region of HIV shown below?
1) Maraviroc 2) Enfuvirtide 3) NRTIs: tenofovir, emtricitabine, abacavir, lamivudine, zidovudine (AZT), didanosine, stavudine 4) NNRTIs: nevirapine, efavirenz, delavirdine 5) Raltegravir 6) Lopinavir, atazanavir, darunavir, fosamprenavir, saquinavir, ritanovir, indinavir
What antivirals act on each region shown below?
1) IFN-alpha (HBV, HCV) 2) Amantadine, Rimantadine 3) Guanine nucleotide synthesis: Ribavirin (RSV & HCV) 4) DNA polymerase inhibitors: foscarnet/cidofovir (CMV & acyclovir-resistant HSV) 5) Guanosine analogues: acyclovir (HSV, VZV) and ganciclovir (CMV) 6) Neuraminidase inhibitors (oseltamivir and zanamivir)
Antiviral used for treatment and prevention of both influenza A and B virus?
Zanamivir/oseltamivir neuraminidase inhibitors
Antiviral used for treatment of RSV and chronic hepatitis C
Competitive inosine monophosphate dehydrogenase inhibitor: ribavirin. Inhibits synthesis of guanine nucleotides.
Antivirals with good activity against HSV and VZV, weak EBV activity and no activity against CMV or latent cells
Acyclovir, famciclovir and valacyclovir. These are guanosine analogues phosphorylated by HSV/VZV thymidine kinases to form triphosphate. They are incorporated into DNA by polymerase and causes chain termination.
Side effects of acyclovir
Obstructive crystalline nephropathy.
Antiviral with good activity against CMV in immunocompromised patients
Ganciclovir and valganciclovir. These are guanosine analogous that react with CMV kinases to form 5’-monophosphates. They are incorporated into DNA by polymerase and cause chain termination.
Side effects of ganciclovir
Pancytopenia and renal toxicity
Antivirals to use in immunocompromised patients with ganciclovir-resistant CMV retinitis and acyclovir-resistant HSV.
Foscarnet inhibits DNA polymerase by binding to pyrophosphate-binding sites on the enzyme. Note that this drug is also effective in latent cells because it does not require activation by a viral kinase. Cidofovir does the same thing.
2 NRTIs + 1 backbone drug (NNRTI, protease inhibitor or integrase inhibitor)
How do you know if a drug is a protease inhibitor?
It ends in “navir"
How do protease inhibitor function to contain HIV infection?
Inhibition of pol gene cleavage prevents HIV mRNA from dividing into its functional parts.
What drug is often given in HAART to boost the effect of protease inhibitors?
Ritanovir inhibits CYP450.
Side effects of protease inhibitors
Hyperglycemia, GI intolerance, lipodystrophy, nephropathy and hematuria.
Which NRTI is the only nucleotide?
Side effects of NRTIs
Marrow suppression, peripheral neuropathy, lactic acidosis, rash, anemia (ZDV) and pancreatitis (didanosine)
How do NNRTIs differ from their NRTI counterparts?
The bind reverse transcriptase and inhibit it without having to be phosphorylated
Side effects of NNRTIs?
Rash, hepatotoxicity, vivid dreams (efavirenz).
How does enfuvirtide work to prevent HIV progression?
Inhibits viral entry by binding gp41
How does maraviroc work to prevent HIV progression?
Inhibits CCR-5 on T-cell and inhibits interaction with gp120.
What can you use IFN-beta for?
What can you use IFN-gamma for?
Chronic granulomatous disease.
What can you use IFN-alpha for?
Hep B, Hep C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell CA and malignant melanoma.
What cells express MHC I and MHC II?
I: all nucleated cells (not RBCs). II: APCs.
How are antigens from foreign microbes loaded onto the surface of most regular cells in the body?
Beta2-microglobulin transports the antigen to the cell surface for expression on MHC I.
Diseases associated with HLA B27
“PAIR”: Psoriatic arthritis, Ankylosing spondylitis, IBD, Reactive arthritis.
Diseases associated with HLA DR2
MS, Hay fever, SLE, Goodpasture
Diseases associated with HLA DR3
DM1, SLE and Graves
What cytokines play a role in enhancing activity of NK cells?
IL-2, IL-12, IFN-alpha and IFN-beta
Where in the thymus does positive selection occur?
Cortex, determines if T cells are capable of binding MHCs
Where in the thymus does negative selection occur?
Medulla, determines if T-cells have high affinity for self.
Surface molecules involved in stimulation of a naive T cell
MHC + TCR. B7 + CD28
Surface molecules involved in stimulation of B-cells
MHC + TCR. CD40L + CD40.
How do the cytokines secreted from a Th1 cell differ from those secreted by a Th2 cell?
Th1: IFN-gamma secreted in response to IL-12 to activate macrophages and CTLs. Th2: IL-4: promotes isotope switching in B cells, and Th1 differentiation IL-5: recruits eosinophils, IL-6: fever and acute-phase proteins.
Transcription factor that determines if a T cell will become a regulatory T cell? What cytokines to regulatory T-cells secrete?
FOXP3 transcription factor. IL-10 and TGF-beta secreted as anti-inflammatory cytokines (especially inhibitory against Th1)
How do type 1 interferons help prepare the body to fight viral infections?
1) RNAase L upregulation causes degradation of host AND viral mRNA 2) Protein kinase upregulation cause inhibition of host AND viral protein synthesis. Both processes lead to apoptosis.
Immune response stimulated by a live attenuated vaccine. What vaccines do this?
Cell-mediated, hence a stronger immunity develops: MMR, Sabin polio, nasal flu mist, VZV and yellow fever.
Immune response stimulated by a killed vaccine. What vaccines do this?
Humoral response, weaker immunity develops: cholera, HepA, Salk polio, IM flu and rabies.
A patient presents 5 days after receiving vaccination for tetanus. He complains of fever, urticaria, arthralgias, proteinuria and lymphadenopathy. What is causing his condition?
Serum sickness happens when antibodies to foreign proteins are produce and form immune complexes that deposit in membranes and fix complement.
A patient comes to the allergist and has allergens injected into his skin. Around the injection site edema and necrosis develops. What is causing his condition?
Intradermal injection of antigen induces antibodies that form complexes in the skin and activate complement. This is called the Arthus reaction.
Hypersensitivity seen in transplant patients, Tb patients and contact dermatitis patients.
Type IV: sensitized T lymphocytes release lymphokines that lead to macrophage activation.
What type of hypersensitivity is involved in bee stings, peanut allergies, rhinitis, hay fever, eczema, hives and asthma?
Type I (anaphylactic, allergic and atopic disorders)
What type of hypersensitivity is involved in autoimmune hemolytic anemia, pernicious anemia, ITP, erythroblastosis fetalis, acute hemolytic transfusion reactions, rheumatic fever, Goodpasture syndrome, bulls pemphigoid and pemphigus vulgaris?
What type of hypersensitivity is involved in SLE, polyarteritis nodosa, post-strep glomerulonephritis, serum sickness, and the Arthus reaction?
What type of hypersensitivity is involved in MS, Guillain-Barre, Graft-versus-host disease, M. Tb PPD and contact dermatitis?
A 6 month old boy presents with recurrent bacterial and enteroviral infections. Labs show normal CD19 B cell count, decreased pro-B cell count and decreased Ig in all classes. Lymph node biopsy shows scanty lymph nodes. What is causing his condition?
X-linked agammaglobulinemia. This is caused by a defect in the Bruton Tyrosine Kinase (BTK) gene that results in no B cell maturation. It presents at 6 months because that is when IgG from the placenta begins to fall.
A patient presents with airway/GI infections, autoimmune disease, atopy and anaphylaxis after receiving blood products. What is likely causing his condition?
The most common cause of primary immunodeficiency is selective IgA deficiency.
A 20-30 year old patient presents with autoimmune disease, bronchiectasis, lymphoma and sinopulmonary infections. Labs show decreased plasma cells and immunoglobulins. What is likely causing his condition?
Common variable immunodeficiency results in defects in B-cell differentiation.
A patient presents with recurrent viral and fungal infections, a conotruncal cardiac abnormality that was repaired at birth and tetany. Lab show a decrease in T cells, PTH and calcium. CXR shows absent thymic shadow. What is causing his condition?
22q11 deletion results in failure to develop 3rd and 4th pharyngeal pouches and DiGeorge syndrome.
A patient presents with miliary Tb and disseminated fungal infections. Labs show a decrease in interferon-gamma. What is causing his condition?
IL-12 receptor deficiency results in a decreased Th1 response. This is an autosomal recessive disorder.
A patient presents with coarse facies, cold staph abscesses, retained primary teeth and eczema. Labs show increased levels of IgE and decreased levels of IFN-gamma. What is causing his condition?
Autosomal dominant hyper-IgE syndrome is a consequence of Th17 deficiency due to STAT3 mutations. This results in impaired PMN recruitment to sites of infection.
A baby presents with failure to thrive, chronic diarrhea and thrush. He has had recurrent viral, bacterial, fungal and protozoal infections. CXR shows absent thymic shadow, biopsy shows absent germinal centers and flow cytometry shows lack of T cells. What is causing this child’s condition? How do you treat him?
Autosomal recessive severe combined immunodeficiency (SCID). This can be a result of defective IL-2 receptors or adenosine deaminase deficiencies. Must treat with bone marrow transplant.
A patient presents with sever pyogenic infections early in life, PCP and CMV. Labs show increased IgM and decreased IgG, IgA and IgE. What is causing his condition?
Hyper-IgM is and X-linked recessive mutation that causes defective CD40L on Th cells. This prevents B-cells from class switching.
A patient presents with recurrent bacterial skin and mucosal infections, no pus formation, impaired wound healing and delayed separation of the umbilical cord at birth. Labs show elevated PMNs on CBC. What is causing his condition?
Autosomal recessive Leukocyte adhesion deficiency (type 1) is a result of defective LFA-1 integrin (CD18) protein on phagocytes. This prevents them from migrating in response to chemotactic signaling from inflamed areas.
A patient presents with increased susceptibility to pseudomonas, listeria, aspergillus, candida, E. coli, S. aureus and serratia. Labs show abnormal dihydrorhodamine flow cytometry and nitroblue tetrazolium dye reduction test is negative. What is causing his condition?
Chronic granulomatous disease is a result of X-linked recessive mutation in NADPH oxidase that prevents formation of ROS and respiratory burst in neutrophils.
A patient receives a renal allograft and the graft becomes ischemic and necrotic with widespread thrombosis within minutes. What type of transplant rejection is this?
Hyperacute, due to pre-existing antibodies to the donor antigen that activate complement.
A patient presents with vasculitis and dense lymphocytic infiltrate in a renal allograft weeks to months after implantation. What is causing this?
Acute rejection. CTLs are activated against donor MHCs and antibodies against the donor tissue develop after implantation.
A patient presents with irreversible vascular fibrosis and glomerulopathy after renal allograft that happened months to years ago. What is causing this?
Chronic rejection. This is because recipient T cells perceive the donor MHC as self that is presenting foreign antigen. This can cause atherosclerosis in heart transplants, bronchiolitis obliterans in lung transplants and vanishing bile ducts in liver transplants.
A patient presents with a maculopapular rash, jaundice, diarrhea and hepatosplenomegaly after receiving a bone marrow transplant. What is likely causing his condition?
Graft-versus-host disease. This is due to donor T cell proliferation in the immunocompromised host.
Cyclosporine mechanism and use.
Binds cyclophilin and prevents IL-2 transcription. Used in transplants, psoriasis and RA.
Cyclosporine main toxicities
Nephrotoxicity and gingival hyperplasia.
Tacrolimus mechanism and use
Binds FKBP and prevents IL-2 transcription. Used in transplants.
Tacrolimus main toxicities
Increased risk for diabetes and neurotoxicities, no gingival hyperplasia.
Sirolimus mechanism and use
Binds FKBP and inhibits mTOR signal transduction after IL-2 binds IL-2 receptor. Used in renal transplantation and cardiac stents.
Sirolimus main toxicities
Basiliximab mechanism and use
Blocks IL-2 receptor. Renal transplants.
Azathioprine mechanism and use
6-MP metabolite that inhibits nucleotide synthesis. Use in transplants, RA, Crohn’s, glomerulonephritis.
Azathioprine main toxicities
Allopurinol increases toxicity because it inhibits xanthine oxidase (degrades 6-MP). Anemia.
Recombinant cytokine used for anemia
Epoetin alfa (EPO)
Recombinant cytokine used for bone marrow rescue
Filgastrim (G-CSF) and sargramostim (GM-CSF)
Clinical use of IFN-alpha
HepB, HepC, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, RCC and malignant melanoma
Clinical use of IFN-beta
Clinical use of IFN-gamma
Chronic granulomatous disease
Rituximab mechanism and use
Anti-CD20: RA (w/MTX)
Infliximab and adalimumab mechanism and use
Anti-TNF-alpha. Used in IBD, RA, ankylosing spondylitis and psoriasis.
Natalizumab mechanism and use
Anti-alpha4-integrin (prevents leukocyte adhesion). Used in MS and Crohn’s.
Major side effect of natalizumab
PML in patients with JC virus
Omalizumab mechanism and use
Anti-IgE. Allergic asthma
Palivizumab mechanism and use
Anti-F protein for RSV prophylaxis in high-risk infants.
What immunomodulatory drugs work at the sites shown below?
1) Basiliximab 2) Azathioprine 3) Sirolimus (rapamycin) 4) Tacrolimus 5) Cyclosporine 6) Corticosteroids
Most common neurologic complication in AIDS