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What is the screening test for HIV?
ELISA which detects antibodies to HIV proteins.
A positive HIV ELISA test is confirmed by what test?
Western Blot which detects antibodies to HIV proteins.
What are the limitations to the HIV ELISA and Western Blot tests?
False negatives in the first 1-2 months following infection, and false positives in neonates born to HIV positive mothers)
What test is currently used to monitor HIV therapy effects on viral load? It can also be used to detect infection within the first 2 months of infection.
PCR/Viral load test
A CD4+ count less than what is diagnostic for AIDS?
<200
What are the 4 stages of HIV infection?
Flulike (acute), Feeling fine (latent), Falling CD4+ count, Final crisis (= the four F's)
Where does HIV replicate during the latent phase infection?
Lymph nodes
What opportunistic infections affect the brain in AIDS?
Cryptococcal (meningitis), toxoplasmosis, CMV (encephalopathy), PML (JC virus)
What opportunistic infections affect the eyes in AIDS?
CMV (retinitis)
What opportunistic infections affect the mouth and throat in AIDS?
Thrush (Candida albicans), HSV, CMV, EBV (hairly leukoplakia)
What opportunistic infections affect the lungs in AIDS?
P. jiroveci (carnii)pneumonia, TB, histoplasmosis
What opportunistic infections affect the GI in AIDS?
Cryptosporidium, Mycobacterium avium, CMV, EBV (non-Hodgkin's lymphoma)
What opportunistic infections affect the skin in AIDS?
Shingles (VZV), Kaposi's sarcoma (HHV-8)
What opportunistic infections affect the genitals in AIDS?
Herpes, warts, cervical cancer (HPV)
What types of infections are AIDS patients at risk for with CD4+ counts less <400
Thrush, tinea pedis, shingles, TB, and other bacterial infections
What types of infections are AIDS patients at risk for with CD4+ counts less <200
HSV, cryptosporidium, coccidiodomycosis, Pneumocystis pneumonia
What types of infections are AIDS patients at risk for with CD4+ counts less <100
Candidal esophagitis, toxoplasmosis, histoplasmosis
What types of infections are AIDS patients at risk for with CD4+ counts less <50
CMV retinitis, M. avium, cryptococcal meningitis
How does HIV gain access to the brain causing HIV encephalitits? What are the histological characteristics of HIV encephalitis?
Virus gains access via infected macrophges. Appears as microglial nodules with multinucleated giant cells
What is a prion?
A infectious particle containing only protein (NO genetic material) encoded my cellular genes
What is the difference in protein structure between normal prions and pathological prions?
Normal are alpha helices, pathological are beta-pleated sheets
What are some of the diseases caused by prions?
Creutzfeldt-Jakob disease, kuru, scrapie (sheep), and mad cow disease
Spongiform encephalopathy is associated with what type of infection?
Prion
Normal flora of the skin?
Staph. epidermidis
Normal flora of the nose?
Staph. epidermidis and colonized by S. aureus
Normal flora of the oropharynx?
Strep. viridans
Normal flora of dental plaque?
Strep. mutans
Normal flora of the colon?
Bacteroides fragilis > E. coli
Normal flora of the vagina?
Lactobacillus, and colonized by E. coli, and group B Strep
Common causes of pneumonia in neonates (<4wks)
Group B strep and E. coli
Common causes of pneumonia in children (4wk-18yr)
RSV, Mycoplasma, Chlamydia pneumonia, Strep. Pneumoniae (Runts My Cough Sputum)
Common causes of pneumonia in adults (18yr-40yr)
Mycoplasma, Chlamydia pneumonia, Strep. Pneumoniae
Common causes of pneumonia in adults (40yr-65yr)
Strep. Pneumoniae, H. influenzae, anaerobes, viruses, Mycoplasma
Common causes of pneumonia in the elderly (65+)
Strep. Pneumoniae, viruses, anaerobes, H. influenzae, gram- rods
Nosocomial pneumonia is caused by what organisms?
Staph, and enteric gram- rods
Pneumonia in immunocompromised patients is caused by what organisms?
Staph, enteric gram- rods, fungi, viruses, P. jiroveci (in HIV)
What organism is typically associated with pneumonia in a patient with cystic fibrosis?
Pseudomonas
What are the organisms that cause atypical pneumonia?
Mycoplasma, Legionella, Chlamydia
What are the three most common bacterial causes of newborn meningtitis?
Group B strep, E. coli, and Listeria
What are some of the common bacterial causes of meningitis in children?
Strep.pneumoniae, N. meningitidis, H. influenzae
What are some of the common bacterial causes of meningitis in adults?
N. meningitidis, enteroviruses, S. pneumoniae
What are some of the common bacterial causes of meningitis in the elderly?
S. pneumoniae and gram- rods
What group of enteroviruses is a common cause of meningitis?
coxsackievirus
Compared to normal what would be the CSF findings in a patient with bacterial meningitis in regards to Pressure, Cell type present, Protein, and Sugar?
Pressure - increased
Cell type - PMNs
Protein - increased
Sugar - decreased
Compared to normal what would be the CSF findings in a patient with fungal/TB meningitis in regards to Pressure, Cell type present, Protein, and Sugar?
Pressure - increased
Cell type - lymphociytes
Protein - increased
Sugar - decreased
Compared to normal what would be the CSF findings in a patient with viral meningitis in regards to Pressure, Cell type present, Protein, and Sugar?
Pressure - normal/increased
Cell type - lymphocytes
Protein - normal/increased
Sugar - normal
Osteomyelitis is most commonly caused by which organism?
S. aureus
Osteomyelitis in a patient with sickel cell disease is usually caused by which organism?
Salmonella
Osteomyelitis in the vertabrae (i.e. Pott's disease) is most commonly caused by which organism?
M. tuberculosis
In osteomyelitis, which two inflammatory tests are classicly seen to be elevated, although they are not specific?
CRP and ESR
What are the symptoms of a UTI?
Dysuria, polyuria, increased urgency, suprapubic pain
What are the symptoms of pyelonephritis?
fever, chills, flank pain, and CVA tenderness
The most common cause of UTIs are by ascending infections. What organism most frequently the cause?
E. coli
What are some predisposing factors to developing a UTI?
obstruction, kidney surgery, catheters, gynecologic abnormalities, diabetes, and pregnancy
Fact Card on UTI diagnosis
A positive leukocyte esterase test = bacterial UTI
Fact Card on UTI diagnosis
A positive nitrite test = gram negative bacterial UTI
What organisms are part of ToRCHeS infections?
Toxoplasma gondii, Rubella, CMV, HIV, HSV-2, Syphilis
What is the classic triad in neonatal Toxoplasma gonii infection?
Chorioretinitis, intracranial calcifications, and hydrocephalus. May be asymptomatic at birth.
A neonate presents with deafness, cataracts, and patent ductus arteriosis, microcephaly, mental retardation, and blueberry muffin rash. What are they infected with?
Rubella
What are the symptoms of CMV infection in neonates?
petechial rash, intracranial calcifications, mental retardation, hepatosplenomegaly, microcephaly, and jaundice. 90% are asymptomatic at birth.
How is HSV-2 transmitted to the fetus?
During birth
What are some of the symptoms associated with HSV-2 infections in a newborn?
Encephalitis, conjuctivitis, and vesicular skin lesions
Syphilis in a newborn presents as what?
skin lesions, jaundice, saddle nose, saber shins, CN VIII deafness, rhinits
Clinical features of gonorrhea are?
urethritis, cervicitis, PID, prostatitis, epididymitis, arthritis, and a purulent discharge
What stage of syphilis do you see painless chancre?
Primary
Seconday syphilis has what clinical features?
Fever, skin rashes, lymphadenopathy, condylomata lata
Gummas, tabes dorsalis, and aortits of characteristic of which stage of syphilis?
Tertiary
What agent is responsible for genital herpes?
HSV-2
What are the symptoms of active genital herpes ?
painful ulcers…Systemic symptoms MAY include fever, headache, myalgia
Reiter's syndrome, urethritis, cervicitis, conjuctivitis are all symptoms of what STD?
Chlamydia
Lymphogranuloma venereum is caused by what organism?
Chlamydia
A strawbery-colored cervix with corskscrew motility on wet prep indicates infection with what?
Trichomonas vaginalis
What diagnostic type of cells would you see in the epithelium of someone infected with HPV6 or HPV11?
koilocytes
Chancroid is characterized by painful genital ulcers and inguinal adenopathy. What is the offending organism?
Haemophilus ducreyi
Bacterial vaginosis is caused by what organism? What are clinical features?
Gardnerella vaginalis -- malodorous discharge (fishy), positive whiff test
Fact Card on Salpingitis and what it is a Risk Factor For
Ectopic pregnancy, infertility, chronic pelvic pain, and adhesions
What is the most common STD in the U.S.?
C. trachomatis
Nosocomial UTIs are caused by what organism most often?
E. coli
Nosocomial wound infections are caused by what organism most often?
S. aureus
Which bug causes a nosocomial infection by living in respiratory therapy equipment?
Pseudomonas
Bug Hints for the Boards (if all else fails) -- Pus, empyema, abscess
S. aureus
Bug Hints for the Boards (if all else fails) -- Pediatric infection
H. influenzae
Bug Hints for the Boards (if all else fails) -- Branching rods in oral infection
Actinomyces israelii
Bug Hints for the Boards (if all else fails) -- Traumatic open wound
Clostridium perfringes
Bug Hints for the Boards (if all else fails) -- Surgical wound
S. aureus
Bug Hints for the Boards (if all else fails) -- Dog or cat bite
Pasturella multocida
Bug Hints for the Boards (if all else fails) -- Currant jelly sputum
Klebsiella
Bug Hints for the Boards (if all else fails) --Sepsis/meningitis in newborn
group B strep
What nematodes infect orally (ingested)?
Enterobius, Ascaris, Trichinella (mnemonic: EAT)
What nematodes infect through the skin (cutaneous)?
Stongyloides, Ancylostoma, Necator
What parasite causes brain cysts and seizures?
Taenia solium (cysticercosis)
What parasite causes liver cysts?
Echinococcus granulosus
What helminth causes vitamin B12 deficiency?
Diphyllobothrium latum
What trematode causes biliary tract disease?
Clonorchis sinensis
What clinical findings are associated with Schistosoma haematobium?
Hematuria and Bladder cancer
What nematodes causes microcytic anemia?
Ancylostoma and Necator
What nematode causes perianal pruritus?
Enterobius (pinworm)
What organism causes Typhoid fever?
Salmonella typhi
What organism causes Typhus?
Rickettsia rickettsii (endemic) and Rickettsia prowazekii
What is the most common STD?
Chlamydia trachomatis
What flagellated protozoan causes greenish vaginal discharge?
Trichomonas vaginalis
What organism causes Chagas' disease?
Trypanosoma cruzi
What nematode can be found in undercooked meat?
Trichinella spiralis
What is the only DNA virus that is single stranded?
Parvovirus
What are the 3 DNA viruses with circular DNA?
Papilloma, Polyoma, Hepadnavirus
What is the only virus with double stranded DNA?
Reovirus
What are the naked (non-enveloped) viruses?
RNA: Calcivirus, Picornavirus, Reovirus DNA: Parvovirus, Adenovirus, Papilloma, Polyoma
What is the only virus that does not acquire its envelope from the host plasma membrane? Where does it acquire its membrane?
Herpesviruses acquired envelopes from nuclear membrane of host cell.
What is the only class of virus that is diploid?
Retroviruses (contain 2 identical ssRNA molecules)
Where do DNA viruses replicate?
Nucleus
Where do all but 2 RNA viruses replicate?
Cytoplasm
What 2 RNA viruses replicate in the nucleus?
Influenza and Retroviruses
What is the name of the structure that contains the nucleic acid in an enveloped virus?
Capsid
What is the only DNA virus that is NOT icosahedral?
Poxvirus
What is the only DNA virus that does not replicate in the nucleus?
Poxvirus
What causes zoster (shingles)?
Varicella Zoster Virus (VZV)
What causes heterophile antibody positive mononucleosis?
Epstein Barr Virus (EBV)
What infection is most common in transplant recipients?
CMV
What virus is associated with Kaposi's sarcoma?
HHV-8
What STD remains latent in sensory ganglia and causes genital vesicles?
HSV-2
What virus can be visualized using a Tzanck preparation?
HSV-2
What causes pink eye (conjunctivitis)?
Adenovirus
What virus is a common causes of febrile pharyngitis?
Adenovirus
What virus causes aplastic crises in sickle cell disease?
Parvovirus B19
What virus causes erythema infectiosum (fifth disease)? What is the physical finding associated with this disease?
Parvovirus B19; Slapped cheek appearance
What virus is associated with condylomata acuminata (venereal warts)?
HPV types 6 and 11
What virus is associated with cervical cancer?
HPV types 16 and 18
What disease does JC virus cause?
Progressive Multifocal Leukoencephalopathy (PML) in HIV patients
What virus causes molluscum contagiosum?
Poxvirus
What killed vaccine is used to prevent polio?
Salk
Is the measles/mumps/rubella vaccine live attenuated or killed?
MMR vaccine is live attenuated
What vaccines are killed?
Rabies, Influenza, Salk Polio, HAV (mnemonic: RIP Always)
What vaccine is recombinant?
HBV (HBsAg)
What causes worldwide influenza pandemics?
Reassortment (exchange of segments between genomes)
What is recombination?
Exchange of genes between 2 chromosomes by crossing over
How is Varicella Zoster Virus (VZV) transmitted?
Respiratory secretions
What causes negative heterophile antibody mononucleosis?
CMV
What virus is often cultured from urine and whose cells have owl's eye appearance?
CMV
What test is used to assay HSV-1, HSV-2 and VZV?
Tzanck test (intranuclear eosinophilic inclusions can be seen)
What cells does EBV infect?
B cells
What are the signs and symptoms of mononucleosis caused by EBV?
Fever, hepatosplenomegaly, pharyngitis, lymphadenopathy
What virus is associated with Burkitt's Lymphoma (t8;14)?
EBV
What three virus families do not have envelopes?
Picornavirus, Calcivirus, and Reovirus
What virus family has double stranded RNA?
Reovirus
What virus family does SARS belong to?
Coronavirus
What viruses are in the picornavirus class?
Poliovirus, Echovirus, Rhinovirus, Coxsackievirus, HAV (PERCH)
Mechanism of picornavirus replication?
RNA translated into large polypeptide that is cleaved by proteases
Cause of the common cold?
Rhinovirus, sometimes Coronavirus
Symptoms of yellow fever virus?
High fever, black vomitus, jaundice
What virus family is Rubella virus in?
Togavirus
Cause of German (3-day) measles?
Rubella virus
Major cause of acute diarrhea and gastroenteritis in infants?
Rotavirus
Genome of rotavirus?
dsRNA
What virus family are the influenza viruses in?
Orthomyxoviruses
Genome of influenza viruses?
ssRNA
Influenza vaccine type?
Killed viral vaccine
Major antigens on influenza viruses (2)?
Hemagglutinin and neuraminidase
What is reassortment of viral genomes called (e.g. human flu A + swine flu A)?
Genetic shift
What are minor changes in flu genomes called (based on random mutations)?
Genetic drift
Treatment/prophylaxis of influenza A?
Amantadine & rimantadine
Treatment of both influenza A & B?
Oseltamivir & zanamivir
Viruses in the paramyxovirus class?
Parainfluenza (croup), mumps, measles, RSV
What are Koplik spots?
Diagnostic finding in measles (red spots with blue-white center on buccal mucosa)
What are the 3 C's of measles (clinical findings)?
Cough, Coryza, and Conjunctivitis
Symptoms of mumps virus?
Parotitis, Orchitis, and Meningitis (Parotid/testes as big as POMs)
What virus family does rabies virus belong to?
Rhabdovirus
Characteristic cytoplasmic inclusions found in rabies?
Negri bodies
What is the time course for rabies infection?
Long incubation period of weeks-months
What class of virus is typically transmitted by arthropods?
Arboviruses
What is the primary transmission route of HAV?
Fecal-oral
What virus class is HAV?
RNA picornavirus
What virus class is HBV?
DNA hepadnavirus
How is HBV typically spread?
Parenteral, sexual, or maternal-fetal
Mechanism of HBV replication?
DNA-->RNA via RNA polymerase; RNA-->DNA via reverse transcriptase
What virus class is HCV?
RNA flavivirus
Which hepatitis virus most likely causes chronic hepatitis and hepatic cancer?
HCV
What virus must be present for hepatitis D virus to infect?
HBV
Which hepatitis virus causes high mortality in pregnant women?
HEV
What serologic test indicates prior infection with hepatitis A?
IgG HAVAb
What serologic test indicates current infection/carrier state with hepatitis B?
HBsAg
What antibody provides immunity from hepatitis B?
HBsAb (antibody to surface antigen)
What does the antibody against hepatitis B core antigen show?
Window period: IgM HBcAb shows recent disease and IgG HBcAb shows chronic disease
What enzyme creates dsDNA from RNA in HIV?
Reverse transcriptase
What two envelope proteins does HIV use to gain entry into human cells?
gp41 and gp120
What proteins does HIV bind to on human cells?
CXCR4 and CCR5
Name the fluoroquinolones
Ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, enoxacin. Nalidixic Acid is a quinolone
Mechanism of fluoroquinolones
Inhibit DNA Gyrase (topoisomerase II). Bactericidal. DON'T TAKE WITH ANTACIDS
Clinical Use of fluoroquinolones
gram neg. rods of urinary and GI tracts - Pseudomonas, Neisseria; some gm. Positives
Toxicity of fluoroquinolones
GI upset, superinfection, skin rash, headache, dizziness. Contraind. In pregnancy and children (damage to cartilage). Causes tendonitis in adults, leg cramps in children
Mechanism of Metronidazole
Forms toxic metabolites in the bacterial cell that damage DNA. Bactericidal.
Clinical Use of metronidazole
Antiprotozoal. GET GAP - Giardia, Entamoeba, Trichomonas, Gardnerella, Anaerobes (Bacteriodes, Clostridium). Use with bismuth and amoxicillin for triple therapy vs. H Pylori
Toxicity of metronidazole
Disulfiram-like reaction with alcohol, headache, metallic taste
Mechanism of polymixins (E+B)
Binds to cell membranes of bacteria and disrupts their osmotic properties. Cationic, basic proteins = act like detergent
Clinical use of polymixins
reistant gm. Neg. infections
Toxicity of polymixins
Neurotoxicity, acute renal tubular necrosis
Mycobacterium Prophylaxis and Treatment
Proph - Isoniazid; Treat - Isoniazid, rifampin, ethambutol, pyrazinamide
M. avium-intracellulare Prophylaxis and Treatment
Proph - Azithromycin; Treat - Azithromycin, rifampin, ethambutol, streptomycin
M. leprae Prophylaxis and Treatment
Proph - N/A; Treat - Dapsone, rifampin, clofazimine
Anti TB Drugs
INH-SPIRE - Streptomycin, Pyrazinamide, Isoniazid, rifampin, ethambutol. Cycloserine 2nd line. Impt SE of ethambutol = optic neuropathy, SE of others = hepatotoxicity
Mechanism of Isoniazid
Decrease synth of mycolic acids
Clinical use of isoniazid
Mycobact. Tuberculosis. Only agent used solo as prophylaxis
Toxicity of isoniazid
Hemolysis if G6PD defic, neurotoxicity, hepatotoxicity, SLE-like symps. PYRIDOXINE (vit B6) can prevent neurotoxicity
Mechanism of rifampin
Inhibit DNA-dep. RNA polymerase
Clinical Use of rifampin
Myco. TB, delay resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contact of children with H. Influenze B
Toxicity of rifampin
Minor hepatotoxicity and drug interactions (inc. P450s); orange body fluids
Resistance to penicillins/cephalosporins
beta-lactamase cleavage of beta-ring, or altered PBP (MRSA)
Resistance to Aminoglycosides
modification via acetylation, adenylation, or phosphorylation
resistance to vancomycin
terminal D-Ala of cell wall replaced with D-lac = decr. Affin
resistance to chloramphenicol
modification via acetylation
resistance to macrolides
methylation of rRNA near erythromycin's ribosome-binding site
resistance to tetracycline
decr. Uptake or incr. transport out of cell
resistance to sulfonamides
altered enzyme, decr. Uptake or incr. PABA synth
resistance to quinolones
altered gyrase of reduced uptake
Meningococcal prophylaxis
rifampin, minocycline
gonorrhea prophylaxis
ceftriaxone
syphilis prophylaxis
benzathine penicillin G
History of recurrent UTI prophylaxis
TMP-SMX
Pneumo. Jiroveci prophylaxis
TMP-SMX (drug of choice), aerosolized pentamidine
Endocarditis with surg/dental procedure prophylaxis
penicillins
treatment of resistant MRSA/VRE
MRSA - vancomycin; VRE - linezolid and streptogramins
mechanism of amphotericin B
binds ergosterol, forms membrane pores that allow leakage of electrolytes
clinical use of amphotericin B
wide spectrum of systemic mycoses (Cryptococcus, Blastomyces, Cocciodes, Aspergillus, Histoplasma, Candida, Mucor. Intrathecal for fungal meningitis. Does not cross BBB
toxicity of amphotericin B
fever/chills, hypotension, nephrotoxic (decr. With hydration), arrhythmias, anemia, IV phlebitis. Use LIPOSOMAL amphoB to decr. toxicity
mechanism of nystatin
binds ergosterol, disrupt fungal membranes. Too toxic for systemic use
clinical use of nystatin
swish and swallow for oral candidiasis, topical for diaper rash/vaginal candidiasis
Azoles
fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole
mechanism of azoles
inhibit fungal steroid synthesis (ergosterol)
clinical use of azoles
systemic mycoses. Fluconazole - cryptococcal meningitis in AIDS and all candidal infections. Ketoconazole - blastomyces, cocciodes, histoplasma, candida albicans, hypercortisolism. Clotrimazole and miconazole - topical fungal infections
toxicity of azoles
hormone synthesis inhibition (gynecomastia), liver dysfunction (inhib CYP450), fever and chills
mechanism of flucytosine
inhibit DNA synth by conversion to fluorouracil - compete with uracil
clinical use of flucytosine
systemic fungal infections (candida, cryptococcus) and in combo with ampB
toxicity of flucytosine
naus/vomit, diarrhea, BM suppression
mechanism of caspofungin
inhibit cell wall synthesis
clinical use of caspofungin
invasive aspergillus
toxicity of caspofungin
GI upset, flushing
mechanism of terbinafine
inhibit fungal enzyme squalene epoxidase
clinical use of terbinafine
dermatophytoses (onchomycoses specifically)
mechanism of griseofulvin
interfere with microtubule function, disrupt mitosis. Deposits in keratin-containing tissues (nails)
clinical use of griseofulvin
oral treatment of superficial infections, inhib growth of dermatophytes (tinea, ringworm)
toxicity of griseofulvin
teratogenic, carcinogenic, confusion, headaches, inc. P450 and warfarin metabolism
mechanism of amantadine
block viral penetration/uncoating (M2 prot), may buffer pH of endosome. Also causes release of dopamine from intact nerve signals
clinical use of amantadine
prophylaxis and treatment for Influenza A, Parkinsons Dz
toxicity of amantadine
ataxia, dizziness, slurred speech - fewer SEs with Rimantidine
resistance to amantadine
mutated M2 protein. 90% of influenza strains resistant = NOT USED ANYMORE
mechanism of zanamivir/oseltamivir
inhibit influenza neuraminidase = decr. Release of progeny virus
clinical use of zanamivir/oseltamivir
Influenza A & B
mechanism of ribavirin
inhib synth of guanine nucleotides by competitively inhibiting IMP dehydrog.
clinical use of ribavirin
RSB, chronic HCV
toxicity of ribavirin
hemolytic anemia. SEVERE TERATOGEN
mechanism of acyclovir
monophosphorylation by HSV/VZV thymidine kinase. Triphosphate formed by cellular enzymes. Preferentially inhib viral DNA polymerase by chain termination
clinical use of acyclovir
HSV, VZV, EBV. HSV-induced mucocutaneous and genital lesions as well as encephalitis. Prophylaxis in immunocomp pts. VZV = use FAMCICLOVIR. No effect on latent HSV/VZV
toxicity of acyclovir
well tolerated
resistance to acyclovir
lack thymidine kinase
mechanism of ganciclovir
5'-monophosphate formed by a CMV viral kinase or HSV/VZV thymidine kinase. Triphosphate formed by cellular kinases. Preferentially inhib viral DNA polymerase
clinical use of ganciclovir
CMV, especially in immunocomp pts
toxicity of ganciclovir
leukopenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir.
resistance to ganciclovir
mutated CMV DNA polymerase or lack of viral kinase
mechanism of foscarnet
viral DNA polymerase inhibitor that binds to the pyrophosphate binding site of the enzyme. Does not require activation by viral kinase
clinical use of foscarnet
CMV retinitis in immunocomp pts when ganciclovir fails, acyclovir-resistant HSV.
toxicity of foscarnet
nephrotoxicity
resistance to foscarnet
mutated DNA polymerase
Which bacteria are gram positive cocci?
Staphyylococcus, Streptococcus, Enterococcus
How do you distinguish S. aureus from S. epidermis and S. saprophyticus?
Staph aureus is catalase positive, coagulase positive. The other 2 are catalase positive and coagulase negative.
Describe Streptococcus vs. Staphyloccocus characteristics microscopically.
Strep is gram positive (purple/blue) chains. Staph is gram positive clusters (like grapes)
Which Bacteria are gram positive rods (bacilli)?
Clostridium (anaerobe), Corynebacterium, Listeria, and Bacillus
Which bacteria are alpha hemolytic?
S. pneumoniae and Viridans streptococci--plate is green (partial hemolysis)
Which bacteria are beta hemolytic?
Group A strep: S. pyogenes--plate is clear (complete hemolysis)
Which gram positive cocci can cause no hemolysis, alpha or beta hemolysis?
Enterococci (E. faecalis)
What bacteria are quellung positive, optochin sensitive and bile soluble?
S. pneumoniae Note: OVRPS (overpass) = Optochin Viridans is resitant, pneumoniae is sensitive.
What is a defining microscopic characteristic of Strep pneumoniae?
Lancet diplococci
What bacteria are optochin resistant and not bile soluble?
Viridans streptococci
How do you distinguish Group A Strep from Group B strep?
Grp A is bacitracin sensitive, GpB is bacitracin resistant Note: B-BRAS = Bacitracin- grp B strep resistant; gp A strep sensitive
Which Streptococcus has a capsule?
Strep pneumoniae (quellung positive)
What bacteria are Novobiocin Resistant? Novobiocin senstive?
Staph saprophyticus is Resistant; Staph epidermis is Sensitive; NOTE: NO StRES
What does an alpha hemolytic plate look like? Beta-hemolytic?
Alpha forms a green ring around colonies on blood agar; Beta form a clear area of hemolysis on blood agar.
What are the qualities of Listeria monocytogenes microscopically?
Listeria monocytogenes are gram positive rods with tumbling motility.
What characteristic of Staph aureus allows it to evade the immune system?
Protein A (virulence factor) binds Fc-IgG, inhibiting fixation and phagocytosis
Which organisms cause Toxic shock syndrome?
Caused by either Staph aureus TSST-1 toxin or Strep pyogenes.
What toxins does Staph aureus produce and what diseases do they cause?
TSST-1 superantigen: Toxic shock syndrome; Exfoliative toxin: scalded skin syndrome; Enterotoxins (preformed): rapid-onset food poisoning.
Which inflammatory disease can Staph aureus produce?
Skin infections, organ abscesses and pneumonia. Also causes acute bacterial endocarditis and osteomyelitis.
How does TSST-1 produce it effects?
It is a superantigen that binds to MHC II and T-cell receptor, resulting in polyclonal T-cell activation
What is the mechanism of resistance of a MRSA infection?
Methicillin Resistant S. aureus is resistant to B-lactams due to altered penicillin-binding proteins. *Important cause of serious nosocomial and community-acquired infections
How does rheumatic fever present and who is the culprit?
No rheum for SPECCulations: Subcutaneous nodules, Polyarthritis, Erythema margination, Chorea, Carditis. **Strep pyogenes.
What test can be used to detect recent S. pyogenes infection?
ASO titer
Antibodies to what part of S. pyogenes can enhance host defenses but also give rise to a serious infection?
M protein. Antibodies can give rise to rheumatic fever.
What complications can occur due to a Strep pyogenes pharyngitis?
Rheumatic fever and glomerulnephritis. Note: Pharyngitis gives you rheumatic PHever and glomerulonePHritis.
What pyogenic, toxigenic and immunologic diseases can Strep pyogenes cause?
Pyogenic: Pharyngitis, cellulitis, impetio; Toxigenic: scarlet fever, toxic shock syndrome; Immunologic: rheumatic fever and acute glomerulonephritis.
What are the 4 main diseases does Strep pneumoiae causes?
MOPS: Meningitis, Otitis media, Pneumonia, Sinusitis. It is also associated with rusty sputum, sepsis in sickle cell anemia and splenectomy
What characteristics of Strep pneumoniae help it evade the immune system?
Encapsulated and IgA protease
What are 3 main diseases Gp B streptococci is associated with?
Pneumonia, meningitis, and sepsis; mainly in babies
What diseases does Enterococci cause?
UTIs and subacute meningitis. Vancomycin resistant enterococci (VRE) are an important cause of nosocomial infections.
What are enterococci resistant to?
Penicillin G and some are Vancomycin resistant
What is Lancefield grouping based on and what is included in Lancefield group D?
It is based on differences in the C carbohydrate on the bacterial wall. Group D includes enterococci and nonenteroccal gp D streptococci.
Where can Staphylococcus epidermidis be found?
Component of normal skin flora, infects prosthetic devices, catheters, and blood cultures.
How is Listeria monocytogenes spread?
Ingestion of unpasteurized milk/cheese or by vaginal transmission during birth.
How does Listeria monocytogenes move from cell to cell?
They form actin rockets
What diseases/complications can Listeria monocytogenes cause in pregnant women?
amnionitis, speticemia, and spontaneous abortion
What disease can Listeria monocytogenes cause in infants?
Granulomatosis infantseptica, neonatal meningitis
What disease can Listeria monocytogenes cause in the immunocompromised? How about healthy individuals?
Immunocompromised: meningitis; Healthy: mild gastroenteritis
What is unique about Actinomyces and Nocardia microscopically?
They are both gram positive rods that form long branching filaments resembling fungi
What does Actinomyces israelii cause?
It is a gram positive anaerobe that causes oral/facial abscesses that may drain through sinus tracts in skin. **Normal oral flora
Where is Nocardia asteroides found and what disease can it cause?
It is found in the soil. It is a weakly acid-fast gram-positive aerobe that causes pulmonary infections in immunocompromised.
What can Actinomyces and Nocardia be treated with?
SNAP: Sulfa for Nocardia Actinomyces use Penicillin.
What pathological findings distinguish Primary Tuberculosis from Secondary TB?
Primary TB: Ghon Complex=TB granulomas (Ghon Focus- usually lower lobes) with lobar and perihilar lymph node involvement. Secondary TB has fibrocaseous cavitary lesions.
Where is extrapulmonary tuberculosis found?
CNS (parenchymal tuberculoma or meningitis), vertebral body, lymphadenitis, renal or GI
What is Pott's disease?
Extrapulmonary TB in the vertebral bodies
What does PPD+ signify?
The patient either has a current Tuberculosis infection, past exposure or BCG vaccination
What is a distinguishing microscopic characteristic of Mycobacteria?
They are all acid-fast organisms
What are the symptoms of Tuberculosis?
Fever, night sweats, weight loss, and hemoptysis
What are the two types of Leprosy and which has a worse Prognosis?
Tuberculoid (self-limited) and Lepromatous (due to failed cell-mediated immunity--its worse). Note: LEpromatous = LEthal
What are the main treatments for Leprosy?
Long term Dapsone (#1), alternates: rifampin, clofazimine/dapsone combo.
What are the side effects/toxicity of dapsone?
Hemolysis and methemoglobinemia
Where does Mycobacterium leprae infect and what is the reservoir in the U.S?
Infects the skin and superficial nerves. Armadillos are the reservoir in the U.S.
How does Mycobacterium kansaii present?
pulmonary TB-like symptoms
How does Mycobacterium scrofulaceum present and what age group?
Cervical lympadenitis in kids
What population does Mycobacterium avium-intracellulare present in and how?
Disseminated disease in AIDS, often multi-drug resistant.
are fungal spores asexual or sexual?
most asexual
budding yeast with pseudohyphae at 20 ⁰C and germ tube formation at 37⁰C
candida albicans
treatment for fungus that causes esophagitis in immunocompromised, endocarditis in IV drug users, vaginitis
candida albicans. nystatin if superficial infection; amphotericin B for systemic
tiny yeast inside macrophages in bat droppings causes?
pnemumonia. Histoplasmosis
fungi with broad-based budding that causes lung disease that can disseminate
Blastomycosis
Fungus endemic to SW US and California. Causes pneumonia and meningitis
Coccidiodomycosis
fungus with spherule filled with endospores
Coccidiodomycosis
budding yeast with Captain's wheel formation
Paracoccidiodomycosis
treatment for systemic fungal infection with granulomas?
amphotericin B
treatment for histo, blasto, or coccidiodomycosis that has not disemminated
fluconazole, ketoconazole
Malassezia furfur causes? Treatment?
tinea versicolor. Topical miconazole
treatment for pruritic annular lesions caused by dermatophytes
topical azoles
diagnostic test for thrush, vulvovaginitis, disseminated candidiasis
germ tube test
mold with septate hyphae that branch at 45⁰ angles
apergillus fumigatus
what does aspergillus cause?
bronchopulmonary aspergillosis, fungus ball in lung, invasive aspergillosis in immunocompromised with Chronic granulomatous disease
opportunistic fungal infections
Candida albicans, Aspergillus, Cryptococcus neoformans, Mucor and Rhizopus
encapsulated yeast that causes meningitis
cryptococcus neoformans
yeast found in soil or pigeon droppings. Identified by India ink stain
cryptococcus neoformans
mold with nonseptate hypahe braching at wide angles
mucor and rhizopus
who gets mucormycosis?
ketoacidotic diabetic and leukemic patients
diabetic patient with black necrotic tissue in nasal cavity and frontal lobe abscesses. What fungus is the cause?
mucor and rhizopus
yeast that causes diffuse interstitial pneumonia, especially in AIDS patients
pneumocystis jiroveci
patient has diffuse bilateral infiltrates on CXR and you suspect a fungal cause. Treatment?
TMP-SMX, pentamidine, dapsone for P. jiroveci
thorn prick causes pustule with ascending lymphangitis. Cause?
sporothrix schenckii
treatment for sporotrichosis?
itraconazole or potassium iodide
person went camping and now has diarrhea. Organism and treatment?
giardia lamblia. Metronidazole
green vaginal discharge with itching and burning. Organism and treatment?
trichomonas vaginalis. Metronidazole
cause of Chagas' disease
trypanosoma cruzi
characteristics of Chagas' disease?
dilated cardiomyopathy, megacolon, megaesophagus
Reduviid bug transmits?
Trypansoma cruzi to cause Chagas disease
African sleeping sickness carrier
tsetse fly
organisms that cause African sleeping sickness
Trypansoma gambiense and rhodesiense
person has spiking fevers, hepatosplenomegaly, and pancytopenia. Disease and organism?
Visceral leishmaniasis (kal-azar) caused by Leishmania donovani
transmits leishmaniasis
sandfly
treatment for leishmaniasis
sodium stibogluconate
cyclic fever with headache, anemia and splenomegaly
malaria
diagnosis of malaria
blood smear
treatment of malaria
cholorquine (primaquine if have P. Vivax or P ovale), sulfadoxine + pyrimethamine, mefloquine, quinine
malaria organisms with dormant forms in liver
Plasmodium vivax and P. Ovale
organism in northeastern US that causes fever and hemolytic anemia
babesia, transmitted by Ixodes tick
blood smear shows Maltese crosses. Causative protozoa?
babesia, transmitted by Ixodes tick
treatment of babesiosis
quinine, clindamycin
causes severe diarrhea in AIDS patients
cryptosporidium
causes brain abscesses in AIDS patients. Also causes birth defects
toxoplasma gondii
treatment for toxoplasma gondii
sufadiazine + pyrimethamine
why should pregnant women avoid cats?
to avoid toxoplasma gondii, found in cat feces
bloody diarrhea/dysentery, liver abscess, RUQ pain
Entamoba histolytica
treatment for amebiasis?
metronidazole and iodoquinol
protozoan that causes rapidly fatal meningoencephalitis?
Naegleria fowleri
transmission of Naegleria fowleri?
swimming in freshwater lakes; enters through cribriform plate
worm that causes anal pruritis and treatment
enterobius vermicularis (pinworm). Mebendazole/pyrantel pamoate
treatment for intestinal infection caused by ascaris lumbricoides?
mebendazole/pyrantel pamoate
roundworm found in pork. Muscle inflammation and periorbital edema
trichinella spiralis
treatment for trichinella spiralis
thiabendazole
worm that penetrates skin. Treatment?
strongyloides. Ivermectin/thiabendazole
worm found in drinking water that causes skin ulcerations and inflammation
dracunculus medinensis. Treat with niridazole
cause of river blindness
onchocerca volvulus, transmitted by blackfly
treatment for river blindness?
ivermectin
transmits loa loa?
deer fly, horse fly, mango fly
worm that blocks lymphatics?
wuchereria bancrofti
treatment for wuchereria bancrofti and toxocara canis
diethylcarbamazine
undercooked pork worm
taenia solium
taenia solium causes what?
cysticercosis and neurocysticercosis
treatment for neurocysticercosis?
albendazole
helminth in dog feces that causes liver cysts
Echinococcus granulosus
Schistosoma presentation?
granulomas, fibrosis, and inflammation of spleen and liver
worm in undercooked fish that causes pigmented gallstones and cholangiocarcinoma
clonorchis sinensis
worm in undercooked crab meat that causes inflammation and bacterial infection of the lung
Paragonimus westermani
treatment of Schistosoma, clonorchis sinensis, and Paragonimus westermani
Praziquantel
General mechanism of action of penicllins and cephalosporins?
Block cell wall synthesis by inhibition of peptidoglycan cross-linking
Which drug class acts by disrupting bacterial cell membranes?
Polymyxins
What bacterial enzymes do quinolones block?
DNA topoisomerases
Which drugs block peptidoglycan synthesis?
Bacitracin, Vancomycin
Which bacterial process is blocked by sulfonamides and trimethoprim?
Nucleotide synthesis
Which drugs block protein synthesis at 50S ribosomal subunit?
Chlormaphenicol, acrolides, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid
Where do aminoglycosides and tetracyclines act?
30S ribosomal subunit
Clinical use of penicillin?
Bactericidal for Gram-pos cocci, rods; Gram-neg cocci and spirochetes.
Toxicity of penicillin?
Hypersensitivity reactions, hemolytic anemia
Mechanism of penicillin?
Bind PBPs, block transpeptidase cross-linking of cell wall, activate autolytic enzymes
Which penicillins are penicillinase-resistant?
Methicillin, nafcillin, dicloxacillin
Clinical use of penicllinase-resistant penicillins?
Staph aureus (except MRSA)
Are ampicillin and amoxicillin penicillinase-resistant?
No (penicillinase-sensitive; use with clavulanic acid)
Clinical use of ampicillin and amoxicillin?
Haemophilus influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, enterococci
Toxicity of ampicillin and amoxicillin?
Hypersenstivity, ampicllin rash, pseudomembranous colitis
Clinical use of ticarcillin, carbenicillin, piperacillin?
Pseudomonas and Gram-neg rods (penicillinase sensitive; use with clavulanic acid)
Mechanism of cephalosporins?
beta-lactams, inhibit cell wall synthesis, less sensitive to penicillinase, bactericidal
Clinical use of 1st generation cephalosporins?
Gram-pos cocci (Proteus, E.coli, Klebsiella)
Names of 1st generation cephalosporins?
Cefazolin, cephalexin
Names of 2nd generation cephalosporins?
Cefoxitin, cefaclor, cefuroxime
Clinical use of 2nd generation cephalosporins?
Gram-pos cocci (Haemophilus, Enterobacter aerogenes, Neisseria, Proteus, E.coli, Klebsiella, Serratia)
Names of 3rd generation cephalosporins?
Ceftriaxone, cefotaxime, ceftazidime
Clinical use of 3rd generation cephalosporins?
Serious Gram-neg infections resistant to other beta-lactams- meningitis, Psuedomonas, gonorrhea
Name of 4th generation cephalosporin?
Cefepime
Clinical use of 4th generation cephalosporin?
Increased activity against Pseudomonas and Gram-pos organisms
Toxicity of cephalosporins?
Cross hypersenstivity with penicillins, increased nephrotoxicity of aminoglycosides, disulfiram-like reaction with EtOH
Mechanism of aztreonam?
Monobactam resistant to beta-lactamases; inhibits cell wall synthesis; synergistic with aminoglycosides
Clinical use of aztronam?
Gram-neg rods (Klebsiella, Pseudomonas, Serratia) For penicillin-allergic patients and those with renal insuff (can't use aminoglycosides)
Toxicity of aztreonam?
Occasional GI upset; well-tolerated
What drug is always co-administered with imipenem? Why?
Cilastatin- an inhibitor of renal dihydropeptidase I to reduce imipenem inactivation in renal tubules
Is imipenem beta-lactamase resistant?
Yes
Clinical use of imipenem and meropenem?
Gram-pos cocci, Gram-neg rods and anaerobes. Drug of choice for Enterobacter.
Toxicity of imipenem and meropenem?
GI distress, skin rash and CNS toxicity (seizures) at high plasma levels (less with meropenem)
Mechanism of vancomycin?
Inhibits cell wall mucopeptide formation by binding D-ala-D-ala portion of precursors. Bactericidal
Mechanism of resistance to vancomycin?
Amino acid change of D-ala-D-ala to D-ala-D-lac
Clinical use of vancomycin?
Serious Gram-pos multidrug-resistant organisms (S.aureus, C.diff)
Toxicity of vancomycin?
Nephrotoxicity, ototoxicity, thrombophlebitis, red man syndrome (pretreat with antihistamines)
Names of aminoglycosides?
Gentamicin, neomycin, amikacin, tobramycin, streptomycin
Mechanism of aminoglycosides?
Inhibit formation of initiation complex and cause misreading of mRNA. Bactericidal
Why are aminoglycosides ineffective against anaerobes?
Require oxygen for uptake
Clinical use of aminoglycosides?
Severe Gram-neg rod infections. Synergistic with beta-lactams
Toxicity of aminoglycosides?
Nephrotoxicity (esp if used with cephalosporins), ototoxicity (esp when used with loop diuretics), teratogenic
Names of tetracyclines?
Tetracycline, doxycycline, demclocycline, minocycline
Mechanism of tetracyclines?
Bind to 30S and prevent attachment of aminoacyl-tRNA
What inhibits tetracycline absorption in the gut?
Divalent cations (calcium, iron)
Use of demeclocylcine?
Diuretic in SIADH because ADH antagonist
Clnical use of tetracyclines?
Vibrio cholerae, acne, Chlamydia, Ureasplasma, Urealyticum, Mycoplasma, Tularemia, H.pylori, Borrelia, Rickettsia
Toxicity of tetracyclines?
GI distress, discoloration of teeth, inhibition of bone growth in kids, photosensitivity, teratogen
Names of macrolides?
Erythromycin, azithromycin, clarithromycin
Mechanism of macrolides?
Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic
Clinical use of macrolides?
URIs, pneumonias, STDs--Gram-pos cocci (strep), Mycoplasma, Legionella, Chlamydia, Neisseria
Toxicity of macrolides?
GI discomfort, acute cholestatic heptatitis, eosinophilia, skin rashes. Drug interations (increased plasma conc) with theophyllines, oral anticoags
Mechanism of chloramphenicol?
Inhibits 50S peptidyltransferase activity. Bacteriostatic
Clinical use of chloramphenicol?
Meningitis (H.influenze, N.meningitidis, S.pneumoniae)
Toxicity of chlormphenicol?
Anemia, aplastic anemia, gray baby syndrome
Mechanism of clindamycin?
Blocks peptide bond formation at 50S ribosomal subunit. Bacteriostatic
Clinical use of clindamycin?
Treat anaerobic infections (Bacteroides fragilis, C.perfringens)
Toxicity of clindamycin?
Pseudomembranous colitis, fever, diarrhea
Names of sulfonamides?
Sulfamethoxazole (SMX), sulfisoxazole, triple sulfas, sulfadiazine
Mechanism of sulfonamides?
PABA antimetabolites inhibit dihydropteroate synthetase. Bacteriostatic
Clnical use of sulfonamides?
Gram-pos, Gram-neg, Nocardia, Chlamydia, UTI
Toxicity of sulfonamides?
Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity, photosensitivity, kernicterus, displace other drugs from albumin
Mechanism of trimethoprim?
Inhibits bacterial dihydrofolate reductase. Bacteriostatic
Clinical use of trimethoprim?
Used in combo with SMX- causing sequential block of folate synthesis. Recurrent UTIs, Shigella, Salmonella, Penumocystis jiroveci
Toxicity of trimethoprim?
Megaloblastic anemia, leukopenia, granulocytopenia (supplement folic acid)
Which drugs should be avoided in pts with sulfa drug allergies?
Sulfonamides, sulfasalazine, sulfonylureas, thiazide diuretics, acetazolamide, furosemide
Which bugs do not gram stain well?
Treponema, Rickettsia, Mycobacteria, Mycoplasma, Legionella pneumophila, Chlamydia (pneumonic: These Rascals May Microscopically Lack Color)
Why doesn't Treponema gram stain well?
too thin to be visualized
Why doesn't Rickettsia gram stain well?
intracellular parasite
Why doesn't Mycobacteria gram stain well?
high-lipid-content cell wall requires acid-fast stain
Why doesn't Mycoplasma gram stain well?
no cell wall
Why doesn't Legionella pneumophila gram stain well?
primarily intracellular
Why doesn't Chlamydia gram stain well?
intracellular parasite; lacks muramic acid in cell wall
How can you visualize treponemes?
darkfield microscopy & fluorescent Ab staining
How can you visualize Mycobacteria?
acid fast
How can you visualize Legionella?
silver stain
Describe the phases of the bacterial growth curve?
lag phase, log phase, stationary phase, death phase (graph is shown on a log scale)
What is the lag phase?
period of little bacterial growth-- metabolic activity without division
What is the log phase?
linear bacterial growth on the log scale- rapid cell division
What is the stationary phase?
no growth- nutrient depletion slows growth, spore formation in some bacteria
What is the death phase?
linear decrease in number of bacterial cells on log scale- prolonged nutrient depletion and buildup of waste products lead to death
What is the source of exotoxins?
certain species of gram+ and gram- bacteria
What is the source of endotoxins?
outer cell membrane of most gram- bacteria and listeria
Are exotoxins secreted from the cell?
YES
Are endotoxins secreted from the cell?
NO
What is the chemistry of exotoxins?
polypeptide
What is the chemistry of endotoxins?
lipopolysaccharide
Where is the location of genes for an exotoxin?
plasmid or bacteriophage
Where is the location of genes for an endotoxin?
bacterial chromosome
What is the toxicity of an exotoxin?
high (fatal dose is about 1ug)
What is the toxicity of an endotoxin?
low (fatal dose is hundreds of micrograms)
What are the clinical effects from an exotoxin?
Various
What are the clinical effects from an endotoxin?
fever, Shock
What is the mode of action of an exotoxin?
various modes
What is the mode of action of an endotoxin?
includes TNF and IL-1
What is the antigenicity of an exotoxin?
induces high-titer antibodies called antitoxins
What is the antigenicity of an endotoxin?
poorly antigenic
What are vaccines to an exotoxin?
toxoids used as vaccines
What are vaccines to an endotoxin?
No toxoids formed and no vaccine available
What is the heat stability of an exotoxin?
destroyed rapidly at 60 deg Celsius (except Staphylococcal enterotoxin)
What is the heat stability of an endotoxin?
stable at 100 deg Celsius for 1 hr
What are typical diseases from an exotoxin?
Tetanus, botulism, diptheria
What are typical diseases from an endotoxin?
meningococcemia, sepsis by G- rods
What is the definition of bacterial virulence factors?
Promote evasion of host immune response
Describe the virulence of protein A? What bacteria is it part of?
Binds Fc region of Ig; S. aureus
Describe the virulence of IgA protease? What bacteria is it secreted by?
Enzyme that cleaves IgA; polysaccharide capsules also inhibit phagocytosis; secreted by S. pneumoniae, H. influenza, Neisseria
Describe the virulence of Group A streptococcal M protein?
helps prevent phagocytosis
Describe the action of superantigens?
bind directly to MHC II and T-cell receptor simultaneously, activating large numbers of T cells to stimulate release of IGN-gamma and IL-2
Describe the S. aureus superantigen. Is it an exotoxin or endotoxin?
TSST-1 superantigen causes toxic shock syndrome (fever, rash, shock). EXOTOXIN
What are the other S. aureus toxins?
enterotoxins that cause food poisoning, exfoliatin that causes staphylococcal scalded skin syndrome
Describe the S. pyogenes superantigen. Is it an exotoxin or endotoxin?
scarlet fever- erythrogenic toxin causes toxic shock-like syndrome. EXOTOXIN
What does an ADP ribosylating A-B toxin do?
interferes with host cell function. B (binding component) binds to receptor on surface of host cell, enabling endocytosis. A (active component) then attaches an ADP-ribosyl to a host cell protein (ADP-ribosylation), altering protein function.
Describe the cornebacterium diphtheriae ADP ribosylating A-B toxin. Is it an exotoxin or endotoxin?
inactivates elongation factor (EF-2)- similar to Psuedomonas exotoxin A; causes pharyngitis and pseudomembrane in throat; EXOTOXIN
Describe the Vibrio cholerae ADP ribosylating A-B toxin. Is it an exotoxin or endotoxin?
ADP ribosylation of G protein stimulates adenylyl cyclase; incresase pumping of Cl- into gut and decreased Na+ absorption. Water moves into gut lumen; causes voluminous rice-water diarrhea. EXOTOXIN
Describe the E. coli ADP ribosylating A-B toxin. Is it an exotoxin or endotoxin?
heat-labile toxin stimulates Adenylate cyclase. Heat-stable toxin stimulates Guanylate cyclase. Both cause watery diarrhea. Labile like the Air, stable like the Ground. EXOTOXIN
Describe the Bordetella pertussis ADP ribosylating A-B toxin. Is it an exotoxin or endotoxin?
Increases cAMP by inhibiting G-alpha-inhibitory; causes whooping cough; inhibits chemokine receptor causing lymphocytosis. EXOTOXIN
Describe the action of clostridium perfringens toxin? Is it an exotoxin or endotoxin?
alpha toxin causes gas gangrene; get double zone of hemolysis on blood agar. EXOTOXIN
Describe the action of C. tetani toxin? Is it an exotoxin or endotoxin?
blocks the release of inhibitory neurotransmitters GABA and glycine; causes lockjaw; SPASTIC paralysis; EXOTOXIN
Describe the action of C. botulinum toxin? Is it an exotoxin or endotoxin?
blocks the release of Ach; causes anticholinergic symptoms, CNS paralysis, especially cranial nerves; spores found in canned food, honey (causes floppy baby); FLACCID paralysis; EXOTOXIN
Describe the action of bacillus anthracis toxin? Is it an exotoxin or endotoxin?
1 toxin in the toxin complex is an adenylate cyclase; EXOTOXIN
Describe the action of Shigella toxin? Is it an exotoxin or endotoxin?
shiga toxin (also produced by E. Coli O157:H7) cleaves host cell rRNA; also enhances cytokine release, causing HUS. EXOTOXIN
Describe the action of S. pyogenes toxin? Is it an exotoxin or endotoxin?
Streptolysin O is a hemolysin; antigen for ASO Ab, which is used in the diagnosis of rheumatic fever. EXOTOXIN
What is the definition of an endotoxin?
A lipopolysaccharide found in the cell wall of G- bacteria (N-dotoxin is an integral part of gram-Negative cell wall.)
Endotoxin is heat___________ (labile/ stable?)
stable
What is an example of an endotoxin?
lipid A
What does an endotoxin do?
activates macrophages, activates complement (alternative pathway), activates Hageman factor
After an endotoxin activates macrophages, what important components are released?
IL-1, TNF, Nitric oxide
What does IF-1 cause?
fever
What does TNF cause?
Fever, hemorrhagic tissue necrosis
What does nitric oxide cause?
hypotension (shock)
After an endotoxin activates complement, what is released?
C3a, C5a
What does C3a cause?
hypotension, edema
What does C5a cause?
neutrophil chemotaxis
After an endotoxin activates Hageman factor, what occurs?
the coagulation cascade--> DIC
How do you differentiate Neisseria species?
on the basis of sugar fermentation
What do Neisseria meningococci ferment?
maltose and glucose (MeninGococci)
What do Neisseria gonococci ferment?
Glucose (Gonococci)
What color is the pigment produced by S. aureus?
yellow
What color is the pigment produced by Pseudomonas aeruginosa
blue-green
What color is the pigment produced by Serratia marcescens?
red
What gram (-) cocci is a Maltose and Glucose fermenter?
Neisseria meningitidis (MeninGococci)
What gram (-) cocci only ferments Glucose?
Neisseria gonorrhoeae (Gonococci)
What are 2 gram (-) coccoid rods?
Haemophilus influenzae and Bordetella pertussis
What 2 gram (-) rods are fast fermenters of lactose?
Klebsiella and Escherichia coli (Enterobacteriaceae)
What gram (-) rod is a lactose nonfermenter and oxidase (+)?
Pseudomonas
What 3 gram (-) rods are lactose nonfermenters and oxidase (-)?
Shigella, Salmonella, and Proteus (Enterobacteriaceae)
What Neisseria species has a polysaccharide capsule, ferments maltose, and has a vaccine?
N. meningitidis
What are 4 pathologies caused by N. gonorrhoeae (Gonococci)?
Gonorrhea, septic arthritis, neonatal conjunctivitis, and Pelvic Inflammatory Disease (PID)
What are 2 pathologies caused by N. meningitidis (Meningococci)?
Meningitis (meningococcemia) and Waterhouse-Friderichsen syndrome (hemorrhagic adrenalitis)
What gram (-) cocci ferment glucose and produce IgA proteases?
Neisseria (gonorrhoeae and meningitidis)
What 4 pathologies can HaEMOPhilus cause?
Epiglottitis, Meningitis, Otitis media, and Pneumonia
What factors do H. influenzae require when cultured on chocolate agar?
Factors V (NAD) and X (hematin)
What does the H. influenzae type B vaccine contain and is it given?
Type B capsular polysaccharide conjugated with diphtheria toxoid; between 2-18 months of age
Name 7 species of Enterobacteriaceae.
E. coli, Salmonella, Shigella, Klebsiella, Enterbacter, Serratia, and Proteus
What antigen is the endotoxin of Enterobacteriaceae?
Somatic (O) antigen
What antigen determines virulence of Enterobacteriaceae?
Capsular (K) antigen
What antigen is found in motile species of Enterobacteriaceae?
Flagellar (H) antigen
Name 4 characteristics of Enterobacteriaceae.
COFFEe: Capsular, O antigen, Flagellar antigen, Ferment glucose, Enterobacteriaceae
What causes pneumonia in alcoholics and diabetics with red currant jelly sputum?
Klebsiella
What are the 3 A's of Klebsiella?
Aspiration pneumonia, Abscess in lungs, Alcoholics
What agar is used to culture pink colonies of lactose-fermenting enteric bacteria?
MacConkey's agar (Lactose is KEE. MacConKEE's agar)
What non-lactose-fermenting Enterobacteriaceae invade intestinal mucosa and cause bloody diarrhea?
Salmonella and Shigella
How is Salmonella's motility different from Shigella's?
Salmonella: flagella; Shigella: actin polymerization
Which produces H2S, Salmonella or Shigella?
Salmonella
Which is more virulent, Salmonella or Shigella?
Shigella
What are 4 symptoms of Salmonella typhi (typhoid fever)?
Fever, diarrhea, headache, and rose spots on abdomen
How is Salmonella and Shigella transmitted?
Food, Fingers, Feces, Flies
Where are outbreaks of Yersinia enterocolitica common?
Day-care centers
How is Y. enterocolitica transmitted?
Pet feces, contaminated milk, and pork
What 2 pathologies can Y. enterocolitca mimic?
Crohn's disease or appendicitis
What gram (-) rod is urease (+) and creates an alkaline environment?
Helicobacter pylori (urease breath test)
What are 2 common pathologies caused by H. pylori?
Gastritis and 90% of duodenal ulcers
What 3 things is H. pylori a risk for?
Peptic ulcer, gastric adenocarcinoma, and lymphoma
Name a genus of obligate intracellular parasites that need CoA and NAD and have an arthropod vector.
Rickettsiae
What is the triad of symptoms for rickettsiae?
Headache, fever, and rash (vasculitis)
What rickettsia causes Q fever (pneumonia), is transmitted by aerosol, has no rash, and has no vector?
Coxiella burnetii
Compared to typhus, where do rickettsial rashes start?
Hands and feet (Rickettsia on the wRists, Typhus on the Trunk)
What pathology, caused by Rickettsia rickettsii, presents with rash on palms and soles, headache, and fever?
Rocky Mountain spotted fever (tick vector)
What 3 pathologies present with rash on palms and soles?
Rocky Mountain spotted fever, syphilis, and coxsackievirus A (hand, foot, and mouth disease)
What does R. typhi cause?
Endemic typhus (flea vector)
What does R. prowazekii cause?
Epidemic typhus (louse vector)
What is the vector for Ehrlichia?
Tick (Ehrlichiosis)
What does the Weil-Felix reaction assay for?
Antirickettsial antibodies (cross-react with Proteus antigen)
What rickettsial disease has a (-) Weil-Felix?
Q fever (Coxiella)
What can be seen on Giemsa or fluorescent antibody-stained smear for Chlamydiae?
Cytoplasmic inclusions
What 4 things can C. trachomatis cause?
Reactive arthritis, conjunctivitis, urethritis, and PID
What can C. pneumoniae and C. psittaci cause?
Atypical pneumonia
What is unusual about the Chlamydial cell wall?
Lacks muramic acid
What form of Chlamydia Enters cell via endocytosis?
Elementary body
What form of Chlamydia Replicates in cells?
Reticulate body
What does C. trachomatis serotypes A, B, and C cause?
ABC: Africa/Blindness/Chronic infection
What does C. trachomatis serotypes L1, 2, and 3 cause?
L1-3: Lymphogranuloma venereum
What does C. trachomatis serotypes D-K cause?
Urethritis/PID, ectopic pregnancy, neonatal pneumonia or conjunctivitis
What are 3 spirochetes?
BLT: Borrelia (B is Big), Leptospira, and Treponema
Which spirochete is the only one that can be visualized by dyes in light microscopy?
Borrelia
Which spirochete is visualized with dark-field microscopy?
Treponema
How are spirochetes mobile?
Axial filaments
What question mark-shaped spirochete can cause Weil's disease (icterohemorrhagic leptospirosis)?
Leptospira interrogans (Weil's: jaundice, azotemia, fever, hemorrhage, and anemia)
What can Borrelia burgdorferi cause and via what vector?
Lyme disease (Ixodes tick)
What 2 symptoms are found during Stage 1 of Lyme disease?
Erythema chronicum migrans (bull's eye rash) and flu-like symptoms
What 2 manifestations are found during Stage 2 of Lyme disease?
Neurologic and cardiac manifestations
What 2 symptoms are found during Stage 3 of Lyme disease?
Chronic monoarthritis and migratory polyarthritis
What does Treponema pallidum cause?
Syphilis
What does T. pertenue cause?
Yaws (tropical infection with + VDRL test)
What is characteristic of primary syphilis?
Painless chancre (localized)
What is characteristic of secondary syphilis?
Maculopapular rash on palms and soles and condylomata lata (Secondary=Systemic)
What is characteristic of tertiary syphilis?
Gummas, aortitis, neurosyhphilis (tabes dorsalis), and Argyll Robertson pupil
What 4 things are characteristic to congenital syphilis?
Saber shins, saddle nose, CN VIII deafness, and Hutchinson's teeth
What is characteristic of an Argyll Robertson pupil?
Prostitute's pupil: accomodates but does not react to light (tertiary syphilis)
What is the FTA-ABS test specific for?
Treponemes; FTA-ABS: Find the Ab-ABSolutely; most specific, earliest (+), long (+) duration
Interpret +VDRL and +FTA.
Active Treponema infection
Interpret +VDRL and -FTA.
Probably false positive Treponema infection
Interpret -VDRL and +FTA.
Successfully treated Treponema infection
What does VDRL detect?
Nonspecific Ab reacts with beef cardiolipin (Dx: syphilis, Viruses [mononucleosis and hepatitis), Drugs, Rheumatic fever, SLE, and Leprosy)
zidovudine (AZT)
thymidine nucleoside analog phosphorylated by cellular kinases to tri-P active form (host thymidine kineses are S-phase specific inhibiting RT; also acts as DNA chain terminator (b/c N3 group on 3'OH)
lamivudine (3TC) See above
nucleoside analog inhibitor of RT, phosphorylated by cell enzymes to active Rx
tenofovir
like AZT inhibits RT by competing w/dATP for incorporation into DNA, causing chain termination; unlike AZT it is a nucleotide prodrug (adenosine monophosphate analog that is hydrolyzed to tenofovir phosphonate, which is further phosphorylated by cellular enzymes be active at inhibiting RT
Emtricitabine
Fluorinated analog of 3TC that inhibits RT by competing for dCTP incorporation into DNA; chain termination
efavirenz
non-nucleoside/non-competitive inhibitor or RT that does not require phosphorylation for activity
lopinavir
prevents viral protease from cleaving gag-pol polypeptide into separate functional proteins; fits into protease active site and acts as a competitive inhibitor; results in non-infectious viral particles
ritonavir
Used to boost levels of ther Protease Inhibitors
enfuvirtide
inhibits the fusion of viral (HIV-1) and cellular (CD4+) membrances to block initial entry; binds gp41 subunit of HIV glycoprotein
Maraviroc
Chemokine co-receptor (CRR5) antagonist to block entry of HIV into cells
Raltegravir
Inhibitis HIV-1 integrase, prevents integration into the genome
Mechanism of Interferon
Block stages of viral RNA and DNA synthesis, induce ribonuclease
Alcoholic vomits gastric contents and has foul-smelling sputum. Organism? Etiology? Treatment?
Anaerobes (aspiration pneumonia). Rx: Ceftriaxone + azithromycin/moxifloxacin.
Middle-aged male presents with acute onset monoarticular joint pain and bilateral Bell's palsy. Disease? Transmission? Organism? Rx?
Lyme disease. Ixodes (tick)--> Borrelia burgdorferi (spirochete). Rx: doxycycline
Patient's UA shows WBC casts. Disease/problem? Organism? Rx?
Pyelonephritis. Org: E. coli (most common), Enterococcus, Staph, Proteus. Rx: TMP/SMX (Quinolone if Enterococcus).
Patient presents with 'rose gardener's' scenario (thorn prick with large ulcers along lymphatic drainage). Organism?
Sporothrix schenckii (rare fungus. House episode: guy gives his wife roses because he cheated and got critically ill.)
Med student has a burning feeling in his gut after meals. Gastric mucosa biopsy=G- rods. Diagnosis (test?)? Tx? Pathogenicity factors (of organism)?
H. pylori (peptic ulcer disease, stomach CA (risk)). Urea breath test. Pathogen: cagA (type 4 secr syst->makes IL-8), NAP (activates neutrophils), VacA (vacuolizing toxin). Pathogenicity=inflammation!
32-y/o M has 'cauliflower' skin lesions. Biopsy=broad-based budding yeast. Organism? Rx?
Blastomyces. Rx=Itraconazole
Breast-feeding F suddenly develops redness & swelling of right breast. PE=fluctuating mass. Diagnosis?
Mastitis caused by S. aureus.
20-y/o college student presents w/ lymphadenopathy, fever & hepatosplenomegaly. His serum agglutinates sheep RBCs. What cell is infected? Etiology?
B cells (infectious mononucleosis; EBV ('owl eye inclusions').
3 hrs after eating custard at a picnic, a whole family began vomiting (awesome)! 10 hrs later they were better. Organism? Pathophysiology?
S. aureus (preformed enterotoxin (superantigen) caused vomiting w/in hours…heat stable)
Infant becomes flaccid after eating honey. Organism? Mechanism? Compare to a related (same genus) spp.?
Clostridium botulinium (Clostridia=G+ anaerobes, 'drumstick-shaped' (spores)). Mech: inhibits vSNAREs->ACh release into post-synaptic cleft blocked). C. tetani-->inhib GABA release at inh interneurons in CNS (retroaxonal transport). Tetanus=immunization (Px) / TT IgG (acute, sx). Botox=anti-toxin.
Male presents with squamous cell carcinoma on his penis. Etiology? Tx?
HPV. No treatment (for HPV). Immunizaiton for women.
Patient develops endocarditis 3 wks after receiving a prosthetic heart valve. Organism (be specific down to species)? Tx?
S. epidermidis. Rx: Vancomycin (or resistance analysis d/t MDR).
55-y/o smoker & heavy drinker presents with a (new) cough and flu-like sx. Gram stain=no organisms. Silver stain=G- rods. Diagnosis? Tx?
Legionella pneumophila (pleomorph, b-lactamase(+), prevent vacuole<->lysosome fusion, sources: pools, water towers). Rx=Rifampin + erythromycin.
After taking clindamycin, patient develops toxic megacolon and diarrhea. Organism? Tx?
Clostridium difficile (Enterocolitis). Rx=metronidazole or vancomycin. 'Q: How do you get off the C. diff train? A: take the metro or a van.'
25-y/o presents with 3 days fever, chills & a painful, swollen knee. Diagnosis? Tx?
Septic arthritis (key: unilat/asymmetrical; many etiologies, common=N. gonorrheae). Rx=ceftriaxone (if etio uncertain), Pen G if certain N. gonorrheae.
19-y/o F college student presents with vaginal pruritis and a thick, curdy discharge. Etiology? Tx?
Candida albicans. Clotrimazole (topical or oral, but oral C/I with alcohol consumption (consideration)).
30-y/o F returns from a camping trip and complains of watery diarrhea and cramps. Organism? Tx?
Giardia lamblia (Traveler's diarrhea; 2nd most common (parasitic) cause of diarrhea (#1=cryprosporidium)). Rx: Metronidazole (adults), Nitazoxanide (peds), Paromomycin (pregnant F). Pathophys: d/t hosts own immune rxn. Immunity: IgA (in endemic areas-contam water).
Bacterial peptidoglycan: composition and function? What class of antibiotics targets this structure?
Carb backbone (N-Ag~N-Am) + x-linked peptide side chains (thin in G-/thick in G+); support, resists osmotic pressure. Beta-Lactams target the x-link D-Ala-D-Ala (last 2 of pentapeptide).
Bacterial cell wall: composition, function & clinical significance?
Supported by peptidoglycan (inner), techoic acid induces IL-1/TNF-a (Fxn: surface antigen). Only G+.
Bacterial outer membrane (& periplasm): composition, function & significance?
Lipid A induces IL-1/TNF-a (Antigen=polysaccharide). Fxn: site of LPS/endotoxin (surface Ag)=only G-. Periplasm=only in G- (space btw. outer & inner membrane).
Bacterial plasma membrane: composition & function?
Lipoprotein bilayer. Site of oxidative & transport enzymes.
Bacterial ribosomes: structure & function, clinical significance, examples?
50S + 30S = 70S (protein synthesis from mRNA). Different from eukaryotic ribosomes=Rx target (Aminoglycosides, tetracyclines, tigecycline, chloramphenicol, macrolides, clindamycin & linezolid).
Bacterial capsule: structure, function, clinical significance & examples?
Polysaccharide (except: B. anthracis D-Glutamate=glycoprotein); protects against phagocytosis=immune evasion/chronic infections. Examples: S. pneumoniae, H. influenzae (b), Klebsiella pneumoniae, P. aeruginosa, N. meningitidis, Cryptococcus neoformans ('Some killers have pretty neat capsules'). Hib and Strep vaccines are directed at capsule.
Bacterial pilus/fimbriae: structure/function?
Glycoprotein (mostly CHO); adherence, sex pilus forms during conjugation.
Bacterial flagellum: structure/function?
Protein/motility (Notably: H. pylori).
Bacterial spore: structure, function, clinical significance?
Keratin-like coating--resistance to env't stressors. B. anthracis, Clostridium spp.
Bacterial plasmids: structure, function, clinical significance?
DNA (circular)-contains variety of genes for antibiotic resistance (beta-lactamase), enzymes and toxins (shigella toxin).
Bacterial glycocalyx: structure, function, clinical significance?
Polysaccharide-mediates adherence to surfaces (esp. foreign). Catheters, medical implants (P. aeruginosa, S. epidermidis).
Bacteria with unusual structures: Mycoplasma vs. Mycobacteria
Mycoplasma: sterols (no cell wall)-->'walking pneumonia'. Mycobacteria: mycolic acid (high lipid content)--> TB, leprosy, MAC complex (AIDS).
Common structures to G+ and G- (name 5). 1 unique structure of each (G+, G-)?
Common: flagellum, pilus, capsule, peptidoglycan (G+ >> G-), cytoplasmic membrane. G- only: LPS/endotoxin, outer membrane. G+: cell wall (techoic acid).