Micro, USMLE Part 2 Flashcards
Levels as HIV infxn progresses: CD4+ lymphocytes? Anti-p24 Abs? Anti-gp120 Abs? Virus, p24 Ag?
CD4+ T-cells have an early dip, stabilize, and fall during stages 3-4 (years after infxn) Anti-p24 and Anti-gp120 Abs rise starting ~1 mo. post-infxn, stabilize @ 3 mos (at end of acute infxn). Virus, p24 Ag: spike early (w/ start of acute Sx’s), drop to low level until stages 3-4 (years later), when they take off
Organ system affected in AIDS: Brain (what is the infxn/dz associated?)
Infxn/dz associated w/ AIDS: Crytococcal meningitis Toxoplasmosis CMV encephalopathy AIDS dementia PML (JC virus)
Organ system affected in AIDS: Eyes (what is the infxn/dz associated?)
Infxn/dz associated w/ AIDS: CMV retinitis
Organ system affected in AIDS: Mouth and throat (what is the infxn/dz associated?)
Infxn/dz associated w/ AIDS: Thrush (Candida albicans) HSV CMV Oral hairy leukoplakia (EBV)
Organ system affected in AIDS: Lungs (what is the infxn/dz associated?)
Infxn/dz associated w/ AIDS: Pneumocystis jiroveci pneumonia (PJP) TB histoplasmosis
Organ system affected in AIDS: GI (what is the infxn/dz associated?)
Infxn/dz associated w/ AIDS: Cryptosporidiosis Mycobacterium avium-intracellulare complex CMV colitis Non-Hodgkin’s lymphoma (EBV) Isopora belli
Organ system affected in AIDS: Skin (what is the infxn/dz associated?)
Infxn/dz associated w/ AIDS: Shingles (VZV) Kaposi’s sarcoma (HHV-8)
Organ system affected in AIDS: Genitals (what is the infxn/dz associated?)
Infxn/dz associated w/ AIDS: Genital herpes warts cervical cancer (HPV)
HIV-assicated infxns that increase in risk at CD4+ count:
Infxn: Oral thrush Tinea pedis (athlete’s foot) Reactivation VZV Reactivation tuberculosis Other bacterial infxns (e.g., H. influenzae, S. pneumoniae, Salmonella)
HIV-assicated infxns that increase in risk at CD4+ count:
Infxn: Reactivation HSV cryptosporidosis Isopora Disseminated coccidioidomycosis Pneumocystis pneumonia
HIV-assicated infxns that increase in risk at CD4+ count:
Infxn: Candidal esophagitis Toxoplamosis histoplasmosis
HIV-assicated infxns that increase in risk at CD4+ count:
Infxn: CMV retinitis and esophagitis Disseminated M. avium-intracellulare Cryptococcal meningitis
Neoplasms associated w/ HIV
Kaposi’s sarcoma (HHV-8) Invasive cervical carcinoma (HPV) Primary CNS lymphoma non-Hodgkin’s lymphoma
HIV encephalitis
Occurs late in the course of HIV infxn. Virus gains CNS access via infected Macrophages. Microglial nodules w/ multinucleated giant cells.
Prions What are they? What dz’s do they cause? Normal vs. pathologic prions?
Infectious agents that do not contain RNA or DNA (consist only of proteins); encoded by cellular genes. Dz’s: Creutzfeldt-Jakob dz (CJD – rapidly progressive dementia), kuru, srapie (sheep), mad cow dz Associated w/ spongiform encephalopathy . Normal prions have alpha-helix conformation; pathologic prions (like CJD) are beta-pleated sheets. Pathologic conformation accumulates b/c it is resistant to proteinase digestion.
Dominant normal flora of the: Skin
Staphylococcus epidermis
Dominant normal flora of the: Nose
S. epidermis; colonized by S. aureus
Dominant normal flora of the: Oropharynx
Viridans group streptococci
Dominant normal flora of the: Dental plaque
Streptococcus mutans
Dominant normal flora of the: Colon
Bacteroides fragilis > E. coli
Dominant normal flora of the: Vagina
Lactobacillus, colonized by E. coli and GBS
Neonates and normal flora
Neonates delivered by cesarean section havve no flora, but are rapidly colonized after birth.
Food poisoning from: Vibrio parahemolyticus and V. vulnificus
Food: Contaminated seafood (V. vulnificus can also cause wound infxn from contact w/ contaminated water or shellfish)
Food poisoning from: Bacillus cereus
Food: reheated rice. (Food poisoning from reheated rice? Be Serious! [B. cereus])
Food poisoning from: S. aureus
Food: Meats, mayonnaise, custard (pre-formed toxin)
Food poisoning from: Clostridium perfringens
Food: reheated meat dishes
Food poisoning from: Clostridium botulinum
Food: improperly canned foods (bulging cans)
Food poisoning from: E. coli O157:H7
Food: Undercooked meat
Food poisoning from: Salmonella
Food: poultry, meat, and eggs.
What are two bacteria that cause a food poisoning that starts quickly and ends quickly?
S. aureus and B. cereus
Bugs that cause diarrhea: Campylobacter Type of diarrhea? Findings?
Bloody diarrhea. Comma- or S-shaped organisms; growth at 42C; Oxidase (+) [bugs that cause diarrhea: type of diarrhea and findings]
Bloody diarrhea. Comma- or S-shaped organisms; growth at 42C; Oxidase (+) [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Campylobacter
Bugs that cause diarrhea: Salmonella Type of diarrhea? Findings?
bloody diarrhea. Lactose (-); Flagellar motility [bugs that cause diarrhea: type of diarrhea and findings]
bloody diarrhea. Lactose (-); Flagellar motility [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Salmonella
Bugs that cause diarrhea: Shigella Type of diarrhea? Findings?
Bloody diarrhea Lactose (-) Very low ID50 Produces Shiga toxin [bugs that cause diarrhea: type of diarrhea and findings]
Bloody diarrhea Lactose (-) Very low ID50 Produces Shiga toxin [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Shigella
Bugs that cause diarrhea: Enterohemorrhagic E. coli (EHEC) Type of diarrhea? Findings?
Bloody diarrhea O157:H7 Can cause HUS Makes Shiga-like toxin [bugs that cause diarrhea: type of diarrhea and findings]
Bloody diarrhea O157:H7 Can cause HUS Makes Shiga-like toxin [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Enterohemorrhagic E. coli (EHEC)
Bugs that cause diarrhea: Enteroinvasive E. coli (EIEC) Type of diarrhea? Findings?
Bloody diarrhea. Invades colonic mucosa. [bugs that cause diarrhea: type of diarrhea and findings]
Bloody diarrhea. Invades colonic mucosa. [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Enteroinvasive E. coli (EIEC)
Bugs that cause diarrhea: Yersinia enterocolitica Type of diarrhea? Findings?
Bloody diarrhea Day-care outbreaks Pseudoappendicitis [bugs that cause diarrhea: type of diarrhea and findings]
Bloody diarrhea Day-care outbreaks Pseudoappendicitis [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Yersinia enterocolitica
Bugs that cause diarrhea: C. difficile Type of diarrhea? Findings?
Can cause both watery and bloody diarrhea. Pseudomembranous colitis. [bugs that cause diarrhea: type of diarrhea and findings]
Can cause both watery and bloody diarrhea. Pseudomembranous colitis. [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: C. difficile
Bugs that cause diarrhea: Entamoeba histolytica Type of diarrhea? Findings?
Bloody diarrhea. Protozoan. [bugs that cause diarrhea: type of diarrhea and findings]
Bloody diarrhea. Protozoan. [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Entamoeba histolytica
Bugs that cause diarrhea: Enterotoxigenic E. coli (ETEC) Type of diarrhea? Findings?
Watery diarrhea. Traveler’s diarrhea Produces ST and LT toxins [bugs that cause diarrhea: type of diarrhea and findings]
Watery diarrhea. Traveler’s diarrhea Produces ST and LT toxins [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Enterotoxigenic E. coli (ETEC)
Bugs that cause diarrhea: Vibrio cholerae Type of diarrhea? Findings?
Watery diarrhea. Comma-shaped organisms Rice-water diarrhea. [bugs that cause diarrhea: type of diarrhea and findings]
Watery diarrhea. Comma-shaped organisms Rice-water diarrhea. [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Vibrio cholerae
Bugs that cause diarrhea: C. perfringens Type of diarrhea? Findings?
Watery diarrhea. Also causes gas gangrene. [bugs that cause diarrhea: type of diarrhea and findings]
Watery diarrhea. Also causes gas gangrene. [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: C. perfringens
Bugs that cause diarrhea: Protozoa Type of diarrhea? Findings?
Watery diarrhea Giardia, Cryptosporidium (in immunocompromised) [bugs that cause diarrhea: type of diarrhea and findings]
Watery diarrhea Giardia, Cryptosporidium (in immunocompromised) [bugs that cause diarrhea: type of diarrhea and findings]
Bugs that cause diarrhea: Protozoa
Bugs that cause diarrhea: Viruses Type of diarrhea? Findings?
Watery diarrhea. Rotavirus, adenovirus, Norwalk virus (norovirus). [bugs that cause diarrhea: type of diarrhea and findings]
Common causes of pneumonia in neonates (
Group B streptococci E. coli
Common causes of pneumonia in children (4wks - 18yrs)
Viruses (R SV) M ycoplasma C hlamydia pneumoniae S treptococcus pneumoniae (R unts M ay C ough S putum)
Common causes of pneumonia in adults (18-40yrs)
Mycoplasma Chlamydia pneumoniae Streptococcus pneumoniae
Common causes of pneumonia in Adults (40-65yrs)
Streptococcus pneumoniae H. influenzae Anaerobes Viruses Mycoplasma
Common causes of pneumonia in the elderly (>65)
Streptococcus pneumoniae Viruses Anaerobes H. influenzae Gram (-) rods
Common causes of nosocomial (hospital-acquired) pneumonia
Staphylococcus Enteric Gram (-) rods
Common causes of pneumonia in the immunocompromised
Staphylococcus Enteric Gram (-) rods Fungi Viruses Pneumocystis jiroveci (w/ HIV)
Common cause of pneumonia w/ aspiration
Anaerobes
Common cause of pneumonia in alcoholics/IV drug users
Streptococcus pneumoniae Klebsiella Staphylococcus
Common causes of pneumonia in CF
Pseudomonas
Common causes of post-viral pneumonia
Staphylococcus H. influenzae
Common causes of atypical pneumonia
Mycoplasma Legionella Chlamydia
Common causes of meningitis in newborn (0-6 months
Group B streptococci E. coli Listeria
Common causes of meningitis in children (6mos - 6yrs)
Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae type B Enteroviruses
Common causes of meningitis (6-60yrs)
N. miningitidis Enteroviruses S. pneumoniae HSV
Common causes of meningitis in 60+ year-olds
Streptococcus pneumoniae Gram (-) rods Listeria
Viral causes of meningitis
Enteroviruses (esp. coxsackievirus) HSV HIV West Nile virus VZV
Common causes of meningitis in HIV
Cryptococcus CMV Toxoplasmosis (brain abscess) JC virus (PML)
Incidence of H. influenzae meningitis?
Has decreased greatly w/ introduction of H. influenzae vaccine in last 10-15 years.
CSF findings in meningitis: Bacterial [Pressure? Cell type? Protein? Sugars?]
Increased pressure Increased PMNs Increased protein Decreased sugar
Increased pressure Increased PMNs Increased protein Decreased sugar [CSF findings in meningitis – what is the bug?]
Bacterial
CSF findings in meningitis: Fungal/TB [Pressure? Cell type? Protein? Sugars?]
Increased pressure Increased lymphocytes Increased proein Decreased sugar
Increased pressure Increased lymphocytes Increased proein Decreased sugar [CSF findings in meningitis – what is the bug?]
Fungal/TB
CSF findings in meningitis: Viral [Pressure? Cell type? Protein? Sugars?]
Normal/increased pressure Increased lymphocytes Normal/increased protein Normal sugar
Normal/increased pressure Increased lymphocytes Normal/increased protein Normal sugar [CSF findings in meningitis – what is the bug?]
Viral
Osteomyelitis in most ppl is due to…? Who gets most osteomyelitis?
Staph aureus in most ppl. Most osteomyelitis occurs in children.
Elevated CRP and ESR in osteomyelitis?
Classic findings, but nonspecific
Osteomyelitis in sexually active pt
Neisseria gonorrhoeae (rare) Septic arthritis more common
Osteomyelitis in diabetics and drug addicts
Pseudomonas aeruginosa
Osteomyelitis in Sickle cell
Salmonella
Osteomyelitis in prosthetic replacement
S. aureus and S. epidermis
Osteomyelitis in vertebra
Mycobacterium tuberculosis (Pott’s dz)
Osteomyelitis with cat and dog bites/scratches
Pasteurella multocida
3 Most common causes of ambulatory UTI
1.) E. coli (50-80%) 2.) Staphylococcus saprophyticus (10-30%): 2nd most common cause of UTI in young, sexually active, ambulatory women 3.) Klebsiella (8-10%)
Common causes of UTI in a hospital setting
E. coli Proteus Klebsiella Serratia Pseudomonas
Gender and epidemiology of UTIs
10:1 women to men (b/c of short urethra colonized by fecal flora)
Predisposing factors to UTIs
Flow obstruction Kidney surgery Catheterization Gynecologic abnormalities Diabetes Pregnancy
Mechanisms of UTI infxn
Mostly caused by ascending infxns. In males: babies w/ congenital defects, elderly w/ enlarged prostates
Sx of UTI
Dysuria Frequency Urgency Suprapubic pain
Sx of Pyelonephritis
Fever Chills Flank pain CVA tenderness (costovertebral angle – tender above kidneys on back)
UTI bugs: Serratia maracescens Features?
Some strains produce a red pigment; often nosocomial and drug-resistant.
Features: Some strains produce a red pigment; often nosocomial and drug-resistant. Which UTI bug is this?
Serratia maracescens
UTI bugs: Staphylococcus saprophyticus Features?
2nd leading cause of community-acquired UTI in sexually active women.
Features: 2nd leading cause of community-acquired UTI in sexually active women. Which UTI bug is this?
Staphylococcus saprophyticus
UTI bugs: Escherichia coli Features?
Leading cause of UTI. Colonies show metallic sheen on EMB agar.
Features: Leading cause of UTI. Colonies show metallic sheen on EMB agar. Which UTI bug is this?
Escherichia coli
UTI bugs: Enterobacter cloacae Features?
Often nosocomial and drug resistant.
Features: Often nosocomial and drug resistant. Which UTI bug is this?
Enterobacter cloacae
UTI bugs: Klebsiella pneumoniae Features?
Large mucoid capsule and viscous colonies
Features: Large mucoid capsule and viscous colonies Which UTI bug is this?
Klebsiella pneumoniae
UTI bugs: Proteus mirabilis Features?
Motility cuases swarming on agar. Produces urease; associated w/ struvite stones.
Features: Motility cuases swarming on agar. Produces urease; associated w/ struvite stones. Which UTI bug is this?
Proteus mirabilis
UTI bugs: Pseudomonas aeruginosa Features?
Blue-green pigment and fuity odor. Usually nosocomial and drug-resistant.
Features: Blue-green pigment and fuity odor. Usually nosocomial and drug-resistant. Which UTI bug is this?
Pseudomonas aeruginosa
List of UTI bugs
SSEEK PP S erratia marcescens S taphylococcus saprophyticus E scherichia coli E nterobacter cloacae K lebsiella pneumoniae P roteus mirabilis P seudomonas aeruginosa
Diagnostic markers of UTI
Leukocyte esterase: (+) = bacterial Nitrite test: (+) = Gram(-) organism
ToRCHeS infxns What are they? List?
These important infxns are transmitted in utero or during vaginal birth: T oxoplasma gondii o R ubella C MV H IV H SV-2 e S yphilis
Other important congenital infxns that do not fit into ToRCHeS
Listeria E. coli Group B streptococci All can be acquired placentally or from birth canal.
ToRCHeS infxns, organism: Toxoplasma gondii Major clinical manifestations?
Classic triad of chorionitis, intracranial calcifications, and hydrocephalus. May be asymptomatic at birth.
Major clinical manifestations: Classic triad of chorionitis, intracranial calcifications, and hydrocephalus. May be asymptomatic at birth. Which ToRCHeS organism is this?
Toxoplasma gondii
ToRCHeS infxns, organism: Rubella Major clinical manifestations?
Deafness Cataracts Heart defects (PDA, pulmonary artery stenosis) Microcephaly Mental retardation Blueberry muffin baby due to rash
Major clinical manifestations: Deafness Cataracts Heart defects (PDA, pulmonary artery stenosis) Microcephaly Mental retardation Blueberry muffin baby due to rash Which ToRCHeS organism is this?
Rubella
ToRCHeS infxns, organism: CMV Major clinical manifestations?
Petechial rash Intracranial calcifications Mental retardation Hepatosplenomegaly Microcephaly Jaundice 90% are asymptomatic at birth.
Major clinical manifestations: Petechial rash Intracranial calcifications Mental retardation Hepatosplenomegaly Microcephaly Jaundice 90% are asymptomatic at birth. Which ToRCHeS organism is this?
CMV
ToRCHeS infxns, organism: HIV Major clinical manifestations?
Hepatosplenomegaly Neurologic abnormalities Frequent infxns
Major clinical manifestations: Hepatosplenomegaly Neurologic abnormalities Frequent infxns Which ToRCHeS organism is this?
HIV
ToRCHeS infxns, organism: HSV-2 Major clinical manifestations?
Encephalitis Conjuntivitis Vesicular skin lesions Often asymptomatic at birth Most infxns are transmitted during birth thru an infected maternal genital tract.
Major clinical manifestations: Encephalitis Conjuntivitis Vesicular skin lesions Often asymptomatic at birth Most infxns are transmitted during birth thru an infected maternal genital tract. Which ToRCHeS organism is this?
HSV-2
ToRCHeS infxns, organism: Syphilis Major clinical manifestations?
Cutaneous lesions Hepatosplenomegaly Jaundice Saddle nose Saber shins Hutchinson teeth CN VIII deafness Rhinitis (snuffles)
Major clinical manifestations: Cutaneous lesions Hepatosplenomegaly Jaundice Saddle nose Saber shins Hutchinson teeth CN VIII deafness Rhinitis (snuffles) Which ToRCHeS organism is this?
Syphilis
Red rashes of childhood
Measles Rubella HHV-6 (roseola) Scarlet fever (group A streptococcus) Parvovirus B19 (slapped cheek rash)
STD’s: Gonorrhea Organism? Clinical features?
Neisseria gonorrhoeae Urethritis, cervicitis, PID, prostatitis, epididymitis, arthritis, creamy purulent discharge
Neisseria gonorrhoeae Urethritis, cervicitis, PID, prostatitis, epididymitis, arthritis, creamy purulent discharge Disease?
Gonorrhea
STD’s: Primary syphilis Organism? Clinical features?
Treponema pallidum Painless chancre
Treponema pallidum Painless chancre Disease?
Primary syphilis
STD’s: Secondary syphilis Organism? Clinical features?
Treponema pallidum Fever, lymphadenopathy, skin rashes, condylomata lata
Treponema pallidum Fever, lymphadenopathy, skin rashes, condylomata lata Disease?
Secondary syphilis
STD’s: Tertiary syphilis Organism? Clinical features?
Treponema pallidum Gummas (a non-cancerous growth, a form of granuloma) Tabes dorsalis General paresis Aortitis Argyll Robertson pupil
Treponema pallidum Gummas (a non-cancerous growth, a form of granuloma) Tabes dorsalis General paresis Aortitis Argyll Robertson pupil Disease?
Tertiary syphilis
STD’s: Genital herpes Organism? Clinical features?
HSV-2 Painful penile, vulvar, or cervical ulcers; can cause systemic Sx such as: fever, HA, myalgia
HSV-2 Painful penile, vulvar, or cervical ulcers; can cause systemic Sx such as: fever, HA, myalgia Disease?
Genital herpes
STD’s: Chlamydia Organism? Clinical features?
Chlamydia trachomatis (D-K) Urethritis, cervicitis, conjunctivitis, Reiter’s syndrome, PID
Chlamydia trachomatis (D-K) Urethritis, cervicitis, conjunctivitis, Reiter’s syndrome, PID Disease?
Chlamydia
STD’s: Lymphogranuloma venereum Organism? Clinical features?
Chlamydia trachomatis (L1-L3) Ulcers, lymphadenopathy, rectal strictures.
Chlamydia trachomatis (L1-L3) Ulcers, lymphadenopathy, rectal strictures. Disease?
Lymphogranuloma venereum
STD’s: Trichomoniasis Organism? Clinical features?
Trichomonas vaginalis Vaginitis Strawberry-colored mucosa
Trichomonas vaginalis Vaginitis Strawberry-colored mucosa Disease?
Trichomoniasis
STD’s: AIDS Organism? Clinical features?
HIV Opportunistic infxns, Kaposi’s sarcoma, lymphoma
HIV Opportunistic infxns, Kaposi’s sarcoma, lymphoma Disease?
AIDS
STD’s: Condylomata accumulata Organism? Clinical features?
HPV 6 and 11 Genital warts, koilocytes
HPV 6 and 11 Genital warts, koilocytes Disease?
Condylomata accumulata
STD’s: Hepatitis B Organism? Clinical features?
HBV Jaundice
HBV Jaundice Disease?
Hepatitis B
STD’s: Chancroid Organism? Clinical features?
Haemophilus ducreyi (it’s so painful, you do cry ) Painful genital ulcer, inguinal adenopathy.
Haemophilus ducreyi (it’s so painful, you do cry ) Painful genital ulcer, inguinal adenopathy. Disease?
Chancroid
STD’s: Bacterial vaginosis Organism? Clinical features?
Garnderella vaginalis Noninflammatory, malodorous discharge (fishy smell) Positive whiff test Clue cells
Garnderella vaginalis Noninflammatory, malodorous discharge (fishy smell) Positive whiff test Clue cells Disease?
Bacterial vaginosis
Top bugs that cause Pelvic inflammatory dz
Chlamydia trachomatis (subacute, often undiagnosed) Neisseria gonorrhoeae (acute, high fever) Chlamydia trachomatis (the most common STD in the USA: 3-4milliion cases/year)
Signs and Sx’s of Pelvic inflammatory dz
Cervical motion tenderness (chandelier sign) Purulent cervical discharge. May include: Salpingitis, endometritis, hydrosalpinx, and tubo-ovarian abscess.
Pelvic inflammatory dz can lead to… ?
Fitz-Hugh-Curtis Syndrome: infxn of the liver capsule and violin string adhesions of parietal peritoneum to liver.
What is salpingitis a risk factor for?
Ectopic pregnancy Infertility Chronic pelvic pain Adhesions
Other STD’s that cause PID
Garnderella (clue cells) Trichomonas (corkscrew motility on wet prep)
Nosocomial pathogen: CMV, RSV Risk factor?
Newborn nursery
Risk factor for a nosocomial pathogen: Newborn nursery
What is the pathogen? CMV, RSV
Nosocomial pathogen: E. coli, Proteus mirabilis Risk factor?
Urinary catheterization
Risk factor for a nosocomial pathogen: Urinary catheterization What is the pathogen?
E. coli, Proteus mirabilis
Nosocomial pathogen: Pseudomonas aeurginosa Risk factor?
Respiratory therapy equipment
Risk factor for a nosocomial pathogen: Respiratory therapy equipment What is the pathogen?
Pseudomonas aeurginosa
Nosocomial pathogen: HBV Risk factor?
Work in renal dialysis unit
Risk factor for a nosocomial pathogen: Work in renal dialysis unit What is the pathogen?
HBV
Nosocomial pathogen: Candida albicans Risk factor?
Hyperalimentation
Risk factor for a nosocomial pathogen: Hyperalimentation What is the pathogen?
Candida albicans
Nosocomial pathogen: Legionella Risk factor?
Water aerosols
Risk factor for a nosocomial pathogen: Water aerosols What is the pathogen?
Legionella
The 2 most common causes of nosocomial infxns?
E. coli (UTI) S. aureus (wound infxn)
Presume Pseudomonas aeruginosa as the cause of a nosocomial infxn when…?
Presume Pseudomonas AIR uginosa when AIR or burns are involved.
When do you suspect Legionella as a cause of nosocomial infxn?
Suspect Legionella when a water source is involved.
Bug hints (if all else fails):Pus, empyema (collection of pus in pre-existing anatomical cavity), abscess What is the bug?
S. aureus
Bug hints (if all else fails):Pediatric infxn What is the bug?
haemophilus influenzae (including epiglottitis)
Bug hints (if all else fails):Pneumonia in CF, burn infxn What is the bug?
Pseudomonas aeruginosa
Bug hints (if all else fails):Branching rods in oral infxn What is the bug?
Actinomyces israellii
Bug hints (if all else fails):Traumatic open wound What is the bug?
Clostridium perfringens
Bug hints (if all else fails):Surgical wound What is the bug?
S. aureus
Bug hints (if all else fails):Dog or cat bite What is the bug?
Pasteurella multocida
Bug hints (if all else fails):Currant jelly sputum What is the bug?
Klebsiella
Bug hints (if all else fails):Sepsis/meningitis in newborn What is the bug?
group B strep
Antimicrobials by mechanism of action: Block cell wall synthesis by inhibition of peptidoglycan cross-linking
Drugs? Penicillin, ampicillin, ticarcillin, piperacillin, imipenem, aztreonam, cephalosporins [#1 below]
Antimicrobials by mechanism of action: Block peptidoglycan synthesis Drugs?
Bacitracin, Vancomycin [#2 below]
Antimicrobials by mechanism of action: Disrupt bacterial cell wall membranes Drugs?
Polymyxins [#3 below]
Antimicrobials by mechanism of action: Block nucleotide synthesis Drugs?
Sulfonamides, Trimethoprim [#4 below]
Antimicrobials by mechanism of action: Block DNA topoisomerases Drugs?
Quinolones [#5 below]
Antimicrobials by mechanism of action: Block mRNA synthesis Drugs?
Rifampin [#6 below]
Antimicrobials by mechanism of action: Block protein synthesis at 50S ribosomal subunit Drugs?
Chloramphenicol, macrolides, clindamycin, streptogramins (quinipristin, dalfopristin), linezolid [#7]
Antimicrobials by mechanism of action: Block protein synthesis at the 30S ribosomal subunit Drugs?
Aminoglycosides, tetracyclines [#8 below]
Bacterostatic antibiotics
E rythromycin C lindamycin S ulfamethoxazole T rimethoprim T etracylcines C hloramphenicol (We’re ECST aT iC about bacteriostatics )
Bacteriocidal antibiotics
V ancomycin F luoroquinolones P enicillin A minoglycosides C ephalosporins M etronidazole V ery F inely P roficient A t C ell M urder
Forms of Penicillin
Penicillin G (IV form), Penicillin V (oral form). Prototype Beta-lactam antibiotics.
Mechanism of penicillin
1.) Bind penicillin-binding proteins 2.) Block transpeptidase cross-linking of cell wall 3.) Activate autolytic enzymes
Mechanism of penicillinase-resistant penicillins: Methicillin, nafcillin, dicoxacillin
Same as penicillin*. Narrow speectrum; penicillinase resistant b/c of bulkier R group. * mechanism of PCN: 1.) Bind penicillin-binding proteins 2.) Block transpeptidase cross-linking of cell wall 3.) Activate autolytic enzymes
Mechanism of aminopenicillins: Ampicillin, amoxicillin
Same as penicillin*. Wider spectrum; Penicillinase sensitive. Also combine w/ clavulanic acid (a penicillinase inhibitor) to enhance spectrum. AmO xicillin has greater O ral bioavailability than ampicillin. *Mechanism of PCN: 1.) Bind penicillin-binding proteins 2.) Block transpeptidase cross-linking of cell wall 3.) Activate autolytic enzymes
Mechanism of antipseudomonals: Ticarcillin, carbenicillin, piperacillin
Same as penicillin*. Extended spectrum. *Mechanism of penicillin: 1.) Bind penicillin-binding proteins 2.) Block transpeptidase cross-linking of cell wall 3.) Activate autolytic enzymes
Clinical use of penicillin
Bactericidal for Gram(+) cocci, Gram(+) rods, Gram(-) cocci, and spirochetes. Not penicillinase resistant.
Toxicity of penicillin
Hypersensitivity rxtns. Methicillin: interstitial nephritis.
Clinical use of aminopenicillins (ampicillin, amoxicillin)
Extended spectrum penicillin*: certain gram(+) bacteria and gram(-) rods: H aemophilus influenzae, E . coli, L isteria monocytogenes, P roteus mirabilis, S almonella, enterococci (Ampicillin/amoxicillin HELPS kill enterococci) *Think of amp icillin/amoxicillin as AMP ed up penicillin
Toxicity of aminopenicillins (ampicillin, amoxicillin)
Hypersensitivity rxtns; Ampicillin rash; Pseudomembranous colitis.
Clinical use of: Ticarcillin, carbenicillin, piperacillin
(antipseudomonals – TCP : T ake C are of P seudomonas) Used for Pseudomonas spp. and gram(-) rods; susceptible to penicillinase; Use w/ clavulinic acid (Beta-lactamase inhibitor).
Toxicity of antipseudomonals (Ticarcillin, carbenicillin, piperacillin)
Hypersensitivity rxtns.
Mechanism of cephalosporins
Beta-lactam drugs that inhibit cell wall synthesis, but are less susceptible to penicillinases. Bactericidal.
Clinical use of 1st generation cephalosporins (Cefazolin, cephalexin)
Gram(+) cocci, P roteus mirabilis, E . c oli, K lebsiella pneumoniae (1st gen = PEcK )
Clinical use of 2nd generation cephalosporins (cefoxitin, cefaclor, cefuroxime)
Gram(+) cocci, H aemophilus influenzae, E nterobacter aerogenes, N eisseria spp. P roteus mirabilis, E. c oli, K lebsiella pneumoniae, S erratia marcescens (2nd Gen = HEN PEcKS )
Clinical use of 3rd generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime)
Serious gram(-) infxns resistant to other beta-lactams; meningitis (most penetrate the BBB). Examples: Ceftazidime for Pseudomonas Ceftriaxone for gonorrhea
Clinical use of 4th generation cephalosporins (Cefepime)
Increased activity against Pseudomonas and gram(+) organisms.
Toxicity of cephalosporins
Hypersensitivity rxtn. Cross-hypersensitivvity w/ penicillins occurs in 5-10% of pts. Increased nephrotoxicity of aminoglycosides; disulfiram-like rxtn w/ ethanol (in cephalosporins w/ methylthitetrazole group, e.g., cefamandole)
Mechanism of aztreonam
A monobactam resistant to beta-lactamases. Inhibits cell wall synthesis (binds to PBP3). Synergistic w/ aminoglycosides. No cross-allergenicity w/ penicillins.
Clinical use of aztreonam
Gram(-) rods - Klebsiella spp., Pseudomonas spp., Serratia spp. No activity against gram(+)’s or anaerobes. For penicillin-allergic pts and those w/ renal insufficiency who cannot tolerate aminoglycosides.
Toxcity of Aztreonam
Usually nontoxic; occasional GI upset. No cross-sensitivity w/ penicillins or cephalosporins.
Mechanism of Imipenem/cilastatin, meropenem
Imipenem is a broad-spectrum, beta-lactamase-resistant carbapenem. Always administer w/ cilastatin (inhibitor of renal dihydropeptidase I) to decrease inactivation in renal tubules. (With imipenem, the kill is LASTIN’ with ciLASTATIN )
Clinical use of imipenem/cilastatin, meropenem
Gram(+) cocci, gram(-) rods, and anaerobes. DOC for Enterobacter. The significant side effects limit use to life-threatening infxns, or after other drugs have failed. Meropenem, howevver, has a reduced risk of seizures and is stable to dihydropeptidase I.
Toxicity of Imipenem/cilastatin, meropenem
GI distress, skin rash, and CNS toxicity (seizures) @ high plasma levels
Mechanism of vancomycin
Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal. Resistance occurs w/ AA change of D-ala D-ala to D-ala D-lac
Clinical use of vancomycin
Used for serious, gram(+) multidrug-resistant organisms, including S. aureus and Clostridium difficile (pseudomembranous colitis)
Toxicity of vancomycin
N ephrotoxicity, O totoxicity, T hromophlebitis, diffuse flushing - red man syndrome (can largely prevent by pretreatment w/ antihistamines and slow infusion rate) Well toleraterd in general – does NOT have many problems.
Protein synthesis inhibitors: 30S inhibitors
A = A minoglycosides (streptomycin, gentamycin, tobramycin, amikacin) [bacteriostatic] T = T etracyclines [bacteriostatic] (But AT 30 , CCELL (sell) at 50) [*note different specific sites of action of Aminoglycosides and TCNs below]
Protein Synthesis Inhibitors: 50S inhibitors
C = C hloramphenicol, C lindamycin [bacteriostatic] E = E rythromycin [bacteriostatic] L = L incomycin [bacteriostatic] L = L inezolid [variable] (But AT 30, CCELL (sell) at 50 ) [note different specific sites of action below]
Aminoglycosides (list)
G entamycin N eomycin A mikacin T obramycin S treptomycin (Mean GNATS [mean = amin oglycosides)
Mechanism of aminoglycosides (gentamycin, neomycin, amikacin, tobramycin, streptomycin)
Bactericidal; inhibit formation of initiation complex and cause misreading of mRNA. Require O2 for uptake; therefore ineffective against anaerobes. (Mean GNATS canNOT kill anaerobes)
Clinical use of aminogyclosides (gentamycin, neomycin, amikacin, tobramycin, streptomycin)
Severe gram (-) rod infxns. Synergistic w/ beta-lactam ABX. Neomycin for bowel surgery.
Toxicity of aminoglycosides (gentamycin, neomycin, amikacin, tobramycin, streptomycin)
N ephrotoxicity (especially when used w/ cephalosporins) O totoxicity (especially when used w/ loop diuretics) T eratogen. (Mean GNATS canNOT kill anaerobes)
Tetracyclines (list)
Tetracylcine Doxycycline Demeclocycline Minocycline
Mechanism of tetracyclines (tetracycline, doxycycline, demeclocyclline, minocycline)
Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA. Limited CNS penetration. Doxycyline is fecally eliminated and can be used in pts w/ renal failure. Must NOT take w/ milk, antacids, or iron-containing preparations b/c divalent cations inhibit absorption in gut. D emeclocycline is an ADH antagonist (acts as a D iuretic in SIADH)
Clinical use of tetracyclines (tetracycline, doxycycline, demeclocyclline, minocycline)
V ibrio cholerae A cne C hlamydia U reaplasma U realyticum M ycoplasma pneumoniae T ularemia H . pylori B orrelia burgdorferi (Lyme dz) R ickettsia (VACUUM TH e B edR oom)
Toxicity of tetracyclines (tetracycline, doxycycline, demeclocyclline, minocycline)
GI distress Discoloration of teeth and inhibition of bone growth in children Photosensitivity Contraindicated in pregnancy.
Macrolides (list)
Erythromycin, azithromycin, clarithromycin
Mechanism of macrolides (Erythromycin, azithromycin, clarithromycin)
Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.
Clinical use of macrolides (Erythromycin, azithromycin, clarithromycin)
URIs, pneumonias STDs – gram(+) cocci (streptococcal infxns in pts allergic to penicillin) Mycoplasma Legionella Chlamydia Neisseria
Toxicity of macrolides (Erythromycin, azithromycin, clarithromycin)
GI discomfort (most common cause of noncompliance) Acute cholestatic hepatitis Eosinophilia Skin rashes Increases serum concentration of theophyllines, oral anticoagulants.
Mechanism of chloramphenicol
Inhibits 50S peptidyltransferase activity. Bacteriostatic.
Clinical use of chloramphenicol
Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) Conservative use, owing to toxicities.
Toxicity of chloramphenicol
Anemia (dose dependent) Aplastic anemia (dose independent) Gray baby syndrome (in premature infants b/c they lack liver UDP-glucuronyl transferase)
Mechanism of clindamycin
Blocks peptide bond formation at 50S ribosomal subunit. Bacteriostatic.
Clinical use of clindamycin
Tx anaerobic infxns (e.g., Bacteroides fragilis, Clostridium perfringens) (Treats anaerobes above the diaphragm)
Toxicity of clindamycin
Pseudomembranous colitis (C. difficile overgrowth) Fever Diarrhea
Sulfonamides (list)
Sulfamethoxazole (SMX) Sulfisoxazole Sulfadiazine
Mechanism of sulfonamides (sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine)
PABA antimetabolites inhibit dihydropteroate synthetase [see below]. Bacteriostatic.
Clinical use of of sulfonamides (sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine)
Gram(+), gram(-), Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.
Toxicity of sulfonamides (sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine)
Hypersensitivity rxtns Hemolysis if G6PD deficient Nephrotoxicity (tubulointerstitial nephritis) Photosensitivity Kernicterus in infants Displace other drugs from albumin (e.g., warfarin)
Mechanism of trimethoprim (TMP)
Inhibits bacterial dihydrofolate reductase. Bacteriostatic.
Clinical use of trimethoprim (TMP)
Used in combination w/ sulfonamides (trimethoprim-sulfamethoxazole [TMP-SMX]), causing sequential block of folate synthesis. Combination used for recurrent UTIs, Shigella, Salmonella, Pneumocystis jiroveci pneumonia.
Toxicity of trimethoprim (TMP)
Megaloblastic anemia Leukopenia Granulocytopenia (may alleviate w/ supplemental folinic acid) (Trimethoprim = TMP : T reats M arrow P oorly)
Sulfa drug allergies – what do you need to avoid?
Pts who do not tolerate sulfa drugs should not be given sulfonamides or other sulf drugs such as: Sulfasalazine Sulfonylureas Thiazide diuretics Acetazolamide Furosemide
Fluoroquinolones (list)
Ciprofloxacin Norfloxacin Ofloxacin Sparfloxacin Moxifloxacin Gatifloxacin Enoxacin [above are fluoroquinolones] Nalidixic acid [a quinolone]
Mechanism of fluoroquinolones
Inhibit DNA gyrase (topoisomerase II). Bactericidal. Must not be taken w/ antacids.
Clinical use of fluoroquinolones
Gram(-) rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram(+) organisms
Toxicity of fluoroquinolones
GI upset, superinfections, skin rashes, HA, dizziness. Contraindicated in pregnant women and in children b/c animal studies show damage to cartilage. Tendonitis and tendon rupture in adults; leg cramps and myalgias in kids. (FlouroquinoLONES hur the attachments to your BONES )
Mechanism of metronidazole
Forms toxic metabolites in the bacterial cell that damage DNA. Bactericidal, antiprotozoal.
Clinical use of metronidazole
Treats: G iardia E ntamoeba T richomonas G ardnerella vaginalis A naerobes (Bacteroides, Clostridium) Used w/ bismuth and amoxicillin (or TCN) for triple therapy against H. P ylori (GET GAP on the METRO !) Treats anaerobic infxns below the diaphragm.
Toxicity of metronidazole
Disulfiram-like rxtn w/ alcohol Headache Metallic taste
Polymyxins (list)
Polymyxin B Polymyxin E
Mechanism of polymyxins
Bind to cell membranes of baccteria and disrupt their osmotic properties. Polymyxins are cationic, basic proteins that act like detergents. (MYXins MIX up membranes)
Clinical use of polymyxins
resistant gram(-) infxns
Toxicity of polymyxins
Neurotoxicity, acute renal tubular necrosis
Antimycobacterial drugs: for M. tuberculosis
Prophylaxis: Isoniazid Tx: R ifampin I soniazid P yrazinamide E thambutol (RIPE for treatment)
Antimycobacterial drugs: for M. avium-intracellulare
Prophylaxis: Azithromycin Tx: Azithromycin Rifampin Ethambutol Streptomycin
Antimycobacterial drugs for M. leprae
Tx: Dapsone Rifampin Clofazimine
Anti-TB drugs
S treptomycin, P yrazinamide, I soniazid (INH ), R ifampin, E thambutol (INH-SPIRE [inspire]) Cycloserine (2nd-line therapy)
Side effects of anti-TB drugs
Important SE of ethambutol: optic neuropathy (red-green color blindness) For other drugs: hepatotoxicity.
Mechanism of isoniazid (INH)
Decreases synthesis of mycolic acids. *note that there are different INH half-lives in fast vs. slow acetylators.
Clinical use of isoniazid (INH)
Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB.
Toxicity of isoniazid (INH)
Neurotoxicity, hepatotoxicity. Pyridoxine (Vitamin B6) can prevent neurotoxicity. (INH I njures N eurons and H epatocytes)
Mechanism of rifampin
Inhibits DNA-dependent RNA polymerase
Clinical use of rifampin
Mycobacterium tuberculosis. Delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children w/ Haemophilus influenzae type B.
Toxicity of rifampin
Minor hepatotoxicity and drug interactions (induces P-450) Orange body fluids (nonhazardous side effect)
Rifampin’s 4 R’s
R NA polymerase inhibitor R evs up microsomal P-450 R ed/orange body fluids R apid resistance if used alone
Most common resistance mechanism for: Penicillins/cephalosporins
Beta-lactamase cleavage of beta-lactam ring, or altered PBP in cases of MRSA or penicillin-resistant S. pneumoniae.
The following is the most common mechanism of resistance for what drug? Beta-lactamase cleavage of beta-lactam ring, or altered PBP in cases of MRSA or penicillin-resistant S. pneumoniae.
Penicillins/cephalosporins
Most common resistance mechanism for: Aminoglycosides
Modification via acetylation, adenylation, or phosphorylation.
The following is the most common mechanism of resistance for what drug? Modification via acetylation, adenylation, or phosphorylation.
Aminoglycosides
Most common resistance mechanism for: Vancomycin
Terminal D-ala of cell wall component replaced with D-lac, decreased affinity.
The following is the most common mechanism of resistance for what drug? Terminal D-ala of cell wall component replaced with D-lac, decreased affinity.
Vancomycin
Most common resistance mechanism for: Chloramphenicol
Modification via acetylation
The following is the most common mechanism of resistance for what drug? Modification via acetylation
Chloramphenicol
Most common resistance mechanism for: Macrolides
methylation of rRNA near erythromycin’s ribosome-binding site
The following is the most common mechanism of resistance for what drug? methylation of rRNA near erythromycin’s ribosome-binding site
Macrolides
Most common resistance mechanism for: Tetracycline
Decreased uptake or increased transport out of cell.
The following is the most common mechanism of resistance for what drug? Decreased uptake or increased transport out of cell.
Tetracycline
Most common resistance mechanism for: Sulfonamides
Altered enzyme (bacterial dihydropteroate synthetase), decreased uptake, or increased PABA synthesis.
The following is the most common mechanism of resistance for what drug? Altered enzyme (bacterial dihydropteroate synthetase), decreased uptake, or increased PABA synthesis.
Sulfonamides
Most common resistance mechanism for: Quinolones
Altered gyrase or reduced uptake.
The following is the most common mechanism of resistance for what drug? Altered gyrase or reduced uptake.
Quinolones
Nonsurgical antimicrobial prophylaxis of: meningococcal infxn
Rifampin (DOC), minocycline
Nonsurgical antimicrobial prophylaxis of: gonorrhea
Ceftriaxone
Nonsurgical antimicrobial prophylaxis of: syphilis
Benzathine penicillin G
Nonsurgical antimicrobial prophylaxis of: Hx of recurrent UTIs
TMP-SMX
Nonsurgical antimicrobial prophylaxis of: Pneumocystis jiroveci pneumonia
TMP-SMX (DOC), aerosolized pentamidine.
Nonsurgical antimicrobial prophylaxis of: endocarditis w/ surgical or dental procedures
Penicillins.
Tx of highly resistant bacteria
MRSA: vancomycin
Mechanism of Amphotericin B
Binds ergosterol (unique to fungi); Forms membrane pores that allow leakage of electrolytes. (Amphotear acin ‘tears’ holes in fungal membranes by forming pores) [on left, below]
Clinical use of Amphotericin B
Use for wide spectrum of systemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross BBB.
Toxicity of Amphotericin B
Fever/chills (shake and bake), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (amphotericin = amphoterrible). Hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity.
Mechanism of Nystatin
Binds to ergosterol, disrupting fungal membranes. Too toxic for systemic use. [on left w/ amphotericin, below]
Clinical use of nystatin
Swish and swallow for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis.
Azoles (list)
Fluconazole
Mechanism of azoles
Inhibit fungal sterol (ergosterol) synthesis [below, top/middle]
Clinical use of azoles
Systemic mycoses. Fluconazole for cyptococcal meningitis in AIDS pts (b/c it can cross the BBB) and candidal infxns of all types (i.e., yeast infxns). Ketoconazole for Balstomyces, Coccidioides, Histoplasma, Candida albicans, hypercortisolism. Clotrimazole and miconazole for topical fungal infxns.
Toxicity of azoles
Hormone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), fever, chills
Flucytosine mechanism
Inhibits DNA synthesis by conversion to 5-fluorouracil [below, middle]
Clinical use of flucytosine
Used in systemic fungal infxns (e.g., Candida, Cryptococcus) in combination w/ amphotericin B
Toxicity of flucytosine
Nausea, vomiting, diarrhea, bone marrow suppression
Mechanism of Caspofungin
Inhibits cell wall synthesis by inhibiting synthesis of beta-glucan. [not included in image of anti-fungal mechanisms]
Clinical use of caspofungin
Invasive aspergillosis
Toxicity of caspofungin
GI upset, flushing.
Mechanism of terbinafine
Inhibits the fungal enzyme squalene epoxidase. [below, top/right]
Clinical use of terbinafine
Used to Tx dermatophytoses (especially onychomycosis)
Mechanism of griseofulvin
Interferes w/ microtubule fxn; disrupts mitosis. Deposits keratin-containing tissues (e.g., nails). [below, bottom/right]
Clinical use of griseofulvin
Oral Tx of superficial infxns; inhibits growth of dermatophytes (tinea, ringworm)
Toxicity of griseofulvin
Teratogenic, ccarcinogenic, confusion, HA, induces P-450 (increasing warfarin metabolism).
Mechanism of amantadine
Blocks viral penetration/uncoating (M2 protein); may buffer pH of endosome. (A man to dine [amantadine] takes of his coat .) Also causes the release of dopamine from intact nerve terminals. [below, top/right]
Clinical use of amantadine
Prophylaxis and Tx for influenza A; Parkinson’s Dz. (A mantadine blocks influenza A and rubellA , and causes problems w/ the cerebellA )
Toxicity of amantadine
Ataxia, dizziness, slurred speech. (A mantadine blocks influenza A and rubellA , and causes problems w/ the cerebellA ) Rimantidine is a derivative w/ fewer CNS side effects (does not cross BBB)
Mechanism of resistance to amantadine
Mutated M2 protein. 90% of all influenza A strains are resistant to amantadine, so not used.
Mechanism of: Zanamivir, oseltamivir
Inhibit influenza neuraminidase, decreasing the release of progeny virus. [below, bottom/left: Neuraminidase inhibitors]
Clinical use of Zanamivir, oseltamivir
Both influenza A and B
Mechanism of ribavirin
Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase. [not included in figure, but acts at point of NA synthesis, bottom/right]
Clinical use of ribavirin
RSV Chronic hepatitis C
Toxicity of ribavirin
Hemolytic anemia. Severe teratogen.
Mechanism of acyclovir
Monophosphorylated by HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination. [fits w/ NA analogs below, bottom/right]
Clnicial use of acyclovir
HSV, VZV, EBV. Used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis. Prophylaxis in immunocompromised pts. For herpes zoster, use a related agent (famciclovir). No effect on latent forms of HSV and VZV.
Toxicity of acyclovir
Generally well-tolerated.
Mechanism of resistance to acyclovir
Lack of thymidine kinase
Mechanism of ganciclovir
5’-monophosphate formed by a CMV viral kinase or HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase. [fits in w/ NA analogs below, bottom/right]
Clinical use of ganciclovir
CMV, especially in immunocompromised pts
Toxicity of ganciclovir
Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir.
Mechanism of resistance to ganciclovir
Mutated CMV DNA polymerase or lack of viral kinse.
Mechanism of foscarnet
Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Does not require activation by viral kinase. (FOS carnet = pyroFOS phate analog) [would fit into DNA synthesis on bottom/right]
Clinical use of foscarnet
CMV retinitis in immunocompromised pts when ganciclovir fails; acyclovir-resistant HSV.
Toxicity of foscarnet
Nephrotoxicity.
Mechanism of resistance to foscarnet
Mutated DNA polymerase.
HIV therapy: Protease inhibitors (list)
Saquinavir Ritonavir Indinavir Nelfinavir Amprenavir [all protease inhibitors end in -avir ] (NAVIR (never) TEASE a proTEASE )
HIV therapy: Mechanism of protease inhibitors
Inhibit maturation of new virus by blocking protease in progeny of virus.
HIV therapy: Toxicity of protease inhibitors
GI intolerance (nausea, diarrhea) Hyperglycemia Lipodystrophy Thrombocytopenia (indinavir)
HIV therapy: Reverse transcriptase inhibitors –> nucleosides (list)
Zidovudine (ZDV, formerly AZT) Didanosine (ddI) Zalcitabine (ddC) Stavudine (d4T) Lamivudine (3TC) Abacavir (Have you dined (vudine ) with my nuclear (nucleosides ) family?)
HIV therapy: Reverse transcriptase inhibitors –> non-nucleosides (list)
N evirapine, E favirenz, D elaviridine (N ever E ver D eliver nucleosides.)
HIV therapy: Mechanism of reverse transcriptase inhibitors
Preferentially inhibit reverse transcriptase of HIV; prevent incorporation of DNA copy of viral genome into host DNA. [below, bottom/right]
HIV therapy: Toxicity of reverse transcriptase inhibitors
Bone marrow suppression* (neutropenia, anemia) Peripheral neuropathy Lactic acidosis (nucleosides) Rash (non-nucleosides) Megaloblastic anemia (ZDV) *GM-CSF and erythropoietin can be used to reduce BM suppression.
HIV therapy: Clinical use of reverse transcriptase inhibitors
Highly active antiretroviral therapy (HAART) generally entails combination Tx w/ protease inhibitors and reverse transcriptase inhibitors. Initiated when pts have low CD4 counts (
HIV therapy: Fusion inhibitor (there’s one – what is it?)
Enfuvirtide
HIV therapy: Mechanism of fusion inhibitors (enfuvirtide)
Bind viral gp41 subunit; inhibit conformational change required for fusion w/ CD4 cells. Therefore block entry and susequent replication.
HIV therapy: Toxicity of fusion inhibitors (enfuvirtide)
Hypersensitivity rxtns Rxtns at subcutaneous injection site Increased risk of bacterial pneumonia
HIV therapy: Clinical use of fusion inhibitors (enfuvirtide)
In pts w/ persistent viral replication in spite of antiretroviral Tx. Used in combination w/ other drugs.
Mechanism of interferons (as antimicrobials)
Glycoproteins from human leukocytes that block various stages of viral RNA and DNA synthesis. Induce ribonuclease that degrades viral mRNA.
Clinical use of interferons
IFN-alpha: chronic hepatitis B and C, Kaposi’s sarcoma IFN-beta: MS IFN-gamma: NADPH oxidase deficiency
Toxicity of interferons
Neutropenia
Antibiotics to avoid in pregnancy (list – what are they, and why for each one?)
S ulfonamides – kernicterus
