What is a live-attenuated vaccine?

Answer: Attenuated vaccine has microbe with selective deletions of genes involved in pathogenesis. Organisms replicate in the host, greatly increasing antigenic stimulation.

Methemoglobinemia occurs when the ferrous (Fe2+) form of iron in hemoglobin is oxidized to the ferric (Fe3+) form and cannot bind O2. What are the clinical manifestations of methemoglobinemia?

Answer: Dyspnea, headaches, dizziness, altered mental status with cyanosis of extremities, and darkened blood. Treat with methylene blue.

Which antibiotic is a PABA analog with a side effect profile that includes hemolysis and methemoglobinemia?

Answer: Dapsone

Name the three drugs commonly used in the treatment of leprosy:

1. Dapsone

2. Rifampin

3. Clofazimine

What are important side effects of INH?

Answer: Hepatotoxicity (avoid alcohol), peripheral neuropathy (vitamin B6 depletion), sideroblastic anemia (vitamin B6 depletion)

What is the mechanism of action for INH?

Answer: Although not proven, it is thought to inhibit mycolic acid synthesis

What are some common side effects of rifampin?

Answer: Red-orange urine, induces P450 potentially leading to impaired efficacy of other drugs, GI symptoms, headache, fever, rash

Why shouldn't rifampin be used as monotherapy?

Answer: Resistance occurs rapidly when used as monotherapy. It can be used alone briefly for N. meningitidis or H. influenzae prophylaxis.

What are common indications for rifampin?

Answer: Treatment of M. tuberculosis and prophylaxis for N. meningitidis or H. influenzae

What is the mechanism of action of rifampin?

Answer: Inhibits DNA-dependent RNA poly-merase by binding to RNA polymerase and blocking elongation of RNA

What is the mechanism of action of ethambutol and what is its unique side effect?

Answer: Inhibits arabinosyl transferase, an enzyme necessary to make the mycobac-terial cell wall. Also causes decreased visual acuity and color vision

Which drugs are commonly used to treat Mycobacterium tuberculosis infection?

Answer: Ethambutol, rifampin, isoniazid (INH), and pyrazinamide

What is the drug of choice for treating simple recurrent UTIs?

Answer: Trimethoprim-sulfamethoxazole (TMP-SMX). Give ciprofloxacin if patient has sulfa allergy.

What are important side effects of trimethoprim?

Answer: Adverse effects include megaloblastic anemia, leukopenia, and granulocytope-nia. Alleviate these symptoms with supplemental folinic acid.

What is the mechanism of action of trimethoprim?

Answer: Inhibits bacterial dihydrofolate reductase

What are some other side effects of sulfonamides?

Answer: Induce hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient patients, photosensitivity, and hypersensitivities

What is the main risk of giving sulfonamides during pregnancy?

Answer: Sulfonamides can displace bilirubin from plasma albumin-binding sites and induce kernicterus in the newborn.

Can bacteria obtain folic acid by diffusion or active transport?

Answer: No, bacteria must synthesize folic acid from PABA.

Which enzyme in bacterial folate synthesis is inhibited by sulfonamides?

Answer: Dihydropteroate synthetase

Name two antibiotics that inhibit bacterial growth by acting as p-aminobenzoic acid (PABA) analogs:

1. Sulfonamides

2. Dapsone

Why are fluoroquinolones contraindicated in pregnant women and in children?

Answer: Interfere with cartilage formation. In elderly, associated with Achilles tendonitis/tendon rupture

How does resistance to fluoroquinolones develop?

Answer: Resistance develops by point mutations of the DNA gyrase enzyme.

What are common indications for fluoroquinolones?

Answer: Urinary tract infections (UTIs), sexually transmitted diseases (STDs) (Chlamydia and N. gonorrhoeae), diarrhea (enterotoxigenic E. coli[ETEC], Shigella, Salmonella, and Campylobacter), and pneumonia (Mycoplasma, Legionella)

What is the mechanism of action of fluoroquinolones (ciprofloxacin, norfloxacin)?

Answer: Inhibit DNA gyrase (topoisomerase II), leading to inhibition of DNA replication and breakdown of DNA. They are bactericidal.

Which new class of antibiotics that inhibit protein synthesis can also treat VRSA and VRE?

Answer: Streptogramin class; quinupristin and dalfopristin (Synercid) combination inhibits 50S and 70S ribosomes.

What important infections does linezolid treat?

Answer: Vancomycin-resistant S. aureus (VRSA), methicillin-resistant S. aureus (MRSA), and vancomycin-resistant enterococci (VRE)

What is the mechanism of action for linezolid?

Answer: Inhibits the formation of the initiation complex in bacterial translation

What is the major side effect of clindamycin?

Answer: Pseudomembranous colitis due to over-growth of Clostridium difficile. Remember, clindamycin isn't the most common cause of pseudomembranous colitis because it's not used as much as cephalosporins or ampicillin.

What is the mechanism of action of clindamycin?

Answer: Blocks peptide bond formation at the 50S ribosomal subunit. It is bacteriostatic.

How do bacteria usually become resistant to macrolides?

Answer: Methyltransferases that alter the drug-binding site on the 50S ribosome and increase active transport of the drug out of the cell

Why are macrolides used for the treatment of community-acquired pneumonia?

Answer: They are effective in treating

M. pneumoniae, Chlamydia pneumoniae, S. pneumoniae, and Legionella pneumophilia; so they effectively cover the most common causes of community-acquired pneumonia.

What is the mechanism of action of macrolide (erythromycin, azithromycin, clarithromycin) antibiotics?

Answer: They bind to the 50S ribosomal subunit and prevent the translocation step in protein synthesis.

Mnemonic:

Macrolide stops the slide

What are the two distinct side effects of chloramphenicol on bone marrow?

1. Dose-dependent bone marrow suppression

2. Dose-independent aplastic anemia

It also causes gray baby syndrome in neonates because they lack uridine diphosphate (UDP)-glucuronyl transferase.

What is the mechanism of action of chloramphenicol? For which conditions is it used?

Answer: It prevents peptide bond formation by binding the 50S subunit of rRNA. It is used for bacterial meningitis in penicillin-allergic patients and serious Salmonella infections in some parts of the world.

How do bacteria usually become resistant to tetracyclines?

Answer: Increased ability to pump tetracycline out of cell (efflux pumps)

What is the risk from taking expired tetracyclines?

Answer: May cause a Fanconi-like syndrome (proximal renal tubular dysfunction)

Do tetracyclines work synergistically with penicillins

Answer: Unlike aminoglycosides, tetracyclines theoretically decrease the effect of penicillins.

Why should tetracyclines be taken on an empty stomach?

Answer: They can be chelated and inactivated by calcium, magnesium, aluminum, iron, and other multivalent cations.

What is unique about doxycycline in comparison with other tetracyclines in regard to the means of elimination?

Answer: Doxycycline is eliminated in the feces (70%-80%) and is not dependent on either the liver or kidneys. It is safe for a patient with liver and kidney dysfunction and dose adjustments are not necessary.

Which tetracycline can be used in the treatment of SIADH (syndrome of inappropriate antidiuretic hormone)? Why?

Answer: Demeclocycline causes nephrogenic diabetes insipidus by blocking antidiuretic hormone (ADH) receptor in the renal collecting ducts.

Tetracyclines are commonly used to treat which common dermatological condition in teenagers?

Answer: Acne vulgaris

What are some important side effects of tetracyclines?

Answer: Photosensitivity, staining of teeth (avoid in children), liver dysfunction in pregnant women, esophageal irritation (ulceration), and vertigo

What species of bacteria are generally susceptible to tetracyclines?

Answer: Chlamydia, Mycoplasma, Rickettsia, Borrelia burgdorferi, E. coli, Neisseria gonorrhoeas, Vibrio, streptococci, community-acquired methicillin-resistant S. aureus, Legionella, Brucella

How do bacteria usually become resistant to aminoglycosides?

Answer: Enzymatically inactivate aminoglycosides by conjugation (most important mechanism because this can be transferred between bacteria by transposons or pla-smids). Aminoglycoside resistance may also be due to ribosome alteration or decreased cell permeability to aminoglycosides.

What are the common side effects of aminoglycosides?

Answer: Nephrotoxicity (6%-7%), ototoxicity (2%; more common with loop diuretics), birth defects (teratogen), and neuromuscular blockade via decreased acetylcholine (ACh) release

Mnemonic:

aminoglycosides Need Oxygen To Work = Nephrotoxicity, Ototoxicity, Teratogen, Weakness

Which aminoglycoside is often given orally before GI surgery because it is poorly absorbed and prevents organisms from reaching the peritoneal cavity?

Answer: Neomycin. It is effective against gram-negative enteric flora.

What is the benefit and mechanism of giving β-lactam antibiotics with aminoglycosides?

Answer: β-Lactam antibiotics facilitate the entry of aminoglycosides into bacterial cells by damaging the cell wall.

Why are aminoglycosides ineffective against anaerobic bacteria?

Answer: They require oxygen for uptake into the bacterium.

What is the mechanism of action of aminoglycosides?

Answer: They inhibit the formation of ribosomal initiation complex and cause misreading of the mRNA.

Which antibiotics target the 30S and 50S ribosomal subunits respectively?

Answer: 

30S: aminoglycosides (neomycin, amikacin, tobramycin, gentamicin) and tetracyclines (minocycline, doxycycline)

50S: chloramphenicol, macrolides (erythromycin, azithromycin, clarithromycin), clindamycin, linezolid, streptogramins

What is the mechanism of action of fosfomycin which is used for UTIs?

Answer: Inhibits enolpyruvate transferase, preventing the formation of N-acetylmuramic (NAM) acid

Cycloserine is a second-line agent for tuberculosis. What is the mechanism of action of cycloserine? What are its side effects?

Answer: Analog of D-alanine that prevents the formation of the D-alanyl-D-alanine dipeptide in cell wall synthesis. CNS toxicity: seizures, acute psychosis, and peripheral neuropathy

Mnemonic:

PSYCHO-serine due to CNS side effects

What is the mechanism of action of bacitracin? What preparation is used clinically?

Answer: Prevents dephosphorylation and thus regeneration of a phospholipid carrier needed for cell wall synthesis. Topical agent (too toxic for systemic use)

How do certain gram-positive bacteria become resistant to vancomycin?

Answer: By mutation of the terminal D-alanine-D-alanine sequence in bacterial cell wall to which vancomycin binds. Vancomycin inhibits cell wall synthesis but it is not a β-lactam drug.

Which drug is the treatment of choice for methicillin-resistant S. aureus (MRSA) and what are its major side effects?

Answer: Vancomycin. Nephrotoxicity, ototoxicity, thrombophlebitis, and diffuse erythema due to histamine release

Mnemonic:

NOTE the side effects of vancomycin (Nephrotoxicity, Ototoxicity, Thrombophlebitis, and diffuse Erythema)

How do bacteria become resistant to β-lactam drugs?

Answer: Production of β-lactamases, mutations in transpeptidases (penicillin-binding proteins), or altered porins

What are the advantages of meropenem over imipenem?

Answer: Meropenem does not need to be administered with cilastatin and causes fewer seizures.

What is the chief concern of having high plasma levels of imipenem?

Answer: Central nervous system (CNS) toxicity/seizures

Why is imipenem, which has the broadest coverage of all the β-lactam drugs, always given with cilastatin?

Answer: Cilastatin is a dehydropeptidase inhibitor that inhibits metabolism of imipenem in the kidneys. This prevents nephrotoxicity and increases the urine concentration of intact imipenem, allowing for therapy of urinary tract infections.

What are the only types of bacteria susceptible to aztreonam?

Answer: Aerobic gram-negative bacteria

Which β-lactam antibiotic is safe for the treatment of gram-negative organisms such as Pseudomonas in patients with penicillin allergies?

Answer: Aztreonam (monobactams)

Why are penicillins and cephalosporins ineffective against Mycoplasma pneumoniae?

Answer: Mycoplasma does not have cell walls.

Which cephalosporins are commonly used as prophylaxis for gastrointestinal (GI) surgery? Why?

Answer: Cefoxitin and cefotetan because they have activity against anaerobes and enteric gram-negative rods

Which cephalosporin antibiotics are often used for the treatment of community-acquired meningitis? Why?

Answer: Ceftriaxone and cefotaxime because they can readily cross the blood-brain barrier and cover most strains of Streptococcus pneumoniae and Neisseria meningitidis (most common causes of adult community-acquired meningitis)

Which cephalosporin antibiotics have the best coverage against P. aeruginosa?

Answer: Cefepime (fourth generation) and ceftazidime (third generation)

What are the potential problems with cephalosporins that contain N-methyl-thiotetrazole side chains?

Answer: Disulfiram-like reaction causing hypotension, nausea, and vomiting when ingested with ethanol and prolonged prothrombin time because of interference with vitamin K activity leading to increased risk of bleeds

What is the standard treatment of meningitis caused by L. monocytogenes?

Answer: Ampicillin and gentamicin

Ampicillin or amoxicillin can be used to treat which organisms?

Answer: Haemophilus influenzae, Escherichia coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, and enterococci. Strains resistant to ampicillin are becoming more common.

Mnemonic:

Ampicillin/amoxicillin HELPS kill enterococci (H. influenzae, E. coli, Listeria, Proteus, and Salmonella)

Do β-lactamase inhibitors such as clavulanic acid or tazobactam improve activity of β-lactams against β-lactam-resistant P. aeruginosa?

Answer: No, β-lactamase inhibitors do not generally improve the activity of β-lactams against Pseudomonas. Resistance is generally by mechanisms other than β-lactamases.

Which penicillin class can be used to treat Pseudomonas aeruginosa?

Answer: Carbenicillin and ticarcillin (the carboxypenicillins) and piperacillin, mezlocillin, and azlocillin (the ureidopenicillins)

What is the Jarisch-Herxheimer phenomenon?

Answer: Acute worsening of symptoms (fever, headache, muscle pains) soon after penicillin G treatment due to released pyrogens from killed organisms, especially with treatment of syphilis

Which penicillins are the semisynthetic (anti-Staph) penicillins that are potentially more resistant to β-lactamases?

Answer: Methicillin, nafcillin, oxacillin, cloxacillin, and dicloxacillin

How does probenecid increase the half-life of penicillin G?

Answer: It blocks active renal secretion of penicillin.

Which bacteria are potentially susceptible to penicillin G?

Gram positives (with exceptions such as Staphylococcus aureus), Neisseria, spiro-chetes, and most anaerobes

Mnemonic:

penicillin G treatment SPANs (Spirochetes, gram positives, Anaerobes, Neisseria)

What is the difference between penicillins G and V? What is the most common adverse effect of penicillin?

Answer: Penicillin G is given intravenously and penicillin V is resistant to gastric acid, allowing it to be given orally. Hypersensi-tivity reactions (< l%-8%) are the most common adverse effect.

What is the mechanism of action of all β-lactam antibiotics?

Answer: They bind to and inactivate transpep-tidases (sometimes known as penicillin-binding proteins), which are involved in bacterial cell wall synthesis.

Name the major categories of β-lactam antibiotics:

Answer: Penicillins, cephalosporins, monobactams, and carbapenems

What are the two specific tests (to detect disease-specific antibodies) for syphilis?

1. FTA-ABS (fluorescent treponemal antibody-absorbed test)

2. MHA-TP (microhemagglutination-Treponema pallidum)

What disease states may cause a false-positive result with a nonspecific syphilis test?

Answer: Hepatitis B, infectious mononucleosis, leprosy, and autoimmune diseases such as systemic lupus erythematosus

What are the two nonspecific tests (to detect nonspecific antibodies) for syphilis?

1. VDRL (Venereal Disease Research Laboratory)

2. RPR (rapid plasma reagin)

What bacterial species causes IgM cold autoimmune antibodies?

Answer: Mycoplasma pneumoniae

How does polymerase chain reaction (PCR) work?

PCR amplifies bacterial DNA using bacterial-specific primers, free DNA bases, and DNA polymerase, allowing for identification of bacteria.

Name two types of bacteria that are identified by immunofluorescence:

1. Chlamydia

2. Spirochetes

Describe direct and indirect immunofluorescence.

Answer: Direct immunofluorescence detects specific bacterial antigens by using antibodies conjugated with fluorescent dyes to directly bind the bacterial antigen which then fluorescences under ultraviolet (UV) light. Indirect immunofluorescence detects serum antibodies by using known antigens to bind the antibodies which can then be detected under UV light by antihuman IgG antibodies conjugated with fluorescent dyes.

How does ELISA (enzyme-linked immunosorbent assay) work?

Answer: An enzyme linked to either a bacterial antigen or antibody reacts in direct proportion to the amount of antigen-antibody complexes formed.

What bacteria is identified by the Elek test? How does the Elek test work?

Answer: Corynebacterium diphtheriae. Antitoxin (antibody to diphtheria toxin)-coated strips are placed onto agar with C. diphtheriae inoculated at right angles to the antitoxin strips. If toxigenic C. diphtheriae is present, toxin-antitoxin complexes precipitate.

What other tests are used to determine the presence of a capsule? How do the tests work?

Answer: Latex agglutination. Latex beads complexed to antibodies precipitate when they bind the capsular antigen of interest. This test is usually used to aid in diagnosis of bacterial meningitis. Wet mount with India ink also can be used to identify Cryptococcus capsule.

Name some bacteria that are Quellung positive:

Cryptococcus (not bacteria), Pseudomonas, 'Neisseria meningitidis, H. influenzae, Klebsiella, and Streptococcus pneumoniae

Mnemonic:

Capsules Protect Naughty Human Killing Strains of bacteria

What does the Quellung test detect?

Answer: Capsule. Quellung is the German word for "swelling."

Which bacteria produce a black pigment on bile-esculin agar?

Answer: Group D streptococci and enterococci

In addition to respiratory bursts, what other free radical-generating system is found in macrophages?

Answer: Inducible nitric oxide synthase (iNOS) produces nitric oxide (NO).

What enzyme forms hypochlorite (HOCL•−) from peroxide (H2O2) and chloride (CI−)?

Answer: Myeloperoxidase. Hypochlorite is 50 times more potent than peroxide at killing bacteria.

What enzyme degrades peroxide (H2O2) into H2O and oxygen, and thereby protects bacteria?

Answer: Catalase

What enzyme converts superoxide (O2•−) to peroxide (H2O2)?

Answer: Superoxide dismutase

What enzyme produces superoxide (O2•−) from oxygen (O2)?

Answer: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the neutrophil cell membrane

Neutrophils and monocytes engulf bacteria and kill them by what mechanism?

Answer: Oxygen-dependent (respiratory burst) and oxygen-independent (muramidase, lactoferrin, low pH, lysozyme)

What group of receptors allows neutrophils and macrophages to recognize conserved bacterial structures such as lipopolysaccharide (LPS)?

Answer: Toll-like receptors (pattern-recognition receptors)

What immune cells are involved in innate immunity?

Answer: NK cells, neutrophils, macrophages

The acute-phase response represents a group of proteins released from the liver as part of innate immunity. Name the function of the following acute-phase proteins: C-reactive protein

Answer: Clears necrotic debris and may activate the classical complement pathway

Macrophages release various cytokines in innate immunity. Name the function of the following cytokines: Tumor necrosis factor-α (TNF-α)

Answer: 

Induces the inflammatory response

lnterleukm-1 (IL-1)

Induces fever, which enhances the immune response

Interleukin-6 (IL-6)

Induces the acute-phase response

Interleukin-8 (IL-8)

Chemotactic factor neutrophils

Interlukin-12 (IL-12)

Activates NK and Th1 cells

What is the role of complement in innate immunity?

Answer: Opsonization/phagocytosis, cytolysis, and chemotaxis

What disease is associated with autosplenectomy?

Answer: Sickle cell anemia

Name two types of DNA forms found in bacteria:

1. Chromosomal DNA

2. PlasmidDNA

Are bacteria haploid or diploid?

Answer: Haploid

By what process do bacteria multiply?

Answer: Binary fission

What are some of the facultative intracellular organisms?

Brucella, Salmonella typhi, Francisella tularensis, Legionella, Mycobacterium, Yersinia, and Listeria monocytogenes

Mnemonic: I'll Telia MY List of facultative intracellular organisms (Brucella/Salmonella/Francisella/Legionella, Mycobacterium, Yersinia, Listeria}

What are facultative intracellular organisms?

Answer: Organisms that can survive both intracellularly and extracellularly

How do obligate intracellular organisms generate ATP?

Answer: They cannot produce their own ATP, so they utilize the ATP of a host cell. Therefore, they can only survive within the host cell.

What are obligate intracellulai organisms?

Answer: Organisms that can only survive within host cells (eg, Chlamydia and Rickettsia)

Mnemonic: Rob Cells of ATP (Rickettsia, Chlamydia)

Why are obligate anaerobes unable to grow in the presence of oxygen?

Answer: Because they do not have enzymes such as superoxide dismutase, catalase, or peroxidase to protect them from free O2 radicals.

How do microaerophilic bacteria tolerate low levels of oxygen?

Answer: They have superoxide dismutase, but no catalase.

How do microaerophilic bacteria generate adenosine triphosphate (ATP)?

Only through fermentation. They do not have an electron transport system.

How are facultative anaerobes different from obligate aerobes?

Facultative anaerobes are aerobic bacteria which have catalase and superoxide dis-mutase, so they can use oxygen as obligate aerobes. However, they can also grow in the absence of oxygen by using fermentation for energy.

Why do obligate aerobes require oxygen?

Obligate aerobes require oxygen because their metabolism requires oxygen as the final electron acceptor. They use glyco-lysis, the tricarboxylic acid (TCA) cycle, and the electron transport chain.

What are some of the obligate anaerobic bacteria?

Gram positive: Clostridium, Actinomyces

Gram negative: Bacteroides

What are some of the obligate aerobe bacteria?

Gram positive: Nocardia, Bacillus Gram negative: Neisseria, Pseudomonas, Bord-etella, Legionella, Brucella

Acid-fast: Mycobacterium, Nocardia (weakly acid-fast)

How are bacteria groups separated according to their oxygen requirements?

Obligate aerobes require oxygen for metabolism (eg, Pseudomonas); facultative anaerobes can use aerobic or anaerobic metabolism (eg, Listeria, Entero-bacteriaceae); microaerophilic bacteria require low oxygen tension (eg, Camp-ylobacter); aerotolerant anaerobes can grow with or without oxygen, but only use anaerobic metabolism (Enterococcus faecalis); and obligate anaerobes cannot survive in oxygen (eg, Clostridium).

During what phase have nutrient sources been exhausted?

Death phase

During what phase do spores form?

Stationary phase

In what phase does bacterial growth equal that of bacterial death?

Stationary phase

During what phase do β-lactam drugs act?

Log phases

During what phase is growth the fastest?

Log phase

During what phase do bacteria have the highest metabolic activity but without cell division?

Lag phase

What are the four phases of bacterial growth?

1. Lag phase

2. Logarithmic phase (log)

3. Stationary phase

4. Death phase

What is a fomite?

An inanimate object that can harbor and spread infections (eg, blankets with smallpox or hospital bed rails with methicillin-resistant Staphylococcus aureus[MRSA])