Microbio 3 2

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memory trick for C. difficile treatment: the METRO train and VAN cruise down the GI tract rather than being absorbed and run over the hapless C. difficile

METROnidazole or VANcomycin by mouth
what should you use to treat Legionnaire's disease?: treat with erythromycin becase the organism is a beta-lactamase making it resistant to penicillins
Beta-lactamases: may exist in the periplasmic space of gram- bacteria; can degrade penicillin
lysozyme: present in human tears, mucus, and saliva, can cleave the peptidoglycan backbone
what is special about the capsule of anthrax bacillus?: instead of being composed of polysaccharide it is composed of D-glutamic acid
what is special about the cell wall of mycoplasma?: it doesn't have one! only surrounded by a cell membrane
defensins: found in lower respiratory tract and GI tract

highly positively charged peptides that create pores in the membranes of bacteria which kills them
which two proinflammatory cytokines are produced by macs?: IFN-Gamma & TNF
what is the main inducer of the acute-phase response?: IL-6
what are the four structural classes of Beta-lactams?: (1) Penicillins

(2) Cephalosporins

(3) Monobactams

(4) Carbapenems
structure of 4 beta-lactam antibiotics: get it?
how are virtually all of the beta-lactams eliminated?: by the kidney, mostly be tubular secretion
why does ceftriaxone represent an exception regarding beta-lactam dosage?: most have short half-life (.5-2 hrs)

ceftriaxone is LONG (6-8 hrs)
has broadest spectrum of any beta-lactam antibiotic: imipenem
DOC for treating infections caused by MRSA, MRSE and enterococci: vancomycin
DOC to treat pseudomembranous colitis: (orally) vancomycin
daptomycin - used for which classes?: used only to treat infections with gram+ cocci (staphylococci, streptococci, enterococci)

alternative to vancomycin for treating S. aureus bacteremia
daptomycin - basic structure - mech of action: water soluble core / lipophilic tail

inserts tail into PM --> makes a pore
how are all macrolides excreted?: by the liver
adverse effects of macrolides: all macrolides bind to and are agonists of GI motilin receptors, causing INC GI motility --> nausea, vomiting, diarrhea, and bloating
DOC for treatment of ALL infections caused by obligate anaerobes: clindamycin
what is the most common adverse event associated with clindamycin?: development of pseudomembranous colitis
why do aminoglycosides have no activity for anaerobic bacteria?: b/c an oxygen-dependent transport system is required to cross the cell membrane

Remember: Aminoglycosides work on protein synth
discuss the selective toxicity of sulfonamides toward bacterial cells: sulfonamides competitively inhibit dihydropteroate synthetase (required for bacterial folic acid synthesis)

doesn't effect humans b/c we only get folic acid from diet
Penicillin-binding protein aka: transpeptidase
what is one way that gram- (and not gram+) bacteria defend themselves from penicillin?: altering the porins (penicillin can't get in)
why is Vancomycin not useful against gram(-) bacteria?: too big to get past gram(-) outer membrane
what are the two most important Beta-lactams?: Penicillin and Cephalosporin
is DEC accumulation of beta-lactams a method of resistance in gram(+) bacteria?: NO, just gram(-)
do beta-lactams make it into the CSF?: no, they're actively pumped out

BUT in inflammation, barriers to beta-lactam entry are disrupted
cephalosporins - spectrum of activity: more active against enteric gram(-) rods than penicillins
what drug has the broadest spectrum of any beta-lactam antibiotic?: imipenem
dose-related adverse effects are uncommon with beta-lactam antibiotics BUT they do occur (esp. in renal failure) -- what are the major dose-related side effects?: seizures, bleeding due to platelet dysfxn
what is THE major side effect to penicillins?: allergic rxns
what is the best orally-absorbed beta lactam?: amoxicillin
Name a parenterally-administered First Generation Cephalosporin: cefazolin (prophylaxin for surgical wound infections)
what oral synth prep containing a beta-lactam is good for animal bites?: amoxicillin plus clavulanic acid
name one second generation cephalosporin: cefoxitin
name two third generation cephalosporins: ceftriaxone and ceftazidime
what monobactam is good for patients with penicillin allergy?: aztreonam
what is the MOA for vancomycin?: binds directly to cell wall dipeptide D-ala-D-ala -- inhibits both transpeptidation and transglycosylation
in what bacteria do we see resistance to Vancomycin, and what is the MOR?: enterococci

D-ala-D-ala --> D-ala-D-lac
for what four conditions is vancomycin one of the DOCs?: MRSA, MRSE, and enterococci

(oral) treatment of pseudomembranous colitis (C. difficile)
is Vancomycin absorbed orally and is there any oral use for the drug?: it is NOT absorbed orally

BUT

there is an oral use --> to treat pseudomembranous colitis due to C. difficile
vancomycin excretion, metabolism: excreted by kidney, no known metabolism
is daptomycin effective in treating pulmonary infections?: NO
daptomycin spectrum: not gram(-)

active against staph, strep, and enterococci
protein synth inhibitors are: a. bactericidal b. bacteriostatic - exception?: bacteriostatic

exception: aminoglycosides
do aminoglycosides and tetracycline work on 30S or 50S?: 30S

Note: most everything else is 50S
what is the DOC for treating Vancomycin Resistant Enterococci (VRE)?: Linezolid (a 50S inhibitor)
what is the only of the protein synth inhibitors to act at the initiation of protein synthesis step?: Linezolid (50S)
MLS(B): in staph, a gene is acquired that methylates adenine nucleotides in ribosomal RNA, preventing the binding of macrolides, lincosamides, and streptogramin B
what class of drugs are the DOCs for the following infections: (1) legionalla pneumoniae (2) mycoplasma pneumoniae (3) bordatella pertussis (4) corynbacterium disphtheriae (5) Chlamydia: Macrolides!
what is the DOC for Chlamydia?: azithromycin
what is the DOC for chancroid?: azithromycin
are macrolides active against enterobacteriacae?: NO, pumped out
how are macrolides excreted?: liver
disc the importance of drug-drug interactions re: macrolides: erythromycin and clarithromycin can block the excretion of other drugs that are metabolized by the hepatic cytochrome P450 enzymes
main adverse effect of macrolides: inc GI motility
for what bunch of infections is Clindamycin the DOC?: obligate anaerobes
what is the most common adverse event re: clindamycin?: pseudomembranous colitis
spectrum for Synercid (streptogramin A+B): mainly just used as bacteriostatic for VREF (vancomycin resistant E. faecium)
drug interactions of synercid: YES, C-P450

thus, method of excretion is liver
do aminoglycosides show concentration-dependent killing?: YES

Note: also show concentration-dependent toxicity
aminoglycosides and synergy: often used in combo with B-lactam

e.g. Amincoglycosides have no activity against E. faecalis (enterococci), but together with ampicillin can get into cell wall and do their job
adverse effects of aminoglycosides: Remember, both are dose-related

(1) reversible tubular necrosis

(2) irreversible hearing loss and vestibular damage
what is the most commonly prescribed member of the tetracyclines class?: doxycycline
absorption of tetracycline: significantly reduced when given with food and di-trivalent cations
minocycline adverse effect: dizziness and vertigo in women
doxycycline adverse effect: erosive esophagitis
what are the two important adverse effects of chloramphenicol?: (1) bone marrow suppression, including an idiosyncratic, irreversible aplastic anemia -- rare but bad

(2) "Gray baby" syndrome
adverse effects of sulfonamides: dermal allergies
what is the most common mech of resistance to sulfonamides?: altered dihydropteroate synthetase that does not bind sulfonamides
Sulfamethoxazole + trimethoprim -- aka: TMP-SMX, Bactrim
TMP-SMX commonly used for: UTI

uncomplicated cystitis
TMP-SMX is a good example of what?: antibiotic synergy

SMX blocks folic acid synth

TMP blocks different step
adverse effects of metronidazole: metallic taste, GI distress, "antabuse-like" rxn (flushing, nausea) with alcohol
generic names of all fluoroquinolones end with what?: "-floxacin"
what are the three most useful quinolones?: (1) Ciprofloxacin (Cipro)

(2) Levofloxacin (Levaquin)

(3) Moxifloxacin (Avelox)
quinolone MOA: Bind to bacterial topoisomerases II & IV (enzymes responsible for DNA replication, repair and transcription)
how are quinolones similar to aminoglycosides?: both exhibit concentration-dependent killing
T/F quinolones are widely used for treatment of respiratory infections: T

e.g. S. pneumoniae, H. influenzae, Legionella pneumophila, Chlamydia pneumoniae
T/F Quinolones are very effective for UTI caused by gram(+) bacteria: F

good for UTI for gram(-)

usually think of quinolones as a gram(-) drug
why are quinolones contraindicated in pregnancy and children?: impair bone growth and cartilage development
bacitracin spectrum of activity: most gram(+) bacteria are susceptible
Polymyxin MOA: Acts like a detergent, disrupts cell membrane.
clinical uses of Polymyxins: Topical: with bacitran

Parenteral: Colistin is reserved for treatment of multidrug-resistant bacteria, usually P. aeruginosa or A. baumannii
enteritis: inflammation of the mucosa of the intestines
enterocolitis: enteritis involving both small and large intestines
gastroenteritis: inflammation of stomach and intestinal linings
dysentery: inflammation of the GI tract with blood and pus in the feces, and symptoms of pain, fever, abdominal cramps; usually a disease of the large intestine
list 6 common GI tract diseases: (1) bacterial infections

(2) antibiotic-associated (disruption of flora)

(3) viral

(4) Protozoan infections (entamoeba, giardia, cryptosporidium)

(5) Worm infections

(6) Food poisoning (e.g. preformed toxins)
what are the two groups of enterobacteriaceae family?: (1) lactose fermentors (coliform bacteria)

(2) Nonlactose fermenters
give 5 examples of lactose fermenters (coliform bacteria): SEKCE ("Sexy")

Serratia
E. coli
Klebsiella
Citrobacter
Enterobacter
give 4 examples of nonlactose fermenters (of the enterobacteriaceae family): Salmonella
Shigella
Proteus
Yersinia
MacConkey Lactose Agar: contains bile salts, which permits growth of enteric bacteria but selectively inhibits growth of gram(+)

incubated aerobically to eliminate anaerobes

contains lactose and pH indicator to discriminate Lac+ vs. Lac-
EMB Agar: contains dyes (eosin and methylene blue) which permit growth of enteric bacteria but selectively inhibits growth of gram(+)
O Antigen: polysaccharide portion of LPS
H Antigens: flagella protein found on motile cells
K Antigens: capsular polysaccharide
E. coli general: lactose-fermenting (Lac+) enterobacteriaceae
ETEC: enterotoxigenic E. coli
ETEC virulence factors: Heat-Labile Toxin (LT): destroyed at 65C 30 min

stim adenylate cyclase --> INC cAMP
ETEC virulence factors: heat-Stabile Toxin (ST): not destroyed at 100C 30 min

stim guanylate cyclase --> INC cGMP
EPEC: enteropathogenic E. coli
EHEC: enterohemorrhagic E. coli

"Hemorrhagic Colitis" -- severe abdominal cramps and copious, bloody diarrhea
transmission of EHEC: undercooked hamburger, raw milk, unpasteurized fruit juice
what is the predominant serotype in the EHEC group worldwide?: E. coli O157:H7
what is the main virulence factor for EHEC?: Shiga-like (Vero) toxin (SLT)

stops protein synth; destroys the intestinal epithelial lining; dead cells slough off causing a bloody diarrhea
Hemolytic-Uremic Syndrome (HUS): most common cause of acute renal failure in children in US

5-10% EHEC cases
EIEC: enteroinvasive E. coli
EAggEC: Anteroaggregative E. coli
Salmonella - basic definition: Lac- Enterobacteriacea

forms H2S and produces gas during glucose fermentation
Shigella basic definition: Lac- enterobacteriaceae, no H2S formation, no gas from glucose
do salmonella, shigella, and pseudomonas aeruginosa ferment lactose?: NO
what is the most common cause of UTI?: E. coli

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