860d EXAM 1

oral flora

very diverse and relative high microbial burden -> streptococci and anaerobes

stomach flora

low microbial burden due to acid -> H. pylori is a common infection that can cause gastritis, ulcers, cancer

duodenum to jejunum flora

increasing presence of gram negative nodes and anaerobic bacteria

- SIBO can occur here

colon flora

very diverse flora - gram positives, gram negatives, high anaerobe content

4 diseases associated with colonic flora

1) dysbiosis associated with IBS/IBD & autoimmune disorders

2) altered flora in many disease states

3) abx associated C. diff

4) bacterial translocation - gram negative bacteremia

what are the 4 major glucose and lactose fermenting gram negative rods?

1) E. coli

2) Citerobacter spp

3) Klebsiella spp

4) Enterobacter spp.

what are 4 major glucose and lactose non fermenting gram negative rods?

1) pseudomonas

2) acinetobacter

3) stenotrophomonas maltophilia

4) burkholderia

which of the 4 major glucose and lactose non fermenting gram negative rods is oxidase positive?

Pseudomonas

firmicute

staph

strep

enterococcus

clostridium

lactobacilli

Proteobacteria

.E. coli

Klebsiella

Citerobacter

Enterobacter

bacteroidetes

bacteriodes (anaerobes)

prevotella

actinobacteria

actinomyces

corynebacterium

which 8 are a true infection until proven otherwise?

1) Staph aureus

2) GAS (S. pyogenes)

3) GBS (S. agalactiae)

4) S. pneumoniae

4) Enterobacterales (gram negatives)

5) Pseudomonas

6) bactericides fragilis

9) Candida spp.

mycobacteria

contain cells walls with a high content of mycolic acid (fatty acid chain) which makes the cell wall very waxy

MAC

mycobacterium avium complex - a more resistant form of TB usually requiring longer and more aggressive tx

T/F: Bacteria lack the ability to transport folic acid across their membranes which is why they must synthesize folic acid in their cytoplasms

TRUE

2 common resistance mechanisms for gram positive organisms?

1) mutation in target (PBP mutations)

2) Beta lactamases (staphlococcus)

3 common resistance mechanisms for gram negative organisms?

1) betalactamases located in periplasmic space (most common resistance mechanism)

2) porins

3) efflux transporters

what are 4 common mechanisms of resistance to beta lactam abx?

1) altered binding to PBP (more common in gram pos)

2) production of beta lactamases (more common in gram negative)

3) abx efflux

4) altered permeability (porin loss)

3 mechanisms of resistance to tetracyclines

1) efflux

2) ribosomal protection proteins (prevent tetracycline binding to ribosome)

3) inactivation

A, C, D beta lactamases

serine in the active site

B beta lactamases

metallo (zn) in active site

what was the goal of making the different generations of cephalosporins?

to make the agents more hydrophilic for better navigation through porins to have more gram negative activity

T/F: cephalosporins are active against enterococcus

FALSE but penicillins are (except E. faceium)

what abx can be used for carbapenem resistant acinetobacter baumanii (CRAB)?

sulbactam/durlobactam

what are two resistance markers for carbapenemase producing organisms?

1) NDM-1

2) KPC-1

important beta lactamase in Staph aureus

Class A (A2a) -> penicillinase (MSSA) -> blaZ

MEC-A gene

PBP2a

what is the change that makes S. aureus resistant to methicillin (aka MRSA)

PBP2a

CTMX gene

produces ESBL gram negative organisms (alteration in class A BL in plasmid)

Class D beta lactamase (OXA)

hydrolyzes oxacillin

Van-A gene

synthesizes D-Ala-D-Lac, an alternative substrate for peptidoglycan synthesis = vancomycin resistance

what does it mean for abx coverage when a bacteria is AmpC producing?

AmpC hydrolyzes 3GC -> resistant to B lactams 3rd gen cephlaspoins and below

AmpC producing enterobacterales

1) Enterobacter cloacae

2) Klebsiella aerogenes

3) Citrobacter fruendii

what is the DOC for AmpC or ESBL producing gram negatives?

Carbapenems

OmpD

carbapenem channel - porin in pseudomonas (smaller, more selective, less porins than E.coli)

what 3 penicillins are penicillinase resistant?

1) methicillin

2) oxacillin/nafcillin

3) dicloxacillin (oral)

does amoxicillin/ampicillin cover MSSA?

no since MSSA produces a beta lactamase -> need to add a BLI to have coverage

why is E. faecium resistant to vancomycin (VRE)?

has Dala Dlac and vancomycin can't bind to peptidoglycan

what are the two DOC for E. faecium infections?

1) linezolid

2) daptomycin

T/F: streptococcus and enterococcus species do not produce beta lactamase so the addition of a BLI will not enhance activity

TRUE

what is cross reactivity between penicillins and other B-lactam abx determined by?

the B lactam side chain (if they are similar, there is more of a likelihood that there will be cross reactivity)

which abx is commonly used orally for C. diff

vancomycin as it stays in gut when given orally

daptomycin coverage

gram + -> alternative for MRSA and VRE

why cant daptomycin be used for MRSA causing pneumonia?

the surfactant in the lungs inactives it

linezolid coverage

gram + only -> MRSA, VRE, norcardia, mycobacterium

why is ertapenem more narrow spectrum than the other carbapenems?

it does not cover pseudomonas, enterococci, or acinobacter

Pts with NAT2 deficiencies are more susceptible to liver injury by which abx?

isoniazid -> shunts the metabolism to CYP2E1 which will increase the production of toxic metabolite

metronidazole spectrum of activity

1) obligate anaerobes

2) H. pylori

3) giardia intestinali

4) trichomonas vaginalis

what are the 6 organisms that cause pneumonia?

1) streptococcus pneumoniae

2) haemophilus influenzae

3) morexella catarrhalis

4) Chlamydia pneumoniae

5) mycoplasma pneumoniae

6) legionella spp.

4 antibacterial drugs causing nephrotoxicity

1) aminoglycosides

2) polymyxins

3) Sulfadiazine

4) vancomycin

4 antiviral drugs causing nephrotoxicity

1) acyclovir

2) foscarnet

3) cidofovir

4) tenofovir disoproxil fumarate

major antifungal drug that causes nephrotoxicity

amphotericin B (non lipophilic formulations)

which 3 classes of abx commonly cause acute interstitial nephritis (AIN)?

1) anti staphylococcal penicillins (oxacillin & nafcillin)

2) FQ

3) sulfonamides

how do aminoglycosides cause renal toxicity?

they undergo uptake into the proximal tubular cells & can lead to accumulation

how do polymyxin abxs cause renal toxicity?

transported into proximal tubular cells (apical side) into the cell and accumulate within the cell.

how does vancomycin cause renal toxicity?

oxidative damage to mitochondria in the proximal tubular cell & produce urinary casts which may cause obstruction

T/F: vancomycin toxicity is more rapidly reversible than aminoglycoside toxicity

TRUE as with aminoglycoside toxicity, Scr can rise even after d/c drug since it accumulates in renal cells

how does tenofovir cause renal toxicity?

accumulates in the tubular cell when MRP becomes dysfunctional or inhibited leading to less drug getting out

what tenofovir drug can be used that causes less renal toxicity and why?

Tenofovir alafenamide (TAF); prodrug that works after uptake into lymphocytes to deliver more drug to site of action

how does ampho B cause renal toxicity?

causes constriction of afferent arterioles & membrane damage (due to similarity of ergosterol & cholesterol)

what forms of ampho B are less toxic?

Lipid formulations (AmpB liposome & Amp B lipid complex)

how can acyclovir and sulfadiazine cause renal toxicity?

limited solubility and can crystalize in the renal tubules and urine when its solubility is exceeded

how does foscarnet cause renal toxicity?

can form crystals by itself and as salts of sodium and calcium. Crystals have been observed in the glomeruli and proximal tubules leading to progressive glomerulonephritis with hematuria and proteinuria.

pharmacodynamic monitoring for Beta lactams

Time/MIC

pharmacodynamic monitoring for aminoglycosides

peak/MIC

pharmacodynamic monitoring for most other abx such as vanco

AUC/MIC

What is PAE?

post antibiotic effects which means that bacteria do not immediately start growing once the abx is removed

order for donning PPE

wash hands

gown

mask/respirator

googles/face shield

gloves

order for removing PPE

gloves

googles/face shield

gown

mask/respirator

wash hands

T/F: aminoglycosides against gram negatives have long PAE which is what allows for one large dose to be given (instead of TID)

TRUE

Uncomplicated UTI

infection confined to the bladder, no systemic symptoms

complicated UTI

infection that spreads beyond the bladder; systemic symptoms

what are 3 examples of a complicated UTI?

1) pyelonephritis (kidney infection)

2) catheter associated UTI (CAUTI)

3) prostatitis

recurrent UTIs (rUTI)

two separate episodes or acute bacterial cystitis and associated sx within < 6 months

prostatitis

inflammation of the prostate gland likely due to reflux of infected urine into the gland

- commonly seen in older men with rUTIs

- commonly caused by E. coli

T/F: prostatitis is difficult to treat since abx do not penetrate well into prostatic tissues or fluids

TRUE

typical tx and tx duration with prostatitis

FQ (in AZ since tmp/smx not susceptible) or cephalosporins/penicillins (but resistance is also rising)

- 4-6 weeks

T/F: bacteria in the urine or an abnormal urinalysis results in the diagnosis of a UTI

FALSE as patients must have UTI symptoms + an abnormal urinalysis in order to treat

what 3 incidences do we treat asymptomatic bateruria?

1) pregnant

2) receiving a urinary procedure

3) immunocompromised

signs and symptoms of a lower UTI (uncomplicated UTI)

1) dysuria

2) urgency

3) frequency

4) nocturne

5) suprapubic heaviness

signs and symptoms of a upper UTI (complicated UTI)

1) fever

2) flank pain

3) costovertebral angle (CVA) tenderness

4) malaise

T/F: most UTIs are caused by a single organism

TRUE

what are the 2 virulence factors that make E. coli the most common organism for a UTI?

1) fimbriae (hair like structures)

2) adhesions (attach to host cell receptors)

UTI causing bacteria

1) E. coli (90%)

2) Staphylococcus

saprophyticus

3) Enterococcus

4) other enterobacterialies (K. pneumoniae, proteus mirabilis)

5) pseudomonas (rarely seen in community acquired)

if using cranberry for UTI prevention, how many PACs are needed?

at least 36

T/F: methanamine hippurate is a good prevention option for rUTIS

does fosfomycin cover Staphylococcus saprophyticus

NO

Sulopenem etzadroxil-probenecid

newer agent that is reserved for UTIs with abx resistance

major layers of the skin (from most superficial to most deep)

epidermis

dermis

subQ

T/F: deeper skin infections are typically more complicated and serious

TRUE

what are 4 factors that can lead to increased risk of skin infection?

1) skin damage (break the barrier)

2) inadequate blood flow

3) excessible moisture on skin

4) high bacterial concentrations

what is the most important thing to do for a furuncle or carbuncle?

incision and drainage (I & D)

cellulitis involves what portions of the skin?

dermis and SubQ

when to hospitalize a patient with cellulitis?

severe infection -> fevers/chills, mental status changes, shock, dramatic infection

what is a common organism found in dog/cat bites?

pasturella spp (GN)

when is abx prophylaxis considered in bite wounds?

1) immunocompromised pts (RA, HIV, drugs)

2) asplenia pts

3) wounds to hands, genitals, face

4) deep puncture wounds with proximity to bone or joint

5) advanced liver disease

indications for surgical prophylaxis?

an unacceptable incidence or consequence of infection

clinical presentation of pneumonia

cough (productive or non-productive)

fever/chills

pleuritic chest pain (knife like pain when inhaling)

dyspnea

rales/crackle breath sounds

what must be done in conjunction with symptoms to rule out acute tracheobroncitis caused more commonly by viruses?

chest X ray