860D exam 1

i'm not a normal uncle i'm a furuncle

normal/ common skin flora

• coagulase negative staph

• corynebacterium

• cutibacteria

• viridans streptococci

• bacillus

normal/ common GI tract flora

• firmicules (strep/staph)

• bacteriodetes (bacteriodies)

• proteobacteria (ham, esch, kleb, citro)

• actinobacteria (coryn, actino)

normal typical flora- anaerobes

• majority Bacteroidetes class

  • otherwise diverse

typical oral microbiome

• streptococci

• anaerobes→ hide in oral biofilm

blood cultures- what to assume is infection until otherwise known

• staph aureus

• strep. pyogenes (GA)

• strep. alalactiae (GB)

• strep. pneumoniae

• enterobacterales

• pseudomonas aeruginosa

• bacteriodies fragilis

• candida

blood culture: typical contaminents

• coag negative staph→ especially staph epi

• bacillus (non anthrax)

• corynebacterium

• viridians strep

• cutibacterium

• clostridium perfengens

• micrococcus

if blood cultures positive- what should you evaluate?

• any sx?

• any IV devices?

• IV thrombus?

• immunocompromised?

• how many cultures were taken, and from what sites?

what is the most important practice in disease control

hand hygiene

steps to put PPE on

1. gown

2. mask

3. goggles/faceshield

4. gloves

how to take PPE off

1. gloves

2. gown

3. goggles/faceshield

4. mask

5. hand hygiene

skin and soft tissue classifications of disease

• necrotizing (deeper) vs non necrotizing

• purulent(abscess or fluid collection) vs non purulent

• complicated vs non complicated

  • deep infections (dermis/subcutaneous)

  • rapidly progressing

  • surgical intervention

  • @ higher risk for complicated pt populations

community associated MRSA- outpt treatment options

• TMP-SMX

• clindamycin (D-test)

• oxazolidinones (linezolid)

• tetracyclines(doxy,mino)

• delafloxacin

MRSA- inpt treatment

gram +/MRSA only

• vancomycin

• linezolid

• daptomycin

• other lipoglycopeptides

if mixed or other failed

• 5th gen cephalosporins: ceftaroline, ceftobiprole

• tetracycline

non bullus impetigo sx

• white/ purulent discharge in vessel

• when bursts leaves a yellow/ brown crust on the skin

bullous impetigo sx

• yellow/ clear fluid in vessel

• red base when burst

impetigo treatment

mild cases:

• topical mupirocin or ozenoxacin($$)

more severe:

• oral dicloxacillin or cephalexin (MSSA)

• oral TMP-SMX, doxycycline OR clindamycin (MRSA, allergy or fail other)

duration: 5-7 days

impetigo treatment duration

5-7 days

folliculitis

• limited to epidermis(hair follicules)

• multiple small lesions

• typically are self limiting- resolve on their own→ otherwise non drug treatments:

  • warm compress

furuncles

• infection of hair follicles, purulent material extends into dermis and subcutaneous tissue→ worsens to carbuncle

carbuncle

• group of inflamed follicles in single mass with drainage from multiple follicles

furuncles and carbuncles treatment

• moist heat compress→ if smaller

larger:

• incision and drainage→ take culture

• oral abx:

  • empiric coverage abx- TMP/SMX, doxycycline, clindamycin

cellulitis presentation

• redness, swelling, warmth and pain + systemic infection

when to hospitalize for cellulitis

• fever

• rigors

• metal status change

• shock

• dramatic skin infection(large fluid collections)

cellulitis inpt treatment

• erysipelas (clear demarkation)

  • IV cefazolin

• non-purulent

  • IV cefazolin: mod/severe @ 50% risk

  • vanco/linezolid: more severe/ high risk +broad spectrum in addition to MRSA coverage (immunocompromised, necro/deep shock, abx failure)

• purulent:

  • vanco or linezolid

cellulitis outpatient treatment

• erysipelas (streptococcus)

  • PCN or amoxicillin

• non-purulent (often strep):

  • dicloxacillin or cephalexin

• purulent (MRSA coverage ± strep)

  • SMX/TMP, doxycycline, clindamycin

duration: 5-14 days

cellulitis outpt treatment duration

5-14 days

what to do for bites?

• irrigate with soap or povidine-iodine

• check immunization record

when is abx prophylaxis indicated for bites?

• immunocompromised

• asplenia

• wounds to hands, face or genitals

• deep puncture wounds or close proximity to bones/joints

• advance liver disease

abx for bite prophylaxis

• amoxicillin- clavualante preferred

alternatives:

• doxycycline, TMP/SMX, cefuroxime

• OR fluoroquiolones + metronizadole/ clindamycin

use PO for less severe

IV for more severe cases:

• amp-sulbactam, ceftriaxone+metronizadole or pip-tazo

• cefoxitin

• ertapenem

• fluoroquinolone w/ metronizadole or clindamycin

ALSO consider post exposure rabies or tetanus

UTI risk factors

• increased age

• female sex

• pregnancy

• obstruction

• DM

• prostatic hypertrophy

• anticholinergic drugs

• neurological disease

• catheterization or instrument

• sexually active

uncomplicated UTI (cystitis) symptoms

• dysuria- painful

• urgency

• frequency

• gross hematuria (blood)

• nocturia

• suprapubic heaviness

complicated UTI (pyelonephritis) symptoms

• fever

• N/V

• malaise

• flank pain

• CVA tenderness

therapy for UNCOMPLICATED cystitis

• nitrofurantoin→ narrow specturum (ecoli, S.saproph)

  • 100mg BID x 5d

  • avoid: CrCl<30, pyelonephritis

  • ADE: mimic CHF or pneumonia

• fosfomycin→ covers VRE, ESBL, KPC, pseudomonas

  • 3g, 1 dose ONLY ($$)

  • avoid: pyelonephritis

  • ADE: GI SE common

• SMX/TMP→ covers typical uropathogens, resistance increasing(do not use for empiric coverage)

  • avoid: sulfa allergies

2nd line- due to increased resistance

• cipro, levo, delafloxacin

  • so many ADE

• beta lactams: pediatric pts, recurrent UTI more common with BL

urethritis

• most likely an STD

  • when negative urine culture w/ +WBC in urinalysis + lack of response to abx treatment

urethritis treatment

• azithromycin 1gm x 1 dose OR

• doxycycline 100mg BID x 7d

definition of recurrent UTI

>2 UTI within 6 months

risk factors for recurrent UTI

• correctable UT abnormality

• sexual practices or use of spermicides or diaphragms

NO evidence for: post coital voiding, hygiene, douching, tight underwear or hot tubs

treatment for prophylaxis of UTI: post coital

• TMP-SMX 40/200

• TMP-SMX 80/400

• nitrofurantoin 50-100mg

• cephalexin 250mg

treatment for prevention of UTI: chronic

• TMP 100mg 1x/d

• TMP-SMX 40/200 1x/d

• TMP-SMX 40/200 3x/week

• nitrofurantoin 50-100mg daily

• cephalexin 125-250mg daily

• fosfomycin 3g q10days

other non drug prophylaxis for recurrent UTI

• hydration(make sure not too much, >1.5L)

• cranberry (not helpful during active infection, make sure is actual active form of cranberry)

other drug prophylaxis for recurrent UTI

• vaginal estrogen in perimeno and postmenopausal women

• methenamine hippurate→ LAST RESORT

  • in the urine is changed to formaldehyde

  • don’t use with vitamin C→ specific pH is needed to change into formaldehyde

complicated UTI

• is beyond the bladder, typically kidney type infection

• treatment will differ based on if the patient is septic or not

treatment of complicated UTI with sepsis- with or without shock

• 3rd GCephalosporin or 4th GC

• carbapenems

• pip-tazo

• fluoroquiolones

treatment of complicated UTI without sepsis- IV route

• 3rd GCephalosporin or 4th GC

• pip-tazo

• fluoroquiolones

treatment of complicated UTI without sepsis- PO

• fluoroquinolones

• SMX-TMP

what IV abx for complicated UTI cover pseudomonas

• cefepime: 1-2g every 8-12 hours

• ceftazidime: 1-2g every 8 hours

• pip-tazo: 4.5g every 8 hours

most common empiric abx for complicated uti

• ceftriaxone: 1-2g daily

can you use another drug as a surrogate marker for susceptibilty

NO- sometimes you can make inferences but specifically for the exam pick one of the drugs that it says it is susceptible to!

duration of therapy for complicated UTI

fluoroquinolones:

• 5-7d

non-fluoroquinolones:

• 7d

what abx can you use for complicated UTI caused by CTX-M(ESBL) bug

• fosfomycin IV

• SMX-TMP IV or PO (if S)

• cipro/levofloxacin IV or PO (if S)

• meropenem, imipenem, ertapenem IV (if S)

  • this is likely what you would start with

what abx can you use for complicated UTI caused by MECA/MECC(MRSA) bug

• vancomycin IV

• daptomycin IV

• linezolid IV or PO

what is true about catheter associated UTIs

• common to see more resistance

• important to remove as soon as possible to decrease risk

carbapenem resistant enterobacteriacae (CRE)

• difficult as it knocks out most:

  • PCN

  • cephalosporins

  • carbapenems

prostatitis

• inflammation of prostate gland from infection→ due to reflux of infected urine back into the gland

prostatitis acute sx

• chills

• fever

• dysuria

• irritation

• increased uriniary frequency

• localized rectal pain

• urinary training

prostatitis chronic sx

• difficulty urinating

• epididymitis

• lower back pain

• recurrent UTIs

• urethritis

acute prostatitis treatment duration

• @ least 2-4w

chronic prostatitis treatment duration

• @ least 6-12 w

outpatient prostatitis treatment options

• ciprofloxacin 500mg BID 10-14d

• levofloxacin 500-750mg daily 10-14d

• SMP-TMP (if S)

inpatient prostatitis treatment

• cipro or levo IV

• pip-tazo + aminoglycoside

• cefotaxime

• ceftazidime

prostatitis treatment monitoring

• improvement should be within 48-72hrs

• follow up urine culture results

• optimization of therapy and monitor drug therapy as needed

UTI in pregnancy

• ALWAYS treat→ even if no symptoms for a total of 7d

  • lower UTI: nitro or cephalosporin

  • upper: IV ampicillin+gentamycin or Extended Spectrum BetaLactam

UTI in pediatrics

• treatment total for 7 days

• avoid fluoroquinolones and tetracyclines

TMP-SMX treatment monitoring

• SCr→ CrCL<30

• K→ prolonged use= increased K

nitrofurantoin monitoring

• SCr→ CrCL<30

• liver (periodic for cholestasis)

fluoroquinolone monitoring

• SCr→ CrCl<50

• liver→ acute or chronic injury

• QTc→ >500 can increase risk of TdP

• blood glucose (hypo/hypers)

beta-lactams monitoring

• SCr→ check CrCl, differs from drug to drug

• anaphylaxis

pros and cons of nitrofurantoin for UTI

pros:

• low resistance rates

• low costs

cons:

• longer treatment duration→ 5d

• not useful for pyelonephritis

• renal issues→ efficacy and toxicity

pros and cons of fosfomycin for UTI

pros:

• single dose

• broad spectrum

• low resistance rates

cons

• high cost

• low availability

• not useful for pyelonephritis

pros and cons of SMX-TMP for UTI

pros:

• good efficacy for cystitis and pyelonephritis

• low cost

cons:

• higher resistance rates

• sulfa allergy

• avoid in 1st trimester of pregnancy

pros and cons of fluoroquinolones for UTI

pros:

• good efficacy for cystitis and pyelonephritis

• likely susceptible if first UTI

• shorter treatment duration(3d)

cons:

• collateral damage

• lots of potential ADE

• avoid in pregnancy, children

pros and cons of BL for UTI

pros:

• lower rates of resistance

• relatively low costs

cons:

• more treatment failures than others

• longer treatment duration(5-7d)

• frequent dosing

• PCN allergies common

asymptomatic bacteriuria treatment indicated for:

• immunocompromised individuals

• pregnant patients- screen @ 1st visit

• prior to invasive urological procedure

NOT indicated for:

• healthy women

• older adults

• people with diabetes, indwelling catheters or spinal cord injuries

nitrofurantoin ADE

• avoid CrCl<30

• avoid in pyelonephritis

• can mimic CHF, pneumonia

TMP-SMX ADE

• not recommended for empiric therapy→ due to increased resistance

• avoid if ‘sulfa’ allergy

• avoid if 1st trimester of pregnancy

fosfomycin ADE

• avoid in pyelonephritis (PO)

• Gi SE are common

fluoroquinolones ADE

• tendonitis/tendon rupture→ any tendon, up to 6mo-1yr after

  • risk if increased with corticosteroid use

  • 50% within 14d of use

    • levofloxacin- most

    • ciprofloxacin

    • moxifloxacin -least

• peripheral neuropathy(sensory and motor)→ can be from a short course

• CNS: can cause seizures(removes inhibition), acute encephalopathy

• CDI: strong association due to collateral damage

• glucose regulation

• phototoxicity

• aortic aneurysm/dissection→ high mortality, 1/1376 collagen turnover

• psychiatric rxn→ some mania or acite anxiety

  • insomnia with levofloxacin

  • delirium with cipro and moxi

• QTc prolongation: cardiotoxicity, increased risk of TdP

• avoid in pregnancy and children

gram negative intrinsic resistance mechanisms

• abx must make it through porins and evade efflux transporters and BLases to get into the site

  • these do not change as much

gram positive intrinsic resistance mechanisms

• receptors change more frequently

  • help increase resistance to abx

  • plus need to avoid BLases to not be inactivated

beta lactamases

• all have serine at the active site

  • Class A

  • Class C

  • Class D

class A beta-lactamases

• ESBL→ SHV, TEM, CTM-X(most common), KPC

• these hydrolyze 3rd GC

class C ‘cephalosporinases’

• AmpC, CMY, FOX, MOX

class D beta lactamases

• OXA (oxacillin hydrolyses)

  • some can also hydrolyze carbapenems

metallo- Blactamases: class B

• Zn at the active site

  • IMP, VIM, NDM-1

ecoli beta-lactamases

WT:

• TEM-1= resistance to PCN, amox and amp

  • due to hyperproduction= R to 1st gen cephalosporins (cefazolin)

• ADD a BLI to overcome this

mutation:

• ESBL 3rd GC hydrolysis

• R to cefepime and pip-tazo

  • typically still S to carbapenems

klebsiella pneumonia beta lactamases

WT:

• SHV-1→ resistance to PCN, amox, and amp

  • usually still S to cephalosporins

• ADD BLI to increase susceptibility- especially with pipercillin

mutation:

• SHV-1= ESBL hydrolyze 3rd GC

  • R to cefepime and pip-tazo

  • still S to carpenems

class C: ampC- HECK YES

Enterobacter cloacae

citrobacter freundii

klebsiella aeruogenes

• assume all are R to 3rd GC (except for cefepime)

class D: OXA- acinetobacter

• some can hydrolyze carbapenems→ this would typically be the DOC for this bug

• overcomes BL stability (bulky R1 group to block hydrolysis)

pseudomonas aeruginosa- MDR (relatively rare→ all come together)

• OM→ <10% of porin proteins found in typical E.coli

  • slow process to cross outer membrane

  • oprD- imipenem and meropenem

• chromosomal BL- ampC(PDC) pseudo derived

  • inducible→ slow hydrolysis/ interaction coupled with slow entry

• efflux: MexAB-oprM

resistance from PBP in gram negative

• PBP is super conserved here→ uncommon for resistance due to mutations to arise here

• carbapenem resistance in Proteus, Providenci and Morganella

resistance in gram + is due to

alternate PBP acquired from an amino acid change

what BLases are inhibited by BLI

• class A

• class C

• class D

• they can also inhibit some metallo b-lactamases→ class B

molecular resistance detection

• not 100% detection

• specific resistance for specific bugs

MRD for enteroccus faecalis/faecium

• VanA (VRE)

MRD for staph aureus

• MecA/C

MRD for enterobacterales (Ecoli, K.pneumoniae)

• CTX-M(ESBL)

• or carbapenemases: KPC, IMP, NDM, OXA, VIM

concentration independent killing

• see MAX kill rate—> @ a certain point does not do better to increase the concentration

concentration dependent killing

• PEAK dependent

• rate and extent of the killing increases when the concentration is greater than MIC

  • examples of this are aminoglycosides, fluoroquinolones

time dependent killing

• continuous infusion

• limited increase in the rate and extent of killing w a concentration greater than MIC

  • BL are MAX killing at 4x MIC

what fluoroquinolone can you not use for CAP

ciprofloxacin