DND ID (midterm): Therapeutics 1- general principles

What are the 3 types of antimicrobial therapy?

Pt, bug, then drug

1.) Prophylaxis

2.) Empiric

3.) Definitive

Prophylactic Therapy

prevents an infection that has NOT YET developed

- high risk pts!

- CD4 <200

- surgical prophylaxis

Empiric Therapy

Suspected or proven infection

- responsible pathogen NOT YET identitfied

- best guess of agents most active against likely pathogens

Definitive Therapy

antibiotic therapy targeted to a specific microorganisms AFTER culture and antimicrobial susceptibility results are known

Which of the following scenarios most describes a pt w. an infectious disease?

A) 72 year old male, T 98.6, WBC 6,000, neutrophils 50%, bands 2%

B) 54 year old female, T 100.4, WBC 15,000, neutrophils 88%, bands 14%

C) 42 year old male, T 99, WBC 9,000, CRP 5 mg/dL, ESR 15 mm/hr

D) 23 year old female, T 98.7, WBC 8,000, procalcitonin <0.01 ng/mL

B) 54 year old female, T 100.4, WBC 15,000, neutrophils 88%, bands 14%

What is a fever?

elevation of body temp above NL

- oral= 98-98.6F

- CDC def= 100.4F

- non-specific symptom of infection

T or F: WBCs are leukocytes

True

- protects against infectious diseases and foreign invaders

What is Leukocytosis?

High WBC count

- in response to infection

- non-specific causes= stress, corticosteroids, malignancy

- normal range= 4000-10000 cells/mm

What do each part of a WBC differential tell you about infections?

Neutro: acute bacterial infections

- viral, fungal

- segs (mature) and bands (immature)

Lympho: viral or fungal infections

- TB

Monocytes: Chronic infections

- TB and lymphoma

Eosino: Parasitic Infections

- also allergic rxns

Baso: RARE allergic rxns

Are CRP and ESR biomarkers of infection?

YES!

- non-specific markers

- does not confirm infection

- RA, acute MI, and Crohn's

- Normal CRP= <10 ng/mL

- Normal ESR= <22 mm (M)/hr <29 (F)

T or F: Lactate is a biomarker for sepsis

true

- impaired tissue oxygenation

- normal= 0.5-1 mmol/L

T or F: Procalcitonin is a more specific marker of "bacterial" infections

True

- used to discontinue antibiotics

- need clinical judgement

- normal= <0.25 ng/mL

What are some local signs of infection?

1) @ site of infection

- pain, erythema, swelling, tenderness, purulent discharge

2) Imaging: x-ray, CT, MRI, echi

- inflammation, infiltrate, collection of lfuid

3) Tissue or fluid sample

- presence fo WBCs and bacteria

- ie) sputum, urine, SF, joint fluid

What changes indicate a more severe infection?

Hemodynamic changes

- HR and BP

Respiratory changes

- RR, rapid breathing, SOB

Neurologic

- altered mental status, lethargy, confusion, psychosis

Establish site of infection:

•Dysuria, flank pain, abnormal urinalysis?

Urinary Tract (UTI)

- Dysuria --> bladder involvement (cystitis)

- flank pain --> upper urinary tract infection (Pyelenophritis)

- and obvs abnormal urinalysis

Establish site of infection:

•Cough, chest pain, sputum, +CXR?

Lungs (Pneumonia)

- positive findings in chest X-ray

- obvs cough, chest pain, sputum

Establish site of infection:

•Headache, altered mental status, +LP?

CNS (meningitis/encephalitis)

- positive findings in lumbar puncture

- AMS and headache

Establish site of infection:

Fever, heart murmur, +blood cultures, +TTE?

Heart (Infective Endocarditis)

- positive findings in blood culture and transthoracic echocardiogram

Establish site of infection:

•Pain at IV site (central line), swelling, erythema, +cultures?

Central Line Catheter Infection

- infection in bloodstream

Non-lactose fermenting, gram-negative rods suggest:

A.Pseudomonas aeruginosa

B.Staphylococcus aureus

C.Streptococcus pneumoniae

D.E. coli

A.Pseudomonas aeruginosa

Gram-positive cocci in clusters suggest:

A.Pseudomonas aeruginosa

B.Staphylococcus species (S. aureus, S. epidermidis)

C.Streptococcus species (S. pneumoniae)

D.E. coli

B.Staphylococcus species (S. aureus, S. epidermidis)

What are the 2 specimen types?

Sterile

- blood

- sputum (deep)

- urine

- CSF and joint fluid

- tissue

- abscess

Non-sterile

- stool

- throat swab

- wound swab

- genital swab

T or F: Blood cultures are collected when pt is acutely ill

true

- incubated for 5-7 days

- 2 sets, 2 body sites

- 1 set= 1 aerobic and 1 anaerobic

How should urine cultures be collected?

clean catch midstream or via catheter

- never collect urine from catheter bag

- use needle to collect from tubing

Urine Dipstick vs Urinalysis

Dipstick: Rapid screening

- leukocytes, nitrites, blood, etc

Urinalysis: under microscope

- appearance and bacteria load

- WBCs (>4000 cells/mm)

- epithelial cells and RBCs

Gram stain on Gram (+) vs Gram (-)

Cell Wall on Gram (+) vs Gram (-) Bacteria

Gram (+)

- no LPS

- no outer membrane

- THICK peptidoglycan layer

Gram (-)

- LPS

- outer membrane

- THIN peptidoglycan layer

Gram (+) aerobes

Cocci

- chains & pairs (strep/entero)

- clusters (stap A. staph ep.)

Bacilli/rods

- corynebacterium

- listeria

Gram (+) anaerobes

Cocci

- pepto

- peptostrepto

Bacilli/rods

- clostridium

Gram (-) aerobes

Bacilli/rods

- lactose fermenting (e. coli, enterbac, klebsiella)

- non-lactose (pseudo a. and acinetobacter)

Cocci

- neisseria

- n. gonorrhoeae

- haemophilius influenzae

Gram (-) Anaerobes

Bacilli/rods

- Bacteroides spp

- fusobacterium spp

- prevotella spp

Atypical bacteria include...

- mycoplasma

- legionella

chlamydophila

Mycobacteria vs Fungi vs Viral Species

Mycobacteria

- mycobactrium tuber, mycobacterium avium

Fungi

- aspergillus, candida, cryptococcus, histoplasma, tinea

Viruses

- flue, hep A/B/C/D/E, HIV, herpes, RSV, EBV

Contaminate vs Colonizer vs Pathogen

Contaminate

- introduced into specimen from external source

- poor technique/sample/collection

Colonizer

- "normal flora" does not cause harm

Pathogen

- damages tissue, elicits host response

Respiratory cultures were sent. Preliminary microbiology report reveals gram negative rods, non-lactose fermenting. Final report: Pseudomonas aeruginosa. Two sets of blood cultures were also sent. Preliminary microbiology report 1 out of 2 sets of blood cultures reveals gram positive cocci in clusters, coagulase negative. Final report: Staphylococcus epidermidis

Patient is currently on piperazillin-tazobactam and vancomycin.

Which of the following is the most appropriate antibiotics for RJ based on his cultures?

A.Continue piperacillin-tazobactam and vancomycin

B.Continue piperacillin-tazobactam and discontinue vancomycin

C.Continue piperacillin-tazobactam, start amikacin, and discontinue vancomycin

D.Discontinue piperacillin-tazobactam and vancomycin and start ciprofloxacin

B.Continue piperacillin-tazobactam and discontinue vancomycin

Which antibiotics cover P. Aeruginosa?

- beta-lactams

- floroquinolones

- aminglycosides

- combination drugs

What is the minimum inhibitory concentration (MIC)?

Lowest drug conc that prevents visible growth of an organism after 24 hrs in vitro

- good indicator of antibiotic potency

- MIC values are different for each organism-antibiotic pair

What is the CLSI? What do they do?

Clinical Lab Standards Institute

- establish MIC breakpoints for each organism to each antibiotic

- updated annually

What are antibiograms used for?

deciding empiric antimicrobial therapy

- cumulative report of antibiotics

- % susceptible or resistant

Vancomycin was discontinued. S. epidermidis was determined to be a contaminate since it only grew in 1 out of 2 sets of blood cultures and it is a common normal skin flora. Respiratory cultures were sent. Preliminary microbiology report reveals gram-negative rods, non-lactose fermenting. Final report: Pseudomonas aeruginosa

Is piperacillin-tazobactam the best choice for empiric antimicrobial therapy for nosocomial gram-negative coverage?

Yes!

- If the strain is susceptible, therapy can continue

- In resistant cases, alternatives may be used

Is it a true allergy, toxicity, or intolerance:

nephrotoxicity w/ gentamicin?

True allergy

Is it a true allergy, toxicity, or intolerance:

diarrhea w/ doxycycline?

Intolerance

Is it a true allergy, toxicity, or intolerance::

Hives and SOB w/ penicillin?

true allergy

Is it a true allergy, toxicity, or intolerance::

thrombocyptopenia w/ linezolid?

toxicity

Is it a true allergy, toxicity, or intolerance::

SJS w/ TMP/SMX?

true allergy

What % of the US reports they're allergic to penicillin? What % is TRULY allergic?

10% reports PCN allergy

- 1% is truly allergic

- if pt is TRULY allergic, use alternative meds, graded challenge, and desensitization

T or F: 80% of pts w/ IgE-mediated PCN allergies lose their sensitivity after 10 years

true

- decreases by 10% per year of avoidance

T or F: Certain antimicrobial drug tx should be avoiding in certain age groups

true

- ie) ceftriaxone in neonates should be AVOIDED

- WHY? hyperbilirubinemia and interactions w/ Ca

What numerical value assesses hepatic function?

Child Pugh Score

T or F: Pregnant and lactating women can shouldn't take certain drugs because it puts them and their child at risk

True

- teratogenicity

- altered PK (increased Vd, renal blood flow, hep and metab activities)

- antibiotics conc. in breast milk

Pts with G6PD may experience hemolytic anemia when taking...

- dapsone

- primaquine

- nitrofurantoin

Pts w/ HLA-B*5701 allele may experience a hypersensitivity reaction with what drug?

Abacavir

Why are diabetes pts more susceptible to infection?

they have poor peripheral blood flow

- causes higher risk of infection

- more difficult to treat

Why are pts w/ chronic lung disease/cystic fibrosis more susceptible to infection?

There are different microorganisms

Why are HIV/AIDS pts more susceptible to infection?

their immune system is suppressed

T or F: different antibiotic dosing is required depending on the location of the infection

True

- aminoglycosides in uncomplicated UTI vs severe infection

Which antibiotic has better penetration/concentration:

Cefepime vs piperacillin/tazobactam in CNS?

Cefepime

Which antibiotic has better penetration/concentration:

Polymyxin B va Colistin in URINE?

Colistin

Which antibiotic has better penetration/concentration:

Daptomycin in PNEUMONIA?

Daptomycin is NOT EFFECTIVE in pneumonia

T or F: You should start antibiotic treatment with IV then switch to PO if an infection is severe

True

What is time-dependent killing (T>MIC)?

Rate/extent of bacterial killing depends on the time the active drug conc remains above MIC

- ie) Beta-lactams

What is concentration-dependant killin (Cmax:MIC)?

Rate/extent of bacterial killing depends on antimicrobial conc

- ie) aminoglycosides and fluoroquinolones

Benefits of prolonged infusion of Beta-Lactams

maximize the duration that pathogen is exposed to beta-lactam

- time-dependent

- T>MIC

- prolonged infusion over 3-4 hrs (not 30 min)

- good for critically ill pts and pathogens w/ high MICs

Benefits of Extended Interval Aminoglycoside Dosing

Decreases nephrotoxicity

- Cmax:MIC for rapid killing

- high dose ONCE daily

- Gentamicin 5-7 mg/kg q24h

- Amikacin 15 mg/kg q24hr

- easy admin and drug monitoring

Why is combination therapy preferred?

Broad spectrum coverage (esp for mixed/nosocomial infection)

- SYNERGISTIC (1+1=2)

- prevent resistance

What is an example of a synergistic drug combo?

Beta-lactam + aminoglycoside

- enterococcal endocarditis --> rapid killing!

What are some disadvantages of combo drug therapy?

- superinfection

- toxicities

- antagonistic effects

- $$$

When do we know its ok to switch antibiotic from IV to PO?

- overall clinical improvement

- no fever for 24 hrs

- decrease WBC

- functioning GI tract

Which antibiotics have great oral bioavailability?

- ciprofloxacin and levofloxacin

- clindamycin

- doxycycine

- metronidazole and moxifloxacin

- linezolid

- TMP/SMX

What antibiotics cover MRSA?

- Vancomycin/Clindamycin/Daptomycin

- Linezolid Tedizolid

- TMP/SMX

- Doxycycline/Tigecycline

- etc!

What is intrinsic resistance?

resistance is natural to the organism

- ie) vancomycin vs gram (-) bacteria

- ie) cephalosporins vs enterococcus

What is acquired resistance?

caused by prior exposure to the antibacterial (inappropriate use of abx)

- decreased permeability

- efflux pump

- drug inactivation/mod

- altered target site

What is MRSA?

methicillin-resistant staphylococcus aureus

- altered target site: PBP2 --> PBP2a

- resistant to meth, oxa, nafc

- 1st line: VANCOMYCIN

- alt: dapto, linezolid, ceftatro

What is VRE?

Vancomycin-resistant Enterococcus

- altered target site: D-ala-D-ala --> D-ala-D-lac

- 1st line: Dapto, linezolid

What is EBSL?

Extended spectrum beta-lactamases

- hydrolyze beta-lactam ring

- inactivate most beta-lactams

- gram (-) bacteria

- 1st line: carbapenams

What is CRE?

Carbapenem-resistant Enterobacterales

- carbapenamases inhibit ALL beta-lactams

- 1st line: combo drugs like polymyxin, ceftazidime/avibactam, meropenem/vaborbactam