Ios 10 Exam 4 Kuma Dlp

Front 1

SEPSIS:
What is the goal of antimicrobial therapy?

Back 1

#1 Cover bug with Correct drug...EARLY

Empiric therapy:
Use intensive empiric regimen for type of infection and patient characteristics (e.g. immunocompromised) then narrow therapy according to culture/sensitivity.

Front 2

SEPSIS:
What is SIRS?

Back 2

Systemic Inflammatory
Response Syndrome
(SIRS)
> or = 2 of the following criteria:
* Temperature >38 C or <36 C
* Heart rate >90 bpm
* Respiratory Rate >20 bpm or PaCO2 <32 torr
* WBC >12,000, <4,000 or >10% bands

Front 3

SEPSIS:
Define sepsis.

Back 3

SIRS + infection

Front 4

SEPSIS:
Define severe sepsis.

Back 4

Sepsis with organ dysfunction, hypoperfusion or hypotension

Front 5

SEPSIS:
Define septic shock.

Back 5

Sepsis with hypotension (SBp < 90 mmHg or drop of 40) and perfusion abnormalities despite adequate volume resuscitation

Front 6

SEPSIS:
What are common causes of SIRS?

Back 6

Pancreatitis
Trauma
Burns
Hemorrhage
Other

Front 7

SEPSIS:
What types if infections lead to sepsis?

Back 7

Bacteremia
Fungemia
Others

Front 8

SEPSIS:
Explain the evolution of Sepsis.

Back 8

Localized infection leads to
Toxin release which leads to
Inflammatory cytokines released which leads to
Neutrophil activation which leads to
Endothelial injury

Front 9

SEPSIS:
What is the final common pathway for sepsis?

Back 9

Endothelial Dysfunction and Microvascular Thrombosis
leads to
Hypoperfusion/Ischemia
leads to
Acute Organ Dysfunction
(Severe Sepsis)
leads to
DEATH

Front 10

SEPSIS:
Acute Organ Dysfunction associated with severe sepsis

Back 10

* Brain
- Altered consciousness
- Confusion
- Psychosis

* Lungs
- Tachypnea
- PaO2 <70 mm Hg
- SaO2 <90%
- PaO2/FiO2 < or = 300
* Liver
- Jaundice
- increased enzymes
- decreased albumin
- increased PT

* Heart
- Tachycardia
- Hypotension
- increased CVP
- increased PAOP

* Kidneys
- Oliguria
- Anuria
- increased creatinine

* Bone marrow
- decreased platelets
- increased PT/APTT
- decreased Protein C
- increased D-dimer

Front 11

SEPSIS:
What are Septic Shock treatment goals?

Back 11

* Objective is to increase preload (PCWP) with fluid replacement (crystalloid, then colloid), then increase afterload (SVR) with vasopressor pharmacotherapy (dopamine, norepinephrine, phenylephrine, vasopressin).
* Always provide fluid resuscitation before vasopressors.
* Therapy to achieve arterial pressure (MAP ≥ 65 mmHg with CVP 8-12 mmHg), urine production (≥ 0.5 mL/kg/hr), skin perfusion, mental status, and indexes of perfusion (↓ lactate, S(c)VO2 ≥ 70%) (grade 1C).

Front 12

SEPSIS:

Case:
59 yo male (95 kg) with Wegener’s disease (low dose steroids) uncontrolled diabetes, dialysis depended end stage kidney disease admitted for altered mental status with fever.
Tx to ICU for SIRS, SOB, anion gap acidosis, requiring MV, altered mental status, anuric, Bp = 76/42 and HR = 120’s. Received 2L NS with minimal response.
APACHE II score > 25 (58).
Platelets = 20,000/L, WBC = 1.8/L, Hct = 0.22, Scr = 8.9, INR = 2.7, Alb = 1.8 g/dL, Ast/Alt = elevated to thousands, tBili = 5.2, Lactate = 8 mmol/L, Glucose = 230 mg/dL.

In conjunction with additional fluid administration, which vasopressor(s) should be initiated and why?

Back 12

Norepinephrine
b/c it is generally better and pts HR is already 120 and NE has less effect on HR.

Front 13

SEPSIS:

Case:
59 yo male (95 kg) with Wegener’s disease (low dose steroids) uncontrolled diabetes, dialysis depended end stage kidney disease admitted for altered mental status with fever.
Tx to ICU for SIRS, SOB, anion gap acidosis, requiring MV, altered mental status, anuric, Bp = 76/42 and HR = 120’s. Received 2L NS with minimal response.
APACHE II score > 25 (58).
Platelets = 20,000/L, WBC = 1.8/L, Hct = 0.22, Scr = 8.9, INR = 2.7, Alb = 1.8 g/dL, Ast/Alt = elevated to thousands, tBili = 5.2, Lactate = 8 mmol/L, Glucose = 230 mg/dL.
Should corticosteroids be initiated?

Back 13

Yes, mainly b/c the patient is already on low dose steroids so bump the dose up to treatment dose.

Front 14

SEPSIS:

Case:
59 yo male (95 kg) with Wegener’s disease (low dose steroids) uncontrolled diabetes, dialysis depended end stage kidney disease admitted for altered mental status with fever.
Tx to ICU for SIRS, SOB, anion gap acidosis, requiring MV, altered mental status, anuric, Bp = 76/42 and HR = 120’s. Received 2L NS with minimal response.
APACHE II score > 25 (58).
Platelets = 20,000/L, WBC = 1.8/L, Hct = 0.22, Scr = 8.9, INR = 2.7, Alb = 1.8 g/dL, Ast/Alt = elevated to thousands, tBili = 5.2, Lactate = 8 mmol/L, Glucose = 230 mg/dL.
Would you use activated protein C in this patient?

Back 14

Possibly, he is pretty sick and his labs support possible liver failure in addition to his already failing kidneys.

Front 15

SEPSIS:
Why does vasodilation occur in septic patients?

Back 15

* Direct vascular mediators of dilation include NO, PGE1, and prostacyclin.
* Reduced adrenergic receptor density.
* Reduced adrenergic receptor sensitivity.
* Relative deficiencies of cortisol and vasopressin.
* Result = tachycardia to increase CO but myocardial contractility dysfunction.

Front 16

SEPSIS:
What role do cytokines play in spesis?

Back 16

* From macrophages and endothelium
* Response regulated by proinflammatory and anti-inflammatory mediators
* Initiate overlapping processes that directly influence endothelial, hemodynamic, and coagulation mechanisms
* Net effect: enhanced inflammation, enhanced coagulation, reduced fibrinolysis

Front 17

SEPSIS:
How is cytokine homeostasis affected in sepsis?

Back 17

The loss of homeostasis in sepsis. The pathophysiology of sepsis includes the activation of inflammation, the activation of coagulation, and impairment of fibrinolysis. This creates an imbalance in normal homeostasis between procoagulant and anticoagulant mechanisms. PAI-1, plasminogen activator inhibitor-1; TAFIa, thrombin activatable fibrinolysis inhibitor

Front 18

SEPSIS:
What type of shock is septic shock and what is the initial driving mechanism?

Back 18

distributive
Decrease in systemic vascular resistance

(This raises CI to compensate but ultimately leads to decreased PCWP and hypotension)

Front 19

SEPSIS:
First initial therapy for sepsis?

Back 19

Fluid replacement

Front 20

SEPSIS:
Types of fluid replacement

Back 20

Crystalloid
- NS (usually first choice)
- Lactated ringers

Colloid
- Albumin 5% (first choice in special circumstances)
- Hetastarch 6%

Blood products
- FFP
- PRBC

Front 21

SEPSIS:
What is the volume effect of NS in a septic patient?

Back 21

0.20-0.25:1
So for every liter you give, the patient's fluid increases by 200 mL - 250 mL. (20-25%)

Front 22

SEPSIS:
What is the duration of action of Normal Saline?

Back 22

Minutes

Front 23

SEPSIS:
What is the volume effect of Albumin 5%?

Back 23

1.3-1.5:1
So it actually brings more fluid into the vasculature from third compartment space.

Front 24

SEPSIS:
What is the duration of action of Albumin 5%?

Back 24

About 6 hours

Front 25

SEPSIS:
What is the volume effect of FFP?

Back 25

1:1
What you give is what they get.

Front 26

ὃπου

Back 26

where
(+ ἂν or ἐάν - wherever, whenever)

Front 27

SEPSIS:
What is the volume effect of PRBC?

Back 27

1-1.5:1

Front 28

SEPSIS:
What is the duration of action of PRBC?

Back 28

> 12 hours

Front 29

What do the studies tell us about using NS vs. Albumin 5% in septic shock?

Back 29

There is no statistically significant difference in mortality, so Normal saline and albumin considered equivalent for resuscitation (grade 1B).

First line: Normal saline (2-10L) is THE preferred initial fluid replacement.

2nd line: Albumin may be agent of choice when tolerance to normal saline occurs (evidence of volume overload) especially if hypoalbuminemia, renal dysfunction, hepatic dysfunction, or heart failure are present.

Front 30

When is PRBC transfusion recommened based on the evidence?

Back 30

PRBC transfusion to maintain Hgb of 7-9 g/dL except resuscitation when goal is Hct ≥ 30% (grade 1C).

Front 31

What receptors does Dopamine act on at a dose of < 5mcg/kg/min?

Back 31

Dopa (++++) which acts to decrease systemic vascular resistance and may increase urinary output.

Beta-1 (+/++) whihc increases cardiac index

Alpha-1 and beta-2 are not effective.

Front 32

What receptors does Dopamine act on at a dose of 5-10 mcg/kg/min?

Back 32

Beta-1 (++++) which increases cardiac index

Dopa (+++) which decreases systemic vascular resistance and may increase urinary output.

Beta-2 (+) which decreases systemic vascular resistance

Alpha-1 (0/+) which acts to increase systemic vascular resistance

Front 33

What receptors does Dopamine act on at a dose of > 10 mcg/kg/min?

Back 33

Beta-1 (++++) which increases cardiac index

Alpha-1 (+++) which acts to increase systemic vascular resistance

Dopa (+) which decreases systemic vascular resistance and may increase urinary output.

Beta-2 (+) which decreases systemic vascular resistance

Front 34

What receptors does Norepinephrine
act on?

Back 34

Alpha-1 (++++) which acts to increase systemic vascular resistance

Beta-1 (++) which increases cardiac index

Beta-2 (+) which decreases systemic vascular resistance

No effect on Dopa

Front 35

What receptors does phenylephrine work on?

Back 35

Alpha-1 (++++) which increases systemic vascular resistence

Beta-1 (0/+) which increases cardiac index

No effect on Beta-2 or Dopa

Front 36

What receptors does Epinephrine work on?

Back 36

ROCKET FUEL
Alpha-1 (++++) which increases systemic vascular resistence

Beta-1 (+++) which increases cardiac index

Beta-2 (+/++) which decreases systemic vascular resistance

No effect on Dopa

Front 37

What receptors does Dobutamine work on?

Back 37

Beta-1 (++++) which increases cardiac index

Beta-2 (++/+++) which decreases systemic vascular resistance

Alpha-1 (+/++) which increases systemic vascular resistence

No effect on Dopa

Front 38

Potential Side Effects of Dopamine?

Back 38

Increased HR
minor increase in Co
minor increase in SVR
minor decrease in gut mucosal oxygenation
decrease in gut motility
minor decrease in T-cell, GH, thyroid

Front 39

Potential Side Effects of Norepinephrine?

Back 39

little to no effect on HR and CO
(small increase if effect)
Increase SVR
little to no effect on gut mucosal oxygenation (small increase if effect)
little to no effect on gut motility (small increase if effect)
no neuro-endocrine effects (?)

Front 40

Possible side effects of phenylephrine?

Back 40

little to no effect on HR and CO (small decrease if effect)
little to no effect on SVR (small increase if effect)
minor increase in gut mucosal oxygenation
little to no effect on gut motility (small decrease if effect)
No neuro-endocrine effects (?)

Front 41

Possible side effects of Epinephrine?

Back 41

Increased HR
Minor increase CO
Minor increase SVR
minor decrease in gut mucosal oxygenation
little to no effect on gut motility (small decrease if effect)
minor increase in glucose, apoptosis, decrease in TNF

Front 42

Possible side effects of Dobutamine?

Back 42

Increase in HR and CO
little to no effect on SVR (small decrease if effect)
increase in gut mucosal oxygenation
no effect on gut motility (small decrease if effect)
Like Epinephrine (?)

Front 43

Possible side effects of Vasopressin?

Back 43

no effect on HR
minor decrease in CO
Increase in SVR
little to no effect on gut mucosal oxygenation (small decrease if effect)
no effect on gut motility
Decrease in Na and Plts

Front 44

What is the titration goal for vasopressors?

Back 44

The goal is to titrate the dose to MAP > or = 65 mmHg

(Except vasopressin)

Front 45

What are the prefered agents for vasopressor therapy?

Back 45

* Dopamine or Norepinephrine (NE) (grade 1C). (Dr. Mueller likes Norepinephrine)
* Epinephrine, phenylephrine, or vasopressin should NOT be the initial vasopressor (grade 2C). Vasopressin 0.03 U/min may be subsequently added to norepinephrine with anticipation of effect equivalent to norepinephrine alone.
* Epinephrine is the FIRST chosen alternative in shock poorly responsive to dopamine or NE (grade 2B).
* Dobutamine in the presence of myocardial dysfunction as evidenced by elevated cardiac filling pressures and low cardiac output (grade 1C).

Front 46

Vasopressin MOA and Dosing

Back 46

* Acts at vasopressin (V) receptors:
- Vascular V1 receptors enhance calcium release from sarcoplasmic reticulum to vasoconstrict. Greatest vasoconstriction in skin, skeletal muscle, fat, pancreas, and thyroid gland.
- Renal V2 receptors enhance fluid retention in collecting tubules but vasoconstriction of efferent > afferent increases GFR: net effect is increase urine output.
- V3 receptors increase ACTH (cortisol) release.
* Dose for sepsis: 0.01 – 0.04 units/min (not to be titrated to response as this is replacement dosage). Dose for HRS: start at 0.02 units/min and titrate by 0.02 units/min q 6hrs until either urine production, 20-25% MAP increase or ADR (ischemia on EKG or lactate). Mean dose for response 0.23 ± 0.19 units/min @ 3.2 ± 2.1 days.

Front 47

Vasopressin release in septic shock

Back 47

* Vasopressin is normally produced in hypothalamus and released from posterior pituitary.
* Becomes elevated within hours of vasodilatory shock but depleted thereafter.
* Stimuli of release: high plasma osmolality, hypovolemia / hypotension, acidosis, hypoxia, hypercarbia, pain, acetylcholine, histamine, nicotine, dopamine, prostaglandins, angiotensin II, proinflammatory cytokines.
* Nitric oxide, corticosteroids, and beta-adrenergic stimulation inhibit release.

Front 48

What was the significance of the VASST trial?

Back 48

* 27-center, R, DB study investigating vasopressin 0.01-0.03 units/min vs. NE as add-on therapy.
* Primary Hypothesis: Low dose vasopressin infusion compared to norepinephrine infusion decreases 28-day mortality from 60% to 50% in severe septic shock (N= 776, power = 80%, α= 0.05).
* Secondary Hypothesis: The beneficial effects of vasopressin are more pronounced in the subgroup of patients with more severe septic shock (≥ 15 μg/min NE).
* Patients: severe septic shock with NE ≥ 5 mcg/min for 6/24 hrs.

Serious Adverse Events were not statistically different between the NE and vasopressin arms.

Front 49

What were the outcomes of the VASST trial?

Back 49

1. Efficacy: Low dose vasopressin (0.03 U/min) plus NE is similar to NE alone in septic shock.
2. Safety: Low dose vasopressin (0.03 U/min) plus NE and NE alone have similar safety in septic shock.
3. Subgroup: Vasopressin plus NE may decrease mortality compared to NE alone in less severe septic shock – NNT = 10.
low lactate quartiles reproduce vasopressin benefit
4. Pharmacokinetics: Vasopressin (0.03 U/min) increases vasopressin levels: 80 – 120 pg/ml.
5. Cohort: Mortality of septic shock is 35 – 40 %.
6. Improved renal function when impending renal insufficiency (abstract data – in press).

Front 50

What are the potential benefits of corticosteroids?

Back 50

* Reverse adrenal insufficiency and overcome corticosteroid resistance.
* Directly and indirectly inhibit NF-kB to:
- reduce inflammation and restore cytokine homeostasis.
- reduce production of NO and increase adrenergic receptor density.
* Inhibit late inflammation to reduce production of direct vasodilators (PGE1 and prostacyclin).

Front 51

Which is better Goal directed or Standard therapy for severe sepsis or septic shock?

Back 51

Goal Directed: showed improved organ function, lowered hospital MORTALITY of 30.5% vs. 46.5% (p=0.009), and shortened hospital LOS of 14.6 ± 14.5 vs. 18.4 ± 15 days (p=0.04).

Front 52

What was the take away from the Annane vs. CORTICUS trials?

Back 52

ACTH stimulation is NOT recommended to identify patients requiring hydrocortisone (grade 2B). Hydrocortisone ≤300 mg/day should be considered when septic shock remains unresponsive to vasopressors (grade 2C).

Front 53

Activated Protein C Abnormalities in Sepsis

Back 53

* Cytokines cause down regulation of thrombomodulin expression and decrease ability to cleave thrombomodulin
* Leads to a decreased conversion of Protein C to Activated Protein C

* Net effect: decreased levels Activated Protein C

Front 54

Explain how activated protein C can help in severe sepsis or septic shock.

Back 54

The inflammatory and procoagulant host responses to infection are intricately linked. Infectious agents and inflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin-1 activate coagulation by stimulating the release of tissue factor from monocytes and the endothelium. The presentation of tissue factor leads to the formation of thrombin and a fibrin clot. Inflammatory cytokines and thrombin can both impair the endogenous fibrinolytic potential by stimulating the release of plasminogen-activator inhibitor 1 (PAI-1) from platelets and the endothelium. PAI-1 is a potent inhibitor of tissue plasminogen activator, the endogenous pathway for lysing a fibrin clot. In addition, the procoagulant thrombin is capable of stimulating multiple inflammatory pathways and further suppressing the endogenous fibrinolytic system by activating thrombin-activatable fibrinolysis inhibitor (TAFI). The conversion of protein C, by thrombin bound to thrombomodulin, to the serine protease activated protein C is impaired by the inflammatory response. Endothelial injury results in decreased thrombomodulin levels. The end result of the host response to infection may be the development of diffuse endovascular injury, microvascular thrombosis, organ ischemia, multiorgan dysfunction, and death. Activated protein C can intervene at multiple points during the systemic response to infection. It exerts an antithrombotic effect by inactivating factors Va and VIIIa, limiting the generation of thrombin. As a result of decreased thrombin levels, the inflammatory, procoagulant, and antifibrinolytic response induced by thrombin is reduced. In vitro data indicate that activated protein C exerts an antiinflammatory effect by inhibiting the production of inflammatory cytokines (TNF-α, interleukin-1, and interleukin-6) by monocytes and limiting the rolling of monocytes and neutrophils on injured endothelium by binding selectins. Activated protein C indirectly increases the fibrinolytic response by inhibiting PAI-1.

Front 55

What was the PROWESS trial looking at and what was the result?

Back 55

The use of Drotrecogin (activated protein C) vs. placebo in patients with severe sepsis.
Outcome: 6.1% decrease in absolute mortality
19.4% decrease in RR of death
38.1% increase in odds of survival
The higher the apache II score the more significant the benefit

In addition patients treated wit Drotrecogin alpha were off ventilaror a day earlier and off vasopressors a day and a half earlier than placebo.

Front 56

During the PROWESS trial, what was the main side effect they were looking for to access safety.

Back 56

Serious Bleeding Events
defined as:
* Any intracranial hemorrhage
* Any life threatening bleed (at risk of death at time of event)
* > or = 3 units of packed red blood cells/day for 2 consecutive days
* Any bleeding event that met the definition of a serious adverse event

Front 57

What were the PROWESS conclusions:

Back 57

* Reduced mortality in severe sepsis patients with acute organ dysfunction
- 1 life saved for every 16 patients treated
* Patient disposition more “efficient”
* Serious bleeding requires monitoring but frequently related to procedures

Indications (grade 2B and 2C - postop):
* APACHE II score > or = 25
* > or = 2 organ failures
* shock

Front 58

What are contraindications for Drotrecogin Alfa therapy?

Back 58

* active internal bleeding
* surgery < 12 hrs
* hemorrhagic stroke < 3 months
* CNS trauma < 2 months
* trauma with bleeding risk
* epidural catheter
* intracranial mass lesion
* hypersensitivity

Front 59

Drotrecogin Alfa Controversies

Back 59

PROWESS and ADDRESS have conflicting outcomes. PROWESS resulted in less mortality in the Drotrecogin group while Advance showed more.

Front 60

SO, bottom line...How do you treat severe sepsis/septic shock?

Back 60

* Fluid
- 2-10L normal saline quickly
- PRBC for Hct of 30% then Hgb 7-9 g/dL
* Vasopressors
- norepinephrine 0.05-1.5 µg/kg/min  phenylephrine
- vasopressin ≤ 0.04 U/min (if requiring dose escalation of other vasopressors)
- dobutamine if cardiac index < 2.5 L/min/m2 or ScVO2 < 70%
* Corticosteroids
- use stress-dose if steroid history, adrenally insufficient, and/or refractory shock requiring vasopressors
* Activated Protein C
- within 48 hours of severe sepsis (APACHE II > 25, > or = 2 organ failures, or presence of shock and if no exclusion criteria)

Front 61

What constitutes an uncomplicated UTI?

Back 61

* Healthy females aged 15-50 years
* Controversial: healthy women > 50 years

Front 62

What constitutes an complicated UTI?

Back 62

Structural abnormality
Stone
Catheter
BPH
Obstruction
Neurologic abnormalities
Male sex
Pregnant women
Immunocompromised patients
Kidney failure
Kidney transplant
Diabetes
CKD
Hospital-acquired
Greater risk

Front 63

Define Cystitis

Back 63

infection of the bladder

Front 64

Define Pyelonephritis

Back 64

infection involving the kidneys

Front 65

enjambment

Back 65

A technique in poetry that involves the running on of a line or stanza. It enables the poem to move and to develop coherence as well as directing the reader with regard to form and meaning. Walt Whitman uses this continually.

Front 66

Pathophysiology of UTI

Back 66

* Bacteria usually originate from bowel flora
* Most common route of entry = ascending, retrograde
* Women are at increased risk:
- Colonization of the female urethra and vagina with bacteria
- Shorter urethra which is in close proximity to perirectal area

Front 67

What host defenses work to prevent UTIs?

Back 67

* Urine: low pH, extremes in osmolality, high urea concentrations, high organic acid concentrations
* Micturition (complete emptying of the bladder)
* Prostatic secretions in men
* Lactobacillus in the vaginal flora
* One-way vesicoureteral valve
* Epithelial cells of the bladder coated with glycosaminoglycan (urinary mucus)
* Tamm-Horsfall protein – bind to bacteria with Type 1 fimbriae, prevents binding of bacteria to uroepithelial cells

Front 68

How do bacterial virulence factors overcome host defences?

Back 68

* Innoculum size
* Pathogenic organisms with mannose-resistant P-fimbriae bind to uroepithelial cells
- Resistance to removal by glycosaminoglycans, PMNs, secretory IgA
* Production of lysin enzymes: lyses leukocytes

Front 69

What are risk factors for UTIs in children?

Back 69

Congenital abnormalities

Front 70

What are risk factors for UTIs in young women?

Back 70

Maternal history of UTIs
Sexual activity
Diaphragm or condom use with spermicide
Pregnancy
Genetics

Front 71

What are risk factors for UTIs in young men?

Back 71

Instrumentation
Lack of circumcision (?)

Front 72

What are risk factors for UTIs in the elderly?

Back 72

Uterine prolapse
Decreased estrogen
BPH
Incontinence
Diabetes
Tumors
Neurologic disorders

Front 73

Bacterial Etiology of uncomplicated UTIs

Back 73

* Gram-negative enteric bacilli account for >80% of all infections

Acute uncomplicated cystitis:
- E. coli 75-90%
- Staphylococcus saprophyticus 5-15%
- Other enteric Gram-negative bacilli 5-10%
- Enterococcus 1-3%

Front 74

Bacterial Etiology of complicated UTIs

Back 74

Complicated cystitis:
- E. coli 40-55%
- Other enteric Gram - bacilli 25-35%, Pseudomonas aeruginosa
- Staphylococci, enterococci, yeast 15-25%

Front 75

What type of Evaluation/diagnosis is needed for proper management of UTI?

Back 75

Need to determine the type of UTI
- Uncomplicated vs. Complicated
* patient demographics & medical history

- Lower Tract vs. Upper tract infection
* presence of specific signs & symptoms
* diagnostic tests

Front 76

What are the main steps in the management of UTI?

Back 76

1. Evaluation/Diagnosis to determine type of UTI
2. Selection of Antimicrobial Agent
3. Selection of Duration of Treatment
4. Appropriate Monitoring and Follow-up

Front 77

How are lower and upper UTIs differentiated?

Back 77

Lower Tract Infection (Cystitis)
* Local symptoms are almost always present:
- dysuria
- frequency
- urgency
- suprapubic tenderness
- hematuria
- NO vaginal symptoms or discharge
* Systemic symptoms are rarely present

Upper Tract Infection (Pyelonephritis)
* Local symptoms experienced with Lower Tract infections are frequently NOT present in Upper Tract infections
* Systemic symptoms are usually present
- malaise
- fever
- flank pain (CVA tenderness)
- abdominal pain
- nasusea
- vomiting
- increased WBCs

Front 78

What diagnostic tests can be used to diagnose and evaluate a UTI?

Back 78

Urinalysis
- Macroscopic analysis (standard dipstick method): color, pH, glucose, protein, ketones, bilirubin, blood, nitrite, leukocyte esterase
- Microscopic analysis of urine sediment: WBCs, RBCs, epithelial cells, casts, bacteria
Urine culture

Front 79

How are Macroscopic analyses interpreted?

Back 79

* Appearance (normal = clear): cloudy or turbid may indicate infection
* Color (normal = yellow): red or dark brown may indicate hematuria
* pH (normal = 4.5-8.0):
- Crude measure of acid/base balance
- High urinary pH may indicate the presence of urease-producing bacteria
+ Catalyzes urea creating ammonia + CO2
+ Most common = Proteus spp.

* Nitrite:
- Detects the presence of nitrite in the urine
- (+) result indicates the presence of bacteria which reduce nitrates to nitrites in the urine
- Most common Gram-negative bacteria are capable of reducing nitrates
+ Pseudomonas is a notable exception
- False-negative results are common, false-positives are rare

* Leukocyte esterase
- Enzyme produced by activated leukocytes (neutrophils)
- Positive result = surrogate indicator for the presence of intact or lysed neutrophils (WBCs)

Front 80

Interpretation of Microscopic Analysis (Urine Sediment)

Back 80

* WBCs (normal = 0-10/hpf):
- >10/hpf indicates the presence of inflammation and possibly infection (pyuria)
* RBCs (normal = 0-5/hpf):
- > or = 5/hpf may indicate infection (hematuria)
* Casts:
- White blood cell casts indicates renal source of inflammation/infection
- WBC casts frequently found in pyelonephritis
* Presence of Bacteria:
- Semiquantitative (dipstick)
- Usually reported as either:
+ Occasional, few, moderate or many
+ 1+, 2+, 3+, etc.
* Culture & sensitivity = quantitative
- 95% of the time only a single organism is present
- > or = 103 CFU bacteria/ml urine in the presence of classic symptoms

Front 81

Goals of Treatment for UTIs

Back 81

- Resolution of clinical signs & symptoms
- Eradication of pathogens from the urinary tract
- Prevention of complications

Front 82

Considerations in Selection of Antibiotics

Back 82

* Most likely pathogen
Complicated vs. uncomplicated
* Severity/location of infection
Cystitis vs. pyelonephritis
* Antibiotic characteristics
High urinary concentrations
* Sensitivity patterns
* Previous experiences
* Cost
* Formulary
* Side-effects
* Patient allergies
* Renal function
* Drug interactions
* Patient compliance

Front 83

Diagnosis of acute uncomplicated cystitis

Back 83

* Classic symptoms w/o vaginal symptoms or discharge = 90% likelihood of UTI and can treat without urinalysis
* Culture not necessary
* May need to screen for STDs

Front 84

Treatment of acute uncomplicated cystitis

Back 84

* Treatment of choice = 3-day short course
* Trimethoprim/sulfamethoxazole (TMP/SMX), nitrofurantoin or fluoroquinolone = empiric drugs of choice for most patients

* TMP/SMX DS 1 tablet PO BID x 3 days
* Trimethoprim 100 mg PO BID x 3 days
* Fluoroquinolone x 3 days: norfloxacin 400 mg PO BID, ciprofloxacin 250-500 mg PO BID, Cipro XR 500-1,000 mg PO QD, or levofloxacin 250-500 mg PO QD
* Nitrofurantoin 100 mg PO BID x 5-7 days
* Amoxicillin/clavulanate 500 mg PO BID x 7 days
Other treatment considerations:
* Amoxicillin 500 mg PO TID may be okay empirically if E. coli resistance is low (<20%)
* Avoid empiric TMP/SMX where E. coli resistance is >20%, recent exposure to antibiotics (last 3 months)

Front 85

Follow-up and Monitoring for acute cystitis

Back 85

* Resolution of symptoms (within 24-48 hrs)
* Re-evaluated only if symptoms persist or reoccur

Front 86

What are some non-Rx and non-pharm recommendations for acute uncomplicated cystitis?

Back 86

* Fluids – lots! (To flush the bacteria out)
* Phenazopyridine (Pyridium or Uricalm) – urinary analgesic
- 200 mg PO TID x 2 days
- Usually not necessary & can mask signs/symptoms if patient is not responding
- Can cause reddish-orange discoloration of the urine
* Cranberry juice or extract: PREVENTION ONLY
- Appears to interfere with adherence of bacteria
- Decreased recurrence by ~ 35%
- Cranberry supplements available in capsule, tablet & soft gel form or can consume ~ 16 oz (25 % cranberry) juice per day

Front 87

How prevalent is recurrence of uncomplicated cystitis?

Back 87

20% of all UTIs recurr
- 80% of these are due to re-infections
- New microorgansim
- > two weeks after treatment
- Another 20 percent are relapses
+ Same microorganism
+ with in 2 wks after treatment

Front 88

How are relapses of UTI treated?

Back 88

* Culture/susceptibility testing
* Investigate underlying cause
* Treat for an additional 2-6 weeks

Front 89

How are re-infections of UTI treated?

Back 89

* Culture/susceptibility
* Treat new infection & consider prophylaxis

If the patient has > or = 3 UTIs in a year:
- No relation to intercourse - give prophylaxis for 6 months then stop and observe
- Relation to intercourse - give intercourse prophylaxis and voiding afterintercourse

If the patient has < or = 2 UTIs in a year
- Treat individual episodes
- Consider patient-initiated therapy

Front 90

Prophylaxis regimens for Post intercourse

Back 90

* TMP/SMX SS 1 tablet PO
* Nitrofurantoin 50-100 mg PO
* Cephalexin 250 mg PO
* Ciprofloxacin 125 mg PO

One dose post-intercourse

If the patient becomes infected while on prophylaxis, need to give full dose treatment.

Front 91

Prophylaxis regimens for Recurrent cystitis

Back 91

* TMP/SMX SS 1/2 tablet PO
* Nitrofurantoin 50-100 mg PO
* Trimethoprim 100 mg PO

Once daily for six months

Front 92

What is the likely cause of Recurrent UTIs in Post-menopausal Women

Back 92

Lack of estrogen results in changes in bacterial flora of the vagina leading to increased colonization of uropathogenic E. coli

Front 93

Treatment of Recurrent UTIs in Post-menopausal Women

Back 93

* Topical (vaginal) estrogen
- Normalizes vaginal flora: increased lactobacillus leads to decreased pH which decreases colonization of E. coli
- One study demonstrated a decrease in episodes from 6/year to 0.5/year

Front 94

Evaluation and Diagnosis
of Acute Complicated Cystitis

Back 94

* Symptoms can be the same as an uncomplicated UTI or symptoms can be vague (especially in the elderly)
* Need to obtain:
- Urinalysis
- Urine culture/susceptibility
- Serum creatinine/BUN to evaluate renal function

Front 95

Treatment of acute complicated cystitis

Back 95

* Oral fluoroquinolones = empiric treatment of choice (more broad-spectrum)
* TMP/SMX DS 1 tablet PO BID
(Avoid empiric TMP/SMX where E. coli resistance is >20%, recent exposure to antibiotics (last 3 months) & recent hospitalization)
* Cephalexin 500 mg PO QID
* Amoxicillin/clavulanate 500 mg PO BID or amoxicillin 500 mg PO TID okay empirically if Enterococcus is suspected
* Duration of treatment = 7-14 days

Front 96

Follow-up monitoring for
Acute Complicated UTI

Back 96

* Resolution of symptoms (within 24-48 hrs)
* Alter antimicrobial choice based on culture & susceptibility testing if necessary
* Obtain follow-up culture 2 weeks post-therapy to confirm eradication

Front 97

Evaluation/Diagnosis of Acute Pyelonephritis

Back 97

* Signs/symptoms can range from mild/moderate to moderate/ severe
* Systemic signs/symptoms with or without s/s of cystitis
* Abnormal urinalysis (e.g., WBC casts)
* Elevated WBC with left shift
* Fever (>38.3oC/100.9oF)
* Need to obtain
- Urine culture/susceptibilities
- May need blood cultures (depending on severity)
- Evaluate renal function

Front 98

Treatment of Acute Pyelonephritis

Back 98

* Symptomatic relief
- Analgesics, antipyretics, fluids
* Mild-moderate symptoms:
- May be able to manage with oral therapy as an outpatient
+ Clinically stable
+ Able to take & retain oral medications
- Fluoroquinolone = empiric drug of choice
+ Ciprofloxacin or levofloxacin (not norfloxacin)
- May also use TMP/SMX DS 1 tablet PO BID
* Total duration of therapy = 7-14 days

* Moderate-Severe symptoms:
- Hospitalization, IV antibiotics initially recommended
+ Fluoroquinolones (ciprofloxacin or levofloxacin)
+ 3rd –gen. cephalosporins (e.g. ceftriaxone)
+ Ampicillin + gentamicin
+ Ampicillin/sulbactam
+ Piperacillin/tazobactam
- Switch to oral therapy once clinical improvement, afebrile x 24 hrs
- Fluoroquinolones can be switched to oral therapy earlier if able to tolerate
- Total duration of therapy (IV + PO) = 10-14 days
+ Aminoglycoside should only be used for first 3 days

Front 99

Follow-up Monitoring for Acute Pyelonephritis

Back 99

* Patient should stabilize in 12-24 hrs
* Significant improvement in symptoms, WBC & temperature should occur within 72 hours
* Utilize culture & susceptibility results to confirm appropriate antimicrobial activity, narrow the antibiotic spectrum of activity if possible
* Obtain follow-up cultures 2 weeks post-therapy to confirm eradication

Front 100

UTI in Catheterized Patients

Back 100

* Most common hospital-acquired infection
* Rate of infection ~ 5% per each day catheterized
* Need to differentiate between colonization & infection
* Asymptomatic:
- Remove catheter (if possible)
- Treat if at risk for endocarditis or immunocompromised
* Symptomatic = remove catheter & treat as complicated UTI
- Culture/susceptibility important for drug selection

Front 101

UTI via Candida

Back 101

* May occur with catheterization and/or broad-spectrum antibiotic use
* Abnormal urinalysis, but no bacteria seen
* Yeast can be seen on Gram stain
* Need to send fungal culture
* Most common fungi = Candida albicans
* Other common fungi = Candida glabrata, C. krusei

* Asymptomatic
- May not always need to treat
- If catheterized, attempt to removal catheter if possible
- ICU patients = may want to treat to prevent candidemia
* Treatment (symptomatic):
- Candida albicans = fluconazole 200-400 mg PO QD x 7-14 days

Front 102

Bacterial Prostatitis

Back 102

* 50% of men will develop prostatitis sometime during their lives
* Can be acute or chronic
* Gram-negative enteric bacilli are most common pathogens
- E. coli = 75%
- Enterococci account for a relatively small proportion of cases

Front 103

Signs/Symptoms of Acute Prostatitis

Back 103

* Sudden onset of fevers, chills, myalgias, urinary symptoms;
* Prostate: firm, warm, indurated (swollen) & tender

Front 104

Signs/Symptoms of Chronic Prostatitis

Back 104

* Typically seen in men with recurrent UTIs
* Symptoms are vague: voiding problems, low back pain, urgency

Front 105

Treatment of Acute Prostatitis

Back 105

* Fluoroquinolone or TMP/SMX
* Mild/Mod: Oral x 2-4 wks
* Mod/Severe: may need IV initially, followed by oral x 2-4 weeks total

Front 106

Treatment of Chronic Prostatitis

Back 106

* Oral Fluoroquinolone or TMP/SMX for 4-6 weeks

* If relapse, may need to treat for up to 12 weeks