ID (Meningitis / Endocarditis / C. Difficile / TB) Flashcards
Define what “C. Dif-Associated Diarrhea” is.
1) 3 or more unformed stools per day for 2 or more days
2) Detected Toxin A / B or C. difficile bacteria in stool
3) Pseudomembranes in Colon are visualized
What are the clinical manifestations of C. difficile infection?
Fever
Abdom Pain
High WBC Count
Smelly Diarrhea
In what settings is C. difficile most commonly contracted?
Hospitals or Nursing Homes
Through what mechanism does C. difficile spread?
Spores
C. difficile is a ___ _____ (Gram Positive or Gram Negative), _____ (aerobic or anaerobic) bacteria.
Gram Positive, Anaerobic
All ABs are associated with C. difficile infection. However, which ones are considered highest risk?
-Clindamycin
-FQ’s
-Ampicillin
-Carbapenems
-3rd / 4th Gen Cephalosporins
Which ABs are considered lowest risk for C. difficile infection?
-Penicillin
-Macrolides
-Tetracycline
-TMP/SMX
-Aminoglycosides
For how many months post-AB therapy does C. difficile infection risk last?
3mths
What puts someone at risk for C. difficile infection?
-Old
-GI Disorders / Surgery
-Rectal Thermometer Use
-Enteral Tube Feeding
-Antacids (PPI > H2RA)
-Number days in hospital
What percentage of total C. difficile infections are recurrent in nature?
15 - 30%
If a person contracts C. difficile & has co-morbid Meningitis, should we discontinue the offending antibiotic?
NOOOOOOOO SEVERE INFECTION!!! ONLY LESS SEVERE INFECTIONS!
Patient comes to your pharmacy with confirmed C. difficile infection & is complaining about diarrhea. She grabs her antibiotic from you and picks up a package of Loperamide on the way out. What should you tell her before she pays and leaves the store?
No to the Loperamide… Avoid anti-peristaltic drugs (want to clear the infection)!
Lab parameters indicative of severe C. difficile infection would see leukocyte count being elevated above _____ cells / uL &/or a SCr above ___x baseline.
15 000 cells / uL; SCr of > 1.5x baseline
First line AB for C. difficile infection?
Vancomycin 125mg QID x 10-14d
When the cost of Vancomycin or Fidaxomicin is prohibitive to a patient, what can be used 2nd line in cases of C. difficile with minor diarrhea?
Metronidazole 500mg TID x 10-14d
What are the two ABs we use in cases of Severe, Uncomplicated (ie. Hypoalbuminemic) C. difficile infection?
1) Vanco 125mg QID x 10-14d
2) Fidaxomicin 200mg BID x 10d
In cases of Fulminant (ie. Severe, Complicated) C. difficile infection, what ABs can be used?
1) Vanco 125 - 500mg QID x 10-14d
+
Metro 500mg IV q8h
Can use Fidax + Metro IV if severe Vanco allergy!
In cases of Recurrent C. difficile infection, what therapy form saw even greater success rates than ABs?
Fecal Microbiotica Transplantation (FMT)
Which of the following MABs bind to C. difficile-produced Toxin A?
Bevacizumab
Golimumab
Actoxumab
Bezlotoxumab
Rituximab
Actoxumab (A = Toxin A)
Which of the following MABs bind to C. difficile-produced Toxin B?
Golimumab
Bezlotoxumab
Bevacizumab
Rituximab
Actoxumab
Bezlotoxumab (B = Toxin B)
Rates of asymptomatic C. difficile colonization in pediatric patients are high up until ___ years of age.
two
SA is a 6yr old patient with their second recurrence of confirmed C. difficile infection. Her doctor wants to start Vancomycin to treat the recurrent infection. Provide the doctor a suitable pulsatile dosing regimen.
1) 40mg / kg / day (divided QID) x 10-14d
2) Same dose TID x 1wk
3) Same dose BID x 1wk
4) Same dose OD x 1wk
5) Same dose every 2nd or 3rd day x 2-8wks
SA’s doctor phones you back and apologizes, noting that this was actually her first C. difficile recurrence. How might your Vancomycin regimen change? What if SA had an allergy to Vancomycin & needed Metronidazole treatment instead?
Vanco: 40mg / kg / day (divided QID) x 10d… Do not exceed 125mg maximum per dose!
Metro: 30mg / kg / day (divided QID) x 10d… Do not exceed 500mg maximum per dose!
What are some preventative strategies that address C. difficile infection?
-Good hygiene / handwashing
-Deprescribe unnecessary PPIs
-No anti-motility agents
-Avoid unnecessary AB use
-Don’t treat asymptomatic C. difficile
Meningitis infections occur within what brain space?
Subarachnoid Space (beneath the Dura Mater & Arachnoid layers, above the Pia Mater)
What percentage of all Meningitis infections occur in kids?
70% (highest in Neonates with rates around 400 per 100 000)
Cases of Aseptic Meningitis can be caused by what?
-Viral / Fungal Infection
-Atypical Bacteria
-Syphilis / TB / Lyme Dx
-Chem Irritation
-Malignancies
-Drug Induced
What properties make H. influenza, N. meningitidis, & S. pneumoniae good candidates for causing Meningitis?
-Immunoglobulin A Proteases (allows for colonization in nasopharyngeal mucosa)
-Pili (specifically N. meningitidis) allowing for sticky cellular adherence
-Polysaccharide Capsules (inhibits phagocytosis & complements activity in the blood)
Provide risk factors that increase the development of Meningitis.
-Congenital / Traumatic Defects
-Old & Young
-Prev. Viral Infection
-Low SES
-Crowded Occupations / Living Situations
-Pathogenic Exposure
-Immunosuppressed
The two most common pathogens responsible for Meningitis are typically S. pneumoniae & N. meningitidis. However, in newborns less than a month old, what are the most common organisms?
-E. coli
-S. agalactiae
-L. monocytogenes
-Klebsiella
How do the organisms that cause Meningitis infection from surgery or trauma differ from routine organisms?
-Staph
-Gram Negative Bacilli
How come H. influenza rates of Meningitis have dropped substantially over the years?
Vaccination
Classic symptomatic triad seen with Meningitis?
Headache, Fever, Neck Stiffness
What other symptoms aside from the triad are seen in cases of Meningitis?
-Altered Mental Status
-Malaise
-Seizures
-Vomiting
Infants often demonstrate atypical Meningitis presentation (ie. Irritable, Lethargic, Poor Feeding, Fever, Seizures)… What unique Fontanelle feature can sometimes be seen with Meningitis developments?
Bulging Fontanelle (Sunken Fontanelle much more common in other conditions)
Lab samples for the sake of obtaining Gram Stains & Culture / Sensitivity Tests are gathered via what technique?
Lumbar Puncture
What are the acute complications of Bacterial Meningitis?
-Shock
-Resp Failure
-Apnea
-Altered Mental Status
-Increase ICP
-Seizures
Conditions which can be brought upon by Bacterial Meningitis?
-Seizure Disorder
-Impaired Cognition
-Personality Changes
-Gait Disturbances
-Deafness
-Blindness
-Paresis
T or F: The prognosis for Meningitis gets better with age.
FALSE… Gets worse (much worse) as we age.
What is the trend seen with antibiotic penetration of Central Nervous tissues in cases of Meningitis?
Initial: Inflammation increases the penetrative abilities of the AB.
LT: See reduced AB penetrance.
In what cases would extending AB therapy durations for a Meningitis patient be warranted?
-Subdural Abscess
-Delayed CSF Sterilization
-Prolonged Fever
-Persistent Signs & Sx
HR’s CSF sample confirmed presence of S. pneumoniae with a case of Meningitis. What would our treatment duration be, provided he’s responding well to therapies?
10 - 14d
If HR’s CSF sample contained N. meningitidis, how would treatment length differ? H. influenzae? Group B Strep?
Neisseria: 5 - 7d
H. influenzae: 7 - 14d
Group B: 14 - 21d
If HR had a Subdural Abscess, how long would we treat his Meningitis?
4 - 6wks
I have a presenting patient with Meningitis. They are 8yrs old, and we want to initiate empiric AB therapies. What would you give them?
Vanco + 3rd Gen CS (ie. Cefotaxime or Ceftriaxone)
1mth - 50yrs this is the empiric regimen for everybody!
55yr old patient with Meningitis… What is the empiric AB regimen we give them?
Vanco + 3rd Gen CS + Ampicillin
Why are Aminoglycoside antibiotics not suitable 1st line drugs for treating Meningitis?
Poor CSF penetrance (even in the presence of inflammation), reduced activation within CSF.
In addition to antibiotic therapies, what sorts of supportive therapies should be added onto a Meningitis treatment regimen?
Mannitol (osmotic diuretic that reduces ICP)
Shunts (cases of Hydrocephalus where we need to drain out excess fluid from the brain)
Steroids (to decrease inflammatory response)
Dexamethasone is often the steroid of choice for Meningitis supportive therapy. What is its typical dosing regimen?
0.15mg / kg q6h x 2-4d
When should Dexamethasone be administered (relative to antimicrobial agents) when treating Meningitis?
Either before ABs or within 2hrs
What Meningitis complication (both in youth & adults) is greatly reduced by administering a course of steroids?
Hearing Loss
If a culture from a Meningitis patient comes back negative for H. influenzae or S. pneumoniae, when should their steroid courses be discontinued?
Within 48hrs
Prophylactic Meningococcal therapy regimens?
Rifampin 600mg BID x 2d (adults); 10mg / kg q12h x 2d (1 to 12yrs); 5mg / kg q12h x 2d (infants)
Ciprofloxacin 500mg as one dose (adults only)
Ceftriaxone 250mg IM as one dose (> 12yrs) or 125mg IM as one dose (< 12yrs)
Describe the prophylactic AB regimen for Pneumococcal Meningitis.
There isn’t one! Not given!
In what two populations is Endocarditis most prevalent?
Old Adults (> 50yrs)
Injectable Drug Users
Which microorganism is the most common culprit of Acute Endocarditis?
Staph Aureus
Subacute Endocarditis usually involves some form of ___ ___ ____, and often a history of ____ ___ or other procedures.
prior valve disease; dental work
What are the two most common microorganisms that cause Subacute Endocarditis?
Streptococcus, Enterococcus
Provide risk factors for Endocarditis.
-Over 60yrs & Male
-Structural Heart Dx
-Prosthetic Valves / Catheters
-Diabetic
-Hemodialysis
-Poor Oral Hygiene
-Injectable Drug Use
Streptococci-Induced Endocarditis often originates from what types of procedures?
Dental / Resp Tract Procedures (bacteria introduced to bloodstream this way)
Enterococci-Induced Endocarditis often originates from what types of procedures?
GI / GU Procedures (introduced to blood)
Most common symptom associated with Endocarditis infection?
Fever (86 - 96%)
Other symptoms seen with Endocarditis?
-Heart Murmur
-Fatigue
-Weakness
-Wt. Loss
-Joint / Muscle Pains
-Nightsweats
Weird side effects that are often unique to Endocarditis?
-Osler Nodes
-Janeway Lesions
-Splinter Hemorrhages
-Petechiae
-Vascular Embolic Events
IV drug users who obtain Endocarditis often present with “Pulmonary Syndrome”. What comprises this?
-Fever
-Cough / Coughing Blood
-Pleuritic Chest Pains
What imaging technique in diagnosing Endocarditis is useful, as it enables visualization of vegetation & cardiac function / abnormalities?
Echocardiogram
Endocarditic mortality rates are highest when what organism is gathered from a culture?
Fungal (90% mortality rate)
What sorts of complications can arise from Endocarditis?
-Destruction of Valve Tissues, Fibrosis, Abscesses
-HF
-Cardiomyopathy
-Septic Emboli
-Glomerulonephritis
-Stroke
Treatment length for Endocarditis infections are typically how long?
4 - 6wks
What is our empiric AB choice for those with Endocarditis (unknown bacterial source & native valves)?
Pen G or Amp + AMG
-If we suspect S. aureus, add Clox or use Vanco + AMG
Bacterial cultures from a suspected Endocarditis patient came back positive for Streptococcus. What is our 1st line AB treatment if they have native valves? Prosthetic valves?
Native: Pen G or Ceftriaxone x 4wks
Prosthetic: Pen G or Ceftriaxone x 6wks (+/- Gentamicin first 2wks)
If an Endocarditis patient with a positive culture for Streptococcus demonstrates intolerance to either Pen G or Ceftriaxone, what can we use instead?
Vanco x 4wks (trough levels between 10 - 15ug / mL)
A patient with confirmed Native Valve Endocarditis has a bacterial culture done, and it comes back positive for MSSA. What is:
1) The AB regimen of choice?
2) How would it differ if they had Prosthetic Valve Endocarditis?
1) Beta Lactam AB (either IV Nafcillin or Oxacillin) x 6wks
2) Same as above but add an AMG (ie. Gentamicin x 2wks) + Rifampin (6wks)
A patient with confirmed Prosthetic Valve Endocarditis has a bacterial culture done, and it comes back positive for MRSA. What is the AB regimen of choice?
Vancomycin x 6wks + AMG (ie. Gentamicin x 2wks) + Rifampin (6wks)
A patient comes into the hospital with suspected Endocarditis. You gather that they recently underwent a GI surgical procedure and that cultures show positive tests for Enterococcus bacteria. What is your choice of AB regimen?
1) Ampicillin Na+ or Pen G
+
2) Ceftriaxone
+
3) Gentamicin or Double Beta-Lactam Ampicillin
All therapies for 4-6wks!
In patients with mechanical heart valves, what do we do to their anticoagulant therapies if they experience a CNS embolic event?
D/C the anticoagulant for at least 2wks.
What sorts of Endocarditic monitoring parameters should be kept track of?
-Blood Cultures q24h (until negative cultures come back)
-Drug Side Effects
-Temp / WBC / Fatigue / Appetite
-SOB / Edema / Wt. Gain (signs & sx of HF)
What is the prophylactic drug regimen of choice for those who are at high risk of acquiring Infective Endocarditis?
None! Risks»_space;> Benefits (ie. Drug side effects»_space;> Prevention of relatively small number of infections).
Only dental procedures (in highest risk populations) that warrant Endocarditis AB Prophylaxis?
Manipulation of the Gums or Tooth Roots… Imaging, Bracket Adjustments, Bleeding from Lips or Oral Mucosa does not warrant prophylaxis!
For high risk populations, what is the chosen oral prophylactic AB regimen for dental procedures?
Amox 2g 30-60mins before the procedure… Kids get 50mg / kg dose!
If a patient misses their oral Amoxicillin dose for preventing Dental Procedure-Induced Endocarditis, how long post-procedure can they take it for?
Up to 2hrs after!
If a patient who requires dental AB prophylaxis for Endocarditis has a Penicillin allergy, what can we give them instead?
Cephalexin 2g (Peds = 50mg/kg)
Clindamycin 600mg (Peds = 20mg/kg)
Azith or Clarithromycin 500mg (Peds = 15mg/kg)
How do prophylactic AB regimens differ in cases of Respiratory Tract Procedures? Skin / MSK Infection Procedures? GI / GU Tract Procedures?
RTP: Exact same as Dental.
S/MSK: Exact same as Dental.
GI / GUT: Not recommended at all (due to potential AB resistance development)!
How is Tuberculosis spread?
Airborne Droplet Inhalation (either from coughing or sneezing)
Risk factors that increase likelihood of TB infection?
-Indigenous
-Close Contacts
-Homeless
-Incarcerated
-Alcoholic / IVDU
-Malnourished
-HIV Co-Infection
Explain the process of “TB Reactivation Disease”.
Macrophagic granulomas (formed during the Primary Infection Process) release organisms into Apices of the Lungs, where they multiply in number. These organisms then eat away at lung tissues, leading to hypoxia, respiratory acidosis, & death.
Explain how HIV co-infection enhances TB progression.
CD4+ immune cells multiply in response to TB… However, HIV multiplies at the same time within these cells, leading to T Cell death & thus disease progression (as immune cells fighting infection are depleted).
Presentation of Tuberculosis?
-Coughing Blood
-Wt. Loss / Fever / Fatigue
-Nightsweats
-Increased WBC
-Cavitation / Nodular Infiltrates on Chest X-Ray
-Dullness to Chest Percussion
Standard treatment for an active TB infection?
1) Isoniazid + Rifampin + Pyrazinamide + Ethambutol OD x 2mths
2) Isoniazid + Rifampin OD x 4mths
Explain Isoniazid’s MOA.
Inhibits bacterial cell wall synthesis
How should Isoniazid be administered?
On an empty stomach
Side effect profile of Isoniazid?
-Neurotoxic / Hepatotoxic
-GI Irritation
-Rash
-Elevate Serum Transaminase Enzymes (espec. in first 8-12wks)
Important DDIs of Isoniazid?
-ACs (ie. Phenytoin / CBZ / VA)
-Warfarin
-Tylenol
-Inhibits the metabolism of these drugs!
Explain Rifampin’s MOA.
Binds Beta Subunit of RNA Polymerase, blocks bacterial RNA transcription.
How do we administer Rifampin? What is the usual weight-based dose?
Empty stomach; 10mg / kg
Rifampin side effects?
-Elevated Liver Enzymes
-Hepatotoxic
-Rash / Fever / GI
-Allergic Rxn (Fever / Joint Pain / Chills)
-Acute Renal Failure / Hemolytic Anemia
Rifampin is a potent CYP3A4 Inducer… Thus, what DDIs should we be wary of?
-Steroids
-Anticoagulants
-Anticonvulsants
-Levothyroxine
-SSRIs
-Contraceptives
-Warfarin
-Simvastatin
Many more…
What similar medication can often be used in place of Rifampin if DDIs are particularly concerning?
Rifabutin
Side effects of Pyrazinamide?
-GI
-Joint Pain
-Increase Uric Acid
-Hepatotoxic
What is the purpose of adding Ethambutol onto a TB drug regimen?
To prevent drug resistance developments (bacteriostatic in nature).
Weird Ethambutol side effect?
Retrobulbar Neuritis (reduced visual acuity / inability to see green)
What drug should we avoid concurrently dosing with Ethambutol?
Antacids
If a latent TB infection is present, how can we treat it (note that quad therapy seen earlier is for active TB infection)?
1) Rifampin OD x 4mths
2) Isoniazid OD x 9mths
3) Isoniazid TW x 9mths
TB monitoring parameters?
-Baseline Labs
-CXR / Visual Acuity / Color Vision Testing
-Adherence to Drugs (DOT)
-Sputum Smears
-Weight Assessments
