Exam 5 Flashcards
What are the common opportunistic infections that occur with progressive CD4 cell depletion in patients with HIV infections? (5 diseases) What are the common clinical manifestations of the most prevalent opportunistic infections?
Candida: more common at CD4 <200, but can occur at any time.
- oropharyngeal
- esophageal
- vulvovaginal
Pneumocystis jirovecii pneumonia (PJP): CD4 <200
- symptoms worsen over days to weeks (opposite of sudden onset)
- need to know the arterial blood gas (ABG). If hypoxemia (pO2 < 70mmHg), we will treat differently.
- CXR shows diffuse, bilateral, symmetrical “ground glass” interstitial infiltrates; Histoplasmic demonstration, induced sputum, or bronchoalveolar lavage fluid shows definitive diagnosis
Cryptococcus neoformans: CD4 <100
- cryptococcal meningitis (fever, malaise, headache, behavioral changes
- pneumonia (rare)
Toxoplasma gondii (parasite): CD4 <100
- occurs from reactivation of latent tissue cysts
- manifestation includes focal encephalitis with headache, confusion, motor weakness, and fever
- can detect by PCR in CSF analysis, serum IgG antibody, MRI of the brain (ring enhancing lesions)
Mycobacterium avium complex (MAC): CD4 <50
- gradual onset of systemic symptoms, such as fever, night sweats, weight loss, diarrhea, abdominal pain, fatigue, etc.
- may find fever, lymphadenopathy, and hepatosplenomegaly on exam
- acid-fast bacilli (AFB) cultures of blood, bone marrow, lymph node, stool, or other sterile fluid/tissue reveal the presence of MAC
What is the difference between primary and secondary prophylaxis of opportunistic infections in patients with HIV infections?
Primary prophylaxis - administration of an anti-infective agent to prevent the first episode of a particular OI
Secondary prophylaxis - administration of anti-infective therapy to prevent further recurrences of a particular OI (chronic maintenance or chronic suppressive therapy)
What is the immune reconstitution inflammatory syndrome (IRIS)? In what opportunistic infections can IRIS occur with the initiation of antiretroviral therapy?
Initiating ART in PML, cryptosporidiosis, or Kaposi’s sarcoma can be helpful, since there’s no other effective therapy. BUT if there is effective therapy, it can be disadvantageous to start ART during OI therapy.
Immune reconstitution inflammatory syndrome - high fever, malaise, and worsening clinical manifestations of the OI due to an exaggerated inflammatory response. This can develop if ART is started during OI therapy.
- Can be seen when treating MAC, TB, PJP, Toxoplasma gondii encephalitis, hep B and C, CMV, Cryptococcus neoformans meningitis, Histoplasma capsulatum, and Varicella zoster virus.
- More likely in pts with low CD4 count (<50) and high viral load (>100,000 copies/mL).
- Typically develops within the first 4-8 weeks of initiation of ART.
What is the treatment of oropharyngeal and esophageal candidiasis?
Oropharyngeal candidiasis (thrush) - fluconazole 100mg PO QD for 7-14 days
Candida esophagitis - fluconazole 200mg IV or PO QD for 14-21 days
What is the treatment for cryptococcal meningitis?
Induction: Liposomal amphotericin B 3-4mg/kg IV QD with flucytosine 25mg/kg/dose PO q6h for at least 2 weeks
Consolidation: fluconazole 800mg PO or IV QD for at least 8 weeks
Maintenance: fluconazole 200mg PO for at least 1 year
What is the treatment for mild to moderate PJP? Moderate to severe?
Mild/Mod: TMP-SMX 15-20mg/kg/day of TMP PO divided q6-8h for 21 days
Mod/Sev: TMP-SMX 15-20mg/kg/day of TMP PO or IV divided q6-8h for 21 days
- Should be given with adjunctive prednisone if pO2 < 70 on room air
*watch for hyperkalemia
What is the treatment for toxoplasmosis? What is the 1st line alternative? When do you need adjunctive dexamethasone?
Pyrimethamine 200mg PO x1 dose, then 50mg (≤ 60kg) to 75mg (> 60kg) PO QD + sulfadiazine 1000mg (≤ 60kg) to 1500mg (> 60kg) PO q6h + leucovorin 10-25mg PO QD for at least 6 weeks
Alternative: TMP/SMX 5mg/kg/dose (or 10?) of TMP IV or PO q12h (need PJP prophy if CD4 <200)
Adjunctive dexamethasone in patients with mass effect from focal lesions or associated edema
*Pyrimethamine can cause rash, nausea, bone marrow suppression that is reduced by leucovorin
What is the treatment for disseminated Mycobacterium avium complex (MAC)?
[Clarithromycin 500mg PO BID or azithromycin 500mg PO QD] + ethambutol 15mg/kg PO QD +/- rifabutin 300mg PO QD (for patient with CD4 count <50, high mycobacterial load (>2 log CFU), or not on ART) for ≥ 12 months
Is primary and/or secondary prophylaxis recommended in oropharyngeal/esophageal/vulvovaginal candidiasis?
Primary prophylaxis not routinely recommended, suppressive therapy not recommended unless patient has frequent or severe recurrences.
Is primary and/or secondary prophylaxis recommended in cryptococcal meningitis?
Primary: not routinely recommended
Secondary: required after completion of therapy for an acute infection
- fluconazole 200mg PO QD for at least 12 months
- can consider stopping secondary prophylaxis in asymptomatic pts with CD4 counts at least 100 for over 3 months and a suppressed HIV viral load from ART
- restart prophy if CD4 count decreases to ≤ 100 again
Is primary and/or secondary prophylaxis recommended in PJP?
Primary: give to all patients with CD4 count < 200 or CD4 percentage <14% of total lymphocyte count
Secondary: Must be given after completion of therapy for acute infection
- can consider stopping if CD4 count >200 for >3 months
Drug of choice: Bactrim DS PO QD or Bactrim SS PO QD
- alternative: dapsone 100mg PO QD
Is primary and/or secondary prophylaxis recommended in toxoplasma gondii encephalitis?
Primary: give to pts with positive toxoplasma gondii IgG antibody AND CD4 <100
- DOC: Bactrim DS PO QD
- can stop when CD4 >200 for > 3 months
Secondary: required after acute therapy
- DOC: pyrimethamine 25-50mg PO QD plus sulfadiazine 2000-4000mg PO daily (in 2-4 divided doses) plus leucovorin 10-25mg PO QD
- can stop when CD4 > 200 for > 6 months
Is primary and/or secondary prophylaxis recommended in MAC?
Primary: NOT recommended who immediately initiate ART, but IS recommended in pts not on fully suppressive ART and have CD4 count <50
- DOC: azithromycin 1200mg PO weekly
- can stop in patient initiated on ART (or CD4 count > 100 for ≥ 3 months)
Secondary: required after acute therapy
- DOC: clarithromycin 500mg PO BID with ethambutol 15mg/kg PO QD +/- rifabutin 300mg PO QD
- can stop in pts who completed 12 months of therapy, asymptomatic, CD4 > 100 or ≥ 6 months in response to ART
How do you treat the various types of gonococcal infections? (uncomplicated gonococcal infections of the cervix/urethra/rectum and pharynx)
Uncomplicated gonococcal infections of the cervix, urethra, and rectum:
- ceftriaxone 500mg IM as a single dose if person is <150kg
- if chlamydia is not excluded, do doxycycline 100mg PO BID x7 days
- if chlamydia is not excluded and pt is pregnant, do azithromycin 1g PO single dose
Uncomplicated gonococcal infection of the pharynx:
- ceftriaxone 500mg IM as single dose if person is <150kg
- test of cure is recommended 7-14 days after initial treatment
How do you treat primary, secondary, tertiary, congenital, and neurosyphilis? What if the patient was penicillin-allergic?
Penicillin G benzathine!!! For ALL stages (except pregnancy)!!!
Primary, secondary, early latent:
- Benzathine penicillin G 2.4 million units IM x 1 dose
- If penicillin allergic: doxycycline 100mg PO BID for 14 days OR tetracycline 500mg PO QID for 14 days
If late latent or tertiary:
- Benzathine penicillin G 2.4 mil units IM once weekly for 3 weeks
- If penicillin allergic: doxycycline 100mg PO BID for 28 days OR tetracycline 500mg PO QID for 28 days
Neurosyphilis:
- Aqueous crystalline penicillin G 3-4 mil units IV q4h for 10-14 days (or 18-24 million units per day as a continuous infusion)
- Can administer benzathine penicillin 2.4 million units IM once weekly x3 weeks after completion of IV therapy
- If penicillin allergic: ceftriaxone 2g IM or IV once daily for 10-14 days
Pregnancy: penicillin
How do you treat chlamydia in adults, pregnancy, and newborns/infants?
Most common notifiable infectious disease
Adolescents and adults:
- Doxycycline 100mg PO BID x7 days
Pregnancy:
- Azithromycin 1g PO as single dose
Nothing on newborns/infants
How do you treat genital herpes (focusing on first clinical episode and recurrent infections and daily suppressive therapy)?
First clinical episode - treat for 7-10 days
- acyclovir 400mg PO TID
- famciclovir 250mg PO TID
- valacyclovir 1g PO BID
Episodic recurrent infections - benefit if started in prodome or within 1 day after onset of lesions
- acyclovir 800mg PO BID for 5 days or 800mg TID for 2 days
- famciclovir 125mg PO BID for 5 days or 1g PO BID for 1 day
- valacyclovir 500mg PO BID for 3 days or 1g PO QD for 5 days
Daily suppressive therapy:
- acyclovir 400mg PO BID
- famciclovir 250mg BID
- valacyclovir 500mg PO QD (less effective) or 1g PO QD
What is the treatment of trichomoniasis, including pregnancy and neonates?
Nitroimidazoles are the only drug class with documented clinical efficacy
Women: metronidazole 500mg BID for 7 days
Men: metronidazole 2g PO in a single dose
Do sensitization if they are allergic to metronidazole, since it’s the only drug with efficacy
What are the risk factors for development of infections in immunocompromised hosts? (4)
Neutropenia - low number of neutrophils (esp. ANC <500 and really esp. ANC <100)
- defined by ANC (WBC x (%polys + %bands)
- note the severity of neutropenia, rate of neutrophil decline, and duration of neutropenia (7-10+ days)
Immune System Defects - Cell-mediated or humoral immunity
- Cell-mediated: T lymphocytes and macrophages
- Humoral: B-cells
Destruction of Protective Barriers - skin, mucus membranes or oropharynx or GI tract, surgery
Environmental contamination
**in cancer, prolonged neutropenia is the primary risk factor for aspergillus
What are the common bacterial, viral, fungal, and protozoal pathogens encountered in immunocompromised hosts?
Delete this unless he emphasizes something
What is the clinical presentation of infections in neutropenic cancer patients, including problems associated with documenting the etiology of the infection?
Presentation - fever [≥ 38.3 ºC if no other causes] (most important, may be the only clinical finding)
- consider fever to be an infection until proven otherwise
Problems with documentation - Febrile episodes due to microbiology are only 30-40% of cases. Infections are documented clinically (but not microbiologically) in another 30-40% of cases.
- 45-75% of bacteremic episodes in cancer are due to gram-positive cocci
How should we manage the febrile episodes in neutropenic cancer patients, modification of empiric therapy, and monitoring parameters?
If low risk (neutropenia ≤ 7 days, no or few comorbidities, clinical stable, no identified focus of infection or simple infection [UTI]) -> broad spectrum therapy initially in clinic or hospital setting, then can transition to outpatient IV or oral therapy.
- If outpatient: PO fluoroquinolone + amox/clav
- inpatient IV: pip/tazo, antipseudomonal carbapenem, cefepime, ceftazidime
- If inpatient, step-down to PO when appropriate
If high risk profound (ANC <100) and prolonged (> 7 days) and/or significant comorbidities -> broad spectrum parenteral therapy, admit to hospital for empiric therapy
- inpatient: pip/tazo, antipseudomonal carbapenem, cefepime, ceftazidime
- add IV vanc for cellulitis, pneumonia, severe sepsis/shock, gram-pos bacteremia, suspected IV catheter infection, or known colonization with MRSA, or resistant streptococci
- for septic shock, gram-neg bacteremia, or pneumonia: add aminoglycoside or antipseudomonal fluoroquinolone
Re-evaluate the patient 48-72 hours after implementing empiric therapy.
- Most important determinant of patient outcomes is resolution of neutropenia
What should we add to empiric therapy of febrile episodes of neutropenic cancer patients when: MRSA, VRE, ESBL producer, KPC producer
MRSA: vanc, linezolid, or daptomycin
VRE: linezolid or daptomycin
ESBL producer: carbapenem
KPC: ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam
Why would we use vancomycin as initial empiric therapy and initiation only when clinically indicated in the management of febrile episodes in neutropenic patients?
Vanc (or other gram-pos agent) is not recommended as part of the initial regimen.
Add gram-pos agent if:
- severe sepsis
- pneumonia
- positive blood cultures or gram-pos pathogen before final identification is known
- suspected serious catheter-related information
- skin or soft tissue infection
- colonization with MRSA, VRE, or PRSP
- Severe mucositis (if fluoroquinolone prophylaxis has already been given or if ceftazidime was used for empiric therapy)
What are the nuances between bacteremia, systemic inflammatory response syndrome (SIRS), severe sepsis, septic shock, and multiple organ dysfunction syndrome?
bacteremia - presence of viable bacteria (fungi) in the blood
systemic inflammatory response syndrome (SIRS) - systemic inflammatory response to a variety of severe clinical insults (infectious or non-infectious) manifested by 2 or more of the following conditions:
- temp > 38 ºC (>100.4 ºF) or < 36 ºC (<98.6 ºF)
- heart rate > 90 beats/min
- respiratory rate > 20 breaths/min or PaCO2 <32 mmHg
- WBC count > 12,000, <4,000, or > 10% immature forms (bands)
severe sepsis - life-threatening organ dysfunction caused by a dysregulated host response to infection
- (the SOFA score assesses organ failure. Higher is worse)
septic shock - sepsis, but circulatory, cellular, and metabolic abnormalities are associated with higher risk of mortality than sepsis alone
- patients require vasopressors to maintain MAP ≥ 65mmHg and serum lactate > 2
multiple organ dysfunction syndrome - altered organ function in an acutely ill person so that homeostatis cannot be maintained without intervention
What pathogens more commonly cause morbidity and mortality in sepsis?
Gram-neg bacteria is most commonly associated with septic shock (next is gram-pos)
- E. coli, Klebsiella, Pseudomonas aeruginosa
What is the role of procalcitonin in the initiation, alteration, or discontinuation of antibiotic therapy?
Plasma procalcitonin is released when macrophages are exposed to bacteria or endotoxin (not viruses).
- PCT concentration is ≥1ng/mL, antibiotics are strongly encouraged
- PCT concentration ≥ 0.5 and < 1, antibiotics encouraged
- PCT ≥ 0.25 and < 0.5, antibiotics discouraged
- PCT < 0.25, antibiotics are strongly discouraged
What are the important principles to treating sepsis and septic shock? (12, 2 are most important)
- Admit to ICU ASAP if needed
- Complete history is needed to determine source of the infection
- Comprehensive supportive care is recommended to start immediately
- Early diagnosis and identification of the pathogen is key
- Need source control
- Want to initiate aggressive antimicrobial therapy within the first hour with 1 or more drugs against the most likely pathogens (not if the cause of shock isn’t infection)
- Use a prolonged infusion of b-lactams (after an initial bolus) instead of only bolus
- Optimize PK/PD
- Maintain tissue perfusion (avoid organ failure)
- Within the first 3 hours of presentation, measure lactate, obtain blood cultures, administer broad spectrum antibiotics, administer 30mL/kg LR (or NS) for sepsis-induced hypotension, septic shock, or lactace ≥ 36
- Within the first 6 hours, administer vasopressors (norepinephrine #1), then add vasopressin, then add epinephrine; re-assess volume status if needed, re-measure lactate
- Document reassessment of volume status and tissue perfusion
What is the empiric therapy of sepsis in non-neutropenic adults (ANC ≥ 1000); community-acquired (CAP, urinary tract, intra-abdominal, skin and soft tissue)
Community-acquired:
- CAP: ceftriaxone + azithromycin
- Urinary tract: 3rd or 4th gen cephalosporin (ceftriaxone)
- intra-abdominal source: 3rd or 4th gen cephalosporin (ceftriaxone) + metronidazole; or pip/tazo, or carbapenem (ertapenem), or cipro/levofloxacin + metronidazole
- skin and soft-tissue (cellulitis): vancomycin, linezolid, daptomycin
What is the empiric therapy of sepsis in non-neutropenic adults (ANC ≥ 1000); hospital-acquired (HAP/VAP, urinary tract, intra-abdominal, skin and soft tissue, thermal burn, indwelling vascular catheter)
Hospital-acquired:
- pneumonia (HAP/VAP): antipseudomonal b-lactam + aminoglycoside OR antipseudomonal fluoroquinolone + vanc or linezolid
- urinary tract: cefepime +/- tobramycin or antipseudomonal FQ; or pip/tazo +/- tobramycin or antipseudomonal FQ
- intra-abdominal: pip/tazo, or carbapenem (not erta), or cefepime+metronidazole
- skin (cellulitis/nec fasc): pip/tazo + vanc (+ clinda if nec fasc), or pip/tazo + linezolid (if nec fasc)
- thermal burn: antipseudomonal b-lactam + aminoglycoside + vanc (*remember to adjust renal clearance)
- catheter: vanc or dapto or linezolid
What 3 things qualify as treatment failure for staph aureus bacteremia?
- death within 30 days following treatment
- persistent bacteremia > 10 days after initiation of appropriate therapy
- recurrence of bacteremia within 60 days of discontinuing treatment
What is most important in the clinical approach to SAB? (staph aureus bacteremia)
SOURCE CONTROL!!!
(also figure out if it’s metastatic)
How many of the 4 tubes of blood cultures needs to be positive in order to treat for staph aureus?
Just ONE! Staph aureus is never a contaminant
(repeat blood cultures every 48 hours until they are negative)
What should we think if the patient has staph aureus in the urine?
Since S. aureus is not a common organism in UTIs, we should do a whole bacteremia work up. Translocation of S. aureus from the blood to the urine is what’s likely happening.
What do we use to empirically cover MSSA and MRSA?
vanc or dapto
vanc is horrible for MSSA, so it’s important to use rapid diagnostics to determine if the patient has MSSA or MRSA.
dapto is better than vanc for MSSA, but some people do nafcillin + vanc to cover MSSA and MRSA. Not super common though.
How do we treat MSSA bacteremia?
cefazolin 2g IV q8h
nafcillin 2g IV q4h - gets better CNS concentrations, so if it’s in the brain, nafcillin is better than cefazolin
oxacillin 2g IV q4h
Not:
- vanc
- combinations with rifampin
- combinations with aminoglycosides
How do we treat MRSA bacteremia?
vancomycin 15-20mg/kg IV q8-12h
daptomycin 6mg/kg IV q24h - he likes this one better, can use in septic pulmonary emboli (since these emboli are in the vasculature)
Not:
- combinations with gentamicin or rifampin
- limited data with ceftaroline, but it is sometimes used with dapto
How long do we treat staph aureus bacteremia?
Uncomplicated: 14 days of IV therapy from the first negative blood culture (so may actually be more than 14 days depending on when the negative blood culture happened)
- can’t have endocarditis
- no devices or prosthetics
- follow up blood cultures have to be negative (2-4 days after initiating therapy)
- no metastatic infection
Complicated: 4 weeks
Complicated with metastatic infection: 6-8 weeks
If someone has streptococci bacteremia, what do we use to analyze their status? What do we treat with and what duration?
- HANDOC score
- Treatment duration: 14 days, start with IV then transition to PO (not from first day of negative blood culture. We don’t always have to repeat blood cultures)
S. pyogenes or S. agalactiae: penicillin IV (continuous or q4h) -> high dose amoxicillin PO
S. pneumoniae: ceftriaxone or penicillin (if susceptible)
If someone has enterococci bacteremia, what do we use to analyze their status? What do we treat with and what duration?
- DENOVA score to analyze risk for endocarditis
- Treatment duration: 7 days (not from first day of negative blood culture. We don’t always have to repeat blood cultures)
- E. faecalis: ampicillin (if resistant or severe allergy: vancomycin or daptomycin)
- E. faecium: if vanA and vanB negative -> vancomycin; if vanA or vanB positive (VRE) -> daptomycin or linezolid
How do we treat uncomplicated gram-negative bacteremia?
General treatment duration is 7 days TOTAL (not from first day of negative blood culture. We don’t always have to repeat blood cultures)
- transition from IV to PO if the patient is able to
- PO drugs frequently TMP/SMZ, FQ, or b-lactam
CTX-M -> carbopenem
KPC -> ceftazidime/avibactam, cefiderocol, etc.
NDM, VIM, IMP -> cefiderocol OR aztreonam + ceftazidime/avibactam
- not any good PO options for any of these resistant bugs
How do we treat P. aeruginosa bacteremia?
- around 10 days of therapy, but it depends on the patient’s status
- cipro and levofloxacin are the only PO drugs for P. aeruginosa
- IV drugs for P. aeruginosa: pip/tazo, meropenem, cefepime, etc.
What are the common risk factors and pathogens for pediatric acute otitis media (AOM)?
Risk factors:
- smoke exposure
- formula feeding
- immunization status
- atopy
- daycare
- male
- family history
- onset of first episode before 6-12 months of age
- lower socioeconomic status
- race (non-hispanic white)
- congenital anomalies
- immune deficiency
Pathogens:
- Streptococcus pneumoniae
- Haemophilus influenzae
- Moraxella pyogenes
How can you distinguish between non-severe and severe AOM?
non-severe:
- mild otalgia AND fever < 39 ºC in the past 24 hours
severe:
- moderate to severe otalgia OR fever ≤ 39 ºC
What are the common risk factors and pathogens for pediatric urinary tract infections (UTIs)?
Girls:
- white
- less than 12 months old
- temp ≥ 39 ºC
- fever ≥ 2 days
- no other source of infection
Boys:
- nonblack
- temp ≥ 39 ºC
- fever over 24 hours
- uncircumcised
- no other source of infection
Pathogens:
- E. Coli
- Also Klebsiella, Proteus, Enterobacter, Citrobacter, Staph saprophyticus, and enterococcus
When shouldn’t we treat AOM?
When not to treat:
- over 2 years old and non-severe
- 6 months to 2 years old with non-severe unilateral AOM
- everyone else will need treatment
Can provide symptom relief: *ibuprofen should only be used in children 6 months and older, but we can use APAP in younger children
What is the first line and alternative therapy for an infant/child with AOM?
antibiotics are not indicated in Otitis Media with Effusion (middle ear is sterile, no signs of infection
- start with observation to see if it goes away in 2-3 days
Treatment:
1. amoxicillin 80-90 mg/kg/day divided q12h for 5-10 days
2. amox/clav 90mg/kg/day amoxicillin component divided q12h (clavulanate should be less than 10mg/kg/day); use 600mg amox/42.9mg clav/5mL formulation
2. if allergy: cefdinir, cefpodoxime, cefuroxime
3. severe cases: IM ceftriaxone (avoid if <1mo old)
4. rescue option: clindamycin (not H. flu, maybe PRSP)
Do not use amoxicillin if:
- known resistance, treatment failure, if they’ve used amoxicillin in the last 30 days, allergy
- if concurrent conjunctivitis -> more likely to be moraxella, so give amox-clav
Resistance is a big issue. We will increase doses or add a b-lactamase inhibitor if needed
How do signs and symptoms of a UTI vary by age group (newborns, infants/young children, school-age)
newborns - jaundice, sepsis, failure to thrive, vomiting, fever
infants/young children - fever, strong-smelling urine, hematuria, abdominal/flank pain, new-onset urinary incontinence
school-age - dysuria, frequency, urgency (similar to adults)
What is the preferred method for urine collection for children under 24 months?
Catheterization
What is the gold standard for UTI diagnosis? How many CFUs need to be present?
Urine culture is the gold standard
- see >50,000 CFU/mL if SPA or catheter specimen
- clean catch >100,000 CFU/mL
What is the first line and alternative therapy for an infant/child with UTI?
- Amoxicillin, cephalexin, TMP/SMX whatever
- if IV is needed: ceftriaxone, other cephalosporins, etc.
NOT:
- fluoroquinolones unless MDR pathogen with no safe alternative, if IV therapy isn’t feasable, or if there’s no other effective oral agent
When do bronchiolitis symptoms peak?
Symptoms often peak around 5 days and may take up to 2 weeks to resolve.
Symptoms:
- fever
- runny nose
- cough
- sneezing
- increased work of breathing
How do we prevent or treat pediatric RSV bronchiolitis?
Prevent:
- non-pharm: hand washing, isolation, “sick pods”
- pharm: influenza vaccine for everyone 6 months and older, RSV vaccine
- can vaccinate pregnant people (RSV preF vaccine), 32-26 weeks pregnant, provides protection if given at least 14 days before delivery
- can give monoclonal antibodies for infants (Nirsevimab) if the mother didn’t get the RSV vaccination. This is given for infants <8 mo old
- can give second nirsevimab dose for high risk infants/children aged 8-19months entering their 2nd season of RSV (chronic lung disease of prematurity, severely immunocompromised children, significant congenital heart disease, american indian or alaska native children)
Treat: supportive therapy no real treatment
- oxygen
- hydration
- mechanical ventilation
- ECMO
What is the incidence, inheritance pattern, and prognosis for cystic fibrosis?
Incidence - 1 in 3,000
Inheritance pattern - Autosomal recessive genetic disease, so need to get a recessive gene from each parent
Prognosis - Average life expectancy is 56 years
What is a CF screen? What are the signs and symptoms for CF by age group?
At 24 hours of life, newborns will be tested through a blood spot that tests for a variety of diseases, including CF. Immunoreactive trypsinogen (IRT) is a measure of pancreatic function. A positive test is not diagnositic–futher testing is required for diagnosis.
Neonates: meconium ileus, prolonged obstructive jaundice
Infants and children: cough, recurrent URI, wheezing, failure to thrive, heat intolerance
Adolescents and adults: delayed sexual maturation, nasal polyposis
What is the general pathophysiology of CF?
CF is caused by a mutation that encodes for the CFTR protein. The gene is located on chromosome 7. Normally, chloride goes through the CFTR channel to the mucus. With a dysfunction CFTR channel, chloride cannot get to the mucus, resulting in sodium and water leaving the mucus, as well. This thick mucus is a good environment for bacteria, which attracts immune cells, and leaves DNA around from lysed cells, all further thickening the mucus.
What class of medication is ivacaftor? What age is approved for and what are some clinical pearls?
ivacaftor (Kalydeco): CFTR potentiator (keeps door open longer)
- approved down to 1 month old
- BID tablets
- take with fatty foods
- monitor eye exam, LFTs (dose adjustment for hepatic impairment)
- CYP3A substrate
- approved for responsive mutations
What mutation is ivacaftor/lumacaftor for? What age is approved for and what are some clinical pearls?
ivacaftor/lumacaftor (Orkambi) - used for F508del homozygous mutations (lumacaftor stabilizes and relocates the door)
- Approved down to 1 year old
- Take with fatty foods
- Monitor LFTs (dose adjust in hepatic impairment), eye exam
- Lumacaftor is a CYP3A strong inducer, ivacaftor is CYP3A substrate
- Birth control drug interaction
- Side effect: chest tightness and shortness of breath with initiation in some patients
What mutation is tezacaftor/ivacaftor approved for? What age is approved for and what are some clinical pearls?
tezacaftor/ivacaftor (Symdeko) - approved for F508del/F508 del (homozygous), or people with a responsive mutation
- Approved down to 6 years old
- Take with fatty foods
- Monitor LFTs (dose adjust in hepatic impairment), eye exam
- ivacaftor is CYP3A substrate
What mutation is elexacaftor/tezacaftor/ivacaftor approved for? What age is approved for and what are some clinical pearls?
elexacaftor/tezacaftor/ivacaftor (Trikafta) - approved for F508del heterozygous or homozygous, or other responsive mutations; now we have two agents to relocate the door
- approved down to age 2
- Take with fatty foods
- Monitor LFTs (dose adjust in hepatic impairment), eye exam
- ivacaftor is CYP3A substrate
- if you miss an orange tablet dose by more than 6 hours, take the orange tablets when you remember & skip the blue tablet!
How do we treat CF nasal polyps?
treatment:
- sinus surgery - recurrence is high after surgery
- nasal steroids (Flonase, Nasonex, etc.)
- saline nasal rinses
**do not give steroids or antibiotics if we don’t have to for the risk of ototoxicity
How does CF affect the head?
- allergy symptoms: limit antihistamines, use nasal steroids PRN
- depression is common in CF patients (use SSRIs)
How does CF affect the lungs?
CF associated lung disease is the cause of 85% of the CF deaths. The thickened mucus is hard to clear and is a good environment for bacteria.
- Airway clearance is recommended for all CF patients (ex. manual airway clearance techniques, therapy vest, futter, acapella, huff coughing, meta neb)
What maintenance lung treatments do we have for CF?
Dornase alfa - cleaves the extracellular DNA from the immune/inflammatory cells, thus reducing viscosity and promoting clearance
- nebulized solution
- use down to six year olds, sometimes younger
Hypertonic saline - NaCl creates a gradient that draws water into the airway, thus reducing mucus thickness
- nebulized
- use down to six year olds, sometimes younger
Inhaled mannitol (Bronchitol) - draws water into airways to hydrate the mucus
- dry powder inhaler
- use if 18 years and older
- requires tolerance test before use
Why is azithromyicn used in CF and who can we use it for?
azithromycin - has immunomodulating effects
- recommended in patients with chronic pseudomonas, but consider in patients without chronic pseudomonas
- dosed MWF, can reduce dose if not well tolerated (GI side effects)
Should we use inhaled corticosteroids, leukotriene modifiers, oral corticosteroids for CF?
No, only if they have concurrent asthma symptoms
What bronchodilator can we use in CF?
albuterol - short acting beta agonist
- used to open up airways prior to airway clearance therapy and to decrease bronchoconstriction prior to inhaled hypertonic saline
- inhale or nebulize scheduled or PRN
What are the antibiotic agents can be administered by nebulized mist for treatment of CF?
tobramycin - recommended for initial pseudomonas eradication (28 days course) or suppression therapy in 28 day cycle for patients with chronic pseudomonas
aztreonam - used with chronic pseudomonas in patients that can’t tolerate tobramycin
anikacin liposomal - used for mycobacterium avium infection in 18+ year olds
amikacin and colistin are also inhaled antibiotics
What are the primary pathogens causing pneumonia in patients with CF and what are the appropriate antibiotic(s) and doses for each?
Pathogens: S. aureus (MSSA, MRSA), P. aeruginosa, H. influenza, K. pneumonia, E. Coli, Stenotrophomonas maltophila, Burkholderia cepacia, Aspergillus fumigatus, Achromobacter
MRSA: single coverage needed; bactrim, clindamycin, vanc, tetracyclin, linezolid
MSSA: single coverage needed; cefazolin, unasyn, coverage by anti-pseudomonal beta-lactam
Pseudomonas: double coverage with two different MOAs
- pip/tazo, imipenem/cilast, ceftazidime, meropenem, cefepime
- PLUS aminoglycoside (tobramycin or amikacin)
- cover pseudomonas if they’ve had a hx of pseudomonas, even if it’s not on the current culture
What do we do if the patient has allergic bronchopulmonary aspergillosis (ABPA)?
- prednisone burst then taper
- voriconazole, itraconazole, posaconazole
How is the PK for b-lactams and aminoglycosides altered in CF? What dosage guidelines and monitoring parameters should we keep in mind?
beta lactams - increased renal and non-renal clearance, do max doses at the shortest intervals or prolonged infusion
aminoglycosides - increased clearance and volume of distribution
fluoroquinolones - no specific change
Monitoring: pulmonary function tests, serum drug concentrations, peak/trough (if applicable), serum creatinine
How does CF affect the liver?
- focal biliary cirrhosis: biliary obstruction, progressive periportal fibrosis
- liver steatosis
- liver failure
Any patient with liver problems and CF should see a pharmacist.
Treatment - not ursodiol, CFTR modulators need close monitoring
How does CF affect the pancreas?
- exocrine insufficiency: mucus obstructs exocrine ducts, decreased enzymes
Treat with pancreatic enzymes
Around how many units of pancreatic enzyme should we give per meal? What are our pancreatic enzyme options?
Pancreatic enzymes should be around 1,000units of lipase/kg/meal, do NOT exceed 10,000 units of lipase/kg/day
- Creon (cap), Pancreaze (cap), Zenpep (cap), Pertzye (cap), Viokace (tablet)
- RELiZORB (immobilized lipase cartidge
What can we use to help with stomach pain and indigestion in CF?
PPIs: ome/lanso/esome/pantoprazole
H2RAs: famotidine
Acid suppression helps with pancreatic enzyme activity, but may also decrease calcium absorption
What vitamins may we want to supplement in CF?
- Vitamin A, E, D, K
- Calcium
- Iron
- Zinc
- Sodium
Monitor vitamin levels, may need to monitor PT/INR with vitamin K
How does CF affect the reproductive system?
95% of males are sterile due to the absence of the vas deferens
Women with adequate nutritional and pulmonary reserve can have successful pregnancies
- contraception use is encouraged
What is the anatomy and physiology of the CNS relating to host defenses within the CNS and factors that influence antibiotic penetration?
The brain and spinal cord are suspended in cerebrospinal fluid (CSF), which acts as a shock absorber. The CSF should have fewer than 5 white blood cells per mL of CSF.
Additionally, the brain and spinal cord are ensheathed by the meninges, which is made up of three separate membranes:
- dura mater - outer membrane
- under the dura mater is subdural space
- arachnoid - middle meningeal layer
- subarachnoid space is under the arachnoid (this is what gets infected, called meningitis)
- pia mater - innermost, thin layer of the meninges
The BBB and Blood-CSF Barrier (BCSFB) are barriers between the CNS and the blood.
- BBB: tightly joined capillary endothelial cells. Drugs enter the brain tissue by direct passage through capillary endothelial cells.
- BCSFB: tightly fused ependymal cells. This restricts the diffusion of substances into the CSF and may be a barrier to antibiotic penetration. But when the meninges are enflamed, some antibiotics can get in.
What 5 factors influence CNS/CSF penetration?
- Lipid soluble - more lipid-soluble = better
- Degree of ionization - only unionized compounds
- Protein bound - only free drug can penetrate
- Molecular weight - low molecular weight = better
- Meningeal inflammation - some drugs can penetrate when the meninges are inflamed
What 4 medications are able to penetrate with or without meningeal inflammation? What classes of drugs/drugs are able to penetrate with meningeal inflammation (6)? Which classes/drugs can NOT penetrate ever (7)?
With or without: acyclovir, fluconazole, ganciclovir, metronidazole
With inflammation: penicillins, 3rd/4th gen cephalosporins, aztreonam, meropenem, colistin, vancomycin
Never: 1st/2nd gen cephalosporins, aminoglycosides, b-lactamase inhibitors, amphotericin B, clindamycin, tetracyclines, ertapenem
What is the pathogenesis and bacterial etiology of acute bacterial meningitis and brain abscess?
Meningitis: inflammation of the meninges caused by a pathogen in the subarachnoid space through the BCSFB. One bacteria gains entry into the CSF, host defenses are inadequate to contain the infection and bacteria replicate rapidly.
- hematogenous spread: from blood, this is most common; N/meningitidis, S. pneumoniae, and H. influenzae strains with virulence factors are the most common pathogens
- Contiguous spread - from uncontrolled sinusitis, otitis media, or mastoiditis where the bacteria erodes into the CNS
- Direct inoculation through trauma or surgery
Brain abscess: intracerebrral focus of infection. Pathogen gets in through the BBB.
- contiguous spread most common, hematogenous, and direct inoculation
What are the most likely bacterial causes of meningitis based on these age/comorbidity groups: neonates (<1mo), infants/children (1mo-4y), children and adults (>4-29y), adults (30-50y), older adults (>50), post-neurosurgical, CSF shunt, head trauma, immunocompromised
neonates (<1mo): group B strep, E. coli, Listeria (whatever is in the vaginal canal)
infants/children (1mo-4y): H. influenzae (if not Hib vaccinated), S. pneumoniae, N. meningitidis
children and adults (>4-29y): N. meningitidis, S. pneumoniae
adults (30-50y): S. pneumoniae, N. meningitidis
older adults (>50): S. pneumoniae, N. meningitidis, E. coli, Klebsiella & other gram-neg bacilli, Listeria
post-neurosurgical: Staph aureus, Gram-neg bacilli (inc. E. coli, Klebsiella, Pseudomonas), Staph epidermidis
CSF shunt: Staph epidermidis, Staph aureus
head trauma: Staph aureus, S. pneumoniae, Gram-neg bacilli
immunocompromised: S. pneumoniae, N. meningitidis, Listeria, Gram-neg bacilli
What is the systemic reaction that is specific to meningococcemia (meningitis due to neisseria meningitidis)? Which bacterial cause of meningitis has the highest fatality rate?
Petechial or purpuric rash (this can be really bad due to widespread thrombosis)
Strep pneumoniae meningitis has the highest fatality rate.
Which meningitis does not use prophylaxis in close contacts? What is the recommended therapy for prophylaxis with the other two organisms?
Prophylaxis is not helpful with S. pneumoniae.
For Neisseria meningitidis and haemophilus influenzae, give rifampin for prophylaxis.
What are the most likely bacterial causes of brain abscess based on these age/comorbidity groups: otitis media or mastoiditis, sinusitis (frontoethmoid or sphenoid), dental sepsis, penetrating trauma/postneurosurgical, bacterial endocarditis
otitis media or mastoiditis - streptococci, Bacteroides spp., Prevotella spp., Enterobacterales
sinusitis (frontoethmoid or sphenoid) - Streptococci, Bacteroides spp., Enterobacterales, Staph aureus, H. influenzae
dental sepsis - Mixed fusobacterium, Bacteroides and Prevotella spp., viridans streptococci
penetrating trauma/postneurosurgical - Staph aureus, Streptococci, Enterobacterales, Pseudomonas aeruginosa, Clostridium spp.
bacterial endocarditis - Staph aureus, viridans streptococci
What are the three most common symptoms from brain abscesses?
Headache
Mental status changes
Focal neurologic deficits
What common cerebrospinal fluid analysis findings would be expect for bacterial meningitis/encephalitis?
- Cloudy CSF
- Glucose is less than 50% of serum glucose concentrations (<30-40mg/dL)
- High protein ≥ 100mg/dL
- WBC 400-5,000 (also differential with >80% neutrophils)
What are the principles of treatment for meningitis?
- prompt administration of appropriate antibiotics (within 24-48 hours) is ESSENTIAL
- do not delay the first dose of antibiotics until the culture is back
- high doses (maximal doses) should be used to optimize penetration of the site of the infection
- need CSF penetration and bactericidal activity from the drugs
How do you empirically treat these patients for meningitis: neonates, children, older children/adults, older adults/immunosuppressed, neurosurgery, open head trauma
neonates (E. coli, group B strep, listeria): ampicillin + cefotaxime
children (H. flu, N. meningiditis, S. pneumoniae): 3rd gen cephalosporin + vancomycin
older children/adults (N. meningiditis, S. pneumoniae): 3rd gen cephalosporin + vancomycin
older adults/immunocompromised (S. pneumonia, gram-neg bacilli, listeria): 3rd gen cephalosporin + vancomycin + ampicillin
neurosurgery (s. aureus, gram-neg bacilli): 3rd or 4th gen cephalosporin + vancomycin
open head trauma (s. aureus, gram-neg bacilli): 3rd or 4th gen cephalosporin + vancomycin
How do you directly treat meningitis depending on the organism?
Always use parenteral. Use your spectrum knowledge
Gnerally, penicillins are favored over cephalosporins. Unless b-lactamase positive, pen resistant, gram-negative, or pseudomonas.
Combo therapy with gentamicin is recommended in group B strep and listeria.
Vanc + ceftriaxone or cefotaxime is recommended for pen-resistant strep pneumo
Use pen G for pen-susceptible neisseria meningitidis!
What is the role of dexamethasone in the treatment of bacterial meningitis?
Consider steroids for infants and children > 2 months old with suspected or proven bacterial meningitis (mainly data with H. influenzae).
Give dexamethasone to adults with proven pneumococcal meningitis.
But this is all controversial.
What are the principles of treatment for brain abscess?
- the patient should immediately be taken to surgery
- empiric antibiotic therapy should be initiated immediately
- Corticosteroids should be administered to patients with significant surrounding edema or mass effect
- Once the organism is identified, use directed therapy
- Therapy is usually high dose IV antibiotics for at least 6 to 8 weeks
How do you empirically treat these patients for brain abscess: otitis media or mastoiditis, sinusitis (frontoethmoid or sphenoid), dental sepsis, penetrating trauma/postneurosurgical, bacterial endocarditis, congenital heart disease
otitis media or mastoiditis - 3rd gen cephalosporin + metronidazole
sinusitis (frontoethmoid or sphenoid) - 3rd gen cephalosporin + metronidazole
dental sepsis - penicillin + metronidazole
penetrating trauma/postneurosurgical - vencomycin + 3rd/4th gen cephalosporin
bacterial endocarditis - vancomycin + gentamicin
congenital heart disease - 3rd gen cephalosporin
How do you manage encephalitis?
Mostly, you won’t need to treat. Just do supportive care with fluids, antipyretics, and analgesics.
Treat if:
- HSV1 and 2 or VZV encephalitis: acyclovir 10mg/kg/dose IV q8h for 2-3 weeks
- CMV encephalitis (rare): in HIV patients; ganciclovir + foscarnet
*transition to PO when possible
