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
