Infectious Disease Flashcards
(117 cards)
1
Q
Microbiology 101:
What are the four types of microorganisms? And the subtypes within them?
A
1) Bacteria
a) Gram-positive
b) Gram-negative
c) Other
2) Viruses
3) Fungi
a) Yeasts
b) Moulds
c) Dimorphic
4) Parasites
a) Protozoan
b) Multicellular
2
Q
What are the two main categories of gram-positive cocci, and name examples?
A
1) Clusters
- Staph aureus or CNST (coagulase negative STaph)
2) Pairs/chains
- Streptococcus or Enterococcus
3
Q
What are the three main categories of gram positive bacilli, and name examples?
A
1) Spore-forming
- Bacillus
- Clostridium
2) Non-spore forming
- Corynebacterium
- Listeria
3) Branching
- Actinomyces
- Norcardia
4
Q
Name 3 examples of gram negative cocci.
A
1) Neisseria meningitidis
2) Neisseria gonnorrheae
3) Moraxella
5
Q
What are the two main categories of gram negative bailli, and name examples?
A
1) Lactose fermenters
- Klebsiella
- E. coli
- Enterbacter
2) Non-lactose fermenters
- Pseudomonas
- Stenotrophomonas
6
Q
Name 2 examples of yeast and the type of infection they usually cause.
A
Yeast
- Candida spp.
- Cryptococcus spp.
Asexual, unicellular organisms
Typically superficial infection, but invasive disease in immunocompromised hosts
7
Q
Name an example of a Mould.
A
Aspergillus spp.
Multicellular organisms that have hyphae
8
Q
Name 3 examples of Dimorphic Fungi.
A
1) Blastomycosis spp.
2 ) Histoplasmosis spp.
3) Coccidiomycosis spp.
Mould in the cold, yeast in the heat.
Exist as yeast in body temperature, but becomes mould form in room temperature.
9
Q
High yield antibiotics:
SPICE (HAM) - name the species and treatment (4).
A
Serrtia
Providencia
Indole-positive Proteus
Citrobacter
Enterobacter
Hafnia
Acinetobacter
Morganella
Rx:
Carbapenem
TMP-SMX
Flurorquinolone (FQ)
Aminoglycoside (AG)
10
Q
High yield antibiotics:
ESBL - name the species and treatment (4).
A
E. coli
Klebsiella
Rx:
Carbapenem
TMP-SMX
FQ
AG (if sensitive)
11
Q
High yield antibiotics:
CPE - name the treatment (3 +/- 2)
A
Rx:
Colistin
AG
Tigecycline
Call ID (TMP-SMX or FQ if lucky(
12
Q
High yield antibiotics:
MRSA - name the treatment (7).
A
Vancomycin
Doxycycline
TMP-SMX
Clindamycin
Linezolid
Daptomycin
Ceftobiprole
13
Q
High yield antibiotics:
Pseudomonas - name the treatment (10).
A
Pip/tazo
Ceftazidime
Cefepime
Carbapenems (not Ertapenem)
Ciprofloxacin
AG
Aztreonam
Colistin
Tigecycline
Ceftazidime-Avibactam
14
Q
Enterococcus - name the treatment (3 +/- 1).
A
Vanco (not VRE)
Linezolid
Daptomycin
Amp/piperacillin if lucky
15
Q
Differentiate meningitis vs. encephalitis, based on symptoms and signs.
A
Meningitis - predominately starts with headache, neck stiffness and fever, and can get altered LOC later into the course
Encephalitis - predominantly starts with altered LOC and fever and can get seizures, focal neurological changes associated
Key guideline for CNS infections:
Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management
of bacterial meningitis. Clin Infect Dis 2004;39:1267-84.
16
Q
Does this adult patient have acute meningitis?
A
Meningitis ruled out (99%) if fever, neck stiffness and altered NS all absent
Joint accentuation - high sensitivity (97% in one study)
Kernig’s and Brudzinski’s signs - high specificity
17
Q
What are key signs of basal skull meningitis and what are culprit species?
A
+CN palsies
Long-tract signs
TB
Listeria
Cryptococcus
Syphilis
Lyme
…in the correct host
18
Q
Bacterial Meningitis:
When to CT and when not to CT?
** I do not understand this question - review at IMR
A
** I do not understand this question - review at IMR
19
Q
Meningitis - CSF Parameters
What are the CSF parameters for bacterial, viral, TB and fungal meningitis?
A
See table
- Differential may be unreliable in recent symptom onset
- Individual CSF predictors for bacterial meningitis each with >99 % certainty
- Glucose < 1.9 mmol/L
- CSF:blood glucose < 0.23
- protein > 2.2 g/L
- WBC > 2000 cells/mL
- PMNs >1180 cells/mL
- CSF biochemistry & cell count minimally affected at 2 days of antibiotics, but culture yield decreased
20
Q
Meningitis - Pathogens + Rx
For age 18-50 years, what are the common bacterial pathogens and empiric antimicrobial Rx?
For age > 50 years or immunocompromised, what are the common bacterial pathogens and empiric antimicrobial Rx?
A
21
Q
Meningitis - Pathogens + Rx CSF Gram Stains
What species is…
a) Gram-positive diplococci
b) Gram-negative diplococci
c) Gram-positive bacilli
A
a) Gram-positive diplococci = S. pneumoniae
b) Gram-negative diplococci = N. meningitidis
c) Gram-positive bacilli = L. monocytogenes
22
Q
Meningitis - Pathogens + Rx
For meningitis, what is the duration of treatment for S. pneumoniae, N. meningitidis, and LIsteria monocytogenes?
A
23
Q
Meningitis - Steroids
How would you prescribe steroids in meningitis and what species does it reduce mortality/morbidity in?
A
Dexamethasone 10 mg IV q6h for 4 days PRIOR TO or WITH first dose of antibioitis
- Led to 50% reduction in mortality/morbidity for pneumococcal meningitis
- Two subsequent negative trials
- Cochrane Review (2015): Steroids associated with reduction in mortality for meningitis secondary to Streptococcus pneumoniae (29.9 vs. 36%) and reduction in hearing loss and neurological sequelae for all bacteria
General approach
a) Administer before or with first dose of empiric antibiotics for suspected bacterial meningitis
b) Stop if CSF is non-turbid OR low cell count OR non-pneumococcal by culture
c) Do not start if antibiotics have already been received
24
Q
Neisseria Meningitis - CHEMOprophylaxis
Who should get it, when and what (3 options)?
(high yield question)
A
Who:
- Household contacts
- Persons sharing sleeping arrangements
- Persons who have direct nose/mouse contamination with oral/nasal secretions
- Children and staff in childcare or nursery
- HCWs who have had intensive unprotected contact (without wearing a mask) [e.g., intubating, resuscitating, closely examining oropharynx)
- Airline passengers sitting immediately on either side of the case (but not across the aisle) when total time on aircraft is 8 or more hours
When?
- Within 10 days usually
What?
1) Ciprofloxacin 500 mg PO x 1 dose (increasing resistance conern) OR
2) ceftriaxone 250 mg IM x 1 dose OR
3) Rifampin 600 mg PO BID x 2 days
25
Neisseria Meningitis - IMMUNOprophylaxis
Who should get it and what (2 options)?
(high yield question)
Who?
- Household contacts of a case of invasive meningococcal disease (IMD)
- Persons sharing sleeping arrangements with a case of IMD
- Persons who have direct nose/mouth contamination with oral/nasal secretions of a case with IMD
- Children and staff in contact with a case of IMD in child care or nursery school facilities
What?
- Depends on serotype of index case and age/underlying conditions of contact
- Men-C-ACYW or 4CMenB can be considered
26
Infective Endocarditis - what are the Class I Recommendations for diagnostic work-up, switching to oral Abx, and patient with drug use?
1) At least 2 sets of BCx prior to antibiotics
2) Initial TTE for everyone
3) TEE class I indications - TTE nondiagnostic or IE complications suspected or intracardiac leads (TEE widely used, these are just the Class I indications - e.g., consider in staphylcoccal, enterococcal, fungal infections)
- In patients being considered for an early change to oral antibiotic therapy for treatment of stable IE, baseline TEE before switching to ORAL and repeat TEE 1-3 days before completing antibiotics regimen should be performed
- Patients with suspected or confirmed IE related to drug use should be referred to addictions medicine specialist for opioid substitution therapy
27
Infective Endocarditis:
Diagnosis - Duke Criteria
Name the major criteria, minor criteria, definition of definite IE and definition of possible IE. (insert table)
28
IE - Treatment
What is the treatment of IE, base on species vs. native or prosthetic valve? What is the duration of treatment?
29
For the treatment of IE, what are the Class IIb recommendations for transitioning a patients to oral Abx?
In patients with left sided IE caused by Streptococcus, E. faecalis, S. aureus or CNST deemed stable by the multidisciplinary team after initial IV antibiotics, a change to oral Abx therapy may be considered if:
1) TEE before the switch to oral therapy shows no paravalvular infection AND
2) Frequent and appropriate follow-up can be assured by the care team AND
3) If a f/u TEE can be performed 1-3 days before the complete of the Abx course
(See POET trial for evidence)
30
For IE, what is the most important surgical indication (Class I)?
*High Yield Question
Decisions about surgery should be made by a "multispecialty heart valve team" of cardiologists, cardiovascular surgeons and ID specialists
(Class I Level B)
31
For IE, what are the Class I early surgical indications and delayed surgery indications?
32
For IE, what are the Class II, other surgical indications for Endocarditis?
33
IE - Prophylaxis
What patient populations need prophylaxis and for what specific procedures?
What are the prophylactic options?
34
BONUS Question: POET trial
Patient Oral vs. IV Antibiotic Treatment for Endocarditis
- 400 adults with IE (S. aureus, Strep, E. faecalis, CNST) randomized to IV Abx for duration or oral transition after at least 10 days IV (average 17 days IV)
- Primary endpoint was composite of all cause mortality, unplanned cardiac surgery, embolic events or relapse of bacteremia within 6 months
- Primary outcome occurred in 24 patients (12.1%) in the IV group and 18 patients (9.1%) in oral group (p=0.4) showing non-inferiority
- Caveat was followed 3 times per week and all had TEE, mostly L sided IE, very few (1%) Persons Who Inject Drugs. Not widely adapted into practice.
35
CAP - Diagnosis? Who to hospitalize?
*high yield
Diagnosis
- Clinical (fever, productive cough, SOB, signs of consolidation) + Radiographic (infiltrate on CXR)
Who to hospitalize?
Use clinical judgement + assess severity of illness
- PSI/PORT Score (*preferred in IDSA/ATS 2019)
- CURB-65
- confusion
- RR >/= 30/min
- BUN > 7 mmol/L
- sBP <90 or dBP /= 65
Score 0-1 = outpatient
Score >/= 2 = likely needs admission
Insert PSI score stable
36
CAP Pathogens
a) What are the most common CAP pathogens?
b) Pathogen concerning for severe disease?
c) Pathogens in patients with increasing comorbidities, antibiotics and hospital exposures?
a) Common pathogens
- S. pneumoniae (most common)
- M (mycoplasma). pneumonia
- C (chlamydia). pneumonia
- H (haemophilus). influenzae
- Respiratory viruses (influenza, RSV, parainfluenze, rhinovirus, adenovirus, coronaviruses...)
b) Severe disease
- Legionella pneumophila
c) In patients with increasing comorbidities, antibiotic and hospital exposures:
- increasing gram negatives, e.g., K. pneumoniae, Pseudomonas
- S. aureus (including MRSA)
37
CAP - Microbial Diagnostics
To culture or not to culture?
- Do not obtain sputum or blood C&S on outpatients
*consider for inpatients if severe CAP / intubated / being treated empirically for MRSA or Pseudomonas
- Consider sending urine pneumococcal + legionella Ag +/- lower tract legionella NAAT in severe CAP or when indicated by epidemiological factors (e.g., outbreak)
- Send rapid influenza molecular assay (NAAT) when influenza virus is circulating in community. **not included in 2019 guidelines, but current standing of care would suggest to also send COVID-19 PCR
- Do not send procalcitonin levels to distinguish between viral and bacterial pathogens
38
CAP - Outpatient Treatment
Healthy outpatients without comorbidities or risk factors vs. outpatients with comorbidities
1) Healthy outpatients without comorbidities or risk factors
- ***Amoxicillin 1 g TID (strong, moderate) - high yield
- doxycycline 100 mg BID (conditional, low)
- Azithromycin 500 mg and then 250 mg (or Clarithromycin) - only in areas with pneumococcal resistance < 25% (conditional, moderate) - not appropriate for majority of Canada
2) Outpatient with comorbidities (chronic heart, lung, liver, renal, DM, alcoholism, malignancy, asplenia)
- amox-clav OR cephalosporin (Cefpodoxime, cefuroxime) PLUS macrolide (strong, moderate) OR doxycycline (conditional, low)
- Resp FQ, e.g., levofloxacin, moxifloxacin (strong, moderate)
- Adds additional coverage for H. flu and M. catarrhalis (both produce beta-lactase frequently) and as well provides coverage for S. aureus and gram negatives, which are particularly high risk in COPD
39
CAP - Inpatient Treatment
a) Inpatients, non-ICU, without risk factors for MRSA or PsA
b) Inpatients, severe CAP (e.g., ICU), without risk factors for MRSA, PsA
c) Aspiration PNA
a) Inpatients, non-ICU, without risk factors for MRSA or PsA
i. Beta-lactam (amp-sulbactam, cefotaxime, CTX or ceftaroline) PLUS Macrolide (strong, high)
-doxy is a 3rd line option as alternative if unable to give other options (conditional, low)
ii. Resp FQ
iii. insufficient evidence for Omadacycline (tetracycline) as only single trial of non-inferiority to moxifloxacin
b) Inpatients, severe CAP (e.g., ICU), without risk factors for MRSA, PsA
i. Beta-lactam AND Macrolide (strong, moderate)
- Evidence that macrolide containing combination had lower risk of death, and evidence that combination of beta-lactam and Resp FQ had higher mortality (but poor evidence)
ii. *** Beta-lactam AND Resp FQ - high yield
c) Aspiration PNA
i. Recommend AGAINST adding empiric anaerobic coverage unless empyema or abscess present (conditional, low quality)
40
CAP - when to cover MRSA/Pseudomonas?
- CAP in inpatients - IDSA/ATS recommend abondoning the previous Healthcare Associated Pneumonia (HCAP) terminologu
- Consider MRSA coverage *based upon local risk factors (not as prevelent in Canada)
- * Vancomycin 15 mg/kg IV or linezolid 600 mg q12h
- Consider covering* for PsA based on locally validated risk factors
- *Pip-tazo or Cefepime 2 g q8h or Ceftaz 2 g q8h or Aztreoname or Mero 1 g q8h
41
CAP - other
A) When to transition to PO
B) Duration of Treatment
C) Steroids?
D ) Influenza
A) Transition to PO - when hemodynamically stable, tolerating PO/absorbing from GI tract
B) Duration of Treatment - 5 non-inferior to 10 in well-selected patients
- 5 days of antibiotics therapy OK if afebrile x 48 hours with 100, RR> 24, sBP< 90, paO2 <90%, can take PO, normal mental status)
C) Steroids: No longer recommended unless refractory shock. NB use of steroids for COVID-19 discussed separately - high yield
D ) Influenza: Oseltamivir if symptoms < 48 hours, hospitalized
- consider bactreial superinfection (GAS, S. aureus)
42
HAP/VAP: what are the core pathogens and how do you diagnose? What are the risk factors for multi-drug resistant pathogens: MDR VAP, MDR HAP, MRSA VAP/HAP, and MDR pseudomonas VAP/HAP?
Microbiology:
- Core pathogens = S. pneumoniae, **MSSA,** H. influenzae, **GNB including Pseudomonas**
Diagnosis:
- CPIS score NOT recommended by IDSA
- Clinical gestalt and Sputum/ETT/Blood Cx (non-invasive preferred)
- Tracheobronchitis vs. VAP
See table for MDR RFs
43
HAP/VAP: what is the empiric treatment?
44
Infectious Diarrhea: how do you diagnose?
- Stool cultures for Salmonella, Shigella, Campylobacter, Yersinia, STEC (shiga toxin producing E. coli) in patients with diarrhea AND:
- fever
- bloody or mucoid stools
- *Severe* abdominal pain
- Sepsis
- C. difficle testing in patients with:
- Recent antibiotics
- Work in healthcare/LTC or prison
- Compatible syndrome
- IBD flare
- Blood cultures in patients with:
- immunocompromise
- Sepsis
- Suspicion of entereic fever
- Stool for Ova and Parasites in patients with
- diarrhea ≥ 14 days
- Immunocompromise e.g., HIV
- Travel
- *Increased yield if ordered daily x 3 days*
- Repeat up to 3x to increase yield if high suspicion
45
Diarrhea: when do you empirically treat and with what?
- Empiric therapy in adults with bloody diarrhea not recommended UNLESS:
1. Sick immunocompetent patients with bacillary dysentery (frequent scant bloody stools, abdominal pain, tenesmus, fevers), suggestive of *Shigella*
2. Recent travel with high fever (≥ 38.5) and/or sepsis
3. Sick immunocompromised patients
- Empiric antibiotics choice: **ciprofloxacin or azithromycin**
- May use loperamide - caution if bloody stool, fever
46
Diarrhea Treatment: what is the modified treatment for specific pathogens (while awaiting sensitivities)?
47
C. difficle Infection Diagnosis:
What is the clinical syndrome, criteria for severe C. difficile, complicated C. difficile, and testing?
- Clinical Syndrome:
- Unexplained new onset ≥ 3 unformed stools in 24 hours
- Criteria for severe C. difficile:
- WBC ≥ 15 OR serum Cr 1.5 x pre-morbid level
- Other: Age > 65, immunosuppression, T > 38, Albumin < 30, peritonitis
- Complicated C. difficile:
- Sepsis, shock, ileus, perforation, toxic megacolon (colon dilation > 6 cm)
- Testing
- Stool toxin test, combinations:
- EIA for GDH, toxin
- NAAT PCR for toxin
48
C. difficile infection - what are the treatment regimens?
1st episode (mild-moderate), 1st episode (severe uncomplicated), 1st episode (severe complicated), 1st relapse, 2nd relapse
See chart
49
Intra-abdominal Infections (IAIs): what is the #1 principle of management and what is the initial antimicrobial coverage?
- **Adequate source control** is the #1 principle of management
- Percutaneous if possible, laparotomy otherwise
- Collections 3 cm or smaller can be attempted to be managed with antibiotics alone
- Initial antimicrobial coverage
- Community aquired, no previous hospitalization (E. coli, B. fragilis) = **Ceftriaxone or ciprofloxacin PLUS metronidazole**
- **Consider adding enterococcal coverage (vancomycin)** if immunocompromised, post-operative or recurrent, or if valvular heart disease/intravascular prosthesis
- Targeted antifungal coverage recommended for severe or nosocomial IAI if Candida isolated from intraabdominal or blood cultures. Empiric coverage otherwise does not improve mortality
- STOP-IT Trial (2015): if source control achieved, 3-5 days of antibiotics has similar outcomes to continuing until 2 days after resolution of fever, leukocytosis, and ileus.
50
UTI - Approach to Diagnosis
What is your approach (hint, 3 steps)? How do you diagnose?
**1. Is the patient symptomatic?**
- Symptoms = dysuria, frequency, hematuria, suprapubic pain → nausea, vomiting, fever, chills, flank pain
- [cloudy or smelly urine is not a symptom of UTI]
**2. Where is the urinary tract infection**
- cystitis (lower tract) vs. pyelonephritis (upper tract)
**3. Is it complicated or uncomplicated?** Complicated UTI if:
- Hemodynamically unstable, male, pregnancy
- Indwelling foley catheter, instrumentation
- Functional or anatomic anomalies, urinary tract obstruction
Diagnosis:
- Clinical, supported by: urinalysis and urine culture
- Consider imaging if concerned about upper tract diseases
51
UTI - Empiric Treatment
What is the 1st and 2nd line treatment of Cystitis, and treatment of Pyelonephritis?
**Cystitis**
First Line Treatment:
1. Nitrofurantoin 100 mg PO BID x 5 days
- avoid if concern of pyelonephritis
2. Septra 1 DS tab BID x 3 days
- avoid if recently used or in pregnancy
3. Fosfomycin 3 g sachet x 1
- avoid if concern of pyelonephriits; useful for ESBL organisms
Second Line Tretment:
1. FQ (levofloxacin or ciprofloxacin) or beta-lactam
**Pyelonephritis**
1. IV beta-lactam (preferred in pregnancy x 7-14 days)
2. FQ (if low resistance rates) x 5-7 days
Huttner et al. JAMA 2018
- Nirtofurantoin TID vs. Fosfomycin for uncomplicated UTI
- Date 28 resolution: 70% vs. 58% p=0.004
- Adverse effects comparable
- Bottom line: use nitrofurantoin if suspectible
52
Prostatitis
a) 3 pathogens?
b) Do you treat with aymptomatic?
c) Acute: symptoms, work-up, treatment and durtaion?
d) Chronic: symptoms, treatment, duration?
High Yield
a) E. coli, Pseudomonas, Enterococcus
b) Do not treat if asymptomatic unless elevated PSA, planning or biopsy or infertility
c) **Acute: **fever, intense local pain, sepsis
- Obtain urinalysis + culture prior to Abx
- Abx: empiric piptazo, 3rd gen ceph, FQ if unwell. If well, FQ.
- Duration: 2-4 weeks
d) **Chronic: **bacterial - may or may not have symptoms of prostatitis (nb not chronic pelvic pain syndrome)
- Abx - FQ or other pathogen directed therapy
- Duration: 4-6 weeks if FQ, 8-12 weeks if other Abx
53
Endometritis (post-partum)
a) Pathogens?
b) Symptoms?
c) Empiric treatment?
a) **Pathogens:** Group B streptococci, enterococci, S. aureus, anaerobic GPC, E. coli, Gardnerella, Bacteroides (polymicrobial)
b) **Symptoms:** fever, uterine tenderness, bleeding, foul smelling lochia, can progress to sepsis
- Assess for retained products of conception, abscess
c) **Empiric treatment: clindamycin + AG** (+/- ampicillin or vancomycin if suspect enterococcus)
- Stepdown to oral when defervesces
- No good evidence for duration, minimum?
54
Asymptomatic Bacteriuria:
When to screen?
Areas of limited evidence?
Screening
- Pregnancy - 4-7 days treatment recommended
- Evidence to suggest reduced pyelonephritis, pre-term birth and LBW
- Invasive urological procedures - 1-2 days recommended
- Endoscopic with mucosal damage
- Best to use targeted therapy
**Only indications to treat ASx Bacteriuria: pregnancy, urologic procedures with mucosal transection (e.g., TURP)** - high yield
Areas of limited evidence
- high risk neutropenia (ANC < 0.1, ≥ 7 days)
- kidney transplant in the first month
55
STI Treatment Simplified - Chlamydia
Treatment?
High yield
Azithromycin 1g PO x 1 OR
Doxycycline 100 mg PO BID x 7 days
56
STI Treatment Simplified - Gonorrhea
Treatment?
High Yield
Ceftriaxone 250 mg IM^ x 1 AND azithromycin 1 g PO x 1*
^Give ceftriaxone 2 g IV/IM daily x 7 days minimum for DGI/arthritis
*Azithromycin added both to cover undiagnosed chlamydia AND to ensure Gonorrhea covered
57
STI Treatment Simplified - Syphilis
Treatment?
(Primary, Secondary, Early Latent, Late Latent, Tertiary, Neurosyphilis)
And if PCN allergy, indications for PCN desensitization?
High Yield
**Primary/Secondary/Early Latent** - Benzathine Pen G 2.4 MU IM x1
**Late Latent (>1 year since possible acquisition), Tertiary** - Benzathine Pen G 2.4 MU IM weekly x 3 weeks
**Neurosyphilis** - aqueous penicillin 4 mU q4h IV x 14 days, then Benzathine Pen G MU IM x1, if possible late latent
If PCN allergy, indications for PCN desensitization:
- neurosyphilis
- pregnancy
- late latent or latent of unknown duration, tertiary syphilis
58
Chlamydia/Gonorrhea Diagnosis: what are the signs/symptoms and investigations?
59
Chlamydia/Gonorrhea Treatment: what are the treatments and complications?
60
Chlamydia / Gonorrhea Follow-up:
What is treatment failure? When is a test-of-cure indicated for CT and GC?
**Treatment Failure:**
- Positive gram stain > 72 hours after treatment
- Positive culture > 72 hours after treatment
- Positive NAAT 2-3 weeks after treatment
**Test-of-cure indicated if:**
- CT: suboptimal compliance, unresolved symptoms, alternative Rx used, pregnancy or pre-puberty
- GC: **ALL infections** (due to increasing resistance), especially if treatment failure, suspect drug resistance, suboptimal compliance, unresolved Sx, alternative Rx used, pregnancy or pre-puberty, or pharyngeal infection
61
Syphilis: What are the manifestations and treatments of primary, secondary, early latent, late latent and tertiary syphilis?
62
Syphilis Test Interpretation:
What are the types of tests and how would you interpret them?
Screening CMIA (NTT) vs. Confirmatory RPR (NTT) vs. Confrimatory TPPA (TT)
1. TT = Treponemal test (immunoassays, TPPA, FTA-ABS)
- Specific antibody against T. pallidum, persist over lifetime
2. NTT = Non-treponemal tests (VDRL, RPR)
- Non-specific antibody released during infection
* clinical history is important for test interpretation
63
For Syphilis, what are the indications for PCN desensitization, if PCN allergy? And what are the indications for an LP?
*** For PCN allergy, indications for PCN desensitization:**
– Neurosyphilis
– Pregnancy
– Late latent or latent of unknown duration, tertiary syphilis
*** Indications for LP**
– Neurologic, ocular, or auditory symptoms or signs
– HIV and neurologic symptoms or signs
* HIV and RPR > 1:32
* HIV and CD4 < 350 cells/uL
– Previously treated but failed to achieve adequate serological response
to treatment (ie. four-fold drop in RPR)
64
STI Persistent?
*** Persistent Pelvic Inflammatory Disease, urethritis or cervicitis**
– Particularly if empiric Rx for gonorrhea and chlamydia given, and initial tests for these come back negative
– Consider Mycoplasma genitalium or T. vaginalis
– M. genitalium testing available in national lab in Winnipeg
* Treat with moxifloxacin 400mg po x 7-14 d
* Upcoming chapter of its own in Cndn STI Guidelines
- In a multi-site Canadian study that used remnant samples collected in women for detection of C. trachomatis and N. gonorrhoeae, M. genitalium was detected in 53/396 (13.4%) women infected with C. trachomatis and in 22/406 (5.4%) women not infected with C. trachomatis
65
DDX by symptom
What is your differential if the symptom is a) genital ulcers, b) Urethritis/cervicitis, c) discharge, and d) Misc.?
BONUS
See chart
66
MCQ Miscellany...Extra STIs
Name some additional STIs, notes about them, and treatments.
67
Canadian Immunization Guide
– http://www.phac-aspc.gc.ca/naci-ccni/
» Click on ‘Canadian Immunization Guide’ for key updates and information regarding
specific vaccines
* Rabies, Tetanus
68
Skin and Soft Tissue Infections (SSTIs):
Name and describe some purulent (4) and non-purulent (4) SSTIs.
**PURULENT**
1. Folliculitis: Infection of isolated hair
follicle
2. Furuncle: Infection of hair follicle
extending into dermis + SC tissue
3. Carbuncle: Coalescence of several
infected follicles
4. Abscess: Collection of pus within
dermis + SC tissue
**NON-PURULENT**
* Impetigo: Most often caused by S.
aureus
* Erysipelas: Most often caused by
GAS, infecting epidermis + dermis
* Cellulitis: Most often caused by GAS,
infecting epidermis + dermis + SC
tissue
* Necrotizing fasciitis: discussed later
69
SSTIs: Purulent (Furuncle/Carbuncle/Abscess)
Define its severity (mild, moderate, severe), its corresponding empiric Rx and Defined Rx.
Purulent (Furuncle/Carbuncle/Abscess)
– I&D and C&S should be performed
70
SSTIs: Non-Purulent (Impetigo/Erysipleas/Cellulitis):
Define severity (mild, moderate), corresponding Abx and duration of treatment
71
SSTIs - what is the PATCH I Trial (2013)?
High yield
Penicillin to Prevent Recurrent Leg Cellulitis – PATCH I Trial (Thomas et al, 2013)
* Trial of oral penicillin to prevent cellulitis in individuals with at least 2 episodes/3 years
* Oral Penicillin (or equivalent beta lactam – amoxicillin or cephalexin) daily for at
least 1 year was effective in preventing subsequent attacks while on prophylaxis
– patients with BMI > 33, 3 or more episodes and lymphedema may have less effect
* Guidelines suggest to consider if ≥ 3 episodes/year DESPITE controlling other risk factors: revascularization, wound care, footwear, compression, treat tinea
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Compression Stockings for Recurrent Cellulitis (2020) - what did the study find?
* Participants with chronic leg edema and recurrent cellulitis assigned 1:1 ratio to leg compression therapy plus education on cellulitis compression vs education alone
* Follow-up q6mos for up to 3 years (or until 45 episodes of cellulitis in the trial)
* Primary outcome: recurrence of cellulitis
* Compression therapy resulted in lower incidence of recurrence than conservative treatment
– Interim analysis: 23 episodes, 6 (15%) in the compression group and 17 (40%) in the
control group had had an episode of cellulitis
– 3 participants (7%) in the compression group and 6 (14%) in the control group were
hospitalized for cellulitis (hazard ratio, 0.38; 95% CI, 0.09 to 1.59).
* Trial stopped early for efficacy.
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Necrotizing Fasciitis: what is it, your immediate treatment, and treatments depending on species?
Necrotizing Fasciitis (NF) – erythema with systemic toxicity, gangrene/anesthesia, hard induration, hemorrhagic bullae, pain-out-of-proportion and extending beyond erythema – CANNOT clinically distinguish types
– EMERGENT surgical inspection/debridement to rule out necrotizing process
(SURGERY CONSULT)
– EMPIRIC Abx: PipTazo + Vancomycin + Clindamycin
– Consider IVIG if shock or pre-operative
74
Toxic Shock Sydrome (TSS): Group A Strep, (and S. aureus - tampons, nasal packing)
What is the Streptococcal TSS Criteria and Management?
**Streptococcal TSS Criteria:**
* Hypotension (sBP < 90) AND
* Isolation of GAS from normally sterile
site AND at least two of the following:
* Renal impairment (Cr > 177)
* Coagulopathy (plt < 100 or DIC)
* Liver fx abnormality (ALT/AST/Tbili 2X
Upper limit of normal)
* ARDS
* Generalized erythematous macular
rash that may desquamate
**Management:**
* Contact and droplet precautions
* Volume resuscitation
* Surgery (especially if necrotizing SSTI
suspected)
* Antibiotics: Beta lactam PLUS
clindamycin
* IVIG – limited evidence but consider if
severe infection
* Hyperbaric O2 (HBO)–efficacy unknown
* Chemoprophylaxis – cephalexin x 10d (clinda if PCN allergy)
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SSTI Miscellany (1)
With the following clinical pictures, what is the classic micobiology association?
a) Diabetes
b) Water exposure
c) Rose gardens
d) Meat, butchers, veterinarians
e) Bites
76
SSTI Miscellany (2)
With the following clinical pictures, what is the classic micobiology association?
a) Ecthyma gangrenosum; malignant/invasive otitis externa; hot tub folliculitis;
green nail syndrome
b) “Herpetic” whitlow - can be mistaken for paronychia
c) Eczema herpeticum
d) Rose spots; fever in returned traveler, diarrhea/constipation, faint pink macules
on lower chest/upper abdomen
e) Umbilicated lesions, HIV (CD4 < 50), sub-acute meningitis, ↑ opening pressure
f) Burrows, pruritic and tracks seen in web spaces
g) HIV+ with white plaque on lateral aspect of tongue; does not scrape off
h) Black eschar in nasal mucosa or palate of diabetic
77
“A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses”: what were the findings?
“A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses”
(Daum et al, 2017)
* Compared clindamycin versus TMP-SMX versus placebo x10 days following I&D for skins abscess <5cm
* Cure rates similar between clindamycin and TMP-SMX
* Clindamycin group had less new or recurrent infection at 1 month but more side effects compared to TMP-SMX
**Bottom Line: Clindamycin or TMP-SMX in conjunction with I&D improves short-term outcomes in patients with simple S. aureus
abscesses**
78
Osteomyelitis:
Etiology - hematogenous vs. contiguous
Match the patient populations with organisms.
a) All patients
b) Foreign body, prosthetic infection
c) Nosocomial
d) Diabetes
e) Immunocompromised
Etiology
* Hematogenous (more common in children [long bones] vs. adults [vertebrae]) à
monomicrobial
* Contiguous from SSTI, trauma, or surgery (more common in adults) àpolymicrobial
79
Diabetic Foot Infection
What are the 3 types?
Signs that ulcer is infected?
*Oral exam
What type of foot ulcer is it?
**1. Neuropathic: **Pressure points, punched out appearance, deep ulcer, minimal pain, warm and dry foot
**2. Arterial: **Lateral malleolus, dry and punctate, decreased pulses, cold and dry foot
**3. Venous:** Medial malleolus, irregular margins, shallow depth, mildly painful, venous stasis dermatitis/lipodermatosclerosis
Is the ulcer infected?
**– Pain in chronic wound (LR 11-20)**
– Foul odour (LR 1-3)
– Purulence, exudate, erythema, warmth, and edema (LR < 1.0)
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JAMA: Does this patient with diabetes have OM of the lower extremity?
What clinical findings and investigations increase liklihood ratio? What is the gold standard test?
**- Gold standard = bone biopsy and culture**
- Presence or absence of ulcer inflammation (erythema, swelling, pus) does not modify probability of dz
- Superficial swab cultures do not reliably predict bone microorganisms or diagnose infection
- Many organisms, alone or in combinations, can cause DFI but staphylococci are most common
81
Native Vertebral Osteomyelitis:
What is the etiology, most common and other microbiology, risk factors, and signs/symptoms?
* Etiology: hematogenous seeding disc → bone
* Microbiology:
**– Most common S. aureus***
– Beta-hemolytic streptococci, GNB
– TB, Brucella, fungi much less common
* Risk factors:
– Elderly, immunocompromised, IDU, PICC/Ports
* Signs and symptoms:
– New/worsening back pain and suggestive b/w
– Fever (only 45% of patients)
82
Native Vertebral Osteomyelitis:
How do you diagnose?
Treatment: when to start Abx, Empiric Abx, duration, and when surgery is needed?
What follow-up is required?
Diagnosis:
– Blood cultures (50% Pos if S. aureus), **biopsy**
– ESR, CRP (sensitivity 94-100%)
– MRI (SN 97%, Sp 93%)
*If S. aureus bacteremia in prior 3 months, biopsy likely not needed
Treatment:
– Hold ABx until biopsy result if no sepsis/neuro
compromise (dx 50-60% of time with 1st bx)
– Empiric: ceftriaxone + vancomycin
– Duration: 6 weeks
– Surgery if neuro deficits, spinal cord compression,
progression/recurrence despite appropriate
antibiotics
Follow-up:
– Monitor clinically and repeat inflammatory markers
– Repeat MRI ONLY if poor clinical response after ABx
82
Prosthetic Joint Infection for the Internist:
What are the 3 Principles?
What are the empiric Abx?
Principles:
**1) Make micro diagnosis.**
– Withhold antibiotics if stable pending arthrocentesis / OR to ensure pathogen
determined.
**2) Surgical Management**
- see flow chart
**3) Antibiotics for 4-6 weeks IV or High dose
ORAL.**
– Consider chronic suppression w/ daily oral
abx thereafter (consult ID).
Empiric Abx in a scenario:
Vanco + CTX
Ideally in a scenario according to principle #1 --> you get your gram stain / micro diagnosis FIRST then tailor antibiotics!
82
OVIVA Trial (2019): Oral versus Intravenous Antibiotics for Bone and Joint Infection.
NEJM 2019
What did it find?
Oral versus Intravenous Antibiotics for Bone and Joint Infection. NEJM 2019
– 1054 patients with bone and joint infections randomized to IV vs. oral therapy.
– Primary endpoint was definitive treatment failure within 1 year after randomization.
– Treatment failure occurred in 74/506 (14.6%) of IV group and 67/509 (13.2%) of **oral group showing non-inferiority.**
– Caveat – majority surgically managed with identified organisms and were able to use highly bioavailable oral antibiotics
82
Approach to the New HIV Patient: what are the 6 steps?
(oral exam)
1. Stage the HIV Infection
2. Assessment for Co-Infections / Immunizations
3. Assessment for Opportunistic Infections (OI)
– Prophylaxis / Treatment
– Depending on CD4 count
4. Assessment of general health
5. Initiation of ARV
6. Follow-up Considerations
– HIV in pregnancy
82
HIV - Initial Assessment (oral exam)
What do you order to:
a) Stage the disease
b) Drug safety screening
c) General health
d) Assessing for co-infections
e) STI and sexual health
f) Immunizations
g) Counselling
**STAGE THE DISEASE:**
* Confirm positive test
* CD4 count/OI screen
* Viral load (RNA)
* Genotype (resistance)
* Tropism testing (CCR5)
**DRUG SAFETY SCREENING:**
* HLA-B5701 (ABC hypersensitivity)
* G6PD level
**GENERAL HEALTH:**
* CBC, lytes, Cr, PO4
* Non-fasting lipids/gluc
* Urinalysis/ BHCG
**TB SCREENING:**
* CXR
* TST or IGRA
**SEROLOGIES:**
* CMV IgG
* Toxoplasma IgG
* Hepatitis B/C serology
**STI AND SEXUAL HEALTH:**
* Syphilis screen
* Chlamydia, gonorrhea NAATs +/- cultures
* Pap test (cervical)
* Pap test (anal) – if genital warts
**IMMUNIZATIONS:**
* Hepatitis A (only at risk)
* Hepatitis B
* Annual influenza
* PCV-13 then PPV-23 eight weeks later
* (Hib, meningococcus]
*Caution with live vaccines (varicella, VZV, MMR) if
CD4 < 200
**COUNSELING:**
* Prognosis
* Safe sex practices
* Duty to disclose HIV status
* Side effects of therapy
83
Bonus: JAMA: Does this patient have early HIV infection? (oral exam)
Primary HIV infection (Acute retroviral syndrome) → fever, nausea, emesis, weight loss, arthralgia/myalgia, pharyngitis, oral ulcers, rash and LN
***Limited utility of clinical examination to
detect or rule out early HIV infection
highlights the importance of routine testing
for HIV infection among adults
(check out the 2015 video demonstrating this exam online)
84
HIV - Initiation of ARV
When is ARV recommended, what should the regimen include, what is the recommended initial regimen for most?
- Assess readiness for treatment
- **ARV recommended for all individuals with HIV, regardless of CD4 count** to reduce morbidity and mortality associated with HIV infection
- ARV regimen should include **TWO NRTIs PLUS INSTI** OR NNRTI OR PI
**Recommended Initial Regimen for Most:**
-Bictegravir/tenofovir alafenamide/emtricitabine
(evidence rating: AIa)
-Dolutegravir plus (all evidence ratings: AIa)
* Tenofovir alafenamide/emtricitabine
* Tenofovir disoproxil fumarate/emtricitabine
* Tenofovir disoproxil fumarate/lamivudine
-Dolutegravir/lamivudine with caveats (evidence
rating: AIa)
Tenofovir alafenamide (TAF) has fewer bone and renal toxicities, whereas tenofovir disoproxil fumarate (TDF) is associated with lower lipid levels and lower cost
85
HIV - Opportunistic Prophylaxis (1)
CD4 <200
What OI do we worry about, preferred Px and Alternatives?
- TMP-SMX should be continued if patients have non-life-threatening reactions where feasible, or
re-challenged when mild reaction resolved - consider lower dose
* Dapsone OK for sulfa allergy, NOT OK for SJS/TEN to TMP-SMX
* SJS/TEN is clear contraindication to re-challenge/continuation – give atovaquone
* Prophylaxis with TMP-SMX recommended during pregnancy – supplement with folic acid during first trimester (NT defects)
*** Continue prophylaxis until CD4 count stabilizes >200 for at least 3 months**
86
HIV - Opportunistic Prophylaxis (2)
CD4 <100 and CD4 <50
For each, what OI do we worry about, preferred Px and Alternatives?
*No longer recommended unless patients are not starting ART or not on fully
suppressive ART.
** Continue prophylaxis until CD4 count stabilizes for at least 3 months**
87
HIV - OI Treatment (1)
For PJP/PCP, what is the preferred Rx and alternative Rx?
88
HIV - OI Treatment (2):
For Toxoplasma and MAC, what is the preferred Rx and alternative Rx?
89
HIV - Opportunistic Infections Summary (Oral Exam)
Examples of OIs for CD4 count >500 and 200-500.
Check out aidsinfo.nih.gov/ for more information on managing other infections in HIV.
90
HIV - Opportunistic Infections Summary (Oral Exam)
Examples of OIs for CD4 count <200, <100, and <50.
91
HIV in Pregnancy:
How to manage pre-conception, intra-partum care, and post-partum care?
* Vertical transmission in untreated women is 25-35%, decreased to <1% with effective treatment
* All HIV-infected women contemplating pregnancy need ARV and undetectable VL prior to conception
* Goal of ARV= undetectable VL throughout pregnancy
* Intra-partum care (high yield)
– Continue ARV during labor and before scheduled C/S
– If VL > 1000 copies/mL (or unknown) near delivery, give IV zidovudine and recommend scheduled C/S
* Post-partum care
– If inadequate maternal ARV, infants given zidovudine x6 wks + nevirapine x3 doses
- **Breastfeeding NOT recommended for HIV positive mothers in [US/Canada],
as safe alternatives are available**
**Update 2020 - high yield **
**– Dolutegravir (DTG) now a Preferred drug for pregnant women, irrespective of trimester (AII), and an Alternative drug for women who are trying to conceive (AIII)**
* evidence has shown that the risk of neural tube defects (NTD) on DTG is not as high as previously estimated, and not enough data to determine the risk of NTD of all preferred agents
* Patients should be counselled and informed decision
* Folic acid for all
92
TB Exposure Risk:
what is your TB exposure risk?
93
Latent TB - Diagnosis
a) What are the 2 accepted tests?
b) Can they separate LTBI vs. active TB?
c) Compare the 2 tests.
a) Two accepted tests: TST and IGRA
b) Neither can separate LTBI from active TB
**Decision to test= decision to treat – only check if high risk/occupationally indicated**
94
Latent TB - Diagnosis
Who should be tested?
Who should be tested?
**Patients with higher probability of infection / significant risk factors for reactivation + low risk of toxicity + high probability of treatment completion**
* Contacts of active case of pulmonary TB
* Immigrants from countries with high TB incidence
* Travelers to countries with high TB incidence
* Indigenous communities
* Injection drug users
* Homeless
* Health care workers
* Residents of long-term care facilities or correctional facilities
95
Latent TB - Diagnosis
TB result and Situation in which reaction is considered positive.
0-4 mm vs. ≥ 5mm vs. ≥ 10mm
*high yield
96
Latent TB - Treatment
What is your approach, standard treatment regimen and alternative regimens?
1. Exclude active disease first
2. Balance risk of re-activation versus risks of AEs, age-dependent
97
BONUS - Increased Completion/Safety with Rifampin for LTBI
What did it find?
* Open-label RCT in 9 countries – Canadian study
* 4 mo Rifampin v. 9 mo Isoniazid
* **Non-inferior** (<0.5% difference in subseq. active TB)
* In mITT, 79% completed rifampin v. 63% isoniazid p <0.001
* Grade 3-5 AE with drug stopped and attributed to trial drug: 0.8%
rifampin v. 2.1% isoniazid p < 0.001 (driven by hepatotoxicity)
* ***Not yet in guidelines
98
Active TB - Treatment
How do you treat?
**4-2-2-4 Rule **= 4 drugs for 2 months THEN 2 drugs for 4 months
- EMB (ethambutol) can be stopped if fully susceptible isolate
- PZA (pyrazinamide) should be continued for full two months
- INH (isoniazid) supplementation with vitamin B6 (pyridoxine) to prevent peripheral neuropathy
* Steroids if TB meningitis or pericardial disease
* Consider longer duration if persistent cavity / culture positive at 2 months, CNS or bone.
rifampin (RIF)
99
Active TB - Side Effects - BONUS
What are the side effects of each of the 4 medications?
Isoniazid (INH) - rash (3), hepatitis (2), neuropathy
Rifampin (RMP) - drug interaction, rash (1), t (3)
Pyrazinamide (PZA) - hepatitis (1), rash (2), arthralgia
Ethambutol (EMB) - eye toxicity, rash (1)
1 (most likely), 4 (least likely)
100
Bonus - Active TB in Pregnancy
How to treat?
**Risk of untreated active TB to a pregnant woman and her fetus
outweighs risk of toxic effects of drugs used in its treatment**
* INH, RIF, EMB are considered SAFE in pregnancy, so all three should
be used as initial treatment
* What about PZA?
– WHO recommends use of PZA in pregnancy
– Some uncertainty about its safety in pregnancy but no reports of
teratogenicity (used in millions of pregnant patients worldwide)
* PZA can be given in women with extensive disease and/or women
who do not tolerate other first line drugs
101
TB and HIV
How to treat?
* Anyone diagnosed with latent or active TB should have an HIV test done
* All HIV positive patients with latent TB should be treated due to risk of
reactivation
* Active TB
– Assess for extra-pulmonary TB (more likely), drug interactions and IRIS
(immune reconstitution inflammatory syndrome)
* When to start ART (in ART-naive pts)?
– If CD4 < 50 → within 2 weeks
– If CD4 > 50 → within 8 weeks
– If TB meningitis → defer for ~8 weeks given ↑ risk of IRIS (especially if low CD4 count)
https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunisticinfection/mycobacterium-tuberculosis-infection-and?view=brief
102
TB and HIV 2019 Updates - BONUS
Latent TB and HIV preferred regimen?
Updates from 2019 HIV Guidelines
– Latent TB + HIV Preferred regimen: Isoniazid 300 mg PO daily plus
pyridoxine 25–50 mg PO daily x 9 mos (AI)
* Alternatives: weekly INH and Rifapentin for 3 months (AII) OR Rifampin daily for 4 months (BI)*
– INH preventative therapy in pregnancy not recommended until after delivery unless close contact of known TB case
– Prednisone not recommended in TB pericarditis
– If high risk for TB-IRIS, can give pre-emptive prednisone
103
Misc Updates - BONUS
Latent TB for healthcare workers.
Fluoroquinolone black box wardning.
* Latent TB Infection (LTBI) for healthcare workers
– CDC has changed its stance and no longer recommend:
* No routine serial TB testing in the absence of known exposure
* Annual symptom screening for those with untreated LTBI
* MMWR. Tuberculosis Screening, Testing, and Treatment of US Healthcare
Personnel. 2019.
* Fluoroquinolones Black Box Warning
– Jan 2019 FDA released a warning that FQ use is associated with
increased risk of aortic rupture or tear.
104
Non-tuberculous Mycobacteria
What is the diagnostic criteria and treatment?
*high yield
Over 190 species and subspecies: M avium complex, M. kansasii, M xenopi, M abscesses
Diagnostic criteria (NTM pulmonary disease): Both clinical (pulmonary or systemic sx) AND radiologic (nodular or cavitary lesions on CXR, or CT with bronchiectasis)
Plus one of:
* 2 or more sputum positive for same species NTM
* 1 BAL/bronch culture positive for NTM
* Biopsy with mycobacterial histology (AFB/granuloma) and positive culture
Treatment: Requires discussion around clinical factors, infecting species and patient priorities.
* Ideally susceptibility-based therapy (not empiric)
* Minimum 3-drug regimen (macrolide, ethambutol, +/-rifampicin +/- aminoglycoside)
105
Fever in Returned Traveler
a) Information to obtain from pre-travel and travel
b) Post-travel - timing of fever and what infections that could be. Pattern of fever and what infections that could be.
*BONUS + Oral exam
**Pre-Travel**
* Past medical history, medications
* History of a pre-travel consultation
* Travel immunizations (hepatitis A/B, yellow fever, typhoid, traveler’s diarrhea, rabies, meningitis, influenza)
* Adherence to malaria chemoprophylaxis
**Travel**
* Purpose of travel (VFR [visiting friends and relatives] greatest risk)
* Travel itinerary (exact dates and locations, including layovers), season
* Type of accommodations (urban versus rural)
* Insect precautions taken (repellant, bed nets)
* Individual exposures
– Ingestion of raw meat, seafood, street foods, unclean water, unpasteurized dairy products
– Freshwater exposure (e.g. swimming, rafting)
– Visits to farms, slaughterhouses, funerals, hospitals
– Animal bites or scratches, insect or arthropod bites, hiking/caving
– Body fluid exposures (e.g. tattoos, **sexual activity**)
* Medical care while overseas (e.g. injections, transfusions)
**Post-Travel**
* Timing of fever / clinical symptoms in relation to international travel
– Short incubation periods < 2 weeks = **Malaria**, Dengue, Chikungunya,
traveller’s diarrhea, viral URTI, influenza
– Longer incubation periods > 2 weeks = **Malaria**, TB, hepatitis, HIV, enteric fever due to Salmonella spp.
* Pattern of fever
– Daily: **Malaria**, traveller’s diarrhea, viral RTI, enteric fever
– Biphasic: **Malaria**, Dengue
– Relapsing: **Malaria**, enteric fever
106
Fever in Returned Traveler
What is your differential diagnosis and investigations to order?
**Differential Diagnosis**
A) * Infectious – Travel-related
**– Malaria, malaria, malaria!!!**
– Typhoid /enteric fever
– Dengue, Chikungunya, Zika virus
– Viral hepatitides
– Others: Rickettsiae, Brucellosis,
Leptospirosis, Q-fever, Ebola
– STIs, acute HIV
B) * Infectious – Non-travel related
– UTI, CAP, mono, meningitis, C. diff,
influenza, COVID-19
C) * Non-infectious
– VTE, drug fever, illicit drugs S/E
**Investigations**
* CBC + diff, peripheral smear
* Electrolytes, Cr, urea, glucose
* ALT, AST, ALP, Tbili, INR/PTT
* Blood cultures x2, urine culture
* CXR
* Malaria smears x3 (over 24h)
– RDT (e.g. Binax)
+/- Stool C&S; Stool O&P; C. difficile
+/- Dengue/chikungunya/zika PCR or serology
+/- Hepatitis serology
+/- HIV, STI screen
+/- NP swab for viral PCR (including SARS-COV2)
107
Malaria - Diagnosis
What are the species and diagnostic techniques?
**Species:**
* Plasmodium falciparum
– Can be severe
– Present within 3 months
– Infects RBCs of all stages
* P. ovale and P. vivax
– May present years later due to hypnozoites in liver
* Others:
– P. malariae
– P. knowlesi
**Diagnostic Techniques:**
Thick and thin blood smear x3, separated by at least 6 hours over 24 hour period
- Thick smear: Looks for any parasite (sensitivity 87%)
- Thin smear: Identifies parasitemia (%) and speciation by stain
Rapid detection test (RDT)
Separate tests for P. falciparum and others; highest Sn for P. falciparum
108
BONUS - JAMA
Does this patient have Malaria?
Clinical findings (signs and symptoms, lab findings) that suggest malaria or don't suggest malaria?
109
Malaria - Severity Criteria
What is the criteria for severe malaria?
**Criteria for Severe Malaria:
* Essentially any end organ
dysfunction**
* Neurologic = confusion, prostration
(severe weakness), seizures
* Respiratory = ARDS, pulmonary edema
* Hematologic = DIC (anemia,
thrombocytopenia, elevated LDH),
jaundice, hemoglobinuria --> Black water fever
* Severe anemia (Hgb < 50)
* Hypoglycemia (glucose < 2.2)
* Acidosis (pH < 7.25, HCO3 < 15)
* Renal impairment (Cr > 265)
* Hyperlactatemia
* Hyperparasitemia (UPDATED 2020) [RBCs infected with malaria parasites]
– ≥5% for non-immune adults
– ≥10% for semi-immune adults
110
Malaria - Management
How do you treat malaria based on severity, species and resistance?
111
Malaria - Chemoprophylaxis - BONUS
What medications can you use?
112
Some other travel infections to know - Bonus
List 5 infections, the incubation, features and Rx.
113
