Infection Flashcards
Criteria of IV to PO switch
o Clinical: haemodynamically stable, clinical improvement, afebrile > 24h, reliable GI tract function
o Lab: WBC normalising
o Drugs: good oral bioavailability
• Exceptions: meningitis, infective endocarditis (selected cases now allowed by [POET] trial), neutropenia
Sepsis and septic shock
Definitions
• Sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection
o Criteria: suspected/documented infection + acute in total SOFA score ≥ 2 points
o SOFA score: 6 components - assess lung (PaO2/FiO2 ratio), neuro (GCS), CVS (MAP & use of
vasopressors), RFT (Cr, urine output), liver (bilirubin), haematological system (platelet)
o Quick SOFA (qSOFA) as a screening test: mental status (altered), RR (≥22), SBP (≤ 100)
- qSOFA ≥ 2 should prompt calculation of SOFA score and further investigations
• Septic shock: sepsis + persistent hypotension (require vasopressors to maintain MAP ≥65 mmHg) + lactate > 2
mmol/L despite adequate volume resuscitation
Clinical features
• Non-specific: occur in systemic inflammation (e.g. trauma)
• Tachycardia, tachypnoea
• Temperature: fever or hypothermia
• Acute organ failure: GI (diarrhoea, vomiting), brain (delirium), etc
Management
1-hour sepsis bundle = IV crystalloid ± vasopressor + blood culture + lactate + broad-spectrum IV antibiotics
• Resuscitation: ABC
o 30ml/kg IV crystalloid for hypotension or lactate ≥ 4
o Add vasopressor (e.g. noradrenaline) if target MAP 65mmHg not met after fluid resuscitation
o O2 to keep SaO2 ≥ 96%
• Investigations: septic workup
o Blood culture x 2
o Urine for Pneumococcal & Legionella antigen, pregnancy test
(AG and tetracyclines teratogenic)
o Sputum & CXR
o Bloods (as in SOFA): serum lactate, ABG, CBC, RFT, LFT
• Broad-spectrum IV antibiotics given within 1h of diagnosis, adjusted according to C/ST result
o Not to be delayed because of sample collection
o Choice depends on possible site of infection
• Source control: assess for abscess (drainage), dead tissue (debridement), artificial device (removal)
• Adjunctive therapy:
o Hydrocortisone: adrenal insufficiency possible in sepsis; used in refractory vasopressor-dependent shock
o Transfusion: only when Hb < 7
o Glucose control: target ≤ 10
Pneumonia
Definitions
• Pneumonia:
o Syndrome of fever/ hypothermia, chills, SOB, cough, chest pain, sputum production, etc
o PLUS Compatible consolidation on X-ray imaging
• CAP: pneumonia in patients not hospitalised or residing in a long-term care facility for ≥14 days before onset
• HAP: pneumonia that develops ≥48h after hospitalisation
• Ventilator-associated pneumonia: ≥48h after intubation
Clinical features
• Clinical features not present in all patients, esp. elderly
• Clinical & imaging features cannot reliably distinguish “typical” from “atypical”
- Typical
Clinical:
- Fever
- Cough with purple not sputum
CXR:
- Lobar pneumonia: consolidation, air bronchogram - Atypical
Clinical:
- low grade fever
- Non-productive cough
CXR:
- Bronchopneumonia: Bilateral patchy
reticulonodular infiltrates at lung bases
• Severe pneumonia is defined by
o CURB-65: Confusion (AMTS ≤ 8/10), Urea > 7, RR ≥ 30, BP < 90/60, age ≥65
- 0-1: low mortality (1.5%) —> home treatment
- 2: intermediate mortality (9.2%) —> hospital short-stay treatment
- ≥3: high mortality (22%) —> assess for ICU admission
o ATS criteria for severe CAP: 1 major or 3 minor
- Major: invasive mechanical ventilation, septic shock, acute renal failure
- Minor: CURB (confusion, urea > 7, RR > 30, BP < 90/60), multi-lobar involvement, PaO2/FIO2 < 250, …
o Pneumonia severity index (PSI)
Ix:
• Microbiology:
o Sputum for Gram stain + C/ST (largely
replaced by MALDI-TOF)
o Sputum for AFB smear & TB culture
o Blood for C/ST x 2 (if severe CAP)
o Urine antigen tests: Strep pneumoniae, Legionella pneumophila serogroup 1
o NP aspirate / swab for RV RADT & PCR
- Seasonal influenza, RSV, parainfluenza, adenovirus
- SARS-CoV-2
- Atypicals e.g. Mycoplasma
o ± Pleural fluid for Gram stain, C/ST, pH and WBC - if pleural effusion >1cm thick on a lateral decubitus film
• Biochemical: ABG, CBC d/c, CRP, RFT, LFT
• Imaging:
o CXR (gold standard!): initial sensitivity ~70% (repeat if necessary),
differentiate lobar pneumonia vs bronchopneumonia
o CT: only if
- Respiratory failure with apparently normal CXR
- Lack of response suspecting complications, e.g. abscess
- Persistent CXR opacity 4-6 weeks after
Pathogen-specific presentation
• Strep pneumoniae: rapid onset, high fever, pleuritic chest pain
• Klebsiella pneumoniae: a/w UTI, liver abscess, endophthalmitis (consult eye!)
• Mycoplasma pneumoniae: haemolytic anaemia (cold AIHA), dermatological (erythema nodosum, erythema multiforme, SJS,), neurological (GBS, meningitis/encephalitis), arthritis
• Legionella: found in cooling system; flu-like symptoms e.g. CNS (headache, altered mental state), GI symptoms (vomiting,
Suspect TB:
• Unresolving > 2 weeks (esp. with night sweat)
• Cavitary infiltrates
• CXR shows upper lobe involvement
• CBC: WBC < 12 or lymphopenia
Causes of cavitating lung lesion
Infection
• Staph aureus
• Klebsiella
• Pseudomonas
• TB
• Aspergilloma
Non-infective
• Malignancy
• GPA
• Caplan’s syndrome (RA + pneumoconiosis)
Management
• General: fluid, O2
• Droplet precaution
• Early antibiotic treatment (best within 4h) to reduce mortality (typical duration 5-7 days)
- CAP
- Typical: Strep pneumonia, H influenza, Moraxella catarrhalis
- Atypical: (20-25%): Mycoplasma
pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila
- Viruses (20-25%): Influenza A/B,
RSV, Parainfluenza, adenovirus, metapneumovirus
Others: MTB, G- bacteria, CA-MRSA
• Outpatient (CURB-65 0-1)
—> PO augmentin +/- doxycycline (Penicillin allergy or suspected Legionella: Respi FQ e.g. levofloxacin, moxifloxacin, 14 days)
• Hospitalized with CURB-65 =2
—> PO/IV Augmentin +/- doxycycline ± oseltamivir (Consider Tazocin if chronic lung disease e.g. bronchiectasis)
• Hospitalized with severe pneumonia (CURB-65 3-5 / ATS)
—> IV Tazocin +/- doxycycline +/- oseltamivir - HAP
- Non-MDR (multi-drug resistant): typicals + S aureus
—> Onset < 4d after admission + no previous abx use
—> IV/ PO Augmentin
- MDR: MRSA, Pseudomonas aeruginosa, Acinetobacter, Stenotrophomonas maltophilia, ESBL-producing Enterobactericeae
—> Onset ≥ 4d after admission, recent use of antibiotics (90 days), Mechanical ventilation, septic shock
—> IV Tazocin
Change to IV meropenem if ESBL concern +/- vancomycin if MRSA concern - Aspiration pneumonia
- GNR, e.g. Pseudomonas, Klebsiella
- Oral flora, e.g. S aureus, anaerobes
—> Alcoholism, UGI disease
Neuro: dementia, DM
Mechanical: intubation, NG tube
—> IV Augmentin +/- metronidazole
Subsequent Mx:
- Monitoring: CRP, procalcitonin (guide antibiotics discontinuation - when PCT <0.5ng/ml)
- IV to PO switch
- Discharge if clinically stable and PO antibiotics started
- FU CXR at 4-6 weeks
Complications:
- Parapneumonic effusion
- Lung abscess: circumscribed collection of pus, mostly due to aspiration pneumonia
- Necrotising pneumonia: pneumonia with development of necrosis within infected lung tissue; pathogens include Klebsiella and S aureus
- Metastatic infection, e.g. endocarditis, meningitis
Prevention
1. 23-valent polysaccharide vaccine (PPSV23)
- Polysaccharide from capsule, weaker immune response
2. 13-valent protein conjugate vaccine (PCV13)
- Weak Ag (polysaccharide) attached to a strong Ag
- More powerful immune response
Recommendations by CHP (2017)
• Child < 2: PCV13 at 2m, 4m, 6m & 12m
• At risk individuals between 2y & 64y (e.g. asplenia, DM): PCV13, then PPSV23 at least 8w later
• Elderly > 65: PPSV23 + PCV13
Aspiration pneumonia
Pathogenesis
• Chemical pneumonitis: aspiration of acidic content
• Infection: oropharyngeal flora (mainly anaerobes, Strep, S. aureus)
Investigations
• CXR: usually recurrent RLL consolidation
• Video fluoroscopic swallowing study (VFSS)
Management:
• Augmentin ± metronidazole (better anaerobic coverage)
• Feeding method: careful hand feeding / Ryles tube (does not completely prevent aspiration!)
Lung abscess
Causes of non-resolving pneumonia
Definitions: failure to resolve clinically & radiologically after 12 weeks despite 10 days of antibiotics
• Infectious:
o Resistant bacteria
o Atypical organisms (TB, fungal)
o Persistent sources (IE, aspiration)
o Complications (empyema, abscess)
• Non-infectious:
o PE
o Inflammatory (vasculitis, BOOP)
o Malignancy
o Drug-induced pneumonitis (MTX, amiodarone)
Definition:
Localised collection of pus that forms a thick- walled cavity within the lung
S/S:
Insidious onset of cough, fever, night sweat
CXR:
Acute angle with chest wall
Spherical shape: similar size in different
projections
Air-fluid level
CT:
Thick irregular walls
Mx:
Prolonged antibiotics (months): Augmentin / clindamycin
Drainage: postural drain, image-guided
Surgical resection: if failed medical Tx
Empyema
Collection of pus within the pleural cavity
Risk factors:
- Poor denture
- Aspiration risk
- IC state: DM, HIV, malignancy
Microbiology
- GP: Strep milleri group, S aureus
- GN: Klebsiella (esp. in DM)
- Anaerobes
Clinical features
- Similar to pneumonia, except
- Decreased vocal resonance
CXR
- Obtuse angle with chest wall
- Lenticular shape: much larger on 1
projection than another
CT:
Split pleura sign (fibrin coating both parietal & visceral pleura)
Mx:
- Prolonged antibiotics (weeks)
- Large-bore chest drain
- ± Intrapleural tPA + DNAse
- Surgical decortication / thoracoplasty / drainage
Tuberculosis
Pathogenesis
Upon infection,
• 5% have primary TB disease
• 95% have LTBI, in which 5% lifetime risk of reactivation, and 90% remain latent for life
Screening test
• Positive in active TB, LTBI, past infection and non-TB mycobacterial infection
• Target population: household contacts, HIV-infected, biologics, silicosis
• Mantoux test (tuberculin skin test TST/ purified protein derivative PPD)
o Inject 5-TU intradermally, then palpate for max diameter of induration (not erythema) 48-72h after
o Positive: >10mm / >15mm (if BCG vaccinated)
o Note false positive (BCG vaccination) & false negative (non-intradermal injection, acute TB < 10 weeks)
• Interferon-gamma release assay (IGRA): more useful in BCG-vaccinated individuals
• Treatment of latent TB: isoniazid + pyridoxine for 9 months, after ruling out active infection
Clinical features
• Chronic cough: sputum, haemotypsis
• Systemic: fever, malaise, LOA, LOW
Complications (SAQ!)
• Acute: pleural effusion / empyema, lung collapse (Brock’s syndrome – RML collapse due to hilar LN), TB larynx, respiratory failure, extrapulmonary TB
• Chronic: apical fibrosis, bronchiectasis, cor pulmonale, aspergilloma (in old TB cavity)
Extrapulmonary TB
• Tuberculous lymphadenitis (scrofula): MC
extrapulmonary TB, usually involve cervical LN
• Tuberculous meningitis (TBM)
• Skeletal: Pott’s disease (spine), osteomyelitis
• Cutaneous: lupus vulgaris
• GI: mostly involve caecum
• TB peritonitis: due to rupture of caseous abdominal LN
• GU: sterile pyuria, epididymitis
Investigations
• Early morning sputum x 3: AFB smear (35% negative!), LJ medium culture & PCR
• CXR: hilar LN with ML/ LL consolidation (primary), apex (reactivation)
• Bloods: CBC, ESR/CRP, ADA
• Pre-Tx baseline: LRFT, urate, HBsAg ± anti-HIV, refer Eye for baseline visual acuity
Management (SAQ!)
• Contact tracing & report to DH
• Report to Labour Department if health-care worker / high-risk occupations
• DOTS (directly observed treatment, short-course): HRZE x 2 months + HR x 4 months, 3x/week in chest clinic
• Airborne precaution if AFB smear positive (open TB)
Isoniazid
- S/E: rash, hepatitis, peripheral neuropathy, encephalopathy
- add pyridoxine (vitamin B6) 10mg/day to prevent peripheral neuropathy especially those at risk (pregnancy, DM, alcoholism, CRF, HIV infection)
- CYP inhibition, DDI with phenytoin and carbamazepine
Rifampicin
- S/E: rash, thrombocytopenia
- red orange urin
- CYP inducers, council female for decrease efficiency of OCP
Pyrazinamide
- S/E: hepatitis, hyperuricaemia / Gout
- treat gout
Ethambutol
- S/E: retrobulbar neuritis, rash, arthralgia
- may be unilateral, document VA before Tx, closely monitor VA during Tx and consult Eye prn
• Anti-TB drug resistance
o MDR-TB (< 1%): resistance to at least rifampicin and isoniazid
o XDR-TB (< 0.1%): MDR-TB + resistance to any 1 FQ + ≥1 of 3 injectable 2nd lines (i.e. amikacin, kanamycin,
capreomycin)
• Liver derangement
o Discontinue if ALT > 3x ULN or bilirubin > 2x ULN
o Rule out other causes of hepatitis, e.g. alcohol, HBV, HCV
o Switch to interim regimen: streptomycin, levofloxacin, ethambutol (S-L-E)
o Rechallenge sequentially after ALT normalised: rifampicin —> isoniazid —> pyrazinamide (most hepatotoxic)
• Pregnancy: All 4 first-line drugs are safe – streptomycin and fluoroquinolones are C/I
• Children: Same drugs, but different dosage
Prevention: BCG vaccination
• Most effective for miliary TB and TB meningitis, less effective for pulmonary TB (0-80%)
Influenza
Diagnosis
• Clinical: cough, fever, myalgia
• Investigations:
o NPA for antigen detection (IF/EIA) or RT-PCR (gold standard, available as routine during winter surge)
o Lower respiratory tract specimen (e.g. BAL) preferred if suspected pneumonia / novel influenza
o Acute and convalescent sera for antibody titre rise (retrospective diagnosis)
Complications
• Chest: secondary bacterial pneumonia (esp. Staph aureus)
• Extra-pulmonary: myocarditis, myositis, rhabdomyolysis, Guillain-Barre syndrome, Reye’s syndrome (a/w use of aspirin), transverse myelitis
Treatment
Infection control: droplet precaution for seasonal influenza, airborne precaution for novel influenza
Antivirals: most beneficial if started early
- Oseltamivir PO 75mg BD x 5 days
(Tamiflu) - Zanamivir inhaled 10mg BD x 5/7
—> neuramindidase inhibitor
—> S/E: n/v, headache
—> Require renal adjustment (QD if CrCl < 30) - S/E: bronchospasm (caution in asthma/ COPD)
Baloxavir PO single dose
-Viral polymerase inhibitor
- S/E: n/v, headache
Prevention - influenza vaccination
• Tri-valent inactivated vaccine (A H1N1 + A H3N2 + B) or quadrivalent inactivated vaccine (A H1N1 + A H3N2 + B
(Victoria & Yamagata)) —> Efficacy depends on matching between vaccine strains and circulating strains
• Eligible groups: age ≥ 65, pregnancy, children on long-term aspirin, poultry workers
• C/I: egg allergy, neomycin allergy, previous allergic history to flu vaccine, high fever (>38.5)
Urinary tract infection
Definitions
• Asymptomatic bacteriuria: treatment not required (except in pregnancy, post-transplant, pre-op uro surgery)
• Uncomplicated UTI: UTI in healthy pre-menopausal, non-pregnant women without underlying urinary tract
abnormalities
• Complicated UTI: UTI with underlying urological abnormalities / in children, men and pregnant women
Risk factors
General
• Non-modifiable: female, post-menopausal (decrease estrogen)
• Behavioural: sexually active, use of diaphragm, spermicides
• Urologic: urinary incontinence, obstruction (e.g. BPH)
Complicated UTI
• Anatomical abnormalities, e.g. VUR, neurologic bladder
• Instrumentation, e.g. indwelling urinary catheters
• Immunocompromised: CKD, DM
Investigations - overview
• Urinalysis: leukocyte esterase (presence of WBC), nitrite (GNB), microscopy (pyuria)
• Urine culture: diagnostic if >10(5) colonies/mL
o Indications (important!): treatment failure, upper UTI, complicated UTI (i.e. pregnant women, men, children), recurrent UTI, post-treatment culture in pregnant women
• CT abdomen/pelvis (or renal USG if C/I contrast): if recurrent or severe
Management
1. Acute uncomplicated cystitis
• S/S:
- suprapubic pain, dysuria, Irritative symptoms, haematuria
• pathogens:
- E-coli
- Staph sacrophytes
- Group B Strep
- Enterococcus
• Ix:
- Urinalysis
- urine culture: not required for adults <65yr
• Mx:
Analgesics, increase fluid intake
Antibiotics for 3-7 days
- Nitrofurantoin (Side effects: brown urine, pneumonitis; C/I G6PD deficiency, renal impairment (CrCl < 30))
- Augmentin
- Fosfomycin (ESBL)
- Septrin / FQ: increase resistance
- Acute uncomplicated pyelonephritis
• S/S:
- fever + loin pain + n/v
• Pathogens
- E. coli
- Enterococcus
• Ix:
- urinalysis + urine culture
- imaging if no response in 3 days
• Mx:
Analgesics, anti-pyretics
IV antibiotics for 14 days
- Augmentin
- 3rd gen cephalosporin
- FQ - Complicated pyelonephritis
• S/S:
- renal failure, septic shock
• pathogens:
- Enterobacteriaceae
- Enterococcus
- P. Aeruginosa
• Ix:
- urinalysis + urine culture + blood culture
• Mx:
- Change / remove catheters
- IV meropenum / Tazocin - Emphysematous pyelonephritis
• S/S:
- gas formation
• pathogens:
- E. coli
• Ix:
- Renal USG
- CT abdomen
- HbA1C (DM)
• Mx:
- antibiotics, PCN +/- nephrectomy
Acute prostatitis
- Avoid vigorous PR exam (promote bacteraemia)
- Cotrimoxazole for 4 weeks
Chronic prostatitis
- Urine culture after prostatic massage
- Cotrimoxazole for 3 months
UTI in pregnancy
- Urinalysis + urine culture before & after treatment
- Treat even if asymptomatic bacteriuria
- Ampicillin (nitrofurantoin increases risk of haemolytic anaemia due to G6PD deficiency in newborn)
Recurrent UTI
- (≥3 infections in 12 months)
- Workup for urological causes
- Post-coital voiding, vaginal estrogen cream
- Antibiotic prophylaxis for 6 months (post-coital), ?cranberry juice
ESBL producers: can also be treated by Augmentin / FQ if tested susceptible in-vitro
Sex-transmitted disease (STI)
- Genital ulcer: sore preceded by blisters / vesicles
• Syphilis
- Treponema pallidum
- Ix (2 out of 4): VDRL, TP-EIA, TPPA, FTA-abs (if VDRL -ve, other +ve —> latent syphilis
- IM benzathine penicillin G
PCN allergy: doxycycline,erythromycin, PCN desensitisation (in pregnancy – other Tx not proven)
Monitoring: VDRL
• Herpes progenitalis
- HSV-2
- Viral culture & PCR
- Oral acyclovir (topical ineffective)
Inform OBS if pregnant
Analgesics - Urethral discharge and Dysuria
• Gonorrhoea
- Neisseria gonorrhoea
- Urine microscopy, urethral and vaginal swab for culture and PCR
- ceftriaxone IM
Azithromycin PO to cover NGU &
resistant strains of Neisseria
• Non-gonococcal urethritis NGU
- Chlamydia trachomatis
- Urine microscopy, urethral and vaginal swab for culture and PCR
- Azithromycin or doxycycline - Growth
• Genital warts
- HPV 6,11
- Clinical Dx, biopsy occasionally required
- Topical, e.g. imiquimod cream
- Ablative: cryotherapy, CO2 laser, curettage and cauterisation
• Condylomata lata / 2nd syphilis
- Treponema palidum
- Ix and Mx as syphilis
• Molluscum contagious
- pox virus
- clinical Ix
- Mx similar to genital warts
Acute dholangitis
- S/S:
• RUQ pain, fever, jaundice, chills, decrease BP - Pathogens:
• Enterobacteriaceae (68%)
• Enterococcus (14%)
• Bacteroides (10%) - Ix:
• Bloods: CBC D/C, LRFT, clotting, glucose
• Blood C/ST
• Abdominal USG
• ERCP ± C/ST - Mx:
• Active resuscitation and monitor vitals
• IV antibiotics for 4-7 days unless difficult
to achieve biliary decompression
o Mild-to-moderate: - Augmentin (± aminoglycoside)
- Cefuroxime + metronidazole (±
aminoglycoside) - Levofloxacin + metronidazole (if penicillin allergy)
o Severe: Tazocin / carbapenems
• Early biliary decompression (ERCP /
PTBD)
o Indications for emergency ERCP:
pain/guarding, decrease BP, high fever,
mental confusion
o Correct coagulopathy and fast patient
beforehand
Liver abscess
S/S:
RUQ pain, hepatomegaly, PUO, deranged LFT
Pathogens:
• Enterobacteriaceae: e.g. Klebsiella
pneumoniae (diabetic man; risk of
endophthalmitis, meningitis, other
metastatic infections)
• Enterococci
• Bacteroides
• Entamoeba histolytica: ± associated colitis,
WBC, eosinophilia
Ix:
• Bloods: CBC D/C, LRFT, clotting, HbA1c
• Blood C/ST
• Serology x E. histolytica
Mx:
• Active resuscitation and monitor vitals
• IV antibiotics (Augmentin / cefuroxime +
metronidazole)
o Suspected Klebsiella: high dose 3rd
generation cephalosporin, watch out
for metastatic infections
• Drainage
Enteric infections
Pathogens
• Bacterial: most common
o Pathogens that require antibiotics: typhoid fever, Shigella, Campylobacter, Vibrio
o C difficile: if recent antibiotics use
• Viral: norovirus, rotavirus
• Amoebic/ parasitic: Entamoeba histolytica, Giardia
Clinical features
1. Secretory diarrhoea (Non-inflammatory)
- Non-typhoid Salmonella, Vibrio cholerae,
Norovirus
- Cholera: Profuse painless rice-water diarrhoea
Norovirus: severe vomiting
- Dysentery (inflammatory)
- Shigella
Vibrio parahaemolyticus
Plesiomonas shigelloides
Entamoeba histolytica
- Abdominal pain
Fever, tenesmus
Blood & mucus in stool - Typhoid / parathyroidectomy fever (Enteric fever)
- Salmonella typhi
Salmonella paratyphi
- High fever with relative bradycardia (HR not proportional to temperature)
Rose spot (transient macular rash seen on trunk during 2nd week of illness)
Hepatosplenomegaly
Leucopenia, thrombocytopenia - CDAD
- Clostridium difficile - Enteric infections with systemic complications
- E coli O157:H7: hemolytic uremic syndrome
- Campylobacter enteritis: Guillain-Barre syndrome
- Non-polio enteroviruses: HFMD, myocarditis, encephalitis
Investigations
• Indications of stool C/ST, viral antigen and ova & cyst (need to know!)
o No improvement after 48h
o Severely symptomatic
o Immunocompromised
• Suspected typhoid/ paratyphoid fever: C/ST from stool, blood, bone marrow aspirate
o Widal’s test (serology): not sensitive nor specific
Management
• Rehydration therapy: adequate fluid and electrolyte replacement
• Routine antibiotics NOT recommended for mild-to-moderate gastroenteritis
• Empirical antibiotic
o Indications (need to know!)
- Specific pathogens: Shigella, Campylobacter, Vibrio, traveller’s diarrhea (ETEC/ Giardia)
- Severely symptomatic: bloody, ≥ 6 unformed stools/ day, fever ≥38.5, tenesmus
- Immunocompromised
o Antibiotic choice:
- Febrile dysentery (e.g. Shigella): ciprofloxacin 500mg BD PO / levofloxacin 500mg PO x 3-7 days
- Campylobacter: azithromycin 500mg PO x 3 days (FQ resistance)
- Cholera: doxycycline 300mg PO once
- Typhoid/ paratyphoid fever (FQ resistance is common!): IV ceftriaxone 2g Q24h for 10-14 days
Prevention
• Typhoid vaccine (ineffective for paratyphoid)
• Hand hygiene
CNS infection
Disease entities
1. Meningitis
Bacterial:
• Neonates: GBS, E coli, Listeria
• Infants & adults: Neisseria meningitidis, Strep pneumoniae, Hemophilus influenzae
• Elderly: E coli, Listeria
Viral: HSV, enterovirus, Japanese encephalitis, rabies, mumps
- Encephalitis
- Viral MC
- DDx: autoimmune encephalitis - Brain abscess
- Bacterial MC
• Haematogenous spread (MC, e.g. chest, IE): Strep pneumoniae, Staph aureus
• Direct extension from sinuses / scalp: Staphylococcus - Subdural empyema
Collection of pus between dura and arachnoid
• Spread from sinusitis / AOM / mastoiditis, or trauma / operative wounds - Ventriculitis
Complication of severe meningitis / rupture of brain abscess, high mortality - Myelitis
- Idiopathic, infection, autoimmune (e.g. SLE), demyelinating (e.g. MS, NMOSD)
Clinical features:
fever + neurological symptoms = CNS infection until proven otherwise
- Triad of meningitis: headache, fever, neck stiffness —> photophobia, kernig’s sign, bruzinski’s sign
- Signs of encephalitis: altered mental state, seizure
- Brian abscess: fever, seizures, FND
Strep pneumoniae (MC bacterial)
- URTI / pneumonia / otitis media/ sinusitis/ mastoiditis, CSF leak
- Risk factors: alcoholism, splenectomy, HIV, DM, CKD
Neisseria meningitidis
- S/S: ILI (e.g. myalgia, vomiting), purpura, DIC, Waterhouse-Friedrichsen syndrome
- Risk factors: children/young adults, crowding (e.g. dormitories, barracks)
Listeria monocytogenes
- Exposure to unpasteurized milk and dairy products
- Risk factors: neonates, elderly, immunocompromised
Group B Strep
- Neonatal: prevented by 35-37wk screening and IV ampicillin during labour
- Adult: associated with DM, cirrhosis, malignancy
Strep suis
- Exposure to pig; complication: SNHL
Enteroviruses (MC viral)
- Subgroups: echovirus, coxsackie A and B, poliovirus
- Associated with rash, mouth blisters, pericarditis, conjunctivitis, HFMD
HSV
Tend to affect temporal lobe (hippocampal region)
- CT brain: unilateral temporal oedema (difficult to visualise), hydrocephalus
- EEG: periodic lateralised epileptiform discharges (PLED) with high risk of seizure
VZV
- S/S of reactivation: zoster, meningoencephalitis, Ramsay-Hunt syndrome, GBS-like
Japanese B encephalitis
- High mortality
- S/S: movement disorders (basal ganglia / thalamus involvement), psychosis, seizures
- MRI brain: scattered T2-hyperintense lesions
HIV / immuno-compromised
- Associated disease entities:
- TB meningitis: AFB +ve in only <10%, C/ST +ve in 10-60%
- Toxoplasma encephalitis: MRI shows multiple rim-enhancing lesions
- PML: demyelinating disease due to JC virus reactivation
- Cryptococcal meningitis: ICP is frequent
- HIV encephalopathy
- CMV encephalitis / retinitis: fundoscopy shows “cheese and ketchup” pattern
- Primary CNS lymphoma
CJD
- Types: sporadic (85%), variant (via cattle), familial, iatrogenic
- MRI DWI: cortex signal changes (sCJD), pulvinar signs (vCJD; S/S hypersomnolence)
- EEG: periodic sharp wave complexes ~ ECG (advanced stage)
Neurosyphilis
- Brain syndrome: general paresis of the insane (progressive dementia, brisk reflex,
tremor)
- Spinal syndrome: tabes dorsalis (ataxia, areflexia, sensory loss)
• Other relevant history
o Travel: SE Asia (malaria, TB, Jap B, Dengue)
o Occupation: butchers (Strep suis)
o Contact: pigs (JBE, Dengue, Strep suis), mosquitoes (JBE, Dengue, malaria), dogs (Rabies)
o Drug: natalizumab/rituximab (PML)
Investigations
Sequence in [acute med]: Blood C/ST —> Dexamethasone —> Antibiotics —> CT scan —> LP
• Bloods: CBC d/c, LRFT (for SIADH), clotting profile, glucose, blood C/ST ± EEG, XR skull/sinus/mastoid
• CT brain to rule out SOL if suspect ICP
• LP (crucial!) for CSF analysis: cell count, protein, glucose (with paired blood glucose), microbiology, cytology, ADA, PCR
• Microbiological tests to confirm pathogens:
o Viral: PCR (HSV, VZV, enterovirus)
o Bacterial: gram stain, C/ST, latex agglutination x bacterial Ag
o TB: AFB smear, C/ST, PCR, ADA (adenosine deaminase)
o Cryptococcal: India ink (75%), CSF/ blood culture, latex agglutination / PCR for cryptococcal Ag
Neuroimaging
o Contrast CT brain: leptomeningeal enhancement, rim-enhancing lesion (abscess)
o MRI brain T2/FLAIR: hyperintensity in mesial temporal lobe / inferior frontal lobe (HSV encephalitis),
tuberculoma (TB meningitis)
CSF gram stain findings:
• S pneumoniae: GP diplococci
• N meningitidis: GN diplococci
• Hib: pleomorphic GN coccobacilli
• L monocytogenes: GP rods
Management (SAQ!)
Empirical treatment: IV ceftriaxone 2g Q12h + acyclovir 10mg/kg Q8h
• Likely pneumococcal / TB: + IV dexamethasone 0.15mg/kg Q6h
• Advanced age (≥50) / pregnancy / immunocompromised: + IV ampicillin 2g Q4h
• Risk of Pseudomonas: + IV meropenem (CNS dosage)
• ± IV vancomycin 500mg Q12h (cover drug resistant S. pneumoniae – not common in HK)
Definitive treatment
- 1. Bacterial meningitis
IV dexamethasone 0.15mg/kg Q6H for 4 days (1st dose before / together with antibiotics)
- IV ceftriaxone 2g Q12h (meningitic dose) ± IV vancomycin 500mg Q12h
• Ceftriaxone: meropenem if PCN allergy
• ± Vancomycin: continue until r/o Strep pneumoniae; target trough 15-20mcg/ml
• Add ampicillin 2g IV Q4h if risk of Listeria infection
Duration of treatment: depends on pathogen (do NOT change to PO antibiotics)
• H. influenzae: ≥ 7 days
• S. pneumoniae: 10-14 days
• L. monocytogenes / S. agalactiae: 14-21 days
• Gram -ve (e.g. E. coli, N. meningitidis): ≥21 days
- Brain abscess
- IV ceftriaxone 2g Q12h + IV metronidazole 500mg Q8h
- Dexamethasone if with significant cerebral oedema
- Consult NS for drainage
- Duration of treatment: 6-8 weeks - HSV encephalitis
- IV acyclovir 10mg/kg Q8h for 2 weeks - Japanese B encephalitis
- Serology x 2 (14 days apart)
- No specific treatment - TBM
- HRZE x 2 months + HR x 10 months (total 12 months)
IV dexamethasone for 6-8 weeks
HIV testing ± repeat LP to monitor CSF changes - Cryptococcal meningitis
- IV Amphotericin B 1mg/kg over 4-6h + PO 5-flucytosine for ≥2 weeks,
- Then PO fluconazole 400mg daily for ≥8 weeks - CJD
- No specific treatment
- Prevention: disposable equipment - Neurosyphilis
- Ix: EIA (screening), FTA-abs or TPPA (confirmatory)
- Tx: IM procaine penicillin 2.4MU daily + probenecid QID for 17 days (stop but not
reverse the disease)
• Role of dexamethasone:
o Anti-inflammatory actions: reduce rate of hearing loss, other neurological complications and mortality
o Indications: pneumococcal meningitis (4 days), TBM (6-8 weeks), brain abscess with cerebral oedema
o NOT for Cryptococcal meningitis
• Prophylaxis for contacts of meningococcal meningitis (direct contact of <3ft for ≥8h)
o Regimen: PO rifampicin 600mg Q12h x 2 days / ciprofloxacin 500mg x 1
- Alternative IM ceftriaxone 250mg x 1 (for pregnant /lactating women)
• Consider prophylactic anticonvulsant for brain abscess / subdural empyema
Reasons for treatment failure
• Resistant pathogens
• TB / opportunistic infections
• Autoimmune encephalitis
Complications of CNS infection
• Hydrocephalus
• Cranial nerve palsy
• Seizure
• SNHL (esp. Strep suis)
• Vasculitic infarcts
Skin and soft tissue infections
- Impedigo
- S/S: golden yellow stuck-on crusts, painless vesicles
- Group A strep + Staph A
- PO cloxacillin + topical fusidic acid - Erysipelas
- supficial cellulitis
- group A strep
- PO cloxacilin, PO Augmentin - Cellulitis
- fever, pain, erythema, non-toxic looking
- Group A strep, staph A
- PO cloxacilin, PO Augmentin
- recurrent: look for tines pedis - Necrotising fasciitis
- high fever, toxic looking, dusky skin colour with blisters, haemorrhagic Bullard, excruciating pain disproportional to physical finding
- seawater / seafood: vibrio vulnificus, aeromonas hydrophilia —> IV levofloxacin + Augmentin
- Cuts/IVDA/varicella: Group A strep —> IV penicillin G + rifampicin / linezolid
- after intra-abdominal / gynae surgery: polyicrobial (enterobacteriacaea, strep, anaerobeas) —> IV meropenem
—> ICU support, aggressive surgical exploration and debridement
—> IVIG for strep toxic shock Sx
—> hyperbaric O2
Infected bite wound
- strep, staph A, anaerobes
- IV Augmentin
Diabetic food infection
- look for secondary osteomyelitis
- Staph A, GAS, polymicrobial
- IV Augmentin
HIV infection
Overview
• Stats at 2022: annual incidence ~450 (peak at 2015, downtrend after START trial), cum. incidence ~11500
• 90-90-90 target (90% aware of HIV status —> of which 90% on HIV treatment —> of which 90% virally suppressed)
• Route of transmission:
• Types: HIV-1 (pandemic), HIV-2 (limited to West Africa)
Clinical course
- Acute phase (acute HIV seroconversion
syndrome)
—> Onset: 1-6 weeks after infection
Mononucleosis-like syndrome: fever, rash, LN
Ix: atypical lymphocytes
- Asymptomatic phase (incubation period)
—> Duration: 6-10 years
- Symptomatic phase (AIDS)
—> CD4 < 200 or AIDS-defining conditions (see below)
Diagnostic test
• Indicator condition-guided testing: offer screening test if
o STD
o Ongoing infectious mononucleosis
o Unexplained leucopenia/ thrombocytopenia
• Regular HIV screening (at least Q1y) for key populations:
o MSM / transgender woman (Q3-6m)
o Female sex workers and male clients
o Injecting drug users
o Partners of PLHIV
• Informed consent required (seek from guardian if mentally incompetent)
• Two-step test: both +ve = HIV infection (SAQ!)
Screening test (sensitive)
—> ELISA (4th gen): HIV p24 antigen + HIV Ab combo
—> time to positivity: 14-21 days
Confirmatory test (specific)
—> Western blot assay: to detect HIV Ab +/- HIV RNA PCR for seroconverting patients
—> 10 days
Acquired immunodeficiency syndrome (AIDS)
• Definitions: positive HIV test + AIDS-defining conditions (as below) or CD4 < 200
• AIDS-defining conditions (see Opportunistic infections)
o Most common: PJP > TB > Kaposi’s sarcoma
o CD4 >800: normal
o CD4 200-500: oral candidiasis, pulmonary TB, herpes zoster/ chickenpox, Kaposi’s sarcoma
o CD4 < 200: PJP, extrapulmonary TB
o CD4 < 100: oesophageal candidiasis, cryptococcosis, penicillosis/ talaromycosis, toxoplasmosis
o CD4 < 50: CMV infection, MAC
• Other non-AIDS-defining clinical features
o Unexplained generalised lymphadenopathy
o Unexplained weight loss
o Idiopathic thrombocytopenia
Management of HIV
Principles
• Disease monitoring (clinical, immunological, virological)
• Prevent and treat opportunistic infections
• Antiretroviral therapy (HAART)
• Counselling and psychological support
Baseline evaluation
• Viral activity: CD4 count, HIV RNA
• Co-morbidities: HAV/HBV/ HCV, syphilis, Toxoplasma serology
o HAV: anti-HAV vaccine if non-immune
o HBV: anti-retroviral need to cover HBV
• Drug-related: CBC, LRFT, FBG & lipids, urinalysis, G6PD, genotypic resistance test, HLA-B5701 (abacavir in non-Chinese)
Highly active antiretroviral therapy (HAART)
• Drug cocktail (usually single-tablet) to avoid resistance
• Start regardless of CD4 count / viral load (INSIGHT START trial
• Treatment as Prevention (TasP)
• 6 drug classes
• Generally consist of 2 NRTI + 3rd drug from INSTI (most common) or NNRTI or PI
• 2-drug combo (lamivudine + dolutegravir) is being investigated in trials
• Short delay of ART if opportunistic infection: risk of “immune reconstitution inflammatory syndrome (IRIS)”
NRTI: zidovudine, lamivudine, tenofovir, abacavir
NNRTI: nevirapine, rilpivirine, efavirenz
Integrase inhibitors: dolutegravir, raltegravir in 2015)
Protease inhibitors: ritonavir, saquinavir
Entry inhibitors: maraviroc
NRTI toxicity: lipodystrophic facies
S/E of NNRTI (should be taken before food): dizziness, night dreams, insomnia
Pre-exposure prophylaxis (PrEP)
• Use of antiretroviral medications to prevent acquisition of HIV infection by uninfected people
• Regimen: oral daily Truvada (tenofovir + emtricitabine) / vaginal gel
• Indications: MSM in previous 6 months with
o Unprotected receptive anal sex with partners outside monogamous relationship
o ChemFun (e.g. metamphetamine)
o Newly acquired STI
Opportunistic infections
- PJP
- Pneumocystis jirovecii
- CD4 <200
- S/S; dry cough, SOBOE, Desaturation in 10 min walking test, pneumothorax
- Ix: ABG (increase A-a gradient), CXR (bilateral perihilar opacities / symmetrical interstitial infiltrates without cardiomegaly), induced sputum / BAL for silver stain / toluidine blue stain / Grocot’s stain, bloods: LDH, beta-D-glucan
- Mx: O2, high dose septrin x 3 weeks, steroid x 3/52 if hypoxemia (to reduce pulmonary inflammation), IV pentamidine, Secondary prophylaxis: Septrin - esophageal candidiasis
- <100 CD4
- whitish plaque that cannot e washed away by OGD
- Ix: OGD
- Mx: Fluconazole PO x 2/52, echinocandin for liver impairment - Cryptococcosis
- cryptococcosis neoformans
- <100
- S/S: meningitis, pneumonia
- Ix: CSF for India ink stain, latex agglutination test for cryptococcal Ag / PCR
- Mx: Amphotericin B + flucytosine,
then long-term fluconazole PO - Penicillosis
- penicillium marneffei
- <100
- S/S; ubilicated erythematous applies (resembling molluscum contagiosum)
- Ix: culture (blood, BM), serum galactomannan
- Mx: Amphotericin B then long-term itraconazole PO - Toxoplasmosis
- toxoplasma gondii
- <100
- S/S: encephalitis
- Ix:serology (Ab), MRI brain (multiple ring-enhancing lesions)
- Mx: Septrin - CMV infection
- <50
- Reitinitis, encephalitis, colitis, multiple GI ulcer, pneumonia is, CMV antigenaemia (fever)
- Ix: Fundoscopy: cheese and ketchup pattern, CMV pp65 antigen, viral PCR
- Mx: Ganciclovir IV, Valganciclovir PO - MAC infection
- <50
- TB symptoms
- Mx: Macrolide + ethambutol + rifampicin for 12 months
- prophylaxis: azithromycin if CD4<50
*Side effects of Septrin: myelosuppression, liver/ renal impairment, skin rash
Investigations prior to treatment: G6PD status, CBC, LFT, RFT Indications for PJP prophylaxis:
Indications for PJP prophylaxis
• HIV infection: CD4 < 200 or Hx of PJP
• Non-HIV:
o Haematological: ALL, HSCT (6 months)
o Solid organ transplant (6-12 months, lifelong for lung transplant)
o Multiple high-dose immunosuppressants
o Primary immunodeficiencies
Malaria
Pathogens
- Plasmodium falciparum: MC, incubation 10-14 days, more severe
- P vivas
- P ovale
- P malariae (longest incubation)
- P Knowlesi
- S/S:
ID emergency: rapid fatal
Non-specific ILI: fever, malaise, myalgia, pallor, hepatomegaly
No rash, LN
Infected RBC sequestered in end-organ capillaries —> splenic rupture
Clinical criteria for severe malaria
• Prostration (generalized weakness)
• decrease consciousness
• convulsions
• Respiratory distress (acidosis / ARDS)
• Circulatory collapse
• Radiological pulmonary edema
• Abnormal bleeding, jaundice, Hburia
-Ix:
Thick and thin blood smear x 3 (12 h apart)
Lab finding of severe malaria
• Hypoglycemia
• Metabolic acidosis
• Anaemia
• Hyperparasitemia >5%
• increase lactate > 5
• AKI
- Mx:
Severe malaria (any 1 clinical/lab)
• Artemisinin-combination therapy (ACT) x 7 days: IV artesunate + doxycycline
• ICU x organ support: ABC, antipyretic, monitor Hstix, control seizures, transfusion, NIV, RRT, broad-spectrum antibiotics
Non severe
• Options: Malarone (atovaquone/proguanil), Coartem (artemether/lumefantrine), quinine + doxycycline
• Primaquine 45mg x1 at the end to eradicate gametocytes
Non-severe malaria (other spp.): chloroquine + primaquine x 14 days to eradicate hypnozoites if P. Vivax/ovale
- prevention
• Insect bite: physical barrier (e.g. light-coloured clothing), insect repellents (DEET ≥20%), mosquito coils
• Chemoprophylaxis: doxycycline, mefloquine, Malarone
Lepospirosis
Leptospira species
RF: contaminated fresh water, rats, water sports
S/S:
Fever, myalgia, headache, rash
Severe : ARDS, lug haemorrhage, hepatic and renal involvement
Conjunctival suffusion
Ix:
CBC: decrease Pt, normal WBC
LFT: increase ALT, bilirubin, increase CK
Dx: serology
Mx:
IV penicillin G / doxycycline
• Jarisch-Herxheimer reaction: antibiotics (e.g. Augmentin) reacting with spirochetes (e.g. syphilis, leptospirosis) causing fever, hypotension, tachycardia; Mx NSAID
• Chemoprophylaxis: doxycycline
Dengue fever
Dengue virus: 4 serotypes
Incubation 4-10 days
Dengue fever:
High fever, severe headache, retrobulbar pain, myalgia, n/v, +ve tourniquet test
Rash: White Island in a sea of red
Dengue with warning signs:
Abdominal pain, persistent vomiting, fluid retention, mucosal bleeding, hepatomegaly >2cm, increase Hct with rapid decrease platelet
Severe dengue: at least 1
• Severe plasma leakage: shock, fluid
after Day 4 accumulation with resp distress
• Severe bleeding
• Severe organ involvement: ALT > 1000,
impaired consciousness, organ failure
Ix:
Decrease WBC, platelet
Atypical lymphocytes
Deranged LFT
Specific test:
• Dengue virus NS1 antigen / RT-PCR (preferred in 1st week)
• Serology (IgM): after day 4
Mx;
No specific antiviral
Supportive therapy
• Monitor: vitals, I/O, Hct (guide fluid Mx), WCC, Plt, LRFT
• Bed rest, antipyretics
• Fluid replacement: isotonic crystalloids (NS, Hartmann)
• Monitor closely when fever goes down: critical phase (lasting 24-48h) usually occurs around that time, with increase capillary permeability causing plasma leakage
• ICU care if severe Dengue
Discharge if:
- Afebrile x 48h
- improved clinical status
- increase platelet, stable Hct
Amoebiasis
Entamoeba histolytica
RF: long-term travel > 6 month, immunocompromised
S/S:
GI: diarrhoea, abdominal pain, weight loss
Extra-intestinal: fever, RUQ pain (liver abscess)
Ix:
Fresh stool microscopy
Serology
PCR to distinguish species
Mx:
- symptomatic: metronidazole then diloxanide
- asymptomatic: diloxanide
COVID19
Nirmatrelvir/ritonavir PO
- 5 days
- mild to moderate
- renal adjustment
- C/I if eGFR < 30, <12yr / BW <40kg, child’s C
- multiple DDI
Baricitinib PO (JAK1-2 inhibitor)
- 14 days
- indications: severe
- renal adjustment
- C/I if eGFR <15
Tocilizumab IV (anti-IL6)
- X1
- 8mg/kg
- Severe
- Used with steroids
Molnupiravir PO
- 5 days
- 800mg Q12h
- mild to moderate
- C/I: pregnancy, breastfeeding, <18yr
Dexamethasone
- up to 10 days
- indicate on O2/mechanical ventilation
