1
Q
acute bronchitis
A
Acute cough (<3wks) due to inflammation of trachea, lower airways
* Acute cough + preexisting health conditions, exposure hist
* Start in viral upper resp tract infection
- Self-limiting
2
Q
Differential diagnosis of acute bronchitis
A
Ensure its viral, not sinister:
* Common cold
* Cough variant asthma
* Acute exacerbation of chronic bronchitis (smoker)
* Acute exacerbation of bronchiectasis
○ Fibrosis in lungs. Smoker damaged lungs caused over-repaired
* Acute rhinosinusitis
* Pneumonia
* Acute asthma
* Exacerbation of COPD
3
Q
diagnostic testing for bronchitis
A
Not indicated in absence of other signs and sx of bact infection
4
Q
treatment for bronchitis
A
- NO ABX TREATMENT OF ACUTE (regardless of duration of cough)
- Abx only for complication of bacterial infection susp
- Further diagnostic to confirm
*Treat bacterial infection, not the acute bronchitis (does not shorten duration of cough)
- Further diagnostic to confirm
5
Q
Use of pharm & non-pharm management for acute bronchitis instead
A
- cough may last >3wks (Abx not hasten resolution)
○ Return to clinic if develop:
§ Fever
§ SOB
§ Chest pain
§ Cough incr extent
§ Cough incr freq
§ Significant cough persist > 3wk
6
Q
definition of LRTI
A
- Lower resp tract infection
- Infection of lung parenchyma
- Due to proliferation of microbial pathogens in alveolar level
- Causes:
- Common = BACTERIAL
- Less common = fungi, viral
Top 3 cause of death in SG
7
Q
pathophysiology for LRTI
A
1) Aspiration or oropharyngeal secretions
* Bact in oropharyngeal sections enter lungs
2) Inhalation of aerosols
* Inhalation of aerolised droplets containing bacteria
3) Hematogenous spreading
* Bacteremia from extra-pulmonary source
- But bacteremia can also be caused from pneumonia complication
8
Q
infection of host process
A
- When exposed to pathogen
a. Inhalation, aspiration, contiguous, hematological mechanism - Susceptible host/ virulent pathogen
a. If have innate defense mechanism, not susceptible. - Proliferation of microbe in lower airways & alveoli
9
Q
risk factors of LRTI (incr susceptibility of host)
A
1) Smoking
a. Suppressed neutrophil function
b. Damage lung epithelium
2) COPD, asthma, lung cancer
a. Destroys lung tissue
b. Pathogen more niduses (areas) to multiple and infect
3) Immune suppression (HIV, sepsis, glucocorticoids, chemotherapy)
a.Make host susceptible
10
Q
1) confirm presence of infection
A
- sx presentation (localised, systemic) (physical examination)
- objective evidence
radiographic findings, general lab, urinary antigen tests, resp gram stain & culture, blood culture
11
Q
- sx presentation (localised, systemic) (physical examination)
A
- Systemic presentation
○ Fever, chills, malaise, change in mental status (elderly), tachycardia, hypotension - Localised sx
○ Cough, chest pain, PLEURITIC CHEST PAIN (chest pain on coughing) SOB, tachypnoea, hypoxia
○ Incr sputum production
§ Innate immunity to protect airways - Physical examination
○ Lung auscultation
§ Diminished breath sounds over affected areas (less O2)
§ Inspiratory crackles during lung expansion
Not as accurate
12
Q
- Objective evidence
Radiographic findings
A
Radiographic findings
○ Chest x-rays
○ Lung CT
○ Lung ultrasonography
§ Evidence: new infiltrates, dense consolidations, look for abscess
§ Usually mono-lobe
□ (if both side – likely fluid consolidation, HF)
§ Must be NEW
□Not from TB cavity, infiltrate there alr
13
Q
General lab findings
A
○ WBC (4-10x10^9 /L), CRP (normal <10mg/L, infection > 40 mg/L), PROCAL (0.5-1ug/L)
§ Signs of systemic infection
§ Non-specific for pneumonia
14
Q
Urinary antigen tests
A
○ Show pt exposure to certain bact (but may not be infected NOW)
§ Remains +ve for days-wks despite Abx treatment
○ what pt was infected with before, cover it (resistance)
○ Esp for CAP pneumo SEVERE/ hosp pts
15
Q
Resp gram-stain and cultures
A
○ Sputum
§ Low yield (>50% no yield)
§ Contamination by oropharyngeal secretions
□ High epithelium cells
□ High coloniser bact
○ Lower resp tract samples
§ Invasive sampling
□ Bronchoalveolar lavage (BAL)
□ Requires trained personnel to retrieved the flushed sample from tube
§Less contamination
16
Q
Blood cultures
A
○ Rule out bactermia
Only in hosp// complication of pneumo
17
Q
*** pre treatment: blood and resp gram-stain and cultures
Empiric broad spect first —> narrow in 1-3 days
A
- hosp: severe CAP
- hosp: risk factors for drug-resistant pathogens (MRSA, psudeo)
○ Being empirically treated
○ Previously infected in last 1year
○ Hosp/ received IV Abx in last 90days
18
Q
CAP-pneumo classification definition
A
Onset in comm
<48hrs after hosp admission
* Serious and sig ○ ~10% of pt require admission to ICU ○ ~10% mortality ~50% ICU
19
Q
HAP-pneumo classification definition
A
- Onset > 48hrs after hosp admission
- 2nd most common cause of HAI
- Sig healthcare cost
○ Prolong hospitalisation
○ >50% of Abx use - Mortality rate at least 20-30%
(HAP = 18.8%)
20
Q
VAP-pneumo classification definition
A
Onset >48hr after mechanical ventilation
* 2nd most common cause of HAI * Sig healthcare cost ○ Prolong hospitalisation ○ >50% of Abx use * Mortality rate at least 20-30% (HAP = 29.3%)
21
Q
risk factors and ways to prevent CAP
A
- Risk factors for CAP
○ History of pneumo
○ Smoke, chronic resp disease, immunosupp - Prevention
○ Smoking cessation, immunisation (not 100% but lowers risk)
§ Influenza
§Pneumococcal
22
Q
outpt CAP pathogen
A
- Streptococcus pneumoniae
- Haemophilus influenzae
- Atypicals
○ Mycoplasma pneu
○ Chlamydophila pneu
○Legionella pneumophilia
23
Q
Inpatient (non severe) CAP pathogen
A
Based on risk factors, MRSA, pseudomonas aeruginosa
- Streptococcus pneumoniae
- Haemophilus influenzae
- Atypicals
○ Mycoplasma pneu
○ Chlamydophila pneu
○Legionella pneumophilia - influenza
24
Q
inpt severe CAP pathogen
A
ALLLLL +
- Staphylococcus aureus
- Gram neg:
○ Klebsiella pneumonia
○ Burkholderia pseudomallei
(Pathogen for severe CAP in tropical countries) - Based on risk factors, MRSA, pseudomonas aeruginosa
- influenza considered and tested for all inpt during circulating season
* nov-feb// may-july
25
CAP inpt non severe MRSA
- MRSA risk factors
- resp isolation of MRSA in last 1 yr
- hosp / IV ABx use in last 90d + MRSA screen +ve
26
CAP inpt non severe pseudo risk factor
resp isolation of pseudo in last 1 year
27
CAP inpt severe MRSA cover risk factors:
- MRSA risk factors
- resp isolation of MRSA in last 1 yr
- hosp / IV ABx use in last 90d
28
CAP inpt severe pseudo risk factors
- resp isolation of pseudo in last 1 yr
- hosp or IV abx use in last 90d
29
why is risk stratification of CAP needed
* Location of treatment
○ Outpt/ inpt/ ICU
* Orgs to be covered
* Empiric Abx selection
○ Covers possible causative org
○ Narrow: limit toxicity, selection P.
* ROA admin
○ (swallow?)
30
use these 3 for risk stratification
1) pneumonia severity index (PSI)
2) CURB 65
3) severe CAP (IDSA/ ATS)
31
PSI
a. 20 variables stratify pt into
i. Class I, II (outpt)
ii. Class III: short hosp, observ
iii. Class IV, V: inpt
Disadv: complex, not freq used
Adv: accurate, recc in guideline
32
CURB-65 score
a. 5 variables
i. Confusion (new onset)
ii. Urea > 7mmol/L
iii. RR > 30/min
iv. BP hypo <90/60
v. Age > 65yrs old
b. Mortality classes
i. 0-1 = outpt
ii. 2 = inpt
iii. >3-5 = inpt, ICU
□ Esp if low O2, hypoxia need intubation
Adv: easy to use, readily avail parameters
33
Severe CAP (IDSA/ATS)
Major criteria (any 1)
i. Mechanical ventilation
ii. Septic shock require vasoactive medications (haemodynamic instability)
Minor criteria (>3)
i. RR >30breath/min
ii. PaO2/ FiO2 < 250
iii. Multilobar infiltrate (Extensive infection)
iv. Confusion/ disorientation (elderly)
v. Uremia (urea>7 mmol/L)
vi. Leukopenia (WBC <4/L) ( Must not be from other causes, chemo etc)
vii. Hypothermia (<36*C)
viii. Hypotension, aggressive fluid resuscitation
34
Abx for outpt CAP, without comorbidities
Pathogen: Streptococcus pneumoniae
○ amoxicillin 1g q8H
§ High dose, no amox resistant strep pneu, change in PBP
○ Resp FQ levo/moxi
□ CI/ allergy
35
Abx for Outpt with comorbidities CAP
(chronic, heart, lung, liver, renal, DM, alcoholism, malignancy, asplenia)
Pathogen:
○ Streptocohadddccus pneumoniae
○ Haemophilus influenzae
○ Atypicals (myco pneu, chlam pneu, legionella pneu)
b-lactams + macrolide/ doxy
or
resp FQ
36
outpt w/ comor: dose
b-lactams + macrolide/ doxy
or
resp FQ
○ Amoxicillin/clavu
□ Penicillinase producing haemophilus influenzae
○ Cefuroxime
□ 1st gen not cover step pneu
+
macrolide (A>C, less CYP3A4i --- QT prolong) / doxy --- GIT
OR
resp FQ (LM, strep pneumo)
37
Abx for CAP inpt (nonsevere)
○ Streptococcus pneumoniae
○ Haemophilus influenzae
○ Atypicals
○ Mycoplasma pneu
○ Chlamydophila pneu
○ Legionella pneumophilia
○ b-lactams
-Amox/clav, Cefuroxime, ceftriaxone
+ Macrolide (C, A) // DOXY
OR
resp FQ (levo, moxi)
38
CAP inpt (nonsevere) modify
MRSA: IV vancomycin/ IV,PO linezolid
Daptomycin (X lung surfactant)
pseudo: Piperacillin/ tazobactam, cefepime, ceftaroline, meropenem, levofloxacin
○ Ceftazidime (X cover strep)
○ All still need atypical cover!
- Change to Abx that cover haemo influ, strep pneumo
39
CAP inpt (nonsevere) risk factors
MRSA:
-resp of MRSA in last 1 year
- hosp or IV Abx use in last 90d & MRSA PCR screen +ve
pseudo:
- resp isolation of pseudo inlast 1 year
40
Inpt, severe (1 major/3 minor/ intubation, vasopressors) Abx
○ Pathogen:
○ All of outpt above
○ Staphylococcus aureus
○ Gram neg:
○ Klebsiella pneumonia
○Burkholderia pseudomallei
- b-lactams
○ Amoxicillin/clavu
○ Penicillin G
- add ceftazidime
○ Cover Burkholderia pseudomallei
○ Or meropenem
○ But cefta (no strep pneu, only haemo, no gram +ve cover)
□ Penicillin G for narrow cover, but poorer cover of strep aurea
- add macrolide
OR
- resp FQ (moxi, levo) --- no doxy, X IV
○ + ceftazidime
41
severe inpt CAP risk factors
MRSA
○ Resp isolation of MRSA in last 1 yr
○ Hosp/ IV Abx use in last 90 days
○ IV vanco or IV/PO linezolid
□ Vanco (cover strep pneumo, +ve
+ macrolide + ceftazidime)
PSEUDO
○ Resp isolation of P.aeru in last 1 yr
○ Hosp/ IV Abx in last 90 days (more relax, so don’t miss out MDRO)
○ Alr covered with regimen above
○ Levoflox (X moxi)
42
other treatment considerations for CAP inpt
anaerobic cover
influenza cover
CS therapy
43
ANAEROBE COVER
* Modify empiric regimen (include anaerobic) if reported in radiology investigation (CXR, CT scan)
* Lung abscess
* Empyema (pus)
Metronidazole (IV/PO)
Clindamycin (IV/PO)
○ Amox/cavu (anareobe) + macro + ceftazidime
○ Levo + ceftazidime + anaerobe cover needed (metronidazole)
○ Moxi + ceftazidime
+ MRSA cover
44
Influenza
Empiric oseltamivir
○ If susp for influenza
§ ASAP initiate (first 48hr, up to 5 days) of Sx onset
○ +ve influenza PCR
§ Complete 5 day course
§ Discontinue Abx at 48-72hr if no bacterial pathogen (neg culture, low procalcitonin <0.25ng/mL, early clinical stability)
- Show that bact is not the cause
45
why is resp FQ (L,M) not first line?
* HIGH ADR
○ QTc prolongation
○ Tendonitis, tendon rupture
○ Neuropathy
○ CNS disturbances
○ Hypoglycemia
* RESISTANCE
○ Risk collateral damage, 3rd gen cephalosporins
○ Only for GRAM -VE INFECTIONS
§ Levoflox, cirpo
□ Pseudo cover (if have penicillin allergy)
§ Only PO option for pseudo
* DELAY TB DIAGNOSIS
○ Undesirable monotherapy
○ Affects differential diagnosis
46
Adjunct corticosteroid therapy
* Decr inflammation in lungs
* Not to routinely add
○ Shock refractory to fluid resuscitation and vasopressor support
○ No benefit in non-severe CAP
○ Mortality
* Prednisolone (PO), dextromethorphan, hydrocortisone (IV)
47
4) CAP de-escalate when
Pt is hemodynamically stable
Improve clinically
For IV --> PO (able to ingest PO meds)
48
how to de-escalate CAP
+ve culture
□ AST to guide narrow spectrum Abx
□ Choose PO Abx
No +ve culture (invalid)
□ Empiric cover for MRSA, pseudo, Burkholderia stopped in 48hs if pathogen NOT isolated, pt improve
□ IV --> PO
- use either same Abx or another Abx from same class
49
Most CAP pt clinical stability in
within first 48-72hrs
§ Minimum 5day therapy
§ 7 days if suspected/ proven MRSA/ psudeo
§ Stable:
□ Resolution of vital sign abnormalities (HR, RR, BP, O2, temp)
□ Maintain PO intake
□ Baseline mental status
50
longer Abx course of therapy needed for CAP when
minimum 5d
MRSA, pseudo risk 7d
CAP complicated with other deep-seated infections
□ (meningitis, lung abscess: 2-3wk)
Infection with other, less-common pathogens
□ Burkholderia pseudomallei -- 4-6 wk
□ mycobact TB (6mnths)
□ Endemic fungi
51
Therapeutic response of CAP
* Most pt will achieve clinical stability within first 48hr - 72hr
* Elderly pt/ multiple comorbidities take longer
§ Not escalate Abx therapy in first 72hr!!!
§ Unless culture-directed/ sig clinical deterioration
* Radiographic improvement lag behind clinical improvement for resolution
§ Repeat only if clinical deterioration
§ Compare with past CXR (for new progression)
* NO NEED REPEAT microbiological test (sputum/ urine not needed)
* ADR of Abx
§ Diarrhea, CDAD, LFT, ADR (macrolide --- tendonitis, QTc)
52
HAP risk factors
Pt-related
○ Elderly
○ Smokinh
○ COPD, cancer, immunosupp
○ Prolonged hosp
○ Coma, impaired consciousness
○ Malnutrition
Infection control-related
○ Hand hygiene compliance
○ Contaminated resp care devices
Healthcare-related
○ Prior Abx use
○ Sedatives
§ Don’t breathe well, need to be intubated, decr innate defense
○ Opioid analgesic
○ Mechanical ventilation
○ Supine position
53
prevention of VAP
* Practice consistent HH
* Use of Abx, medications with sedative effects
VAP:
○ Limit duration of mechanical ventilation
○ Minimise duration and deep lvl of sedation
○ Elevate head of bed by 30*
Supine position, incr risk
54
prevention of HAP
* Practice consistent HH
* Use of Abx, medications with sedative effects
55
HAP/VAP pathogen empirically covers for
- Pseudomonas Aeruginosa
- Staphylococcus aureus
- MRSA
- GNR (Enterobacter, Klebsiella, E coli)
- Acinetobacter
- Stenotrophomonas maltophilia
56
additional coverage (MRSA, gram neg) when
-MDRO risk factors
- mortality risk factors
- hosp/ unit distribution of pathogen associated with HAP/ VAP and there susceptibilities (antibiogram)
57
choice of Abx in HAP/VAP depends on
choice of Abx depends on pathogen in HAP/VAP + susceptibility
ICU specific antibiogram for VAP
empiric cover (PSEUDO & MRSA)
58
HAP/VAP Abx cover for MRSA when
(risk factors)
□ Prior IV Abx use within 90days
□ Isolation of MRSA in last 1 yr
□ Hosp in unit where >20% S.aureus are MRSA
□ Prevalence of MRSA in hosp not known but pt HIGH RISK OF MORTALITY
-Need of ventilatory support due to HAP
- vent support as Pt in septic shock
59
VAP/ HAP MRSA cover
Add
IV vancomycin
IV/ PO linezolid
60
when do you need pseudomonas cover (double)
(risk factors)
§ Risk factor to antimicrobial resistance
□ Prior IV Abx within 90d
□ Acute renal replacement therapy prior to VAP onset
□ Isolation of Pseudo in last 1 yr
§ Hosp in a unit where > 10% of pseudo isolates are resistant to agent considered for mono (>90% susceptibility)
§ Prevalence of pseudo not known but pt at high risk for mortality
□ Need for ventilatory support due to HAP and septic shock
61
VAP/HAP pseudo aeruginosa & GNR Abx
EMPIRIC: Use double (2) antipseudomonal Abx from diff classes
Anti-pseudomonal b-lactams
○ (pip-tazo, cefepime, meropenem, imipenem)
○ Ceftazidime - not cover gram +ve, no MRSA)
Anti-pseudo FQ
○ Levofloxacin, ciprofloxacin
AG
○ Amikacin, gentamicin
○ Short duration
○ Avoid as sole agent
62
AG for mono pseudo cover?
○ Avoid use of AG as sole antipseudomonal agent
§ Nephrotoxicity.
§ Pt hemodynamic instable, low BP, low kidney perfusion, risk AKI
63
suitable monopseudo cover
piptazo, cefepime,
ceftazidime (no gram +ve cover, need vanco)
Need >90% susp
64
Hosp/ unit distribution of pathogen associated with HAP/ VAP and their susceptibility (antibiogram)
Specific wards/ ICU
○ Stenotrophomonas maltophilia
Resistance to meropenem last line)
§ Highly resistance species
65
De-escalation/ IV --> PO conversion
VAP/HAP
Pt is hemodynamically stable (BP, fever, HR)
Improved clinically
IV --> PO (able to ingest oral meds)
66
how to de-escalate VAP/ HAP
+ve culture
○ AST to guide selection of narrower spectrum/ PO Abx available
○ Pseudomonas --- single anti-pseudo agent
§ no empiric 2 agent
no +ve culture
○ De-escalate: maintain coverage according to local HAP/ VAP antibiogram
○ No antibiogram: maintain for Pseudo, enteric GNR, MSSA cover
○ If pt sig risk for MDRO, keep on IV
○ IV --> PO conversion
§ PO pseudo: cipro (need + Augmentin)/ levo (cover MSSA, GNR)
67
Treatment duration for VAP/ HAP
* Most pt achieve clinical stability within first 48-72hr
* May take longer if other comorbidities (T2DM, HTN)
○ ~4-5 days
* Regardless of pathogen
○ Duration of 7 days (even pseudo, MRSA)
* New evidence suggest no diff in recurrence and mortality
○ If duration is short 7 days ~ 2wk (long)
* Longer course of Abx therapy for pneumonia complicated with deep-seated infections
○ Meningitis (CSF)
○ lung abscess (2-3wk to clear large collection of bact)
68
VAP/ HAP clinical stability
* Pt who achieved clinical stability
○ Resolution of vital sign abnormalities
○ HR, RR, BP, O2 sat, Temp
○ HAP: baseline mental status
○ VAP: Usually heavily sedated
3151 finals
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