Pathogenesis - Aerosolization - direct ___ of pathogen - primaryily ___ , TB, and endemic fungi - ___ nuclei = particles containing pathogen

- inhalation - viruses - droplet

Common Bacterial Pathogens - S. pneumoniae - H. influenzae - atypical pathogens: ___ , ___ , and ___ - S. aureus

- Mycoplasma pneumoniae - Legionella pneumophilia - Chlamydia Pneumoniae

Legionella pneumophila - ___ pathogen - found in water and soil - spread by ___ - increased risk: older ___ , chronic bronchitis, smokers, and immunocompromised - characteristics: multisystem involvement (high ___ , relative ___ , multi-lobar involvement, mental status change, and increased LFTs + SCr)

- atypical - aerosolization - males - fevers, bradycardia,

Clinical Presentation - sudden onset of fever, chills, pleurtitic chest pain, dyspnea, productive cough - ___ onset with ___ severity for mycoplasma and Clamydia pneumoniae Elderly Pts - classic symptoms may be ___ (afebrile, mild leukocytosis) - more likely to have decrease in ___ status, weakness, and ___ status changes Vitals: febrile, ___ cardia, ___ tensive, tachypnea

- gradual, lower - absent - functional, mental - tachycardia, hypotensiver

LRTI Flashcards by Reagan Smith

Host Defense Mechanisms

Nasopharynx (5)

nasal hair
anatomy of upper airways
IgA secretion
mucociliary apparatus
fibronectin

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Host Defense Mechanisms

Trachea/Bronchi (5)

cough
epiglottic reflex
anatomy of conducting airways
mucociliary apparatus
immunoglobulin

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Host Defense Mechanisms

Oropharynx (3)

saliva
slough epithelial cells
complement production

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Host Defense Mechanisms

Alveoli/Terminal Airways (4)

alveolar lining fluid
cytokines
macrophages + PMNs
cell-mediated immunity

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What happens when the body doesn’t do its job?

Host interventions
- ___ and ___
- altered level of consciousness
- endotracheal tubes

Host Disease States
- immunosuppression
- ___
- asplenia
- ___

smoking, alcohol
dibetes mellitus
elderly

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What happens when the body doesn’t do its job?

Pathogen Mediated
- surface ___
- pili
- ___
- enzymes

Defenses Gone Wrong
- alveolar macrophages
- phagocytosis + cytokine release → recruit neutrophils → acidic and hypoxic environment → ___ phagocytosis

adhesions
exotoxins
reduced

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CAP - pneumonia that developed outside the hospital or within the first ___ hours of admission
- most ___ cause of infection related to hospitalization and mortality
- 10% hospitalized

48
common

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Pathogenesis - Aspiration

most common for ___ pnemonia
common during ___
organisms usually clearned if host defenses functioning properly
disorders that impair consciousness and depress gag reflex result in increased inoculum

bacterial
sleep

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Pathogenesis - Aerosolization

direct ___ of pathogen
primaryily ___ , TB, and endemic fungi
___ nuclei = particles containing pathogen

inhalation
viruses
droplet

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Pathogenesis - Bloodborne

translocate to ___ site
extremely unlikely

pulmonary

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Which microorganism class is the most common pathogenic organism for CAP?
a) fungus
b) bacteria
c) virus
d) protozoa

virus

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Common Bacterial Pathogens

S. pneumoniae
H. influenzae
atypical pathogens: ___ , ___ , and ___
S. aureus

Mycoplasma pneumoniae
Legionella pneumophilia
Chlamydia Pneumoniae

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Streptococcus pneumoniae

increased prevalence and severity in pts with the following:
- asplenia
- DM
- immunocompromised
- HIV
- chronic cardiopulmonary/renal disease

Risk factors for drug resistance
- age < __ or > ___ yo
- prior Abx therapy
- co-morbid conditions
- day care
- recent hospitalization
- close quarters

PCN and Macrolide use
- ___ resistance - 3%
- ___ resistance - 45-50%

6, 65
PCN
macrolide

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Mycoplasma pneumoniae

___ pneumonia
___ bacteria
spread by person-person contact (increased risk in close contact populations)
2-3 week incubation period, ___ onset of symptoms
persistent, non-productive coughm fever, headache, sore throat, rhinorrhea, N/V, arthralgia
imaging usually more pronounced with patchy, interstitial infiltrates

walking
atypical
slow

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Legionella pneumophila

___ pathogen - found in water and soil
spread by ___
increased risk: older ___ , chronic bronchitis, smokers, and immunocompromised
characteristics: multisystem involvement (high ___ , relative ___ , multi-lobar involvement, mental status change, and increased LFTs + SCr)

atypical
aerosolization
males
fevers, bradycardia,

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S. aureus

___ prevalence in CAP

important to get ___ ___ ___
- 95-99% negative predictive value for MRSA in CAP

Risk factors for MRSA
- 2-14 days post ___
- previous MRSA infection/isolation
- previous hospitalization
- previous use of ___ antibiotics

low
MRSA nasal PCR
flu
IV

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Risk Factors for Certain Pathogens

S. pneumoniae, anaerobes, K. pnemoniae

Alcoholism

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Risk Factors for Certain Pathogens

S. pneumoniae, H. influenzae, Moraxella cattarhalis, Legionella spp.

COPD/smoker

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Risk Factors for Certain Pathogens

S. pneumonia, S. aureus, H. influenzae

post influenza pneumonia

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Risk Factors for Certain Pathogens

P. aeruginosa, S. aureus
(2)

structural lung disease (cystic fibrosis, bronchiectasis)
recent Abx exposure

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Clinical Presentation

sudden onset of fever, chills, pleurtitic chest pain, dyspnea, productive cough
___ onset with ___ severity for mycoplasma and Clamydia pneumoniae

Elderly Pts
- classic symptoms may be ___ (afebrile, mild leukocytosis)
- more likely to have decrease in ___ status, weakness, and ___ status changes

Vitals: febrile, ___ cardia, ___ tensive, tachypnea

gradual, lower
absent
functional, mental
tachycardia, hypotensiver

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Clinical Presentation

Chest X-ray
- recommended for all patients with suspicion for CAP
- dense lobar consolidation/infiltrates = ___ origin
- patchy, diffuse intersitital infiltrates = ___ or ____ pathogens

Sputum Characteristics
- color, amount, consistency, and odor observed

Gram stain
- only evaluate samples with > ___ PMNs and < ___ epithelial cells
- S. pneumoniae - gram ___ diplococci
- H. influenzae = gram ___ coccobacilli

bacterial
atypical, viral
25, 10
positive
negative

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Microbio Testing and Other Markers

Respiratory Culture
- ___ , can be done with more severe pts (false negatives)
- tracheal aspiration
- bronchoscopy
- bronchoalveolar lavage

Blood Culture
- get __ sets

___ with differential
___, BUN, electrolytes, LFTs
Pulse Ox, O2 sat

Uriniary antigen tests
- ___
- ___ - serogroup 1

Nasopharyngeal PCR Swabs
- ___
- Viral

controversial
2
WBC
SCr
S. pneumoniae
Legionella pneumophila
MRSA

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T or F: only use cultures (respiratory and blood) if patient is severe

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# Severe CAP - Major Criteria (Need 1) 1) Septic shock requiring ___ 2) Respiratory failure requiring ___

- vasopressors - mechanical ventilation

# Severe CAP - Minor Criteria (Need ≥ 3) - RR of ___ bpm or more - PaO2/FlO2 ≤ 250 (outpatient) - ___ inflitrates - ___ /disorientation - uremia (BUN ≥ ___ mg/dL) - Leukopenia (WBC < ___ cells/uL) - Thrombocytopenia (Plt < ____ /uL) - hypothermia (temp < ___ C) - ___ tension requring aggressive fluids

- 30 - multilobar - confusion - 20 - 4,000 - 100,000 - 36 - hypotension

# Other Tools for CAP Procalcitonin - elevated in presence of bacerial infection - SHOULD NOT be used to determine use for ___ for CAP - clinically useful in guiding ___ of treatment if obtained throughout hospitalization

- antibiotics - duration

# Other Tools for CAP - Clinical Prediction Tools Pneumonia Severity Index (PSI) - utilizies demographics, comorbid diseases, physical exam, and lab findings - points < 70 = 0.6% 30 day mortality - points > 90 = 8.2-29.2% 30 day mortality CURB-65 - ___ - ___ (BUN > 19 mg/dL) - RR ≥ 30 bpm - SBP < 90 mmHg, DBP ≤ 60 mmHg - Age ≥ ___

- confusion - Uremia - 65

# Treatment - Supportive Measures - humidified ___ - broncho ___ - fluids - chest physiotherapy

- oxygen - bronchodilators

# Empiric Therapy - Outpatient **healthy** outpatient adults **without** comorbidities or risk factors for antibiotic resistance - ___ 1 g PO q8h - ___ 100 mg PO BID - macrolide resistance < 25%, ___ 500 mg PO day 1, 250 mg day 2-5

- amoxicillin - doxycycline - Z-Pak

# Empiric Therapy - Outpatient outpatient adults with **comorbidities** - chronic heart, lung, renal disease; DM; alcoholism; malignancy; asplenia or immunosuppression Monotherapy - respiratory fluroquinolone - ___ 750 mg PO daily - ___ 400 mg PO daily Combo Therapy - Beta-lactams + ___ or ____ Beta-lactams recommended - ___ 500/125 mg PO q8h or 875/125 mg PO q12h - ___ 200 mg PO q12h - ___ 500 mg PO q12h

- levofloxacin - moxifloxacin - macrolide, doxycycline - amox/clav - cefpodoxime - cefuroxime

# Empiric Therapy - Inpatient Non-severe CAP (no MRSA/P. aeruginosa risk factors) Monotherapy - respiratory fluroquinolone - ___ 750 mg PO daily - ___ 400 mg PO daily Combo Therapy - Beta-lactam + ___ Recommended Beta-lactams - ___ 1.5 g-3 IV q6h - ___ 1-2 g IV q24h - ** ___ IV/PO may be used if FQ or macrolide contrindicated

- levofloxacin - moxifloxacin - macrolide - ampicillin/sulbactam (Unasyn) - ceftriaxone - doxycycline

# Empiric Therapy - Inpatient Severe CAP (no MRSA/P. aeruginosa risk factors) Combo Therapy 1 - respiratory ___ + ___ Combo Therapy 2 - Beta-lactam + ___ Recommended Beta-lactams - ___ 1.5 g-3 IV q6h - ___ 1-2 g IV q24h - ** ___ IV/PO may be used if FQ or macrolide contrindicated

- fluroquinolone, Beta-lactam - macrolide - ampicillin/sulbactam - ceftriaxone - doxycycline

# Empiric Therapy - Inpatient MRSA Risk Factors - ~2-14 days post ___ - previous MRSA respiratory infection/isolation - previous hospitalization and use of IV antibiotics within last ___ days MRSA Coverage - ___ target AUC 400-600 - ___ 600 mg IV/PO q12h

- flu - 90 - vancomycin - linzolid

# Empiric Therapy - Inpatient P. aeruginosa Risk Factors - previous P. aeruginosa respiratory infection - previous hospitalization and use of IV antibiotics within last ___ days Pseudomonas Coverage - ___ 4.5 g IV q6h - ___ 2 g IV q8h - ___ 1 g IV q8h

- piperacillin/tazobactam - cefepime - meropenem

# Pathogen Directed Therapy - Streptococcus pneumoniae Preferred Therapy - PCN G; ___ (if S to PCN) - ___ ; Respiratory ___ Alternative Therapy - Ceftriaxone - respiratory FQ - doxycycline - vancomycin - linezolid

- amoxicillin - ceftriaxone, FQ

# Pathogen Directed Therapy - Haemophilus influenzae Preferred Therapy - ___ / ___ gen cephalosporins - ___ - ___ Alternative - FQ - doxycycline - macrolide

- 2nd/3rd - Unasyn - Augmentin

# Pathogen Directed Therapy - Mycoplasma pneumoniae, Chlamydia pneumoniae Preferred Therapy - ___ - ___ Alternative Therapy - FQ

- macrolide - doxycycline

# Pathogen Directed Therapy - Legionella pneumophila Preferred Therapy - ___ - ___ Alternative Therapy - doxycycline

- FQ - azithromycin

# Pathogen Directed Therapy - MSSA Preferred Therapy - ___ - ___ Alternative Therapy - Vancomycin - Clindamycin

- cefazolin - nafcillin

# Pathogen Directed Therapy - MRSA Preferred Therapy - ___ - ___ Alternative Therapy - Ceftaroline - TMP/SMX

- Vancomycin - Linezolid

# Pathogen Directed Therapy - Anaerobes Preferred Therapy - ____ and inhibitor - add ___ if using cephalosporin Alternative Therapy - Carbapenem - Clindamycin

- Beta-lactam - metronidazole

# Pathogen Directed Therapy - Enterobacterales Preferred Therapy - __ / ___ cephalosporin - ___ Alternative Therapy - Beta-lactam and inhibitor - FQ

- 3rd/4th - carbapenem

# What about Corticosteroids ONLY recommended with Surviving Sepsis Guidelines when patient has CAP and ___

- septic shock

# Duration of CAP Therapy Ensure clinical stability prior to d/c Abx - temp ≤ ___ C (afebrile for ___ - ___ hrs) - HR ≤ ___ bpm - RR ≤ ___ bpm - SBP ≥ ___ mmHg - arterial O2 saturation ≥ ___ % or pO2 ≥ 60 mmHg on room air - basline mental status continue Abx until clinical stability for a minimum of ___ **total days**

- 38, 24-48 - 100 - 24 - 90 - 90 - 5

T or F: there is a definition to differentiate aspiration pneumonia vs pnemonia - recommend against ___ coverage unless lung abscess or empyema present

FALSE - same thing - anaerobic

What would be the most appropriate regimen for outpatient therapy for ST? A) moxifloxacin 400 mg PO daily B) Ceftriaxone 1 g IV daily + doxycycline 100 mg PO BID C) Cefpodoxime 200 mg PO BID + doxycycline 100 mg PO BID D) amoxicillin/clavulanate 875/125 PO BID + azithromycin 500 mg PO daily

C) Cefpodoxime 200 mg PO BID + doxycycline 100 mg PO BID

What would be the most appropriate regimen for this patient? A) Linezolid 600 mg IV q12h + Cefepime 2 g IV q8h + Azithromycin 500 mg IV q24h B) Vancomycin 1250 mg IV q24h + Ceftriaxone 1 g IV q24h + Doxycycline 100 gm IV BID C) Levofloxacin 750 mg IV q24h + Ceftrixone 1 g IV q24h D) Vancomycin 1 g IV q24h + piperacillin/tazobactam 4.5 g IV q6h

A) Linezolid 600 mg IV q12h + Cefepime 2 g IV q8h + Azithromycin 500 mg IV q24h Add linezolid due to MRSA risk with rehospitalization

# Definitions HAP = pneumonia occuring ≥ ___ hours after hospital admission VAP = pneumonia occuring ≥ 48 hours after ___ ___ HCAP = any pt hospitalized for ≥ __ days within the past 90 days of infection; resides in nursing home or LTCF; received recent IV ___ , ___ , or wound care within the past 30 days if infection; ___ - this is old news tho

- 48 - endotracheal intubation - 2, Abx, chemotherapy, hemodialysis

# HCAP Previously part of 2005 HAP/VAP guidelines Since then, ___ to be at an increased risk for multidrug-resistant organisms - increase use of broad-spectrum Abx without an improvement in outcomes - may lead to resistance Moved towards treating as CAP and evaluating for risk factors of ___ and ___

- disproven - MRSA - P. aeruginosa

# Epidemiology + Impact HAP - one of the most ___ hospital-accquired infections - 1.87% 60 day mortality risk VAP - impacts 5-40% of patients on mechanical ventilation > __ days - increases utilization of healthcare resources - prolongs length of mechanical ventilation by ~ __ days and hospitalization by ~ __ days ($40,000 per VAP incident)

- common - 2 - 9 - 12

# Pathogenesis micro-aspiration of oropharyngeal secretions that are colonized with bateria - usually aerobic gram ___ bacteria - after 3-5 days of hospitalization, converts to gram ___ organisms Aspiration of esophageal/gastric content Hematogenous spread from another source Direct inoculation into airways via ___ by healthcare personnel Mechanical ventilation - endotracheal tube ___ all host defenses and decreases LRT defenses

- positive - negative - intubation - bypasses

# Risk Factors for HAP/VAP - advanced ___ - severity of comorbid diseases - duration of ___ - endotracheal intubation - nasgoastric tube - altered ___ status - surgery previous ___ therapy

- age - hospitalization - mental - antimicrobial

# Diagnosis of HAP/VAP **No gold standard for diagnosis** Timing - important for defining ___ -acquired infection - impacts choice of antibiotics Typical Presentation - New lung ___ + clinical signs and symptoms - new onset ___ , purulent sputum, ___ , decline in ___

- hospital - infiltrate - fever, leukocytosis, oxygenation

# Common Pathogens - HAP/VAP ___ gram ___ bacilli = ~70% - pseudomonas aeruginosa = 10-20% - enteric gram-negative bacilli = 20-40% - Acinetobacter baumannii = 5-10% ___ = 20-30% - MRSA greater concern in this population

- aerobic, negative - Staphylococcus aureus

# Microbiology Testing - HAP/VAP ___ Cultures - recommended obtaining for all pts - non-invasive > invasive - invasive respiratory cultures have diagnostic threshold ___ Cultures - obtain from all patients

Respiratory Blood

# Risk Factors for MDP MDR HAP/MRSA HAP/ VAP - prior IV Abx use within ___ days MDR VAP - prior IV Abx use within ___ days - ___ shock at time of diagnosis - ___ prior to diagnosis - acute ___ replacement therapy prior to VAP onset - ≥ 5 days of ___ prior to diagnosis MDR P. aeruginosa - prior IV antibiotic use within ___ days - ___ , broad spectrum beta-lactams, FQs

MDR HAP/MRSA HAP/ VAP - 90 MDR VAP - 90 - septic - ARDS - renal - hospitalization MDR P. aeruginosa - carbapenems - 90

# Empiric Therapy - The Principles Empiric regimens should be based on ___ distribution of pathogens and susceptibility - Utilize yearly antiobiogram If possible, data should stratify for populations such as VAP or ICU population Goal = provide ___ ___ antibiotics while avoiding unnecessary harms of inappropriate coverage

- local - broad spectrum

# Empiric Therapy - Antiobitic Choice: MRSA Coverage Risk Factors - typical risk factors - ICUs where > __ - __ % MRSA isolates - Treatment where prevalence is ___ Treatment: - ___ AUC 400-600 - ___ 600 mg PO/IV q12h

- 10-20 - unknown - Vancomycin - Linezolid

# Empiric Therapy - Antiobitic Choice: P. aeruginosa Coverage Risk Factors for Resistance - ICUs where > ___ % of isolates resistant - Treatment where resistance rates are ___ Treatment: - ___ 4.5 g IV q6h - ___ 2 g IV q8h - ___ 500 mg IV q6h - ___ 1 g IV q8h - ___ 750 mg IV q24h

- 10% - unknown - piperacillin/tazobactam - cefepime - imipenem - meropenem - levofloxacin

# Empiric Therapy - HAP Not at High Risk for Mortality - (aka not on ___ support or ___ shock) Goal - provide coverage for MSSA + P. aeruginosa Treatment - ___ 4.5 g IV q6h - ___ 2 g IV q8h - ___ 500 mg IV q6h - ___ 1 g IV q8h - ___ 750 mg IV q24h

- ventilatory, septic - piperacillin/tazobactam - cefepime - imipenem - meropenem - levofloxacin

# Empiric Therapy - HAP Not at High Risk for Mortality but MRSA risk - (aka not on ___ support or ___ shock) Goal - provide coverage for MRSA + P. aeruginosa Combo Treatment (A + B) Treatment A - ___ 4.5 g IV q6h - ___ 2 g IV q8h - ___ 500 mg IV q6h - ___ 1 g IV q8h - ___ 750 mg IV q24h PLUS Treatment B - ___ AUC 400-600 - ___ 600 mg IV q12h

Treatment A - piperacillin/tazobactam - cefepime - imipenem - meropenem - levofloxacin Treatment B - vancomycin - linezolid

# Empiric Therapy - HAP High Risk for Mortality and MRSA risk - on ___ support or ___ shock Goal - provide coverage for MRSA + MDR P. aeruginosa Combo Therapy Treatment A (Pick 2 from Different Classes) - ___ 4.5 g IV q6h - ___ 2 g IV q8h - ___ 500 mg IV q6h - ___ 1 g IV q8h - ___ 750 mg IV q24h - ___ / ___ IV PLUS Treatment B - ___ AUC 400-600 - ___ 600 mg IV q12h

- ventilatory, septic - piperacillin/tazobactam - cefepime - imipenem - meropenem - levofloxacin - tobramycin/amikacin - Vancomycin - Linezolid

# Empiric Therapy - VAP Goal - Provide coverage for MRSA + P. aeruginosa Choose __ anti-pseudomonals when there are risk factors for resistance Combo Treatment (A +B) Treatment A - ___ 4.5 g IV q6h - ___ 2 g IV q8h - ___ 500 mg IV q6h - ___ 1 g IV q8h - ___ 750 mg IV q24h - ___ / ___ IV PLUS Treatment B - ___ AUC 400-600 - ___ 600 mg IV q12h

- piperacillin/tazobactam - cefepime - imipenem - meropenem - levofloxacin - tobramycin/amikacin - Vancomycin - Linezolid

# Non-Beta Lactam Considedrations T or F: Daptomycin is used for LRTI

FALSE - never

# Non-Beta Lactam Considedrations Daptomycin - never use Aminoglycosides - dont use as ___ - avoid empiric use unless necessary - poor ___ penetration, nephrotoxicity, ototoxicity, reports of lower clinical response rates Polymyxins - avoid empiric use if possible - reserve for pts with high prevalence of ___ pathogens - significant ___ Tigecycline - great for ___ infections - associated with increased ___

- monotherapy, lung - MDR, nephrotoxicity - polymicrobial, mortality

# Pathogen-Specific Therapy MSSA (2)

- cefazolin - nafcillin

# Pathogen-Specific Therapy Enterbacterales (1)

- 3rd gen cephjalosporins

# Pathogen-Specific Therapy ESBL-producer (2)

- carbapenem - ceftazidime/avibactam

# Pathogen-Specific Therapy KPC-producer (3)

- meropenem/vaborbactam - imipenem/relebactan - ceftazidime/avibacam

# Pathogen-Specific Therapy NDM/VIM-producer (2)

- Ceftazidime/avibactam + aztreonam - cefiderocol

# Pathogen-Specific Therapy acinetobacter spp. (3)

- carbapenem - ampicillin/sulbactam - cefiderocol

# Duration for HAP/VAP - ___ day duration if clinically stable VAP - compared to longer durations in VAP, there is no difference in duration of MV, hospital LOS, treatment failurem recurrent pneumonia, or mortality HAP - no significant differences compared to longer durations