Pulmonary Infections

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    Introduction

    • Classified as:
      • Community Acquired Pneumonia (CAP)
        • Acute pneumonia in those not recently hospitalized, and not living in facilities (i.e. nursing home).
        • Risk factors: Age (>65), DMII, CV disease, COPD, chronic bronchitis, alcoholism, neuro diseases.
        • Smokers: high risk of invasive pneumococcal infections even without structural lung disease.
    • Generally caused by microaspiration of organisms that colonize oral pharynx (usually during sleep).
      • Except Legionella - due to aerosolized contaminated water particles.
    • Aspiration pneumonia
      • larve volume aspiration of gastric contents --> chemical pneumonitis --> bacterial infection.
    • Other important points:
      • Use of guidelines to direct therapy decreases mortality in hospitalized patients with CAP

    Community Acquired Pneumonia

    ​Microbiology

    • Community Acquired Pneumonia Organisms 
      • Streptococcus pneumoniae
         
        (often bactermic pneumonia)
      • Haemophilus influenzae
      • Moraxella catarrhalis
      • Klebsiella pneumoniae (less common)
        • (alcoholism)
        • HIGHLY resistance strains possible
    • So-called "Atypical" Organisms
      • Mycoplasma
      • Chlamydophila (prev Chlamydia)
        • Intracellular anaerobe
        • Both Mycoplasma and Clamydophila termed "walking pneumonia" generally in outpatients (mild).
      • Legionella
        • In pts with severe CAP, history of travel.
        • More common in summer, often in epidemics when common-source reservoir aerosolizes bacteria (i.e. water systems, air conditioning units, such as at a hotel or cruise ship)
        • Ass'd with hyponatremia, AST/ALT elevation, GI symptoms, bradycardia.
        • Has urinary antigen test (only picks up Legionella pneumophila type 1)
          • Helpful if positive, but negative test doesn't exclude dx.
    • Other pathogens: (rare)
      • Staph aureusPnCAPcauses.png
        • Less common cause of CAP.
        • Risk Factors: classically following influenza, cavitary pneumonia, no risk factors for aspiration, IVDU, recent history of CA-MRSA skin infection.
        • High mortality rate, cause prolongued hospitalization.
        • often ventilator associated pn.
      • Gram negatives (enteric)
        • uncommon, unless lung disease or alcoholism. (reduced gag reflex). Usually hospitals and nursing homes.
      • Pseudomonas
        • Often underlying structural lung disease
          • Risk Factors: Bronchiectasis, Cystic Fibrosis, frequent COPD Exacerbations, long term steroid therapy.
        •  
      • Anaerobes
        • Often aspiration pneumonias.
      • Viral
        • influenza, parainfluenza, respiratory syncitial virus (RSV), adenovirus (adenovirus Type 14 - severe)
    • Nosocomial Infections:
      • Gram negatives (>50%)
      • Staph aureus (13-40%) (wound infections, burns, intubated, head trauma)
      • Anaerobes (5%)
            
        Risk Factors: (Intubation, >70yrs, reduced  LOC, malnutrition, metabolic acidosis)
    • Aspiration Infections:
      •      (aware of pulmonary burn aspiration of gastric contents, obstructing objects)
      •       (foul-smelling spututm, lung abscesses and empyema)
      •       (OFTEN MIXED ORGANISMS)
      • Mixed Gram negative enteric aerobic rods
      • Anaerobes
      • Staph aureus
      • Rare
        • Actinomycosis (poor oral hygeine, anaerobic)
        • Nocardiosis (inhalation of soil particles)

    Symptoms

    • Acute Cough - purulent sputum.
      • (S. pneumon is rusty colored, red current jelly color is Klebsiella etc..)
    • Fever, chills, pleuritic chest pain, dyspnea
    • Rigor - classically one teeth-chattering chill is Strep. pneumo.
    • Shortness of breath
    • Elderly
      • Often non-specific presentation, present with confusion, exacerbation of chronic cardiopulmonary disease.
      • Tachypnea is the most sensitive finding in edlerly.
    • Rule out risk factors for HAP (Healthcare Associated Pneumonia)
      • Antibiotic therapy or hospitalization in preceeding 90 days.
    • Epidemiologic history for unusual pathogens.

     

    Unusual Pathogens

    • Aspiration - Gram negative enteric pathogens, organ anaerobes.
    • Cough >2w with post-tussive vomiting: Bordetella pertussus.
    • Cavitary infiltrates -  Community MRSA, oral anaerobes, fungal pathogens, TB
    • Alcoholism - Klebsiella, Staph aureus, oral anaerobes.
    • COPD/Smoking - Gram Negatives, Haemophilus, Pseudomonas, Legionella, S. aureus, Moraxella, clamodophila.
    • Bat/Bird Droppings Exposure - Histoplasma capsillatum (if right geographic locale)
    • Bird Expsoure - Clamydophila psittaci
    • Rabbits - Tularemia
    • Farm Animal / Pregnant Cats - Coxiella burnetii (Q-fever)
    • Rodents Excreta - Hantavirus (recent)
    • HIV Infection - Common organisms + PJP, cryptococcus, histoplasma, aspergillosis, pseudomonas, mycobacterium.
    • Hotel/Cruise Ship - Legionella
    • SW United States - Coccidioidomycosis species or Hantavirus. (California, desert)
    • SE or E Africa - Burkholdaria pseudomallei
    • Influenza - Primary influenza, secondary bacterial pneumonia (S. pneumo, S. aureus, H.influ).
    • IVDU - S. aureus, TB, pneumococcus.
    • Endobronchial obstruction - anaerobes, pneumococcus, H.influenzae.
    • Bronchiectasis, Cystic Fibrosis - Pseudomonas or Burkholdaria cepacia
    • Bioterrorism - Anthrax, Plague, Tularemia.

    Classification

    • Classified as:
      • Typical Pneumonia
        • Rapid onset, severe symptoms, productive cough, dense CXR consolidation.
      • Atypical Pneumonia
        • Slower onset, less severe symptoms, less severe cough, minimal sputum, CXR (patchy/interstitial pattern)
      • Community Acquired (<14d in hospital)
      • Hospital Acquired (>14d)
    • Can sometimes narrow down to organism by symptoms and radiologic findings.
    • PnByOrganism.png

     

     

    • Chest Xray findings:
      • 1. Lobar Pneumonia
        • Distinct anatomic segment of the lung.  Respects anatomic boundaries (no proteases/hyaloronidases to break down tissue).
        • S. pneumoniae, H. influenzae, Legionella
          • PnLobarCXR.png
      • 2. Bronchopneumonia
        • Originates in small ariways and spreads to adjacent ones.  "Patchy infiltrates" that involve multiple areas of the lung and extend down bronchi. 
        • S.aureus, Gram negatives, Mycoplasma, Chlamydia, viruses
          • PnBronchopneumonia.png
      • 3. Intersitial pneumonia
        • Lung interstitium inflamed: fine diffuse grandular infiltrate.
        • Influenza, CMV, Pneumocystis jirovecii, Miliary TB (micronodular infiltrates).
          • (Can look like CHF)
          • PnInterstitial.png
      • 4. Lung abscess
        • Tissue necrosis, cavities with inflammatory fluid
        • Do CT
        • Anaerobics and S.aureus.
      • 5. Nodular Lesions
        • Yeasts: (cryptococcus) Moulds (Histoplasmosis, coccidiomycosis) - nodular
        • Do CT
        • "Cannonball lesions" from hematogenous spread of endocarditis.

    Investigations

    • Diagnosis:
      • Clinical findings are often not sufficient to diagnose pneumonia
      • CXR is mandatory, but initial normal CXR does not exclude if has focal resp physical exam findings + symptoms.
        • Repeat CXR in 24-48hrs may show airspace disease.
    • Workup:
      • CBC + differential, O2 sat, arterial gasses (pH <7.35 = bad, or O2 < 60mmHg = bad)
      • BUN > 10.7 mmol/L (kidney hypoperfusion or dehydration)
      • Serum Na < 130 (increased ADH from depleted volume).
      • Glucose > 13.9 (bad prognostic factor)
      • Consider: Blood cultures, sputum gram stain + culture, pneumococcal + legionella urine antigen testing (all required for ICU)
      • Blood cultures x2
        • Draw before first dose of abx, esp in ICU, on hospitalized pts it's unclear.  I.e. is a quality medicare indicator in all hospitalized admissions, but most guidelines for ICU only.
        • Positive in 5-14% of hospitalized CAP pts. --> obtain before abx (quality care indicator for medicare)
        • Initially studies indicated lack of benefit of cultures in non-severe CAP, but now optional. 
        • See table on UpToDate (recreated below)
      • Sputum Gram Stain and Culture
        • Controversial:  Guidelines by Infections Disease Society of America and American Thoracic Society:
          • Optional for outpatients.
          • In hospitalized pts (not in ICU) recommended for:  (optional in the rest)
            • Outpatient therapy ineffective
            • Cavitary infiltrates
            • Alcoholism
            • Chronic Liver Disease
            • Functional or Anatomic Asplenia
            • Severe Obstructive or Structural Lung Disease
            • Leukopenia
        • Lots of pharynx contamination (need to cough deeply to bring up sputum).. may represent colonization. (Check for squamous cells (>10 is poor sample) and PMNs + bronchial epithelial cells (good sample))
        • Sputum for : Gram stain, cultures, sensitivity, PCR
        • PMNs  --> bacterial, Mononuclear cells --> Mycoplasma, Chlamydia, viral
        • Difficult to culture Legionella, mycoplasma, chlamydia, Pneumocystis jirovecii, likely need PCR
          • Can also do urinary antigens.
      • Bronchoalveolar lavage - useful for PJP
      • Legionella urine antigen Indicated for recent travel pts, but often done by specialists on high risk patients.
        • (only picks up Legionella pneumophila type 1).  70-90% Sn, 99% Sp.
      • Pneumococcal urine atigen: 70% Sn, 96% SP, rapid test.
      • NOTE: Severe CAP requiring ICU admission should have blood cultures, Legionella, and pneumococcus urinary antigens, and sputum culture (expectorated or endotrachial aspirate).
      • Indication

        Blood

        Culture

        Sputum

        Culture

        Legionella

        UAT

        Pneumococcal

        UAT

        Other
        ICU Admission X X X X - Endotracheal Aspirate or Bronch or BAL
        Failure of Outpt Abx Therapy   X X X  
        Cavitary Infiltrates X X     - Fungal + TB cultures
        Leukipenia X     X  
        Alcohol Abuse X X X X  
        Chronic Severe Liver Disease X     X  
        Severe Obstructive/Structural Lung Disease   X      
        Asplenia (anatomic or functional) X     X  
        Recent Travel (within past 2 weeks)     X   - Complex (see "Unusual Pathogens")
        Positive Legionella UAT Result   X ---    
        Positive Pneumococcal UAT Result X X   ---  
        Pleural Effusion X X X X - Thoracentesis and pleural fluid cultures

     

    Management

    • Admit or Not Admit

      • Outpatient management is preferrable, several scoring systems help guide hospitalization need.
      • CURB65 is very common (because it's easy compared to PSI)
        • CURB65 Score:

          • Confusion
          • Blood Urea Nitrogen  >20 mg/dL (7.14 mmol/L)
          • Respiratory Rate  ≥ 30 bpm
          • Blood Pressure sBP < 90 or dBP < 60
          • Age ≥ 65

           

          NEW: CRB65 Score - Can drop Urea

          -  0 or 1 --> Outpatient

                             Treatment (Low Mort)

          -  ≥ 2 --> Hospitalization

          -  ≥ 3 --> Consider ICU

        • PnCURB65.png
      • Pneumonia Severity Index (PSI)

        • Complicated calcuation (20 different variables), use online calculator.
        • Assigns to 5 mortality risk groups (I - V)
          • Groups 1-2 => Outpatient Management (Low Mortality Risk Groups)
          • Group 3 => Brief hospitalization for observation
          • Groups 4-5 => Require hospitalization
      • PORT score is also around, but not as common.
      • CURB65 and PSI scoring systems most popular.
        • Studies show that both are effective for predicting mortality.
        • Negative predictive value is greater than positive. 
        • Also predict the time to clinical stability. 
      • However, they are part of the decision.  Pts with poor social supports and underlying chronic disease etc.. require admission that aren't in scoring systems.
      • CAP considered severe if requires early ICU care.
      • Patients admitted to ICU have lower mortality than those transferred to the ICU.  Hence early ICU admission reduces mortality for severe CAP.
        • 50% of ICU deaths due to CAP occurs in patients who were initially admitted to the medical ward
    • Admission to ICU decision criteria:

      • Proposed to the Infectious Diseases Society of America (IDSA) and American Thoracic Society proposed guidelines for ICU admission (major + minor criteria)
      • Major Criteria Minor Criteria
        • Need for mechanical vent and
          vasopressor support
        • Clinical
          • Confusion (new-onset disorientation to person, place, or time)
          • Hypothermia (core temperature <36.0 °C [96.8 °F])
          • Respiration rate ≥30/min
          • Hypotension necessitating aggressive fluid resuscitation
          • Multilobar pulmonary infiltrates
        • Laboratory
          • Arterial PO2/FIO2 ratio ≤250 or requiring NIPP
          • Leukopenia (<4000 cells/µL [4.0 × 109/L])
          • Thrombocytopenia (<100,000 /µL [10 × 109/L])
          • Blood urea nitrogen >20 mg/dL (7.1 mmol/L)
        • Major Criteria => Admit to ICU
        • ≥ 3 Mintor Criteria => Admit to ICU

        This has not undergone extensive validation, but recent investigation has shown that the negative predictive value of the severe CAP minor criteria is greater than 90%.

     

    Antimicrobial Therapy

    • Studies as of 2014: Initial mgmt: no difference between empric therapy and pathogen-directed therapy except in ICU.
      • Pathogen directed therapy may have fewer adverse effects.
      • Confirming etiologic dx helpful if fail to respond to abx.
    • CAPTxGuidelines2.png
    • Key Point: Risk factors for macrolide resistant pneumococcus:
      • Age > 65
      • Recent B-lactam use in <3mo
      • Medical comorbidities (COPD, DMII, Cancer, CKD, Asplenia anatomic or functional)
      • Immunocompromise
      • Alcoholism
      • Child in daycare
    • Empiric Therapy:
      • Start therapy within 4-6 hours of diagnosis (relates to mortality)
      • Choice depends on outpatient vs. inpatient vs. ICU + risk factors. (see chart)
      • General Principles of Therapy:  (Rationale for above guidelines)
        • Azithromycin covers typical and atypical organisms.  However, widespread macrolide use for respiratory infections in 80's and 90's led to pneumococcus resistance to macrolides (~30% depending on locale). 
          • Hence nowadays macrolide monotherapy only used in healthy outpatient populations who can tolerate incomplete coverage - if does not respond, they can be treated as a "non-responder" with a better regimen. 
        • (MAJORITY OF CASES) The patient has comorbidities (cannot afford not covering resistant pneumococcus) or high risk of resistant pneumococcus (Daycare, recent <3mo B-lactam use), or severe infection (requiring admission or ICU), must cover resistant pneumoccocus with:
          • respiratory fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin) (NOT ciprofloxacin as it does not cover aerobic G+'s).  These agents also cover atypical organisms.
            OR
          • macrolide (i.e. azithromycin) for atypical organisms, but combine with an agent that covers macrolide-resistant pneumococcus (i.e. ceftriaxone, ceftazidime, carbepenems, amox-clav etc.. many choices!)
        • If risk factors for pseudomonas (i.e. chronic structural lung disease, steroids, -- see chart)
          • Cover with antipseudomonal agent in addition to previous regimens.
          • US guidelines suggest double-covering pseudomonas (due to high level pseudomonas resistance in US), hence most regimens require combinations of:
            • Anti-pseudomonal B-lactam
            • Ciprofloxacin, levofloxacin
              • NOTE: Common misconception of cipro being more potent than levo.  This is a test-tube phenomenon, in vivo either one can be used based on published guidelines)
            • Aminoglycosides
        • NOTE: For bacteremic pneumococcus, studies indicate that combination of B-lactam and macrolide is better.  Either due to co-infection with an atypical or anti-inflammatory effect of macrolides.
      • Aspiration Outpatient 
        • (Cover mixed G- rods, anaerobes and S. aureus)
        • Penicillin or clindamycin (should cover most oral flora).. Clindamycin better for abscess.
      • Aspiration Inpatient
        • (Cover resistant mixed G- rods, anaerobes and S. aureus)
        • Use 3rd gen cephalosporin or resp fluoroquinolone
        • COMBINE WITH metronidazole
        • OR use pip-tazo or ticarcillin-clavulanate.
      • Duration:
        • 72 hours after afebrile is a good marker.
        • If necrosis of lung  (S. aureus or Klebsiella, anaerobes), may need up to 2 weeks.
      • Switch to oral when improving (keep same class!!!)
    • Large Pleural Effusions
      • Defined "Large" if occupies > 1/2 hemithorax or fluid level >1cm on lateral decubitus.
      • Needs thoracetesis + blood, sputum cultures + Legionella Urine Antigen
    • Monitor Response to treatment:
      • Temperature
      • Resp rate
      • PaO2 / O2 sat
      • Symptoms
      • WBC
      • CANNOT Monitor via CXR.. changes can persist for weeks.
      • NEVER USE CHEST XRAY TO MONITOR RESPONSE TO TREATMENT

        (can take weeks to resolve in absence of infection) 

    • Discharge
      • Criteria to change from IV to Oral Therapy:  (And Discharge, no need to ruotinely observe on oral therapy)
        • Temperature ≤ 37.8
        • HR ≤ 100
        • RR < 24/min
        • sBP ≥ 90    
        • O2sat ≥ 90%
        • PO2 ≥ 60 on room air
        • Tolerating Oral Intake
        • Normal Mental Status
      • Total Duration of Therapy:
        • 7 days (including time in hospital)
        • Long Duration for:
          • Those taking long to be clinically stable
          • Cavitary pneumonia
          • S. aureus or Pseudomonas pneumonia
        • NOTE: Pneumococcal bacteremia: do not usually require longer therapy
      • REQUIRED: Pneumococcal + influenza vaccine (Quality of Care)
    • Charts:
    • PnTx1.png
    • PnTx2.png
    • PnTx3.png

    Complications

    • If not improvement consider:
      • BOOP
      • Vasulitis
      • PE
      • Resistant Pathogen
      • Parapnemonic effusion or empyema (esp if initially improve then relapse).
        • 1/3 develop effusion.
        • Thoracentesis if ≥50% of hemithorax (large pleural effusion) or fail to respond clinically.
          • (If stable, improving, but small-to-moderate effusion, can just observe)
    • Follow-up
      • Chest imaging not indicated in most patients.
      • F/U CXR - consider to document clearance and r/o malignancy (9.2% had pulmonary malignancy)
        • 6-8 weeks for smokers, and >40yo. 
      • Counsel smokers
      • F/U office visit 10-14 days post-therapy.

    Notes on Specific Organisms

    • S. pneumoniae

      • On Microscopy:
        • "Lancet-shaped diplococci"
          • Many subtypes
      • Thick outer capsule blocks phagocytosis (Type 3 is the thickest capsule)
      • Immunoglobulins/opsonins important in phagocytosis
      • Does not cross anatomic barriers (cannot break down tissue?). Host inflammation causes damage.
      • High risk people:
        • Risk is higher in opsonins deficiencies
          • Hypogammaglobulinemia
          • Complement deficiency
          • HIV
        • Splenic dysfunction
        • Chronic diseases:
          • Cirrhosis
          • Alcoholism
          • Nephrotic syndrome
          • CHF
          • COPD
      • Classically  big "rigor/chill", and Sputum can be rusty in color    
      • Lots of penicillin resistance (25%-35%)
      • Treatment:
        • Use penicillin/ampicillin for pen-sensitive strains.
        • High dose parenteral penicillin, a 3rd gen cephalosporin or oral amoxicillin used for intermediate-sensitivity strains (except meningitis!)
        • Resp fluoroquinolone (gatiflox, moxiflox, levoflox) work for high-level pen resistant strains, but do not work for meningitis.  
        • Use vancomycin for meningits
        • GIVE PNEUMOCOCCAL VACCINE! (23 valent)
          • Especially to:
            • >65yo
            • Chronic disease
            • Asplenic
            • Immunocompromised
            • Alcoholic
    • Haemophilus influenzae

      • Small gram-negative coccobacilli
      • CXR:
        • Often Lobar, but sometimes patchy pneumonia.
      • Group B and non-typable cause CAP
      • non-typable more common in elderly and smokers with COPD.
      • Treatment:
        • IV: Ceftriaxone, cefotaxime
        • Oral: amox-clav.
        • TMP-SMX, new macrolides (azithro, clarithro), fluoroquinolones, and extended cephalosporins also work.
    • Staphylococcus aureus

      • Clasically: follows influenza infection
        • Often used as a marker of influenza epidemic.
      • More common in HIV and IV drug use.
      • CXR: bronchopneumonia, lung abscesses
      • MSSA: high dose nafcillin or oxacillin
      • MRSA: vancomycin with blood monitoring 15-20 ug/mL (can also do linezolid, but expensive!!)
    • Legionella pneumophila

      • Gram-negative bacilli
      • Found in standing water and soil
        • Inhallation of contaminated water droplets (shower heads, cooling towers), or excavations - soil particles.
        • Sometimes nosocomial: use of unsterilized tap water.
      • Typical pneumonia features, however:
        • 1. small amounts of sputum
        • 2. confusion/headache.
        • 3. GI symptoms
        • 4. Hyponatremia
      • Need special culture medium (buffered charcoal) with suppresive abx.
      • PCR and urinary antigen also used.
      • Treatment: Use azithromycin or fluoroquinolones.
        • In transplant: use fluoroquinolones (azithromycin interacts with immunosuppressive meds metabolism).
        • Mortality 16-50%
           
    • Atypical pneumonias

      • Treat with a macrolide or tetracycline
      • Mycoplasma pneumoniae

        • Most frequent pneumonia in young <40yo ppl.
        • Most common in late summer and early fall.
        • Sx:
          • Sore throat, bullous myringitis (5%).
          • Tracheobronchitis: Hacking cough, worse at night, lasting several weeks.
        • CXR: patchy infiltrates.
        • No rapid dx test.
        • Treatment
          • Macrolide (azithromycin x5days)
          • Tetracycline
      • Chlamydia pneumoniae

        • Taiwan acute respiratory agent.
        • 5-15% of pneumonias.
        • Presents similar to mycoplasma with same CXR.
        • Treatment:
          • Tetraycycline
          • Macrolides, fluoroquinolones are also effective.
      • Viruses:

        • Influenza A + B, parainfluenza virus, RSV (kids, elderly), adenovirus
        • Rapid tests exist for influenza.
        • Treatment:
          • Influenza A: amantadine, rimantadine.
          • Influenza A, B, + others?: neuramidase inhibitor
          • Treat within 48hr onset.

    Hospital Acquired Pneumonia / Ventilator Associated

    • HAP:
      • Pneumonia that occurs ≥48hrs after hospital admission and not incubating at time of admission
      • 2nd leading cause of hospital infection (after catheter UTI)
      • Mechanical Ventilation is the strongest risk factor for HAP (incidence 6-20 fold grader in ventilator patients), re-intubation is an additional risk factor for HAP/VAP.

    The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines on the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia used the following definitions [2]:

    • Hospital-acquired (or nosocomial) pneumonia (HAP) 
      • ≥ 48 hours or more after admission and did not appear to be incubating at the time of admission.
    • Ventilator-associated pneumonia (VAP)
      • Type of HAP --> 48 to 72 hours after endotracheal intubation.
    • Healthcare-associated pneumonia (HCAP)
      • Nonhospitalized patient with extensive healthcare contact, as defined by one or more of the following:
        • Intravenous therapy, wound care, or intravenous chemotherapy within the prior 30 days
        • Residence in a nursing home or other long-term care facility
        • Hospitalization in an acute care hospital for two or more days within the prior 90 days
        • Attendance at a hospital or hemodialysis clinic within the prior 30 days

    Empiric Therapy:

     

    • Step 1:  Risk Factors for MDR?
      • Use of antibiotics within the preceding 90 days

      • Current hospitalization of ≥5 days

      •  

        High frequency of antibiotic resistance in the community or in the specific hospital unit

      • Immunosuppressive disease and/or therapy

      • (Severe septic shock)

      • HCAP risk factor

    •  

      If Risk Factors for MDR: (ONE of)

      • Antipseudomonal cephalosporin (ceftazidime 2g q8h, cefepime 2g q8h)

      • Antipseudomonal carbepenem (meropenem 1g q8h, imipenem 500mg-1g q6h)

      • Pip-tazo 4.5g q6h

      • If penicillin allergic --> (if mild, rash etc..) can trial cephalosporin or aztreonam (even less cross-reactivity)

      • If penicillin anaphylaxis --> consult allergy specialist

    • Add-on therapies

      • Ciprofloxacin

      • Levofloxacin

      • Gentamycin

      • Tobramycin

    • PLUS ONE of the following (if MRSA is suspected, there are MRSA risk factors, or there is a high incidence of MRSA locally):

      • Linezolid

      • Vancomycin (15-20mg/kg + dose interval by renal function)

      • Telavancin

    Source; IDSA Guidelines / UpToDate.com

     

     

     

     

     

    Ventilator Associated Pneumonia

    • Subset of Hospital Acquired Pneumonia
      • Pneumonia that develops >48-72hrs after mechanical ventilation started.
      • 50% of VAP occur in first 4 days of intubation
    • Classic Symptoms (only present in 30-40% of VAP)
      • CXR pulmonary infiltrate
      • Fever
      • Leukocytosis
      • Purulent Sputum Production
    • Organisms:
      • VAP comes from oral flora organisms.
      • Depends on what patient's oral flora is colonized with.
      • Generally:
        • Staphylococcus aureus
        • Pseudomonas aeruginosa
        • Streptococcus pneumoniae
        • Gram-negative Rods 
        •  
          • vapOrganisms.jpg
    • Diagnosis:
      • very challenging (classic symptoms are not very predictive)
      • Blood cultures (poor operating characteristics)
      • Tracheal Aspirates
        • Tracheal Aspirate (good for ruling out)
        • Protected Specimen Brushings (PSB) - good for confirming VAP
        • Broncho-alveolar Lavage (BAL) - good for confirming and excluding VAP
      • vapCulture.jpg

    • Treatment:

      • Depends on what patient is colonzied with.

      • Risk of colonization with Staph aureus and gram-negative rods:

        • Unlikely Colonized Likely Colonized

          All of:

          - Admitted < 5d ago

          - Admitted from home

          - No other admissions in past 3mo

          - Not dialysis patient

          One of:

          Admitted > 5d ago

          Admitted from nursing home

          Other admissions in past 3mo

          A dialysis patient

          Empiric Antibiotics

          - Ceftriaxone or Quinolone

           

          Empiric Antibiotics

          - Piperacillin-tazobactam or

          - Carbapenem or

          - Ceftazidime or cefepime

          PLUS

          - Vancomycin or linezolid

           (to cover MRSA and vanco-resistant MRSA/VRE)

          AND CONSIDER

          - Quinolone or aminoglycoside

            (to double-cover pseudomonas)

      • Duration: 8 days (traditionallly 14-21 days, but recent study shows 8 equal to 15 days)
    • Prevention:
      • Critically ill patients have oropharynx colonized with potentially pathogenic organisms.
      • Oropharyngeal decontamination is looked at.
      • Study:
        • Bergmans et al (2001): oral decontamination with topical non-absorbable antibiotics reduces VAP
          • Used 2% polymyxin, 2% tobramycin, 2% amphotericin B applied with gloved finger q6h
        • Koeman et al (2006): Chlorhexidine also reduces VAP
          • (Thought to avoid development of antimicrobial resistance, never compared to abx)
          • 2% chlorhexidine in petroleum jelly (Vaseline) appied to orgal mucosa q6h
          • 2% colistin can be added  for gram-negative coverage (chlorhexidine primarily covers G+'s).  Colistin not used as an antibiotic anymore, resistance to it is not a big problem.
      • Oral decontamination is advised to any patient that is likely to be ventilator dependent for more than few days, and continued as long as patient stays in ICU
        • 2% chlorhexidine +/- 2% colistin preferred (theoretical advantage)

    Tuberculosis

     

    Atypical Mycobacteria

    Fungal Pneumonias

    Histoplasmosis

    • Histoplasma capsulatum
    • Primarily in Midwest and Southeast USA.
    • Grows in moist soil in temperate climate --
      • Ohio River and Mississippi River Valleys (CLASSIC)
    • Exposure from soil excavation, construction, and also from Caves/buildings with bats.
    • Exists as mycelia in environment, and yeast in the body.
      • Converts to yeast, upregulates calcium binding protein... frequently see calcifications.
      • Macrophages present histo antigens to T-cells in lymph nodes, and become activated inseveral weeks.
    • Symptoms:
      • Astymptomatic/mild flu-like-illness + clear in healty
      • Young,  Elderly, Immunocompromised:
        • 14 days post-exposure
          • high fever, headache, cough (no sputum), dull CP.
          • CXR- patchy infiltrates, then later to "buckshot" calcifications.
          • Mediastinal lymphadenopathy (like lymphoma and sarcoid).
      • If disseminated disease (10%)
        • Meningitis, lymphocytosis, low glucose.
        • Reticularnodular pattern on CXR. (CXR normal in 1/3)
    • Diagnosis:
      • Culture: needs selective media, lab needs to know. Takes 7 days (Not routine).
      • Lysis-centrifugation.
      • Bronchoscopic lavage fluid -- should test. (90% yield in HIV pts)
      • Urine antigen test.  (90% if disseminated, 40% if cavitary, and 20% pulmonary)
      • Histopathology good too.  Silver stain.
      • Bottom line: Difficult to detect.  
        • If disseminated --> do bone marrow culture
    • Treatment:
      • Itraconazole is good agent.  Recommended for:
        • Acute pulmonary illness that fails to imrpove in 7 days.
        • Extensive mediastinal involvement.
        • Progressive cavitary disease.
      • Amphotericin B if more severe disease.
        • or if no improvement with Itraconazole

    Coccidiomycosis

    • Coccidioides immitis
    • Grows in soil; prefers dry, alkaline soil, hot summers, and winters with few freezes.
      • These conditions exist in California's San Joaquin Valley in southern Arizona, New mexico, and texas
    • Also in Mexico, Central America, and South America.
    • Contracted in summer (dust storms, excavation, earthquakes).
    • Cell-mediated immunity (Endospores).
    • Sx:
      • non-productive cough, fever, pleuritic chest pain, SOB, headache, fatigue.
      • skin manifestations: erythema nodosum, erythema multiforme, nonpruritic papular rash.
      • Eosinophilia.
    • Disseminates in AIDS/HIV.
    • Chronic Lung Infection: fibrosis, nodules, cavities.
    • Chronic pleural effusions in young healthy athletic males.
    • Dx:
      • Sputum examination (or gathered by bronchoscopy)
      • Easy to culture on mycology plates.
      • Serology: IgG, IgM
    • Tx:
      • Only if disseminated disease.
      • Amphotericin B
      • Fluconazole or itraconazole if less severe.

     

    Quick Summary

    • CAP
      • Organisms
        • S. pneumo
        • H. influenzae
        • Moraxella
        • Atypicals  (Legionella, Mycoplasma, Chlamydophila)
        • Rarely: S. aureus, GAS
      • Treatment:
        • Amoxil +/- clavulin  (macroldies or resp Flouroquinolones for atypicals)
        • Can step-up to ceftriaxone
    • HCAP, Hospital Acquired Pneumonia (HAP)
      • Increased rates of Gram-negatives and Pseudomonas.
      • Ctx +/- atypical
      • Piptazo +/- atypicals
    • VAP: Piptazo.
    • Aspiration Pneumonia
      • Day 1-3: Aspiration PNEUMONITIS
      • Day 3-5: Bacteria
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