Executive Summary(4)

1
Executive Summary(4)

• A shorter duration of ABx therapy (7 to 8 days)
  recommended for
• - uncomplicated HAP, VAP, or HCAP
• - with initially appropriate therapy
• - a good clinical response
• - with no evidence of infection with non-
• fermenting gram-negative bacilli

2
Introduction(1)

• HAP pneumonia occurs ? 48 hrs after admission (
  not intubated at admission)
• VAP pneumonia occurs?48-72 hrs after intubation
• HCAP pneumonia occurs including those
• - hospitalized in an acute care hospital
  for ? 2 days
• within 90 days
• - received recent IV antibiotic therapy,
  chemotherapy, or
• wound care within the past 30 days
  
• - resided in a nursing home or long-term
  care facility
• - attended a hospital or hemodialysis
  clinic

3
Introduction(2)

• 4 major principles to manage HAP, VAP, HCAP
• Avoid untreated or inadequately treatment
  because failure to initiate prompt appropriate
  and adequate therapy ? ? increased mortality
• Avoid the overuse of antibiotics by focusing on
  accurate diagnosis, tailoring therapy to the
  results of LRTCs, and shortening duration of
  therapy to the minimal effective period

4
Introduction(2)

• 4 major principles to manage HAP, VAP, HCAP
• Recognize the variability of bacteriology from
  one hospital to another, specific sites within
  the hospital, and from one time period to
  another, and use this information to alter the
  selection of an appropriate antibiotic treatment
  regimen for any specific clinical setting
• Apply prevention strategies aimed at modifiable
  risk factors

5
Epidemiology (1)

• Time of onset of pneumonia an important
  epidemiologic variable and risk factor for
  specific pathogens and outcomes
• Early-onset HAP and VAP( ? 4 days)
• usually better prognosis, more likely to be
  caused by antibioticsensitive bacteria
• (Level II)

6
Epidemiology (2)

• Late-onset HAP and VAP ( ?5 days ) usually with
  increased mortality and morbidity, more likely to
  be caused by multidrug-resistant (MDR) pathogens
  (Level II)
• Early-onset HAP with prior ABx or prior
  hospitalization within the past 90 days are at
  greater risk for colonization and infection with
  MDR pathogens? treat as late-onset HAP or VAP
  (Level II)

7
Epidemiology (3)
8
Epidemiology (4)

• HAP/VAP Pts ? risk for colonization and
  infection with MDR pathogens (Level II)
• Incidence of HAP/VAP difficult to define exactly
  (overlap with tracheobronchitis) (Level III)
• The exact incidence of HAP usually between
  515/1,000 admissions (Level II)
• The exact incidence of VAP 620-fold greater
  than in non-ventilated patients (Level II)

9
Epidemiology (5)

• Causes of most cases of HAP, VAP, and HCAP
  Bacteria, usually polymicrobial especially high
  rate in patients with ARDS (Level I)
• Common bacteria (Level II)
• - Aerobic GNB P. aeruginosa, K. pneumoniae,
  and
• Acinetobacter species
• - Aerobic GPC, such as S. aureus ( much MRSA)
• - Anaerobes uncommon .

10
Epidemiology (6)

• Rates of L. pneumophila vary between hospitals,
  occurs commonly in serogroup1 with colonized
  water supply and ongoing construction (Level II)
• Nosocomial virus and fungal infections uncommon
  in immunocompetent patients (Level I)
• Outbreaks of influenza occurred sporadically and
  risk of infection reduced with widespread
  effective infection control, vaccination, and use
  of antiinfluenza agents (Level I)

11
Epidemiology (7)

• Prevalence of MDR pathogens varies by patient
  population, hospital, and type of ICU need for
  local surveillance data (Level II)
• MDR pathogens (Level II)
• more commonly isolated from patients
• - with severe, chronic underlying disease
• - with risk factors for HCAP
• - with late-onset HAP or VAP

12
Pathogenesis (1)

• Sources of pathogens (Level II)
• - healthcare devices
• - the environment (air, water, equipment,
  and fomites)
• - transfer of microorganisms between
  patients and staffs
• Host- and treatment-related colonization factors
• important pathogenesis (Level II)
• - the severity of underlying disease
• - prior surgery
• - exposure to antibiotics
• - other medications
• - exposure to invasive respiratory devices
  and equipment

13
Pathogenesis (2)

• Primary routes of bacterial entry (Level II)
• - aspiration of oropharyngeal pathogens
• - leakage of secretions
• which containing bacteria around tube cuff
• Uncommon pathogenic mechanisms (Level II)
• - inhalation or direct inoculation of
  pathogens
• - hematogenous spread from infected
  intravenous
• catheters
• - bacterial translocation from GI tract

14
Pathogenesis (3)

• Infected biofilm in the endotracheal tube, with
  subsequent embolization to distal airways, may be
  important in the pathogenesis of VAP (Level III)
• Stomach and sinuses potential reservoirs of
  pathogens, contribute to bacterial colonization
  of the oropharynx, but their contribution is
  controversial (Level II)

15
Modifiable Risk Factors (1)

• General prophylaxis.
• Effective infection control measures (Level I)
• -staff education
• -alcohol-based hand disinfection
• -isolation? cross-infection with MDR
  pathogens
• Surveillance of ICU infections (Level II)
• to identify and quantify endemic and new MDR
  pathogens, and preparation of timely data for
  infection control

16
Modifiable Risk Factors (2)

• Intubation and mechanical ventilation
• Avoid intubation and reintubation (?risk of VAP)
  (Level I)
• Noninvasive ventilation should be used whenever
  possible in selected patients (Level I)
• Orotracheal intubation and orogastric tubes are
  preferred over nasotracheal intubation and
  nasogastric tubes to prevent nosocomial sinusitis
  and to reduce the risk of VAP ( direct causality
  has not been proved) (Level II)

17
Modifiable Risk Factors (3)

• Intubation and mechanical ventilation
• Continuous aspiration of subglottic secretions?
  risk of early-onset VAP (Level I)
• Cuff pressure ? 20 cm H2O to prevent leakage of
  bacterial pathogens (Level II)
• Clear contaminated condensate from ventilator
  circuits and prevent to enter either the
  endotracheal tube or inline medication nebulizers
  (Level II)

18
Modifiable Risk Factors (4)

• Intubation and mechanical ventilation
• Passive humidifiers or heatmoisture exchangers
  ?circuit colonization, but not consistently
  incidence of VAP? not a pneumonia prevention
  tool (Level I)
• ?duration of intubation and MV may prevent VAP,
  achieved by the use of sedation and to accelerate
  weaning (Level II)

19
Modifiable Risk Factors (5)

• Aspiration, body position, and enteral feeding.
• Kept in the semirecumbent position (3045) rather
  than supine to prevent aspiration, especially
• when receiving enteral feeding (Level I)
• Enteral nutrition preferred over parenteral
  nutrition (Level I)
• - ? risk of complications related to CVP
• - prevent reflux villous atrophy of
  intestinal mucosa ( which?risk of bacterial
  translocation)

20
Modifiable Risk Factors (6)

• Modulation of colonizationoral antiseptics and
  ABx
• Routine prophylaxis of HAP with oral antibiotics
  with or without systemic antibiotics
• -?incidence of VAP
• -has helped contain outbreaks of MDR bacteria
  (Level I)
• Not recommended especially in patients who
  may be colonized with MDR pathogens (Level II)
• Onset of infection with prior systemic ABx
• ??suspicious infection with MDR pathogens
  (Level II)

21
Modifiable Risk Factors (7)

• Modulation of colonizationoral antiseptics and
  ABx
• Prophylactic systemic ABx for 24 hrs at the time
  of intubation demonstrated to prevent HAP in
  patients with closed head injury, but not
  recommended a routine until more data become
  available (Level I)
• Modulation of oropharyngeal colonization by the
  use of oral chlorhexidine has prevented HAP in
  CABG, but not recommended a routine until more
  data become available (Level I)

22
Modifiable Risk Factors (8)

• Modulation of colonizationoral antiseptics and
  ABx
• Use daily interruption or lightening of sedation
  to avoid constant heavy sedation and try to avoid
  paralytic agents, both of which can depress cough
  and thereby ? risk of HAP (Level II)

23
Modifiable Risk Factors (9)

• Stress bleeding prophylaxis, transfusion
• Sucralfate ?VAP, but slightly ?rate of
  significant gastric bleeding compared with H2
  antagonists. Stress bleeding prophylaxis H2
  antagonists or sucralfate is acceptable (Level I)
• Transfusion of RBC with a restricted policy
  leukocyte-depleted RBC transfusions can ? HAP in
  selected patient populations (Level I)

24
Modifiable Risk Factors (9)

• Hyperglycemia
• Intensive insulin therapy recommended to
  maintain BS between 80 and 110 mg/dl in ICU
  patients?
• - ?nosocomial blood stream infections
• - ?duration of mechanical ventilation
• - ? ICU stay
• - ? morbidity
• - ? mortality
• (Level I)

25
Diagnose (1)
26
Diagnosis (2)

• Ccomprehensive medical history, PE, CXR, severity
  of HAP, exclude other potential infection,
  specific conditions that can influence the likely
  etiologic pathogens (Level II)
• Tracheal colonization does not require therapy
  or diagnostic evaluation in the absence of
  clinical findings or sign of infection (Level II)

27
Diagnosis (3)

• Blood cultures All patients should collect A
  positive result indicate pneumonia or
  extra-pulmonary infection (Level II)
• Sample collection Protected specimen brush
  samples- specificitygtsensitivity Endotracheal
  aspirate, BAL-sensitivitygtspecificity (Level II)
• Diagnostic threshold of quantitative culture
• PSB 103 cfu/ml BAL 104105 cfu/ml
• tracheal aspirates 106 cfu/ml

28
Diagnosis (4)

• A sterile culture without a new antibiotic in the
  past 72 hours virtually rules out the presence
  of bacterial pneumonia (NPV 94), but viral or
  Legionella infection is still possible (Level II)
• Semiquantitative cultures of tracheal aspirates
  cannot be reliably as quantitative cultures to
  define the presence of pneumonia and the need for
  antibiotic therapy (Level I)

29
Diagnosis (5)

• Bronchoscopic bacteriologic strategy ? 14-day
  mortality, compared with a clinical strategy in
  VAP (Level I)? should not postpone diagnostic
  studies in clinically unstable (Level II)

30
Treatment (1)
31
Treatment (2)
32
Treatment (3)
Penicillin-resistant S. pneumoniae and
multidrug-resistant S. pneumoniae ?frequency
levofloxacin or moxifloxacin are preferred to
ciprofloxacin and the role of other new
quinolones, such as gatifloxacin, has not been
established
33
Treatment (4)

• ESBL strain such as K.
• pneumoniae or
• Acinetobacter
• carbepenem is a
• reliable choice.
• L. pneumophila
• combination antibiotic
• regimen should include
• macolide (azithromycin)
• or a fluoroquinolone
• (e.g., ciprofloxacin or
• levofloxacin)
• MRSA risk factors are
• present or there is a
• high incidence locally
• Vancomycin or linezolid

34
Treatment (5)
Trough levels for gentamicin and tobramycin ? 1
g/ml and for amikacin ? 45 g/ml for
vancomycin 1520 g/ml.
35
Treatment (6)

• Initial IV form a switch to oral/enteral
  therapy Highly bioavailable agents, such as
  quinolones and linezolid, may be easily switched
  to oral therapy (Level II)
• Aerosolized antibiotics have not been proven to
  have value in the therapy of VAP (Level I)
  However, they may be considered as adjunctive
  therapy in MDR gram-negatives pathogens, not
  responding to systemic therapy (Level III)

36
Treatment (7)

• Combination therapy for possible MDR pathogens
  (Level II) No documented superiority compared
  with monotherapy, except to enhance likelihood of
  initially appropriate empiric (Level I)
• Combination with aminoglycoside stopped after
  57 days in responding patients (Level III)
• Monotherapy Only in the absence of resistant
  pathogens (Level I)

37
Treatment (8)

• If initially appropriate ABx efforts to shorten
  duration from the traditional 1421 to 7 days,
  except P. aeruginosa, and with good clinical
  response resolution of clinical features (Level
  I)
• In P. aeruginosa pneumonia combination
  recommended ( ? resistance on monotherapy)
  combination will not necessarily prevent the
  development of resistance, but avoid
  inappropriate and ineffective tx (Level II)

38
Treatment (9)

• In Acinetobacter species the most active agents
  are the carbapenems, sulbactam, colistin, and
  polymyxin no data documenting an improved
  outcome with combination regimen (Level II)
• In ESBL Enterobacteriaceae monotherapy with a
  third-generation cephalosporin should be avoided.
  The most active agents are carbapenems (Level II)

39
Treatment (10)

• Adjunctive inhaled aminoglycoside or polymyxin
  should be considered for MDR gram-negative
  pneumonia, especially not improving with systemic
  therapy (Level III)
• Linezolid an alternative to vancomycin for MRSA
  (Level II), preferred in renal insufficiency or
  receiving other nephrotoxic agents, but more data
  are needed (Level III).

40
Treatment (11)

• Antibiotic restriction limit epidemic infection
  with specific resistant pathogens
• Heterogeneity of antibiotic prescriptions
  including formal antibiotic cycling
• ? ? overall frequency of antibiotic resistance
• ?long-term impact of this practice unknown
  (Level II)

41
Response (1)

• Serial assessment of clinical parameters to
  define the response to initial empiric therapy
  (Level II)
• Clinical improvement takes 4872 hours? dont
  change therapy during this time unless rapid
  clinical decline (Level III)
• Non-response evident by Day 3, using an
  assessment of clinical parameters (Level II)

42
Response (2)
43
Response (3)

• In responding patient de-escalation of
  antibiotics, narrowing therapy to the most
  focused regimen on the basis of culture data
  (Level II)
• In nonresponding patient evaluate for
• -noninfectious mimics of pneumonia
• -drug-resistant organisms
• -extrapulmonary sites of infection
• -complications of pneumonia and its therapy.
  (Level III)