1. Hospital Acquired Pneumonia

2. Hospital Acquired Pneumonia
Pneumonia that occurs 48 hrs or more after admission, which was not incubating at the time of admission.
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

3. Hospital Acquired Pneumonia
Epidemiology
Common hospital-acquired infection
25% of all ICU acquired infections
2nd most common type of nosocomial infection after UTI.
Incidence increases by 6-20 fold in patients being ventilated mechanically.
Occurs at the rate of 5-10 cases per 1000 hospital admissions
HAP is usually caused by bacteria, is currently the second most common nosocomial infection in the United States, and is associated with high mortality and morbidity. HAP accounts for up to 25% of all ICU infections and for more than 50% of the antibiotics prescribed (16). VAP occurs in 9–27% of all intubated patients. Although HAP is not a reportable illness, available data suggest that it occurs at a rate of between 5 and 10 cases per 1,000 hospital admissions, with the incidence increasing by as much as 6- to 20-fold in mechanically ventilated patients.
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

4. Hospital Acquired Pneumonia
Epidemiology
Associated with substantial morbidity
Has an associated crude mortality of 30-70%
In ICU nearly 90% episodes of HAP occur during mechanical ventilation.
Hospital stay increases by 7-9 days per patient
Produce an excess cost of more than $40,000 per patient
The presence of HAP increases hospital stay by an average of 7 to 9 days per patient and has been reported to produce an excess cost of more than $40,000 per patient. In ICU patients, nearly 90% of episodes of HAP occur during mechanical ventilation. The presence of HAP increases hospital stay by an average of 7 to 9 days per patient and has been reported to produce an excess cost of more than $40,000 per patient. The crude mortality rate for HAP may be as high as 30 to 70%, but many of these critically ill patients with HAP die of their underlying disease rather than pneumonia. The mortality related to the HAP or "attributable mortality" has been estimated to be between 33 and 50% in several case-matching studies of VAP.
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

5. What is VAP?
Pneumonia developing in a patient receiving mechanical ventilation for longer than 48–72 hours after tracheal intubation. [1]
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

6. Ventilator Associated Pneumonia (VAP) – Key Points -
VAP is 15% of all hospital acquired infections
Incidence = 9% to 27% of patients on ventilators
Increased avg. hospital stay 1 to 3 weeks
Mortality = 13% to 55%
Added costs of $40,000 - $50,000 per stay
VAP occurs in 9–27% of all intubated patients. In ICU patients, nearly 90% of episodes of HAP occur during mechanical ventilation. In mechanically ventilated patients, the incidence increases with duration of ventilation.
Centers for Disease Control and Prevention, 2003.
Rumbak, M. J. (2000). Strategies for prevention and treatment. Journal of Respiratory Disease, 21 (5), p. 321;

7. Ventilator Associated Pneumonia (VAP) – Key Points -
Risk of VAP is highest early in the course of hospital stay, and is estimated to be
3%/day during the first 5 days of ventilation,
2%/day during Days 5 to 10 of ventilation, and
1%/day thereafter
The risk of VAP is highest early in the course of hospital stay, and is estimated to be 3%/day during the first 5 days of ventilation, 2%/day during Days 5 to 10 of ventilation, and 1%/day after this . Because most mechanical ventilation is short term, approximately half of all episodes of VAP occur within the first 4 days of mechanical ventilation. The intubation process itself contributes to the risk of infection, and when patients with acute respiratory failure are managed with noninvasive ventilation, nosocomial pneumonia is less common.
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

8. Hospital Acquired Pneumonia
Pathogenesis

9. Hospital Acquired Pneumonia
Pathogenesis
Invasion of the lower respiratory tract by:
Aspiration of oropharyngeal/GI organisms
Inhalation of aerosols containing bacteria
Hematogenous spread
Bacteria can invade the lower respiratory tract by aspiration of oropharyngeal organisms,inhalation of aerosols containing bacteria, or, less frequently, by hematogenous spread from a distant body site (Figure 1). In addition, bacterial translocation from the gastrointestinal tract has been hypothesized recently as a mechanism for infection. Of these routes, aspiration is believed to be the most important for both nosocomial and community-acquired pneumonia.
MMWR, January 3,1997/vol.46/No.RR-1

10. Hospital Acquired Pneumonia
Microaspiration may occur in up to 45% of healthy volunteers during sleep
Oropharynx of hospitalized patients is colonized with various pathogenic bacterias depending on the severity and type of underlying illness
Multiple factors are associated with higher risk of colonization with pathogenic bacteria and higher risk of aspiration
In radioisotope-tracer studies, 45% of healthy adults were found to aspirate during sleep. Persons who swallow abnormally (e.g., those who have depressed consciousness, respiratory tract instrumentation and/or mechanically assisted ventilation, or gastrointestinal tract instrumentation or diseases) or who have just undergone surgery are particularly likely to aspirate.
Several large studies have examined the potential risk factors for nosocomially acquired bacterial pneumonia (Table 2) (6,34,35,135,136 ). Although specific risk factors have differed between study populations, they can be grouped into the following general categories: a) host factors (e.g., extremes of age and severe underlying conditions, including immunosuppression); b) factors that enhance colonization of the oropharynx and/or stomach by microorganisms (e.g., administration of antimicrobials, admission to an ICU, underlying chronic lung disease,
or coma); c) conditions favoring aspiration or reflux (e.g., endotracheal intubation, insertion of nasogastric tube, or supine position); d) conditions requiring prolonged use of mechanical ventilatory support with potential exposure to contaminated respiratory equipment and/or contact with contaminated or colonized hands of HCWs; and e) factors that impede adequate pulmonary toilet (e.g., undergoing surgical procedures that involve the head, neck, thorax, or upper abdomen or being immobilized as a result of trauma or illness).
MMWR, January 3,1997/vol.46/No.RR-1

11. Pathogenesis
MMWR, January 3,1997/vol.46/No.RR-1

12. Colonization Aspiration
MRSA*
HAP

13. Risk Factors Intubation & mechanical ventilation Supine positioning
Inadequate infection control practices
Inadequate surveillance of ICU infections
Nasal intubation
Emergent or re-intubation
Underlying pulmonary disease
Enteral feeding
Risk factors for the development of HAP can be differentiated into modifiable and nonmodifiable conditions. Risk factors may also be patient related (male sex, preexisting pulmonary disease, or multiple organ system failure) or treatment related (intubation or enteral feeding). Modifiable risk factors for HAP are obvious targets for improved management and prophylaxis in several studies .
Intubation and mechanical ventilation increase the risk of HAP 6- to 21-fold and therefore should be avoided whenever possible. Noninvasive positive-pressure ventilation, using a face mask, is an attractive alternative for patients with acute exacerbations of chronic obstructive pulmonary disease or acute hypoxemic respiratory failure, and for some immunosuppressed patients with pulmonary infiltrates and respiratory failure.
VAP may also be related to colonization of the ventilator circuit. A large number of prospective, randomized trials have shown that the frequency of ventilator circuit change does not affect the incidence of HAP, but condensate collecting in the ventilator circuit can become contaminated from patient secretions.
Nasogastric & Naso tracheal intubation seems to increase the incidence of the VAP. There is definite increase in the incidence of VAP in the patient who has been reintubated.
Supine patient positioning may also facilitate aspiration, Using radioactive labeled enteral feeding, cumulative numbers of endotracheal counts were higher when patients were placed in the completely supine position (0°) as compared with a semirecumbent position (45°).
Enteral nutrition has been considered a risk factor for the development of HAP, mainly because of an increased risk of aspiration of gastric contents.
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

14. Risk Factors for MDR Pathogens Causing HAP/ VAP
Antimicrobial therapy in the preceding 90 days
Current hospitalization for >5 days or recent hospitalization (<90 days)
High rate of antibiotic resistance in hospital or ward
Transfer from nursing home or rehab center
Hospitalization for 2 days or more in the preceding 90 days
Home infusion therapy (including antibiotics)
Family member with multidrug – resistant pathogen
Immunosuppressive disease and/or therapy
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

15. Early Vs. Late Onset VAP
Early onset VAP occurs on day 1-4 of intubation
Late onset occurs on or after day 5
Early onset often associated with more pan-sensitive, endogenous pathogens and has a better prognosis
Late onset often associated with multi-drug resistant pathogens (MDRs) and has poorer prognosis
Patients recently hospitalized or transferring from an extended care facility are more likely to harbor resistant pathogens
Time of onset of pneumonia is an important epidemiologic variable and risk factor for specific pathogens and outcomes in patients with HAPand VAP . Early-onset HAP and VAP, defined as occurring within the first 4 days of hospitalization, usually carry a better prognosis, and are more likely to be caused by antibiotic sensitive bacteria. Late-onset HAP and VAP (5 days or more) are more likely to be caused by multidrug resistant (MDR) pathogens, and are associated with increased patient mortality and morbidity.
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

16. Preventive Strategies
Avoid intubation by using noninvasive ventilatory support
Shorten intubation period with switch to noninvasive ventilatory support
Inflate pilot balloon to 20 mm to diminish aspiration of subglottic secretions
Remove subglottic secretions by periodic oral suctioning or by employing double-lumen catheter with continuous subglottic suction
Noninvasive positive-pressure ventilation, using a face mask, is an attractive alternative for patients with acute exacerbations of chronic obstructive pulmonary disease or acute hypoxemic respiratory failure, and for some immuno suppressed patients with pulmonary infiltrates and respiratory failure . Data suggest that use of noninvasive ventilation to avoid reintubation after initial extubation may not be a good strategy.
Maintaining endotracheal cuff pressure at greater than 20 cm H2O, continuous aspiration of subglottic secretions, through the use of a specially designed endotracheal tube, has significantly reduced the incidence of early-onset VAP in several studies.
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

17. More Preventive Strategies
Head of bed elevation to 30 – 45 degrees demonstrated a threefold reduction in the incidence of ICU – acquired HAP.
Orally intubate; nasal intubation prevents drainage of sinuses, increasing risk of sinusitis and VAP
Use oro-gastric instead of nasal-gastric tube for gastric drainage/nutrition
Check gastric residual and prevent distention
Supine patient positioning may also facilitate aspiration, which may be decreased by a semirecumbent positioning . Using radioactive labeled enteral feeding, cumulative numbers of endotracheal counts were higher when patients were placed in the completely supine position (0 ) as compared with a semirecumbent position (45). One randomized trial demonstrated a threefold reduction in the incidence of ICU-acquired HAP in patients treated in the semirecumbent position compared with patients treated completely supine
The use of oral endotracheal and orogastric tubes, rather than nasotracheal and nasogastric tubes, can reduce the frequency of nosocomial
sinusitis and possibly HAP, although causality between sinusitis and HAP has not been firmly established.
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

18. More Preventive Strategies
Minimize use of antibiotics to decrease selection pressure on resident flora that produces MDR’s
Tightly control glucose levels to reduce risk of infection
Provide optimal nutrition early – TPN vs. enteral
Efforts to reduce the likelihood of aspiration of oropharyngeal bacteria around the endotracheal tube cuff and into the lower respiratory tract include limiting the use of sedative and paralytic agents that depress cough and other host-protective mechanisms.
Enteral nutrition has been considered a risk factor for the development of HAP, mainly because of an increased risk of aspiration of gastric contents.
American Thoracic Society. Am J Respir Crit Care Med 2005;171:

19. Common Pathogens of VAP
25%
20%
15%
10% 5% 0%
P. aeruginosa
Acinetobacter
spp
GNEB
Haemophilus
S. aureus
S. Pneumoniae
Other
In several studies it has been found that the Staph. Aureus is one of the major pathogens known to cause the VAP. P. aeruginosa remains the most common pathogen.
* 43 series (3650 episodes) 1984 – 2003, etiology confirmed by blood, BAL or PSB cultures
Luna CM et al. Archiv Bronconeumol 2005;41: 439

20. Pathogens of VAP in different World Areas
USA
Europe
Latin America
25%
20%
15%
10% 5% 0%
30%
S. aureus
P. Aeruginosa
Acinetobacter spp
S. Maltophilia
Enterobacteriaceae*
Haemophilus spp
Luna CM et al. Archiv Bronconeumol 2005;41: 439

21. Treatment Immediate Rx. of patients with VAP Avoid the emergence
of multidrug-resistant
microorganisms
Objective1
Objective2

22. HAP treatment recommendations was published in 2008 for Asian Countries by Asian HAP Working Group

23. Need for Asian HAP Guidelines
HAP & VAP are difficult to treat serious infections
Many treatment options available
ATS/IDSA guidelines may not be applicable in Asian scenario
Different clinical practices in Asian countries:
Availability of specific antibiotics & formulations
Difference in cost of antibiotics
Although guidelines for the diagnosis and treatment of HAP and VAP have been published by various American and European societies, these guidelines may not be applicable in all respects to the diagnosis and treatment of HAP and VAP in Asian countries. In addition, clinical practice may vary among Asian countries, due to such factors as availability of specific antibiotics and formulations and their relative cost.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

24. Need for Asian HAP Guidelines
Other factors:
different epidemiologic, etiologic and resistance patterns (markedly higher incidences of MRSA & MDR pathogens in Asia)
Antimicrobial resistance patterns in Asia may be quite different from those found in the United States and other Western
countries, with markedly higher incidences of methicillin- resistant Staphlyococcus aureus (MRSA) and MDR pathogens. Some of the most serious pathogens are multidrug- or pandrug-resistant Pseudomonas aeruginosa and Acinetobacter strains, which are resistant to
most available treatments. Antimicrobial resistance can lead to inappropriate use of antimicrobial agents, such as overly frequent use or misuse, resulting in more resistance as well as clinical treatment failure. The prevalence of these pathogens has global significance, and this topic is of timely importance for practicing clinicians throughout the Asia-Pacific region.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

25. To address these issues the Asian – Pacific Research Foundation for Infectious Diseases, together with the Asian Network for Surveillance developed consensus treatment recommendations for HAP in Asian Countries based on the current epidemiologic situation in the asia.
The first working group meeting held in Kuala Lumpur, Malaysia and brought together physician from 10 Asian countries (Malaysia, Thailand, Shina, South Korea, India, Taiwan, Hong Kong, Pakistan, Philippines and Singapore).
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

26. Methodology Adopted Reviewed
Existing governmental & institutional guidelines in Asian Countries (only few Asian countries have guidelines
ATS/ IDSA guidelines
International epidemiologic data
National or Local data from the 10 Asian countries representatives
Information regarding clinical practices in Asian countries.
Existing governmental and institutional guidelines for the treatment of HAP and VAP in Asian countries, where available, were reviewed on an individual country or individual hospital basis. International guidelines for the treatment of HAP and VAP, including but not limited to the ATS/IDSA guidelines, also were considered, together with international epidemiologic data. Individual physicians representing 10 Asian countries
supplemented this with national or local data on epidemiology, etiologic pathogens, diagnostic procedures, antimicrobial resistance, and empirical antimicrobial treatment regimens. Information regarding clinical practice issues in Asian countries was exchanged among the participants and critically analyzed. As the need for further data was identified, insofar as possible, such data were collected and added to the summary draft consensus recommendation.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

27. Indian Panel Members Indraprastha Apollo hospital SGR Hospital
Christian Medical College
Four renowned doctors form the three hospitals represented India in the Forum and gave there recommendations.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

28. HAP working Group Observations
Knowledge gaps between evidence or data on epidemiology, etiology, and antibiotic resisitance of pathogens causing HAP and VAP in Asian countries
Evidence based recommendations difficult to implement because of fewer data
It was noted that knowledge gaps currently exist regarding evidence or data on the epidemiology, etiology,
and antibiotic resistance of pathogens causing HAP and VAP in Asian countries. Evidence-based recommendations specific to clinical practice in Asia can be addressed in only certain areas of clinical practice. This situation is neither surprising nor new. The recent ATS/IDSA guidelines also acknowledge this limitation and emphasize VAP-related treatment issues, because fewer data are available regarding HAP in nonintubated
patients. Nonetheless, the evaluation of the current evidence base, and the identification of areas of incomplete knowledge, is considered to be of value in itself to help shape the direction of future research studies.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

29. Treatment Recommendations

30. Initial Approach to Empirical Therapy
HAP or VAP Suspected
Evaluation
Risk Factors for MDR pathogen
Time of onset (early or late )
Local microbiologic data and resistance pattern
Patient status
LRT sample Gram Stain
Allergy to medication
Underlying co-morbidities
Formulary restrictions
Cost
The panel also agreed that the initial empirical antibiotic treatment choice should be guided by such factors as local microbiology and resistance patterns, drug availability and cost, and formulary restrictions on drugs in individual hospitals. These factors are also considered in existing guidelines, but they have greater relevance to practice in Asia, where in particular local microbiology and resistance patterns vary to a
greater degree than in Western countries. Cost is also an issue of relatively greater significance for many patients treated by Asian doctors. Clinically, other factors that need to be weighed when selecting initial empirical antibiotic treatment include the results of lower respiratory tract (LRT) Gram stain, disease severity, medication allergies, and underlying co-morbidities (eg, renal or hepatic insufficiency), and the impact of such agents on creating further resistance.
Select Empirical Antibiotic therapy
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

31. Initial Empiric Antibiotic treatment for early onset HAP (Table I)
Potential Pathogen
Recommended Regimen*
Strep. Pneumoniae$
H. Influenza
MSSA
Antibiotic – sensitive enteric Gram –ve bacilli:
E coli
K. pneumoniae
Enterobacter sp.
Proteus sp.
S. marcescens
3rd generation cephalosporins (ceftriaxone, cefotaxime) or
Fluoroquinolones (moxifloxacin, levofloxacin)
ß-lactum/ß-lactamase inhibitor (amoxicillin/clavulanic acid; ampicillin/ sulbactum)
Carbepenms (ertapenem)
3rd generation cephalosporins + macrolide
monobactum + clindamycin (for ß-lactum – allergic patients
The consensus recommendation of the panel includes several options and overlaps somewhat with existing guidelines (Table 1).1 The third-generation cephalosporins (ceftriaxone or cefotaxime), fluoroquinolones (moxifloxacin, levofloxacin, and gatifloxacin), beta-lactam/beta-lactamase
inhibitor combinations (amoxicillin/clavulanic acid or ampicillin/sulbactam), and ertapenem are recommended when monotherapy is indicated. Because the current knowledge base on the epidemiology and etiology of HAP in Asian countries is incomplete, the panel did not assign an order of priority in the selection of drug treatment. Rather, each of these options is considered more or less therapeutically equivalent to the others, providing coverage against many of the common potential pathogens causing HAP, including S. pneumoniae, H. influenzae, MRSA, and antibiotic-sensitive enteric Gram-negative bacilli. To some extent, the choice of agent should incorporate information on local microbiology. Therapy with a monobactam plus clindamycin or fluoroquinolone used alone is recommended for patients who are allergic to beta-lactam
agents.
*Antibiotic options should depend on local epedimiology of etiologic pathogens.
$ The frequency of macrolide-resistant S. pneum and MDR S pneum is increasing; levofloxacin or moxifloxacin ae preferred to ciprofloxacin and the role of other new quinolones has not been established.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

32. Initial Empiric Antibiotic treatment for late onset HAP (Table II)
Potential Pathogen
Recommended Regimen
Pathogens Listed in table I and MDR pathogens
Pseudomonas aeruginosa
K. pneumoniae (ESBL+) *
Acinetobacter sp. *
MRSA
Legionella pneumophilia *
Antipseudomonal cephalosporins (cefepime, ceftazidime) or
Antipseudomonal carbepene (imipenem or meropenem)
ß-lactum/ß-lactamase inhibitor (piperacillin - tazobactum)
+/-
Fluoroquinolone (ciprofloxaccin or levofloxacin)
Aminoglycoside (amikacin, gentamicin or tobramycin)
Cefoperazone / sulbactum + fluoroquinolones or aminoglycosides + ampicillin/ sulbactum (if sulbactum is not available
Fluoroquinolones(ciprofloxacin) + aminoglycoside + linezolid or glycopeptide (vancomycin or teicoplanin)$ + azithromycin of fluoroquinolone
To treat late-onset HAP in Asian countries, the panel primarily recommended using third- or fourth-generation cephalosporins (ceftazidime or cefepime), carbapenems (imipenem or meropenem) or piperacillin/ tazobactam in combination with fluoroquinolones or aminoglycosides, plus/minus glycopeptides (vancomycin or teicoplanin) or linezolid (Table 2). Other regimens that may be considered by Asian clinicians
include cefoperazone/sulbactam plus fluoroquinolones or aminoglycosides or ampicillin/sulbactam or fluoroquinolones (ciprofloxacin) plus aminoglycosides plus/ minus glycopeptides (vancomycin or teicoplanin).
The regimen containing antibiotics with sulbactam compound (cefoperazone/sulbactam or ampicillin / sulbactam) was especially recommended for the coverage of MDR Acinetobacter spp in some Asian countries.
*if an ESBL strain such as K. pneum or an Acinetobacter sp. Is suspected the a carpenem is a reliable choice. If L. pneumophilia is suspected then the combination antibiotic regimen should include a macrolide (eg. Azithromycin) or a fluoroquinolone (eg. Ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside.
$ If MRSA risk factors are presenr or there is a high incidence locally.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

33. Initial Empiric Antibiotic treatment for early onset VAP (Table III)
Potential Pathogen
Recommended Regimen
Pathogens Listed in table I and MDR pathogens
Pseudomonas aeruginosa
K. pneumoniae (ESBL+)
Acinetobacter sp.
MRSA
Antipseudomonal cephalosporins (cefepime) or
Antipseudomonal carbepene (imipenem or
meropenem)
ß-lactum/ß-lactamase inhibitor (piperacillin –
tazobactum)
+/-
Fluoroquinolone (ciprofloxaccin or levofloxacin)
Aminoglycoside (amikacin, gentamicin or
tobramycin)
Linezolid or glycopeptide ( vancomycin or
teicoplanin)
In patients with early-onset VAP, the panel recommends, with no order of priority, fourth –generation cephalosporins such as cefepime or carbapenems (imipenem or meropenem) or piperacillin/tazobactam plus/minus fluoroquinolones or aminoglycosides, plus/ minus glycopeptides (vancomycin or teicoplanin) or linezolid. Other regimens that may be considered include cefoperazone/sulbactam plus fluoroquinolones
or aminoglycosides or ampicillin/sulbactam or fluoroquinolones (ciprofloxacin) plus aminoglycosides plus/ minus the glycopeptides vancomycin or teicoplanin (Table 3). As in cases of late-onset HAP, the decision regarding which drug to add, either a fluoroquinolone or an aminoglycoside, and the decision of whether to add a glycopeptide or linezolid, is a matter of clinical judgment.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

34. Initial Empiric Antibiotic treatment for late onset HAP (Table IV)
Potential Pathogen
Recommended Regimen
MDR pathogens
Pseudomonas aeruginosa
K. pneumoniae (ESBL+)
Acinetobacter sp.
MRSA
Antipseudomonal carbepene (imipenem or meropenem) or
ß-lactum/ß-lactamase inhibitor (piperacillin - tazobactum)
+/-
Fluoroquinolone (ciprofloxaccin or levofloxacin)
Aminoglycoside (amikacin, gentamicin or tobramycin)
Linezolid or glycopeptide ( vancomycin or teicoplanin)
Cefoperazone / sulbactum + fluoroquinolones or
aminoglycosides + ampicillin/ sulbactum (if sulbactum is not available
Fluoroquinolones(ciprofloxacin) + aminoglycoside
linezolid or glycopeptide (vancomycin or teicoplanin)
In cases of late-onset VAP, the panel recommended the use of carbapenems (imipenem or meropenem) or piperacillin/tazobactam in combination with fluoroquinolones or aminoglycosides plus/minus glycopeptides or linezolid (Table 4). Alternatively, the panel recommended cefoperazone/sulbactam plus fluoroquinolones or aminoglycosides or ampicillin/sulbactam. The use of fluoroquinolones (ciprofloxacin) plus aminoglycosides plus vancomycin or teicoplanin also was recommended. Again, no priorities were assigned among these regimens, due to the lack of objective evidence in Asian countries regarding the comparative clinical efficacy of different regimens. In these recommendations,
the carbapenems (imipenem and meropenem) are preferred over third-or fourth-generation cephalosporins because they are more active against ESBL1 Gram-negative bacilli, that is, those expressing plasmid- or chromosome-mediated ESBL. In addition, they are more active against Pseudomonas and Acinetobacter. Piperacillin/tazobactam is preferred over cefepime because, unlike cefepime, it does not induce ESBL
production in Gram-negative bacteria. In addition, piperacillin/tazobactam does not exhibit an inoculum effect, and it proved to be highly active in vitro against K. pneumoniae and E. coli in a recent Asian study.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

35. Treatment Recommendations for MDR pathogens

36. MRSA First line treatment : Teicoplanin or Vancomycin.
Teicoplanin as compared to Vancomycin has fewer side effects and does not require serum monitoring levels.
Linezolid to be reserved as second tier agent.
The panel recommended vancomycin or teicoplanin as first-line treatment for MRSA Vancomycin therapy requires careful monitoring of blood levels; side effects include nephrotoxicity and ototoxicity. Teicoplanin has fewer serious side effects and does not require monitoring of serum levels.
In addition, panel members concurred that linezolid should be reserved as a second- tier agent (after vancomycin and teicoplanin), to avoid the selection of resistant strains, which would lead to loss of this valuable agent.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

37. P. Aeruginosa
First line : Piperacillin/ tazobactum or carbapenems +/- aminoglycosides or fluoroqinolone
Fluoroqinolones offer theoretical advantage of improved bioavailability in respiratory tract.
Ciprofloxacin or Levofloxacin Fluoroqinolones preferred in combination therapy
In unresponsive patients Polymyxin B or Colistin in combination with fluoroqinolone
For the treatment of MDRP. aeruginosa, the panel recommended piperacillin/tazobactam or carbapenems plus/minus aminoglycoside or fluoroquinolone (ciprofloxacin). Fluoroquinolones offer the theoretical advantage of improved bioavailability in the respiratory tract, although no study is available comparing fluoroquinolone-based combination therapy with beta-lactam monotherapy.When a fluoroquinolone
is used in combination therapy, ciprofloxacin or levofloxacin may be preferred, because they show greater in vitro activity against P. aeruginosa.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

38. Acinetobacter sp.
First Line: Cefoperazone/ sulbactam and/or tigecycline
Sulbactam an enzyme inhibitor has direct activity against Acinetobacter.
In unresponsive patients : Polymyxin B or Colistin
Cefoperazone/sulbactam, colistin, polymyxin B, tigecycline, or a combination is the recommended treatment. Sulbactam, usually used as an enzyme inhibitor, has direct activity against Acinetobacter. Some panel members suggested the use of sulbactam plus moxifloxacin,
levofloxacin plus minocycline, chloramphenicol, or imipenem. Although aminoglycosides generally do not appear to be effective against Acinetobacter and are not recommended in all patients,
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

39. Antibiotic regimens against specific antibiotic – resistant pathogens
MRSA
Vancomycin or Teicoplanin
Linezolid or tigecycline
MDR Pseudomonas Aeruginosa
Piperacillin/ tazobactum or carbapenems +/- aminoglycosides or fluoroqinolone
Polymixin B or Colistin
MDR Acinetobacter
Cefoperazone/ sulbactam and/or tigecyclinne
Polymyxin B or Colistin
ESBL + K. pnumoniae
Carbapenems or tigecycline
Piperacillin/ Tazobactam
ESBL + E. Coli
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

40. Duration of Treatment
Asian HAP Working Group recommends the initial empirical antibiotic treatment should continue for 7 to 14 days.
If MDR pathogen is identified then the treatment may be continued for up to 14 days.
Patient response should be evaluated frequently with consideration given to de-escalating therapy when appropriate.
The panel agreed that initial empirical antibiotic treatment should continue for 7 to 14 days. If an MDR pathogen (eg, MRSA,
P. aeruginosa, Acinetobacter spp, ESBL1 Gram-negative bacilli) is identified, then treatment may be continued
for up to 14 days.
Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

41. Role of Teicoplanin

42. Teicoplanin in Nosocomial Pneumonia
Glycopeptide antibiotics teicoplanin and Vancomycin is the First line therapy against Nosocomial Pneumonia attributable to MRSA.
Hunter J D Postgrad Med J 2006; 82:

43. Conclusions
HAP/ VAP is one of the more frequent causes of nosocomial infection and the first one causing death.
MRSA incidence is on rise.
MRSA is one of the most common cause of HAP/ VAP
No definite guidelines present in Asian countries for HAP/VAP
ARFID & ANSORP recommended treatment for HAP/VAP
Teicoplanin is the First line therapy in MRSA HAP/VAP

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