2. They together are the most common hospital-acquired infections (HAIs)
VAP remains the most common HAI in ICU.
Leaing cause of death among nosocomial infections.
VAP prolongs length of mechanical ventilation by 7.6 to 11.5 days and
prolongs hospitalization by 11.5 to 13.1 days compared to similar patients
without VAP
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.
While the international nosocomial infection control consortium (INICC)
data suggests that the incidence of VAP is as high as 13.6/1000 mechanical
ventilator (MV) days , the occurrence of VAP in Asian countries is much
higher and ranges from 3.5 to 52 infections/1000 MV days
EPIDEMIOLOGY
3. The ventilator-associated pneumonia (VAP) rate is
defined as the number of ventilator-associated
pneumonias per 1,000 ventilator days.
For example, if in February there were 12 cases of
VAP, the number of cases would be 12 for that month.
If 25 patients were ventilated during the month and,
for purposes of example, each was on mechanical
ventilation for 3 days, the number of ventilator days
would be 25 x 3 = 75 ventilator days for February. The
Ventilator-Associated Pneumonia Rate per 1,000
Ventilator Days then would be 12/75 x 1,000 = 160.
VAP RATES—MECANICAL VENTILATOR DAYS
9. • Grossly defined as:
the presence of “new lung infiltrate” in chest radiograph
PNEUMONIA
Clinical evidence that the infiltrate is of an infectious origin,
Which include(any two at least)
• The new onset of fever,
• Purulent sputum,
• Leukocytosis/leukopenia
•And decline in oxygenation.”
IDSA GUIDELINES FOR HAP AND VAP 2016
10. HOSPITAL ACQUIRED PNEUMONIA
(HAP)
A pneumonia that develops 48 hours or more after admission and did not appear to be
incubating at the time of admission.
Health Care associated Pneumonia(HCAP):
A Pneumonia in any patient
who was hospitalized in an acute care hospital for two or more days within 90 days of the
infection
resided in a nursing home or long-term care facility
received recent intravenous antibiotic therapy, chemotherapy,
or wound care within the past 30 days of the current infection;
or attended a hospital or hemodialysis clinic
11. A device used to support, assist, or control respiration (inclusive of the weaning
period) through the application of positive pressure to the airway when delivered
via an artificial airway, specifically oral/nasal endotracheal or tracheostomy
tube.
Ventilation and lung expansion devices that deliver positive pressure to the
airway (for example, CPAP, BiPAP, Bi-level, IPPB, and PEEP) via non-invasive means
(for example, nasal prongs, nasal mask, full face mask, total mask, etc.) are not
considered ventilators unless positive pressure is delivered via an artificial
airway (oral/nasal endotracheal or tracheostomy tube).
VENTILATOR:
12. • A pneumonia where the patient is on mechanical ventilation for > 2 consecutive
calendar days on the date of event, with day of ventilator placement being day 1,
And
• The ventilator was in place on the date of event or the day before.
• If the ventilator was in place prior to inpatient admission, the ventilator day count
begins with the admission date to the first inpatient location.
• If a break in mechanical ventilation occurs for at least one full calendar day,
ventilator day count for ventilator association starts anew upon reintubation
and/or re-initiation of mechanical ventilation.
CDC GUIDELINES ON VAP AND PNEU
VENTILATOR-ASSOCIATED PNEUMONIA
(VAP)
13.
14. TYPES
• Early onset VAP- VAP developing less than 5 days of Endotracheal
Intubation.
• Late onset VAP- VAP developing greater than equal to 5 days
Endotracheal Intubation.
REASON OF CHANGE OF CONCEPT
Intubation may have taken place after several days of hospitalization, thus resulting in a
patient already colonized in the upper and lower airways with typically nosocomial
pathogens.
Presence of risk factors for MDR should take precedence over the distinction between
early- and late-onset pneumonia. Hence, timing of developing VAP should be evaluated in
the context of other risk factors and recent antibiotic treatment.
Therefore,evidence suggests that overall, patients who develop VAP after >5 days of
hospitalization are at higher risk of infection with MDR organisms than patients who
develop VAP earlier in their hospitalization.
OLD
CONCEPT
21. Ventilator-Associated Event (VAE)
•VAEs are identified by using a
combination of objective criteria:
•Deterioration in respiratory status
after a period of stability or
improvement on the ventilator,
•Evidence of infection or
inflammation,
•And laboratory evidence of
respiratory infection.
• There are 3 nested tiers of VAEs in
adults:
• Ventilator-associated conditions
(VACS)
• Infection-related
ventilatorassociated complications
(IVACS),
•And Possible VAP (PVAP).
The CDC created VAE definitions to try to overcome the subjectivity, complexity, and
limited focus of traditional VAP surveillance definitions.
22. • Only ∼25%–33% of VAEs are due to pneumonia
• Many mild pneumonias do not meet the VAE thresholds for increased
ventilator settings.
• Most VAEs in adults and children are caused by
• Pneumonia,
• Fluid overload,
• Atelectasis,
• and/or ARDS.
VAE VAP
23. VENTILATOR ASSOCIATED CONDITION
Patient has a baseline period of stability or improvement on the ventilator, defined by
≥ 2 calendar days of stable or decreasing daily minimum* FiO2 or PEEP values.
The baseline period is defined as the 2 calendar days immediately preceding the first day of increased
daily minimum PEEP or FiO2.
* Daily minimum defined by lowest value of FiO2 or PEEP during a calendar day that is maintained for
> 1 hour
After a period of stability or improvement on the ventilator, the patient has at least one of the
following indicators of worsening oxygenation:
1) Increase in daily minimum* FiO2 of ≥ 0.20 (20 points) over the daily minimum FiO2 of the first day
in the baseline period, sustained for ≥ 2 calendar days.
2) 2) Increase in daily minimum* PEEP values of ≥ 3 cmH2O over the daily minimum PEEP of the first
day in the baseline period†, sustained for ≥ 2 calendar days.
* Daily minimum defined by lowest value of FiO2 or PEEP during a calendar day that is maintained for
> 1 hour.
† Daily minimum PEEP values of 0-5 cmH2O are considered equivalent for the purposes of VAE
surveillance.
25. On or after calendar day 3 of mechanical ventilation and within 2 calendar days before
or after the onset of worsening oxygenation, the patient meets both of the following
criteria:
1) Temperature > 38 °C or < 36°C,
OR white blood cell count ≥ 12,000 cells/mm3 or ≤ 4,000 cells/mm3.
AND
2) A new antimicrobial agent(s) is started and is continued for ≥ 4 qualifying
antimicrobial days (QAD).
Infection-related Ventilator-Associated Complication (IVAC)
INFECTION-RELATED VENTILATOR-ASSOCIATED
COMPLICATION (IVAC)
28. “Normal respiratory flora,” “normal oral flora,” “mixed respiratory flora,” “mixed
oral flora,” “altered oral flora” or other similar results
Any Candida species or yeast not otherwise specified; any coagulase-negative
Staphylococcus species; and any Enterococcus species,
These organisms can be reported as PVAP pathogens if identified from lung tissue or
pleural fluid (where specimen was obtained during thoracentesis or within 24 hours of
chest tube placement; pleural fluid specimens collected after a chest tube is
repositioned or from a chest tube in place > 24 hours are not eligible for PVAP).
Blastomyces, Histoplasma, Coccidioides, Paracoccidioides, Cryptococcus, and
Pneumocystis- when isolated from any eligible specimen type (to include lung tissue
and pleural fluid) because organisms belonging to the following genera are typically
causes of community-associated respiratory infections and are rarely or are not known
to be causes of healthcare-associated infections
EXCLUDED ORGANISMS
31. • Alcohol / drug
withdrawal •
• Postoperative fever •
• Post transfusion fever •
• Drug fever •
• Cerebral infarction •
• Adrenal insufficiency •
• Myocardial infarction •
• Pancreatitis •
• Acalculous cholecystitis
• Ischemic bowel •
• Non Infective-- ARDS
•Subarachnoid hemorrhage
•
• Fat emboli
• Transplant rejection
• Deep venous thrombosis
• Pulmonary emboli
• Gout / pseudogout
• Hematoma / Solid organ
injury •
• Cirrhosis (without
primary peritonitis)
• GI bleed
Thrombophlebitis
• IV contrast reaction
• Neoplastic fevers
• Decubitus ulcer
NON-INFECTIOUS CAUSE OF FEVER
(TO BE EXCLUDED)
32. RADIOLOGICAL
• Chest X-ray- Not so Specific and Sensitive. Often missed out at
initial stage
• Ct scan-Chest computed tomography (CT), without contrast, is
not routine in patients with suspected VAP but may be useful in
patients with a normal chest radiograph who have clinical
symptoms of respiratory tract infection
• Lung ultrasound-more useful for ruling out pneumonia,
although subpleural consolidations and dynamic air
bronchograms may support VAP .
33. PROTECTED SPECIMEN BRUSH is a brush that is contained within
a protective sheath, which minimizes the likelihood that the brush will be contaminated
during bronchoscopy. The procedure involves placing the bronchoscope tip next to the
affected bronchial segmental orifice, pushing the sheath through the bronchoscope
under direct visual guidance, and then advancing the brush out of the sheath and into
the airway.
MINI-BAL is performed by advancing a catheter through the endotracheal tube
blindly until resistance is met, infusing sterile saline through the catheter (typically three
50 mL aliquots) and then aspirating using the syringe (the catheter is estimated to be
located in the distal endobronchial airway (eg, second or third order bronchus )
LUNG BIOPSY — Lung biopsy is not routinely performed in patients with
suspected VAP since a diagnosis of VAP can be made in most patients using lower
respiratory tract sampling and cultures. Lung biopsy may be reserved for patients in
whom infiltrates are progressive despite antibiotic therapy or patients in whom a non-
infectious etiology is suspected.
Choosing between transthoracic needle, transbronchial, or thoracoscopic biopsy is often
clinician-specific with most experts electing to perform thoracoscopic biopsy in ventilated
patients.
34. MICROBIOLOGICAL
Respiratory tract sampling
Timing of sampling — Respiratory samples are ideally obtained prior to the initiation
of antibiotics or change of antibiotic therapy (in those already receiving antibiotics),
because antibiotic therapy reduces the sensitivity of both the microscopic analysis and
culture . However, not uncommonly, severe illness or delays in sampling requires that
empiric antibiotic therapy be initiated prior to diagnostic sampling.
Types:
Invasive respiratory sampling:
Bronchoscopic BALis our preferred method of lower respiratory tract
sampling. The rationale for this approach is that BAL, compared with PSB (and
probably mini-BAL), is a larger sample that obtains a dominant alveolar component
with minimal airway contamination.
35. Noninvasive respiratory sampling — Tracheobronchial
aspiration (ie, endotracheal aspirate) is performed by advancing
a catheter through the endotracheal tube until resistance is
met and suction is applied (likely located in trachea or main
stem bronchus. The sample is directly aspirated into a sterile
specimen trap that can be sent for microbiologic analysis
Mini-BAL - YouTube
Flexible Bronchoscopy Basic Techniques 5 -
Brushing - Bing video
Diagnostic Bronchoscopy - Bing video
36. Quantitative cultures – Bacteria can be counted on any respiratory specimen. VAP is
supported when an established threshold of bacterial growth is exceeded. Only bacteria
that are pulmonary pathogens should be counted. As examples, Staphylococcus
epidermidis and most Gram-positive bacilli (except actinomycosis and nocardia) should
not be counted.
Typical thresholds include the following:
•Endotracheal aspirates – ≥1,000,000 colony forming units (cfu)/mL
•Bronchoscopic- or mini-BAL – 10,000 cfu/mL
•PSB – 1000 cfu/mL
Semiquantitative cultures are typically reported as showing heavy, moderate, light, or no
bacterial growth.
Qualitative cultures do not specify the amount of bacterial growth. Only says if sample is
positive or negative.
Of note, lower respiratory (eg, BAL, mini-BAL, brush, wash, ETA) and sputum
samples should be processed within 2 hours if kept at room temperature and within
24 hours if kept at 4 degrees
CULTURE
37. Noninvasive sampling with semiquantitative cultures to diagnose VAP, rather
than invasive sampling with quantitative cultures and rather than noninvasive
sampling with quantitative cultures (weak recommendation, low quality
evidence)
There is no evidence that invasive microbiological sampling with quantitative
cultures improves clinical outcomes compared with noninvasive sampling with
either quantitative or semiquantitative cultures. Though t there is a potential
that invasive sampling with quantitative cultures could lead to less antibiotic
exposure if growth below defined thresholds (eg, 103 CFU/mL for PSB, 104
CFU/mL for BAL) is used as a trigger to stop antibiotics.
RECOMMENDATION
38. • Though,Noninvasive sampling with semiquantitative cultures is the preferred
methodology to diagnose VAP ; however, the panel recognizes that invasive
quantitative cultures will occasionally be performed by some clinicians.
• For patients with suspected VAP whose invasive quantitative culture results are
below the diagnostic threshold for VAP, we suggest that antibiotics be withheld
rather than continued (weak recommendation, very lowquality evidence).
• Antibiotic discontinuation in patients with suspected VAP whose invasive
quantitative culture results are below the diagnostic threshold for VAP may
decreases unnecessary antibiotic use, which should reduce antibiotic-related
adverse events (eg, Clostridium difficile colitis and promotion of antibiotic
resistance) and costs. Moreover, it improves microbiological outcomes (ie,
fewer superinfections).
• Though in theory it could result in antibiotics being withdrawn from some
patients who would benefit from antibiotic therapy because the quantitative
culture results were misleadingly low due to sampling error or prior exposure
to antibiotics.
RECOMMENDATION
39. • Patients with suspected HAP (non-VAP) be treated according to the
results of microbiologic studies performed on respiratory samples
obtained noninvasively, rather than being treated empirically (weak
recommendation, very low-quality evidence).
• The rationale for this suggestion is that resistant pathogens lead to a
significant risk of inadequate initial empiric antibiotic therapy , which
is associated with an increased risk of mortality in patients with HAP.
• Furthermore, performing cultures of respiratory samples provides the
opportunity to de-escalate antibiotic coverage based on the results,
minimizing unnecessary antibiotic exposure.
RECOMMENDATION
41. PCT is a precursor of calcitonin that is constitutively secreted by C cells of the thyroid
gland and K cells of the lung.
In healthy individuals, PCT is normally undetectable(<0.01) (When stimulated by
endotoxin, PCT is rapidly produced by parenchymal tissue throughout the body ; this PCT
production has also been observed in diverse types of bacterial infections . PCT may
increase in response to sterile inflammation or viral infection, but it is less common .
RECOMMENDATION:
For patients with suspected HAP/VAP, we recommend using clinical criteria alone, rather
than using serum PCT plus clinical criteria, to decide whether or not to initiate antibiotic
therapy (strong recommendation, moderate-quality evidence)
The false-negative and false-positive rates of serum PCT testing plus clinical criteria are
33% and 17%, respectively. Thus leading to delay /over use of antibiotics respectively.
PRO-CALCITONIN(PCT)
42. • TREM-1 is a member of the immunoglobulin superfamily that has been
shown to be strongly expressed on the neutrophils and monocytes
infiltrating tissues invaded by bacteria or fungi . However, its use in
diagnosing infections is uncertain because several recent studies suggest
sTREM-1 may also be elevated in noninfectious causes of inflammation.
RECOMMENDATION:
• For patients with suspected HAP/VAP, we recommend using clinical criteria
alone, rather than using BALF sTREM-1 plus clinical criteria, to decide
whether or not to initiate antibiotic therapy (strong recommendation,
moderate-quality evidence).
• The false-negative and false-positive rates of BALF sTREM-1 are 16% and
51%, respectively. Thus leading to delay /over use of antibiotics respectively.
TRIGGERING RECEPTOR EXPRESSED ON MYELOID
CELLS (TREM-1)
43.
44. C-REACTIVE PROTEIN
Serum CRP is an acute-phase protein exclusively
synthesized in the liver in response to cytokines, in particular
interleukin 6.Its level is not infuenced by immunosuppression
(steroids or neutropenia) nor infuenced by renal failure or
renal replacement therapy, and does not signifcantly difer
between individuals with or without cirrhosis.
RECOMMENDATION:
For patients with suspected HAP/VAP, we recommend
using clinical criteria alone rather than using CRP plus clinical
criteria, to decide whether or not to initiate antibiotic therapy
(weak recommendation, low-quality evidence).
45. The CPIS is a semiobjective assessment of
several clinical factors predictive of
pneumonia;
RECOMMENDATION:
For patients with suspected HAP/VAP, we
suggest using clinical criteria alone, rather
than using CPIS plus clinical criteria, to decide
whether or not to initiate antibiotic therapy
(weak recommendation, low-quality
evidence).
The false-negative and false-positive rates of
the CPIS are 35% and 36%, respectively. Thus
leading to delay /over use of antibiotics
respectively.
CLINICAL PULMONARY
INFECTION SCORE
47. VENTILATOR-ASSOCIATED TRACHEOBRONCHITIS
VAT is defined using all the following criteria:
• Fever (>38°c) with no other recognizable cause
• Purulent sputum production
• Positive (≥10^6 cfu/ml) endotracheal aspirate culture
• No radiographic signs of new pneumonia
RECOMMENDATION:
In patients with VAT, we suggest not providing antibiotic therapy
(weak recommendation, low-quality evidence)
48. • Prospective, RCT study showed no difference in mechanical ventilation
duration and length of ICU stay though subsequent VAP , ICU mortality
were significantly lower in the antibiotic group
• The potential desirable consequence of antibiotic therapy is a decreased
duration of mechanical ventilation; in contrast, the potential undesirable
consequences of antibiotic therapy include side effects such as rash, C.
Difficile colitis, antibiotic resistance, and cost. The panel recognizes the
potential desirable and undesirable consequences, but judged that the
latter outweigh the former, given the uncertainty regarding the benefits.
Can be considered if:
• Resulting in mucus plugging, and resultant weaning difficulty
• Worsening oxygenation and/or increasing ventilator settings even in
the absence of new or progressive persistent infiltrates on portable
chest radiographs.
49. VENTILATOR-ASSOCIATED
PNEUMONIA
Organisms:
• Aerobic Gram-Negative Bacilli, Such As
Acinetobacter baumannii, Klebsiella pneumoniae,
Pseudomonas aeruginosa,
• Or by Gram-Positive Cocci (Staphylococcus aureus).
• In indian ICUs, gram-negative organisms are the
most common etiologic agents (i.e; Acinetobacter,
Klebsiella and Pseudomonas spp).
• Most of these pathogens have been found to be
multidrug resistant.
• The frequency of specific MDR pathogens causing
HAP and VAP may vary by hospital, patient
population, type of ICU patient, and change over
time.
Vishwajith et al. / Indian Journal of Microbiology Research 6 (2019) 194–197
Chidambaram, et al 2016.
Dhruva Chaudhry,et al,2018
50.
51. Risk factor for MDR organism
age >60 years
duration of mechanical ventilation ≥ 7
days
prior antibiotic use within 3 months
the presence of severe sepsis or septic
shock at the time of VAP
ARDS preceding VAP
renal replacement therapy before VAP
and systemic corticosteroid therapy
IDSA 2016 ISCCM 2019
52. EMPERICAL
ANTIBIOTICS
Not at high risk of MDR pathogens
Low prevalence of MRSA (<15% of S.
aureus isolates are methicillin resistant)
and resistant gram-negative organisms
(<10% gram-negative isolate resistant
to the agent being considered for
monotherapy)
Single antibiotic active
against both MSSA and
Pseudomonas is preferred
over combination
antibiotic .
High risk of MDR
pathogens
or a high prevalence of
MRSA (> 15% of S. aureus
isolates are methicillin
resistant.)
and resistant gram-
negative organisms (> 10%
gram-negative isolate
resistant to the agent
being considered for
monotherapy)
An agent active against MRSA and at
least two agents active against
gram-negative organisms including
P. aeruginosa is recommended
Not at high risk of MDR pathogens
High prevalence of resistant gram-
negative organisms (>15% gram-
negative isolate resistant to the
agent being considered for
monotherapy) but low prevalence
of MRSA (<10% of S. aureus
isolates are methicillin resistant.),
two agents active against gram-
negative organism including P.
aeruginosa is recommended
Two agents active
against gram-
negative organism
including P.
aeruginosa is
recommended
53. In ICUs where the distribution of pathogen and antibiotic
resistance pattern is known, empiric treatment should be
designed accordingly, based upon patient risk factors for
MDR pathogens.
In ICUs where gram-negative isolate resistance rate is low
(<10% gram-negative isolate resistant to the agent being
considered for monotherapy) and patients have no risk
factors for antimicrobial resistance, one antipseudomonal
antibiotic may be given
Including an agent active against MRSA for the empiric
treatment of suspected VAP only in patients with any of the
following: a risk factor for antimicrobial resistance , patients
being treated in units where >15% of S. aureus isolates are
methicillin resistant.
GUIDELINES FOR ANTIBIOTICS IN ICU:ISCCM 2019
54. • Colistin is not recommended for routine use as an empirical agent in VAP.
However, it may be used upfront in the ICUs if there is a high prevalence of
carbapenem-resistant Enterobacteriaceae (> 20%)
• In our country or areas with high endemicity of tuberculosis, use of linezolid
may be restricted unless no suitable alternative is available (UPP).
• Fluoroquinolones and aminoglyosides should be cautiously used as
monotherapy in VAP in our country as well as in other areas with high
endemicity of tuberculosis (UPP).
•If patient has structural lung disease increasing the risk of gram-negative infection
(ie, bronchiectasis or cystic fibrosis), 2 antipseudomonal agents are recommended
GUIDELINES FOR ANTIBIOTICS IN ICU:ISCCM 2019
55. Gram Stain:
The role of Gram stains in guiding
empiric therapy for VAP is unclear.
Some studies suggest that the
absence of gram-positive organisms
on Gram stain makes it less likely
that S. aureus will be cultured . A
recent meta-analysis of
observational studies, however,
found relatively poor concordance
between Gram stains and final
cultures.
A nonpseudomonal β-lactam antibiotic was administered when
Gram stain results showed only GPC chains and/or gram-positive
bacilli.
An anti-MRSA agent was administered when Gram stain results
showed GPC clusters without GNR.
An antipseudomonal agent was administered when Gram stain
results showed GNR without GPC clusters.
The combination of an antipseudomonal agent and anti-MRSA
agent was administered when Gram stain results showed both
GPC clusters and GNR.
The most broad-spectrum antibiotic agent among the
categories was administered when Gram stain results showed 2
or more categories.
56. • The sensitivities of MRSA screens vary considerably by anatomical site and by method of isolation
(nares vs oropharynx, conventional culture vs polymerase chain reaction)
• Observational data suggest that concurrent or recent positive MRSA screens increase the
likelihood that clinical infection is due to MRSA . This association is strongest, however, for skin and
soft tissue infections. Only about 30% of respiratory infections are due to MRSA in patients with
positive MRSA surveillance studies
• In settings with low prevalence of respiratory infections due to MRSA, a negative nasal screen
further suggests that pneumonia is unlikely to be due to MRSA and that anti-MRSA coverage can
be withheld
• In settings with higher prevalence rates of MRSA, a negative screen decreases the probability that
infection is due to MRSA but does not rule out the possibility .
• In these settings, some studies have found that up to 75% of critically ill patients with MRSA lower
MRSA SCREENING
57.
58.
59. a Drug levels and adjustment of doses and/or intervals required. b Extended infusions may be appropriate.. c On meta-analysis, aminoglycoside
regimens were associated with lower clinical response rates with no differences in mortality. d The dose may need to be lowered in patients
weighing>70 kg to reduce seiures
e Polymyxins should be reserved for settings where there is a high prevalence of multidrug resistance and local expertise in using this medication.
Dosing is based on colistin-base activity (CBA); for example, One million IU of colistin is equivalent to about 30 mg of CBA, which corresponds to
about 80 mg of the prodrug colistimethate. Polymyxin B (1 mg = 10 000 units) [136]. f In the absence of other options, it is acceptable to use
aztreonam as an adjunctive agent with another β-lactam–based agent because it has different targets within the bacterial cell wall [137].
60.
61.
62. • Antibiotics with activity against P. aeruginosa and other gram-negative
bacilli (strong recommendation, very low-quality evidence).
• For patients with HAP who are being treated empirically and have factors
increasing the likelihood for Pseudomonas or other gram-negative infection
(ie, prior intravenous antibiotic use within 90 days; also see Remarks) or a
high risk for mortality, we suggest prescribing antibiotics from 2 different
classes with activity against P. aeruginosa (weak recommendation, very
low-quality evidence). (Risk factors for mortality include need for
ventilatory support due to HAP and septic shock).
• All other patients with HAP who are being treated empirically may be
prescribed a single antibiotic with activity against P. aeruginosa.
FOR PATIENTS WITH HAP
63. ii. For patients with HAP who are being treated empirically, we recommend
not using an aminoglycoside as the sole antipseudomonal agent (strong
recommendation, very low-quality evidence).
Indication for MRSA coverage include:
• Intravenous antibiotic treatment during the prior 90 days,
• Treatment in a unit where the prevalence of mrsa among s. Aureus
isolates is not known or is > 20%.
• Prior detection of mrsa by culture or non-culture screening may also
increase the risk of mrsa.
64. • RECOMMENDATION
• For patients with VAP due to gram-negative bacilli that are susceptible to only
aminoglycosides or polymyxins (colistin or polymyxin B), we suggest both inhaled
and systemic antibiotics, rather than systemic antibiotics alone (weak
recommendation, very low-quality evidence)
• it is reasonable to consider adjunctive inhaled antibiotic therapy as a treatment of
last resort for patients who are not responding to intravenous antibiotics alone,
whether the infecting organism is or is not MDR.
• The rationale for adjunctive inhaled antibiotic therapy is based in part upon the
observation that antibiotic efficacy against bacteria within purulent secretions may
require antibiotic concentrations >10–25 times the minimum inhibitory
concentration (MIC); these levels cannot be achieved with intravenous therapy
alone and, therefore, the addition of inhaled antibiotic therapy may be
beneficial.Studies showed very poor lung concentration of aminoglycoside and
colistin when used IV alone.
ROLE OF INHALED ANTIBIOTIC THERAPY
66. • MRSA HAP/VAP should be treated with either Vancomycin or Linezolid rather
than other antibiotics or antibiotic combinations
• The choice between vancomycin and linezolid may be guided by patient-specific factors
such as blood cell counts, concurrent prescriptions for serotonin-reuptake inhibitors,
renal function, and cost.
• Linezolid and vancomycin appear to confer no clear difference in nephrotoxicity,
thrombocytopenia, serious adverse events, or need for treatment discontinuation due
to an adverse event
• Two randomized clinical trials evaluated teicoplanin vs vancomycin or linezolid for gram-
positive infections. However, multiple sites of infection were included in both studies
and small numbers of patients with pneumonia were evaluated, and a small number of
patients with documented MRSA pneumonia were evaluated. Thus, more evidence is
needed to define the clinical role of teicoplanin in patients with HAP/VAP.
METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS
67.
68. • The choice of an antibiotic for definitive (not empiric) therapy
be based upon the results of antimicrobial susceptibility
testing.
• For patients with HAP/VAP due to P. aeruginosa, we
recommend against aminoglycoside
• Routine antimicrobial susceptibility testing should include
assessment of the sensitivity of the P. aeruginosa isolate to
polymyxins (colistin or polymyxin B) in settings that have a high
prevalence of extensively resistant organisms.
PSEUDOMONAS AERUGINOSA
69. Carbapenems, cephalosporins, antipseudomonal penicillins, aminoglycosides, quinolones,
aztreonam, and tigecycline either alone or in combination had reported significant
differences in clinical response or mortality rates between comparator arms with the
exceptions of tigecycline and doripenem, which were both associated with worse
outcomes.
To recommend against aminoglycoside monotherapy for 2 reasons:
• First, aminoglycosides penetrate the lung poorly; therefore, high peak serum
concentrations are necessary to obtain microbiologically active concentrations in the
alveoli, which increases the risk of nephrotoxicity and ototoxicity . Studies have found no
detectable antipseudomonal activity within bronchial secretions despite therapeutic
aminoglycoside levels in the serum of patients with Pseudomonas pulmonary infection
•Second, there is a lack of studies evaluating the effects of aminoglycoside monotherapy in
HAP/VAP.
70. 1. For patients with HAP/VAP due to P. aeruginosa who are not in
septic shock or at a high risk for death, and for whom the results
of antibiotic susceptibility testing are known, we recommend
monotherapy using an antibiotic to which the isolate is
susceptible rather than combination therapy
2. For patients with HAP/VAP due to P. aeruginosa who remain in
septic shock or at a high risk for death when the results of
antibiotic susceptibility testing are known, we suggest
combination therapy using 2 antibiotics to which the isolate is
susceptible rather than monotherapy
3. For a patient whose septic shock resolves when antimicrobial
sensitivities were known, continued combination therapy is not
recommend
MONOTERAPHY VS DUAL THERAPHY
71. • Extended spectrum beta-lactamases (ESBLs) are defined as enzymes produced
by certain bacteria that are able to hydrolyze extended spectrum
cephalosporin and Atreonams +/- Piperacillin and tazobactam. They are
therefore effective against beta-lactam antibiotics such as ceftazidime,
ceftriaxone, cefotaxime and oxyimino-monobactam.
• Any Gram-negative organism has the potential to harbor ESBL genes; however,
they are most prevalent in Escherichia coli, Klebsiella pneumoniae, Klebsiella
oxytoca, and Proteus mirabilis [7-9]. CTX-M enzymes, particularly CTX-M-15,
are the most common ESBLs
• preferred antibiotics for the treatment of infections outside of the urinary tract
caused by ESBL-E is carbapenem .After appropriate clinical response is
achieved, transitioning to oral fluoroquinolones or trimethoprim-
sulfamethoxazole should be considered, if susceptibility is demonstrated.
EXTENDED SPECTRUM BETA-LACTAMASES (ESBLS)
TREATMENT OF MDR GNB IDSA 2022
72. The clinical trial randomized 391 patients with bloodstream infections due to ceftriaxone
non-susceptible E. coli or K. pneumoniae (87% later confirmed to have ESBL genes) to
piperacillin-tazobactam 4.5 g intravenously every six hours or meropenem 1 g
intravenously every eight hours, both as standard infusions. The primary outcome of 30-
day mortality occurred in 12% and 4% of patients receiving piperacillin-tazobactam and
meropenem, respectively [34].
73. • For patients with HAP/VAP due to ESBL-producing gram
negative bacilli,
• The choice of an antibiotic for definitive (not empiric) therapy
be based upon the results of antimicrobial susceptibility testing
and patient-specific factors
• Patient-specific factors that should be considered when
selecting an antimicrobial agent include allergies and
comorbidities that may confer an increased risk of side effects.
IDSA 2016 VAP GUIDELINES
74. • The CDC defines CRE as members of the Enterobacterales order resistant to at least
one carbapenem antibiotic or producing a carbapenemase enzyme
• Regarding bacteria that are intrinsically not susceptible to imipenem (e.g., Proteus
spp., Morganella spp., Providencia spp.), resistance to at least one carbapenem other
than imipenem is required
• CRE comprise a heterogenous group of pathogens with multiple potential
mechanisms of resistance, broadly divided into those that are carbapenemase-
producing and those that are not carbapenemase-producing.
• CRE that are not carbapenemase-producing may be the result of amplification of
non-carbapenemase βlactamase genes (other than carbapenemase genes) with
concurrent outer membrane porin disruption
• The most common carbapenemases K. pneumoniae carbapenemases (KPCs), which
can be produced by any Enterobacterales, New Delhi metallo-βlactamases (NDMs),
Verona integron-encoded metallo-β-lactamases (VIMs), imipenemhydrolyzing
metallo-β-lactamases (IMPs), and oxacillinases (e.g., OXA-48-like)
CARBAPENEM RESISTANT ENTEROBACTERALES
75. Carbapenemase Testing Results Are Not Available
Ceftazidime-avibactam, Meropenem-vaborbactam, and Imipenem-cilastatin relebactam are
the preferred treatment options for infections outside of the urinary tract caused by CRE when
carbapenemase testing results are either not available or negative.
For patients with CRE infections who:
within the previous 12 months have received medical care in countries with a relatively high
prevalence of metallo-β-lactamaseproducing organisms
or who have previously had a clinical or surveillance culture where a metallo-β-lactamase-producing
isolate was identified,
preferred treatment options include the combination of Ceftazidime-avibactam plus Aztreonam,
or Cefiderocol as monotherapy, if carbapenemase testing results are not available.
TREATMENT OF MDR GNB IDSA 2022
76. CARBAPENEMASE TESTING RESULTS ARE AVAILABLE
Meropenem-vaborbactam, ceftazidime-avibactam, and imipenem-
cilastatinrelebactam are preferred treatment options for KPC-
producing infections outside of the urinary tract.(CLASS A ENZYMES)
Ceftazidime-avibactam in combination with aztreonam, or cefiderocol
as monotherapy, are preferred treatment options for NDM and other
metallo-β-lactamase-producing infections.(CLASS B ENZYMES)
Ceftazidime-avibactam is the preferred treatment option for OXA-48-
like-producing infections.(CLASS D ENZYMES)
TREATMENT OF MDR GNB IDSA 2022
78. • Patients with HAP/VAP caused by a carbapenem-resistant
pathogen that is sensitive only to polymyxins, should be treated
with Intravenous polymyxins (colistin or polymyxin B) and inhaled
colistin (
• Colistin for inhalation should be administered promptly after being
mixed with sterile water. This recommendation was made by the
US food and drug administration (FDA) after a report that a cystic
fibrosis patient died after being treated with a premixed colistin
formulation.
• Intravenous polymyxin B may have potential pharmacokinetic
advantages compared to intravenous colistin, but clinical data are
lacking in patients with HAP/VAP
IDSA 2016 VAP GUIDELINES
79. • Treatment with either a carbapenem or ampicillin/ sulbactam if the isolate is
susceptible to these agents
• In patients with HAP/VAP caused by acinetobacter species that is sensitive only
to polymyxins, we recommend intravenous polymyxin (colistin or polymyxin b)
and we suggest adjunctive inhaled colistin
• In patients with HAP/VAP caused by acinetobacter species that is sensitive
only to colistin, we suggest not using adjunctive rifampicin
• In patients with HAP/VAP caused by acinetobacter species, we recommend
against the use of tigecycline
ACINETOBACTER SPECIES
80. • A single active agent may be sufficient for mild infections caused by CRAB. Of available
options, the panel suggests ampicillin-sulbactam as a preferred agent.
• 9 g IV q8h over 4 hours OR 27 g IV q24h as a continuous infusion For mild infections caused by CRAB
isolates susceptible to ampicillin-sulbactam, it is reasonable to administer 3g IV q4h – particularly if
intolerance or toxicities preclude the use of higher dosages.
• Combination therapy with at least two agents, with in vitro activity whenever possible,
is suggested for the treatment of moderate to severe CRAB infections
• Potential options for consideration as components of combination therapy include
ampicillin-sulbactam (preferred), tetracycline derivatives (with the most experience
available for minocycline, followed by tigecycline, and virtually no clinical data available
for eravacycline or omadacycline), polymyxin B, extended-infusion high dose
meropenem(2 gm 8 hrly over 3 hours), or cefiderocol
• The panel suggests ampicillin sulbactam as a component of combination therapy, even
when resistance to this agent has been demonstrated .The combination of meropenem
and colistin (or polymyxin B), without the addition of a third agent, is not suggested for
the treatment of CRAB infections however, the combination of ampicillin sulbactam,
meropenem, and polymyxin B remains a consideration, keeping in mind the potential
for toxicities from two high-dose β-lactam agents.
CARBAPENEM RESISTANT ACINETOBACTER
BAUMANII
81. •Polymyxin B can be considered as monotherapy for mild CRAB infections and in combination
with at least one other agent for the treatment of moderate to severe CRAB infections.
Colistin is reserved only for urinary CRAB infections.
•Polymyxins be prescribed as a component of combination therapy for moderate to severe
crab infections to increase in light of four major issues with the polymyxins.
• Firstly, concentrations of polymyxins in serum achieved with conventional dosing strategies
are highly variable and may be inadequate for effective bactericidal activity .
•Secondly, dosages required to treat systemic infections approach the threshold for
nephrotoxicity making the therapeutic window very narrow (i.E., ~2 mcg/ml may be required
to achieve 1-log10 reduction in bacterial growth, but this is also the threshold associated with
nephrotoxicity)
•Thirdly, the activity of intravenous polymyxins in pulmonary epithelial lining fluid is
suboptimal and generally does not result in adequate bacterial killing in the lungs
• Finally, there are several reports of clinical failure and resistance emergence during
polymyxin monotherapy [158, 163-166]
• Not suggested in adding nebulized antibiotics for the treatment of respiratory infections
caused by CRAB. Due to the lack of benefit observed in clinical trials, concerns regarding
unequal distribution in infected lungs, and concerns for respiratory complications such as
bronchoconstriction in 10-20% of patients receiving aerosolized antibiotics
TREATMENT OF MDR GNB IDSA 2022
82. • Tetracycline derivatives can be considered as monotherapy for mild CRAB infections and
in combination with at least one other agent for the treatment of moderate to severe
CRAB infections.
• Of these agents, the panel prefers high dose minocycline because of the longstanding
clinical experience with this agent and the availability of CLSI susceptibility interpretive
criteria.
• High-dose tigecycline is an alternative option.
• Several observational studies and a meta-analysis of 15 randomized trials suggested that
tigecycline monotherapy is associated with higher mortality than a variety of alternative
regimens used for the treatment of pneumonia, not exclusively limited to pneumonia
caused by CRAB .
• Subsequent investigations have demonstrated that when high-dose tigecycline is
prescribed (200 mg intravenously as a single dose followed 100 by mg intravenously
q12h) mortality differences between tigecycline and comparator agents are no longer
evident. If tigecycline is prescribed for the treatment of CRAB infections, the panel
recommends that high-doses be used
TREATMENT OF MDR GNB IDSA 2022
83. The incidence of anaerobic bacteria as the causative agent of VAP is 2 to 7%.
Risk factors for VAP due to anaerobes are:
• Altered consciousness,
•Apiration pneumonitis
• high simplified acute physiology score (SAPS).
RECOMMENDATIONS
• empirical antibiotic regimen for VAP should not include coverage for anaerobic organisms
routinely
• in the presence of risk factors for VAP due to anaerobic pathogens, anaerobic antimicrobial
coverage should be added in an empirical regimen
• in patients with risk factors for anaerobic organisms, clindamycin or metronidazole should be
added to empirical antibiotics regimen for VAP, if it does not include carbapenems (meropenem
or imipenem) or piperacillin-tazobactam in the ongoing empirical regimen (UPP).
ANAEROBIC COVERAGE
84. The incidence of atypical bacteria as causative agents of VAP is low (5 to
7.5%).
Risk factors for VAP due to Legionella are:
• Legionella colonization in hospital water supply,
• Prolonged use of corticosteroids,
• Cytotoxic chemotherapy, elderly,
• Chronic renal failure,
• Previous antibiotic use,
• Granulocytopenia, and
• Poor glasgow coma score.
ATYPICAL BACTERIA
85. • Empirical antibiotic regimen for VAP should not include coverage for atypical
organisms routinely
• In the presence of risk factors for VAP due to atypical bacterial pathogens,
atypical antimicrobial coverage should be added to the empirical regimen (2B).
• The preferred atypical coverage in combination antibiotics regimen is
fluoroquinolones (levofloxacin or moxifloxacin) or macrolides (azithromycin or
clarithromycin) (UPP)
RECOMMENDATIONS
86. LENGTH OF THERAPY
VAP:
• Short course (7-8 days) of antibiotic therapy should be used, in the case of VAP
with good clinical response to therapy.
• Longer duration (14 days) of antibiotic therapy should be considered, in case of
VAP caused by NF-GNBs or is associated with severe immunodeficiency, structural
lung disease (COPD, bronchiectasis, and interstitial lung disease), empyema, lung
abscess, necrotizing pneumonia, and inappropriate initial antimicrobial therapy.
87. HAP:
• For patients with HAP, we recommend a 7-day
course of antimicrobial therapy.
• There exist situations in which a shorter or
longer duration of antibiotics may be
indicated, depending upon the rate of
improvement of clinical, radiologic, and
laboratory parameters.
88. • For patients with HAP/VAP, we suggest that antibiotic
therapy be de-escalated rather than fixed
• De-escalation refers to changing an empiric broadspectrum
antibiotic regimen to a narrower antibiotic regimen by
changing the antimicrobial agent or changing from
combination therapy to monotherapy. In contrast, fixed
antibiotic therapy refers to maintaining a broad-spectrum
antibiotic regimen until therapy is completed.
De-escalation
89. • For patients with HAP/VAP, we suggest using PCT
levels plus clinical criteria to guide the discontinuation
of antibiotic therapy, rather than clinical criteria alone
• It is not known if the benefits of using PCT levels to
determine whether or not to discontinue antibiotic
therapy exist in settings where standard antimicrobial
therapy for VAP is already 7 days or less
• the benefits of decreased antibiotic exposure
outweighed the costs, burdens, and uncertain results
associated with PCT testing
90. • For patients with suspected HAP/VAP, we suggest not using the
CPIS to guide the discontinuation of antibiotic therapy
• it may lead to the discontinuation of antibiotics in patients who
need ongoing antimicrobial therapy
91. Re-evaluation at 48 to 72 hours after the initial diagnosis of VAP is the most suitable time.
Evaluation of treatment response for VAP should be on the basis of clinical, laboratory,
radiograph and microbiological results.
Factors associated with treatment failure in VAP includes
Host factors (advanced age, immunosuppressed, chronic lung disease, ventilator
dependence),
Bacterial factors (drug-resistant pathogens, opportunistic pathogens),
Therapeutic factors (inappropriate initiation of therapy, insufficient duration of
therapy, suboptimal dosing, inadequate local concentration of drugs),
Complications of initial VAP episode (lung abscess, empyema),
Other non-pulmonary infections or non-infectious mimics of pneumonia.
NON RESPONDING VAP
93. The Institute for Healthcare Improvement (IHI) had held “100 Mile for Lives” campaign
from 2004 to 2006 by introducing a “bundle” that collectively and reliably per-forms a
small, straightforward set of evidence-based practices, which have been proven to improve
patientoutcomes.
It generally includes five independent and evidence-based interventions.
The VAP bundle,which is derived from the IHI bundle, is composed of the following five
major interventions:
head-of-bed elevation between 30 and 45;
a daily “sedation vacation”and a readiness-to-wean assessment;
peptic ulcer dis-ease prophylaxis;
deep vein thrombosis prophylaxis;
and daily oral care with chlorhexidine (a new intervention added since 2010).
Subglottic suction (2011) (???)
VAP BUNDLE
94.
95. Essential practices for preventing VAP and/or VAEs in adult patients
Avoid intubation and reintubation if possible
•Use high-flow nasal oxygen or noninvasive positive pressure ventilation (NIPPV) as
appropriate whenever safe and feasible
•High-flow nasal oxygen has also been associated with a trend toward less nosocomial pneumonia in patients
with hypoxemic respiratory failure.
•NIPPV is associated with lower rates of intubation, reintubation, VAP, and mortality compared to conventional
oxygen therapy in patients with acute hypercapnic or hypoxemic respiratory failure.
•Helmet ventilation may be associated with better outcomes than facemask ventilation.
•Combining high-flow nasal oxygen with NIPPV immediately after extubation may further decrease the risk of
reintubation in patients at high risk for extubation failure compared to using high-flow nasal oxygen alone
•Placing non intubated patients with COVID-19 acute hypoxemic respiratory failure in the
prone position may lower the risk of intubation compared to standard care
96. Minimize sedation
•Minimize sedation of ventilated patients whenever possible
•Preferentially use multimodal strategies and medications other than benzodiazepines to
manage agitation
Examples include analgesics for pain, reassurance for anxiety, and antipsychotics, dexmedetomidine, and/or propofol
for agitation. Dexmedetomidine and propofol are associated with shorter duration of mechanical ventilation and ICU
length of stay compared to benzodiazepines. A randomized trial of light sedation with dexmedetomidine versus
propofol found no difference in ventilator-free days or mortality. Dexmedetomidine may decrease need for intubation
in patients on noninvasive ventilation.
•. Utilize a protocol to minimize sedation
Potential strategies to minimize sedation include nursedriven protocols for targeted light sedation and daily sedative
interruptions (ie, spontaneous awakening trials) for patients without contraindications.
multicenter randomized trial of no sedation versus light sedation with daily sedative interruptions reported no
difference in ventilator-free days, ICU-free days, or 90-day mortality.
•Implement a ventilator liberation protocol
. Assess readiness to extubate daily in patients without contraindications (i.e., conduct spontaneous breathing trials).
Ventilator liberation protocols are associated with extubating patients an average of 1 day earlier compared to
managing patients without a protocol.1
97. Maintain and improve physical conditioning
Provide early exercise and mobilization
Early exercise and mobilization programs may shorten duration of mechanical ventilation,
reduce ICU length of stay, lower VAP rates, and increase the rate of return to independent
function.There is no consistent association between early mobilization and hospital length
of stay or mortality.
Elevate the head of the bed
Elevate the head of the bed to 30–45°
A meta-analysis of 8 randomized trials reported that elevating the head of the bed was
associated with a significant reduction in VAP rates but no difference in duration of
mechanical ventilation or mortality. Given the simplicity, ubiquity, minimal risk, lack of
cost, and potential benefit of this intervention, we nonetheless classify it as an essential
practice while we await further data
98. Provide oral care with toothbrushing but without
chlorhexidine
Provide daily oral care with toothbrushing but without chlorhexidine
Daily toothbrushing is associated with significantly lower VAP rates, shorter duration of
mechanical ventilation, and shorter ICU length of stay.
Meta-analyses of randomized trials and observational studies allow for the possibility that oral
care with chlorhexidine may increase mortality rates.
Provide early enteral rather than parenteral nutrition
Provide early enteral rather than parenteral nutrition
Early enteral nutrition is associated with a lower risk of nosocomial pneumonia, shorter
ICU length of stay, and shorter hospital length of stay compared to early parenteral
nutrition.
99. Maintain ventilator circuits
Change the ventilator circuit only if visibly soiled or malfunctioning
Changing the ventilator circuit as needed rather than on a fixed schedule has no impact
on VAP rates or patient outcomes but decreases costs.
100. Additional approaches for preventing VAP and/or VAEs in adult
patients
Consider using selective decontamination of the oropharynx and
digestive tract to decrease microbial burden in ICUs with low
prevalence of antibiotic-resistant organisms.
Antimicrobial decontamination is not recommended in countries, regions, or ICUs with
high prevalence of antibiotic-resistant organisms
i. Oral agents that have been used for digestive decontamination include colistin,
tobramycin, and amphotericin B. Parenteral agents include cefotaxime.
ii. ICUs that implement this practice should actively monitor its impact on antibiotic
utilization, antimicrobial resistance, and Clostridioides difficile infections.
iii. There is no consensus on what constitutes “low levels of antibiotic resistance,” but an
arbitrary threshold that has been used by other guidelines and randomized trials is <5%
of bloodstream infections caused by extendedspectrum β-lactamase–producing
Enterobacterales
101.
102. Consider early tracheostomy
Meta-analysis of 17 randomized trials suggests that early tracheostomy (within 7 days of
intubation) may be associated with a 40% decrease in VAP rates, less time on mechanical
ventilation, and fewer ICU days but no difference in mortality.144
Consider using endotracheal tubes with subglottic secretion
drainage ports to minimize pooling of secretions above the
endotracheal cuff in patients likely to require >48–72 hours of
intubation
Intermittent and continuous drainage of subglottic secretions has been studied in at least 20
randomized controlled trials. On meta-analysis, the use of endotracheal tubes with subglottic
drainage reduced VAP rates by 44%. There was no association, however, between subglottic
secretion drainage and duration of mechanical ventilation, ICU length of stay, or hospital
length of stay and also on mortality.
Extubation followed by immediate reintubation to exchange a conventional endotracheal tube
for a subglottic secretion drainage endotracheal tube is not recommended.
103. Consider postpyloric feeding tube placement in patients with
gastric feeding intolerance at high risk for aspiration
Postpyloric feeding is associated with less aspiration and less pneumonia compared to
gastric-tube feeding.
Meta-analyses vary in their assessment of whether postpyloric feeding is associated with
decreases in ventilator, ICU, and/or hospital length of stay.
Postpyloric tube placement requires special expertise that is not available in all centers and
may incur delay in placement. Postpyloric feeding is considered less physiologic than
gastric feeding.
Postpyloric feeding should therefore be reserved for patients with gastric feeding
intolerance and for patients at high risk for aspiration as detailed in nutrition society
guidelines.
104.
105. Suggested Reading:
1.Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia:
2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the
American Thoracic Society
2. SHEA/IDSA/APIC Practice Recommendation Strategies to prevent ventilator-associated
pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in
acute-care hospitals: 2022 Update
3. Infectious Diseases Society of America 2022 Guidance on the Treatment of
ExtendedSpectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant
Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance
(DTRP. aeruginosa)
4. Infectious Diseases Society of America Guidance on the Treatment of AmpC β-
lactamaseProducing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and
Stenotrophomonas maltophilia Infections.2022
5. Guidelines for Antibiotic Prescription in Intensive Care Unit ISCCM 2019
