Treatment
A major problem in the management of patients with suspicion of VAP is when to initiate antibiotics and the prospective susceptibility of the causative pathogens. The indiscriminate and empiric administration of antibiotics, following clinical suspicion, contributes to the emergence of multidrug-resistant (MDR) pathogens and exposes the patient to antibiotic-related adverse effects and higher costs [91]. On the other hand, it is mandatory to initiate prompt treatment of VAP to improve survival [92-95]. However, the choice of the initial antibiotic treatment is challenging, particularly in ARDS patients undergoing long-term antibiotic treatment before VAP
20 Pulmonary Infections in Acute Respiratory Distress Syndrome
Table 20.3
|
Risk factors for ventilator-associated pneumonia caused by multi-drug resistant pathogens |
|
Prior intravenous antibiotic use within 90 days |
|
Septic shock upon diagnosis of VAP |
|
ARDS preceding VAP |
|
Five or more days of hospitalization prior to the occurrence of VAP |
|
Acute renal replacement therapy prior to VAP onset |
|
Risk factors for methicillin-resistant Staphylococcus aureus |
|
Prior intravenous antibiotic use within 90 days |
|
Risk factors for multi-drug resistant Pseudomonas aeruginosa |
|
Prior intravenous antibiotic use within 90 days |
|
ARDS acute respiratory distress syndrome, VAP ventilator-associated pneumonia |
353
development [96]. Also, it is important to consider patient’s inherent risk factors for MDR pathogens (Table 20.3) [82]. Finally, physicians should consider resistance patterns, which vary extremely among countries, regions, hospitals, and ICUs. Rello et al. [97] analyzed variations in VAP etiology among three Spanish ICUs and compared them with data collected in Paris. The authors concluded that VAP pathogens largely changed among the four clinical centers, with marked differences among the microorganisms isolated from the Spanish and French centers. Therefore, clinicians must be aware of the most common microorganisms in their own unit and antimicrobial susceptibility to avoid the administration of inadequate empiric antimicrobial therapy.
The latest guidelines emphasized the risks associated with ARDS for developing late-onset VAP, caused by MRSA and non-glucose-fermenting Gram-negative bacilli [6, 8]. Theoretically, ARDS patients are at very low risk of developing VAP caused by multi-susceptible pathogens, because they require antibiotic therapy for many days before the suspicion of VAP.
Thus, in summary, in ARDS patients, P. aeruginosa should always be covered, preferably with two antibiotics of different classes, particularly in units where >10% of Gram-negative isolates are resistant to an agent being considered for monotherapy, and in ICUs where local antimicrobial susceptibility rates are not available [98]. Likewise, ARDS patients are at high risk of developing MRSA VAP; thus, this pathogen should also be covered either with vancomycin or l inezolid. A detailed description of antibiotic recommendations is reported in Table 20.4. Of note, after the results of antimicrobial susceptibility test become available, the therapy should always be readjusted, narrowed, or fully changed/ withdrawn. Also, for highly resistant Acinetobacter spp. and carbapenem-resis- tant pathogens, intravenous polymyxins (colistin or polymyxin B) and inhaled colistin are highly recommended.
Table 20.4 Suggested empiric treatment options for clinically suspected ventilator-associated pneumonia in ARDS patients
|
Antibiotics for Gram-negative bacteria with anti- pseudomonal activity: P-lactam-based agents |
Antibiotics for Gramnegative bacteria with anti- pseudomonal activity: non-p-lactam-based agents |
Antibiotics for Gram-positive bacteria with MRSA activity |
|
Anti-pseudomonal penicillins1 |
Fluoroquinolones |
Glycopeptides4 |
|
Anti-pseudomonal penicillins1 Piperacillin-tazobactam 4.5 g IV q6h1 |
Ciprofloxacin 400 mg IV q8h Levofloxacin 750 mg IV q24h |
Vancomycin 15 mg/kg IV q8-12 h (consider a loading dose of 25-30 mg/kg x 1 for severe illness) |
|
Or |
Or |
Or |
|
Cephalosporins1 |
Aminoglycosides4,5 |
Oxazolidinones |
|
Cefepime 2 g IV q8h Ceftazidime 2 g IV q8h |
Amikacin 15-20 mg/kg IV q24h Gentamicin 5-7 mg/kg IV q24h Tobramycin 5-7 mg/kg IV q24h |
Linezolid 600 mg IV q12h |
|
Or |
Or |
|
|
Carbapenems1 |
Polymyxind4,6 |
|
|
Imipenem 500 mg IV q6h2 Meropenem 1 g IV q8h |
Colistin 5 mg/kg IV x 1 (loading dose) followed by 2.5 mg x (1.5 x CrCl + 30) IV q12h (maintenance dose) Polymyxin B 2.5-3.0 mg/kg/d divided into two daily IV doses |
|
|
Or |
||
|
Monobactams3 |
||
|
Aztreonam 2 g IV q8h |
||
Monobactams3 Aztreonam 2 g IV q8h
In patients with ARDS, based on the latest guidelines [82], double therapy against P aeruginosa and coverage against MRSA are recommended. The initial doses may need further adjustment for patients with hepatic or renal dysfunction
CrCl creatinine clearance, IVintravenous, MRSA methicillin-resistant Staphylococcus aureus Extended infusions may be appropriate
- 2The dose may need to be lowered in patients weighing <70 kg to prevent seizures 3In the absence of other options, it is acceptable to use aztreonam as an adjunctive agent with another p-lactam-based agent because it has different targets within the bacterial cell wall 4Drug levels and adjustment of doses and/or intervals required
- 5On meta-analysis, aminoglycoside regimens were associated with lower clinical response rates with no differences in mortality
- 6Polymyxins 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)
Adapted from [82]
