delivery of antibiotics is not considered standard therapy for either prophylaxis or the
treatment of lower respiratory tract infections (288).
In the past, aminoglycosides and polymyxins were the most common agents used in
aerosols.
In a prospective randomized trial, the use of intravenous therapy was compared to the
same treatment plus aerosolized tobramycin. The results of this trial suggest no better clinical
outcome, but bacterial cultures of the lower respiratory tract were more rapidly eradicated (295).
At present, aerosolized antimicrobial therapy is mainly limited to MDR pathogens for
which no other treatment exists. Such is the case of MDRP. aeruginosaandA. baumannii, which
are treated with intratracheal colistin (285).
Monotherapy vs. Combination Therapy
When considering the use of a single antimicrobial agent as opposed to combined therapy, we
first need to make the distinction between the use of multiple antimicrobial agents in the initial
empirical regimen (to ensure that a highly resistant pathogen is covered by at least one drug)
and that of combination therapy continued intentionally after the pathogen is known to be
susceptible to both agents. The former use of combination therapy is uniformly recommended,
whereas the latter use remains controversial.
The benefits commonly attributed to combination therapy include synergy between
drugs and the potential reduction of resistance problems. However, the combined regimen has
been even found to fail at avoiding the development of resistance during therapy (283).
Two meta-analyses have recently explored the value of combination antimicrobial
therapy in patients with sepsis (284) and gram-negative bacteremia (289). No benefits of
combination therapy were shown, and nephrotoxicity in patients with sepsis or bacteremia
increased. However, in the subset of bacteremic patients infected with P. aeruginosa,
combination therapy (usually a beta-lactam and an aminoglycoside) reduced the risk of
mortality by half. A trend toward improved survival has been previously observed with
aminoglycoside-including, but not quinolone-including, combinations (8). Combination
therapy could, therefore, be beneficial in patients with severe antimicrobial-resistant infections.
Whether this benefit is due to a more reliable initial coverage or a synergistic effect is unclear
(290). The general consensus at present is to opt for combination therapy with an
aminoglycoside for the initial five days in patients with VAP caused by gram-negative bacilli
(24,178). The nephrotoxicity of aminoglycosides, nevertheless, limits the use of these agents.
Table 7 Antibiotic Dose Adjustment in Patients with Renal Impairment (Continued)
Antibiotic CrCl (mL/min) Dose adjustment
Moxifloxacin No adjustment
Piperacillin–tazobactam > 40 No adjustment
20–40 4.5 g/8 hr
< 20 4.5 g/12 hr
Tobramycin 50 5 mg/kg/24 hr
30–49 5 mg/kg/36 hr
20–29 5 mg/kg/48 hr
< 20 2 mg/kg1 & consult kinetics
Vancomycin > 50 15mg/kg/12 hr
10–50 1g/3–10 day
< 10 1g/5–10 day
CrCl: creatinine clearance calculated using the formula:
Males: [(140 – age)IBW]/ [SrCr72]
where
Age: age in years
IBW: ideal body weight in kg
IBW in men¼50 kgþ2.3 kg per inch of height over 60 inches
IBW in women¼45.5 kgþ2.3 kg per inch of height over 60 inches
SrCr¼serum creatinine in mg/dL
Females¼CrCl (males)0.85
Nosocomial Pneumonia in Critical Care 195