Empiric Antibiotic Treatment for ICU Pneumonia

Joseph Mensa and Jose Antonio Martinez


               The choice of empiric antibiotic treatment in any infectious disease, including ventilator-associated pneumonia (VAP) and ICU pneumonia should take the following points into consideration:

               1) The most likely etiologic microorganisms

               2) The antibiotics likely to be active against these microorganism.

               3) The pharmacokinetic/pharmacodynamics of these antibiotics

The Likely Etiologic Microorganisms

               The microorganism most frequently isolated from the bronchial secretions of patients with VAP are Staphylococcus aureus and Pseudomonas aeruginosa, comprising of around 50% of the isolates. These are followed, in order of frequency, by enterobacteria (Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Serratia spp., and Proteus spp.) representing 15 %, non-fermentative Gram negative bacilli other than P. aeruginosa (Acinetobacter, Stenotrophomonas and Burkholderia) in 10% and Haemophilus influenzae and Streptococcus pneumoniae in the remaining (1,6).

               The microorganisms causing VAP generally originate from the oropharyngeal flora of the patient. The bacterial flora of the oropharynx is maintained by mechanisms responsible for colonization immunity. Chronic diseases (5) and acute inflammatory processes lowers the resistance of the oropharynx to be colonized by Gram negative bacilli (3, 4). As a result, within 3-5 days of admission to the ICU, enterobacteria can colonize the oropharynx following the onset of an acute process. The enterobacteria originate from colonic flora of the patients themselves or to a lesser degree via the hands of the caregivers. Colonization of the oropharynx by Gram negative bacilli occurs predominantly in patients with an underlying comorbidity. So, a healthy person (e.g., a caregiver) rarely has significant colonization of Gram negative bacilli in the oropharynx, even after prolonged exposure in the hospital or in the ICU. Aging facilitates the deterioration of colonization immunity265. Once colonization immunity has been compromised, the specific Gram-negative bacilli colonizing the oropharynx depends primarily on prior exposure to antibiotics. Four patient scenarios can occur (Figure 4):

               1) Healthy subjects are colonized with normal oropharyngeal flora in whom pathogenic microorganisms such as Streptococcus pneumoniae, group A streptococci or meningococci may be transiently found.

               2) Patients with chronic comorbidity or an acute inflammatory process lose their colonization immunity. As a result, S. aureus and enterobacteria can colonize the oropharynx (Figure 5).

               3) Patients who have received antibiotic treatment become colonized with resistant microflora including enterobacteria with extended-spectrum beta-lactamases (ESBL), Enterobacter, P. aeruginosa, or MRSA (Figure 6).

               4) Patients who receive broad spectrum antibiotic schedules for more than 7 days are colonized by multiresistant microorganisms. Intubation is an aggravating factor. This leads to emergence of the more resistant non-fermenting Gram-negative bacilli (Acinetobacter baumanii, Stenotrophomonas maltophilia, Burkholderia cepacia) and Gram-positive microorganisms (coagulase negative Staphylococcus and Enterococcus spp.) (Figure 6).

               Changes in oropharyngeal flora tend to occur progressively so that the microorganisms of one stage can overlap with the next stage (Figure 4).

Empiric Antibiotic Treatment in VAP

Patients with VAP may be classified into two groups with respect to empiric selection:

No Prior Antibiotic Therapy: Patients who have not undergone antibiotic treatment within the previous month may be treated with monotherapy (Figure 4). A beta-lactam without antipseudomonal activity (e.g. third generation cephalosporin such as (ceftriaxone or cefotaxime), ertapenem, amoxicillin-clavulanate or a fluoroquinolone (e.g. levofloxacin or moxifloxacin) (Figure 5). Fluoroquinolones should not be administered in monotherapy in ICUs in which enterobacteria have a high rate of quinolone resistance.

Prior Antibiotic Therapy: Patients who develop VAP after having received antibiotic treatment or after the 7 to 10 days in the ICU may be infected by resistant gram-negative bacilli (Figure 6). An antipseudomonal antibiotic is indicated if the infection is severe or the patient fulfills the risk factors of colonization by multiresistant microorganisms (antibiotic treatment or intubation for more than 7 to 10 days). Priority should be given to treatment with a beta-lactam. The choice of the beta-lactam should take the following into account: 1) in vitro susceptibility of P. aeruginosa in the ICU, 2) the prevalence of ESBL-producing enterobacteria, 3) the result of prior cultures 4) prior antibiotics received in the patient. An antipseudomonal beta-lactam would include a third-generation cephalosporin (ceftazidime or cefepime), piperacillin-tazobactam or a carbapenem (imipenem or meropenem).

Special Situations

MRSA: Whether to add an anti-MRSA antibiotic depends on the prevalence of the MRSA in the ICU and the severity of infection. In geographic areas with documented presence of community-acquired MRSA, severe pneumonia with radiologic images of cavitation, or the presence of Gram-positive cocci in sputum, empiric linezolid or vancomycin may be appropriate. Tigecycline may be an option, although clinical experience is scanty.

Legionella species: Infections by Legionella pneumophila serogroup 1 can be diagnosed by a Legionella urinary antigen test. This test should be routinely obtained if the hospital water supply is known to be colonized with Legionella pneumophila, serogroup 1. A fluoroquinolone would be appropriate.

Adjustment of Therapy

               After 72 hours, the treatment should be adjusted based on the microbiologic results: 1) The initial beta-lactam should be maintained if the microorganism is susceptible to the empiric beta-lactam originally prescribed. If not, another beta-lactam, possibly a carbapenem, may have to be substituted. 2) Empiric antibiotic treatment active against MRSA should be withdrawn if its presence is not confirmed in cultures. 3) Discontinuation of the fluoroquinolone and especially the aminoglycoside should be considered after 3 to 5 days of treatment. The bactericidal activity of aminoglycosides and fluoroquinolones leads to a rapid reduction in the bacterial load during the first days of treatment. After this time, monotherapy may be sufficient. This approach would decrease emergence of resistant mutants, and minimize nephrotoxicity for the aminoglycoside.

Duration of Infection: Most infections can be cured with regimens of 5 to 7 days of duration. Four situations may justify more prolonged treatment: 1) infection by microorganisms which may multiply in the celluar cytoplasm (Legionella spp), 2) the presence of biofilms or prosthetic devices, 2) the development of tissue necrosis, the formation of abscesses, or infection within a closed cavity (empyema) or 4) the persistence of the original infection (perforation, endocarditis, etc.). If the course is favorable, as defined by defervescence, improvement in PaO2/FiO2 and a reduction in the CRP within the first 3-5 days of treatment, treatment may be withdrawn after the completion of 7 days. If the causative microorganism is a non-fermenting Gram negative bacilli, can be extended beyond 14 day treatment. In one study comparing the efficacy of a 7-day schedule versus one of 14 days in the treatment of VAP, it was observed that in the cases of pneumonia produced by non-fermenting Gram negative bacilli the capacity of eradicating the microorganism of the bronchial secretion was less with the shorter regimen. On the other hand, the 14-day treatment regimen was associated with a greater trend to colonization by multiresistant flora and a greater frequency of reinfection (2).

               In patients with clinical suspicion of ICU pneumonia who have a clinical pulmonary infection score, CPIS lower than 6 on the third day of treatment, the treatment may be withdrawn. In this setting the patient probably did not have pneumonia or the pneumonia was sufficiently mild such that prolonged antibiotic treatment was not required (7).



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