Appropriate antibiotics needed for VAP management
Clinicians who manage ventilator-associated pneumonia (VAP) patients should promote appropriate use of antibiotics to optimize patients' outcomes and prevent antibiotic resistance. That's the finding of researchers from St. Louis University Hospital, Washington University School of Medicine, and Barnes-Jewish Hospital's pharmacy department who published their findings in Pharmacotherapy. They said a strategy of de-escalation incorporates their philosophy with administration of broad-spectrum empiric antimicrobial therapy based on patient risk factors, serial assessment of clinical markers to monitor the response to empiric therapy, implementation of locally developed and clinician-accepted protocols to minimize the number of antibiotics when cultures are positive and/or when clinical improvement occurs, as well as shortening therapy to 7-8 days in patients with uncomplicated VAP and an appropriate clinical response to treatment.
Optimizing antimicrobial therapy
According to the researchers, VAP is the most common infection complication in patients receiving mechanical ventilation and accounts for exorbitant resource use in ICUs. Antimicrobial management of VAP incorporates an initial broad-spectrum empiric regimen to ensure appropriate coverage with de-escalation of therapy after 48-72 hours based on culture results and sensitivities.
VAP occurs at a rate of 5-16 cases per 1,000 ventilator days, and accounts for some 80% of all hospital-acquired pneumonias requiring intensive care. Mortality rates are 25-50% and as high as 76% in patients who develop bacteremia or who are infected with high-risk pathogens such as Pseudomonas aeruginosa or Acinetobacter species.
Antimicrobial management of VAP is balanced between providing appropriate initial broad-spectrum treatment in a timely manner and avoiding unnecessary use if antimicrobials by narrowing their spectrum or by discontinuing anti-infective treatment after 48-72 hours based on culture results and susceptibilities.
The researchers said their de-escalation strategy attempts to unify those principles into a single approach that optimizes patient outcomes while minimizing the emergence of antibiotic-resistant pathogens. Optimizing antimicrobial therapy for VAP, they said, requires applying rigorous diagnostic strategies, prescribing appropriate initial empiric therapy based on local pathogens and susceptibility rates, maximizing antimicrobial pharmacokinetic and/or pharmacodynamic profiles, using protocols to change from broad-to narrow-spectrum therapy, and administering a short course of treatment.
First step is diagnosis
Definitive diagnosis is the first step in optimizing VAP treatment. The diagnosis of VAP is generally based on findings of new or worsening infiltrates on chest X-rays, systemic signs of infection (including fever and leukocytosis), and bacteriologic evidence of pulmonary parenchymal infection obtained with bronchoscopic or nonbronchoscopic techniques. Bron-choscopic sampling of the lower airways using a protected specimen brush or bronchoalveolar lavage is the most accurate method of establishing a microbiologic diagnosis of VAP short of direct tissue examination.
After microbiologic specimens are obtained, the next principle of antibiotic de-escalation is expedient administration of an appropriate empiric regimen to patients with suspected VAP. Antimicrobial treatment is defined as appropriate when a documented microbiologic infection (positive culture result) is treated with an agent that demonstrates in vitro activity against the organism at the time the pathogen is identified on culture. Failure to treat with an appropriate initial antimicrobial regimen may increase morbidity and mortality rates. The study reports on other research that prospectively evaluated empiric use of antibiotics in 430 cases of ICU-acquired pneumonia. In the 34% of patients who did not receive appropriate antimicrobial therapy, rates of shock and attributable mortality were significantly higher than those of patients giving appropriate empiric coverage.
Initial antibiotics are generally selected in the absence of identified pathogens. To safeguard against inappropriate empiric regimens and their associated increased risk of mortality, clinicians must be aware of the microorganisms likely to cause VAP in their patients, which vary depending on the onset of infection.
After an initial broad-spectrum antimicrobial regimen is started, the next component of adequate therapy is prescribing the proper dose and interval to achieve sufficient intrapulmonary drug concentrations for a clinical and microbiologic response. To do so, the researchers said, clinicians must understand the pharmacokinetics and pharmacodynamics of antimicrobials and the minimum inhibitory concentrations (MIC) that the Clinical and Laboratory Standards Institute assigns for each bacterial pathogen.Pharmacokinetic parameters such as absorption, dilution, metabolism, and elimination for a given dosage regimen establish the pharmacokinetic profile. And antimicrobial pharmacodynamics relates the concentration of the drug at the site of action with regard to the antibiotic's therapeutic and toxicological effects. The relationship between the pharmacokinetic and pharmacodynamic variables, the pharmacokinetic-pharmacodynamic profile, determines the drug's microbiologic and clinical efficacy.
Steps in Determining Correct Dose
The researchers said prescribing the correct dose and interval of antimicrobial for VAP is a multistep process involving: 1) consideration of the antimicrobial MIC breakpoint for targeted organisms or the microbe-specific MIC for each antimicrobial tested for an isolated organism; 2) the pharmacokinetic-pharmacodynamic parameter associated with clinical benefit and the dose likely to achieve the desired pharmacokinetic-pharmacodynamic endpoint in critically ill patients; 3) the patient's renal and hepatic function; and 4) the characteristics of antimicrobial distribution into the lung and/or the established lung serum concentration ratios, as determined using antibiotic concentrations in lung-tissue samples, epithelial-lining fluid, alveolar macrophages, and intrapulmonary micro dialysis techniques.
Evaluate patient response daily
To ensure that patients are appropriately treated for VAP, the researchers said, their clinical response to therapy should be continuously assessed. Patients' response to the empiric regimen should be evaluated daily using clinical aids such as the clinical pulmonary infection score. Lack of clinical improvement after 48-72 hours of antibiotic therapy is an indication for an intensified search for the etiology of VAP. The researchers said the search might include bronchoscopy if not previously performed, a search for alternative diagnoses or sites of infection, and possible adjustments to the antimicrobial agents used or optimization of pharmacokinetic-pharmacodynamic endpoints.
Using the de-escalation strategy, the initial and appropriate broad-spectrum regimen should be adjusted based on the patient's clinical and microbiologic response. Modifications include decreasing the number and spectrum of antibiotics and shortening the duration of therapy if signs of clinical improvement are observed or if a causative organism is identified.
Shorter treatment durations OK
Treatment durations shorter than the traditional 14- to 21-day regimens appear to have acceptable clinical outcomes, according to the study, with decreased antimicrobial resistance. The optimal duration of antibiotic therapy for uncomplicated, bronchoscopically diagnosed VAP was addressed in a trial comparing eight- and 15-day courses of treatment. The prospectively defined endpoint was death from any cause at 28 days after the onset of VAP. Patients in the eight-day group had a mortality rate of 18.8% compared with 17.2% in the 15-day group, an absolute difference of 1.6%, indicating noninferiority.
Overall, the recurrence of pulmonary infection, the number of mechanical ventilator-free days, and the length of stay in the ICU did not differ between the groups. In the eight-day group, the number of antibiotic-free days by day 28 increased, and the isolation of resistant pathogens when recurrence was diagnosed decreased. Also in the eight-day group, relapse rates tended to increase when the etiologic organism was P. aeruginosa or an Acinetobacter species, without compromising survival.
Clinicians who manage ventilator-associated pneumonia (VAP) patients should promote appropriate use of antibiotics to optimize patients' outcomes and prevent antibiotic resistance.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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