Empiric approach to antibiotic therapy
Facing the challenge of sepsis, nosocomial pneumonias, severe infections
A side from the continuing concern for the rational use of antibiotics, clinicians understand just how crucial their initial choice of antibiotics would be. This is particularly important inside the hospital, where such problems as sepsis and nosocomial pneumonia are continuing threats.
This is why during the 24th International Congress of Chemotherapy (ICC) held in Manila last month, three internationally re-cognized infectious-disease experts spoke at length about adopting an empiric approach to antibiotic therapy. Organized by AstraZeneca Philippines, the symposium focused on three specific issues--facing the challenge of sepsis-related mortality, antibiotic therapy for hospital-acquired and ventilator-related pneumonia, and coming up with hospital policies in using antibiotics in severe infections.
Dr. Jean-Claude Pechère, International Society of Chemotherapy president, discussed why adequate antibiotic therapy could be the best option to manage sepsis. Sepsis--"probably the most traumatic condition that we see as infectious-disease specialists"--he said, is infection plus systemic inflammatory response syndrome (SIRS), which involves at least two of the following--temperature (>38 degrees or <37 degrees Celsius), pulse rate (>90 beats a minute), respiratory rate (>20 breaths per minute), white-blood-cell count (>12,000 cells/mL, <4,000 cells/mL, or >10 percent are immature forms). Severe sepsis, meanwhile, already involves organ failure; septic shock is severe sepsis with hypotension despite adequate resuscitation.
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Pechère noted that sepsis incidence has been rising in recent years, and experts have been trying to know which of the available interventions works best. Of the significant interventions, early adequate antibiotic therapy has been shown to reduce mortality from 63 percent to 31 percent (Valles et al., 2003), something that one study (Tillou et al., 2004) suggested should be done within the first hour. This, Pechère clarified, must be done after sampling and performing a rapid test such as Gram stain.
Dr. James Tan, professor of internal medicine at the Northeastern Ohio Universities College of Medicine, spoke about an empiric approach to antibiotic therapy in nosocomial pneumonias. Quoting Wunderink (2005), he said that excess antibiotic use in ventilated patients is associated with increased mortality.
New recommendations (Am J Respir Crit Care Med, 2005) in managing hospital-acquired, ventilator-associated, and health-care-associated pneumonias emphasize the need for culture and microscopy. Unless there is low clinical suspicion and negative microscopy, empiric antibiotic therapy should be started. If the pneumonia is late onset (five days or more) or if multidrug-resistant (MDR) pathogens are suspected, broad-spectrum antibiotic therapy must be initiated. If not, limited-spectrum antibiotic therapy may be adequate. After initial therapy, cultures and clinical response must be monitored for possible modifications or discontinuation. Aside from the risk of MDR pathogens, other factors should be considered in choosing the agent/s for initial empiric therapy. These include local microbiology, cost, availability, and formulary restrictions. For patients with no known risk factors for MDR pathogens and with early-onset pneumonia, possible agents are ceftriaxone; levofloxacin, moxifloxacin, or ciprofloxacin; ampicillin/sulbactam; or ertapenem.
Certain antibiotic combinations should be considered for initial empiric therapy for those with late-onset disease or with suspected MDR pathogens. The combination should be:
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antipseudomonal cephalosporin (cefepime, ceftazidime), antipseudomonal carbapenem (meropenem or imipenem), or beta-lactam/beta-lactamase inhibitor (piperacillin/tazobactam); PLUS
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antipseudomonal fluoroquinolone or aminoglycoside; PLUS
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linezolid or vancomycin.
Tan emphasized the need for prompt antibiotic therapy, "because delays in administration may add to excess mortality."
Dr. Victor Lim, president of the Western Pacific Society of Chemotherapy, lamented the almost "universal problem" of inappropriate antibiotic prescribing. Therefore, there is a need for rational antibiotic use to improve patient outcomes, contain cost of treatment, and limit resistance.
Certain concepts may be adopted to improve prescribing practices, which should be characterized by antibiotic stewardship and the presence of a hospital antibiotic policy. They must involve all stakeholders, be multifaceted, and be supported by authorities.
Lim stressed that an antibiotic policy "is more than just a set of guidelines." It must involve an education and feedback mechanism, and see the importance of audit and research. Education and feedback involve not just lectures, but also "academic detailing/face-to-face interactions" among colleagues, as well as senior consultants serving as role models. Also, laboratories and pharmacies should work closely with physicians to improve prescribing.
Lastly, principles of pharmacodynamics/pharmacokinetics must be strictly adhered to, and the use of information and communication technology may help not only in providing adequate information but also in surveillance. Also, dealing with external forces--like pharmaceutical marketing strategies and patient awareness--is important.
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