Published in the November 2003 issue of Today’s Hospitalist
The twin evils of a life-threatening condition and the possibility of antimicrobial resistance confront every physician treating ventilator-associated pneumonia (VAP).
Given the high stakes of VAP–a relatively common disease with a mortality rate of about 30%–experts say the principle of hit hard and fast should guide treatment. However, the menace of antimicrobial resistance also requires treatment that is tailored to combat the organisms present–and then discontinued as soon as possible.
Experts say there are several established strategies–and a few emerging techniques “that can help hospitalists achieve both of those goals.
One increasingly popular approach is de-escalation. This strategy involves treating suspected VAP empirically at first, then moving to an antibiotic with a more narrow spectrum. The therapy is shortened or even discontinued altogether based on culture results and the patient’s response.
A key to emerging strategies like de-escalation is assessing levels of drug resistance and sensitivity patterns in your facility. You need enough information to initially choose an antibiotic that best covers the pathogens that are most likely to be resistant.
We asked some pulmonologists and infectious disease specialists how they are tailoring therapies to treat VAP. Here are their tips, as well as some of the latest thinking in treating the condition.
One of the most effective ways to initially select antibiotics is to combine overall ICU resistance pattern data with patient-specific risk factors.
While the severity of the patient’s condition is an obvious concern, it should not be the only factor that guides your decision-making. Experts say that time is an equally critical factor.
When it comes to time, there are two important considerations: How long has the patient been in the hospital, and how soon after being intubated did the VAP symptoms first appear? If the answer to either question is five days or more, you face an increased risk that multidrug resistant organisms are present.
Another factor to consider: Was the patient transferred from a different hospital or long-term care facility? Finally, determine whether the patient has already been taking antibiotics.
“If one or two of these factors are present, you need fairly broad coverage for gram-negative and gram-positive organisms tailored to local resistance patterns,” explains Michael S. Niederman, MD, chair of medicine at Winthrop-University Hospital in Mineola, N.Y., and professor of medicine at the State University of New York at Stony Brook.
There’s no hard-and-fast rule about the best combination of drugs when treating severe disease or suspected resistance, or monotherapy in the case of milder disease where there is likely little resistance. Physicians interviewed for this story, however, gave some basic rules of thumb.
- Severely ill patients. If the patient is severely ill or likely harbors drug-resistant pathogens, you have several choices. For gram-negative bacteria, experts suggest cefepime, imipenem, meropenem or piperacillin/tazobactam (often with the addition of an aminoglycoside or antipseudomonal fluoroquinolone).
For gram-positive cocci (especially methicillin-resistant Staphylococcus aureus), they say, consider drugs like linezolid or vancomycin.Both Thomas File, MD, and Victor Cardenas, MD, say that they often prescribe three antibiotics when treating severely ill patients or individuals they think have a drug-resistant form of VAP. Dr. File is professor of internal medicine at Northeastern Ohio Universities College of Medicine in Rootstown, Ohio, and chief of infectious disease service at Summa Health System in Akron, Ohio. Dr. Cardenas is director of the medical ICU at John Sealy Hospital and associate professor of pulmonology and critical care medicine at the University of Texas Medical Branch in Galveston (UTMB).
- Less severe cases. For less severe cases of suspected VAP, and instances in which the patient is less likely to harbor drug-resistant organisms, good choices include a second-generation cephalosporin, a nonpseudomonal third-generation cephalosporin, or an extended-spectrum quinolone such as levofloxacin.
Physicians at Memorial Hermann Katy Hospital, for example, typically handle those kinds of cases with a third-generation cephalosporin, according to Paul Bing, MD, care management medical director at the facility in Katy, Texas. If a VAP patient had recently been receiving an antibiotic, physicians prescribe another drug.
Qualitative or quantitative cultures should be obtained before antibiotic treatment starts and then used in conjunction with other clinical findings to refine the initial antibiotic selection.
The standard at UTMB is to perform bronchoalveolar lavage (BAL) on most cases of suspected VAP. “We do BAL as a general rule, except on patients with high respiratory support who are very critically ill and it’s too risky to do, or when there’s been a change in antibiotic in the last day or so and it renders the positive predictive value of BAL mute,” Dr. Cardenas explains.
Once you have culture results in hand, you can adjust antibiotic therapy as needed. The goal, experts say, should be to reduce any unnecessary therapies.
“If there’s not a resistant pathogen present, you don’t need to cover for it,” explains Dr. Niederman. If only gram-negative rods are detected, for example, linezolid or vancomycin can safely be discontinued.
Dr. Niederman adds that effective monotherapies for VAP not caused by multidrug-resistant pathogens include ciprofloxacin, imipenem, meropenem, cefepime and piperacillin/tazobactam.
Knowing when to stop
Choosing antibiotics to match the organisms in your facility is critical, but so is stopping antibiotic therapy when it’s not needed.
“I don’t think broad spectrum coverage for two or three days is an issue,” says Dr. Cardenas. “The problem starts when 10 to 12 days after prescribing a drug, you still haven’t diagnosed VAP or other infections and the patient is still taking an antibiotic.”
Some physicians are taking a novel approach to discontinue antibiotic therapy in patients without positive cultures or ongoing clinical signs of VAP. They use a measure known as the clinical pulmonary infection score (CPIS) as a guide for antibiotic selection, dosage and duration.
In a 2000 study describing this methodology, patients with a CPIS of six or less received quinolone monotherapy for three days, at which time they were reevaluated. If the CPIS was still at or below six, quinolones were discontinued. (Patients who initially had CPIS scores above six received a full course of standard VAP antibiotic therapy.)
Researchers found that compared to subjects with low CPIS scores who received a full course of multiple antibiotics, individuals who received only three days of one antibiotic therapy experienced lower mortality. Their length of stay was also significantly lower, as was their overall rate of antimicrobial resistance. In addition, the costs of treating these patients with antibiotics totaled nearly $10,000 less per case.
“We now realize that we have underestimated the harm that excessive antibiotic use can bring, including C. difficile colitis, antibiotic-induced nephrotoxicity, superinfection with MRSA, etc.,” says Victor Yu, MD, professor of medicine at the University of Pittsburgh and a co-author of the study. He adds that these adverse effects directly cause not only morbidity, but also increase mortality.
Since the study was conducted, the strategy has been adopted in ICUs at the Veterans Affairs Medical Center in Pittsburgh and throughout the University of Pittsburgh Medical Center hospitals, according to Dr. Yu.
“We realized that physicians who are treating critically ill patients feel they have to get the antibiotic immediately,” he explains. When they’re not sure whether or not a patient has VAP, Dr. Yu adds, “they treat everyone, even though 70% ultimately won’t need antibiotics.
“Antibiotic resistance is a problem today and it will only get worse,” Dr. Yu says, “so we took the operational view of whether we could afford to give antibiotics to every suspected case of pneumonia. We used the CPIS score as a guide to identify people who were less likely to have pneumonia and need an antibiotic.”
Dr. File from Summa reports that he also uses the CPIS to de-escalate antibiotic therapy. “We use it as a guide to follow the concept of de-escalation, but we don’t use it in protocol form,” he says.
Summa also uses an antibiotic support team that includes infectious disease specialists and pharmacists to monitor antibiotic usage. The team also makes sure that the right drugs and dosages are used, and it accounts for each patient’s comorbidities. Members of the team also look for possible drug interactions with other medications.
Getting the dosage right
Especially when using a de-escalation strategy, it’s important to ensure that the dosage of the antibiotic is sufficient to eradicate the organisms in question. “You need to be aware of how an antibiotic works against a pathogen when determining dosage,” says Dr. File. For example, fluroquinolones are concentration-dependent, so you need to use dosages that achieve an adequate ratio of peak concentration or total drug amount for an optimal outcome. Likewise, antibiotics such as cephalosporins that use time-dependent mechanisms of action require “a duration long enough to achieve the optimal effect, say through continuous infusion,” Dr. File explains.
While de-escalation implies shortening the duration of antibiotic coverage “even for patients with moderate or severe disease “there have been no definitive studies of the optimal time frame. There is definitely a movement, however, away from blanket 14- or 21-day coverage in the absence of multidrug resistant organisms.
“Treatment has to be individualized based on the response of the patient, but our duration is now shorter, usually seven to 10 days, assuming the patient’s fever has decreased and oxygenation has improved,” reports Dr. File.
Dr. Cardenas typically prescribes a 14-day regimen when Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus are present. For nonresistant organisms, he usually prescribes an eight-day course.
Another potential strategy to maximize antibiotic effectiveness and decrease resistance is to routinely rotate or cycle antibiotics. While this strategy holds much promise, it may not be widely adopted until there are more definitive studies demonstrating its benefit.
Swedish Medical Center in Seattle is one of many institutions beginning to consider the concept. “We’ve talked about it, but we haven’t instituted an antibiotic rotation methodology,” says Per Danielsson, MD, medical director of the adult hospitalist program.
And to counter the growth of drug-resistant strains of VAP, some hospitals are taking an even simpler approach and prohibiting the use of certain antibiotics without the approval of the infectious disease service.
The long-term potential of this strategy is unclear, according to Dr. Niederman. “It has been helpful in stemming epidemics of individual pathogens with specific antibiotics,” he says, “but it has not been effective in dealing with broad resistance.”
Gina Rollins is a freelance writer specializing in health care. She is based in Silver Spring, Md.