ICUs called good target for anti-resistance efforts
October 1, 1997 6 minutes read
ICUs called good target for anti-resistance efforts
Study shows high drug resistance in ICU
Emerging data from ongoing studies indicate the frontline fight against antibiotic-resistant bacteria must take place in intensive care units, where increasing patient census trends may be followed by a corresponding rise in resistant pathogens.
Initial data from a continuing study called ICARE (Intensive Care Antimicrobial Resistance Epidemiology) reveal a step-wise decrease in resistant pathogens across a spectrum of care. In general, researchers found the greatest percentages of antibiotic-resistant isolates in ICU patients, followed by non-ICU hospital patients and outpatients, respectively.1 Increases in the rate of antimicrobial resistance are resulting in the use of much more expensive drugs, more prolonged hospitalizations, higher death rates, and higher health care costs an estimated $4 billion annually in the United States, the ICARE researchers report.
"In this day of cuts and limited resources, where do you focus your efforts? The answer is the ICU," says lead author Lennox Archibald, MD, MRCP (UK), medical epidemiologist in the Centers for Disease Control and Prevention’s hospital infections program.
The study included data from eight geographically dispersed sentinel hospitals in the CDC’s National Nosocomial Infections Surveillance (NNIS) system and was conducted in cooperation with the Rollins School of Public Health at Emory University in Atlanta. The data were reported in terms of percentage of resistant isolates of the total number of isolates tested for inpatients (ICU and non-ICU) and outpatients. For example, 6.3% of enterococci isolated from inpatients were vancomycin-resistant (VRE), compared with 1.4% VRE among outpatients. (See table, p. 149.)
Most of these pathogens are resistant to all currently available antibiotics, the authors noted. Likewise, overall NNIS data for gram-negative bacilli indicate that the percentage of Klebsiella pneumoniae resistant to extended-spectrum beta-lactam agents increased from 1.5% in 1986 to 12.8% by 1993. In at least one case the resistant Klebsiella strains first "appeared in an ICU in one hospital and then spread to other hospitals in the surrounding area," the authors pointed out.
Improving the arsenal
As the rate of antimicrobial resistance increases, more resources should be allocated to attack the problem in ICUs, including heightened surveillance activities and improved use of antibiotics, the researchers concluded. While the need for more "scrupulous and stricter infection control" was cited in the study, the researchers say no new infection control measures are being advised based on the study’s phase I data. A similar expanded study of antibiotic resistance in 50 NNIS hospitals was launched in early 1996 as phase II of the project, but results are not yet available. In any case, it appears the primary answer to the problem is going to be in the form of surveillance for infections, identifying specific drug resistance patterns, and then implementing antibiotic controls. That means, for example, that infection control professionals and others working in critical care settings should begin focusing infection surveillance and antibiotic control efforts on ICU patients, rather than trying to attack the problem globally.
"Hospitalwide surveillance is a thing of the past," Archibald says.
Indeed, focusing surveillance on ICUs may allow early detection of outbreaks of resistant infections. For example, in a Canadian study, clinicians comparing isolates from ICU patients with other hospital isolates detected and effectively curtailed an outbreak of multidrug-resistant Pseudomonas aeruginosa in an ICU.2 Without the targeted effort, the P. aeruginosa ICU outbreak might have gone undetected and spread throughout the hospital, they concluded.
Patients admitted to ICUs are at greater risk of acquiring nosocomial infections because of their serious underlying disease, prolonged use of invasive devices, and extended hospital stays. "Moreover, antimicrobial resistance in pathogens is more likely encountered in the ICU because of the selection effect of treatment with multiple antimicrobials for a single patient, which may result in amplification of antimicrobial resistance in organisms," ICARE researchers concluded.
Another emerging trend that may compound the problem is that ICU bed census is on the rise even as overall hospital census is falling due to the transition to outpatient care, Archibald says. The trend is occurring in the NNIS system hospitals and is starting to appear in other surveys. The impact of emerging antimicrobial resistance in ICUs may increase as hospitals devote more beds and resources to those units.
"The chief risk factor for acquisition of a osocomial infection is [invasive] device use," Archibald explains. "The more critical [the condition of the patient], the higher probability you will have a device. If you have a high rate of nosocomial infections, there is going to be a parallel increase in antimicrobial use."
Match the bug to the drug
As such infections are treated with increasing amounts of antibiotics in the ICU, certain "bug-drug" combinations are appearing in the initial ICARE data that show a direct relationship between the level of use of the antibiotic and an attendant rise of resistant pathogens, he adds.
"There’s a directly proportional relationship in mathematical terms. As usage increases, resistance increases," Archibald says. "One good example is ceftazidime use and ceftazidime-resistant Entero-bacter cloacae; also ceftazidime use and ceftazidime-resistant Pseudomonas aeruginosa. The third one is anti-staphylococcal agents penicillin and first-generation cephalosporins and percentage of methicillin-resistant Staphylococcus aureus."
That raises the question of whether it is possible, as some researchers suggest, to detect "thresholds" of antibiotic use that begin to create resistance. Use of the drug in question could then be decreased as resistant microorganisms appear.3 A recent position paper on antibiotic resistance by the Society for Healthcare Epidemiology of America (SHEA) referred to the theory, noting that the threshold for selection of resistant organisms may differ by individual and by patient population.4 "This may explain why, in ICUs, where there is usually a small population undergoing intensive antibiotic therapy or prophylaxis, resistance tends to be more common, pathogens are more often multiply resistant, and spread within the population is more likely," SHEA stated.
Attempts to detect drug-bug interactions in ICUs and implement interventions, however, must be tailored to the specific situation in each critical care setting, the ICARE researchers note.
There are no silver bullets
"There isn’t going to be one size that fits all," says co-author John E. McGowan Jr., MD, pro-fessor of epidemiology at the Rollins School of Public Health at Emory. "It’s going to require looking at what is going on in the specific institution or health care system and making plans accordingly. Benchmarking from the data will be useful, but that benchmarking is going to have to be turned into local circumstances to be either effective or cost-effective."
In the interim, an obvious general area to review is empiric prescribing for patients without a definitive diagnosis, Archibald notes.
"A lot of that is subjective," he says. "If we could control that so doctors [are not] prescribing willy-nilly for every fever but that is a difficult proposition. How can someone tell doctors how to prescribe?"
As a general guide, clinicians may want to consider the following recommendations for control of antibiotic use in the ICU by Dennis Maki, MD, chief of infectious diseases at the University of Wisconsin Hospitals and Clinics in Madison:5
• If fever is the patient’s only sign of infection, the patient should not automatically be placed on an antibiotic.
• For treatment of a presumed infection, appropriate diagnostic tests, such as cultures, should always be done before starting treatment with antibiotics.
• A single drug and the most narrow-spectrum drug or drugs should be used whenever possible, especially if the infecting organism or organisms are known at the outset.
• Reassess the need for continued antimicrobial therapy daily and modify therapy based on culture results.
• Don’t extend surgical antimicrobial prophylaxis beyond 24 hours postoperatively. Patients undergoing most surgeries can receive a single dose of preoperative antibiotic.
References
1. Archibald L, Phillips L, Monnet D, et al. Antimicrobial resistance in isolates from inpatients and outpatients in the United States: Increasing importance of the intensive care unit. Clin Infect Dis 1997; 24:211-215.
2. Bryce EA, Smith JA. Focused microbiological surveillance and gram-negative beta-lactamase-mediated resistance in an intensive care unit. Infect Control Hosp Epidemiol 1995; 16:331-334.
3. Levy SB. Balancing the drug-resistance equation. Trends Microbiol 1994; 2:341-342.
4. Shales DM, Gerding DN, John Jr JF, et al. Society for Healthcare Epidemiology of America and Infectious Disease Society of America Joint Committee on the Prevention of Antimicrobial Resistance. Guidelines for the prevention of antimicrobial resistance in hospitals. Infect Control Hosp Epidemiol 1997; 18:275-291.
5. Maki DG. "Nosocomial Infection in the Intensive Care Unit." In: Parrillo JE, Bone RC, eds. Critical Care Medicine: Principles of Diagnosis and Management. St. Louis: Mosby Year Book Inc.; 1995, pp. 893-954.
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