Management of Health-Care–Associated Infections in the Oncology Patient
Management of Health-Care–Associated Infections in the Oncology Patient
ABSTRACT: Each year, 2.4 million patients in the United States develop healthcare– associated infections (HAIs), requiring treatment at an annual cost of approximately $4.5 billion. HAI is the primary cause of death in approximately 30,000 patients and contributes to the death of 70,000 annually. Oncology patients are more susceptible than other patients to HAIs due to compromised immune systems, surgery (drains), invasive technology (catheters), and environmental factors. This paper will review each of these risk factors and discuss preventive steps such as a predictive index, antibiotic therapy, and infection control practices.
Health-care-associated infections (HAIs) pose a major public health problem for patients, their families, and society. According to the Centers for Disease Control and Prevention (CDC), 2.4 million patients in the United States developed an HAI in 1998. Among these patients, HAI was the primary cause of death in 30,000, and contributed to the deaths of an additional 70,000. By contrast, 17,171 Americans died of the acquired immunodeficiency syndrome (AIDS) in 1998, and 44,190 died of breast cancer in 1997. These infections cost approximately $4.5 billion to treat.
HAIs are defined as infections that develop within a health-care facility or are produced by microorganisms acquired during hospitalization. They usually occur within 48 to 72 hours after admission to a healthcare facility. In most cases, HAIs become clinically apparent while the patient is still hospitalized, but they can develop after discharge for diseases with long incubation periods (such as hepatitis B) or as a result of early discharge or same-day surgery.
Most Common HAIs
The most frequent HAIs are urinary tract infections, pneumonia, surgical site infections, and bloodstream infections. Although urinary tract infections are the most common, they are not associated with high morbidity rates in otherwise healthy patients. However, they do present a problem in immunosuppressed cancer patients and can lead to bacteremia as a result of long-term catheter use.
Pneumonia is the second most common HAI in the United States. Most health-care-associated pneumonia is caused by aspiration of bacteria colonizing the patient's oropharynx or upper gastrointestinal tract. Seventy different underlying diseases are considered strong predictors of death in patients with pneumonia.[4-6] The CDC guidelines for the prevention of health-care-associated pneumonia have identified a variety of risk factors, including immunosuppression in the presence of underlying diseases such as Legionnaire's disease, aspergillosis, respiratory syncytial virus, and influenza.
Surgical site infections are the third most frequent HAI and are associated with high morbidity and mortality rates. Cancer patients often receive drains after their surgery, and this puts them at high risk for an HAI.
Finally, bloodstream infections (bacteremia) account for about 200,000 HAIs each year and are related to the use of some intravascular catheter devices. Cancer patients frequently receive treatment via Hickman catheters or intra-arterial devices that remain in place long-term, and thus, carry a risk of infecting the blood with bacteria. Mortality from bacteremia can be as high as 20%. This paper will review specific risk factors for HAIs in oncology patients, reported outbreaks of HAI, and preventive programs.
HAI Risk Factors in Oncology Patients
Oncology patients are more susceptible than other patients to acquiring an HAI because of compromised immune systems, surgery, the use of invasive technology (ie, catheters), and environmental factors. Each of these risk factors are discussed in light of current research in infection control.
Compromised Immune System
The susceptibility of oncology patients to HAIs is related to the underlying malignancy, treatment, and the immune response. Any malignant process will diminish host defense capabilities to some degree. For example, patients receiving stem cell transplants are at higher risk of developing an HAI than are patients with solid tumors because of prolonged neutropenia and the graft response. Alternatively, patients with impaired humoral immunity are at greater risk for HAIs with encapsulated organisms such as Streptococcus pneumoniae or Cryptococcus neoformans. Increased use of indwelling tubes, transplanted tubes, and potent drugs also diminish the host's immune response and make patients more susceptible to bacteremia, pneumonia, or urinary tract infection.
Antineoplastic chemotherapies have improved survival rates but are also associated with more severe, prolonged immunosuppression, and in turn, a higher susceptibility to HAIs. A few studies have shown that adult cancer patients are at greater risk for HAIs than adults treated in highly attended intensive care units.[8,9] Velasco et al reported on a comparison of device use and health-care- associated infections and found a strong correlation between the presence of a central venous catheter (CVC) and HAI development. Moreover, they found that the median infection rate was much higher in the oncology intensive care unit than in the nononcology intensive care unit-50.0 infections per 100 patients or 91.7 infections per 1,000 patient days compared to 9.2 infections per 100 patients or 23.7 infections per 1,000 patient days-and concluded that this was the result of a combination of factors related to underlying illnesses, neutrophil count, and the use of invasive procedures and catheters.
A total of 27 million surgical procedures are performed each year in the United States, leading to the development of at least 920,000 surgical wound infections. Surgical site infection rates ranging from 1.5% to 13.0% have been reported.[12-15] Studying cancer patients only, Barber et al found an 8.03% rate of surgical site infections.
Treating patients who have intraabdominal cancer requires aggressive surgical intervention for proper diagnosis, staging, and cure and carries a high incidence of surgical site infections. Moreover, surgery for abdominal cancer is associated with a higher degree of morbidity and mortality than other standard procedures.
A study at The Hospital of Cancer in Rio de Janeiro evaluated 236 consecutive patients who underwent surgery for intra-abdominal cancer. The surgical site infection rate was 22.5%, with 77 (32.6%) developing one or more infectious complications. The researchers also found that the effect of antimicrobial prophylaxis decreased with increasing duration of surgery (> 2 hours). Factors associated with a significant risk of surgical site infections included duration of surgery beyond the predetermined cut-off point (5 hours), presence of remote infection at the time of surgery, length of preoperative stay (beyond 22 days), and use of abdominal drains. For surgeries that exceeded 5 hours, the infection rate jumped to 30.6% for the 215 to 300 minute range, and to 56.4% for the > 300 minute range. The mortality rate was higher among patients with postoperative HAIs than among patients without postoperative infections (24.7% vs 5%). Surgical site infections were the most prevalent (49.2%).
Similar results were reported by the National Cancer Institute in Mexico.[ 19] These investigators followed 3,372 surgeries to identify risk factors associated with infections in cancer patients. They found that surgical drains, diabetes, and obesity were associated with an increased risk of surgical site infections. The authors pointed out that, in their hospital, 57.5% of all surgeries require a drain. Moreover, they noted, in mastectomies and groin or axilla dissections, surgical drains remain in place for long periods, with the patient often being discharged with a drain in place. Emptying and cleaning the drain-often done by the patient- can allow bacteria to enter.
Table 1 lists the significant variables associated with the development of a postoperative infection. It has been shown that drains placed through an operative incision increase the risk of surgical site infections, and closed suction drains decrease the risk.
Potent neoplastic chemotherapies and advances in supportive care have resulted in prolonged survival rates for patients with malignancies. These powerful therapies have produced more severe and prolonged immunosuppression and thus a higher susceptibility to HAIs. In many cases,these HAIs stem from CVCs or intraarterial catheters.[22-24] The main sources of contamination are the hands of health-care personnel, the patient's own microflora, the needle hub, contaminated fluid, and contamination on insertion with subsequent spread through the bloodstream.
• Central Venous Catheters—Infection rates in one pediatric hematology/ oncology study showed CVCs to be the most frequent source of HAIs. Of 143 patients observed using a standardized surveillance system based on the National Nosocomial Infection Surveillance System, 28 (19.6%) had 40 documented HAIs, and the overall HAI rate was 10.8 per 1,000 patient-days. Of the 40 nosocomial infections, 26 (65%) were CVC-associated bloodstream or local infections-more than any other cause of infection. Hospitalized patients are at great risk of acquiring infections via CVC, because the catheter is manipulated more frequently while they are in the hospital.
The authors also noted that there is a higher degree of reduced compliance with the catheter-care protocol in a busy or overcrowded hospital environment than in a home-management program. Studies such as this one provide a good basis for recording specific infection rates in the hope of identifying risk factors that can be targeted with better preventive infection control programs.
Hickman catheters are a specific type of CVC that are most commonly used in supportive care measures in oncology patients. In many hospitals, their use is preferred because of their low cost ($90 as opposed to a $450 implantable port system), durable nature, and lower risk of infectious complications.[25,26] One study of Hickman catheter-related infection in 316 cancer patients found that 156 (40%) acquired an infection. The risk of acquiring such an infection increased as the time the catheter remained in place increased, with a median time to infection of 90 days. A catheter-related infection developed in 50% at 90 days and in 62% by 180 days.
Peripheral inserted central venous catheters are associated with fewer mechanical complications and a lower rate of infection than are other nontunneled CVCs. This may be due to the fact that the antecubital fossa is less colonized, less oily, and less moist than the chest and neck.[28-30]
• Intra-arterial Catheters—Although intra-arterial catheters have been used for over 3 decades for infusion of chemotherapy, little has been published on associated infection complications. In 1979, Maki et al found a 1.6% risk of Staphylococcus aureus bacteremia with the use of intra-arterial devices. However, this risk index was calculated during an outbreak.
More recently, Raad et al reported a very low risk of bacteremia associated with intra-arterial devices and attributed their finding to a relatively short period in which the catheters were inserted (median: 1 day; range: 1-6 days, compared to a mean of 21 days in the previous studies).[ 24] Therefore, it appears that a short placement period and excellent sterile barrier precautions are associated with a low risk of infectious complications.
• Prevention—During the past decade, new technologies to prevent intravascular catheter-related bloodstream infections have been pursued.[ 32] Among the technologic advances shown to reduce the risk of bloodstream infections are (1) an iodinated alcohol solution in the catheter hub (which produced a fourfold reduction in incidence of infection),[ 33] (2) short-term placement of a chlorhexidine/silver sulfadiazine- impregnated catheter (catheters in place ≤ 10 days reduced infection from 52% to 3%), (3) minocycline/ rifampin-impregnated catheters (catheters in place for an average of 6 to 7 days had a lower incidence of infections than chlorhexidine-silver sulfadiazine-impregnated catheters[ 35-37]-as with other antibiotics, however, resistance may develop as their use becomes more widespread), and (4) chlorhexidineimpregnated sponge dressing (which produced a threefold reduction in infections).[ 38]
Finally, nontechnologic strategies for reducing the incidence of infection should include barrier precautions during insertion, specialized nursing teams, and prospective infection control surveillance.
Oncology patients-especially those with neutropenia-vary in their susceptibility to HAIs, depending on the severity and duration of immunosuppression. They are generally at risk for bacterial, fungal, parasitic, and viral infections from both endogenous and exogenous sources. In addition, recent updates have shown that malignancy is a significant risk factor for vancomycinresistant bloodstream infection. One study reported that mucositis was independently associated with vancomycin- resistant bloodstream infection and that the risk of this infection increased with increasingly severe mucositis.
Although the incidence of vancomycin- resistant infections in oncology patients is related to a depressed immune system, other opportunistic organisms are seen more often in immunosuppressed patients and are referred to as environmental risk factors. For example, Aspergillus (a fungal organism) and Legionella (a bacterial organism) are associated with high mortality rates among oncology patients but are strongly associated with the environment.
Aspergillus is commonly found in the soil, water, and decaying vegetation. The most important HAI caused by Aspergillus is pneumonia, and the primary risk factor is severe and prolonged granulocytopenia with bone marrow transplants. Mortality from Aspergillus has been reported to range from 13% to 80% in leukemia patients.[ 41] The presence of Aspergillus spores in the hospital environment has been linked to periods of construction or renovation during which the number of spores increases. Other sources of infection in the hospital have been traced to such reservoirs as contaminated fireproofing material, damp wood, and bird droppings in air ducts.
Legionella also manifests as pneumonia in the immunosuppressed cancer patient. It is commonly found in aquatic environments and may enter hospital water systems in low or indeterminable numbers. Patients with a hematologic malignancy are at greater risk for Legionella infection than patients with a nonhematologic malignancy. The mortality rate is 40% among patients who acquire the bacteria nosocomially.