Commentary (Baraboutis/Noskin): Management of Health-Care–Associated Infections in the Oncology Patient

Drs. Guinan, McGuckin, and Nowell have nicely reviewed the risk factors associated with increased susceptibility to hospital- acquired infection in oncology patients and also discussed preventive steps to attenuate those risks. We agree that patients with malignancies present a challenge to the health-care provider, as infection will develop at some point in almost all cancer patients[1] and may be associated with significant mortality.[2]

Over the past 2 decades, the advent of more intensive chemotherapy, the introduction of hematopoietic stem cell transplantation and an aging population of patients with neoplastic disease have resulted in an increased susceptibility to a broad array of potential pathogens. A significant portion of these infections are acquired during hospitalization. However, a more accurate description is "health-care associated," as many of these infections are the result of contact with the health-care system. This is particularly true because many patients receive cytotoxic chemotherapy at ambulatory care sites.

Impaired Host Immunity

In general, oncology patients have a compromised immune system compared to that of other patients. As a result of granulocytopenia, impaired mucosal integrity, defects of cellular and humoral immunity, and organ dysfunction, these patients are predisposed to a variety of bacterial, fungal, viral, and protozoal infections. The risk of infection is the product of an interplay between many different lines of defense that can be breached simultaneously.

The authors distinguish between the risk of infection based on the underlying malignancy and the risk related to its treatment. For example, recipients of allogeneic stem cell transplants are at higher risk than patients with solid tumors because of the duration and depth of neutropenia as well as superimposed graft-vshost disease. Alternatively, patients with multiple myeloma or chronic lymphocytic leukemia have impaired humoral immunity, putting them at risk for infections with encapsulated organisms.

Surgical Interventions

Surgery is also problematic in oncology patients, as it may represent another immunosuppressive event in an already compromised host and predispose the patient to a surgical site infection. The risk is highest among malnourished patients undergoing surgery, as they have a significantly higher incidence of both infectious and noninfectious complications as well as death.[3]

Sepsis is one of the most important risk factors for the development of postoperative adult respiratory distress syndrome in the cancer patient.[ 4] Other important risk factors for infection following surgery for malignant disease include the type of surgical procedure, American Society of Anesthesiologists (ASA) physical status, duration of the procedure, diabetes mellitus, obesity, and prolonged presence of surgical drains.[5,6]

Several studies have demonstrated superior survival in postoperative cancer patients as opposed to cancer patients admitted to the intensive care unit (ICU) for "medical" causes.[7,8] Of course, the differences likely represent selection bias, given the fact that cancer patients undergoing surgery usually are in suitable physical condition for an operation. Nevertheless, this suggests that patients benefit from ICU admission after cancer surgery.

Central Venous Access Devices

Semipermanent centrally placed venous access devices are commonly used in cancer patients to administer chemotherapy, blood products, antimicrobial agents, and parenteral nutrition, as well as to obtain blood specimens for laboratory analyses. Central venous catheters (CVCs) reduce the risk for phlebitis but are associated with as much as a 20-fold higher rate of catheter-related infections than peripheral venous catheters.[9]

Subcutaneously implanted ports have been associated with fewer infections than CVCs in patients with solid tumors.[10] In general, patients with solid tumors and any vascular device experience longer infectionfree times compared with those in patients with hematologic malignancies,[ 11] possibly due to different degrees of immunosupression but also because they receive fewer infection- prone catheter manipulations or therapies.

Recently, the use of antimicrobialimpregnated catheters has increased. A meta-analysis of 11 studies-most of them included cancer patients- showed that antimicrobial-impregnated and heparin-bonded CVCs significantly reduced the incidence of catheter-related infections by 2.32% with a modest additional cost, and their use was considered cost-effective.[12] Data on the use of peripherally inserted CVCs also suggest that infection rates are lower than for other centrally placed venous catheters.[13]

Whether the number of catheter lumens affects the rate of catheterrelated infections remains controversial, although in most series,[14,15] the infectious complications and rates of removal increased with the number of lumens. Perhaps the most important factor to reduce the incidence of catheter-related infections is proper insertion of these devices using full barrier precautions.[16]

Hospital Infection Control

Environmental pathogens such as Aspergillus spp and Legionella spp pose a serious threat to immunocompromised patients, especially those with neutropenia. Prospective cohort studies support the use of high-efficiency particulate air (HEPA) filtration for hematopoietic stem cell recipients to reduce exposure to Aspergillus.[ 17] In addition, hospital rooms should be under positive airflow compared to the adjacent hallway, and the room well sealed. Patient travel outside the room should be limited, particularly when he or she is neutropenic. Patients should be separated from construction and renovation sites, and they should be closely monitored by infection control professionals.[18]

Legionella can colonize hospital water systems for long periods, resulting in an ongoing risk to the oncology population, with high-dose steroid use most strongly linked to disease development. Measures to contain outbreaks have included extensive modifications to the water system, hyperchlorination, coppersilver ionization, and reduction of patient exposures to aerosols.[19]

Emerging Pathogens in Cancer Patients

Although the Enterobacteriaceae and Pseudomonas aeruginosa have been classically associated with a high mortality rate in neutropenic cancer patients, in the past decade several cancer centers have noticed a decline in the incidence of gram-negative pathogens followed by an increase in gram-positive bacteria.[20] Factors considered responsible for this changing epidemiology include more aggressive chemotherapy and radiotherapy leading to severe mucositis, profound and prolonged neutropenia, increased long-term use of CVCs, use of H2 blockers, and use of trimethoprim/ sulfamethoxazole and particularly the newer quinolones for prophylaxis.

Among gram-positive organisms, the most important resistant pathogens are oxacillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, penicillin-resistant viridans streptococci, and multidrug-resistant pneumococci. Important examples of resistance among gramnegative organisms include extended- spectrum beta-lactamases in Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis, as well as high-level, third-generation cephalosporin (Amp C) beta-lactamase resistance among Enterobacter spp and Citrobacter freundii.[21] Furthermore, an increasing number of new microorganisms have emerged in the neutropenic host, most of them originating from the patient's endogenous flora but also potentially acquired from the environment (eg, Rhodococcus equi, Burkholderia cepacia, Legionella micdadei).

Similarly, with the more widespread use of antifungal prophylaxis, an increasing frequency of azole-resistant Candida spp as well as invasive infections by new or unusual fungal strains and species are observed in the compromised host with limited therapeutic options.

Conclusions

The management of patients with cancer has become increasingly complex due to rapid changes in the epidemiology of infections in those with host immunity defects. The nature of the underlying malignancy, the immunodeficiencies associated with it, and the treatments directed against it are all important determinants of infection. The increasing use of central venous access devices and antimicrobial prophylaxis have also contributed to these epidemiologic changes. As the epidemiology of infection in cancer patients continues to evolve, it is critical that clinicians use antimicrobial agents judiciously and adhere to well-accepted infection control practices.

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