Infections continue to be a major cause of morbidity and mortality in cancer patients, particularly in those receiving intensive chemotherapy, or undergoing hematopoietic cell transplantation. Antimicrobial agents are commonly prescribed to these populations for both treatment and prevention of infectious complications. Benchmarking studies demonstrate high antimicrobial utilization on oncology and hematopoietic cell transplant units. Antimicrobial stewardship efforts, to optimize not only the selection but also dosing and duration of anti-infective therapy, are extremely relevant to this particular patient population. Cancer patients are not a homogenous group in terms of infectious risk. Patient level factors dictate an individual's infectious risk. These include the net state of immunosuppression, the level of organ dysfunction and pathogen exposure. The net state of immunosuppression takes into account; tumor burden, neutropenia, treatment-related effects on humoral immunity, cellular immunity and splenic function, nutritional status and the presence of other co-morbidities. Host defenses are also contingent on proper organ function. This includes intact skin, Patient mucosal lumens and intact lymphatics. When these are breached, patients can develop infections. Breaks in the skin due to vascular access devices, radiation damage or surgical incisions can lead to central line-related infections or skin and soft tissue infections. Mucosal lumens can be affected either by chemo and/or radiation-induced inflammation such as mucositis ortoflytis or by tumor instruction. Finally, lymph node dissection can lead to recurring episodes of cellulitus in the affected region. Infections arise from two types of pathogen exposure. Endogenous, meaning the patient's own flora or exogenous environmental pathogens such as respiratory viruses. Those who have impairments and cellular immunity can also reactivate latent infections such as Pneumocystis jiroveci, Toxoplasma gondii or cytomegalovirus. Disease-pecific risk factors also influence the infectious risk faced by oncology and hematopoietic cell transplant patients. Several common risk factors for different types of cancer diagnoses are listed in the following tables. Risk factors for infection that are shared by solid tumor patients include obstruction of bronchi, intestines, ureters or bile ducts by tumor; local tissue injury from chemo or radiation therapy; postoperative infections; the presence of vascular access devices, and; malnourishment. If neutropenia secondary to chemotherapy occurs, it is generally mild and resolves within a week. In contrast, patients with hematologic malignancies or recipients of hematopoietic cell transplantation can have significant neutropenia, varying degrees of a asplenia, hypogammaglobulinemia, or T-cell defects. They have extended use of vascular access devices, frequent blood product administration, clinically significant mucositis, and more frequent prolonged anti-infective use. Autologous transplant recipients have fewer infectious complications than their allogeneic counterparts and their infections occur when they are neutropenic. For allogeneic transplant patients, the types of infections to which they are most vulnerable can be roughly divided based upon the time elapsed from transplantation, and can be visualized in this figure from the 2009 guideline for preventing post-transplant infectious complications by Tomblyn et al. The specialized nature of oncology and transplant medicine lend itself nicely to antimicrobial stewardship programs since health care providers in these fields are used to working in multidisciplinary teams. Collaborating together to create local guidelines is a simple way to get prescriber cooperation. Evidence-based infectious disease guidelines on a number of topics from the United States and Europe are available. These include for example the management of fever and neutropenia, the prevention of opportunistic infections, and hematopoietic cell transplant recipients and management of invasive Aspergillosis. However, these should be modified within the parameters of an institution-specific patient characteristics, resources and local epidemiologic factors. Implementing these guidelines and providing feedback to the prescribers is also essential. For example routine antibiotic prophylaxis was not practice before 2006 at a Tertiary Cancer Center in New York City, but the prevention of pre-engraftment viridans streptococcal sepsis and allogeneic hematopoietic cell transplant patients was a high priority due to an incidence of 7.4% and an attributable mortality of 21%. Vancomycin base prophylaxis was started in 2006 and was associated with complete elimination of viridans streptococci bacteremia in a joint antimicrobial stewardship, infectious disease and transplant service analysis. Ongoing surveillance is being conducted to follow changes in epidemiology and resistance patterns. Other key partners for antimicrobial stewardship programs include: the pharmacy and therapeutics committee, to ensure that appropriate antimicrobial agents are available to support oncology and hematopoietic cell transplant patients; clinical pharmacists who can assist with extended interval dosing for serious gram-negative infections and therapeutic drug monitoring; the microbiology laboratory for the timely diagnosis of infections including adoption of rapid diagnostics; and infection control to assist in analyzing the relationship between antibiotic use and trends and microbial resistance. Adoption of health care information technology, the electronic medical records, computer order entry and clinical decision support facilitates antimicrobial stewardship efforts by improving prescribing and reducing medication errors. Fever and neutropenia is a common problem that occurs during receipt of cytotoxic therapy for the underlying malignant disease. The 2010 Infectious Diseases Society of America guideline provides a blueprint for the antimicrobial management of febrile neutropinic patients. Adherence to these guidelines is an easy target for stewardship programs. One key point that this guideline emphasizes is a categorization of neutropinic patients into high versus low risk to determine the delivery, venue and duration of empiric therapy. High-risk patients are anticipated to have an absolute neutrophil count less than 100 for more than seven days after cytotoxic chemotherapy and/ or have significant co-morbidities such as hypotension, pneumonia, new onset abdominal pain, or neurologic symptoms. These patients should be admitted for intravenous therapy. Low-risk patients or neutropinic for less than seven days with few or no co-morbidities. They can receive initial oral or intravenous doses in a clinic or hospital and then be transitioned to outpatient oral or intravenous treatment, provided they meet specific criteria. The combination of an oral quinolone and Amoxicillin clavulanate is a well-studied regimen. If outpatient therapy is arranged, then vigilant observation and prompt access to medical care should be ensured 24 hours a day, seven days a week. Patients whose clinical condition worsens should be able to reach their local medical facility within an hour. Recurrent fever or new signs of infection warrant admission and management as for high-risk patients. Stewardship programs can create an institution-specific guidelines for the management of febrile neutropenic patients. In addition, because multi-drug resistant gram-negative bacteria are increasingly responsible for infections in this population, antimicrobial stewardship teams can assist prescribers in making modifications to initial empiric therapy for patients who are known to be colonized and/or have prior infection due to multi-drug resistant organisms as clinically warranted. Established stewardship strategies such as prospective audit and feedback, and antimicrobial deescalation can be effectively performed in cancer patients. While complete adherence is not likely to occur, clinical guidelines that are geared toward common infectious problems such as fever and neutropenia, or management of invasive Aspergillosis can improve clinical outcomes in this patient population. Finally, the disproportionate use of antifungal drugs in immunocompromised patients has also led to an emerging literature on antifungal stewardship. Several institutions have used a multipronged approach incorporating pre-authorization and/or prospective audit and feedback in addition to education and guideline development to improve antifungal prescribing. In conclusion, cancer and hematopoietic cell transplant patients are important targets for antimicrobial stewardship since they are frequently exposed to prolonged courses of anti-infective agents. Antimicrobial stewardship team members should appreciate that these patients can have varying immunosuppressed states that then inform their infectious risks. Being able to assess the type and degree of immunosuppression, thus requires a level of expertise by antimicrobial stewardship personnel involved in the care of cancer patients. US and European guidelines are available as resources for antimicrobial stewardship teams to develop locally relevant guidelines. Finally, there is a slowly growing body of literature that shows an antimicrobial stewardship programs can effectively apply a variety of established stewardship strategies in the oncologic and hematopoietic cell transplant patient population
