Prevention, management of health care-associated infections critical to cancer care

The most recent data from the CDC suggest 1.7 million health care-associated infections occurred in the United States in 2002.

Approximately 100,000 people died from causes related to those infections, including 40,000 from pneumonia and 30,000 from bloodstream infections.

Although all hospitalized patients are at risk for acquiring health care-associated infections (HAIs), those with cancer — specifically solid tumors, hematological malignancies and those treated with invasive devices — are at increased risk. Those patients often are immunocompromised, making it easier for bacteria and viruses to strike the immune system.

“Cancer patients are probably the highest risk group for HAIs,” Jorge Parada, MD, MPH, professor of medicine and medical director of the infection control program at Loyola University Health System in Maywood, Ill., told HemOnc Today. “Many of these patients are receiving chemotherapy, but these chemotherapy agents also do collateral damage to their healthy cells, especially white blood cells. In these patients, we often see their ability to fight off infection drop dramatically because white blood cells are the ‘front-line army’ used to combat infections.”

HemOnc Today spoke with Parada and several other experts about why patients with cancer are so susceptible to infections, how infections complicate cancer treatment and the best ways to prevent infections in this high-risk population.

“Most of us don’t realize the benefit of having a competent immune system that keeps us well, despite being constantly exposed to organisms that can potentially cause infections,” Parada said. “It’s one of those things that you don’t miss until it’s gone. When you suddenly don’t have these defenses, these organisms can invade and cause very aggressive infections.”

Increased susceptibility

The immunosuppression that patients with cancer face can be the result of the cancer itself, according to Brian Bolwell, MD, FACP, chairman of the Taussig Cancer Institute at Cleveland Clinic. Leukemia, for example, generates malignant white blood cells and suppresses the number of normal white blood cells.

“Chemotherapy not only lowers the white blood cell count, but it can also alter other parts of the immune system and make people susceptible to infections,” Bolwell said in an interview. “Even newer therapies frequently carry the side effect of potential damage to different parts of the immune system.”

Besides the effect on white blood cells, aggressive chemotherapy regimens are associated with mucositis and bloodstream infection due to gut bacteria. Additionally, invasive devices such as indwelling catheters pose an infectious risk for patients with cancer, according to Lynne Strasfeld, MD, associate professor of medicine in the division of infectious diseases at Oregon Health & Science University’s Knight Cancer Institute.

“Many patients with cancer have indwelling catheters,” Strasfeld said. “Although a necessary element for treatment, these devices represent a potential portal of entry for bacteria and can result in catheter-related bloodstream infections.”

Tumors themselves also can be a reason behind infections. Solid tumors cause blockages of a bioduct or the urinary tract, for example.

When these blockages happen, they can allow secretion and bacteria to build up behind the blockage and cause infection, said Erik Dubberke, MD, assistant professor of medicine and director of the section for transplant infectious diseases at Washington University School of Medicine in St. Louis.

“As solid tumors get bigger and become necrotic, bacteria can get into the tumor,” Dubberke said in an interview. “Thus, the tumor provides a protected area for the bacteria to cause infections that are difficult for the immune system to get to.”

Clostridium difficile

Clostridium difficile infections (CDI) — bacterial infections that often develop in patients who have illnesses that require prolonged use of antibiotics — lead to about 14,000 deaths each year, according to the CDC.

They are among the most common infections experienced by cancer patients. Symptoms can include severe diarrhea, fever, nausea, abdominal pain and loss of appetite.

CDIs are increasing in frequency and severity for several years for three reasons — an increasing number of patients at risk, increased nosocomial transmission and the emergence of the hypervirulent strain NAP1/BI/027.

Researchers investigating the causes of infections in cancer patients published results of a laboratory study in Infection and Immunity in January. Their findings suggest just one dose of the commonly prescribed antibiotic clindamycin could increase a patient’s susceptibility to CDI.

Researchers at the Sloan-Kettering Institute, an affiliate of Memorial Sloan-Kettering Cancer Center, embarked on the study to determine whether clindamycin eliminates many forms of nonharmful bacteria in a patient’s intestine, thereby making it easier for C. difficile and other harmful bacteria to thrive.

In the study, 40% of mice that were given clindamycin and exposed to

C. difficile died of severe weight loss, and those that were given only one dose of the antibiotic were susceptible to infection for up to 10 days, the researchers said.

Eighty-seven percent of bacterial species that were present prior to treatment with antibiotics were destroyed, DNA sequencing results showed.

“Loss of bacterial diversity can allow Clostridium difficile, normally a small part of the microbial makeup in the intestines, to take over,” Eric G. Pamer, MD, head of the division of general medicine at Sloan-Kettering Institute, said in a press release. “Understanding the mechanisms by which nonharmful bacteria protect against infection with more harmful pathogens is an important and exciting frontier in research. Our ultimate goal is to identify bacterial species that prevent Clostridium difficile-caused colitis and to find ways to replenish them in vulnerable patients.”

Treatment complications

Infections can pose significant risks to a patient’s cancer outcome because the infection most often must be treated before cancer treatment can begin or continue.

“Any sort of infection can complicate cancer treatment,” Kent Sepkowitz, MD,

attending physician in the infectious diseases service and leader of the infection control program at Memorial Sloan-Kettering Cancer Center, told HemOnc Today. “If a patient develops an infection after surgery to remove a tumor, and the patient’s treatment plan includes chemotherapy after surgery, then the chemotherapy would need to be delayed while the patient’s infection is treated. The need to delay or adjust cancer treatment is a real problem.”

Roy Chemaly, MD, associate professor in the department of infectious diseases and director of the infection control program at The University of Texas MD Anderson Cancer Center, said it is important to control the infection before “hitting” a patient’s immune system again, especially with chemotherapy. When treatment is delayed for some cancers, it may have an effect on the patient’s cancer outcome or prognosis.

Special considerations

There are several things to consider when treating this patient population. One is to be aware of the potential for uncommon infections that patients with compromised immune systems may acquire.

“These infections may require different diagnostic procedures than one might normally use when trying to diagnose infections,” Bolwell said. “Fungal infections and specific viral infections, which may be uncommon in the normal population, can be common in patients with cancer.”

Treating infections in patients with cancer also can prove to be problematic and, therefore, drug interactions should be considered.

Many broad-spectrum antimicrobial agents may interact with chemotherapy agents as well as other medications, Chemaly said.

Some antibiotics can affect the level of cancer treatment drugs in the body, requiring a dosage adjustment of the chemotherapy to make sure the levels stay in the right range.

Another issue to consider is that the adverse effects of antimicrobial therapies often mimic those of chemotherapy.

“Antimicrobials are not benign therapy, especially in patients with cancer,” Chemaly said. “They can put the patient at risk for serious side effects, like allergic reactions, and some antiviral medications can affect the kidneys or cause low white blood cell counts.”

When patients with cancer present with an infection, it is necessary to determine whether the infection is potentially communicable and whether the patient should be in isolation to prevent the spread of the infection to other immunocompromised patients.

“We take extraordinary measures to lower the risk for transmission,” Sepkowitz said. “As molecular diagnostics have improved, we can diagnose infections faster and get the patient into isolation faster. There should be an ‘isolate first, then send off the confirmatory test’ approach to dealing with possible infections. We would much rather isolate those who didn’t need to be isolated, than to find out too late that somebody should have been isolated.”

Fungal infections are a concern for patients with cancer because antifungal agents, more often than antibiotics, have drug-drug interactions, Parada said. In addition, fungal infections, such as aspergillosis, can result in life-threatening invasive pulmonary infections that can pose risk for serious morbidity and even mortality, Strasfeld said.

Another common infection is pneumonia — bacterial, fungal or viral. Pneumonia can arise from common respiratory viral infections, can be life-threatening and can be hard to treat in patients with cancer, Chemaly said.

Prevention efforts

The CDC estimates the overall annual direct medical cost of health care-associated infections across US hospitals ranges from $28.4 billion to $45 billion. With the addition of infection control interventions, the annual direct cost could decrease by between $5.7 billion and $31.5 billion.

“The best way to treat infections in patients with cancer is to prevent them,” Parada said. “A tremendous amount of effort should be made to prevent infections. This can be as simple as advising our patients to take certain precautions, such as avoiding raw foods — as there may be pathogens in the food — or not having plants or flowers in their room.”

All of the measures used to prevent infections in hospitalized patients are especially important when treating patients who have cancer. The most important of these measures is hand hygiene.

“We like to see 100% compliance of hand washing measures, regardless of whether it’s a patient with cancer or another patient,” Dubberke said.

For those with indwelling catheters, it is important for hospital staff to follow correct procedures when changing catheters to prevent catheter-related infections. Catheter care bundles have been adapted to access and manage intravascular device systems, Strasfeld said. These bundles have been shown to reduce the risk for catheter-related infections. Many hospitals also use checklists that encourage every caregiver to be methodical with regard to sterile techniques for handling catheters.

A major risk factor for fungal infections is ongoing construction at hospitals, Dubberke said. In this case, proper precautions must be taken to make sure that fungal spores in the soil or duct work are not aerosolized and exposed to patients.

In addition, a common feature in hospitals — healing gardens — may pose a risk for Legionnaires’ disease outbreaks associated with water features. When these gardens are designed, infection prevention should be considered early on in the decision-making process.

“All of these methods of prevention are extremely important to cancer patients because the morbidity of the infections tends to be more severe in patients with cancer than in other populations,” Bolwell said. “A huge part of what we do in clinical care of patients with cancer is to try to prevent and manage infections, because the risk for significant complications is so large.” – by Emily Shafer

References:

• Buffie CG. Infect Immun. 2012;80:62-73.
• Klevens RM. Public Health Rep. 2007;122:160-166.
• Scott RD. The direct medical costs of health care-associated infections in US hospitals and the benefits of prevention, 2009. Available at: www.cdc.gov/HAI/pdfs/hai/Scott_costpaper.pdf.

Disclosures:

• Drs. Bolwell, Chemaly, Dubberke, Parada, Sepkowitz and Strasfeld report no relevant financial disclosures.

What is the appropriate protocol for treating a neutropenic cancer patient who has symptoms of infection but no positive cultures?

It is very common for cancer patients to experience neutropenic fever when they are on chemotherapy. Typically, you want to treat infectious diseases by isolating the organism and determining the antibiotic based on the organism. However, this isn’t always possible.

Traditionally, gram-negative organisms have been considered the worst, because they lead to complications and death faster than other organisms. As a result, you want to start treatment with an antibiotic that definitely covers gram-negative organisms. In addition, most cancer patients have some type of catheter, which serves as a portal of entry for gram-positive organisms.

Empiric coverage for someone who is neutropenic should include two antibiotics, one for gram-negative coverage and one for gram-positive coverage. For gram-negative organisms, we use third-generation cephalosporins, and for gram-positive organisms, we use penicillin-based antibiotics or vancomycin.

Typically, for most patients with neutropenia, the only symptom is neutropenic fever. Once the fever is resolved, antibiotic treatment should continue for 2 weeks, or until the patient is no longer neutropenic. Duration of treatment depends on the duration of the neutropenia.

Robert W. Chen, MD, is a staff physician and assistant professor of hematology and hematopoietic cell transplantation at City of Hope in Duarte, Calif. Disclosure: Dr. Chen reports no relevant financial disclosures.

Patients who receive chemotherapy frequently develop neutropenic fever, and a source is identified by positive culture in less than 30% to 50% of these cases. Hence, the majority of patients with neutropenic fever require empirical antibiotic therapy, until either resolution of the fever or the neutropenia.

The Infectious Diseases Society of America published the updated treatment guidelines for cancer patients with neutropenic fever in 2010. Broad-spectrum antibacterial agents — such as cefepime or piperacillin-tazobactam — are usually started, and if fevers persist or the patient is unstable, transition to meropenem with or without an aminoglycoside is recommended.

Based on the patient’s status, risks, presence of lines and concerns for possible gram-positive infection, vancomycin may be added to the regimen. However, a significant number of these patients will continue to have fevers, despite broad-spectrum antibacterial coverage. In such cases, and based on multiple different studies, a broad-spectrum antifungal agent is routinely started 5 to 7 days later. This is based on the presumption that a fungal infection may be the source of neutropenic fever.

Dennis Neofytos, MD, is assistant professor for the division of infectious diseases, and a member of the transplant and oncology infectious disease service at Johns Hopkins University. Disclosure: Dr. Neofytos received research grants from Pfizer and participated in scientific advisory boards for Roche.