Prophylactic Antibiotics Reduce Mortality in Highly Immunocompromised Cancer Patients

Roxanne Nelson

December 23, 2008

December 23, 2008 — The mortality risk in immunocompromised cancer patients can be significantly reduced by a combination of prophylactic antibiotics, barrier isolation, and air-quality-control measures. These interventions have been shown to reduce all-cause mortality by 40% at 30 days posttreatment. However, according to the results of a meta-analysis published online December 17 in Lancet Infectious Diseases, prophylactic antibiotics are the most effective treatment within the protective environment.

Israeli researchers observed that improved survival among this population was demonstrated only when antibiotic and antifungal prophylaxis was used in conjunction with air-quality control or barrier isolation. The relative risk (RR) of mortality was 0.66 among patients who were given prophylaxis, as compared with an RR of 0.93 when antimicrobial prophylaxis was not used.

"Our belief is that antibiotic and antifungal prophylaxis should be used in conjunction with isolation precautions," said author Mical Paul, MD, from the unit of infection control at Rabin Medical Center and Sackler faculty of medicine at Tel-Aviv University, in Israel. "This [view] is based on a reduction in mortality with the use of prophylaxis alone and the fact that infection-control interventions without prophylaxis did not reduce mortality, as shown in our paper."

Dr. Paul points out that there are strong opinions both in favor of and against antibiotic prophylaxis. "The opinions against are based on current resistance profiles of bacteria in oncologic patients, the fear of further resistance, and the fact that Clostridium difficile, induced by antibiotic treatment, is on the rise in cancer patients in general and hemato-oncological patients in particular," he told Medscape Oncology.

In their review, however, they did not find that the beneficial effect of antibiotic prophylaxis had decreased in recent years as compared with older studies, thus lending support to the continued use of prophylaxis. "But the debate is ongoing," he said.

Infections Risks Vary, Guidelines Limited

Infections are a frequent complication of cancer treatment and are the most common preventable cause of death in cancer patients, the researchers note. A number of strategies are employed to prevent infection, including correction of neutropenia or other immunological deficiencies, prophylaxis and preemptive antimicrobials, and infection-control interventions that range from simple measures such as hand hygiene and use of barriers (eg, gowns, gloves, masks) to protective isolation that includes air-quality control.

The researchers point out that cancer patients vary considerably in their risk for infection, with those undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) and/or who have acute leukemia at the highest risk. However, formal guidelines regarding infection control currently address only HSCT patients. Current Centers for Disease Control and Prevention guidelines recommend protective isolation only for patients undergoing allogeneic HSCT, the authors point out in their paper, but precautions should be tailored to the individual patient.

"The protective effect of combined intervention on mortality was similar among patients undergoing allogeneic HSCT and those with acute leukemia and autologous HSCT assessed in the studies included in our review," explained Dr. Paul. "Consideration should be given to identifying high-risk patients with acute leukemia and to provide full protective measures for these patients as well."

Reduction in All-Cause Mortality

Dr. Paul and colleagues conducted a systematic review of prospective comparative studies with the goal of quantifying evidence for infection-control interventions among high-risk cancer patients and recipients of HSCT.

The analysis included 40 studies published between 1971 and 2008, of which 26 assessed protective isolation. Patients with acute leukemia were included in 29 studies, and in 22 studies all patients underwent HSCT. None of the papers reviewed addressed patients with solid tumors, who were at a lower risk of infection.

Results of the analysis showed that a protective environment, which included air-quality control, prophylactic antibiotics, and barrier isolation, was associated with a significant reduction in all-cause mortality at 30 days (RR 0.60), 100 days (RR 0.78), and at the longest available follow-up between 100 days and 3 years (RR 0.86). But without the use of prophylactic antibiotics, control of air quality and barrier isolation did not show an effect on survival.

In 3 nonrandomized trials (5154 patients), the control of air quality alone proved beneficial, but this benefit did not reach significance in the 2 randomized studies (66 patients). There were 11 nonrandomized prospective studies that evaluated inpatient vs outpatient management following autologous stem-cell transplantation, and all-cause mortality was lower in the outpatient setting (RR 0.72)

Need for Further Studies

The authors note that contemporary data on infection-control practices in bone-marrow transplantation and other cancer centers are largely lacking, as the last survey of 180 centers listed in the European Group for Bone and Marrow Transplantation was conducted nearly a decade ago. They were also unable to find data on current practice in the United States.

However, they point out that there may be a need for further study of barrier precautions, given the high rates of resistant pathogens in hospitals. Barrier precautions might also increase the efficacy of prophylaxis and permit improvements in empirical treatment by reducing cross-transmission of resistant nosocomial microbes.

"The question is whether randomized controlled trials on air filtration and other infection-control measures are ethical," said Dr. Paul. "As mentioned in our paper, in locations where these interventions are not routine or not available to all patients, trials would be ethical. Alternatively, well-conducted observational studies are important."

Further studies are needed for a range of related topics. Assessing the safety of outpatient management in randomized trials is important, as well as assessing simpler interventions for lower-risk cancer patients with neutropenia, which were not evaluated in any of the available studies, explained Dr. Paul. "New studies assessing full infection-control intervention are needed, especially looking at the applicability of studies done in the 1970s and 1980s to current and future practice."

The authors declare no conflicts of interest.

Lancet Infect Dis. Published online December 17, 2008. Abstract

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