Results of a study conducted in Switzerland indicate that selective digestive decontamination, a controversial strategy designed to reduce the risk of in­fec­tions, may be effective in myeloma patients undergoing au­tol­o­gous (own) stem cell trans­plan­ta­tion.

The authors of the new study retro­spec­tive­ly reviewed data for over 200 myeloma patients who underwent an inpatient stem cell trans­plant at two hos­pi­tals in Zurich, Switzerland, be­tween 2009 and 2015. About half the patients underwent selective digestive decontamination (SDD) during their trans­plants, while the other half did not.

The patients who underwent SDD were sig­nif­i­cantly less likely to devel­op bacterial in­fec­tions during their inpatient stay for trans­plan­ta­tion com­pared to patients who did not undergo SDD.

Only 8 per­cent of the patients who underwent SDD devel­oped a bacterial in­fec­tion, com­pared to 24 per­cent of the patients who did not undergo SDD.

Patients undergoing SSD also were noticeably less likely to develop neu­tro­penic fever (high fever accompanied by a low white blood cell count) while in the hos­pi­tal for their trans­plant.

Selective digestive decontamination involves the use of multiple antibiotics to sig­nif­i­cantly reduce bacteria levels in a patient’s digestive sys­tem. Its goal is to reduce the patient’s risk of devel­op­ing a serious in­fec­tion. SDD is controversial because its use could en­cour­age the spread of antibiotic-resistant bacteria.

In the Swiss study, the researchers did not find evi­dence that SDD led to the devel­op­ment of resistant strains of bacteria. The authors note, how­ever, that this finding should be interpreted with caution, as the patients in their study were not routinely tested for the presence of resistant bacteria. In addi­tion, antibiotic resistance has not been an issue at the hos­pi­tals where the patients in the Swiss study received their trans­plants.

Based on their findings, the Swiss researchers believe that SDD should be con­sidered as a strategy to reduce the risk of serious in­fec­tions in myeloma patients undergoing au­tol­o­gous stem cell trans­plants. The authors also rec­om­mend that further studies be carried out to assess both the poten­tial benefits and the poten­tial risks of carrying out SDD during au­tol­o­gous stem cell trans­plants.

Background

Two common com­pli­ca­tions of stem cell trans­plan­ta­tion are low white blood cell counts and mucositis, an inflammation of the mucous membranes lining the mouth and the rest of the digestive track. The com­bi­na­tion of low white blood cell counts and mucositis make stem cell trans­plant patients par­tic­u­larly sus­cep­tible to in­fec­tions.

Various strategies have been in­ves­ti­gated to reduce the rate of in­fec­tions in cancer patients experiencing treat­ment-related low white blood cell counts, in­­clud­ing patients undergoing stem cell trans­plants. One such strategy is selective digestive decontamination (SDD), which involves the admin­istra­tion of several antibiotics to reduce bacteria and fungi in a patient’s digestive tract. This strategy should reduce the risk of in­fec­tion because, according to the authors of the Swiss study, most in­fec­tions originate from microorganisms in the digestive tract.

Researchers for several decades have been investigating the poten­tial benefit of using SDD in critically ill and immunocompromised patients. Many studies have found that the strategy is effective in reducing in­fec­tions in those patients. SDD is controversial, how­ever, due to con­cerns that using it on a regular basis could en­cour­age the devel­op­ment of bacteria highly resistant to a wide range of antibiotics.

Indeed, con­cerns about the impact of SDD on bacterial resistance have been sufficient to limit its use to a handful of countries in continental Europe. SDD is not commonly carried out in North America, the United Kingdom, Australia, or New Zealand.

There have been several studies in recent years exploring the poten­tial value of SDD in allo­geneic (donor) stem cell trans­plan­ta­tion for patients with leukemia. Little research exists, how­ever, con­cern­ing the poten­tial impact of SDD when used during au­tol­o­gous (own) stem cell trans­plan­ta­tion.

Thus, the authors of the current study sought to assess the benefits and risks of selective digestive contamination in multiple myeloma patients undergoing au­tol­o­gous stem cell trans­plan­ta­tion.

Study Design

The Swiss researchers retro­spec­tive­ly analyzed data for 203 multiple myeloma who received their first au­tol­o­gous stem cell trans­plant be­tween No­vem­ber 2009 and Octo­ber 2015 at the two hos­pi­tals in the Zurich (Switzerland) stem cell trans­plant pro­gram.

Due to dif­fer­en­t SDD-related policies within the Zurich trans­plant pro­gram be­tween 2009 and 2015, some patients underwent SDD during their trans­plants, while others did not. No formal criteria were in place for selecting patients for SDD. Thus, the patients who underwent SDD were very similar to those who did not undergo SDD – just as they would be in a ran­dom­ized clin­i­cal trial designed to in­ves­ti­gate the efficacy and safety of SDD.

Of the 203 patients in the Swiss researchers’ sample, 90 (44 per­cent) underwent selective digestive decontamination during their trans­plant, while 113 patients did not.

SDD at the Zurich trans­plant pro­gram consisted of three orally admin­istered anti­biotics:

1. Vancomycin - to counter gram-positive bacteria, including Clostridium difficile
2. Gentamicin - to counter gram-negative bacteria, including Pseudonomas aeruginosa
3. Amphotericin B - to counter fungal infections.

This three-drug regi­men was slightly dif­fer­en­t, how­ever, in 2013, when metronidazole was used instead of vancomycin.

Patients who underwent SDD during their trans­plants did so for a median of 12.5 days.

Study Results

The results of the researchers’ analysis show that multiple myeloma patients who underwent selective digestive decontamination were sub­stan­tially less likely to ex­peri­ence bacterial in­fec­tions during the inpatient hos­pi­tal stay for their trans­plant than patients who did not undergo SDD.

Among the patients who underwent SDD, only 8 per­cent devel­oped a bacterial in­fec­tion, com­pared to 24 per­cent of the patients who did not undergo SDD.

Patients who underwent SDD ex­peri­enced fewer bacterial in­fec­tions of all types – bloodstream, catheter-related, skin, urogenital, gastro­in­tes­ti­nal, and pul­mo­nary – com­pared to patients who did not undergo SDD. The dif­fer­ence was par­tic­u­larly pronounced, how­ever, for bloodstream bacterial in­fec­tions; 3 per­cent of SDD patients ex­peri­enced bloodstream in­fec­tions versus 13 per­cent of patients who did not undergo SDD.

The researchers also found that patients who underwent selective digestive decontamination were less likely to require addi­tional oral or injected antibiotics during their inpatient stay com­pared to those who did not undergo SDD (62 per­cent versus 77 per­cent).

Mucositis And Neutropenic Fever

Somewhat to their surprise, the Swiss researchers found that SDD may reduce the likelihood of muco­sitis in myeloma patients undergoing a trans­plant. Forty per­cent of the patients who under­went SDD ex­peri­enced no mucositis, com­pared to 22 per­cent who did not undergo SDD.

SDD also appears to de­crease a patient’s risk for develop­ing neu­tro­penic fever (very high fever accompanied by low white blood cell counts) during their trans­plant inpatient stay. Among the patients who underwent SDD, 36 per­cent ex­peri­enced neu­tro­penic fever, com­pared to 58 per­cent of the patients who did not undergo SDD.

Diarrhea

Most of the 203 patients in the Swiss researchers’ sample ex­peri­enced diarrhea during the hos­pi­tal stay for their trans­plants. Patients who underwent SDD, how­ever, were more likely to ex­peri­ence diarrhea, and the average severity of diarrhea was somewhat greater for the patients who underwent SDD.

At the same time, the most severe grade of diarrhea never occurred among the patients in the study who underwent SDD, but it occurred in three of the patients who did not undergo SDD.

Similarly, none of the patients who underwent SDD devel­oped a Clostridium difficile in­fec­tion, com­pared to 4 cases of C. difficile among patients who did not undergo SDD. (C. difficile in­fec­tions can cause diarrhea that is especially debilitating.)

Outcomes Unaffected By SDD

The duration of the inpatient hos­pi­tal stay for the stem cell trans­plant was similar for both patient groups; 14 days for patients who underwent selective digestive decontamination, and 15 days for those who did not.

The remission status 100 days post trans­plant also was com­parable be­tween the two patient groups, and there was no statistically sig­nif­i­cant dif­fer­ence in either pro­gres­sion-free or over­all survival be­tween the two groups (although both survival measures were marginally better for the patients who underwent SDD).

There were three treat­ment-related deaths within 100 days of trans­plan­ta­tion among the 203 patients in the study sample. One death occurred among the 90 patients who underwent SDD, and two deaths occurred among the 113 patients who did not undergo SDD.

Development Of Antibiotic Resistance

The Swiss researchers also in­ves­ti­gated whether the bacteria found in blood samples from patients who underwent SDD revealed signs of antibiotic resistance. In par­tic­ular, they com­pared the antibiotic resistance of the bacteria from those samples to bacterial resistance reported for their hos­pi­tal.

“The resistance patterns of the various pathogens isolated from the blood cul­tures,” the researchers wrote, “did not show higher rates of resistance as com­pared to the reported in­ci­dences of resistance within our institution." The researchers there­fore conclude that the use of SDD "did not result in the devel­op­ment of highly resistant pathogen strains.”

The study authors recog­nize, how­ever, that this finding needs to be interpreted with caution. Resistance testing was carried out using samples from only a limited number of patients in the study who underwent SDD, and antibiotic resistance is not an issue at the Zurich trans­plant center.

For more in­­for­ma­tion, please see the study by Mürner, C. M, et al., “Efficacy of selective digestive decontamination in patients with multiple myeloma undergoing high-dose chemo­ther­apy and au­tol­o­gous stem cell trans­plan­ta­tion,” in Leukemia & Lymphoma, August 21, 2018 (abstract).