Nondrug Intervention for Opportunistic Infections in Individuals With Hematological Malignancy: Systematic Review
Authors: Muhamad Nor Asiah , Ma'amor Nur Hasnah , Mustapha Normi , Leman Fatin Norhasny , Rosli Izzah Athirah , Umar Marilyn , Aris Tahir , Lai Nai Ming 
Published: March 2023

Background
Hematological malignancies disturb the blood, lymph nodes, and bone marrow. Taking medications for treating opportunistic infections (OIs) in these individuals may enhance the risk of medication interaction as well as adverse drug reactions.

Objective
This review aims to evaluate the effectiveness of nondrug interventions in reducing OIs among patients with hematological cancers.

Methods
The PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase databases were searched on December 26, 2022, for all randomized controlled trials (RCTs). The primary endpoint was OIs. The quality of included studies was assessed by the Cochrane Risk-of-Bias tool.

Results
A total of 6 studies were included in this review with 4 interventions: (1) types of mouthwash received, (2) presence of coating on central venous catheters (CVCs), (3) use of well-fitted masks, and (4) types of diet consumed. The results were presented in 8 different comparisons: (1) chlorhexidine-nystatin versus saline mouth rinse, (2) chlorhexidine versus saline mouth rinse, (3) nystatin versus saline mouth rinse, (4) chlorhexidine silver sulfadiazine–coated CVCs versus uncoated catheters, (5) well-fitted masks versus no mask, (6) amine fluoride-stannous fluoride versus sodium fluoride mouthwash, (7) low-bacterial diet versus standard hospital diet, and (8) herbal versus placebo mouthwash. No clear differences were reported in any of the outcomes examined in the first 3 comparisons. There were also no clear differences in the rate of catheter-related bloodstream infection or insertion site infection between the use of chlorhexidine silver sulfadiazine–coated CVCs versus uncoated catheters in the patients. Further, no significant differences were seen between patients who used a well-fitted mask and those without a mask in the incidence of OI. The all-cause mortality and mortality due to OI were similar between the 2 groups. There was no clear difference in all-cause mortality, although common adverse effects were reported in patients who used sodium fluoride mouthwash compared with those using amine fluoride-stannous fluoride mouthwash. There was no evidence of any difference in the incidence of possible invasive aspergillosis or candidemia between patients who consumed a low-bacterial diet and a standard diet. For the last comparison, no significant difference was seen between patients who received herbal and placebo mouthwash.

Conclusions
Very limited evidence was available to measure the effectiveness of nondrug interventions in hematological cancers. The effectiveness of the interventions included in this review needs to be evaluated further in high-quality RCTs in a dedicated setting among patients with hematological malignancies.

Trial Registration
PROSPERO International Prospective Register of Systematic Reviews CRD42020169186; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=169186