Nondrug Intervention for Opportunistic Infections in Individuals With Hematological Malignancy: Systematic Review

Interactive Journal of Medical Research · 8 authors, 5 centres

AI SUMMARY

FIDELITY 97%

POPULATIONAdult patients with hematological malignancies (leukemia, lymphoma, Hodgkin disease) including those receiving chemotherapy or stem cell transplantation

INTERVENTIONNondrug interventions: chlorhexidine-nystatin mouth rinse, chlorhexidine mouth rinse, nystatin mouth rinse, chlorhexidine silver sulfadiazine–coated central venous catheters, well-fitted FFP2 masks, amine fluoride-stannous fluoride mouthwash, low-bacterial diet, herbal mouthwash

COMPARISONSaline mouth rinse, uncoated catheters, no mask, sodium fluoride mouthwash, standard hospital diet, placebo mouthwash

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TL;DR

This systematic review of 6 randomized controlled trials found very low-quality evidence on the effectiveness of nondrug interventions (mouthwash types, coated central venous catheters, well-fitted masks, and low-bacterial diet) for preventing opportunistic infections in patients with hematological malignancies. No intervention showed a clear benefit over controls for any major clinical outcome, including infection rates, mortality, or oral mucositis. The authors conclude that high-quality RCTs are urgently needed before any firm practice recommendations can be made.

Full summary

4,063 CHARS

**Background:** Hematological malignancies are cancers of the blood, bone marrow, and lymph nodes. Patients are highly susceptible to opportunistic infections (OIs) due to both disease-related immune impairment and immunosuppressive cancer therapies. OIs affect 5%-60% of these patients, with mortality ranging from 15% to 41%. While pharmacological treatments carry risks of drug interactions and adverse reactions, nondrug interventions (barrier methods, environmental controls, personal hygiene modifications) may offer safer alternatives. This systematic review aimed to evaluate the effectiveness of nondrug interventions for preventing OIs in patients with hematological cancers.

**Methods:** The review followed PRISMA guidelines and searched PubMed, CENTRAL, and Embase databases from inception to December 26, 2022. Additional searches included conference archives and clinical trial registries. Eligible studies were RCTs or cluster RCTs involving adult patients with hematological cancer, comparing any nondrug intervention (alone or combined) against no intervention, placebo, or pharmacological prophylaxis. Primary outcomes included OI incidence, all-cause mortality, and OI-related mortality. Two authors independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk-of-Bias tool. Meta-analysis was not possible as no comparison included more than one study with usable data.

**Key Results:** From 4700 initial records (1746 CENTRAL, 1067 MEDLINE, 1887 Embase), 4641 remained after deduplication, 4615 were excluded, 26 full texts were assessed, and 6 studies (519 participants) were included. Four intervention types were identified across 8 comparisons: (1) mouthwash types, (2) coated central venous catheters (CVCs), (3) well-fitted masks, and (4) diet. For chlorhexidine-nystatin vs. saline mouth rinse (n=52), no clear difference was found in mucositis score (MD 0.96, 95% CI –0.09 to 2.01) or ulcer size (MD 1.65 mm, 95% CI –7.48 to 10.78). Chlorhexidine vs. saline (n=36) showed no difference in mucositis (MD 0.56, 95% CI –0.59 to 1.71) or ulcer size (MD 2.17 mm, 95% CI –8.17 to 12.51). Nystatin vs. saline (n=34) showed no difference in mucositis (MD 0.90, 95% CI –0.23 to 2.03). For chlorhexidine silver sulfadiazine–coated CVCs vs. uncoated (184 catheters), coated catheters reduced colonization (RR 0.37, 95% CI 0.20 to 0.69) but not catheter-related bloodstream infection (RR 0.45, 95% CI 0.12 to 1.68) or insertion site infection (RR 0.94, 95% CI 0.66 to 1.33). Well-fitted masks vs. no mask (n=80) showed no difference in possible (RR 0.48, 95% CI 0.09 to 2.45), probable (RR 1.90, 95% CI 0.37 to 9.81), proven aspergillosis (RR 0.95, 95% CI 0.14 to 6.43), combined OIs (RR 0.95, 95% CI 0.40 to 2.29), all-cause mortality (RR 1.00, 95% CI 0.14 to 6.93), or OI mortality (RR 1.00, 95% CI 0.06 to 15.71). Amine fluoride-stannous fluoride vs. sodium fluoride mouthwash (n=152) showed no difference in all-cause mortality (RR 0.67, 95% CI 0.11 to 3.88) but higher adverse effects with sodium fluoride (RR 9.33, 95% CI 1.34 to 64.89). Low-bacterial vs. standard diet (n=20) showed no difference in possible invasive aspergillosis (RR 0.2, 95% CI 0.01 to 3.70) or candidemia (RR 1.00, 95% CI 0.07 to 13.87). Herbal vs. placebo mouthwash (n=60) showed no difference in oral mucositis (RR 0.81, 95% CI 0.64 to 1.04). Overall risk of bias varied; most studies had insufficient information on selection bias and half had high performance bias due to lack of blinding.

**Clinical Implications:** The evidence for all nondrug interventions examined is of very low quality, precluding any firm clinical recommendations. Coated CVCs reduced catheter colonization but not bloodstream infections or mortality. The lack of demonstrated benefit must be weighed against costs, feasibility, and potential adverse effects. High-quality, adequately powered RCTs in dedicated hematological malignancy settings are urgently needed to guide evidence-based infection prevention practices in this vulnerable population.

PICO

PPOPULATION

Adult patients with hematological malignancies (leukemia, lymphoma, Hodgkin disease) including those receiving chemotherapy or stem cell transplantation

IINTERVENTION

Nondrug interventions: chlorhexidine-nystatin mouth rinse, chlorhexidine mouth rinse, nystatin mouth rinse, chlorhexidine silver sulfadiazine–coated central venous catheters, well-fitted FFP2 masks, amine fluoride-stannous fluoride mouthwash, low-bacterial diet, herbal mouthwash

OOUTCOME

Opportunistic infections (including aspergillosis, candidemia, catheter-related bloodstream infections), all-cause mortality, mortality due to OI, oral mucositis scores and ulcer size, catheter colonization, adverse effects

STUDY TYPE

systematic_review

SPECIALTY

hematology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

97% · A

ORIGINAL PAPER

PMC10132047

Nondrug Intervention for Opportunistic Infections in Individuals With Hematological Malignancy: Systematic Review

Interactive Journal of Medical Research

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ABSTRACT

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

CITATION EXPORT

Nor Asiah Muhamad, Nur Hasnah Ma'amor, Normi Mustapha et al.. Nondrug Intervention for Opportunistic Infections in Individuals With Hematological Malignancy: Systematic Review. Interactive Journal of Medical Research. (2023). https://doi.org/10.2196/43969

AUTHORS

8 · 5 CENTRES

Nor Asiah Muhamad, Nur Hasnah Ma'amor, Normi Mustapha, Fatin Norhasny Leman, Izzah Athirah Rosli, Marilyn Umar, Tahir Aris, Nai Ming Lai

1 Sector for Evidence-based Healthcare National Institutes of Health Ministry of Health Shah Alam Malaysia
2 Faculty Science and Technology Open University Kuala Lumpur Malaysia
3 Non-Communicable Disease Section, Sarawak State Health Department Ministry of Health Sarawak Malaysia
4 Director's Office, Institutes for Medical Research National Institutes of Health Ministry of Health Shah Alam Malaysia
5 School of Medicine, Faculty of Health & Medical Sciences Taylor's University Subang Jaya Malaysia

EDITOR / REVIEWER

Amaryllis Mavragani, Aliza Mohd Yacob, Vincent Gosselin Boucher, Kim An Nguyen