Effect of alcohol-based hand rub on hand microbiome and hand skin health in hospitalized adult stem cell transplant patients: a pilot study

Healthcare-associated infections cause considerable burden of disease and mortality,¹ and hand hygiene [e.g. using alcohol-based hand rub (ABHR)] is strongly recommended for infection control and prevention.² The effect of hand hygiene on bacterial and fungal microbiome (bacteriome and mycobiome, respectively) of patients has not been investigated.

In this prospective pilot clinical study, we used culture assay and Ion-Torrent sequencing to determine the effect of ABHR on hand bacteriome and mycobiome of 20 hospitalized adult (≥18 years old) stem cell transplant patients [enrolled following Institutional Review Board-approved protocol (IRB 10-14-11), with written informed consent from all participants]. Participants were randomized to two groups [Group 1: ABHR and routine hand hygiene standard-of-care (SOC) over a 7-day period, Group 2: SOC]. Swabs were obtained from both hands on days 1, 7, and 30, and cultured (trypticase soy blood agar) or sequenced to identify fungi and bacteria [targeting Internally Transcribed Spacer 1 (ITS1) and 16S rDNA (V4 region), respectively].³ Skin hydration (moisture) and pH were measured using routine methods.⁴

There were no significant differences in age, gender, and use of concomitant treatments between groups (Supplemental Table 1). Colonies of pathogenic bacteria (Staphylococcus aureus, Serratia marcescens, Klebsiella oxytoca, and Escherichia coli) were significantly reduced in ABHR-treated patients compared to untreated patients on Day 30 (P = .038, Supplementary Figure 1).

Principal components analysis showed clustering of bacteriome varied considerably on Days 1 and 7 in the ABHR group, while Day 30 samples clustered similar to Day 1 (Supplementary Figure 2A–B), suggesting the microbiota had recovered by Day 30. Bacteriome remained perturbed in SOC group. There was no significant difference in diversity or core biome between groups. Three bacterial phyla (Actinobacteria, Firmicutes, Proteobacteria) and two fungal phyla (Ascomycota and Basidiomycota) were most abundant (Supplementary Figure 2C–F). Relative abundance of two bacterial phyla and seven bacterial genera were significantly different between untreated and ABHR-treated groups (Supplementary Table 2), while fungal phyla/genera did not differ. We found 572 and 776 unique significant correlations on Day 7 in untreated and ABHR-treated groups, respectively. Inter-kingdom correlations involving 89 bacterial and 26 fungal species were detected only in untreated group on Day 7, and included pathogenic bacteria (e.g. Bacillus cereus, Enterobacter cloacae, and Enterococcus cecorum) and fungi (e.g. Fusarium sp, Candida albicans, C. dubliniensis, Cryptococcus sp., and Emericella nidulans) (Table 1, and Supplementary Figure 3). ABHR had no effect on skin hydration over time, but led to significantly higher change in pH between Day 1 and Day 7 compared to SOC group (0.18 vs. −0.22, P = .008).

Table 1.

Bacterial and fungal species with unique inter-kingdom interactions in the ABHR and SOC groups^*

ABHR				SOC
Bacteria	Number	Fungi	Number	Bacteria	Number	Fungi	Number
Actinomyces yovaginalis	15	uncultured fungus	46	Actinokineospora iospyrosa	16	Emericella nidulans	26
Afipia elis	15	Fusarium oxysporum	40	Alicyclobacillus olerans	16	Candida albicans	22
Alloiococcus titis	15	Fusarium oxysporum f cubense	40	Arthrobacter eyseri	16	Fusarium incarnatum	22
Arthrobacter ulfureus	15	Fusarium oxysporum f sp carthami	40	Arthrobacter olychromogenes	16	Fusarium sp Pr13	22
Bifidobacterium ifidum	15	Fusarium solani	40	Clostridium enationis	16	Hebeloma cylindrosporum	22
Bifidobacterium reve	15	Fusarium sp ASR 18	40	Microbacterium aritypicum	16	Monoblepharis polymorpha	22
Bosea enosp.	15	Fusarium sp ASR 258	40	Microbacterium hocolatum	16	Pichia fermentans	22
Burkholderia lathei	15	Fusarium sp ASR 80	40	Paenibacillus autus	16	Trametes versicolor	22
Capnocytophaga chracea	15	Gibberella avenacea	40	Paenibacillus hondroitinus	16	Typhula ishikariensis	22
Corynebacterium ilosum	15	Nectria haematococca	40	Pannonibacter hragmitetus	16	Aureobasidium pullulans	19
Corynebacterium ubricantis	15	Nectria haematococca mpVI	40	Pseudoclavibacter ifida	16	Bullera formosana	19
Dietzia imorensis	15	Scleroderma sp.	40	Salinibacterium murskyense	16	Candida dubliniensis	19
Ehrlichia uminantium	15	Fusarium sp ASR 168	38	Serratia arcescens	16	Cryptococcus albidus var diffluens	19
Eubacterium dolichum	15	uncultured Fusarium sp	38	Streptomyces ureofaciens	16	Cryptococcus sp BF73	19
Halomonas ribbensis	15	Fusarium sp EML GYP1	36	Weeksella irosa	16	Epicoccum sp CHTAM6	19
Helosis ayennensis	15	Leccinum quercinum	15	Williamsia erinedens	16	Fusarium sp A2	19
Hydrogenobacter hermophilus	15	Candida frijolesensis	14	Schumannella uteola	15	Fusarium sp ASR 82	19
Kingella enitrificans	15	Candida sp.	14	Carnobacterium iridans	14	Fusarium sp KC 2010ba	19
Lamprocystis urpurea	15	Candida tropicalis	14	Corynebacterium imulans	14	Gibberella intermedia	19
Listeria eihenstephanensis	15	Hyphoderma praetermissum	14			Phaeangium lefebvrei	19
Oceanobacillus rofundus	15	Laccaria laccata	14			Pichia jadinii	19
Pelistega uropaea	15	Rhodotorula cresolica	14			Trichophyton fischeri	19
Plesiomonas higelloides	15	Tuber indicum	14			Rhodotorula mucilaginosa	18
Porphyromonas ndodontalis	15	Rhodotorula mucilaginosa	13			Epicoccum sp Co4 ITS14	17
Prevotella anceiensis	15	Dactylosporina macracantha	12			Fusarium sp ASR 168	17
Prevotella igrescens	15	Galactomyces geotrichum	12			Psathyrella lutensis	17
Prevotella tercorea	15	Phaeangium lefebvrei	12			uncultured Fusarium sp	17
Rathayibacter aricis	15
Roseburia aecis	15
Salinispora ropica	15
Salinivibrio osticola	15
Stenoxybacter cetivorans	15
Streptomyces adiopugnans	15
Teredinibacter urnerae	15
Corynebacterium roppenstedtii	14
Corynebacterium urum	14
Oenothera erteroana	14
Propionibacterium cnes	14
Carnobacterium iridans	13
Corynebacterium imulans	13

^*Species with 10 or more interactions are listed here. For complete list of species with unique inter-kingdom interactions, please see Supplemental Figure 3.

ABHR reduced the burden of pathogenic organisms on the hands of transplant patients without affecting skin health or inducing a significant change in the hand microbiome of patients, which agrees with recent studies.⁵ Incorporating microbes/microbial products in ABHR may modulate inter-kingdom microbial interactions and host-microbe interplay. There may be potential links between hand microbiome and oral/gut microbiome, acting as reservoirs of microbes that impact intrinsic/extrinsic variables critical for skin health. Further studies are warranted to validate these findings and ascertain their clinical relevance.