Psychotropic drugs have long been known to possess antimicrobial activity against several groups of microorganisms. Although this property has been extensively studied both alone and when combined with antibiotics against antimicrobial-resistant bacterial and fungal species, relatively little attention has been given to their ability to contribute to the emergence of antimicrobial resistance (AMR). We have recently reported the acquisition of multidrug resistance in Escherichia coli after exposure to gut-relevant concentrations of the antipsychotic quetiapine. Considering these observations, this review attempts to establish if a relationship between psychotropics and AMR in microorganisms has been defined in the scientific literature.
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References
1.
AgostinhoFR, JornadaLK, SchröderN, et al.Effects of chronic haloperidol and/or clozapine on oxidative stress parameters in rat brain. Neurochem Res, 2007; 32(8):1343–1350; doi: 10.1007/s11064-007-9311-3
2.
Ait ChaitY, MottaweaW, TompkinsTA, et al.Unravelling the antimicrobial action of antidepressants on gut commensal microbes. Sci Rep, 2020; 10(1):17878; doi: 10.1038/s41598-020-74934-9
3.
AlkhalifaBA, BulatovaNR, abuRokbaW, et al.Serotonin reuptake inhibitors effect on fluconazole activity against resistant Candida glabrata strains. J Glob Antimicrob Resist, 2022; 29:49–54; doi: 10.1016/j.jgar.2022.01.030
4.
AmaralL, KristiansenJE, Frolund ThomsenV, et al.The effects of chlorpromazine on the outer cell wall of Salmonella typhimurium in ensuring resistance to the drug. Int J Antimicrob Agents, 2000; 14(3):225–229; doi: 10.1016/s0924-8579(00)00136-9
5.
Amitriptyline [package insert]. Merck & Co., Inc.: West Point, PA; 1999.
6.
BachtarziR, BoureauAS, MascartC, et al.Psychoactive drug prescription and urine colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae. Infect Drug Resist, 2019; 12:1763–1770; doi: 10.2147/IDR.S200029
7.
BretlerT, WeisbergH, KorenO, et al.The effects of antipsychotic medications on microbiome and weight gain in children and adolescents. BMC Med, 2019; 17(1):112; doi: 10.1186/s12916-019-1346-1
8.
ButtsA, ReitlerP, NishimotoAT, et al.A systematic screen reveals a diverse collection of medications that induce antifungal resistance in Candida species. Antimicrob Agents Chemother, 2019; 63(5):e00054-19; doi: 10.1128/AAC.00054-19
9.
CaldaraM, MarmiroliN. Antimicrobial properties of antidepressants and antipsychotics—Possibilities and implications. Pharmaceuticals, 2021; 14(9):915; doi: 10.3390/ph14090915
10.
ChungASJ, ChengJNC, TseV. Psychotropic drugs and their effects on lower urinary tract function: An update. Curr Bladder Dysfunct Rep, 2016; 11(3):258–265; doi: 10.1007/s11884-016-0372-5
11.
CussottoS, StrainCR, FouhyF, et al.Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function. Psychopharmacology (Berl), 2019; 236(5):1671–1685; doi: 10.1007/s00213-018-5006-5
12.
DeochandDK, GroveA. MarR family transcription factors: dynamic variations on a common scaffold. Crit Rev Biochem Mol Biol, 2017; 52(6):595–613; doi: 10.1080/10409238.2017.1344612
13.
DwyerDJ, BelenkyPA, YangJH, et al.Antibiotics induce redox-related physiological alterations as part of their lethality. Proc Natl Acad Sci U S A, 2014; 111(20):E2100–E2109; doi: 10.1073/pnas.1401876111
14.
DzahiniO, SinghN, TaylorD, et al.Antipsychotic drug use and pneumonia: Systematic review and meta-analysis. J Psychopharmacol, 2018; 32(11):1167–1181; doi: 10.1177/0269881118795333
15.
EyreHA, AirT, PradhanA, et al.A meta-analysis of chemokines in major depression. Prog Neuropsychopharmacol Biol Psychiatry, 2016; 68:1–8; doi: 10.1016/j.pnpbp.2016.02.006
16.
FerrarisA, BlascoB, TentoniN, et al.Antipsychotic use and bloodstream infections among adult patients with chronic obstructive pulmonary disease: A cohort study. J Clin Psychiatry, 2021; 82(3):20m13516; doi: 10.4088/JCP.20m13516
17.
FlowersSA, EvansSJ, WardKM, et al.Interaction between atypical antipsychotics and the gut microbiome in a bipolar disease cohort. Pharmacotherapy, 2017; 37(3):261–267; doi: 10.1002/phar.1890
18.
Fluoxetine [package insert]. Lilly USA, LLC.: Indianapolis, IN; 2015.
19.
GashawM, MarameZH, AberaM, et al.Assessment of gut bacteria profile and antibiotic resistance pattern among psychotropic drug users: Comparative cross-sectional study. Infect Drug Resis, 2021; 14:1875–1881; doi: 10.2147/IDR.S305992
20.
GillardK, MillerHB, BlackledgeMS. Tricyclic amine antidepressants suppress β-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) by repressing mRNA levels of key resistance genes. Chem Biol Drug Des, 2018; 92(5):1822–1829; doi: 10.1111/cbdd.13361
21.
GuM, ImlayJA. The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide. Mol Microbiol, 2011; 79(5):1136–1150; doi: 10.1111/j.1365-2958.2010.07520.x
22.
HaoZ, LouH, ZhuR, et al.The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli. Nat Chem Biol, 2014; 10(1):21–28; doi: 10.1038/nchembio.1380
23.
HeiserP, SommerO, SchmidtAJ, et al.Effects of antipsychotics and vitamin C on the formation of reactive oxygen species. J Psychopharmacol, 2010; 24(10):1499–1504; doi: 10.1177/0269881109102538
24.
ImhannF, BonderMJ, Vich VilaA, et al.Proton pump inhibitors affect the gut microbiome. Gut, 2016; 65(5):740–748; doi: 10.1136/gutjnl-2015-310376
25.
ImlayJA.The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nat Rev Microbiol, 2013; 11(7):443–454; doi:10.1038/nrmicro3032
26.
Jensen-DahmC, ChristensenAN, GasseC, et al.The use of opioids and antipsychotics in elderly with dementia—Have opioids replaced antipsychotics in treating behavioral symptoms in dementia?. J Alzheimers Dis, 2020; 73(1):259–267; doi: 10.3233/JAD-190787
27.
JinM, LuJ, ChenZ, et al.Antidepressant fluoxetine induces multiple antibiotics resistance in Escherichia coli via ROS-mediated mutagenesis. Environ Int, 2018; 120:421–430; doi: 10.1016/j.envint.2018.07.046
28.
KathwateGH, ShindeRB, KaruppayilSM. Antiepileptic drugs inhibit growth, dimorphism, and biofilm mode of growth in human pathogen Candida albicans. Assay Drug Dev Technol, 2015; 13(6):307–312; doi: 10.1089/adt.2015.29007.ghkdrrr
29.
KerenI, WuY, InocencioJ, et al.Killing by bactericidal antibiotics does not depend on reactive oxygen species. Science, 2013; 339(6124):1213–1216; doi: 10.1126/science.1232688
30.
KiralyB, GunningK, LeiserJ.Primary care issues in patients with mental illness. Am Fam Physician, 2008; 78(3):355–362.
LiuL, ChenX, SkogerbøG, et al.The human microbiome: A hot spot of microbial horizontal gene transfer. Genomics, 2012; 100(5):265–270; doi: 10.1016/j.ygeno.2012.07.012
33.
LiuY, ImlayJA. Cell death from antibiotics without the involvement of reactive oxygen species. Science, 2013; 339(6124):1210–1213; doi: 10.1126/science.1232751
34.
MayM, BeaucheminM, VaryC, et al.The antipsychotic medication, risperidone, causes global immunosuppression in healthy mice. PLoS One, 2019; 14(6):e0218937; doi: 10.1371/journal.pone.0218937
35.
MaierL, PruteanuM, KuhnM, et al.Extensive impact of non-antibiotic drugs on human gut bacteria. Nature, 2018; 555(7698):623–628; doi: 10.1038/nature25979
36.
MemarMY, GhotaslouR, SamieiM, et al.Antimicrobial use of reactive oxygen therapy: current insights. Infect Drug Resist, 2018; 11:567–576; doi: 10.2147/IDR.S142397
37.
MurrayCJ, IkutaKS, ShararaF, et al.Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet, 2022; 399(10325):629–655; doi: 10.1016/S0140-6736(21)02724-0
38.
Obuobi-DonkorG, NkireN, AgyapongVIO. Prevalence of major depressive disorder and correlates of thoughts of death, suicidal behaviour, and death by suicide in the geriatric population—A general review of literature. Behav Sci (Basel), 2021; 11(11):142; doi: 10.1177/1054773819838678
39.
Paes LemeRC, da SilvaRB. Antimicrobial activity of non-steroidal anti-inflammatory drugs on biofilm: Current evidence and potential for drug repurposing. Front Microbiol, 2021; 12:707629; doi: 10.3389/fmicb.2021.707629
40.
PradelE, PagèsJM. The AcrAB-TolC efflux pump contributes to multidrug resistance in the nosocomial pathogen Enterobacter aerogenes. Antimicrob Agents Chemother, 2002; 46(8):2640–2643; doi: 10.1128/AAC.46.8.2640-2643.2002
41.
PulsenMØ, SchølerL, NielsenA, et al.Combination therapy with thioridazine and dicloxacillin combats meticillin-resistant Staphylococcus aureus infection in Caenorhabditis elegans. J Med Microbiol, 2014; 63(Pt 9):1174–1180; doi: 10.1099/jmm.0.071837-0
42.
ResnickB, KolanowskiA, Van HaitsmaK, et al.Current psychotropic medication use and contributing factors among nursing home residents with cognitive impairment. Clin Nurs Res, 2021; 30(1):59–69; doi: 10.1177/1054773819838678
43.
ShiD, HaoH, WeiZ, et al.Combined exposure to non-antibiotic pharmaceutics and antibiotics in the gut synergistically promote the development of multi-drug-resistance in Escherichia coli. Gut Microbes, 2022; 14(1):2018901; doi: 10.1080/19490976.2021.2018901
44.
TavíoMM, AquiliVD, FàbregaA, et al.Overexpression of the quorum-sensing regulator sdiA and soxS is involved in low-level multidrug resistance induced in Escherichia coli AG100 by haloperidol, diazepam and NaCl. Int J Antimicrob Agents, 2012; 39(1):91–93; doi: 10.1016/j.ijantimicag.2011.08.008
45.
TavíoMM, VilaJ, PerilliM, et al.Enhanced active efflux, repression of porin synthesis and development of Mar phenotype by diazepam in two enterobacteria strains. J Med Microbiol, 2004; 53(Pt 11):1119–1122; doi: 10.1099/jmm.0.45613-0
46.
ThomasK, SaadabadiA. Olanzapine. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 [cited December 12, 2021]. Available from: www.ncbi.nlm.nih.gov/books/NBK532903/Bookshelf ID:NBK532903 [last accessed: August 15, 2022].
47.
U.S. Census Bureau. Household Pulse Survey [Internet]. National Center for Health Statistics; 2022 [cited 2022 Apr 29]. Available from: https://www.census.gov/data/experimental-data-products/household-pulse-survey.html [last accessed: August 15, 2022].
48.
van StrienAM, SouvereinPC, KeijsersCK, et al.Antipsychotic drug use associated with urinary tract infections in older women. Maturitas, 2017; 98:46–50; doi: 10.1016/j.maturitas.2017.01.009
49.
Vich VilaA, CollijV, SannaS, et al.Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat Commun, 2020; 11(1):362; doi: 10.1038/s41467-019-14177-z
50.
WangY, LuJ, MaoL, et al.Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera. ISME J, 2019; 13(2):509–522; doi: 10.1038/s41396-018-0275-x
51.
ZhangW, QuW, WangH, et al.Antidepressants fluoxetine and amitriptyline induce alterations in intestinal microbiota and gut microbiome function in rats exposed to chronic unpredictable mild stress. Transl Psychiatry, 2021; 11(1):131; doi: 10.1038/s41398-021-01254-5
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