Drug-resistant oral candidiasis in patients with HIV infection: a systematic review and meta-analysis.
Candida
Drug Resistance
HIV
Opportunistic infections
Oral candidiasis
Journal
BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551
Informations de publication
Date de publication:
31 May 2024
31 May 2024
Historique:
received:
15
01
2024
accepted:
27
05
2024
medline:
1
6
2024
pubmed:
1
6
2024
entrez:
31
5
2024
Statut:
epublish
Résumé
Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients. Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model. Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1-35.8%), fluconazole (24.8%, 95% CI: 17.4-32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0-26.0%), voriconazole (20.0%, 95% CI: 1.9-38.0%), miconazole (15.0%, 95% CI: 5.1-26.0%), clotrimazole (13.4%, 95% CI: 2.3-24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5-5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin. The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).
Sections du résumé
BACKGROUND
BACKGROUND
Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients.
METHODS
METHODS
Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model.
RESULTS
RESULTS
Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1-35.8%), fluconazole (24.8%, 95% CI: 17.4-32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0-26.0%), voriconazole (20.0%, 95% CI: 1.9-38.0%), miconazole (15.0%, 95% CI: 5.1-26.0%), clotrimazole (13.4%, 95% CI: 2.3-24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5-5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I
CONCLUSIONS
CONCLUSIONS
Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin.
REGISTRATION
BACKGROUND
The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).
Identifiants
pubmed: 38822256
doi: 10.1186/s12879-024-09442-6
pii: 10.1186/s12879-024-09442-6
doi:
Substances chimiques
Antifungal Agents
0
Fluconazole
8VZV102JFY
Types de publication
Journal Article
Systematic Review
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
546Informations de copyright
© 2024. The Author(s).
Références
Vila T, Sultan AS, Montelongo-Jauregui D, Jabra-Rizk MA. Oral candidiasis: a Disease of Opportunity. J Fungi (Basel Switzerland). 2020;6(1):15.
pmcid: 7151112
Mardani M, Abolghasemi S, Darvishnia D, Lotfali E, Ghasemi R, Rabiei MM, et al. Oral candidiasis in hematological malignancy patients: identification and antifungal susceptibility patterns of isolates. Jundishapur J Microbiol. 2020;13(8):e103290.
Deepa A, Nair BJ, Sivakumar T, Joseph AP. Uncommon opportunistic fungal infections of oral cavity: a review. J oral Maxillofacial Pathology: JOMFP. 2014;18(2):235–43.
pubmed: 25328305
pmcid: 4196293
doi: 10.4103/0973-029X.140765
Mushi MF, Bader O, Taverne-Ghadwal L, Bii C, Groß U, Mshana SE. Oral candidiasis among African human immunodeficiency virus-infected individuals: 10 years of systematic review and meta-analysis from Sub-saharan Africa. J oral Microbiol. 2017;9(1):1317579.
pubmed: 28748027
pmcid: 5508360
doi: 10.1080/20002297.2017.1317579
Balasubramaniam M, Pandhare J, Dash C. Immune Control of HIV. Journal of life sciences (Westlake Village. Calif). 2019;1(1):4–37.
Gondivkar S, Sarode SC, Gadbail AR, Yuwanati M, Sarode GS, Gondivkar RS, et al. Oro-facial opportunistic infections and related pathologies in HIV patients: a comprehensive review. Dis Mon. 2021;67(9):101170.
pubmed: 33618831
doi: 10.1016/j.disamonth.2021.101170
Ramadian EE, Pradono SA, Wimardhani YS. Successful treatment of persistent oral ulcers in patients with HIV/AIDS. J Int Dent Med Res. 2016;9:398–402.
Malele Kolisa Y, Yengopal V, Shumba K, Igumbor J. The burden of oral conditions among adolescents living with HIV at a clinic in Johannesburg, South Africa. PLoS ONE. 2019;14(10):e0222568.
pubmed: 31618211
pmcid: 6795420
doi: 10.1371/journal.pone.0222568
Taverne-Ghadwal L, Kuhns M, Buhl T, Schulze MH, Mbaitolum WJ, Kersch L, et al. Epidemiology and prevalence of oral candidiasis in HIV patients from Chad in the Post-HAART era. Front Microbiol. 2022;13:844069.
pubmed: 35250957
pmcid: 8891798
doi: 10.3389/fmicb.2022.844069
Patil S, Majumdar B, Sarode SC, Sarode GS, Awan KH. Oropharyngeal Candidosis in HIV-Infected Patients-An update. Front Microbiol. 2018;9:980.
pubmed: 29867882
pmcid: 5962761
doi: 10.3389/fmicb.2018.00980
Hellstein JW, Marek CL. Candidiasis: Red and White manifestations in the oral cavity. Head Neck Pathol. 2019;13(1):25–32.
pubmed: 30693459
pmcid: 6405794
doi: 10.1007/s12105-019-01004-6
Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;62(4):e1–50.
doi: 10.1093/cid/civ933
Lortholary O, Petrikkos G, Akova M, Arendrup MC, Arikan-Akdagli S, Bassetti M, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: patients with HIV infection or AIDS. Clin Microbiol Infection: Official Publication Eur Soc Clin Microbiol Infect Dis. 2012;18(Suppl 7):68–77.
doi: 10.1111/1469-0691.12042
Pfaller MA, Carvalhaes CG, DeVries S, Rhomberg PR, Castanheira M. Impact of COVID-19 on the antifungal susceptibility profiles of isolates collected in a global surveillance program that monitors invasive fungal infections. Med Mycol. 2022;60(5):myac028.
Pfaller MA, Diekema DJ, Turnidge JD, Castanheira M, Jones RN. Twenty years of the SENTRY Antifungal Surveillance Program: results for Candida Species from 1997–2016. Open Forum Infect Dis. 2019;6(Suppl 1):S79–94.
pubmed: 30895218
pmcid: 6419901
doi: 10.1093/ofid/ofy358
Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017;17(12):e383–92.
pubmed: 28774698
doi: 10.1016/S1473-3099(17)30316-X
Khedri S, Santos ALS, Roudbary M, Hadighi R, Falahati M, Farahyar S, et al. Iranian HIV/AIDS patients with oropharyngeal candidiasis: identification, prevalence and antifungal susceptibility of Candida species. Lett Appl Microbiol. 2018;67(4):392–9.
pubmed: 30019443
doi: 10.1111/lam.13052
Shivaswamy U, Sumana MN. Antifungal Resistance of Candida Species isolated from HIV patients in a Tertiary Care Hospital, Mysuru, Karnataka. Indian J Dermatology. 2020;65(5):423–5.
doi: 10.4103/ijd.IJD_385_19
Junqueira JC, Vilela SF, Rossoni RD, Barbosa JO, Costa AC, Rasteiro VM, et al. Oral colonization by yeasts in HIV-positive patients in Brazil. Revista do Instituto de Medicina Tropical de Sao Paulo. 2012;54(1):17–24.
pubmed: 22370749
doi: 10.1590/S0036-46652012000100004
Nweze EI, Ogbonnaya UL. Oral Candida isolates among HIV-infected subjects in Nigeria. J Microbiol Immunol Infect = Wei Mian Yu Gan ran Za Zhi. 2011;44(3):172–7.
pubmed: 21524610
doi: 10.1016/j.jmii.2011.01.028
Li X, Lei L, Tan D, Jiang L, Zeng X, Dan H, et al. Oropharyngeal Candida colonization in human immunodeficiency virus infected patients. APMIS: acta pathologica, microbiologica. et Immunol Scand. 2013;121(5):375–402.
Lu SY. Oral candidosis: pathophysiology and best practice for diagnosis, classification, and successful management. J Fungi (Basel Switzerland). 2021;7(7):555.
Forsberg K, Woodworth K, Walters M, Berkow EL, Jackson B, Chiller T, et al. Candida Auris: the recent emergence of a multidrug-resistant fungal pathogen. Med Mycol. 2019;57(1):1–12.
pubmed: 30085270
doi: 10.1093/mmy/myy054
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg (London England). 2010;8(5):336–41.
doi: 10.1016/j.ijsu.2010.02.007
Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. JBI Evid Implement. 2015;13(3):147–53.
Magaldi S, Mata S, Hartung C, Verde G, Deibis L, Roldán Y, et al. In vitro susceptibility of 137 Candida sp. isolates from HIV positive patients to several antifungal drugs. Mycopathologia. 2001;149(2):63–8.
pubmed: 11265163
doi: 10.1023/A:1007237711099
Sant’Ana Pde L, Milan EP, Martinez R, Queiroz-Telles F, Ferreira MS, Alcântara AP, et al. Multicenter Brazilian study of oral Candida species isolated from AIDS patients. Mem Inst Oswaldo Cruz. 2002;97(2):253–7.
pubmed: 12016452
doi: 10.1590/S0074-02762002000200019
Silva MRR, Costa MR, Miranda AT, Fernandes OF, Costa CR, Paula CRd. Evaluation of Etest and macrodilution broth method for antifungal susceptibility testing of Candida Sp strains isolated from oral cavities of AIDS patients. Rev Inst Med Trop Sao Paulo. 2002;44:121–5.
pubmed: 12163903
doi: 10.1590/S0036-46652002000300002
Migliorati CA, Birman EG, Cury AE. Oropharyngeal candidiasis in HIV-infected patients under treatment with protease inhibitors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98(3):301–10.
pubmed: 15356467
doi: 10.1016/j.tripleo.2004.05.017
Enwuru C, Ogunledun A, Idika N, Enwuru N, Ogbonna E, Aniedobe M, et al. Fluconazole resistant opportunistic oro-pharyngeal Candida and non-candida yeast-like isolates from HIV infected patients attending ARV clinics in Lagos, Nigeria. Afr Health Sci. 2008;8(3):142–8.
pubmed: 19357740
pmcid: 2583271
Nadagir SD, Chunchanur SK, Halesh LH, Yasmeen K, Chandrasekhar MR, Patil BS. Significance of isolation and drug susceptibility testing of non-candida albicans species causing oropharyngeal candidiasis in HIV patients. Southeast Asian J Trop Med Public Health. 2008;39(3):492–5.
pubmed: 18564689
Hamza OJ, Matee MI, Moshi MJ, Simon EN, Mugusi F, Mikx FH, et al. Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis. BMC Microbiol. 2008;8:1–9.
doi: 10.1186/1471-2180-8-135
Jeddy N, Ranganathan K, Devi U, Joshua E. A study of antifungal drug sensitivity of Candida isolated from human immunodeficiency virus infected patients in Chennai, South India. J oral Maxillofacial Pathology: JOMFP. 2011;15(2):182–6.
pubmed: 22529577
pmcid: 3329697
doi: 10.4103/0973-029X.84490
Castro L, Álvarez MI, Martínez E. Pseudomembranous candidiasis in HIV/AIDS patients in Cali. Colombia Mycopathologia. 2013;175(1–2):91–8.
pubmed: 23086383
doi: 10.1007/s11046-012-9593-0
Katiraee F, Khalaj V, Khosravi AR, Hajiabdolbaghi M. Sequences type analysis of Candida albicans isolates from Iranian human immunodeficiency virus infected patients with oral candidiasis. Acta Medica Iranica. 2014;52(3):187–91.
pubmed: 24901719
Gaona-Flores V, Guzmán R, Tovar R, Martínez E, Arrieta M. In vitro sensitivity to Fluconazole through Vitek II Systems, of strains of Candida Spp. Patients with Oropharyngeal Candidiasis and HIV/AIDS. J AIDS Clin Res. 2013;4(230):2.
Dos Santos Abrantes PM, McArthur CP, Africa CW. Multi-drug resistant oral Candida species isolated from HIV-positive patients in South Africa and Cameroon. Diagn Microbiol Infect Dis. 2014;79(2):222–7.
pubmed: 24726686
doi: 10.1016/j.diagmicrobio.2013.09.016
Shyamala R, Parandekar P. Identification and in vitro azole resistance of Candida species isolated from oropharyngeal candidiasis in human immunodeficiency virus infected patients. Int J Curr Microbiol Appl Sci. 2014;3:816–22.
Katiraee F, Teifoori F, Soltani M. Emergence of azole-resistant Candida species in AIDS patients with oropharyngeal candidiasis in Iran. Curr Med Mycol. 2015;1(3):11–6.
pubmed: 28680991
pmcid: 5490324
doi: 10.18869/acadpub.cmm.1.3.11
Murtiastutik D, Maharani CS, Listiawan MY. Nystatin profile on Candida species in HIV/AIDS patients with oral candidiasis: a phenomenology study. J pure Appl Microbiol. 2019;13(4):183–5.
doi: 10.22207/JPAM.13.4.12
Lamichhane K, Adhikari N, Bastola A, Devkota L, Bhandari P, Dhungel B, Auckland, et al. Biofilm-Producing Candida Species Causing Oropharyngeal Candidiasis in HIV Patients Attending Sukraraj Tropical and Infectious Diseases Hospital in Kathmandu, Nepal. HIV/AIDS (Auckland, NZ). 2020;12:211–20.
Ambe NF, Longdoh NA, Tebid P, Bobga TP, Nkfusai CN, Ngwa SB, et al. The prevalence, risk factors and antifungal sensitivity pattern of oral candidiasis in HIV/AIDS patients in Kumba District Hospital, South West Region, Cameroon. Pan Afr Med J. 2020;36:23.
pubmed: 32774600
pmcid: 7392032
doi: 10.11604/pamj.2020.36.23.18202
Quansah HA, Opintan JA. Distribution and susceptibility profile of Candida isolates from HIV patients with oropharyngeal candidiasis. Health Sci Investigations J. 2020;1(1):43–9.
doi: 10.46829/hsijournal.2020.6.1.1.43-49
Tamai IA, Pakbin B, Fasaei BN. Genetic diversity and antifungal susceptibility of Candida albicans isolates from Iranian HIV-infected patients with oral candidiasis. BMC Res Notes. 2021;14(1):93.
pubmed: 33691787
pmcid: 7945322
doi: 10.1186/s13104-021-05498-8
Murtiastutik D, Listiawan MY, Bintanjoyo L, Hidayati AN, Widyantari S, Sari M, Ketoconazole. A re-emerging choice for oral candidiasis in patients with human immunodeficiency virus infection/acquired Immunodeficiency Syndrome. Res J Pharm Technol. 2022;15(3):1071–6.
doi: 10.52711/0974-360X.2022.00179
Erfaninejad M, Zarei Mahmoudabadi A, Maraghi E, Hashemzadeh M, Fatahinia M. Low level of antifungal resistance in Candida species recovered from Iranian HIV-associated oral infection. Lett Appl Microbiol. 2023;76(3):ovad029.
Freitas VAQ, Santos AS, Zara A, Costa CR, Godoy CSM, Soares RBA, et al. Distribution and antifungal susceptibility profiles of Candida species isolated from people living with HIV/AIDS in a public hospital in Goiânia, GO, Brazil. Brazilian J Microbiology: [publication Brazilian Soc Microbiology]. 2023;54(1):125–33.
doi: 10.1007/s42770-022-00851-w
Ekwealor C, Nweke C, Anaukwu C, Anakwenze V, Ogbukagu C, Mba A. Prevalence and antifungal susceptibility pattern of oral candidiasis among HIV-infected patients in a Mission Hospital, Southeast Nigeria. Afr J Clin Experimental Microbiol. 2023;24(3):289–98.
doi: 10.4314/ajcem.v24i3.9
Anuța V, Talianu MT, Dinu-Pîrvu CE, Ghica MV, Prisada RM, Albu Kaya MG, et al. Molecular mapping of antifungal mechanisms accessing biomaterials and new agents to target oral candidiasis. Int J Mol Sci. 2022;23(14):7520.
Patil S, Rao RS, Majumdar B, Anil S. Clinical appearance of oral Candida infection and therapeutic strategies. Front Microbiol. 2015;6:1391.
pubmed: 26733948
pmcid: 4681845
doi: 10.3389/fmicb.2015.01391
Maninder J, Usha A. Isolation, characterization and antifungal susceptibility pattern of Candida species causing oropharyngeal candidiasis in HIV positive patients. J Commun Dis. 2008;40(3):177–81.
pubmed: 19245155
Salari S, Khosravi AR, Mousavi SA, Nikbakht-Brojeni GH. Mechanisms of resistance to fluconazole in Candida albicans clinical isolates from Iranian HIV-infected patients with oropharyngeal candidiasis. J De Mycol Medicale. 2016;26(1):35–41.
doi: 10.1016/j.mycmed.2015.10.007
Alves SH, Da Matta DA, Azevedo AC, Loreto ES, Boff E, Santurio JM, et al. In vitro activities of new and conventional antimycotics against fluconazole-susceptible and non-susceptible Brazilian Candida spp. isolates. Mycoses. 2006;49(3):220–5.
pubmed: 16681814
doi: 10.1111/j.1439-0507.2006.01226.x
Delma FZ, Al-Hatmi AMS, Brüggemann RJM, Melchers WJG, de Hoog S, Verweij PE, et al. Molecular mechanisms of 5-Fluorocytosine resistance in yeasts and Filamentous fungi. J Fungi (Basel Switzerland). 2021;7(11):909.
pmcid: 8623157
Quindós G, Gil-Alonso S, Marcos-Arias C, Sevillano E, Mateo E, Jauregizar N, et al. Therapeutic tools for oral candidiasis: current and new antifungal drugs. Med oral Patologia oral y Cir Bucal. 2019;24(2):e172–80.
WHO Guidelines Approved by the Guidelines Review Committee. Guidelines on the treatment of skin and oral HIV-associated conditions in children and adults. Geneva: World Health Organization Copyright © World Health Organization 2014; 2014.
Osaigbovo II, Lofor PV, Oladele RO. Fluconazole Resistance among oral Candida isolates from People Living with HIV/AIDS in a Nigerian Tertiary Hospital. J Fungi (Basel Switzerland). 2017;3(4):69.
pmcid: 5753171
Moges B, Bitew A, Shewaamare A. Spectrum and the In Vitro Antifungal susceptibility pattern of yeast isolates in Ethiopian HIV patients with Oropharyngeal Candidiasis. Int J Microbiol. 2016;2016:3037817.
pubmed: 26880925
pmcid: 4736391
doi: 10.1155/2016/3037817
Albertson GD, Niimi M, Cannon RD, Jenkinson HF. Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance. Antimicrob Agents Chemother. 1996;40(12):2835–41.
pubmed: 9124851
pmcid: 163632
doi: 10.1128/AAC.40.12.2835
Kaur R, Dhakad MS, Goyal R, Haque A, Mukhopadhyay G. Identification and Antifungal Susceptibility Testing of Candida Species: a comparison of Vitek-2 System with Conventional and Molecular methods. J Global Infect Dis. 2016;8(4):139–46.
doi: 10.4103/0974-777X.192969
Kumar D, Bhattacharyya S, Gupta P, Banerjee G, Singh M. Comparative analysis of Disc Diffusion and E-test with Broth micro-dilution for susceptibility testing of clinical Candida isolates against amphotericin B, Fluconazole, Voriconazole and Caspofungin. J Clin Diagn Research: JCDR. 2015;9(11):Dc01–4.
Terças AL, Marques SG, Moffa EB, Alves MB, de Azevedo CM, Siqueira WL, et al. Antifungal Drug Susceptibility of Candida Species isolated from HIV-Positive patients recruited at a Public Hospital in São Luís, Maranhão, Brazil. Front Microbiol. 2017;8:298.
pubmed: 28303122
pmcid: 5332371
doi: 10.3389/fmicb.2017.00298
Thompson GR 3rd, Patel PK, Kirkpatrick WR, Westbrook SD, Berg D, Erlandsen J, et al. Oropharyngeal candidiasis in the era of antiretroviral therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(4):488–95.
pubmed: 20156694
pmcid: 2843789
doi: 10.1016/j.tripleo.2009.11.026