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Revista Brasileira de Ginecologia E... 2024• The balanced vaginal microbiome is the main factor defending the vaginal environment against infections. Lactobacilli play a key role in this regard, maintaining the... (Review)
Review
• The balanced vaginal microbiome is the main factor defending the vaginal environment against infections. Lactobacilli play a key role in this regard, maintaining the vaginal pH within the normal range (3.8 to 4.5). •Hormonal and immune adaptations resulting from pregnancy influence changes in the vaginal microbiome during pregnancy. •An altered vaginal microbiome predisposes to human immunodeficiency virus (HIV) infection. •Bacterial vaginosis is the main clinical expression of an imbalanced vaginal microbiome. •Vulvovaginal candidiasis depends more on the host's conditions than on the etiological agent. • is a protozoan transmitted during sexual intercourse. •The use of probiotics is not approved for use in pregnant women.
Topics: Humans; Female; Pregnancy; Pregnancy Complications, Infectious; Vulvovaginitis; Microbiota; Vagina; Vaginosis, Bacterial
PubMed: 38765512
DOI: 10.61622/rbgo/2024FPS03 -
Canadian Journal of Microbiology May 2024Boric acid is a broad-spectrum antimicrobial used to treat vulvovaginal candidiasis when patients relapse on the primary azole drug fluconazole. Candida albicans is the...
Boric acid is a broad-spectrum antimicrobial used to treat vulvovaginal candidiasis when patients relapse on the primary azole drug fluconazole. Candida albicans is the most common cause of vulvovaginal candidiasis, colloquially referred to as a "vaginal yeast infection". Little is known about the propensity of C. albicans to develop BA resistance or tolerance (the ability of a subpopulation to grow slowly in high levels of drug). We evolved 96 replicates from eight diverse C. albicans strains to increasing BA concentrations to test the evolvability of BA resistance and tolerance. Replicate growth was individually assessed daily, with replicates passaged when they had reached an optical density consistent with exponential growth. Many replicates went extinct quickly. Although some replicates could grow in much higher levels of BA than the ancestral strains, evolved populations isolated from the highest terminal BA levels (after 11 weeks of passages) surprisingly showed only modest growth improvements and only at low levels of BA. No large increases in resistance or tolerance were observed in the evolved replicates. Overall, our findings illustrate that there may be evolutionary constraints limiting the emergence of BA resistance and tolerance, which could explain why it remains an effective treatment for recurrent yeast infections.
PubMed: 38754137
DOI: 10.1139/cjm-2023-0225 -
The Journal of Antibiotics Jul 2024Mixed vaginitis due to bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) is the most prevalent form and presents a significant therapeutic challenge globally....
Mixed vaginitis due to bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) is the most prevalent form and presents a significant therapeutic challenge globally. Since, the administration of monotherapy leads to subsequent recurrent infections, synergistic therapy that completely eradicates both pathogens is of dire need to manage mixed vaginities scenario and to prevent its recurrence. The current investigation was focused on exploring the synergistic inhibitory efficacy of phytochemicals against the virulence traits of individual and mixed species of C. albicans and G. vaginalis in vitro and in vivo (Galleria mellonella). Out of five phytochemicals (carvacrol, thymol, cinnamaldehyde, eugenol, and borneol) screened for synergism with citral [(Ct) as the prime molecule owing to its myriad therapeutic potential], carvacrol (Ca) in combination with citral exhibited promising synergistic effect. Time-kill kinetics and one-minute contact-killing assays demonstrated the phenomenal microbicidal effect of Ct-Ca combination against both mono and dual-species within 30 min and one-minute time intervals, respectively. Furthermore, the sub-CMICs (synergistic combinatorial MIC) of Ct-Ca have significantly eradicated the mature biofilms and remarkably reduced the virulence attributes of both C. albicans and G. vaginalis (viz., yeast to hyphae transition, filamentation, protease production, and hydrophobicity index), in single and dual species states. The non-toxic nature of Ct-Ca combination was authenticated using in vitro (human erythrocyte cells) and in vivo (Galleria mellonella) models. In addition, the in vivo efficacy evaluation and subsequent histopathological investigation was done using the invertebrate model system G. mellonella, which further ascertained the effectiveness of Ct-Ca combination in fighting off the infection caused by individual and mixed species of C. albicans and G. vaginalis. Concomitantly, the current work is the first of its kind to delineate the in vitro interaction of C. albicans and G. vaginalis mixed species at their growth and biofilm states, together emphasizes the promising therapeutic potential of acclaimed phytochemicals as combinatorial synergistic therapy against mixed vaginitis.
Topics: Candida albicans; Female; Cymenes; Animals; Acyclic Monoterpenes; Drug Synergism; Gardnerella vaginalis; Candidiasis, Vulvovaginal; Virulence; Microbial Sensitivity Tests; Moths; Monoterpenes; Antifungal Agents; Vaginosis, Bacterial; Humans; Biofilms
PubMed: 38750249
DOI: 10.1038/s41429-024-00728-0 -
Journal of Midwifery & Women's Health 2024
Topics: Humans; Female; Candidiasis, Vulvovaginal; Antifungal Agents; Pregnancy
PubMed: 38738848
DOI: 10.1111/jmwh.13650 -
Nutrients Apr 2024Vulvovaginal candidiasis (VVC) is the most common cause of vaginal discharge among women. The present study aimed to investigate the synergistic anticandidal effect of...
Vulvovaginal candidiasis (VVC) is the most common cause of vaginal discharge among women. The present study aimed to investigate the synergistic anticandidal effect of lactobacillus cultures supplemented with plant extracts. Among 600 isolates of lactic acid bacteria, 41 isolates exhibited inhibitory activity against ATCC10231. Six out of 41 cell-free supernatants demonstrated the most potent antibacterial and anticandidal activities. They also inhibited the clinical isolates of causing VVC and non-. The synergistic effect between 84/7 and 89/4 was demonstrated by the lowest fractional inhibitory concentration index (FICI = 0.5). The synbiotic culture of bacterial combination, cultured with Jerusalem artichoke () extract, also exhibited the strongest inhibition against the tested . Biofilm formation decreased after 12 h of incubation in the selected cell-free supernatants of this synbiotic culture. The anticandidal activity of crude extracts was lost after treatment with proteinase K and trypsin but not with heating conditions, suggesting that it may be a heat-stable substance. In conclusion, the combination of 84/7 and 89/4 with may be a promising candidate for inhibiting infection and biofilm formation, with the potential use as ingredients in vaginal biotherapeutic products.
Topics: Candida albicans; Plant Extracts; Female; Humans; Candidiasis, Vulvovaginal; Synbiotics; Vaginal Discharge; Biofilms; Lactobacillus; Limosilactobacillus reuteri; Lactobacillus crispatus; Antifungal Agents
PubMed: 38732618
DOI: 10.3390/nu16091372 -
Pharmacotherapy Jun 2024Management of invasive fungal infections is challenging with growing antifungal resistance. Broad antifungal use has resulted in greater intrinsic and acquired... (Review)
Review
Management of invasive fungal infections is challenging with growing antifungal resistance. Broad antifungal use has resulted in greater intrinsic and acquired resistance among Candida spp. It is important for clinicians to recognize the relationship between host susceptibility, site of infection, Candida resistance profiles, specific drug pharmacokinetics and pharmacodynamics, and the role of novel antifungal agents. This narrative review covers the role of rezafungin, ibrexafungerp, and fosmanogepix in the management of invasive candidiasis (IC). The PubMed Database, Embase, and ClinicalTrials.gov were searched between January 2006 and January 2024 using the following terms: rezafungin, CD101, ibrexafungerp, SCY-078, fosmanogepix, APX001, candidemia, and invasive candidiasis. Review articles, prospective clinical trials, and observational studies published in the English language were reviewed. Studies evaluating pharmacology, pharmacokinetics, efficacy, and safety in animals and humans were also reviewed. Promising data continues to emerge in support of novel drug therapies for IC and candidemia. Rezafungin possesses a unique pharmacodynamic profile that might be advantageous compared to other echinocandins, with a practical, once-weekly dosing interval. Ibrexafungerp, currently approved for vulvovaginal candidiasis, has been studied off-label for use in IC and candidemia, and initial data is encouraging. Lastly, fosmanogepix, a mechanistically novel, investigational antifungal agent, may be a potential future option in the management of IC and candidemia. Future research is needed to evaluate the potential use of these agents among diverse patient populations.
Topics: Humans; Candidiasis, Invasive; Antifungal Agents; Echinocandins; Animals; Drug Resistance, Fungal; Glycosides; Triterpenes
PubMed: 38721866
DOI: 10.1002/phar.2926 -
Expert Review of Anti-infective Therapy May 2024In the face of increased frequency of non-albicans Candida vulvovaginitis (VVC) reported worldwide, there is a paucity of effective oral and topical antifungal drugs... (Review)
Review
INTRODUCTION
In the face of increased frequency of non-albicans Candida vulvovaginitis (VVC) reported worldwide, there is a paucity of effective oral and topical antifungal drugs available. Drug selection is further handicapped by an absence of data of clinical efficacy of available antifungal drugs for these infections.
AREAS COVERED
In this review, attention is directed at the cause of drug shortage as well as increased frequency of non-albicans Candida (NAC) vulvovaginitis. There is widespread recognition of reduced in vitro azole drug susceptibility in NAC species. Moreover, antifungal susceptibility tests have not been standardized or validated for NAC isolates, hence clinicians rely on an element of empiricism especially given the absence of randomized controlled comparative studies targeting NAC species. Clinical spectrum of NAC species isolates is highly variable with ongoing difficulty in determining a causal role in symptomatic patients.
EXPERT OPINION
We have entered the era of demand for Candida species-specific therapy and although consensus treatment guidelines are emerging, new antifungal agents that target these multiple-azole resistant or relatively resistant vaginal NAC species are urgently needed.
Topics: Humans; Candida; Antifungal Agents; Female; Candidiasis, Vulvovaginal; Microbial Sensitivity Tests; Drug Resistance, Fungal; Azoles; Species Specificity; Practice Guidelines as Topic
PubMed: 38720183
DOI: 10.1080/14787210.2024.2347953 -
American Journal of Obstetrics and... May 2024
PubMed: 38710271
DOI: 10.1016/j.ajog.2024.04.048 -
Microbiology Spectrum Jun 2024Candidiasis places a significant burden on human health and can range from common superficial vulvovaginal and oral infections to invasive diseases with high mortality....
UNLABELLED
Candidiasis places a significant burden on human health and can range from common superficial vulvovaginal and oral infections to invasive diseases with high mortality. The most common species implicated in human disease is , but other species like are emerging. The use of azole antifungals for treatment is limited by increasing rates of resistance. This study explores repositioning bisphosphonates, which are traditionally used for osteoporosis, as antifungal synergists that can improve and revitalize the use of azoles. Risedronate, alendronate, and zoledronate (ZOL) were tested against isolates from six different species of , and ZOL produced moderate antifungal activity and strong synergy with azoles like fluconazole (FLC), particularly in . FLC:ZOL combinations had increased fungicidal and antibiofilm activity compared to either drug alone, and the combination prevented the development of antifungal resistance. Mechanistic investigations demonstrated that the synergy was mediated by the depletion of squalene, resulting in the inhibition of ergosterol biosynthesis and a compromised membrane structure. In , synergy compromised the function of membrane-bound multidrug transporters and caused an accumulation of reactive oxygen species, which may account for its acute sensitivity to FLC:ZOL. The efficacy of FLC:ZOL was confirmed in a infection model, where combinations improved the survival of larvae infected with and to a greater extent than monotherapy with FLC or ZOL, and at reduced dosages. These findings demonstrate that bisphosphonates and azoles are a promising new combination therapy for the treatment of topical candidiasis.
IMPORTANCE
is a common and often very serious opportunistic fungal pathogen. Invasive candidiasis is a prevalent cause of nosocomial infections with a high mortality rate, and mucocutaneous infections significantly impact the quality of life of millions of patients a year. These infections pose substantial clinical challenges, particularly as the currently available antifungal treatment options are limited in efficacy and often toxic. Azoles are a mainstay of antifungal therapy and work by targeting the biosynthesis of ergosterol. However, there are rising rates of acquired azole resistance in various species, and some species are considered intrinsically resistant to most azoles. Our research demonstrates the promising therapeutic potential of synergistically enhancing azoles with non-toxic, FDA-approved bisphosphonates. Repurposing bisphosphonates as antifungal synergists can bypass much of the drug development pipeline and accelerate the translation of azole-bisphosphonate combination therapy.
Topics: Antifungal Agents; Drug Synergism; Microbial Sensitivity Tests; Azoles; Humans; Diphosphonates; Candida; Animals; Drug Resistance, Fungal; Candidiasis; Fluconazole; Biofilms; Candida glabrata; Candida albicans
PubMed: 38695556
DOI: 10.1128/spectrum.00121-24 -
National Journal of Maxillofacial... 2024While fluconazole use is generally considered safe and well-tolerated, there has been an increasing number of reports regarding several adverse events. Therefore, the...
While fluconazole use is generally considered safe and well-tolerated, there has been an increasing number of reports regarding several adverse events. Therefore, the present study aimed to present a unique case in which photobiomodulation therapy (PBMT) was employed to manage bullous erythema multiforme lesions secondary to fluconazole intake. A 32-year-old female patient sought emergency dental care due to painful orofacial lesions that had developed two days after oral fluconazole use for recurrent vulvovaginal candidiasis. Given the acute clinical features, a diagnosis of bullous erythema multiforme secondary to fluconazole was established. Prednisone 20 mg was then prescribed for five days, and fluconazole intake was immediately discontinued. As the initial treatment strategies failed to show improvement in the clinical condition, three PBMT sessions were proposed every other day. Within seven days, almost complete wound healing was observed, and any pain complaints were no longer present. The resolution of orofacial lesions within a short period suggests that PBMT could be a promising tool for managing drug-induced bullous erythema multiforme. However, more studies are needed to confirm this statement.
PubMed: 38690232
DOI: 10.4103/njms.njms_128_22