- Volume 3, Issue 12, 2021
Volume 3, Issue 12, 2021
- Abstracts from the Candida and Candidiasis Meeting 2021
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- Poster Presentations
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The microbial ecology of Candida albicans strains CHN1 and SC5314 in mice
More LessStrain SC5314 is the most widely studied strain of Candida albicans. Despite C. albicans being the most commonly isolated yeast from the human gastrointestinal (GI) microbiome, strain SC5314 does not stably colonize the mouse GI tract long term, even after antibiotic disruption. In contrast, strain CHN1 will stably colonize the mouse GI tract long term. Comparative genomic analysis of strain CHN1 indicates that it belongs to a different evolutionary clade of C. albicans than strain SC5314. Previous studies from our laboratory have shown that colonization by strain CHN1 causes a change in the GI bacterial microbiome of mice and predisposes them to more robust Th2 immune responses. Despite this, little is known about the GI microbial ecology of SC5314 vs. CHN1 and subsequent host responses. Using a short-term antibiotic disruption model in C57BL/6 mice, we have been able to observe significantly different colonization kinetics between these two C. albicans strains, with CHN1 establishing stable long-term colonization. In contrast, colonization by SC5314 was lower, highly variable and cage-dependent. C. albicans colonization kinetics impacted the composition of the bacterial microbiome with a marked effect on the levels of Lactobacillus and Enterococcus. qPCR analysis of 46 host immune response genes did not detect significant differences in host gene expression between SC5134 and CHN1 colonized mice, except for chitinase expression. Thus, these studies suggest that yeast-bacteria interactions in the microbiome may be far more important in determining long-term colonization potential of C. albicans and secondary immunomodulatory effects.
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Tell me what type of extracellular vesicles you secrete, and I will tell you who you are: yeast or hypha
The transition between yeast and hyphal morphologies plays a crucial role in the pathogenicity of Candida albicans. Recent studies have pointed out the great relevance of extracellular vesicles (EVs) secreted by microorganisms in a wide variety of biological processes including interaction with the host. Therefore, the main objective of this work was to compare the EVs secreted by yeast and hyphal forms to shed light on C. albicans-host interaction.
EVs were obtained by ultracentrifugation of the culture medium supernatant and analysed by mass spectrometry. They were characterized by transmission electronic microscopy (TEM) and dynamic light scattering (DLS).
DLS and TEM analysis showed that yeast EVs were significantly bigger than hyphal EVs, being most of them in the range between 400 to 500nm while hyphal EVs were ranged mostly around 100-200nm.
Proteomic analysis showed greater protein diversity in hyphal EVs when compared to yeast EVs (up to 1700 different proteins identified versus 300), although less amount of total protein was obtained. Gene Ontology (GO) analysis showed that yeast EVs were enriched in surface proteins while hyphal EVs, although containing also most of these surface proteins, were also significantly and exclusively enriched in proteins involved in protein metabolism (ribosomal proteins, many aminoacid-pathway enzymes and proteasome) and cellular transport. The differences between YEVs and HEVs also prompted a different immune host response, as tested with macrophage cell cultures and human sera from patients with invasive candidiasis.
All these differences point out a possible different biogenesis and roles of EVs secreted by both morphologies.
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Candida glabrata MSH2 deletion increases antifungal tolerance in vitro and during intra-abdominal candidiasis (IAC), it does not impact pathogenesis of peritonitis or intra-abdominal abscesses
More LessBackground:IAC is the second most common type of invasive Candidiasis, but its pathogenesis is poorly understood. We have shown that Candida albicans DNA damage response genes are strongly induced within intra-abdominal abscesses. Deletion of C. glabrata MSH2, A DNA mismatch repair (MMR) gene, results in a mutator phenotype that facilitates multidrug resistance in vitro and in mouse gastrointestinal tracts. Our goal was to determine if CGMSH2 Contributed to pathogenesis or resistance to the new antifungal rezafungin during IAC.
Methods:We createdΔMSH2 in BG2 using SAT-Flipper, and tested virulence and rezafungin responses in a mouse model of IAC.
Results:ΔMSH2 displayed no growth defects at 30°C in liquid (YPD, Ypglycerol) or solid media (YPD+0.02% MMS, 1MM H2O2, 1M NACL, 20 UG/ML CW, 250 UG/ML OR 0.02% SDS). ΔMSH2 longevity in YPD was comparable to BG2. Caspofungin-, Rezafungin- and Fluconazole-resistant mutants arose 24-, 16- and 3-fold more often, respectively, for ΔMSH2 than BG2 (108-106 CFU overnight in YPD, selected on 8XMIC-Containing plates). However, respective minimum inhibitory concentrations (MICS) were not different, nor were rezafungin time-kills.ΔMSH2 was comparable to BG2 in peritonitis and abscess burdens in mouse IAC.ΔMSH2 demonstrated significantly greater caspofungin- and fluconazole-tolerance than BG2 in abscesses. Rezafungin reduced peritonitis and abscess burdens ofΔMSH2,BG2 ANDFKS mutant strains to similar extents.
Conclusions:CgMSH2 deletionincreased the frequency of spontaneously-arising echinocandin- and fluconazole-resistant colonies in vitro and tolerance in intra-abdominal abscesses, but it did not attenuate virulence or rezafungin responses during IAC.
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Ambisome shows potent anti-Candida auris in vitro and in vivo activity
More LessCandida auris is an emerging multidrug resistant Candida species that has been reported in many parts of the world for causing severe illness in hospitalized patients especially bloodstream infections. The challenge with this type of yeast is its resistance to commonly used antifungal drugs, thus identifying antifungals that are effective against this species is critical.
In this study, we determined the in vitro activity of Ambisome against 35 clinical isolates of C. auris using minimum inhibitory concentration (MIC) assay as well as the efficacy of Ambisome compared to Amphotericin B and fluconazole using a C. auris murine disseminated model.
Antifungal activity of C. auris against Ambisome and comparators was assessed using amicrodilution method performed according to the Clinical and Laboratory Standard Institute (CLSI) M27-A4 methodology. Mice were immunocompromised and challenged with 3 x 107 C. auris blastopores in 0.1 ml of normal saline (via the tail vein). Treatment efficacy was assessed by determining reductions in mortality as well as decrease in tissue fungal burden (CFUs).
Ambisome showed lower MIC50 and MIC90 values (1 and 2 μg/mL, respectively) than the comparators tested. Significant efficacy was observed in the Ambisome 7.5 mg/kg -treated group (100% and 90% survival by day 7- and 14-days post inoculation, respectively). Additionally, Ambisome and fluconazole treated groups showed significant reduction in CFUs in the kidneys (P- values of 0.028 and 0.022, respectively) compared to the untreated group.
Our data shows that Ambisome shows significant antifungal activity against C. auris in vitro as well as in vivo.
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Farnesol abrogates biofilm- and efflux pump- associated genes in drug resistant Candida auris strains
More LessBackground:Candida auris, a decade old Candida species, has been identified globally as a significant nosocomial multidrug resistant (MDR) pathogen responsible for causing invasive outbreaks. Biofilms and over expression of efflux pumps such as Major Facilitator Superfamily and ATP Binding Cassette are known to cause multidrug resistance in Candida species, including C. auris. Therefore, targeting these factors may prove an effective approach to combat MDR in C. auris.
Methods:In this study, 25 clinical isolates of C. auris from different hospitals of South Africa were used. Antifungal susceptibility profile of all the isolates against commonly used drugs was determined following CLSI recommended guidelines. Rhodamine-6-G extracellular efflux and intracellular accumulation assays were used to study active drug efflux mechanism. We further studied the role of farnesol in modulating development of biofilms and drug efflux in C. auris. Down-regulation of biofilm- and efflux pump- associated genes by farnesol was also investigated. CLSM analysis for examining C. auris biofilm architecture among treated and untreated isolates.
Results:Most of the isolates (twenty-two) were found resistant to FLZ whereas five were resistant to AmB. All the isolates were found capable of biofilm formation and ornamented with active drug efflux mechanism. The MIC for planktonic cells ranged from 62.5-125 mM and for sessile cells was 125 mM (0 h and 4 h biofilm) and 500 mM (12 h and 24 h biofilm), CLSM studies also confirmed these findings. Farnesol also blocked efflux pumps and down-regulated biofilm- and efflux pump- associated genes.
Conclusion:Modulation of biofilm- and efflux pump- associated genes by farnesol represent a promising approach in combating C. auris infection.
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Role for the phosphatidylinositol 3-phosphate 5-kinase in antifungal tolerance in Candida glabrata
More LessCandida glabrata is an opportunistic fungal pathogen of humans, which is intrinsically less susceptible to widely used azole antifungals, that block ergosterol biosynthesis. The major azole resistance mechanisms include mitochondrial dysfunction and multidrug efflux pump overexpression. In the current study, we have uncovered an essential role for the actin cytoskeletal network reorganization in survival of the azole stress. We demonstrate for the first time that the azole antifungal fluconazole induces remodelling of the actin cytoskeleton in C. glabrata, and genetic or chemical perturbation of actin structures results in intracellular sterol accumulation and azole susceptibility. Further, we showed that the vacuolar membrane-resident phosphatidylinositol 3-phosphate 5-kinase (CgFab1) is pivotal to this process, as CgFAB1 disruption impaired vacuole homeostasis and actin organization. We also showed that the actin depolymerization factor CgCof1 binds to phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), and CgCof1 distribution along with the actin filament-capping protein CgCap2 is altered upon both CgFAB1disruption and fluconazole exposure. Additionally, while the F-actin-stabilizing compound jasplakinolide rescued azole toxicity in cytoskeleton defective-mutants, the actin polymerization inhibitor latrunculin B rendered fluconazole fully and partially fungicidal in azole-susceptible and azole-resistant C. glabrata clinical isolates, respectively. These data underscore the essentiality of actin cytoskeleton reorganization for azole stress survival. Lastly, we have also shown a pivotal role of CgFab1 kinase activity regulators, CgFig4, CgVac7 and CgVac14, through genetic analysis, in azole and echinocandin antifungal tolerance. Altogether, I shall present our findings on functions and metabolism of the PI(3,5)P2 lipid in antifungal tolerance and virulence of C. glabrata.
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Novel antifungal activity of Q-Griffithsin, a broad-spectrum antiviral lectin
More LessBackgroundThere is a rising global trend in candida strains with high resistance to fluconazole and other antifungal drugs, hence the need for novel agents. Here, we investigated the anti-Candida activity of Q-Griffithsin (Q-GRFT), a lectin naturally produced by the red-sea algae, Griffithsia spp.
MethodsTo assess in vitro growth inhibitory activity, C. albicans was incubated with Q-GRFT on agar plates and in broth media. We investigated GFP-bound Q-GRFT’s ability to adhere to C. albicans using fluorescence microscopy and fluorescence intensity assessments. To demonstrate in vivogrowth inhibitory activity, CBA/J mice were treated per vaginam with Q-GRFT followed by challenge with C. albicans, and fungal burden determined following vaginal lavage.
ResultsWild type fluorescently labeled Q-GRFT displayed higher fluorescence than the lectin-binding site deficient variant following incubation with C. albicans. Q-GRFT localized around the fungal cells and bound to α-mannan in the cell wall. Q-GRFT significantly inhibited C. albicans growth in broth and on agar plates, disrupted the integrity of the cell wall, and induced ROS formation. The lectin significantly inhibited the growth of C. glabrata, C. parapsilosis and C. krusei, with modest activity against C. auris CDC388 and C. auris CDC389 strains in vitro. Topical treatment resulted in a lower fungal burden compared to the vehicle control group in vaginal candidiasis.
ConclusionQ-GRFT binds to and inhibits C. albicans growth both in vitro and in vivo. Further studies are needed to establish the mechanism of growth inhibition.
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CRISPR-Cas9 mutagenesis and single gene reintegration suggests functional diversity within the Candida albicans TLO gene family
More LessCandida albicans has between 10-15 Telomere-associated ORF family(TLO)genes, whereas its closest relative, Candida dubliniensis, has two. The Tlo proteins are components of the Mediator complex which plays an important role in transcriptional regulation. CRISPR-Cas9 mutagenesis was used to generate a TLOnull mutant of C. albicans. Phenotypic analysis of the mutant showed significantly reduced fitness, with major defects in growth rate, morphogenesis, stress resistance and virulence in a Galleria mellonellamodel. Clade representative TLOα1, TLOβ2 and TLOγ11constructs were reintroduced into the null mutant background to determine if members of the TLO gene family exhibit functional differences. The genes were reintroduced under the control of the TET1 and ENO1promoters. TLOα1and TLOβ2expression restored stress tolerance and growth rate, in some cases to the level of the WT. TLOβ2expression also showed a dramatic effect on morphology resulting in constitutive true hyphal growth. Moderate expression of TLOγ11 had no detectable effect on many of the phenotypes tested, however overexpression increased biofilm formation in Spider medium, and also conferred increased resistance to cell wall stressors. These data suggest that individual TLO genes have distinct functions and that the diversity within the TLO family may contribute to the relative success of C. albicans as a coloniser and pathogen of humans.
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Tolerance to fluconazole in Candida albicans is regulated by temperature and aneuploidy
More LessCandida albicans is a prevalent human fungal pathogen. Azoles are the most widely used antifungal drugs. Drug tolerance in bacteria is well defined and thoroughly studied, but in fungi, the definition of drug tolerance and the mechanism that drive it are not well understood. Here, we found that a large proportion of clinical isolates were intrinsically tolerant to fluconazole, and/or could be induced by high temperature (37°C) to become tolerant (conditionally tolerant). When treated with inhibitory doses of fluconazole, non-tolerant strains became tolerant by forming aneuploids involving different chromosomes, with chromosome R duplication as the most recurrent mechanism. Tolerance determines the ability to grow in the presence of fluconazole and other azoles, in a manner independent of the MIC. Both temperature conditional tolerance and the associated aneuploidy were sensitive to FK506, an inhibitor of calcineurin. Intrinsic and conditional tolerance were also abolished by deletions of genes encoding the calcineurin (CMP1 and CNB1). However, the dependence of tolerance on calcineurin could be bypassed by a different aneuploid chromosome. Thus, fluconazole tolerance in C. albicans is regulated by temperature and by aneuploidy and is dependent upon aneuploidy, but this dependence can be bypassed by an additional aneuploidy.
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Preliminary study into the effects of tobacco smoke on Candida albicans
More LessBackground:Denture-stomatitis (DS) is the most common form of oral candidosis with increased prevalence in cigarette smokers (Akram et al. 2018). Interestingly, tobacco condensate (TC) increases Candida albicans adhesion, growth, biofilm-formation, virulence gene expression (Semlali et al. 2014)and hyphal production (Awad and Karuppayil 2018). We hypothesised that TC-treated denture acrylic would therefore affect C. albicans within acrylic biofilms.
Methods:Acrylic discs (pre-conditioned with TC, artificial saliva (AS) or water) were incubated at 37°C with C. albicans (n=6) for 90 min or 24 h. Adherent Candida were stained with calcofluor white and confocal laser scanning microscopy (CLSM) used to assess levels of adherence, biofilm and hyphal numbers. Expressed virulence genes (n=7) were measured by qPCR.
Results:CLSM showed that effects of TC-treatment were strain dependent. Adherence of C. albicans PTR/94 to TC-treated surfaces was significantly (P<0.002) lower than on the untreated control. Biofilm levels of PTR/94 after 24 h were found to be significantly higher on AS-treated acrylic than the TC-treated and untreated control. Five strains had significantly fewer filamentous forms after 90 min on TC-treated surfaces. TC-treatment promoted hyphal levels for strain 705/93 after 24h.
Conclusion:TC pre-conditioning altered adherence and biofilm coverage of C. albicans to acrylic surfaces and influenced hyphal development. Work is ongoing to ascertain the significance of these effects on C. albicans pathogenicity.
Akram et al. (2018). Journal of Oral Science 60(1):115–120.
Awad and Karuppayil (2018). American Journal of Clinical Microbiology and Antimicrobials1(3):1–6.
Semlali et al. (2014). BMC Microbiology. 14:61
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Proteomic study of the effect of metformin on C. albicans
More LessFungal infections are a global health problem. Of them, those produced by Candida albicans are the most important, with a reduced arsenal of antifungals and an increasing problem of antifungal resistance. Thus, the discovery of new antifungal targets and drugs remains interesting. Metformin is a biguanide administered as a first-line treatment for Type II Diabetes Mellitus and it has recently been published its anti-Candida action, especially against C. glabrata, and its synergistic effect with other antifungals. Our studies of the effect of metformin on C. albicans have revealed an inhibition of growth, filamentation and other phenotypes important for virulence. Although metformin has been described as an AMPK agonist, its mechanism of action is partly unknown. To deepen into the anti-Candida mechanism of action, we have addressed the differential proteomic study. A set-up of the conditions for the proteomic study has been carried out, fixing a concentration of 50mM of metformin, 6 h of treatment at 37°C in RPMI medium and with 60 rpm of agitation. The proteomic study using the Labelfree technique and 4 biological replicas, allowed the identification and quantification of a total of 1899 proteins, 206 of them presenting differences in abundance due to metformin exposure. Of these, 127 increased and 79 decreased due to the action of the drug. The most relevant functions of these proteins are related to antifungal response, filamentation, biofilm formation and metabolism, being 9 essential proteins for the microorganism that could be new antifungal targets.
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The gut commensal Bacteroides vulgatus mpk reduces Candida albicans pathogenicity towards epithelial cells
The human body is colonized by various microbes, among them the yeast Candida albicans. Mostly harmless, this opportunist causes also disease, ranging from superficial infections to sepsis. Risk factors are disturbed host defenses, mucosal barrier breakdown, and antibiotic-induced dysbiosis. Hence, residing bacteria are important to protect from Candida-mediated damage or inflammation. Bacteroides vulgatus mpk, e.g., is described as positively immunomodulatory in mouse models of inflammatory bowel disease, but its effect on the mycobiota is unknown.
In this study we aimed to determine if B. vulgatus mpk affects C. albicans pathogenicity.
Therefore, intestinal and oral epithelial cellswere pre-infectedin vitrowith B. vulgatus mpk and then challenged with C. albicans SC5314. The role of soluble factors was investigated by spatial separation or use of Bacteroides-conditioned medium (BCM).
Preincubation of host cells with B. vulgatus mpk strongly reduced C. albicans-mediated damage while fungal burden and hyphal length were unaffected by the bacterium. The protective effect did not depend on direct contact of Bacteroidesto host cellsor Candida and could be mimicked using BCM. Contact independency suggests that diffusible factors modulate host cell susceptibility.
Ongoing experiments aim to identifykey soluble Bacteroides mediators as well as subsequent host cell signaling. Additionally, co-colonization experiments of germ-free mice are planned to investigate B. vulgatus mpk’s potential to mediate colonization resistance towards C. albicans. This will contribute to our understanding of how commensal bacteria affect C. albicans and host protection.
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The effect of acquired triazole resistance on abiotic stress tolerance and virulence in Candida auris micro evolved strains
More LessRecently, C. auris become one of the most prominent members of the genus Candida. Since its occurrence, several C. auris outbreaks have been reported worldwide. These outbreaks were associated with isolates displaying decreased susceptibility towards fluconazole, the first-line agent for prophylaxis. Fluconazole is the most frequently used antifungal drug to treat bloodstream Candida infections.
The physiological effects of acquired antifungal resistance was investigated in this species using fluconazole, posaconazole and voriconazole resistant mutant strains generated by the in vitro microevolution method. Alterations in antifungal susceptibility and cross resistance were determined by the microdilution method, utilizing azoles (fluconazole, voriconazole, posaconazole), echinocandins (caspofungin, micafungin, anidulafungin) and a polyene (amphotericin B). Changes in the abiotic stress tolerance was examined by spotting assay, using osmotic stressors, cell wall perturbants and a membrane detergent. To evaluate the impact of the acquired resistance on sterol biosynthesis, ergosterol composition of all generated mutant strains were examined. A potential relationship between virulence and acquired antifungal resistance was also studied both in vitro and in vivo. Phagocytosis of the generated strains by J774.2 mouse macrophage-like cells was measured and analyzed by flow cytometry. In the murine infection model fungal burden of the triazole evolved strains was determined in spleen, kidney, liver and brain and compared to the fungal burden associated with the initial azole susceptible strain. Significant differences in virulence of the initial and the generated strains was observed suggesting a potential connection between the virulence and antifungal susceptibility of the emerging fungal pathogen, C. auris.
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Extending the proteomic characterization of Candida albicans exposed to stress and apoptotic inducers through data-independent acquisition mass espectrometry
More LessCandida albicans is a commensal fungus that causes systemic infections in immunosuppressed patients. In order to deal with the changing environment during commensalism or infection, C. albicans must reprogram its proteome. Characterizing the stress-induced changes in the proteome that C. albicans uses to survive should be very useful in the development of new antifungal drugs. We studied the C. albicans global proteome after exposure to hydrogen peroxide (H2O2) and acetic acid (AA), using a DIA-MS strategy. More than 2000 C. albicans proteins were quantified using an ion library previously constructed using DDA-MS. C. albicans responded to treatment with H2O2 with an increase in the abundance of many proteins involved in the oxidative stress response, protein folding and proteasome-dependent catabolism, which led to an increased proteasome activity. The data revealed a previously unknown key role for Prn1, a protein similar to pirins, in the oxidative stress response. Treatment with AA resulted in a general decrease in the abundance of proteins involved in amino acid biosynthesis, protein folding, and rRNA processing. Almost all proteasome proteins declined, as did proteasome activity. Apoptosis was observed after treatment with H2O2, but not AA. A targeted proteomic study of 32 proteins related to apoptosis in yeast supported the results found by DIA-MS and allowed the creation of an efficient method to quantify relevant proteins after treatment with stressors (H2O2, AA, and amphotericin B). This approach also uncovered a main role for Oye32, an oxidoreductase, suggesting this protein as a possible apoptotic marker common to many stressors.
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- Personal Views
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- Case Reports
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Detection of invasive Trichosporon asahii in patient blood by a fungal PCR array
Rare invasive fungal infections are increasingly emerging in hosts with predisposing factors such as immunodeficiency. Their timely diagnosis remains difficult, as their clinical picture may initially mimic infections with more common fungal species and species identification may be difficult with routine methods or may require time-consuming subcultures. This often results in ineffective drug administration and fatal outcomes. We report on a patient in their early twenties with mixed cellularity classical Hodgkin lymphoma with a disseminated Trichosporon asahii (T. asahii) infection. Even though pathogen detection and identification was possible via the standard procedure consisting of culture followed by matrix-assisted laser desorption ionisation–time of flight (MALDI-TOF) mass spectrometry, the patient passed away in the course of multi organ failure. Herein, we report on a retrospectively applied experimental diagnostic fungal PCR-analysis used on an EDTA blood sample and consisting of two pan-fungal reactions and seven branch-specific reactions. Regarding invasive T. asahii infection, this PCR array could considerably shorten time to diagnosis and switch to a targeted therapy with triazoles.
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Sneathia amnii bacteraemia and chorioamnionitis leading to second trimester abortion: a case report
More LessBackground. Sneathia amnii (formerly designated as Leptotrichia amnionii ) was first described in 2002 in the USA. Members of the genus Sneathia can be part of the normal flora of the genitourinary tract, but have been implicated in invasive (mostly gynaecological) infections.
Case presentation. To the best of our knowledge, here we present the first case of S. amnii infection in Belgium, in a young woman presenting with fever leading to second trimester septic abortion.
Conclusions. Despite its pathogenicity, S. amnii remains an underrated cause of infections due to inherent difficulties with conventional laboratory methods. By extracting the bacterial DNA directly from the blood culture broth and performing a 16S ribosomal RNA gene sequence analysis we succeeded in identifying S. amnii as the most probable cause of the septic abortion in our patient.
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Penile implant infection resulting in Staphylococcus aureus bacteraemia and infective endocarditis
More LessIntroduction. Penile implant infections are a possible surgical complication that has historically been most commonly associated with Gram-positive bacteria. Staphylococcus aureus is a Gram-positive bacteria and is the most common cause of endocarditis.
Case Presentation. A male patient in his 50s with a past medical history of hypertension, diabetes, end-stage renal disease (ESRD) on peritoneal dialysis (PD) and erectile dysfunction with a penile implant placed 6 years prior to the admission date presented with complaints of scrotal pain. The pump for his implant had eroded through his scrotum and was draining pus. Blood cultures returned positive for Gram-positive cocci in clusters in 4/4 bottles, which was eventually identified as methicillin-sensitive Staphylococcus aureus (MSSA). A transthoracic echocardiogram (TTE) was performed due to concern for infective endocarditis (IE) but did not show any valvular abnormalities. Due to high clinical suspicion, a transesophageal echocardiogram (TEE) was performed and revealed a vegetation on the native mitral valve. His penile implant was removed by urology and intraoperative cultures grew MSSA. Surgical valve replacement was not recommended, and the patient was sent home with IV antibiotics for 6 weeks.
Discussion. Post-operative site infections are a quite uncommon point of entry for infective endocarditis, with penile implant infections being an even rarer cause. While a TTE is often used initially to attempt to diagnose infective endocarditis, it has lower sensitivity than a TEE. If clinical suspicion for infective endocarditis remains high after negative imaging with TTE, then TEE should be performed for better visualization of the heart valves.
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Reactivation of Q fever: case report of osteoarticular infection developing at the site of a soft tissue injury
More LessCoxiella burnetii , the causative agent of Q fever, is known to cause acute and persistent infection, but reactivation of infection is rarely reported. This case demonstrates reactivation of a distant, untreated Q fever infection after a relatively innocuous soft tissue injury in an adjacent joint without pre-existing pathology. A 52-year-old male abbatoir worker sustained an adductor muscle tear in a workplace injury. He was unable to walk thereafter, and developed a chronic, progressive, destructive septic arthritis of the adjacent hip with surrounding osteomyelitis of the femur and acetabulum. He had evidence of prior Q fever infection, with a positive skin test and serology 15 years beforehand. He was diagnosed with chronic osteoarticular Q fever on the basis of markedly elevated phase I antibodies, and symptomatic and serological response to prolonged antibiotic treatment with doxycycline and hydroxychloroquine. He required a two-stage hip arthroplasty. This case illustrates reactivation of latent C. burnetii infection at the site of a soft tissue injury. Clinicians need to be aware of this possibility in patients with previous Q fever infection, and in the setting of undiagnosed osteoarticular pathology following soft tissue injury.
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Dengue 2 serotype and yellow fever coinfection
Case Presentation. Arboviruses primarily consist of RNA, which favours greater genetic plasticity, with a higher frequency of mutations that allow the virus to adapt to different hosts. The initial symptomatology is nonspecific, in that the patient can present fever, myalgia, arthralgia, rash and headache. This makes a clinical diagnosis using laboratory tests difficult and time-consuming. In Brazil, the main arboviruses involved in epidemics belong to the family Flaviviridae. The patient in this case is from the municipality of São Bernardo do Campo, an area endemic for arboviruses. He presented symptoms of fever, myalgia and headache.
Results. The multiplex assay for arboviruses detected genetic material from the dengue 2 and yellow fever viruses.
Conclusion. This result confirms the importance of molecular tests showing high sensitivity and specificity that can assist clinical diagnosis, particularly in endemic areas during periods of outbreak for other arboviruses, like the epidemiological picture in Brazil in 2018, when significant co-circulation of dengue virus and yellow fever virus occurred. The presence of co-circulating arboviruses increases the chance of coinfection and demonstrates the importance of differential diagnosis.
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Corynebacterium striatum thrombophlebitis: a nosocomial multidrug-resistant disease?
Introduction. Corynebacterium striatum is a non-Diphteriae commensal bacterium with a wide range of pathogenicity. The identification of multidrug-resistant (MDR) C. striatum is concerning because drug susceptibility testing is not usually performed in microbiology laboratories. There is no consensus yet on the treatment of septic thrombophlebitis in this situation.
Case report. We report here the first case of a quinquagenarian patient with a history of AIDS and fungic endocarditis, who was diagnosed with a nosocomial thrombophlebitis in the right jugular vein caused by C. striatum . Bitherapy with daptomycin for 12 days and linezolid for 23 days was combined with a therapeutic anticoagulant. The follow-up included weekly cervical ultrasound controls. The efficiency of the treatment and the stability of the lesions allowed us to alleviate the medication with a prophylactic dose of anticoagulant. The patient was discharged from hospital and showed no signs of recurrence after 12 months.
Conclusion. The lack of consensus relative to the management of septic thrombophlebitis precludes the validation of a specific treatment for the condition. Our results suggest that a combination that includes removal of the medical device is needed. A total of 6 weeks of antibiotherapy should be applied, starting with 2 weeks of vancomycin or a combination of antibiotitherapy with daptomycin in order to reduce the bacterial load and avoid resistance. Six weeks of anticoagulation therapy is effective.
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Rapid identification of mcr-1-positive Escherichia coli from patient urine using a novel lipid-based MALDI-TOF-MS assay
More LessMobilized colistin resistance (mcr) genes confer resistance to colistin, a last-resort antibiotic for multidrug-resistant Gram-negative infections. In this case report, we describe a novel lipid-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) diagnostic used to rapidly identify an mcr-1-positive Escherichia coli directly from a patient with a urinary tract infection without the need for ex vivo growth.
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- Case Series
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Spectrum of mycobacterial pathogens responsible for head and neck tuberculosis-like presentation
More LessTuberculosis (TB) of the head and neck can be contained in the lymph nodes, larynx, oropharynx, salivary glands, nose and paranasal sinuses, ear, skin and skull. Head and neck TB presentations are varied in nature and thus difficult to diagnose. The clinical features, radiological findings, microbiological diagnostic modalities, surgical and medical management and outcomes of nine cases of head and neck TB are discussed in detail here, together with a thorough review of the literature. Patients presented with atypical symptoms such as discharging sinus, ear lobule swelling, otitis media, vision loss and facial weakness, long refractory otorrhoea and granulation tissue in the ear canal. We diagnosed tubercular skull base osteomyelitis (one case) and laryngeal tuberculosis (two cases), mastoid tuberculosis (one case) and non-tubercular mycobacterial infection involving the temporal bone (two cases), sino-nasal region (one case), maxilla (one cases) and ear lobule (one case) over a period of 8 months. All patients were managed successfully with a combination of surgery and a well-planned treatment regimen for non-tuberculous mycobacteria (NTM) or anti-tubercular drugs for TB. All had successful outcomes except one patient with tubercular skull base osteomyelitis who expired before the initiation of anti-tubercular therapy (ATT). High clinical suspicion followed by thorough diagnostic work-up for both TB and NTM would enable early diagnosis and complete treatment.
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