Sporotrichosis Cluster in Domestic Cats and Veterinary Technician, Kansas, USA, 2022.

We describe a feline sporotrichosis cluster and zoonotic transmission between one of the affected cats and a technician at a veterinary clinic in Kansas, USA. Increased awareness of sporotrichosis and the potential for zoonotic transmission could help veterinary professionals manage feline cases and take precautions to prevent human acquisition.

Bimodal distribution of azole susceptibility in Sporothrix brasiliensis isolates in Brazil.

Sporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phylogenetic analysis found the in vitro resistant isolates were not clonal and were distributed across three different S. brasiliensis clades. Single nucleotide polymorphism (SNP) analysis was performed to identify potential mechanisms of in vitro resistance. Two of the 28 resistant isolates (MIC ≥16 mg/L) had a polymorphism in the cytochrome P450 gene, cyp51, corresponding to the well-known G448S substitution inducing azole resistance in Aspergillus fumigatus. SNPs corresponding to other known mechanisms of azole resistance were not identified in the remaining 26 in vitro resistant isolates.

Worsening Spread of Candida auris in the United States, 2019 to 2021.

BACKGROUND: Candida auris is an emerging fungal threat that has been spreading in the United States since it was first reported in 2016. OBJECTIVE: To describe recent changes in the U.S. epidemiology of C auris occurring from 2019 to 2021. DESIGN: Description of national surveillance data. SETTING: United States. PATIENTS: Persons with any specimen that was positive for C auris. MEASUREMENTS: Case counts reported to the Centers for Disease Control and Prevention by health departments, volume of colonization screening, and antifungal susceptibility results were aggregated and compared over time and by geographic region. RESULTS: A total of 3270 clinical cases and 7413 screening cases of C auris were reported in the United States through 31 December 2021. The percentage increase in clinical cases grew each year, from a 44% increase in 2019 to a 95% increase in 2021. Colonization screening volume and screening cases increased in 2021 by more than 80% and more than 200%, respectively. From 2019 to 2021, 17 states identified their first C auris case. The number of C auris cases that were resistant to echinocandins in 2021 was about 3 times that in each of the previous 2 years. LIMITATION: Identification of screening cases depends on screening that is done on the basis of need and available resources. Screening is not conducted uniformly across the United States, so the true burden of C auris cases may be underestimated. CONCLUSION: C auris cases and transmission have risen in recent years, with a dramatic increase in 2021. The rise in echinocandin-resistant cases and evidence of transmission is particularly concerning because echinocandins are first-line therapy for invasive Candida infections, including C auris. These findings highlight the need for improved detection and infection control practices to prevent spread of C auris. PRIMARY FUNDING SOURCE: None.

Rapid Environmental Contamination with Candida auris and Multidrug-Resistant Bacterial Pathogens Near Colonized Patients.

BACKGROUND: Environmental contamination is suspected to play an important role in Candida auris transmission. Understanding speed and risks of contamination after room disinfection could inform environmental cleaning recommendations. METHODS: We conducted a prospective multicenter study of environmental contamination associated with C. auris colonization at six ventilator-capable skilled nursing facilities and one acute-care hospital in Illinois and California. Known C. auris carriers were sampled at five body-sites followed by sampling of nearby room surfaces before disinfection and at 0, 4, 8, and 12-hours post-disinfection. Samples were cultured for C. auris and bacterial multidrug-resistant organisms (MDROs). Odds of surface contamination after disinfection were analyzed using multilevel generalized estimating equations. RESULTS: Among 41 known C. auris carriers, colonization was detected most frequently on palms/fingertips (76%) and nares (71%). C. auris contamination was detected on 32.2% (66/205) of room surfaces pre-disinfection and 20.5% (39/190) of room surfaces by 4-hours post-disinfection. A higher number of C. auris-colonized body sites was associated with higher odds of environmental contamination at every time point following disinfection, adjusting for facility of residence. In the rooms of 38 (93%) C. auris carriers co-colonized with a bacterial MDRO, 2%-24% of surfaces were additionally contaminated with the same MDRO by 4-hours post-disinfection. CONCLUSIONS: C. auris can contaminate the healthcare environment rapidly after disinfection, highlighting the challenges associated with environmental disinfection. Future research should investigate long-acting disinfectants, antimicrobial surfaces, and more effective patient skin antisepsis to reduce the environmental reservoir of C. auris and bacterial MDROs in healthcare settings.

Evaluating the Presence of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From Nursing Home Residents With Persistently Positive Reverse Transcription Polymerase Chain Reaction (RT-PCR) Results.

Replication-competent virus has not been detected in individuals with mild to moderate coronavirus disease 2019 (COVID-19) more than 10 days after symptom onset. It is unknown whether these findings apply to nursing home residents. Of 273 specimens collected from nursing home residents >10 days from the initial positive test, none were culture positive.

Tools for Detecting a "Superbug": Updates on Candida auris Testing.

Candida auris is an emerging yeast species that has the unique characteristics of patient skin colonization and rapid transmission within health care facilities and the ability to rapidly develop antifungal resistance. When C. auris first started to appear in clinical microbiology laboratories, it could be identified only by using DNA sequencing. In the decade since its first identification outside of Japan, there have been many improvements in the detection of C. auris. These include the expansion of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) databases to include C. auris, the development of both laboratory-developed tests and commercially available kits for its detection, and special CHROMagar for identification from laboratory specimens. Here we discuss the current tools and resources that are available for C. auris identification and detection.

Positive Correlation Between Candida auris Skin-Colonization Burden and Environmental Contamination at a Ventilator-Capable Skilled Nursing Facility in Chicago.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that contaminates healthcare environments causing healthcare-associated outbreaks. The mechanisms facilitating contamination are not established. METHODS: C. auris was quantified in residents' bilateral axillary/inguinal composite skin swabs and environmental samples during a point-prevalence survey at a ventilator-capable skilled-nursing facility (vSNF A) with documented high colonization prevalence. Environmental samples were collected from all doorknobs, windowsills and handrails of each bed in 12 rooms. C. auris concentrations were measured using culture and C. auris-specific quantitative polymerase chain reaction (qPCR) The relationship between C. auris concentrations in residents' swabs and associated environmental samples were evaluated using Kendall's tau-b (τ b) correlation coefficient. RESULTS: C. auris was detected in 70/100 tested environmental samples and 31/57 tested resident skin swabs. The mean C. auris concentration in skin swabs was 1.22 × 105 cells/mL by culture and 1.08 × 106 cells/mL by qPCR. C. auris was detected on all handrails of beds occupied by colonized residents, as well as 10/24 doorknobs and 9/12 windowsills. A positive correlation was identified between the concentrations of C. auris in skin swabs and associated handrail samples based on culture (τ b = 0.54, P = .0004) and qPCR (τ b = 0.66, P = 3.83e-6). Two uncolonized residents resided in beds contaminated with C. auris. CONCLUSIONS: Colonized residents can have high C. auris burdens on their skin, which was positively related with contamination of their surrounding healthcare environment. These findings underscore the importance of hand hygiene, transmission-based precautions, and particularly environmental disinfection in preventing spread in healthcare facilities.

Clinical and Laboratory Findings in Patients With Potential Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection, May-July 2020.

BACKGROUND: We investigated patients with potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection in the United States during May-July 2020. METHODS: We conducted case finding for patients with potential SARS-CoV-2 reinfection through the Emerging Infections Network. Cases reported were screened for laboratory and clinical findings of potential reinfection followed by requests for medical records and laboratory specimens. Available medical records were abstracted to characterize patient demographics, comorbidities, clinical course, and laboratory test results. Submitted specimens underwent further testing, including reverse transcription polymerase chain reaction (RT-PCR), viral culture, whole genome sequencing, subgenomic RNA PCR, and testing for anti-SARS-CoV-2 total antibody. RESULTS: Among 73 potential reinfection patients with available records, 30 patients had recurrent coronavirus disease 2019 (COVID-19) symptoms explained by alternative diagnoses with concurrent SARS-CoV-2 positive RT-PCR, 24 patients remained asymptomatic after recovery but had recurrent or persistent RT-PCR, and 19 patients had recurrent COVID-19 symptoms with concurrent SARS-CoV-2 positive RT-PCR but no alternative diagnoses. These 19 patients had symptom recurrence a median of 57 days after initial symptom onset (interquartile range: 47-76). Six of these patients had paired specimens available for further testing, but none had laboratory findings confirming reinfections. Testing of an additional 3 patients with recurrent symptoms and alternative diagnoses also did not confirm reinfection. CONCLUSIONS: We did not confirm SARS-CoV-2 reinfection within 90 days of the initial infection based on the clinical and laboratory characteristics of cases in this investigation. Our findings support current Centers for Disease Control and Prevention (CDC) guidance around quarantine and testing for patients who have recovered from COVID-19.

Antifungal activity of nikkomycin Z against Candida auris.

BACKGROUND: Nikkomycin Z is a competitive inhibitor of chitin synthase-an enzyme needed for synthesis of the fungal cell wall. Nikkomycin Z shows promise as a treatment for coccidioidomycoses and mixed activity has been described against other fungi and yeast. To our knowledge, it has not previously been tested against the emerging fungal pathogen Candida auris. OBJECTIVES: To determine the in vitro activity of nikkomycin Z against C. auris. METHODS: Nikkomycin Z was tested by broth microdilution against a panel of 100 isolates of genetically diverse C. auris from around the world. RESULTS: Nikkomycin Z showed mixed activity against the tested isolates, with an MIC range of 0.125 to >64 mg/L. The MIC50 and MIC90 were 2 and 32 mg/L, respectively. CONCLUSIONS: These findings suggest nikkomycin Z has in vitro activity against some, but not all isolates of C. auris.

Regional Emergence of Candida auris in Chicago and Lessons Learned From Intensive Follow-up at 1 Ventilator-Capable Skilled Nursing Facility.

BACKGROUND: Since the identification of the first 2 Candida auris cases in Chicago, Illinois, in 2016, ongoing spread has been documented in the Chicago area. We describe C. auris emergence in high-acuity, long-term healthcare facilities and present a case study of public health response to C. auris and carbapenemase-producing organisms (CPOs) at one ventilator-capable skilled nursing facility (vSNF-A). METHODS: We performed point prevalence surveys (PPSs) to identify patients colonized with C. auris and infection-control (IC) assessments and provided ongoing support for IC improvements in Illinois acute- and long-term care facilities during August 2016-December 2018. During 2018, we initiated a focused effort at vSNF-A and conducted 7 C. auris PPSs; during 4 PPSs, we also performed CPO screening and environmental sampling. RESULTS: During August 2016-December 2018 in Illinois, 490 individuals were found to be colonized or infected with C. auris. PPSs identified the highest prevalence of C. auris colonization in vSNF settings (prevalence, 23-71%). IC assessments in multiple vSNFs identified common challenges in core IC practices. Repeat PPSs at vSNF-A in 2018 identified increasing C. auris prevalence from 43% to 71%. Most residents screened during multiple PPSs remained persistently colonized with C. auris. Among 191 environmental samples collected, 39% were positive for C. auris, including samples from bedrails, windowsills, and shared patient-care items. CONCLUSIONS: High burden in vSNFs along with persistent colonization of residents and environmental contamination point to the need for prioritizing IC interventions to control the spread of C. auris and CPOs.

Insights into the Unique Nature of the East Asian Clade of the Emerging Pathogenic Yeast Candida auris.

The emerging yeast Candida auris can be highly drug resistant, causing invasive infections, and large outbreaks. C. auris went from an unknown pathogen a decade ago to being reported in over thirty countries on six continents. C. auris consists of four discrete clades, based on where the first isolates of the clade were reported, South Asian (clade I), East Asian (clade II), African (clade III), and South American (clade IV). These clades have unique genetic and biochemical characteristics that are important to understand and inform the global response to C. auris Clade II has been underrepresented in the literature despite being the first one discovered. In this issue of the Journal of Clinical Microbiology, Y. J. Kwon et al. (J Clin Microbiol 57:e01624-18, 2019, https://doi.org/10.1128/JCM.01624-18) describe the largest collection of clinical isolates from Clade II, which is also the longest-running span of clinical cases, 20 years, from any single region to date. Clade II appears to have a propensity for the ear that is uncharacteristic of the other clades, which typically cause invasive infections and large-scale outbreaks. This study provides new information on an understudied lineage of C. auris and has important implications for future surveillance.

Phenotypic switching in newly emerged multidrug-resistant pathogen Candida auris.

Candida auris is an emerging, multidrug-resistant yeast that can spread rapidly in healthcare settings. Phenotypic switching has been observed in other Candida species and can potentially interfere with correct identification. The aim of this study is to address misidentification of C. auris by describing alternate phenotypes after broth enrichment and subculturing on CHROMagar Candida. Each isolate displayed different frequencies of phenotypic switching, suggesting a strain to strain variability. Increased knowledge of the multiple phenotypes of C. auris increases the chance of isolating and identifying C. auris by reducing the risk of discarding false negative alternate colony morphologies.

Direct Detection of Emergent Fungal Pathogen Candida auris in Clinical Skin Swabs by SYBR Green-Based Quantitative PCR Assay.

The recent emergence of the multidrug-resistant and pathogenic yeast Candida auris continues to cause public health concern worldwide. C. auris is alarming because it causes health care-associated outbreaks and can establish invasive infections with high mortality rates. Transmission between patients is facilitated by the ability of C. auris to persistently colonize multiple body sites, including the skin, and survive for weeks on surfaces in health care settings. Rapid identification of colonized patients is needed to implement timely infection control measures. Currently, CDC laboratories use an enrichment culture-based approach that can take up to 2 weeks to identify C. auris from composite swabs from the bilateral axillae and groin. A rapid SYBR green quantitative PCR (qPCR) assay that can identify C. auris in a single day was recently described. In this study, we developed the SYBR green qPCR assay further by incorporating a DNA extraction procedure for skin swabs and by including an internal amplification control based on the distinguishable melt curve of a lambda DNA amplicon. The assay was conducted using 103 clinical axilla/groin skin swab samples. Using the enrichment culture-based approach as a gold standard, we determined that the SYBR green C. auris qPCR has a sensitivity of 0.93 and specificity of 0.96. Overall, we found that the SYBR green C. auris qPCR assay can be successfully applied for rapid and accurate detection of C. auris in patient skin swabs, thereby increasing diagnostic options for this emerging pathogen.

Acyl-homoserine lactone quorum sensing: from evolution to application.

Quorum sensing (QS) is a widespread process in bacteria that employs autoinducing chemical signals to coordinate diverse, often cooperative activities such as bioluminescence, biofilm formation, and exoenzyme secretion. Signaling via acyl-homoserine lactones is the paradigm for QS in Proteobacteria and is particularly well understood in the opportunistic pathogen Pseudomonas aeruginosa. Despite thirty years of mechanistic research, empirical studies have only recently addressed the benefits of QS and provided support for the traditional assumptions regarding its social nature and its role in optimizing cell-density-dependent group behaviors. QS-controlled public-goods production has served to investigate principles that explain the evolution and stability of cooperation, including kin selection, pleiotropic constraints, and metabolic prudence. With respect to medical application, appreciating social dynamics is pertinent to understanding the efficacy of QS-inhibiting drugs and the evolution of resistance. Future work will provide additional insight into the foundational assumptions of QS and relate laboratory discoveries to natural ecosystems.

Evaluation of a new T2 Magnetic Resonance assay for rapid detection of emergent fungal pathogen Candida auris on clinical skin swab samples.

Candida auris is a multidrug-resistant pathogenic yeast whose recent emergence is of increasing public-health concern. C. auris can colonise multiple body sites, including patients' skin, and survive for weeks in the health care environment, facilitating patient-to-patient transmission and fueling health care-associated outbreaks. Rapid and accurate detection of C. auris colonisation is essential for timely implementation of infection control measures and to prevent transmission. Currently, axilla/groin composite swabs, used to assess colonisation status, are processed using a culture-based method that is sensitive and specific but requires 14 days. This delay limits the opportunity to respond and highlights the need for a faster alternative. The culture-independent T2 Magnetic Resonance (T2MR) system is a rapid diagnostic platform shown to detect target pathogens of interest from unprocessed blood samples in <5 hours. In this study, a new C. auris-specific T2 assay was evaluated for screening of the skin surveillance samples. Inclusivity and limit of detection of the T2 C.  auris assay were assessed with spiked samples in a representative skin flora background. The T2 C. auris assay recognised isolates from each of the 4 known clades of C. auris and consistently detected cells at 5 CFU/mL. Finally, 89 clinical axilla/groin swab samples were processed with the T2 C. auris assay. The culture-based diagnostic assay was used as a gold standard to determine performance statistics including sensitivity (0.89) and specificity (0.98). Overall, the T2 C. auris assay performed well as a rapid diagnostic and could help expedite the detection of C. auris in patient skin swabs.

Pseudomonas protegens Pf-5 favours self-produced siderophore over free-loading in interspecies competition for iron.

Many microorganisms compete for extracellular iron using strain-specific chelators known as siderophores. The ferric-siderophore complex limits local access to iron because import requires a suitable cognate receptor. Interestingly, many species carry receptors that enable 'cross-feeding' on heterologous siderophores made by neighboring organisms, although little is known about how this ubiquitous behaviour is regulated. Here, we investigated the soil bacterium Pseudomonas protegens Pf-5, a strain remarkable for its ability to use dozens of heterologous siderophores. We characterized the expression of six pyoverdine-type (PVD) siderophore receptors in response to their cognate PVD. In general, we found expression is tightly regulated to reflect availability of their cognate PVD. In contrast, Pf-5 continues to secrete its own primary siderophore, PVDPf-5 , despite the capability and opportunity to cross-feed. We demonstrate that this strategy is beneficial in co-culture with a competing PVDPAO1 -producer, P. aeruginosa PAO1. Although Pf-5 can cross-feed on PVDPAO1 , production of PVDPf-5 is required to maintain a competitive advantage. We attribute this to an antagonistic effect of PVDPf-5 on the growth of PAO1, presumably through limiting access to iron. Our results demonstrate the benefits of excluding competitors out-weigh the incentives associated with a free-loader lifestyle for Pf-5.

Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks.

OBJECTIVE: Despite widespread use of antibiotics for the treatment of life-threatening infections and for research on the role of commensal microbiota, our understanding of their effects on the host is still very limited. DESIGN: Using a popular mouse model of microbiota depletion by a cocktail of antibiotics, we analysed the effects of antibiotics by combining intestinal transcriptome together with metagenomic analysis of the gut microbiota. In order to identify specific microbes and microbial genes that influence the host phenotype in antibiotic-treated mice, we developed and applied analysis of the transkingdom network. RESULTS: We found that most antibiotic-induced alterations in the gut can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues and the effects of remaining antibiotic-resistant microbes. Normal microbiota depletion mostly led to downregulation of different aspects of immunity. The two other factors (antibiotic direct effects on host tissues and antibiotic-resistant microbes) primarily inhibited mitochondrial gene expression and amounts of active mitochondria, increasing epithelial cell death. By reconstructing and analysing the transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria, a finding further validated using in vitro experiments. CONCLUSIONS: In addition to revealing mechanisms of antibiotic-induced alterations, this study also describes a new bioinformatics approach that predicts microbial components that regulate host functions and establishes a comprehensive resource on what, why and how antibiotics affect the gut in a widely used mouse model of microbiota depletion by antibiotics.

Subcutaneous phaeohyphomycosis due to Phaeoacremonium venezuelense: The first clinical case report in Costa Rica.

Phaeoacremonium is a genus of dematiaceous fungi that rarely causes human infections. We describe a case of subcutaneous infection in a 70-year-old diabetic man with lesions on the dorsum of the one foot. The agent was isolated, and for the final identification we performed matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and DNA sequencing. After diagnosis, the patient underwent curettage of the cyst and received 100mg of Itraconazole, twice daily for 6 months. Clinical resolution of the lesion was observed after treatment. This is the first case of infection by Phaeoacremonium venezuelense reported in Costa Rica.