Interleukin inhibitors and the associated risk of candidiasis.

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

Identification of C. auris clade 5 isolates using claID.

Candida auris poses threats to the global medical community due to its multidrug resistance, ability to cause nosocomial outbreaks and resistance to common sterilization agents. Different variants that emerged at different geographical zones were classified as clades. Clade-typing becomes necessary to track its spread, possible emergence of new clades, and to predict the properties that exhibit a clade bias. We previously reported a colony-Polymerase Chain Reaction-based, clade-identification method employing whole genome alignments and identification of clade-specific sequences of four major geographical clades. Here, we expand the panel by identifying clade 5 which was later isolated in Iran, using specific primers designed through in silico analyses.

Candida auris, a multidrug-resistant fungal pathogen, evolves as distinct geographical clades. We describe the identification of clade 5 specific DNA sequence, which was used to design primers that distinguished clade 5 from other clades, adding to the panel of the clade-identification system.

Evaluation of Eazyplex® LAMP test for fast Candida auris direct detection of colonized patients.

Candida auris is a multidrug-resistant pathogen yeast that produces nosocomial outbreaks, due to its ability in colonizing the skin, mucous membranes and surfaces. Rapid diagnosis is essential to control its spread. The aim of this study was to compare the Eazyplex® Candida auris kit (AmplexDiagnostics GmbH) for the rapid identification of patients colonized with C. auris, with the reference method used in our institution (culture and identification by MALDI-TOF). This easy-to-perform test allows obtaining a fast result, in ~30 min. First, we achieved a preliminary study from previously characterized Candida species colonies obtained from 51 clinical samples, with 100% agreement between culture isolation and the Eazyplex® Candida auris LAMP. Second, 152 epidemiological surveillance samples (pharyngeal and axillary-rectal swabs) were tested retrospectively. The sensitivity, specificity, positive and negative predictive values were 91.8%, 98.8%, 98.2% and 94.5%, respectively. Eazyplex® Candida auris showed acceptable results compared with culture in detecting C. auris from surveillance samples with the advantage of single-test and shorter time for handling and result than culture, in addition to its great specificity, positive and negative predictive values.

Identification and infection control response to Candida auris at an academic level I trauma center.

Candida auris, an emerging fungal pathogen with significant morbidity and mortality, can be difficult for health care facilities to identify, isolate, and control. We present our identification and infection control response to Candida auris at a 695-bed academic level I trauma center in Florida.

Clonal Dissemination of Candida auris Clinical Isolates in Northern Italy, 2021.

Candida auris is a concerning pathogen in health care due to its ability to spread in medical settings. In this study, we characterized the genome of three C. auris clinical isolates collected in the Emilia-Romagna region of Northeastern Italy from January 2020 to May 2021. Whole-genome sequencing was performed using Illumina iSeq 100 and Oxford Nanopore MinION systems. Genomes were assembled with Flye. Phylogenetic analysis was carried out with RaxML. The ERG11, TAC1b, and FKS1 genes were examined for known substitutions associated with resistance to azoles and caspofungin using Diamond. All three C. auris isolates belonged to clade I (South Asian lineage) and showed high minimum inhibitory concentrations for fluconazole. Two of the three isolates were closely related to the first Italian index case of C. auris occurred in the 2019 and carried similar mutations associated to azole resistance. The third isolate showed a greater phylogenetic distance from these strains and had a different genetic determinant not previously seen in Italy. Our data suggest that two C. auris clinical isolates may have been epidemiologically related to the first outbreak previously observed in Italy, while the remaining isolate may have originated from a different source. Further research is needed to understand C. auris transmission and resistance and to control its spread.

Candida spondylodiscitis: a systematic review and meta-analysis of seventy two studies.

OBJECTIVES: Knowledge of Candida spondylodiscitis is limited to case reports and smaller case series. Controversy remains on the most effective diagnostical and therapeutical steps once Candida is suspected. This systematic review summarized all cases of Candida spondylodiscitis reported to date concerning baseline demographics, symptoms, treatment, and prognostic factors. METHODS: A PRISMA-based search of PubMed, Web of Science, Embase, Scopus, and OVID Medline was performed from database inception to November 30, 2022. Reported cases of Candida spondylodiscitis were included regardless of Candida strain or spinal levels involved. Based on these criteria, 656 studies were analyzed and 72 included for analysis. Kaplan-Meier curves, Fisher's exact, and Wilcoxon's rank sum tests were performed. RESULTS: In total, 89 patients (67% males) treated for Candida spondylodiscitis were included. Median age was 61 years, 23% were immunocompromised, and 15% IV drug users. Median length of antifungal treatment was six months, and fluconazole (68%) most commonly used. Thirteen percent underwent debridement, 34% discectomy with and 21% without additional instrumentation. Median follow-up was 12 months. The two year survivorship free of death was 80%. The two year survivorship free of revision was 94%. Younger age (p = 0.042) and longer length of antifungal treatment (p = 0.061) were predictive of survival. CONCLUSION: Most patients affected by Candida spondylodiscitis were males in their sixties, with one in four being immunocompromised. While one in five patients died within two years of diagnosis, younger age and prolonged antifungal treatment might play a protective role.

Candida parapsilosis complex in the clinical setting.

Representatives of the Candida parapsilosis complex are important yeast species causing human infections, including candidaemia as one of the leading diseases. This complex comprises C. parapsilosis, Candida orthopsilosis and Candida metapsilosis, and causes a wide range of clinical presentations from colonization to superficial and disseminated infections with a high prevalence in preterm-born infants and the potential to cause outbreaks in hospital settings. Compared with other Candida species, the C. parapsilosis complex shows high minimal inhibitory concentrations for echinocandin drugs due to a naturally occurring FKS1 polymorphism. The emergence of clonal outbreaks of strains with resistance to commonly used antifungals, such as fluconazole, is causing concern. In this Review, we present the latest medical data covering epidemiology, diagnosis, resistance and current treatment approaches for the C. parapsilosis complex. We describe its main clinical manifestations in adults and children and highlight new treatment options. We compare the three sister species, examining key elements of microbiology and clinical characteristics, including the population at risk, disease manifestation and colonization status. Finally, we provide a comprehensive resource for clinicians and researchers focusing on Candida species infections and the C. parapsilosis complex, aiming to bridge the emerging translational knowledge and future therapeutic challenges associated with this human pathogen.

Vertebral Candidiasis, the State of the Art: A Systematic Literature Review.

OBJECTIVE: In recent years, Candida spondylodiscitis has represented an increasingly emerging disease in clinical practice. This condition requires long-term antibiotic therapy and sometimes surgical treatments. The main purpose of this study is to investigate the epidemiology, clinical and radiological aspects, treatment protocols, and outcomes of Candida-mediated vertebral osteomyelitis. METHODS: A systematic review of the English literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.The research was conducted on Medline, Cochrane library, PubMed, and Scopus using as search terms "vertebral"; "spinal"; "infection"; "spondylodiscitis"; "discitis"; "osteomyelitis"; "Candida"; and "Candidosis." A case of vertebral candidiasis that was surgically managed was also reported. RESULTS: In total, 88 articles were included in our systematic review. Including the reported case, our analysis covered 113 cases of vertebral candidiasis. Candida albicans was isolated in 64 cases (56.1%), Candida tropicalis in 21 (18.4%), Candida glabrata in 14 (12.3%), and Candida parapsilosis in five (4.4%). The mean duration of the follow-up was 395 days. Finally, 87 (82%) patients completely recovered, ten (9.4%) died, and nine (8.5%) reported sequelae. CONCLUSION: This systematic review summarized the state of the art on vertebral candidiasis, describing data on its clinical features, diagnostic criteria and current limitations, and treatment alternatives and their outcomes.

Five-year cross-sectional study to determine the burden of Candida spp. infections of the urinary tract system among patients attending tertiary hospital in Northwestern Tanzania.

OBJECTIVE: Urinary tract infections (UTIs) stand as a prominent global health concern. This study entails a 5-year retrospective analysis, using a cross-sectional study design to examine microbiology laboratory data of individuals clinically diagnosed with UTIs at Bugando Medical Centre to gain insights into the prevalence and factors linked to candiduria. METHODOLOGY: Data extracted were meticulously cleaned and coded in an MS Excel sheet, subsequently transferred to STATA V.15 for analysis. Binary logistic regression analysis was used to identify factors associated with candiduria. A probability value below 0.05 at a 95% CI was considered statistically significant. RESULTS: Urine samples for culture and sensitivity comprised 33.4% (20755) of the total biological samples (62335). The median age of the patients stood at 19 years. A slight majority were female, accounting for 52.8% (10051), and two-thirds sought treatment at outpatient departments (67.5%, 12843). Among patients with significant pathogenic growth, the prevalence of candiduria was 4.6% (221 out of 4772). Notably, inpatients exhibited a higher incidence of candiduria compared with outpatients, with rates of 9.4% (1882) versus 1.6% (2890), p value of 0.000. Non-albicans Candida spp. (NAC) remained the most prevalent pathogen. Factors significantly associated with candiduria included being female (OR=1.7, 95% CI 1.3 to 2.3) and hospital admission (OR=6.6, 95% CI 4.7 to 9.2). In conclusion, candiduria affect 5 out of every 100 UTI-diagnosed patients, predominantly among females and those admitted to the hospital. Clinicians at tertiary hospitals should consider urinary candidiasis as a potential diagnosis for patients at risk who present with UTI-like symptoms.

[2021 Epidemiological Survey of Dermatomycoses in Japan].

This is a report of the results of the epidemiological survey on dermatomycoses conducted in 2021. A total of 9,442 patients with dermatomycosis were reported for one year. They include 8,151 (86.3%) with dermatophytosis, 796 (8.4%) with candidiasis, 484 (5.1%) with Malassezia infection, and 11 (0.1%) with deep cutaneous mycosis. In order, the most common types of dermatophytoses were tinea pedis (4,195 cases, 2,341 males and 1,854 females), tinea unguium (2,711 cases, 1,509 males and 1,202 females), tinea corporis (674 cases, 445 males and 229 females), tinea cruris (399 cases, 305 males and 94 females), tinea manus (125 cases, 78 males and 47 females), and tinea capitis (47 cases, 25 males and 22 females). The number of cases of tinea pedis and tinea unguium increased during the summer. A higher percentage of patients were aged 80 or older than in previous surveys. These findings may reflect the increasing percentage of elderly patients seen and the superannuation of the population. As in previous surveys, Trichophyton rubrum and Trichophyton interdigitale were the two most frequently isolated species of fungi causing dermatophytoses. Microsporum canis and Trichophyton tonsurans were the two species most often causing tinea capitis.Regarding cutaneous candidiasis, while candidal intertrigo was the most common in previous surveys, diaper candidiasis in the elderly was the most common in this survey. A background check revealed that this was because a facility included a semi-prophylactic approach to address diaper candidiasis occurring within the ward.Malassezia infections by Malassezia folliculitis clearly increased with each survey. The tendency of certain facilities with many reports of Malassezia folliculitis suggests that it is greatly affected by the presence of physicians familiar with the disease.

Identification of Risk Factors for Intra-Abdominal Candidiasis.

Background: Intra-abdominal candidiasis (IAC) is associated with substantial morbidity and mortality in hospitalized patients. Identifying high-risk populations may facilitate early and selective directed therapy in appropriate patients and avoid unwarranted treatment and any associated adverse effects in those who are low risk. Patients and Methods: This retrospective, case-control study included patients >18 years of age admitted from July 1, 2010 to July 1, 2021 who had a microbiologically confirmed intra-abdominal infection (gastrointestinal culture positive for either a Candida spp. [cases] or bacterial isolate [controls] collected intra-operatively or from a drain placed within 24 hours). Patients receiving peritoneal dialysis treatment or with a peritoneal dialysis catheter in place or treated at an outside hospital were excluded. Multivariable regression was utilized to identify independent risk factors for the development of IAC. Results: Five hundred twenty-three patients were screened, and 250 met inclusion criteria (125 per cohort). Multivariable analysis identified exposure to corticosteroids (odds ratio [OR], 5.79; 95% confidence interval [CI], 2.52-13.32; p < 0.0001), upper gastrointestinal tract surgery (OR, 3.51; 95% CI, 1.25-9.87; p = 0.017), and mechanical ventilation (OR, 3.09; 95% CI 1.5-6.37; p = 0.002) were independently associated with IAC. The area under the receiver operating characteristic (AUROC) and goodness of fit were 0.7813 and p = 0.5024, respectively. Conclusions: Exposure to corticosteroids, upper gastrointestinal tract surgery, and mechanical ventilation are independent risk factors for the development of microbiologically confirmed IAC suggesting these factors may help identify high-risk individuals requiring antifungal therapy.

A Bibliometric Review on Candida auris of the First Fifteen Years of Research (2009-2023).

Introduction: Candida auris is a relatively novel pathogen first described in 2009 in Japan. It has increased its presence worldwide, becoming a public health concern due to its innate resistance to antifungals and outbreak potential. Methods: We performed a query using the word "Candida auris" from the Scopus database, further performing a bibliometric analysis with the open-source R package Bibliometrix. Results: 907 original articles were retrieved, allowing us to map the principal authors, papers, journals, and countries involved in this yeast research, as well as analyze current and future trends and the number of published articles. Conclusion: C. auris will continue to be a pivotal point in fungal resistance research, either for a better understanding of its resistance and pathogenic mechanisms or for developing novel drugs.

The first established microsatellite markers to distinguish Candida orthopsilosis isolates and detection of a nosocomial outbreak in China.

The infection proportion of Candida orthopsilosis, a member of the C. parapsilosis complex, has increased globally in recent years, and nosocomial outbreaks have been reported in several countries. This study aimed to establish microsatellite loci-based typing method that was able to effectively distinguish among C. orthopsilosis isolates. Three reference C. orthopsilosis genome sequences were analyzed to identify repeat loci. DNA sequences containing over eight bi- or more nucleotide repeats were selected. A total of 51 loci were initially identified, and locus-specific primers were designed and tested with 20 epidemiologically unrelated isolates. Four loci with excellent reproducibility, specificity, and resolution for molecular typing purposes were identified, and the combined discriminatory power (DP, based on 20 epidemiologically unrelated isolates) of these four loci was 1.0. Reproducibility was demonstrated by consistently testing three strains each in triplicate, and stability, demonstrated by testing 10 successive passages. Then, we collected 48 C. orthopsilosis non-duplicate clinical isolates from the China Hospital Invasive Fungal Surveillance Net study to compare the DP of the microsatellite-based typing with internal transcribed spacer (ITS) and amplified fragment length polymorphism (AFLP) typing analyses, using ATCC 96139 as a reference strain. These 49 isolates were subdivided into 12 microsatellite types (COMT1-12), six AFLP types, and three ITS types, while all the isolates with the same COMT belonged to consistent AFLP and ITS type, demonstrating the high DP of our microsatellite-type method. According to our results, COMT12 was found to be the predominant type in China, and COMT5 was the second largest and responsible for causing a nosocomial outbreak. This microsatellite-type method is a valuable tool for the differentiation of C. orthopsilosis and could be vital for epidemiological studies to determine strain relatedness and monitor transmission.

Screening of C. auris among Candida isolates from various tertiary care institutions in Lahore by VITEK 2 and real time PCR based molecular technique.

Candida auris is a multidrug-resistant pathogen, that is a well-known cause of nosocomial infections. This pathogen is being identified using advanced diagnostic approaches and epidemiological typing procedures. In underdeveloped nations, several researchers developed and validated a low-cost approach for reliably identifying Candida auris. The goal of this study was to assess the burden of Candida auris in different teaching hospitals of Lahore and to limit its spread to minimize hospital-related illnesses. Candida isolates were obtained from various tertiary care institutions in Lahore in the form of culture on various culture plates. Sabouraud agar culture plates were used to culture the Candida spp. Fluconazole-resistant Candida species were chosen for further identification using VITEK 2 Compact ID and molecular identification using species-specific PCR assay. The current study obtained 636 Candida samples from several tertiary care institutions in Lahore. Fluconazole resistance was found in 248 (38.9%) of 636 Candida samples. No isolate was identified as Candida auris by VITEK 2 Compact ID and real-time PCR-based molecular identification. Thus with limited resources, these two methods may serve as useful screens for Candida auris. However, it should be screened all over the country to limit its spread to break the chain of nosocomial infections.

Alarming Increase of Azole-Resistant Candida Causing Blood Stream Infections in Oncology Patients in Egypt.

Candidemia is a life-threatening invasive fungal infection in immunocompromised patients. The widespread use of azoles and the shift toward non-albicans Candida (NAC) species remarkably increase azole resistance in developing countries. We aimed to study candidemia trends and associated risk factors in oncology patients since they vary geographically, and rapid and appropriate treatment improves outcomes. Vitek 2 was used to identify the Candida species, and the E-test determined their susceptibility to azoles. Candida was the cause of 3.1% (n = 53/1701) of bloodstream infections (BSIs) during a 1-year study. Candida tropicalis was the most predominant species among the 30 candidemia episodes studied (36.7%), followed by C. albicans (33.3%). However, C. krusei, C. guilliermondii, C. pelliculosa, C. parapsilosis, C. famata, and C. inconspicua accounted for 30.0% of the isolates. An increased risk of NAC BSI was significantly associated with chemotherapy and leucopenia (P = 0.036 and 0.016, respectively). However, the multivariable analysis revealed that leucopenia was the only independent risk factor (P = 0.048). Fluconazole and voriconazole resistance were 58.3% and 16.7%, with NAC species showing higher resistance rates than C. albicans. Both fluconazole and voriconazole minimum inhibitory concentration (MIC) median values were higher in NAC than in C. albicans, but only voriconazole was significantly higher (0.220 versus 0.048 µg/ml, P = 0.047). In conclusion, the increased prevalence of NAC BSIs and incredibly high fluconazole resistance rates in cancer patients emphasize the necessity of antifungal stewardship to preserve voriconazole effectiveness, continued surveillance of candidemia, and future studies into azole resistance molecular mechanisms.

Long-range air dispersion of Candida auris in a cardiothoracic unit outbreak in Hong Kong.

BACKGROUND: Nosocomial outbreaks of Candida auris, a multidrug-resistant fungus, are increasingly reported worldwide; the mode of transmission has usually been reported to be via direct contact. Some studies previously suggested potential short-distance air dispersal during high-turbulence activities, but evidence on long-range air dispersal remains scarce. AIM: To describe a C. auris nosocomial outbreak involving two wards (H7, 5E) in two local hospitals. METHODS: Samples were taken from patients, ward surfaces (frequently touched items and non-reachable surfaces) while settle plates were used for passive air sampling to investigate possible contributions by direct contact and air dispersal. Epidemiological and phylogenetic analyses were also performed on the C. auris isolates from this outbreak. FINDINGS: Eighteen patients were confirmed to have asymptomatic C. auris skin colonization. C. auris was expectedly identified in samplings from frequently touched ward items but was also isolated in two samples from ceiling supply air grilles which were 2.4 m high and inaccessible by patients. Moreover, one sample from a corridor return air grille as far as 9.8 m away from the C. auris cohort area was also positive. Two passive air samplings were positive, including one from a cubicle with no confirmed cases for four days, suggesting possible air dispersal of C. auris. Whole-genome sequencing confirmed clonality of air, environment, and patients' isolates. CONCLUSION: This is the first study to demonstrate potential long-range air dispersal of C. auris in an open-cubicle ward setting. Ventilation precautions and decontamination of out-of-reach high-level surfaces should be considered in C. auris outbreak management.

Prevalence of Acinetobacter baumannii and Candida auris in Patients Receiving Mechanical Ventilation.

Importance: To date, only 1 statewide prevalence survey has been performed for Acinetobacter baumannii (2009) in the US, and no statewide prevalence survey has been performed for Candida auris, making the current burden of these emerging pathogens unknown. Objective: To determine the prevalence of A baumannii and C auris among patients receiving mechanical ventilation in Maryland. Design, Setting, and Participants: The Maryland Multi-Drug Resistant Organism Prevention Collaborative performed a statewide cross-sectional point prevalence of patients receiving mechanical ventilation admitted to acute care hospitals (n = 33) and long-term care facilities (n = 18) between March 7, 2023, and June 8, 2023. Surveillance cultures (sputum, perianal, arm/leg, and axilla/groin) were obtained from all patients receiving mechanical ventilation. Sputum, perianal, and arm/leg cultures were tested for A baumannii and antibiotic susceptibility testing was performed. Axilla/groin cultures were tested by polymerase chain reaction for C auris. Main Outcomes and Measures: Prevalence of A baumannii, carbapenem-resistant A baumannii (CRAB), and C auris. Prevalence was stratified by type of facility. Results: All 51 eligible health care facilities (100%) participated in the survey. A total of 482 patients receiving mechanical ventilation were screened for A baumannii and 470 were screened for C auris. Among the 482 patients who had samples collected, 30.7% (148/482) grew A baumannii, 88 of the 148 (59.5%) of these A baumannii were CRAB, and C auris was identified in 31 of 470 (6.6%). Patients in long-term care facilities were more likely to be colonized with A baumannii (relative risk [RR], 7.66 [95% CI, 5.11-11.50], P < .001), CRAB (RR, 5.48 [95% CI, 3.38-8.91], P < .001), and C auris (RR, 1.97 [95% CI, 0.99-3.92], P = .05) compared with patients in acute care hospitals. Nine patients (29.0%) with cultures positive for C auris were previously unreported to the Maryland Department of Health. Conclusions: A baumannii, carbapenem-resistant A baumannii, and C auris were common among patients receiving mechanical ventilation in both acute care hospitals and long-term care facilities. Both pathogens were significantly more common in long-term care facilities than in acute care hospitals. Patients receiving mechanical ventilation in long-term care facilities are a high-risk population for emerging pathogens, and surveillance and prevention efforts should be targeted to these facilities.

Predictors of Underlying Esophageal Motility Disorders in Patients Presenting with Esophageal Candidiasis.

OBJECTIVES: Esophageal motility disorders (EMDs) are a known risk factor for esophageal candidiasis (EC), but this relation has not been described particularly well. We sought to evaluate the predictors of underlying EMDs in patients presenting with EC. METHODS: Cases of EC at a single medical center between 2010 and 2021 were identified retrospectively based on the International Classification of Diseases, Ninth Revision code. Demographic, clinical, endoscopic, and manometric data were reviewed. The diagnosis of EC was based on typical endoscopic appearance. RESULTS: In total, 130 EC patients were identified (mean age 69.5 ± 14.6; 66.2% male). Of these, 12 (9.2%) had an underlying EMD (11 cases of achalasia; 1 case of esophagogastric junction outflow obstruction). Five (41.7%) of these patients had previously been diagnosed as having an EMD, whereas 7 were newly diagnosed only after their presentation with EC. No significant differences were noted between those with or without EMDs in terms of demographics, medical comorbidities, or medication use. Patients with an EMD, however, were more likely to complain of dysphagia (91.7% vs 30.5%, P < 0.001), and on endoscopy, they were more likely to have residual food in the esophagus, residual fluid in the esophagus, a dilated esophagus, and resistance to traversing the esophagogastric junction (all P < 0.001). Sixty-one (46.9%) patients with EC died during follow-up (mean 58 months). CONCLUSIONS: EMDs are present in approximately 10% of patients presenting with EC, with half being diagnosed only after presenting with EC. Similar to non-EC patients, patients with EC with dysphagia and the typical endoscopic findings of achalasia are more likely to have an EMD and warrant prompt manometric evaluation.