Filamentous Fungal Keratitis in Greece: A 16-Year Nationwide Multicenter Survey.

In a multicenter, prospective study of filamentous fungal keratitis in Greece, predisposing factors, etiology, treatment practices, and outcome, were determined. Corneal scrapings were collected from patients with clinical suspicion of fungal keratitis, and demographic and clinical data were recorded. Fungal identification was based on morphology, molecular methods, and matrix assisted laser desorption ionization time-of-flight mass-spectrometry. A total of 35 cases were identified in a 16-year study period. Female to male ratio was 1:1.7 and median age 48 years. Corneal injury by plant material, and soft contact lens use were the main risk factors (42.8% and 31.4%, respectively). Trauma was the leading risk factor for men (68.1%), contact lens use (61.5%) for women. Fusarium species were isolated more frequently (n = 21, 61.8%). F. solani was mostly associated with trauma, F. verticillioides and F. proliferatum with soft contact lens use. Other fungi were: Purpureocillium lilacinum (14.7%), Alternaria (11.8%), Aspergillus (8.8%), and Phoma foliaceiphila, Beauveria bassiana and Curvularia spicifera, one case each. Amphotericin B and voriconazole MIC50s against Fusarium were 2 mg/L and 4 mg/L respectively. Antifungal therapy consisted mainly of voriconazole locally or both locally and systemically, alone or in combination with liposomal AmB. Cure/improvement rate with antifungal therapy alone was 52%, keratoplasty was required in 40% of cases, and enucleation in 8%. In conclusion, filamentous fungal keratitis in Greece is rare, but with considerable morbidity. A large proportion of cases resulted in keratoplasty despite appropriate antifungal treatment.

Otolaryngology in the COVID-19 pandemic era: the impact on our clinical practice.

PURPOSE: To give an overview of the current knowledge about COVID-19 pandemic and its impact on otolaryngology clinical practice. METHODS: Recent findings about SARS-CoV-2 virus and the COVID-19 infection it causes are reviewed. In addition to international databases and in the absence of hard scientific data, literature search included reports published online from scientific societies and other institutions. RESULTS: The role of anosmia as a COVID-19-related symptom is presented. Further, considerations about steroid administration in ENT-related conditions are also discussed. Due to the close work with mucosa surfaces of the upper aerodigestive tract, otolaryngologists and surrounding staff are considered high risk for coronavirus transmission. Hence, staff protection measures for ENT examinations, surgeries and other procedures during COVID-19 pandemic are recommended. CONCLUSION: Knowledge and evidence about the impact of COVID-19 infection on otolaryngology clinical practice are accumulating rapidly. Additionally to patient's management, safety of health care professionals should be a main goal right now by following strict safety guidelines.

ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients.

The European Conference on Infections in Leukemia (ECIL) provides recommendations for diagnostic strategies and prophylactic, pre-emptive or targeted therapy strategies for various types of infection in patients with hematologic malignancies or hematopoietic stem cell transplantation recipients. Meetings are held every two years since 2005 and evidence-based recommendations are elaborated after evaluation of the literature and discussion among specialists of nearly all European countries. In this manuscript, the ECIL group presents the 2015-update of the recommendations for the targeted treatment of invasive candidiasis, aspergillosis and mucormycosis. Current data now allow a very strong recommendation in favor of echinocandins for first-line therapy of candidemia irrespective of the underlying predisposing factors. Anidulafungin has been given the same grading as the other echinocandins for hemato-oncological patients. The beneficial role of catheter removal in candidemia is strengthened. Aspergillus guidelines now recommend the use of either voriconazole or isavuconazole for first-line treatment of invasive aspergillosis, while first-line combination antifungal therapy is not routinely recommended. As only few new data were published since the last ECIL guidelines, no major changes were made to mucormycosis recommendations.

Association Between Candiduria and Candidemia: A Clinical and Molecular Analysis of Cases.

The risk of developing candidemia after candiduria is reportedly very low, but it has not been adequately investigated. The aim of this study was to examine the molecular relatedness between Candida strains isolated from adult patients with candidemia and concomitant candiduria in association with the clinical characteristics of the cases. All episodes of candidemia occurring in a tertiary care academic hospital during a 5-year period were recorded prospectively. Patients with episodes of candiduria occurring two weeks preceding to or one week following a positive for Candida blood culture were included in the study. The genotypic relatedness of Candida strains isolated from blood and urine was investigated by pulsed-field gel electrophoresis after digestion with the BssHII restriction endonuclease. We recorded 141 candidemia episodes, occurring in 134 patients. Twelve episodes of candidemia with concomitant candiduria occurred in 11 patients (8% of all candidemias). In six of these episodes, the strains in the blood-urine pairs belonged to different species. In two episodes, the isolates belonged to the same species but were not genetically related, and only in four (2.8% of all candidemias), the strains were related. All four patients were severely ill and had multiple risk factors for candidemia. These findings indicate that in hospitalized patients with candidemia, concomitant candiduria is rare and usually an independent event, confirming previous reports. In the critically ill, however, the existence of genetically related strains in blood and urine appears to be more frequent, with more probable the hematogenous dissemination.

Invasive mucormycosis in children: an epidemiologic study in European and non-European countries based on two registries.

BACKGROUND: Mucormycosis has emerged as a rare but frequently fatal invasive fungal disease. Current knowledge on paediatric mucormycosis is based on case reports and small series reported over several decades. Contemporary data on a large cohort of patients is lacking. METHODS: Two large international registries (Zygomyco.net and FungiScope™) were searched for mucormycosis cases in ≤19 year-old patients. Cases enrolled between 2005 and 2014 were extracted, and dual entries in the two databases merged. Epidemiology, clinical characteristics, diagnostic procedures, therapeutic management and final outcome were recorded and analysed with SPSS v.12. RESULTS: Sixty-three unique cases (44 proven and 19 probable) were enrolled from 15 countries (54 in European and 9 in non-European countries). Median age was 13 years [Interquartile Range (IQR) 7.7] with a slight predominance (54.1 %) of females. Underlying conditions were haematological malignancies (46 %), other malignancies (6.3 %), haematopoietic stem cell transplantation (15.9 %), solid organ transplantation, trauma/surgery and diabetes mellitus (4.8 % each) and a variety of other diseases (7.9 %); in 9.5%, no underlying medical condition was found. Neutropenia was recorded in 46 % of the patients. The main sites of infection were lungs (19 %), skin and soft tissues (19 %), paranasal sinus/sino-orbital region (15.8 %) and rhino-cerebral region (7.9 %). Disseminated infection was present in 38.1 %. Mucormycosis diagnosis was based on several combinations of methods; culture combined with histology was performed in 31 cases (49.2 %). Fungal isolates included Rhizopus spp. (39.7 %), Lichtheimia spp. (17.5 %), Mucor spp. (12.7 %), Cunninghamella bertholletiae (6.3 %) and unspecified (23.8 %). Treatment comprised amphotericin B (AmB) monotherapy in 31.7 % or AmB in combination with other antifungals in 47.7 % of the cases, while 14.3 % received no antifungals. Surgery alone was performed in 6.3 %, and combined with antifungal therapy in 47.6 %. Crude mortality at last contact of follow-up was 33.3 %. In regression analysis, disseminated disease and prior haematopoietic stem cell transplantation were associated with increased odds of death, whereas the combination of systemic antifungal therapy with surgery was associated with improved survival. CONCLUSION: Paediatric mucormycosis mainly affects children with malignancies, presents as pulmonary, soft tissue, paranasal sinus or disseminated disease and is highly lethal. Outcome is improved when active antifungal therapy and surgery are combined.

Comparative evaluation of conventional and real-time PCR assays for detecting Bacteroides fragilis in clinical samples.

A conventional PCR and a real-time PCR for detecting Bacteroides fragilis were evaluated against clinical specimens. Analytical sensitivities were 100 and 40 fg of DNA, respectively. Detection limits were 100 and 10 CFU/ml, respectively. A total of six culture-negative specimens were positive by PCR. Altering the gold standard from "positive culture" to "positive culture or both PCR assays positive" resulted in sensitivities of 91.7% and 100%, respectively, and in specificities of 100% and 98.6%, respectively.

Future directions in mucormycosis research.

Mucormycosis has emerged as an important opportunistic infection, especially in severely immunosuppressed hosts. The evolving epidemiology, immunopathogenesis, molecular virulence studies, early diagnosis, and pitfalls in designing clinical studies of mucormycosis are discussed in this article.

Extensive Testing and Public Health Interventions for the Control of COVID-19 in the Republic of Cyprus between March and May 2020.

Coronavirus disease 2019 (COVID-19) has significantly affected the well-being of individuals worldwide. We herein describe the epidemiology of COVID-19 in the Republic of Cyprus during the first epidemic wave (9 March-3 May 2020). We analyzed surveillance data from laboratory-confirmed cases, including targeted testing and population screening. Statistical analyses included logistic regression. During the surveillance period, 64,136 tests (7322.3 per 100,000) were performed, 873 COVID-19 cases were diagnosed, and 20 deaths were reported (2.3%). Health-care workers (HCWs) represented 21.4% of cases. Overall, 19.1% of cases received hospital care and 3.7% required admission to Intensive Care Units. Male sex (adjusted Odds Ratio (aOR): 3.04; 95% Confidence Interval (CI): 1.97-4.69), increasing age (aOR: 1.56; 95%CI: 1.36-1.79), symptoms at diagnosis (aOR: 6.05; 95%CI: 3.18-11.50), and underlying health conditions (aOR: 2.08; 95%CI: 1.31-3.31) were associated with hospitalization. For recovered cases, the median time from first to last second negative test was 21 days. Overall, 119 primary cases reported 616 close contacts, yielding a pooled secondary attack rate of 12% (95%CI: 9.6-14.8%). Three population-based screening projects, and two projects targeting employees and HCWs, involving 25,496 people, revealed 60 positive individuals (0.2%). Early implementation of interventions with targeted and expanded testing facilitated prompt outbreak control on the island.

Prevalence of different HPV types and estimation of prognostic risk factors based on the linear array HPV genotyping test.

The aim of the study was to evaluate the prevalence and risk factors of HPV in a gynecologic population attending outpatient clinics using two new molecular tests. The Amplicor HPV test and the Linear Array (LA) HPV Genotyping test were used for the detection of HPV DNA in 320 women. Multiple logistic regression was used to identify independent prognostic factors of HPV positivity. The agreement between the two methods in terms of their qualitative results was 89.3% (kappa: 0.63). Based on the LA results, the overall prevalence of HPV DNA was 49.1%, 95% confidence interval (95% CI: 43.5%, 54.7%). The prevalence of high-risk HPV types was 30.3%. The predominant types were HPV-6 (24.8%) and HPV-16 (20.4%). Among women with normal cytology, the prevalence of HPV was much higher in those presenting other findings, such as inflammation, than those without other abnormal findings (49.5% vs. 31.5%). On the basis of multivariate analysis, the risk of HPV infection was higher among women with multiple sexual partners [>3 vs. 1: OR = 3.1, 95% CI: (1.5, 7.2)], Pap smear findings [low/high-grade lesions vs. negative: OR = 2.8, 95% CI: (1.2, 6.5)], the presence of warts [yes vs. no: OR = 3.0, 95% CI: (1.5, 6.3)] and no history of child birth [no vs. yes: OR = 2.6, 95% CI: (1.0, 6.7)]. Younger age was an additional risk factor for HPV infection with carcinogenic genotypes [OR for 1 year increase = 0.93, 95% CI: (0.89, 0.98)].

Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.

Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

[This corrects the article DOI: 10.3389/fmicb.2018.00516.].

Complicated Lemierre Syndrome Caused by Streptococcus gordonii and Possible Rickettsial Co-Infection in a Patient with Thrombophilia Predisposition.

AIMS: Lemierre syndrome is a life-threating condition characterized by recent oropharyngeal infection, internal jugular vein thrombosis, and anaerobic septicemia. It is usually caused by Fusobacterium necrophorum. METHODS: A young Romanian male presented with fever and rigors, mild tachypnea, hypoxia, sore throat, decayed teeth, and tenderness of the left carotid triangle. Laboratory examination indicated severe sepsis with disseminated intravascular coagulation, acute renal failure, and acute respiratory distress syndrome while the Doppler ultrasonography of the carotids revealed left internal jugular venous thrombosis. The patient was administered piperacillin/tazobactam and vancomycin intravenously, doxycycline orally, and anti-coagulation by enoxaparin based on the diagnosis of Lemierre syndrome. Meanwhile, he was complicated by bilateral diffuse pulmonary cavities and encapsulated pleural effusions and so transcutaneous drainage was performed. The patient was discharged after a month and continued his treatment with oral phenoxypenicillin and doxycycline until full radiographic improvement. He was switched to oral anti-coagulation by vitamin-K antagonists and was referred to a hematologist, a vascular-surgeon, and a dentist. RESULTS: Streptococcus gordonii was isolated from the patient's blood and pleural fluid cultures and serology for Rickettsial spp. IgM was positive. Thrombophilia genetic tests revealed three minor mutations for fibrinogen-455, plasminogen activator inhibitor-1, and methylenetetrahydrofolate reductase. According to the literature, S. gordonii is not usually a causative agent and Rickettsial spp. have as yet not been correlated with Lemierre syndrome. The failure of left jugular vein recanalization shows a possible causative role of the underlying thrombophilic predisposition. DISCUSSION: Because of the syndrome's rarity and the atypical microorganisms isolated in this case, increased awareness is advised for its diagnosis and the underlying mechanisms involved in its genesis. The role of anti-coagulation is debatable. LEARNING POINTS: Very rare condition. Medical practitioners should be vigilant in its diagnosis since septic jugular vein thrombophlebitis could be misdiagnosed as neck lymphadenitis.Duration of antibiotic therapy and additional anticoagulation treatment are still under discussion.Underlying thrombophilia predisposition should be excluded.

In vitro activities of tigecycline against recently isolated Gram-negative anaerobic bacteria in Greece, including metronidazole-resistant strains.

The in vitro activity of tigecycline was compared with those of benzylpenicillin, piperacillin + tazobactam, cefoxitin, imipenem, metronidazole, clindamycin, and tetracycline against 249 Gram-negative anaerobic bacteria (158 Bacteroides fragilis group, 27 non-fragilis Bacteroides spp., 44 Prevotella spp., and 20 miscellaneous), recently isolated from 8 general hospitals in Athens, Greece. Overall tigecycline MIC(50) and MIC(90) were 0.25 and 2 mg/L, respectively, whereas B. fragilis group MIC(50) and MIC(90) were 0.5 and 4 mg/L, respectively. In total, 93% of the isolates were susceptible to tigecycline (MIC /= 32 mg/L) was detected. In addition, tigecycline exhibited good activity against metronidazole- and tetracycline-resistant isolates (MIC(90), 0.5 and 8 mg/L, respectively). In summary, tigecycline exhibits good in vitro activity against Gram-negative anaerobic bacteria isolated in Greece, as well as stability to the most common occurring resistance mechanisms, attributes that make this parenteral agent an attractive alternative for use against infections involving these microorganisms.

An unusual cutaneous tumor: African histoplasmosis following mudbaths: case report and review.

African histoplasmosis, caused by Histoplasma capsulatum var. duboisii, is endemic in Africa. The disease usually involves the skin, subcutaneous tissue, and bones. A case of African histoplasmosis presenting as a cutaneous tumor and non-healing wound in a 66-year-old immunocompetent male residing in Africa, the first ever reported following mudbaths and acupuncture, is hereby reported. Diagnosis was confirmed by means of polymerase chain reaction performed on tissue material. The patient was started on long-term itraconazole therapy and he responded well. African histoplasmosis should be included in the differential diagnosis of non-healing wounds or tumor-like lesions, especially in the context of mudbaths in an endemic area.

Two cases of infections due to multidrug-resistant Bacteroides fragilis group strains.

Bacteroides fragilis group strains are still considered susceptible to most antimicrobial agents used for the treatment of infections caused by anaerobic organisms. We describe two cases of infections due to isolates simultaneously resistant to clindamycin, tetracycline, cefoxitin, piperacillin-tazobactam, and imipenem and, in one of the two cases, to metronidazole. Such infections, although still rare, do exist and tend to complicate treatment.

External Iliac artery stent mucormycosis in a renal transplant patient.

A Mucorales infection of an external iliac artery stent in a renal transplant patient is described. Following a kidney transplantation operation and an acute rejection of the transplant, an aneurysm developed at the site of the arterial ligation and three stents were inserted. Two months following insertion of the stents, recurrent episodes of peripheral thromboembolism occurred. Histological examination of the thrombus revealed hyphae characteristic of mucormycosis. A combination of surgical and medical treatment with intravenous liposomal amphotericin B was applied, which led to complete cure of the disease without infection recurrence after 1 year of follow-up.