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Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus ) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% ( p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

Aspergillus spp. isolated from non-BAL cultures of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) patients may reflect colonization rather than infection. Sera (n = 181) from 49 adult ICU CAPA patients (24 probable and 25 possible CAPA) with bronchial secretions (BS) culture positive for Aspergillus spp. were collected and tested for Aspergillus DNA detection by species-specific real-time PCR. Overall, 30/49 (61%) patients were PCR positive. BS culture/serum PCR agreement was moderate (21/30; 70%). Based on serum PCR positive patients, all CAPAs were due to A. fumigatus (80%), A. flavus (10%), and A. terreus (10%). No A. niger/A. nidulans or mixed infections were found despite positive BS cultures., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

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 MIC 50 s 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., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Metallo-beta-lactamase (MBL)-producing Gram-negative bacteria are increasing worldwide and very few agents are active against these pathogens. Taniborbactam (formerly VNRX-5133) is a newly developed bicyclic boronate beta-lactamase inhibitor that directly inhibits all four Ambler classes of beta-lactamases. In the present study the in vitro activity of cefepime or meropenem combined with taniborbactam against 100 Klebsiella pneumoniae and cefepime combined with taniborbactam against 100 Pseudomonas aeruginosa molecularly characterized MBL-producing strains were investigated using ISO standard broth microdilution assays and compared with a panel of antimicrobial agents that are used in clinical practice (amikacin, aztreonam, ciprofloxacin, levofloxacin, gentamicin, piperacillin/tazobactam, imipenem, tigecycline, ceftolozane-tazobactam, cefepime-tazobactam, meropenem-vaborbactam, ceftazidime-avibactam). For K. pneumoniae isolates, the MIC 90 values were ≥64 mg/L for all drugs except cefepime-taniborbactam (16 mg/L; 87% inhibited at ≤8/4 mg/L), meropenem-taniborbactam (4 mg/L; 94% inhibited at ≤8/4 mg/L) and tigecycline (8 mg/L), with high levels of resistance (≥65%) found for all approved comparator antimicrobials tested. For P. aeruginosa, the MIC 90 values were ≥64 mg/L for all drugs except aztreonam (32 mg/L), cefepime-taniborbactam (32 mg/L; 88% inhibited at ≤16/4 mg/L) and ciprofloxacin (32 mg/L), with high levels of resistance (≥73%) for all approved drugs except aztreonam (27%). Taniborbactam reduced cefepime and meropenem MICs by a median 5 and 7 two-fold dilutions to ≤8 mg/L in 87% and 94% of MBL-producing K. pneumoniae isolates, and cefepime MICs by a median 5 two-fold dilutions to ≤16 mg/L in 86% of MBL-producing P. aeruginosa, respectively. The combinations cefepime-taniborbactam and meropenem-taniborbactam are promising alternative treatment options for infections by MBL-producing isolates., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Neisseria meningitidis is considered as an obligate human pathogen and can cause life-threatening diseases like meningitis and/or septicaemia. Occasionally, it can be recovered from infections outside the bloodstream or central nervous system, like respiratory, ocular, joint, urogenital or other unusual sites. Herein, we present two rare cases of female genital infections due to N. meningitidis within a two-year period (2019-2020), identified as serogroup B (MenB) and Y (MenY), respectively. Genotypic analysis for PorA, FetA and MLST revealed the following characteristics: MenB: 7-12, 14, F5-36, 1572cc and MenY: 5-1,10-1, F4-5, 23cc, respectively. Such unusual presentations should alert the clinicians and microbiologists not to exclude N . meningitidis from routine diagnosis and the need of early detection. This is the first report in Greece, and, to our knowledge, in Europe since 2005 describing meningococcal female genital infections.

Objectives: We evaluated the in vitro activity of ceftolozane/tazobactam and comparator agents against MDR non-MBL Pseudomonas aeruginosa isolates collected from nine Greek hospitals and we assessed the potential synergistic interaction between ceftolozane/tazobactam and amikacin., Methods: A total of 160 non-MBL P. aeruginosa isolates collected in 2016 were tested for susceptibility to ceftolozane/tazobactam and seven comparator agents including ceftazidime/avibactam. Time-kill assays were performed for synergy testing using ceftolozane/tazobactam 60 or 7.5 mg/L, corresponding to the peak and trough concentrations of a 1.5 g q8h dose, respectively, in combination with 69 mg/L amikacin, corresponding to the free peak plasma concentration. Synergy was defined as a ≥2 log10 cfu/mL reduction compared with the most active agent., Results: Overall, ceftolozane/tazobactam inhibited 64.4% of the P. aeruginosa strains at ≤4 mg/L. Colistin was the most active agent (MIC50/90, 0.5/2 mg/L; 96.3% susceptible) followed by ceftazidime/avibactam (MIC50/90, 4/16 mg/L; 80.6% susceptible). GES-type enzymes were predominantly responsible for ceftolozane/tazobactam resistance; 81.6% of the non-producers were susceptible. MICs for the P. aeruginosa isolates selected for synergy testing were 2-32 mg/L ceftolozane/tazobactam and 2-128 mg/L amikacin. The combination of ceftolozane/tazobactam with amikacin was synergistic against 85.0% of all the isolates tested and against 75.0% of the GES producers. No antagonistic interactions were observed., Conclusions: Ceftolozane/tazobactam demonstrated good in vitro activity against MDR/XDR P. aeruginosa clinical isolates, including strains with co-resistance to other antipseudomonal drugs. In combination with amikacin, a synergistic interaction at 24 h was observed against 85.0% of P. aeruginosa strains tested, including isolates with ceftolozane/tazobactam MICs of 32 mg/L or GES producers., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A 13-year-old Greek girl with pyruvate kinase deficiency and moya moya angiographic pattern is reported. She also had raised serum lipoprotein (a) concentration and was homozygous for the C677T mutation of the methylenetetrahydrofolate reductase gene. She presented with neonatal onset of anemia, hemolytic and aplastic crises, especially during infections, stroke, and also progressive motor and mental deterioration. A digital cranial angiography at 13 years revealed the typical angiographic findings of moya moya angiopathy. This is likely the first patient with pyruvate kinase deficiency and moya moya syndrome and also the combination of elevated serum lipoprotein (a) concentration and the C677T mutation of the methylenetetrahydrofolate reductase gene to be reported. In patients with pyruvate kinase deficiency and moya moya syndrome, a search for raised serum lipoprotein (a) concentrations and the C677T mutation of the methylenetetrahydrofolate reductase gene should be considered.

This study aimed to investigate whether carbamazepine, sodium valproate or phenobarbital as monotherapy in ambulatory epileptic children with adequate sun exposure have some effect on their bone metabolism based on the determination of total serum alkaline phosphatase (AP) levels and its bone isoenzyme activity. Blood samples were obtained from 118 epileptic children (37 on carbamazepine, 47 on sodium valproate and 34 on phenobarbital) and from corresponding healthy controls matched for age, gender and anthropometric parameters. AP and its liver, bone and intestinal isoenzyme levels, other common biochemical markers of bone and liver metabolism and drug levels were measured in the study participants. Patients on carbamazepine or phenobarbital had significantly elevated AP levels accompanied by increased bone and liver isoenzyme activity compared to controls. An increase of bone AP isoenzyme values, correlated with the duration of treatment ( r= 0.49, P= 0.002), was found in children on sodium valproate without, however, a concomitant significant elevation of total AP values. We conclude that children who receive antiepileptic drugs as monotherapy, even when residing in a Mediterranean country with adequate sunlight, may have their bone metabolism affected as indicated by the elevated levels of bone AP isoenzyme. This isoenzyme, but not total AP values, could therefore be used as a marker for the selection of patients who would be benefited by a thorough evaluation of their bone metabolism profile.

Acute necrotizing encephalopathy following influenza A is frequently reported from Japan and Taiwan but is very rarely seen in Western countries. We describe a 10-year-old boy with acute necrotizing encephalopathy, who developed symmetrical thalamic and brain stem lesions seen on magnetic resonance imaging (MRI). Serological confirmation of influenza A was made 2 weeks after the onset of symptoms. The child made a full recovery. This case is interesting because of its rarity in European countries, the striking brain MRI findings and the good neurological outcome.