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The aim of this study was to review fungal bloodstream infections at a large tertiary care hospital to evaluate the incidence of fungemia and the distribution of causative species during the period 2001–2005. Another aim was to assess the extent of antifungal resistance. A review of all episodes of fungemia at the University Hospitals of Leuven (Belgium) was conducted between January 2001 and December 2005. For the first yeast isolate collected from each non-mould fungemic episode during a 1-year period (June 2004–June 2005), susceptibility to seven antifungal agents was determined using Sensititre YeastOne plates (Trek Diagnostic Systems, East Grinstead, UK), and the antifungal therapy was reviewed. The annual incidence of fungemia ranged between 1.30 and 1.68 episodes per 10,000 patient-days (on a total of 2,680,932 patient-days), with a decreasing trend observed over the 5-year study period. The most common species were Candida albicans (59%), Candida glabrata (22%), Candida parapsilosis (10%), and Candida tropicalis (4%). Overall, fluconazole resistance was rare (1.6%) and was detected only in C. glabrata and C. krusei. Voriconazole and caspofungin inhibited 100% of the isolates at a concentration of ≤1 μg/ml. Fluconazole was used to treat 75% of fungemic patients. Caspofungin was the second most commonly used antifungal agent (used to treat 11.7% of patients). The incidence of fungemia was higher than usually reported in other European countries. The low proportion of resistance supports the use of fluconazole as the treatment of first choice for candidemia in patients not previously exposed to this drug. [ABSTRACT FROM AUTHOR]

We report a case of cryptococcal meningitis in an immunocompetent female patient with exposure to a pet magpie (Pica pica). Genetically indistinguishable isolates were cultured from the cerebrospinal fluid of the patient and excreta of the bird. Our data strongly suggest zoonotic transmission of Cryptococcus neoformans var. grubii from a magpie to this patient. [ABSTRACT FROM AUTHOR]

Lagrou K, Van Eldere J, Keuleers S, Hagen F, Merckx R, Verhaegen J, Peetermans WE, Boekhout T (University Hospital Leuven, Leuven, Belgium; and Centraalbureau voor Schimmelcultures, CT Utrecht, the Netherlands) Zoonotic transmission ofCryptococcus neoformansfrom a magpie to an immunocompetent patient (Case report).J Intern Med2005;257:385–388.We report a case of cryptococcal meningitis in an immunocompetent female patient with exposure to a pet magpie (Pica pica). Genetically indistinguishable isolates were cultured from the cerebrospinal fluid of the patient and excreta of the bird. Our data strongly suggest zoonotic transmission ofCryptococcus neoformansvar.grubiifrom a magpie to this patient. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this project was to study the influence of pneumococci on nasopharyngeal epithelial integrity as a function of time and pneumococcal density. Materials and methods Cell layers of an in vitro model of human nasopharyngeal epithelium were inoculated with different pneumococcal strains. The transepithelial electrical resistance (TEER), a measure of the integrity of the cell layers, and the pneumococcal concentration in the apical fluid on the epithelial cells were measured at different times after inoculation. Results Pneumococci caused a decrease in the TEER when a density of 1 × 107 CFU mL -1 was reached. The growth rate of pneumococci in our in vitro model differed between the strains tested and, for the same strain, between in vitro culture on the epithelial cells and broth culture. Differences in timing of the onset of decrease in the TEER between strains were the result of differences in growth rate on the epithelial cells. Antibiotic-induced lysis of pneumococci caused an immediate decrease in the TEER of the cell layers. Conclusion Pneumococci cause a decrease in the TEER at a density of 1 × 107 CFU mL -1 . Our hypothesis is that this decrease in the TEER is the result of quorum-induced lysis of the pneumococci. [ABSTRACT FROM AUTHOR]

This article, titled "OC19.02: First trimester congenital cytomegalovirus infections: prevalence and chronology of prenatal ultrasound findings," explores the prevalence and timing of ultrasound signs for primary cytomegalovirus (CMV) seroconversion in the first trimester of pregnancy. The study analyzed data from 473 patients who underwent amniocentesis for CMV seroconversion between 2006 and 2022. The findings revealed that ultrasound remains an important tool for detecting intracranial and extracranial abnormalities, while MRI can identify additional anomalies. Higher CMV viral load in amniotic fluid was associated with a higher risk of adverse imaging and outcomes. [Extracted from the article]

Different reports of Pneumocystis jirovecii pneumonia (PcP) outbreaks on oncology and transplant units suggest the possibility of a person-to-person transmission. Based on these reports, we searched retrospectively for possible PcP clusters in UZ Leuven in 2013. A movement and transmission map was established for all patients ( n = 21) with a positive PcP PCR on BAL fluid. BAL fluid samples from all patients with a positive PCR on the mitochondrial large subunit mRNA of P. jirovecii and possible cross exposure were typed with multilocus sequence typing (MLST). Five patients with a positive PcP PCR could have contact with another PcP patient. Another five patients with a weak positive PcP PCR on BAL fluid during the same period were also included. Based on the MLST typing of the BAL samples of these ten patients, there was no evidence of a PcP outbreak in UZ Leuven in 2013. MLST has proven to be a useful tool in genotyping and outbreak detection. From this case series, it could be concluded that current infection control precautions for P. jirovecii are appropriate in UZ Leuven. However, there is need for an international Pneumocystis database and more clarity in the geographic distribution of different P. jirovecii genotypes. [ABSTRACT FROM AUTHOR]

Renal transplant recipients are highly susceptible to infections caused by uncommon pathogens because of their immunocompromised state. We report a case of disseminated Mycobacterium genavense infection in a patient with a combined renal and cardiac transplant. Diagnosing M. genavense infections remains a challenge because of the absence of specific clinical symptoms in combination with the difficulties of culturing the organism using standard mycobacterial culture procedures. This clinical case demonstrates the importance of molecular techniques as part of the initial work-up in order to rapidly establish the diagnosis. [ABSTRACT FROM AUTHOR]

The authors reflect on the prevalence of pulmonary diseases due to the emergence of European hantavirus Puumula virus (PUUV) worldwide. They relate the severe cases of pulmonary infections and renal involvement in the manifestation of PUUV. Moreover, they note the role of reverse transcription polymerase chain reaction (RT-PCR) in pinpointing the exact origin of hantavirus species and pathogens without the application of virus isolation.

OBJECTIVE: : The impact of cytomegalovirus reactivation during critical illness remains unclear and studies investigating prophylaxis in cytomegalovirus seropositive patients are being considered. This study investigates the association between cytomegalovirus seropositivity and outcome in a large population of nonimmunocompromised critically ill patients. DESIGN: : Cytomegalovirus serostatus was determined on prospectively collected serum samples. The primary end point was intensive care unit mortality. The secondary end points were in-hospital mortality, time to alive discharge from intensive care unit and hospital, time to alive weaning from mechanical ventilation, and need for renal replacement therapy. SETTING: : This retrospective study was performed in a 17-bed medical and 56-bed surgical intensive care unit in a 1,900-bed referral hospital. PATIENTS: : We analyzed serum of 1,504 nonimmunocompromised critically ill patients with an intensive care unit length of stay of 3 days or more. Patients with hematologic malignancy, transplantation, immunosuppressive therapy (calcineurin inhibitors, antitumor necrosis factor-[alpha] drugs, antilymphocyte antibodies, or chemotherapeutic agents), or a do-not-resuscitate order were excluded. INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : Sixty-four percent of the studied patients were cytomegalovirus seropositive. Multivariable analysis revealed no associated risk for intensive care unit or hospital mortality, or for time to alive discharge from intensive care unit or hospital. The risk for alive weaning from mechanical ventilation and the need for renal replacement therapy were also comparable in seropositive and seronegative groups. CONCLUSION: : No association was found between the cytomegalovirus serostatus and the studied major clinical outcomes. Based on these results, the design of an intervention study assessing the impact of cytomegalovirus prophylaxis in all cytomegalovirus seropositive critically ill patients appears premature. [ABSTRACT FROM AUTHOR]

Pattern recognition receptors (PRRs) are responsible for Aspergillus fumigatus recognition by innate immunity and its subsequent immune signaling. The triggering receptor expressed on myeloid cells 1 (TREM1) is a recently characterized pro-inflammatory receptor constitutively expressed on the surface of neutrophils and macrophages. A soluble form (sTREM1) of this protein that can be detected in human body fluids has been identified. Here we investigated the role of TREM1 during invasive pulmonary aspergillosis (IPA). IPA patients displayed significantly higher levels of sTREM1 in bronchoalveolar lavages when compared to control patients. Functional analysis in TREM1 showed that the levels of sTREM1 and TREM1 pathway-related cytokines were influenced by single nucleotide polymorphisms in TREM1. In addition, we confirmed a role of TREM1 on antifungal host defense against A. fumigatus in a murine model of IPA. TREM1 deficiency increased susceptibility to infection in the immunosuppressed murine host. Deletion of TREM1 showed delayed innate and adaptive immune responses and impaired pro-inflammatory cytokine responses. The absence of TREM1 in primary macrophages attenuated the TLR signaling by altering the expression of both receptor and effector proteins that are critical to the response against A. fumigatus. In this study, and for the first time, we demonstrate the key role for the TREM1 receptor pathway during IPA. [ABSTRACT FROM AUTHOR]

Of 233 erythromycin-resistant pneumococcal isolates collected in Belgium in 1999–2000, 89.7% carried theerm(B) gene, 6% themef(A) gene, and 3.5%erm(B) plusmef(A). Two isolates contained neithererm(B) normef(A); one contained anerm(A) subclasserm(TR) gene, while the other contained an A2058G mutation in domain V of the 23S rRNA gene. Of 209erm(B)-positive isolates, 191 had clindamycin MICs> 16 mg/L and 18 had MICs≤ 16 mg/L.Mef(A)-positive isolates all displayed the M resistance phenotype. Telithromycin remained active against erythromycin-resistant isolates, with the highest telithromycin MIC50 being found inmef(A)-positive isolates. No difference in the prevalence of different resistance mechanisms was observed compared to isolates collected in 1995–1997. [ABSTRACT FROM AUTHOR]

Pattern recognition receptors (PRRs) are responsible for Aspergillus fumigatus recognition by innate immunity and its subsequent immune signaling. The triggering receptor expressed on myeloid cells 1 (TREM1) is a recently characterized pro-inflammatory receptor constitutively expressed on the surface of neutrophils and macrophages. A soluble form (sTREM1) of this protein that can be detected in human body fluids has been identified. Here we investigated the role of TREM1 during invasive pulmonary aspergillosis (IPA). IPA patients displayed significantly higher levels of sTREM1 in bronchoalveolar lavages when compared to control patients. Functional analysis in TREM1 showed that the levels of sTREM1 and TREM1 pathway-related cytokines were influenced by single nucleotide polymorphisms in TREM1. In addition, we confirmed a role of TREM1 on antifungal host defense against A. fumigatus in a murine model of IPA. TREM1 deficiency increased susceptibility to infection in the immunosuppressed murine host. Deletion of TREM1 showed delayed innate and adaptive immune responses and impaired proinflammatory cytokine responses. The absence of TREM1 in primary macrophages attenuated the TLR signaling by altering the expression of both receptor and effector proteins that are critical to the response against A. fumigatus. In this study, and for the first time, we demonstrate the key role for the TREM1 receptor pathway during IPA. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic performance of seven rapid IgG/IgM tests and the Euroimmun IgA/IgG ELISA for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 patients. Specificity was evaluated in 103 samples collected before January 2020. Sensitivity and time to seropositivity was evaluated in 167 samples from 94 patients with COVID-19 confirmed with RT-PCR on nasopharyngeal swab. Specificity (confidence interval) of lateral flow assays (LFAs) was ≥91.3% (84.0–95.5) for IgM, ≥90.3% (82.9–94.8) for IgG, and ≥85.4% (77.2–91.1) for the combination IgM OR IgG. Specificity of the ELISA was 96.1% (90.1–98.8) for IgG and only 73.8% (64.5–81.4) for IgA. Sensitivity 14–25 days after the onset of symptoms was between ≥92.1% (78.5–98.0) and 100% (95.7–100) for IgG LFA compared to 89.5% (75.3–96.4) for IgG ELISA. Positivity of IgM OR IgG for LFA resulted in a decrease in specificity compared to IgG alone without a gain in diagnostic performance, except for VivaDiag. The results for IgM varied significantly between the LFAs with an average overall agreement of only 70% compared to 89% for IgG. The average dynamic trend to seropositivity for IgM was not shorter than for IgG. At the time of hospital admission the sensitivity of LFA was <60%. Sensitivity for the detection of IgG antibodies 14–25 days after the onset of symptoms was ≥92.1% for all seven LFAs compared to 89.5% for the IgG ELISA. The results for IgM varied significantly, and including IgM antibodies in addition to IgG for the interpretation of LFAs did not improve the diagnostic performance. [ABSTRACT FROM AUTHOR]

Both fracture-related infections (FRIs) and periprosthetic joint infections (PJIs) include orthopaedic implant-associated infections. However, key aspects of management differ due to the bone and soft tissue damage in FRIs and the option of removing the implant after fracture healing. In contrast to PJIs, research and guidelines for diagnosis and treatment in FRIs are scarce. This narrative review aims to update clinical microbiologists, infectious disease specialists and surgeons on the management of FRIs. A computerized search of PubMed was performed to identify relevant studies. Search terms included 'Fracture' and 'Infection'. The reference lists of all retrieved articles were checked for additional relevant references. In addition, when scientific evidence was lacking, recommendations are based on expert opinion. Pathogenesis, prevention, diagnosis and treatment of FRIs are presented. Whenever available, specific data of patients with FRI are discussed. Management of patients with FRI should take into account FRI-specific features. Treatment pathways should implement a multidisciplinary approach to achieve a good outcome. Recently, international consensus guidelines were developed to improve the quality of care for patients suffering from this severe complication, which are highlighted in this review. [ABSTRACT FROM AUTHOR]

The primary aim of this study was to collect national epidemiological data on candidaemia and to determine the reporting time of species identification and antifungal susceptibility in clinical practice. During a 1-year period (March 2013 until February 2014), every first Candida isolate from each episode of candidaemia was included prospectively from 30 Belgian hospitals. Identification and susceptibility testing were performed according to local procedures and isolates were sent to the National Reference Center for Mycosis. Species identification was checked by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and internal transcribed spacer (ITS) sequencing in case no reliable identification was obtained by MALDI-TOF MS. Antifungal susceptibility testing was performed according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology. A total of 355 isolates were retrieved from 338 patients. The mean incidence rate of candidaemia was 0.44 (range: 0.07 to 1.43) per 1000 admissions or 0.65 (range: 0.11 to 2.00) per 10,000 patient days. Candida albicans was most frequently found (50.4 %), followed by C. glabrata (27.3 %) and C. parapsilosis sensu lato (9.8 %). The overall resistance to fluconazole was 7.6 %, ranging from 3.9 % in C. albicans to 20.0 % in C. tropicalis. Only one C. glabrata isolate was resistant to the echinocandins. Four days after blood culture positivity, 99.7 % of the identifications and 90.3 % of the antifungal profiles were reported to the treating clinician. Candidaemia incidence rates differed up to 20-fold among Belgian hospitals; no clear factors explaining this difference were identified. The overall antifungal resistance rates were low but high azole resistance rates were recorded in C. tropicalis. [ABSTRACT FROM AUTHOR]

A response by J. Maertens, K, Lagrou and J. Van Eldere to the letter to the editor about their article on preemptive antifungal therapy among neutropenic patients is presented.

Objectives: In patients with invasive aspergillosis (IA), fungal cultures are mostly negative. Consequently, azole resistance often remains undetected. The AsperGenius® multiplex real-time PCR assay identifies clinically relevant Aspergillus species and four resistance-associated mutations (RAMs; TR34/L98H/T289A/Y121F) in the Cyp51A gene. This multicentre study evaluated the diagnostic performance of this assay on bronchoalveolar lavage (BAL) fluid and correlated the presence of RAMs with azole treatment failure and mortality.Methods: Stored BAL samples from patients with haematological diseases with suspected IA were used. BAL samples that were galactomannan/culture positive were considered positive controls for the presence of Aspergillus. Azole treatment failure and 6 week mortality were compared in patients with and without RAMs that had received ≥5 days of voriconazole monotherapy.Results: Two hundred and one patients each contributed one BAL sample, of which 88 were positive controls and 113 were negative controls. The optimal cycle threshold cut-off value for the Aspergillus species PCR was <38. With this cut-off, the PCR was positive in 74/88 positive controls. The sensitivity, specificity, positive predictive value and negative predictive value were 84%, 80%, 76% and 87%, respectively. 32/74 BAL samples were culture negative. Azole treatment failure was observed in 6/8 patients with a RAM compared with 12/45 patients without RAMs (P = 0.01). Six week mortality was 2.7 times higher in patients with RAMs (50.0% versus 18.6%; P = 0.07).Conclusions: The AsperGenius® assay had a good diagnostic performance on BAL and differentiated WT from Aspergillus fumigatus with RAMs, including in culture-negative BAL samples. Most importantly, detection of RAMs was associated with azole treatment failure. [ABSTRACT FROM AUTHOR]

A challenge panel of bacterial strains useful for clinical laboratories to validate their European Committee on Antimicrobial Susceptibility Testing (EUCAST) antimicrobial susceptibility test (AST) system was established. A total of 117 strains, obtained from Belgian Reference Centres ( n = 57) and from routine clinical samples ( n = 60) was selected based on resistance pattern. These strains were analysed in seven different laboratories by three different automated AST systems (Vitek ( n = 2), Phoenix ( n = 2) and Microscan ( n = 2)) and by disc diffusion from five different manufacturers (Rosco ( n = 2), Becton-Dickinson ( n = 2), Biomérieux ( n = 1), Bio-rad ( n = 1) and i2a ( n = 1)). To select the challenge panel, selection criteria were set for categorical agreement between the different systems and the number of very major errors, major errors and minor errors. Very major and major errors for at least two antibiotics were observed in 43% of all strains, leading to the exclusion of these strains from the selected panel. In only 10% of all tested strains was there 100% categorical agreement for all antibiotics. Finally, 28 strains (14 Gram-positive and 14 Gram-negative) covering a wide spectrum of resistance mechanisms were selected. Pilot-testing of this challenge panel in 20 laboratories mainly confirmed the results of the validation study. Only six strains withheld for the pilot study could not be used as challenge strain due to an overall (very) major error rate of >5% for a particular antibiotic ( n = 5) or for two antibiotics ( n = 1). To conclude, this challenge panel should facilitate the implementation and use of EUCAST breakpoints in laboratories. [ABSTRACT FROM AUTHOR]

Hantavirus infections, recently renamed 'hantavirus fever' (HTVF), belong to the most common but also most underestimated zoonoses in the world. A small number of reports described the so-called 'lipid paradox' in HTVF, i.e. the striking contrast between a very low serum total cholesterol and/or high-density lipoprotein cholesterol (HDLc), and a paradoxical concomitant hypertriglyceridaemia. In a prospective study, with patients being their own control after illness, we wanted to verify if this quick and easy 'bedside test' was robust enough to warrant a preliminary diagnosis of acute kidney injury (AKI) caused by HTVF. The study cohort consisted of 58 Belgian cases (mean age 44 years), admitted with varying degrees of AKI and of thrombocytopaenia, both characteristic for presumptive HTVF. All cases were sero-confirmed as having acute HTVF. At or shortly after hospital admission, a significant ( p < 0.001) decrease of total cholesterol and HDLc was found in comparison with normalised levels in the same cohort, quantified a few days after spontaneous AKI recovery. Conversely, fasting triglyceride levels during HTVF infection were significantly ( p < 0.001) higher during illness than after recovery. This 'lipid paradox' was most outspoken in severe HTVF cases, often accompanying, or even predicting, major kidney or lung complications. Thus, this 'bedside assessment' seems to hold even promise for presumptive diagnosis of more severe so-called 'hantavirus cardio-pulmonary syndrome' (HCPS) cases, mostly described hitherto in the New World. In more severe AKI cases, the mean total cholesterol was significantly lower ( p = 0.02) than in milder cases, i.e. cases with peak serum creatinine levels of < 1.5 mg/dL. Thrombocytopaenia, generally accepted as the severity index in HTVF, appeared, moreover, significantly correlated with serum levels of total cholesterol (R = 0.52, p < 0.001) and with serum levels of HDLc (R = 0.45, p < 0.01). A link with the novel clinical entity of haemophagocytic syndromes, also characterised by manifest hypertriglyceridaemia, is discussed. [ABSTRACT FROM AUTHOR]

The Architect Syphilis TP is considered to be a suitable screening test due to its high sensitivity and full automation. According to the International Union against Sexually Transmitted Infections (IUSTI) 2014 guidelines, however, positive screening tests need confirmation with Treponema pallidum particle agglutination (TP.PA). Among Architect-positive results, samples with a negative non-treponemal test present the major diagnostic challenge. In this multicenter study, we investigated if other, preferable less labor-intensive treponemal tests could replace TP.PA. A total of 178 rapid plasma reagin (RPR)-negative sera with an Architect value between 1 and 15 S/CO were prospectively selected in three centers. These sera were analyzed with TP.PA and six alternative treponemal tests: three immunoblots and three tests on random-access analyzers. The diagnostic performance of the treponemal tests differed substantially, with the overall agreement between the six alternative tests ranging from 44.6 to 82.0 %. Based on TP.PA as the gold standard, the INNO-LIA IgG blot, the BioPlex 2200 IgG, and the Syphilis TPA showed a high sensitivity, while the EUROLINE-WB IgG blot, recomLine Treponema IgG blot, and the Chorus Syphilis screen showed a high specificity. However, an Architect cut-off of 5.6 S/CO can serve as an alternative for these confirmatory treponemal tests in case of an RPR-negative result. Treponemal tests show poor agreement in this challenging group of Architect-positive/RPR-negative sera. The most optimal algorithm is obtained by assigning sera with an Architect value >5.6 S/CO as true-positives and sera with a value between 1 and 5.6 S/CO as undetermined, requiring further testing with TP.PA. [ABSTRACT FROM AUTHOR]

To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles. [ABSTRACT FROM AUTHOR]

We present a case report of a patient with diffuse skin and systemic Kaposi's sarcoma ( KS), 1 year after renal transplantation. A concomitant Pyrenochaeta romeroi granuloma of the right hallux was diagnosed and illustrated an important immunodysfunction in our patient. Four months after reduction in immunosuppression and switch to everolimus, a total regression of the KS was observed. Reduction in the immunosuppression and treatment with terbinafine cleared the P. romeroi infection, while lowering immunosuppression and changing the type of immunosuppressive therapy were important steps in the successful management of the KS. In recent years, evidence of the antitumor effects of everolimus is increasing: total regression of KS in combination with renal function preservation in renal graft recipients is possible with mammalian target of rapamycin ( mTOR) inhibitor-based regimens. In addition, with increasing numbers of human immunodeficiency virus-positive transplant recipients, mTOR inhibitors may play a more crucial role in the management of KS. [ABSTRACT FROM AUTHOR]

Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae. The number of organisms implicated in hyalohyphomycosis is increasing and the most clinically important species belong to the genera Fusarium, Scedosporium, Acremonium, Scopulariopsis, Purpureocillium and Paecilomyces. Severely immunocompromised patients are particularly vulnerable to infection, and clinical manifestations range from colonization to chronic localized lesions to acute invasive and/or disseminated diseases. Diagnosis usually requires isolation and identification of the infecting pathogen. A poor prognosis is associated with fusariosis and early therapy of localized disease is important to prevent progression to a more aggressive or disseminated infection. Therapy should include voriconazole and surgical debridement where possible or posaconazole as salvage treatment. Voriconazole represents the first-line treatment of infections due to members of the genus Scedosporium. For Acremonium spp., Scopulariopsis spp., Purpureocillium spp. and Paecilomyces spp. the optimal antifungal treatment has not been established. Management usually consists of surgery and antifungal treatment, depending on the clinical presentation. [ABSTRACT FROM AUTHOR]

These European Society for Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology Joint Clinical Guidelines focus on the diagnosis and management of mucormycosis. Only a few of the numerous recommendations can be summarized here. To diagnose mucormycosis, direct microscopy preferably using optical brighteners, histopathology and culture are strongly recommended. Pathogen identification to species level by molecular methods and susceptibility testing are strongly recommended to establish epidemiological knowledge. The recommendation for guiding treatment based on MICs is supported only marginally. Imaging is strongly recommended to determine the extent of disease. To differentiate mucormycosis from aspergillosis in haematological malignancy and stem cell transplantation recipients, identification of the reverse halo sign on computed tomography is advised with moderate strength. For adults and children we strongly recommend surgical debridement in addition to immediate first-line antifungal treatment with liposomal or lipid-complex amphotericin B with a minimum dose of 5 mg/kg/day. Amphotericin B deoxycholate is better avoided because of severe adverse effects. For salvage treatment we strongly recommend posaconazole 4 × 200 mg/day. Reversal of predisposing conditions is strongly recommended, i.e. using granulocyte colony-stimulating factor in haematological patients with ongoing neutropenia, controlling hyperglycaemia and ketoacidosis in diabetic patients, and limiting glucocorticosteroids to the minimum dose required. We recommend against using deferasirox in haematological patients outside clinical trials, and marginally support a recommendation for deferasirox in diabetic patients. Hyperbaric oxygen is supported with marginal strength only. Finally, we strongly recommend continuing treatment until complete response demonstrated on imaging and permanent reversal of predisposing factors. [ABSTRACT FROM AUTHOR]

The aetiological agents of many invasive fungal infections are saprobes and opportunistic pathogens. Some of these fungi are darkly pigmented due to melanin production and traditionally have been named 'dematiaceous'. The melanized fungi cause a wide array of clinical syndromes ranging from superficial to deep-seated infections. Diagnosis relies on histopathological examination of clinical specimens and on examination of cultures. Sequencing is recommended for accurate species identification, especially for unusual or newly described pathogens. In cases of mycetoma and chromoblastomycosis, pathognomonic histological findings are useful and the Fontana–Masson stain, specific for melanin, usually confirms the diagnosis. There are no standardized therapies but voriconazole, posaconazole and itraconazole demonstrate the most consistent in vitro activity against this group of fungi. Oral itraconazole has been considered the drug of choice, given the extensive clinical experience with this drug. However, voriconazole may presumably be superior for central nervous system infections because of its ability to achieve good levels in the cerebrospinal fluid. Posaconazole is a well-tolerated alternative drug, backed by less clinical experience but with excellent salvage treatment results after failure of other antifungals. Amphotericin B has been useful as alternative therapy in some cases. Combination antifungal therapy is recommended for cerebral abscesses when surgery is not possible and for disseminated infections in immunocompromised patients. [ABSTRACT FROM AUTHOR]

Wildlife-originated zoonotic diseases in general are a major contributor to emerging infectious diseases. Hantaviruses more specifically cause thousands of human disease cases annually worldwide, while understanding and predicting human hantavirus epidemics pose numerous unsolved challenges. Nephropathia epidemica (NE) is a human infection caused by Puumala virus, which is naturally carried and shed by bank voles ( Myodes glareolus). The objective of this study was to develop a method that allows model-based predicting 3 months ahead of the occurrence of NE epidemics. Two data sets were utilized to develop and test the models. These data sets were concerned with NE cases in Finland and Belgium. In this study, we selected the most relevant inputs from all the available data for use in a dynamic linear regression (DLR) model. The number of NE cases in Finland were modelled using data from 1996 to 2008. The NE cases were predicted based on the time series data of average monthly air temperature (°C) and bank voles' trapping index using a DLR model. The bank voles' trapping index data were interpolated using a related dynamic harmonic regression model (DHR). Here, the DLR and DHR models used time-varying parameters. Both the DHR and DLR models were based on a unified state-space estimation framework. For the Belgium case, no time series of the bank voles' population dynamics were available. Several studies, however, have suggested that the population of bank voles is related to the variation in seed production of beech and oak trees in Northern Europe. Therefore, the NE occurrence pattern in Belgium was predicted based on a DLR model by using remotely sensed phenology parameters of broad-leaved forests, together with the oak and beech seed categories and average monthly air temperature (°C) using data from 2001 to 2009. Our results suggest that even without any knowledge about hantavirus dynamics in the host population, the time variation in NE outbreaks in Finland could be predicted 3 months ahead with a 34% mean relative prediction error (MRPE). This took into account solely the population dynamics of the carrier species (bank voles). The time series analysis also revealed that climate change, as represented by the vegetation index, changes in forest phenology derived from satellite images and directly measured air temperature, may affect the mechanics of NE transmission. NE outbreaks in Belgium were predicted 3 months ahead with a 40% MRPE, based only on the climatological and vegetation data, in this case, without any knowledge of the bank vole's population dynamics. In this research, we demonstrated that NE outbreaks can be predicted using climate and vegetation data or the bank vole's population dynamics, by using dynamic data-based models with time-varying parameters. Such a predictive modelling approach might be used as a step towards the development of new tools for the prevention of future NE outbreaks. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study was to evaluate the frequency of 'occult' bacteremia/fungemia as well as the diversity of pathogens involved in hematology patients treated with corticosteroids. Methods: Daily surveillance blood cultures were taken from patients treated with corticosteroids as part of their intensive chemotherapy or during graft-versus-host disease following hematopoietic stem cell transplantation during a 3-year period (2006-2009). We reviewed the frequency of occult bacteremia/fungemia as well as the pathogens involved. Results: During the 3-year period, 3,821 bottles were cultured from 215 patients and 4.9 % of the bottles tested were positive. Surveillance blood cultures revealed bloodstream infection in 24 % of the patients (definite bloodstream infection in 16 %). Seventy-five percent of patients were still afebrile when microorganisms were detected. The main risk group was acute lymphocytic leukemia patients undergoing remission induction chemotherapy. The pathogens cultured most frequently were coagulase-negative staphylococci, enterococci, Escherichia coli, and Pseudomonas aeruginosa. Conclusions: A high incidence of occult bacteremia was detected by surveillance blood cultures. Further studies are needed to evaluate if a strategy based on surveillance blood cultures can reduce mortality related to bloodstream infections. [ABSTRACT FROM AUTHOR]

Abstract: The strong correlation between environmental conditions and abundance and spatial spread of the tick Ixodes ricinus is widely documented. I. ricinus is in Europe the main vector of the bacterium Borrelia burgdorferi, the pathogen causing Lyme borreliosis (LB). Humidity in vegetated systems is a major factor in tick ecology and its effects might translate into disease incidence in humans. Time series of two remotely sensed indices with sensitivity to vegetation greenness and moisture were tested as explanatory variables of LB incidence. Wavelet-based multiresolution analysis allowed the examination of these signals at different temporal scales in study sites in Belgium, where increases in LB incidence were reported in recent years. The analysis showed the potential of the tested indices for disease monitoring, the usefulness of analyzing the signal in different time frames and the importance of local characteristics of the study area for the selection of the vegetation index. [Copyright &y& Elsevier]

Clin Microbiol Infect 2011; 17: 1859-1867 Abstract Zygomycosis is an important emerging fungal infection, associated with high morbidity and mortality. The Working Group on Zygomycosis of the European Confederation of Medical Mycology (ECMM) prospectively collected cases of proven and probable zygomycosis in 13 European countries occurring between 2005 and 2007. Cases were recorded by a standardized case report form, entered into an electronic database and analysed descriptively and by logistic regression analysis. During the study period, 230 cases fulfilled pre-set criteria for eligibility. The median age of the patients was 50 years (range, 1 month to 87 years); 60% were men. Underlying conditions included haematological malignancies (44%), trauma (15%), haematopoietic stem cell transplantation (9%) and diabetes mellitus (9%). The most common manifestations of zygomycosis were pulmonary (30%), rhinocerebral (27%), soft tissue (26%) and disseminated disease (15%). Diagnosis was made by both histology and culture in 108 cases (44%). Among 172 cases with cultures, Rhizopus spp. (34%), Mucor spp. (19%) and Lichtheimia ( formerly Absidia) spp. (19%) were most commonly identified. Thirty-nine per cent of patients received amphotericin B formulations, 7% posaconazole and 21% received both agents; 15% of patients received no antifungal therapy. Total mortality in the entire cohort was 47%. On multivariate analysis, factors associated with survival were trauma as an underlying condition (p 0.019), treatment with amphotericin B (p 0.006) and surgery (p <0.001); factors associated with death were higher age (p 0.005) and the administration of caspofungin prior to diagnosis (p 0.011). In conclusion, zygomycosis remains a highly lethal disease. Administration of amphotericin B and surgery, where feasible, significantly improve survival. [ABSTRACT FROM AUTHOR]

To the editor Although fracture-related infection (FRI) after open fractures is a well-known clinical challenge for orthopaedic trauma surgeons, standardized, internationally accepted guidelines are still lacking for the kind and duration of systemic perioperative antibiotic prophylaxis (PAP) [1]. Indeed, Yusuf et al. [3] found that in patients with Gustilo-Anderson type III injuries 47% of strains were resistant to amoxicillin/clavulanic acid at initial surgery, and 88% of strains were resistant at revision surgery. Currently, it remains at the discretion of the treating physicians (multidisciplinary team approach) to modify the spectrum of systemic PAP in individual patients with Gustilo-Anderson type III fractures based on local epidemiology and host status. [Extracted from the article]

The incidence of invasive infections caused by the Aspergillus niger species complex was 0.043 cases/10 000 patient-days in a Belgian university hospital (2005-2011). Molecular typing was performed on six available A. niger complex isolates involved in invasive disease from 2010 to 2011, revealing A. tubingensis, which has higher triazole minimal inhibitory concentrations, in five out of six cases. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 34-year-old man with persistent cough. The chest radiograph and computed tomography scan indicated that the patient had nodular pulmonary lesion in his left lower lobe, enlarged hilar and mediastinal lymph nodes and bilateral paraseptal emphysema. He also underwent pulmonary function testing and found that he had impaired lung diffusion capacity.

Pseudomonas aeruginosa (PA) is an established risk factor for chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx). PA eradication in cystic fibrosis patients prevents pulmonary function decline. Therefore, we investigated the effect of PA eradication after LTx on CLAD-free survival, graft survival and pulmonary function. Patients transplanted between 07/1991 and 02/2016 in our hospital with sufficient pulmonary function data, without redo LTx or CLAD onset before 09/2011 were retrospectively included and classified according to PA presence in respiratory samples between 09/2011 and 09/2016. PA positive patients were subsequently stratified according to success of PA eradication. CLAD-free and graft survival were compared between PA positive and PA negative patients and between patients with or without successful PA eradication. In addition, pulmonary function was assessed during the first year following PA isolation in both groups. CLAD-free and graft survival of PA negative patients (n=443, 82%) was better compared to PA positive patients (n=95, 18%) (p=0.0005, p=0.0011). PA eradicated patients (n=76, 80%) had better graft survival compared to patients with persistent PA (n=19, 20%) (p<0.0001) (fig 1A). Similarly, PA eradicated patients demonstrated better CLAD-free survival compared to patients with persistent PA (p=0.018) (fig 1B). Pulmonary function was better in successfully PA eradicated patients compared to unsuccessfully eradicated patients (p=0.035) (fig 1C). PA eradication after LTx improves CLAD-free and graft survival and helps maintain pulmonary function. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Diversity and combinations of infectious agents in 38 adults with an infection-triggered reactive haemophagocytic syndrome: a multicenter study," by N. Lerolle and colleagues in the 2016 issue.

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging. [ABSTRACT FROM AUTHOR]

Objectives For adequate management and therapy of infective endocarditis (IE), identification of the causative pathogen is crucial but molecular testing results are not currently included in diagnostic criteria. The added diagnostic value and impact on antimicrobial therapy of 16S rRNA PCR and amplicon sequencing (16S rRNA PCR) performed on excised heart valves from patients with IE was evaluated alongside the effect of pre-operative antibiotics on the performance of blood culture (BC), valve culture (VC) and 16S rRNA PCR. Methods All patients undergoing valve surgery for definite or possible IE, according to modified Duke Criteria, were prospectively included from July 2013 up to and including June 2016. Results In all, 127 patients were included. Sensitivity for detecting the causative micro-organism in 120 post-operative definite IE patients was 26% for VC and 87% for BC and 16S rRNA PCR. 16S rRNA PCR, VC and BC were equally sensitive for different valve types and causative pathogens. In 27 (21%) definite IE patients, 16S rRNA PCR clarified discrepant culture results or was the only method identifying the causative pathogen. In 12 (10%) post-operative definite IE cases, molecular testing results influenced antimicrobial therapy. Conclusions The very good performance characteristics, added diagnostic value and impact on antimicrobial therapy of molecular testing of heart valves should support the incorporation of molecular testing in diagnostic criteria and guidelines for IE. [ABSTRACT FROM AUTHOR]

Objectives A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. Methods A total of 370 cases from 21 countries were evaluated. Results The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). Conclusions Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs. [ABSTRACT FROM AUTHOR]

The Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST) has determined breakpoints for isavuconazole and Aspergillus and for itraconazole and Candida spp., released a new document summarizing existing and new minimum inhibitory concentration ranges for quality control strains and revised the method documents for yeast and mould susceptibility testing. This technical note is based on the EUCAST isavuconazole and itraconazole rationale documents, version 1.0 of the routine and extended internal quality control for antifungal susceptibility testing as recommended by EUCAST, and the E.Def 7.3, E.Def 9.2 and E.Def 9.3 method documents ( http://www.eucast.org ). [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Cytomegalovirus: a retrospective comparative analysis of fetal ultrasound and magnetic resonance imaging in predicting fetal outcome," by L. Lannoo and colleagues is presented.