De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier ...to its implementation. We aimed to determine whether de-escalation from an antipseudomonal β-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia.
An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal β-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim–sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin–clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal β-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3–5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the –10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete.
2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI –5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths.
De-escalation from an antipseudomonal β-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting.
Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligence Growth 2014–2020.
Although fortunately very rare in countries with a temperate climate, certain factors, such as clinical or pharmacological immunosuppression, may cause Fusarium-related fungal infections to become an ...emerging problem. Moreover, Fusarium is one of the most important etiological agents in exogenous endophthalmitis, which is often favored by the disruption of the epithelial barriers.
The aim of this series of clinical cases is to identify characteristic clinical findings that may allow an early diagnosis and more efficient management of this ophthalmologic emergency.
Three cases of endophthalmitis due to Fusarium solani and Fusarium oxysporum, diagnosed in 2009, 2010, and 2014 in patients from two different health regions belonging to the same health system and separated by around 43 miles, are presented. The Fusarium isolates were initially identified microscopically and the species subsequently confirmed by sequencing the elongation factor alpha (EFα) and internal transcribed spacers (ITS). Susceptibility to antifungal agents was determined using the EUCAST broth dilution method.
Evolution was poor as two of the three patients progressed to phthisis bulbi despite surgical measures and broad-spectrum antifungal antibiotic therapy.
It is essential to rapidly instigate multidisciplinary measures to combat suspected endophthalmitis due to Fusarium given the poor prognosis of this type of infection.
Abstract
Objectives
To provide a basis for clinical management decisions in Paecilomyces variotii infection.
Methods
Unpublished cases of invasive P. variotii infection from the FungiScope® registry ...and all cases reported in the literature were analysed.
Results
We identified 59 cases with P. variotii infection. Main baseline factors were presence of indwelling devices in 29 cases (49.2%), particularly peritoneal catheters (33.9%) and prosthetic heart valves (10.2%), haematological or oncological diseases in 19 (32.2%), major surgery in 11 (18.6%), and diabetes mellitus in 10 cases (16.9%). The most prevalent infection sites were peritoneum (n = 20, 33.3%) and lungs (n = 16, 27.1%). Pain and fever were frequent (n = 35, 59.3% and n = 33, 55.9%, respectively). Diagnosis was established by culture in 58 cases (98.3%). P. variotii caused breakthrough infection in 8 patients. Systemic antifungals were given in 52 patients (88.1%). Amphotericin B was administered in 39, itraconazole in 15, and posaconazole in 8 patients. Clinical isolates were frequently resistant to voriconazole, whereas the above-mentioned antifungals showed good in vitro activity. Infections of the blood and CNS caused high mortality. Overall mortality was 28.8% and death was attributed to P. variotii in 10 cases.
Conclusions
P. variotii causes life-threatening infections, especially in immunocompromised and critically ill patients with indwelling devices. Patients undergoing peritoneal dialysis are at particular risk. Multidisciplinary management is paramount, including molecular techniques for diagnosis and treatment with efficacious systemic antifungals. Amphotericin B, itraconazole and posaconazole are regarded as treatments of choice. Combination with flucytosine may be considered. Surgical debridement and removal of indwelling devices facilitate favourable outcome.
Fundamento: Recientemente se han registrado brotes de
parotiditis en España y en otros países desarrollados. Los
motivos barajados son la baja cobertura vacunal de las poblaciones
afectadas y/o la ...baja efectividad de las cepas vacunales
empleadas. Este trabajo describe un brote de parotiditis ocurrido
en Bizkaia y valora la efectividad de las cepas vacunales y
la utilidad de las pruebas diagnósticas actualmente empleadas.
Métodos: Se etiquetaron como casos aquéllos con clínica
compatible y vínculo epidemiológico en el periodo de estudio
(febrero-mayo-2006). Se recogieron muestras de sangre para
estudio de IgM e IgG y de saliva para detección de RNA y
genotipo. Se averiguó el estado vacunal y la cepa empleada
mediante los registros del reparto vacunal. Se realizó un análisis
univariante de los datos y se obtuvieron riesgos relativos
según las cepas vacunales empleadas.
Resultados: Se detectaron 63 casos; 52 eran alumnos del
mismo colegio. El 50% tenía entre 9 y 13 años. El 88,5% de
los casos del colegio estaba correctamente vacunado. La sensibilidad
de la IgM fue del 9% y la de la PCR del 37%. El riesgo
relativo de los alumnos vacunados con una primera dosis de
cepa Rubini frente a los vacunados con cepa Jeryl-Lynn fue de
3,8 (IC95% 2,27-6,49).
Conclusiones: La elevada cobertura vacunal no impide el
desarrollo de brotes en lugares con un alto grado de exposición.
La IgM se muestra poco sensible para el diagnóstico de
parotiditis. Parece necesario replantearse las estrategias vacunales
y los métodos diagnósticos actuales.
Abstract
Background
Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, ...this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established.
Objective
To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF.
Methods
We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF.
Results
Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5–64), amphotericin B 2 mg/L (range 0.25–64), posaconazole 16 mg/L (range 0.5–64), itraconazole 32 mg/L (range 4–64), and isavuconazole 32 mg/L (range 8–64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality.
Conclusions
Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF.
We aimed to assess the percentage of azole resistance in Aspergillus fumigatus in Spain.
Thirty participating Spanish hospitals stored all morphologically identified A. fumigatus sensu lato clinical ...isolates—regardless their clinical significance—from 15 February to 14 May 2019. Isolates showing azole resistance according to the EUCAST 9.3.2 methodology were molecularly identified and the cyp51A gene was studied in A. fumigatus sensu stricto isolates.
Eight hundred and forty-seven isolates from 725 patients were collected in 29 hospitals (A. fumigatus sensu stricto (n = 828) and cryptic species (n = 19)). Isolates were mostly from the lower respiratory tract (94.0%; 797/847). Only cryptic species were amphotericin B resistant. Sixty-three (7.4%) out of the 847 isolates were resistant to ≥1 azole(s). Azole resistance was higher in cryptic species than in A. fumigatus sensu stricto (95%, 18/19 vs. 5.5%, 45/828); isavuconazole was associated to the lowest number of non-wild type isolates. The dominant mechanism of resistance was the presence of TR34-L98H substitutions (n = 24 out of 63). Out of the 725 patients, 48 (6.6%) carried either cryptic species (n = 14) or A. fumigatus sensu stricto (n = 34; 4.7%) resistant isolates. Aspergillus fumigatus sensu stricto harbouring either the TR34-L98H (n = 19) or TR46/Y121F/T289A (n = 1) mutations were detected in patients in hospitals located at 7/24 studied cities.
Of the patients, 6.6% carry azole-resistant A. fumigatus sensu lato isolates in Spain. TR34-L98H is the dominant cyp51A gene substitutions, although its presence is not widespread.
Saprochaete capitata (formerly known as Geotrichum capitatum and Blastoschizomyces capitatus) is a ubiquitous fungus found in soil, water, air, plants and dairy products. It colonizes the skin, and ...bronchial and intestinal tract of healthy people producing serious opportunistic infections in patients with haematological malignancies, especially in those with acute leukaemia. Since 1960s its presence is being increasingly recognized in this group of patients. The clinical spectrum of S. capitata disseminated infections is very similar to that produced by Candida, being easily misinterpreted. The associated high mortality and low susceptibility to fluconazole and echinocandins of S. capitata require the acknowledgement of this emergent infection so that it can be properly treated.
We report 5 new cases of S. capitata disseminated infection in patients with advanced haematological malignancies observed in the haematology unit between the years 2004 and 2010, and review the state-of-the-art for diagnosis and treatment of this infection.
Based on our experience, the prophylactic use of or the empirical antifungal treatment with fluconazole and/or echinocandins would not be adequate for oncohaematological patients in those hospitals where S. capitata infection may be highly prevalent.
Diagnosis of invasive mycoses is a difficult challenge due to the limitations and low sensitivity of traditional microbiology methods which lead to diagnostic and therapeutic delays. The aim of this ...review is to summarise the state of the art of the molecular diagnosis of invasive fungal disease and to clarify its current role in the clinical practice. Conventional microbiological methods could be complemented with molecular methods in the rapid and definitive identification of fungal isolates. Biomarkers (β-glucan, galactomannan) are very useful in immunocompromised patients and have been included as probable invasive mycoses by the EORTC/MSG. Nucleic acid detection is currently used as a complementary tool for diagnosis. However, PCR can be very useful in mould invasive mycoses. Finally, the combined detection using biomarkers can improve the diagnosis. However, their applicability in the microbiology laboratory is not so easy and further studies are required for the appropriate evaluation of its clinical usefulness.
This work was aimed to study the HIV-1 subtype B epidemics in the Basque Country, Spain. 1727 HIV-1 subtype B sequences comprising protease and reverse transcriptase (PR/RT) coding regions, sampled ...between 2001 and 2008, were analyzed. 156 transmission clusters were detected by means of phylogenetic analyses. Most of them comprised less than 4 individuals and, in total, they included 441 patients. Six clusters comprised 10 or more patients and were further analyzed in order to study their origin and diversification. Four clusters included men who had unprotected homosexual sex (MSM), one group was formed by intravenous drug users (IDUs), and another included both IDUs and people infected through unprotected heterosexual sex (HTs). Most of these clusters originated from the mid-1980s to the mid-1990s. Only one cluster, formed by MSM, originated after 2000. The time between infections was significantly lower in MSM groups than in those containing IDUs (P-value <0.0001). Nucleoside RT and non-nucleoside RT inhibitor (NRTI and NNRTI)-resistance mutations to antiretroviral treatment were found in these six clusters except the most recent MSM group, but only the IDU clusters presented protease inhibitor (PI)-resistance mutations. The most prevalent mutations for each inhibitor class were PI L90M, NRTI T215D/Y/F, and NNRTI K103N, which were also among the most prevalent resistant variants in the whole dataset. In conclusion, while most infections occur as isolated introductions into the population, the number of infections found to be epidemiologically related within the Basque Country is significant. Public health control measures should be reinforced to prevent the further expansion of transmission clusters and resistant mutations occurring within them.
•We have analyzed PR/RT sequences of HIV-1 from the Basque Country (Spain).•Sequences were sampled in 2001–2008 from 1727 different patients.•Transmission clusters were determined by phylogenetic analyses.•Six clusters comprised more than 10 patients and were analyzed in detail.•Average transmission intervals were shorter for clusters conformed by MSM.•Some antiretroviral resistance mutations were prevalent in the large clsuters.
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