Endocarditis due to <i>Aspergillus flavus</i>

We analyzed 270 cases of fungal endocarditis (FE) that occurred over 30 years. Vascular lines, non-cardiac surgery, immunocompromise and injection drug abuse are increasing risk factors. Delayed or mistaken diagnosis (82% of patients), long duration of symptoms before hospitalization (mean +/- standard deviation, 32+/-39 days) and extracardiac manifestations were characteristic. From 1988 onwards, 72% of patients were diagnosed preoperatively, compared with 43% before 1988 (P=.0001). The fungi most commonly isolated were Candida albicans (24% of patients), non-albicans species of Candida (24%), Apergillus species (24%), and Histoplasma species (6%); recently-emerged fungi accounted for 25% of cases. The mortality rate was 72%. Survival rates were better among patients who received combined surgical-antifungal treatment, were infected with Candida, and had univalvular involvement. Improvement in the survival rate (from <20% before 1974 to 41% currently) coincided with the introduction of echocardiography and with improved diagnostic acumen. Fungal endocarditis recurs in 30% of survivors. It is recommended that fungal endocarditis be diagnosed early through heightened diagnostic acumen; that patients be treated with combined lipid-based amphotericin B and early surgery; and that patients be followed up for > or =4 years while on prophylactic antifungal therapy.

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“…This could reflect the introduction of echocardiography as a diagnostic tool. However, diagnostic delay continues to be reported [19].…”

Section: Discussionmentioning

confidence: 99%

Fungal Endocarditis: Evidence in the World Literature, 1965-1995

Ellis

Al-Abdely

Sandridge

et al. 2001

Clinical Infectious Diseases

450

363

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“…Aspergillus flavus is the second most important species causing localized as well as systemic infections [2,5-7]. The species is of particular significance in North Africa, India and the Middle East, where it is predominantly associated with nasal/sinus infections [8-12]. In 2008, Clinical and Laboratory Standards Institute produced standard guidelines based on broth microdilution (BMD) method for determining antifungal susceptibilities of spore-forming filamentous fungi [13].…”

Section: Introductionmentioning

confidence: 99%

Molecular identification and antifungal susceptibility profile of Aspergillus flavus isolates recovered from clinical specimens in Kuwait

2013

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BackgroundWithin the genus Aspergillus, A. flavus is the second most important species of clinical significance. It is predominantly associated with infections involving sinuses, eye and skin, mostly in geographic regions with hot and arid climate, including the Middle East. Recent reports on emergence of resistance to triazoles among Aspergillus spp. is a cause of concern for treatment of patients with invasive aspergillosis. In this study we present data on genetic characterization and antifungal susceptibility profile of clinical and environmental isolates of A. flavus.MethodsNinety-nine Aspergillus section Flavi isolates, originating from clinical (n=92) and environmental (n=7) sources, initially identified by morphological characteristics, were analyzed by partial sequencing of β-tubulin and calmodulin gene fragments and their susceptibilities to six antifungal agents was determined by Etest on RPMI1640 and Muller-Hinton agar media. Etest minimum inhibitory concentrations (MICs) of amphotericin B and voriconazole were also compared with zone of inhibition diameters obtained by disc diffusion test on RPMI agar medium.ResultsThe identity of all clinical and environmental isolates was confirmed as A. flavus species by combined analysis of β-tubulin and calmodulin genes. The mean MIC90 (μg/ml) values on RPMI medium for amphotericin B, voriconazole, posaconazole, anidulafungin, micafungin and caspofungin were 3, 0.25, 0.25, 0.002, 0.002 and 0.032, respectively. No environmental isolate exhibited MIC value of >2 μg/ml for amphotericin B. For clinical isolates, the zone of inhibition diameters for amphotericin B and voriconazole ranged from 7–16 mm and 24–34 mm, respectively. Linear regression analysis between Etest MIC values and disk diffusion diameters revealed a significant inverse correlation with amphotericin B (p <0.001) and voriconazole (p<0.003).ConclusionsThe β-tubulin and calmodulin gene sequences confirmed that all 92 clinical isolates identified phenotypically belonged to A. flavus taxon, thus suggesting that the other species within Aspergillus section Flavi are of little clinical significance. Triazoles and echinocandins showed very good in vitro activity against the A. flavus, however, 10% clinical isolates showed MICs of >2 μg/ml for amphotericin B.

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“…Invasive and allergic infections by this filamentous fungus are more common in tropical and subtropical countries, particularly India and Pakistan and in the Middle East (2-4), whereas A. fumigatus is the most common cause of aspergillosis in the United States and Europe (5)(6)(7). Climate factors, particularly temperature and humidity, are important determinants of the presence of A. flavus in regions with arid conditions, including Southeast Asia, the Middle East, and Africa, where it is reported to be the predominant agent of sinusitis, keratitis, and cutaneous infections (3,8,9). Voriconazole (VRC) is the preferred antifungal agent for the primary therapy of invasive aspergillosis (IA) according to guideline recommendations of the Infectious Diseases Society of America in all clinical sites (10).…”

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confidence: 99%

Investigation of Multiple Resistance Mechanisms in Voriconazole-Resistant Aspergillus flavus Clinical Isolates from a Chest Hospital Surveillance in Delhi, India

Sharma

Kumar

et al. 2018

Antimicrob Agents Chemother

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Invasive and allergic infections by are more common in tropical and subtropical countries. The emergence of voriconazole (VRC) resistance in impacts the management of aspergillosis, as azoles are used as the first-line and empirical therapy. We screened 120 molecularly confirmed isolates obtained from respiratory and sinonasal specimens in a chest hospital in Delhi, India, for azole resistance using the CLSI broth microdilution (CLSI-BMD) method. Overall, 2.5% ( = 3/120) of isolates had VRC MICs above epidemiological cutoff values (>1 μg/ml). The whole-genome sequence analysis of three non-wild-type (WT) isolates with high VRC MICs showed polymorphisms in azole target genes (, , and). Further, four novel substitutions (S196F, A324P, N423D, and V465M) encoded in the gene were found in a single non-WT isolate which also exhibited overexpression of (, -, and -) genes and transporter genes, namely, ,, , and The homology model of the non-WT isolate suggests that substitutions S196F and N423D exhibited major structural and functional effects on cyp51C drug binding. The substrate (drug) may not be able to bind to binding pocket due to changes in the pocket size or closing down or narrowing of cavities in drug entry channels. Notably, the remaining two VRC-resistant isolates, including the one which had a pan-azole resistance phenotype (itraconazole and posaconazole), did not show upregulation of any of the analyzed target genes. These results suggest that multiple target genes and mechanisms could simultaneously contribute to azole resistance in.

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Endocarditis due to Aspergillus flavus

Cited by 15 publications

References 18 publications

Fungal Endocarditis: Evidence in the World Literature, 1965-1995

Fungal Endocarditis: Evidence in the World Literature, 1965-1995

Molecular identification and antifungal susceptibility profile of Aspergillus flavus isolates recovered from clinical specimens in Kuwait

Investigation of Multiple Resistance Mechanisms in Voriconazole-Resistant Aspergillus flavus Clinical Isolates from a Chest Hospital Surveillance in Delhi, India

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