Posts filed under ‘Antimicoticos’

Gentamicin synergises with azoles against drug-resistant Candida albicans

International Journal of Antimicrobial Agents January 2018 V.51 N.1 P.107–114

Mengjiao Lu, Cuixiang Yu, Xueyan Cui, Jinyi Shi, Lei Yuan, Shujuan Sun


  • Gentamicin (GM) synergises with azoles against planktonic cells of resistant Candida albicans.
  • GM synergises with fluconazole (FLC) against pre-formed biofilms of C. albicans.
  • GM enhanced the in vivo efficacy of FLC against resistant C. albicans.
  • GM suppresses the efflux pump of resistant C. albicans.
  • GM?+?FLC reduces phospholipase activity of resistant C. albicans.

Candida spp. are the primary opportunistic pathogens of nosocomial fungal infections, causing both superficial and life-threatening systemic infections. Combination therapy for fungal infections has attracted considerable attention, especially for those caused by drug-resistant fungi. Gentamicin (GM), an aminoglycoside antibiotic, has weak antifungal activity against Fusarium spp. The aim of this study was to investigate the interactions of GM with azoles against Candida spp. and the underlying mechanisms. In a chequerboard assay, GM was found not only to work synergistically with azoles against planktonic cells of drug-resistant Candida albicans with a fractional inhibitory concentration index (FICI) of 0.13–0.14, but also synergised with fluconazole (FLC) against C. albicans biofilms pre-formed in <12?h. Synergism of GM with FLC was also confirmed in vivo in a Galleria mellonella infection model. In addition, mechanism studies showed that GM not only suppressed the efflux pump of resistant C. albicans in a dose-dependent manner but also inhibited extracellular phospholipase activity of resistant C. albicans when combined with FLC. These findings suggest that GM enhances the efficacy of azoles against resistant C. albicans via efflux inhibition and decreased activity of extracellular phospholipase.




February 5, 2018 at 6:10 pm

Development and Validation of a Real-Time PCR Assay for Rapid Detection of Candida auris from Surveillance Samples

Journal of Clinical Microbiology February 2018 V.56 N.2

Leach, Y. Zhu and S. Chaturvedi

aMycology Laboratory, Wadsworth Center, New York State Department of Health, Albany, New York, USA

bDepartment of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York, USA

Candida auris is an emerging multidrug-resistant yeast causing invasive health care-associated infection with high mortality worldwide.

Rapid identification of C. auris is of primary importance for the implementation of public health measures to control the spread of infection.

To achieve these goals, we developed and validated a TaqMan-based real-time PCR assay targeting the internal transcribed spacer 2 (ITS2) region of the ribosomal gene.

The assay was highly specific, reproducible, and sensitive, with the detection limit of 1 C. auris CFU/PCR.

The performance of the C. auris real-time PCR assay was evaluated by using 623 surveillance samples, including 365 patient swabs and 258 environmental sponges.

Real-time PCR yielded positive results from 49 swab and 58 sponge samples, with 89% and 100% clinical sensitivity with regard to their respective culture-positive results.

The real-time PCR also detected C. auris DNA from 1% and 12% of swab and sponge samples with culture-negative results, indicating the presence of dead or culture-impaired C. auris.

The real-time PCR yielded results within 4 h of sample processing, compared to 4 to 14 days for culture, reducing turnaround time significantly.

The new real-time PCR assay allows for accurate and rapid screening of C. auris and can increase effective control and prevention of this emerging multidrug-resistant fungal pathogen in health care facilities.



January 24, 2018 at 3:55 pm

EDITORIAL – Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses

Clin Infect Dis  Jan 15, 2018 V.64 N.134.

Shawn R. Lockhart  Kizee A. Etienne  Snigdha Vallabhaneni  Joveria Farooqi Anuradha Chowdhary  Nelesh P. Govender  Arnaldo Lopes Colombo  Belinda Calvo Christina A. Cuomo  Christopher A. Desjardins


Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries.


To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012–2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS).


Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9–36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade.


  1. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.



January 6, 2018 at 12:07 pm

Candiduria: A Randomized, Double-Blind Study of Treatment with Fluconazole and Placebo

Clinical Infectious Diseases January 2000 V.30 N.1 P.19-24

D. Sobel, C. A. Kauffman, D. McKinsey, M. Zervos, J. A. Vazquez, A. W. Karchmer, J. Lee, C. Thomas, H. Panzer, W. E. Dismukes, and the National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group

1Wayne State University, Detroit, Michigan

2University of Michigan and Veterans Affairs Medical Center, Ann Arbor, Michigan

3Infectious Disease Associates of Kansas City, Kansas City, Missouri

4Harvard Medical School, Boston, Massachusetts

5University of Alabama at Birmingham, Birmingham, Alabama

6Pfizer, Inc., Groton, Connecticut

Management of candiduria is limited by the lack of information about its natural history and lack of data from controlled studies on the efficacy of treating it with antimycotic agents.

We compared fungal eradication rates among 316 consecutive candiduric (asymptomatic or minimally symptomatic) hospitalized patients treated with fluconazole (200 mg) or placebo daily for 14 days.

In an intent-to-treat analysis, candiduria cleared by day 14 in 79 (50%) of 159 receiving fluconazole and 46 (29%) of 157 receiving placebo (P < .001), with higher eradication rates among patients completing 14 days of therapy (P < .0001), including 33 (52%) of 64 catheterized and 42 (78%) of 54 noncatheterized patients.

Pretreatment serum creatinine levels were inversely related to candiduria eradication.

Fluconazole initially produced high eradication rates, but cultures at 2 weeks revealed similar candiduria rates among treated and untreated patients.

Oral fluconazole was safe and effective for short-term eradication of candiduria, especially following catheter removal. Long-term eradication rates were disappointing and not associated with clinical benefit.


December 2, 2017 at 7:56 am

Infección por Candida spp. sobre prótesis articulares

Rev Esp Quimioter 2011:24(1):37-41



Las infecciones periprotésicas por Candida spp.constituyen una entidad poco frecuente. El objetivo de este trabajo fue revisar la experiencia en dos centros hospitalarios.

Material y métodos

Se realizó una revisión retrospectiva de los casos de infección protésica de etiología fúngica atendidos en dos hospitales de Barcelona entre febrero de 2002 y octubre de 2010. Se incluyeron todos aquellos pacientes con criterios clínicos de infección y aislamiento de Candida spp. Se recogieron las principales variables demográficas, microbiológicas, terapéuticas y evolutivas.


Se identificaron 10 casos, 8 mujeres y 2 varones, cuya edad media fue de 77,7 (rango 66-92) años. Nueve pacientes habían tenido una infección bacteriana previa, por la que recibieron tratamiento antibiótico durante más de 15 días y precisaron desbridamiento en más de una ocasión. La especie más frecuente fue Candida albicans con 6 casos. Todos los pacientes recibieron fluconazol y tratamiento quirúrgico consistente en desbridamiento sin retirada de la prótesis en 3 casos y recambio en 2 tiempos con un espaciador en los 7 restantes. El tratamiento fracasó en los 10 casos y fue necesario practicar un desbridamiento adicional en 1 caso, artroplastia de resección en 8 y tratamiento “supresivo”con fluconazol en uno. Tras un seguimiento medio de 31 meses (rango 2-67) dos pacientes estaban libres de enfermedad.


La infección protésica por Candida spp. se observa en pacientes que han recibido tratamiento antibiótico previo prolongado y han sido intervenidos en más de una ocasión. El tratamiento con fluconazol y desbridamiento o recambio en 2 tiempos con un espaciador se asoció a una elevada tasa de fracaso.


September 3, 2017 at 7:05 pm

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials

Journal of Antimicrobial Chemotherapy August 2017 V.72 N.8 P.2368–2377

Bart Jan Kullberg; José Vasquez; Piroon Mootsikapun; Marcio Nucci; José-Artur Paiva …


To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non-albicans Candida species.


Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200 mg on day 1, followed by 100 mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5–10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for ≥14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population.


In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%–80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin.


These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population.


August 11, 2017 at 9:11 am

Candida vertebral osteomyelitis (CVO) 28 cases from a 10-year retrospective study in France

MEDICINE August 2017 V.96 N.31

Richaud, Clémence; De Lastours, Victoire; Panhard, Xavière; Petrover, David; Bruno, Fantin; Lefort, Agnès


Although increasingly frequent, little is known about the clinical presentation, radiological signs, and outcome of Candida vertebral osteomyelitis (CVO).

We performed a nationwide retrospective study of laboratory-confirmed cases of CVO over a 10 year-period in France with a prolonged follow-up.

We describe demographic, clinical, biological, and radiological characteristics of patients with CVO, patients’ management, and long-term outcome and determine factors associated with a poor outcome.

In total, 28 patients with laboratory-confirmed CVO were included. A prior systemic Candida infection was evidenced in 13/28 (46%), occurring a median of 6 weeks before CVO was diagnosed.

Twenty-six of 28 (93%) had at least 1 underlying condition at risk of invasive fungal disease, and in 19/28 (68%) CVO was health-care related.

C albicans was most frequently identified (21/28; 75%) Lumbo-sacral involvement was the most prevalent (20/28—71%). Nearly half patients had no fever at presentation, but all had pain.

Initial antifungal therapy consisted in fluconazole in 15/28 (53%); surgery was needed in 5 (18%) cases.

One-year mortality was 21% (6/28), directly related to fungal infection in 2 patients.

Risk-factors associated with 1-year mortality were age (P=.02), a high Charlson comorbidity index (P = .001), and a shorter treatment duration (median, 3 months vs 6 months; P = .02).

Among 22 patients who survived, the median follow up duration was 15.5 months (8–93.5); 10 had sequelae, consisting in pain in all and neurological deficit in one.

A longer treatment duration was significantly associated with healing without sequelae (P = .04).

CVO concerns patients with serious underlying conditions and risk-factors for invasive candidiasis.

Prolonged antifungal treatment appears to improve survival without sequelae.


August 5, 2017 at 9:18 am

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