Breakthrough candidaemia in the era of broad-spectrum antifungal therapies.

We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidaemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a multicentre study of hospitalized adults with candidaemia at six hospitals in three countries. BrC episodes were compared with the remaining episodes (non-BrC). Of 409 episodes of candidaemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% versus 46%, p 0.010) whereas Candida krusei was more frequent (16% versus 2.4%, p < 0.001). BrC was associated with infections caused by fluconazole non-susceptible isolates (50% versus 18%, p < 0.001). Candida albicans BrC was associated with previous fluconazole treatment whereas Candida parapsilosis candidaemia was mostly catheter-related and/or associated with previous echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% versus 74%, p 0.055). No significant differences were found in outcomes (early and overall mortality: 11% versus 13% p 0.802 and 40% versus 40% p 0.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (adjusted OR 5.57; 95% CI 1.45-21.37). In conclusion, BrC accounted for 9% of the episodes in our multicentre cohort. The Candida spp. isolated were different depending on the previous antifungal therapy: previous azole treatment was associated with fluconazole non-susceptible strains and previous echinocandin treatment was associated with BrC caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.

Environmental variables associated with an increased risk of invasive aspergillosis.

Information on the environmental variables that may affect the incidence of invasive aspergillosis (IA) is scarce. We sought to determine the relationship between airborne spore counts, climatic conditions and IA. We also examined whether circulating respiratory viruses predispose patients to IA in a multicentre cohort study of hospitalized adults with IA. Data on environmental mould spores, climatic conditions and circulating respiratory viruses were obtained from the Environmental Department of the Autonomous University of Barcelona, the Meteorological Service of Catalonia and the Acute Respiratory Infection Surveillance Project in Catalonia, respectively. Between 2008 and 2011, 165 patients with IA were identified. Diagnosis was based on one or more of the following: culture (125 cases), galactomannan antigen (98) and histology (34). One hundred and twenty-seven cases (77%) had criteria for probable IA and the remainder for proven IA. Environmental mould spore counts from the period 28-42 days preceding infection presented significant associations with admissions due to IA. None of the climatic conditions were associated with an increased risk of IA, but the presence of circulating respiratory viruses was associated with a higher risk of infection: the most strongly associated viruses were respiratory syncytial virus, influenza A(H1N1)pdm09 and adenovirus. In conclusion, the presence of high numbers of spores in the air increases the risk of admission due to IA. Circulating respiratory viruses appear to be associated with a higher risk of developing IA. Physicians should be aware of this association in order to optimize prevention and diagnosis strategies for IA during viral epidemic periods.

First Report of Orange Rust Disease of Sugarcane in the Dominican Republic.

In June 2011, uredinial leaf lesions typical of rust disease were observed on the two main commercial sugarcane (a complex Saccharum spp. L. hybrid) cultivars CR87339 (30% of acreage), CR83323 (17% of acreage) as well as cultivars BR9806, BR9816, and BT88133 at La Romana in the Dominican Republic. Morphological analysis of the lesions using both light and scanning electron microscopy identified obovoid spores (36 × 24 µm) with apical wall thickenings which are distinctive features of Puccinia kuehnii (W. Krüger) E.J. Butler, the causal agent of orange rust disease of sugarcane (4). DNA from dried leaf samples containing urediniospores was extracted and PCR-amplified using the P. kuehnii specific primers (Pk1-F/Pk1-R) (1). A 527-bp fragment representing the ITS rDNA region was obtained and sequenced. A GenBank BLAST search of the database of the consensus sequence showed 100% sequence identity to the GenBank accession GU564421 along the entire sequence length. Based on field observations, urediniospore morphology, PCR amplification, and DNA sequence analysis, the causal agent of the observed rust disease was therefore confirmed to be P. kuehnii. Since its initial discovery, orange rust disease has been observed in 15 additional sugarcane cultivars at the Central Romana Sugarcane Corp. Ltd. at La Romana and has persisted during the years 2012 and 2013. Central Romana Sugarcane Corp. Ltd. is the largest sugarcane grower (70,000 ha) and sugar producer (430,000 t annually) in the Caribbean. Although an economic impact assessment of the disease has not been performed at La Romana, orange rust disease has the potential to cause significant yield loss (1). Orange rust has been reported previously in several parts of Central America and in the neighboring islands of Cuba and Jamaica in 2010 (2,3). To our knowledge, this is the first confirmed report of orange rust disease of sugarcane in the Dominican Republic. References: (1) J. C. Comstock et al., J. ASSCT. 29:82, 2009. (2) N. C. Glynn et al. Plant Pathol. 59:703, 2010. (3) L. Pérez-Vicente et al. Plant Pathol. 59:804, 2010. (4) E. V. Virtudazo et al., Mycoscience 42:167, 2001.

Risk factors, clinical characteristics, and outcomes of invasive fungal infections in solid organ transplant recipients.

BACKGROUND: Invasive fungal infection (IFI) is an important cause of morbidity and mortality among solid organ transplant (SOT) recipients. We sought to assess risk factors, clinical characteristics, and current outcomes of IFI in SOT recipients. METHODS: We reviewed all episodes of IFI occurring among SOT recipients in a university hospital from 2008 to 2011. To determine risk factors for IFI we carried out a matched case-control study (1:2 ratio). Control subjects were matched for transplant type and timing. RESULTS: We documented 20 episodes of IFI among 744 SOT recipients (2.7%). Sixty-five percent of cases were proven IFI and 35% were probable IFI. The types of IFI documented were aspergillosis in 8 cases, candidiasis in 7, pneumocystosis in 3, Emmonsia species in infection 1, and disseminated cryptococcosis in 1. Ninety-nine percent of the patients had received a prior antibiotic therapy (3 months), 40% presented allograft rejection (3 months), and 40% had prior kidney injury. Complications of IFI included septic shock (50%), respiratory failure (55%), multiple-organ dysfunction (55%), and intensive care unit (ICU) admission (50%). Median days from transplantation to diagnosis was 103 for candidiasis (range, 27-4644) and 1195 for aspergillosis (range, 0-4319). In a comparison of case patients with 40 matched control subjects, case patients more frequently presented prior ICU stay (3 months; P = .05), hemodialysis requirement (P = .02), receipt of high-dose prednisone (6 months; P = .006), and prior antibiotic therapy (P < .001). Prior use of antibiotic treatment was the only risk factor for IFI (odds ratio [OR] 93; 95% confidence interval [CI], 8.3-1042). Case-fatality rate was 60%. CONCLUSIONS: In our recent experience, 2.7% of SOT recipients developed IFI, mainly aspergillosis followed by candidiasis. Prior ICU admission, hemodialysis, receipt of high-dose prednisone, and prior antibiotic use were more frequent in cases when compared with control subjects, with the latter factor being the only independent risk factor for developing IFI. Case-fatality rate was high (60%).

Disseminated adiaspiromycosis: case report of a liver transplant patient with human immunodeficiency infection, and literature review.

Disseminated adiaspiromycosis is a rare infection that is sometimes associated with immunocompromised situations. We report the case of a patient, infected with human immunodeficiency virus and receiving highly active antiretroviral therapy, who had a liver transplant for hepatocellular carcinoma. The patient presented skin and pulmonary lesions due to adiaspiromycosis during immunosuppressive therapy. A review of >60 cases in the literature shows that adiaspiromycosis is a rare infection and Emmonsia is a dimorphic fungus that is difficult to grow. It should be considered a possible diagnosis in case of fungal infection and pulmonary granulomatosis. We should be aware of emerging adiaspiromycosis in patients with risk factors of immunosuppression, particularly transplant recipients. In these patients in particular, liposomal amphotericin B therapy should be considered.

Predictors of candidaemia caused by non-albicans Candida species: results of a population-based surveillance in Barcelona, Spain.

Although Candida albicans (CA) is the most common cause of Candida bloodstream infections (BSIs), recent studies have observed an increasing percentage of candidaemias caused by non-albicans Candida species (NAC). In the present study, we attempted to identify the predictors of candidaemia due to NAC compared to CA. We analyzed data from an active population-based surveillance in Barcelona (Spain) from January 2002 to December 2003. Factors associated with NAC fungaemia were determined by multivariate analysis. A total of 339 episodes of Candida BSI, in 336 patients (median age 63 years, interquartile range: 41-72 years), were included. CA was the most commonly isolated (52%), followed by Candida parapsilosis (23%), Candida tropicalis (10%), Candida glabrata (8.6%), Candida krusei (3.4%) and other NAC spp. (3%).Overall, 48% of cases were due to NAC spp. Multivariate logistic regression analysis identified factors associated with a risk of BSI due to NAC spp.: having received a haematologic transplant (OR 10.8; 95% CI 1.31-90.01; p 0.027), previous fluconazole exposure (OR 4.47; 95% CI 2.12-9.43; p <0.001) and neonatal age (OR 4.42; 95% CI 1.63-12.04; p 0.004). Conversely, previous CA colonization (OR 0.33; 95% CI 0.19-0.57; p 0.001) and previous antibiotic use (OR 0.42; 95% CI 0.21-0.85; p 0.017) were associated with CA fungaemia compared to NAC. In conclusion, NAC candidaemia comprised 48% of cases in our series. Predictors of NAC include having received a haematologic transplant, neonatal age and previous fluconazole use.

Staphylococcus aureus nasal carriage in patients on haemodialysis: role of cutaneous colonization.

We performed a prospective study of Staphylococcus aureus nasal carriage in patients on chronic haemodialysis to determine the role of cutaneous colonization in the aetiology of recurrent nasal colonization. From February 2000 to September 2001, 71 patients on chronic haemodialysis in the dialysis unit at a university hospital were screened monthly for S. aureus nasal carriage. Carriers received nasal mupirocin for five days and were tested for nasal and cutaneous carriage two days later and monthly thereafter. Using genotyping results, recurrence was defined as relapse if pretreatment and subsequent nasal isolates were clonally identical; if the isolates were different, it was considered recolonization. Thirty-nine patients (55%) were nasal carriers: 11 initially and 28 during follow-up. Among the mupirocin-treated patients, the eradication of S. aureus nasal carriage rate was 88.5%. Nasal recurrence was documented in 17 patients (43.5%), and S. aureus nasal strains were available for molecular typing in 14 patients with a total of 23 recurrence episodes. On the basis of pulsed-field gel electrophoresis analysis, 16 (70%) recurrence episodes were considered relapses and seven were considered (30%) recolonizations. Among the episodes of relapse, prior cutaneous colonization was detected in only three cases. In haemodialysis patients, the majority of nasal carriage recurrences after mupirocin therapy were due to relapses. Cutaneous colonization does not appear to be relevant in the development of these relapses.

Carcinoma primario intraóseo y quiste odontogénico: tres casos clínicos y revisión de la literatura

Introducción: Los Carcinomas Intraóseos Primarios Odontogénicos (PIOC) son un raro grupo de tumores malignos con unos estrictos criterios diagnósticos clínicos y anatomo-patológicos. Las diferentes clasificaciones sugeridas para estos tumores y el escaso número de casos descritos en la literatura hacen difícil conocer con exactitud cuantos son los casos reales publicados hasta el día de hoy.Material y métodos: presentamos tres nuevos casos de PIOC originados a partir de una lesión quística previa que fueron tratados en nuestro centro. Dos en región posterior mandibular que es el lugar de más frecuente aparición, y un tercero en maxilar superior. Explicamos el tipo de cirugía llevado a cabo en cada caso y la reconstrucción estético-funcional utilizada que son dos injertos osteomiocutáneos de peroné y un injerto de hueso de cresta iliaca con posterior colocación de implantes. Se discute la clasificación, el diagnóstico clinico-radiológico, el tratamiento y su supervivencia.Resultados: en los tres casos se pudo constatar en la anatomía patológica un epitelio celular bien diferenciado acompañando a células carcinomatosas afectando al hueso exclusivamente sin afectación de la mucosa oral circundante ni de tejidos vecinos a la lesión así como ausencia de patología tumoral en otra zona del organismo. Uno de los pacientes falleció por recidiva cervical masiva precoz mientras que los otros dos están libres de enfermedad en la actualidad después de 10 años en uno de ellos y 15 meses en el otro.Conclusiones: es muy importante el análisis anatomo-patológico de todas las lesiones de características quísticas a nivel maxilar por el riesgo de coexistir con células carcinomatosas. El tratamiento de estos tumores debe ser la práctica de una cirugía agresiva y, en algunos casos, asociados a radio y/o quimioterapia post intervención.

Efficacy of colistin versus beta-lactams, aminoglycosides, and rifampin as monotherapy in a mouse model of pneumonia caused by multiresistant Acinetobacter baumannii.

The treatment of life-threatening infections due to carbapenem-resistant Acinetobacter baumannii has become a serious challenge for physicians worldwide. Often, only colistin shows in general good in vitro activity against these carbapenem-resistant strains, but its antibacterial efficacy in comparison with the antibiotics most used in clinical practice is not well known. We studied the efficacy of colistin versus those of imipenem, sulbactam, tobramycin, and rifampin in an experimental pneumonia model with immunocompetent mice. We used three strains of A. baumannii corresponding to the main clones (A, D, and E) involved in the outbreaks of our hospital, with different grades of resistance to imipenem (imipenem MICs of 1, 8, and 512 microg/ml, respectively) and to the other antibiotics. The MIC of colistin was 0.5 microg/ml for the three strains. Reduction of log(10) CFU/g in lung bacterial counts, clearance of bacteremia, and survival versus results with controls were used as parameters of efficacy. Imipenem and sulbactam (Deltalung counts: -5.38 and -4.64 log(10) CFU/ml) showed the highest level of bactericidal efficacy in infections by susceptible and even intermediate strains. Tobramycin and rifampin (-4.16 and -5.15 log(10) CFU/ml) provided good results against intermediate or moderately resistant strains, in agreement with killing curves and pharmacodynamics. On the contrary, colistin showed the weakest antibacterial effect among the antibiotics tested, both in killing curves and in the in vivo model (-2.39 log(10) CFU/ml; P < 0.05). We conclude that colistin did not appear as a good option for treatment of patients with pneumonia due to carbapenem-resistant A. baumannii strains. Other alternatives, including combinations with rifampin, may offer better therapeutic profiles and thus should be studied.

Short-term effect of the application of selective decontamination of the digestive tract on different body site reservoir ICU patients colonized by multi-resistant Acinetobacter baumannii.

The effect of a selective decontamination of the digestive tract (SDD) regimen including polymyxin and tobramycin on several body site reservoirs was compared between a test group and a control group in intensive care unit (ICU) patients with faecal multi-resistant Acinetobacter baumannii colonization. SDD significantly reduced faecal and pharyngeal carriage when compared with the control group at the end of ICU stay (48% versus 91%, P = 0.001, and 38.5% versus 78%, P = 0.01, respectively), but failed to reduce axillary colonization (75% versus 78%, P = 0.6). In addition, the isolation of A. baumannii from new clinical samples was lower in patients with SDD (45.5% versus 81%, P = 0.05). No resistance to polymyxin was observed. We conclude that the digestive tract reservoir of A. baumannii in ICU patients may be decreased by a SDD regimen.

Jacob's disease: report of two cases and review of the literature.

Jacob's disease is a rare condition consisting of new joint formation between the coronoid process of the mandible and the inner aspect of the zygomatic arch. Strictly speaking, it was first described by the French anatomist Oscar Jacob in 1899, although in 1853 von Langenbeck had described coronoid process hyperplasia. The pathogenesis of both conditions remains unknown. In this paper we present two new cases and a complete review of the literature on Jacob's disease, of which we have found only 12 cases. Due to the low prevalence of this condition, its diagnosis is not straight forward.

Emergence and rapid spread of carbapenem resistance during a large and sustained hospital outbreak of multiresistant Acinetobacter baumannii.

Beginning in 1992, a sustained outbreak of multiresistant Acinetobacter baumannii infections was noted in our 1,000-bed hospital in Barcelona, Spain, resulting in considerable overuse of imipenem, to which the organisms were uniformly susceptible. In January 1997, carbapenem-resistant (CR) A. baumannii strains emerged and rapidly disseminated in the intensive care units (ICUs), prompting us to conduct a prospective investigation. It was an 18-month longitudinal intervention study aimed at the identification of the clinical and microbiological epidemiology of the outbreak and its response to a multicomponent infection control strategy. From January 1997 to June 1998, clinical samples from 153 (8%) of 1,836 consecutive ICU patients were found to contain CR A. baumannii. Isolates were verified to be A. baumannii by restriction analysis of the 16S-23S ribosomal genes and the intergenic spacer region. Molecular typing by repetitive extragenic palindromic sequence-based PCR and pulsed-field gel electrophoresis showed that the emergence of carbapenem resistance was not by the selection of resistant mutants but was by the introduction of two new epidemic clones that were different from those responsible for the endemic. Multivariate regression analysis selected those patients with previous carriage of CR A. baumannii (relative risk [RR], 35.3; 95% confidence interval [CI], 7.2 to 173.1), those patients who had previously received therapy with carbapenems (RR, 4.6; 95% CI, 1.3 to 15.6), or those who were admitted into a ward with a high density of patients infected with CR A. baumannii (RR, 1.7; 95% CI, 1.2 to 2.5) to be at a significantly greater risk for the development of clinical colonization or infection with CR A. baumannii strains. In accordance, a combined infection control strategy was designed and implemented, including the sequential closure of all ICUs for decontamination, strict compliance with cross-transmission prevention protocols, and a program that restricted the use of carbapenem. Subsequently, a sharp reduction in the incidence rates of infection or colonization with A. baumannii, whether resistant or susceptible to carbapenems, was shown, although an alarming dominance of the carbapenem-resistant clones was shown at the end of the study.