Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia.

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia.

Comparison between nerve conduction study and high-resolution ultrasonography with color doppler in type 1 and type 2 leprosy reactions.

OBJECTIVE: To analyze the role of high-resolution ultrasonography with color Doppler (HRUS with CD) to diagnose inflammatory activity (IA) in nerves of leprosy patients under type 1 (RT1) and 2 (RT2) reactions compared to Nerve Conduction Studies (NCS). METHODS: Leprosy patients with signs or symptoms suggestive of neuritis (RT1 and RT2) without corticosteroids use were selected. They were evaluated by NCS and subsequently by HRUS with CD. Subacute segmental demyelination and the presence of blood flow, respectively, were considered signs of IA. The two methods were compared for their ability to diagnose patients with leprosy reactions. RESULTS: A total of 257 nerves from 35 patients were evaluated. NCS and HRUS with CD diagnosed IA in 68% and 74% of patients, respectively. When both methods were used concomitantly, the diagnosis rate was 91.4%. HRUS with CD was particular helpful when there was minimal neurophysiological compromise in NCS or when motor potentials were not detected. CONCLUSION: HRUS with CD was able to detect leprosy reactions, especially when combined with NCS. It was especially useful in two opposite situations: nerves with only minor changes and those without motor response in NCS. SIGNIFICANCE: Our data shows the usefulness of HRUS and CD, similar to NCS, as a tool to diagnose leprosy reactions.

Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients.

BACKGROUND: Lung transplant recipients are frequently exposed to respiratory viruses and are particularly at risk for severe complications. The aim of this study was to assess the association among the presence of a respiratory virus detected by molecular assays in bronchoalveolar lavage (BAL) fluid, respiratory symptoms, and acute rejection in adult lung transplant recipients. METHODS: Upper (nasopharyngeal swab) and lower (BAL) respiratory tract specimens from 77 lung transplant recipients enrolled in a cohort study and undergoing bronchoscopy with BAL and transbronchial biopsies were screened using 17 different polymerase chain reaction-based assays. RESULTS: BAL fluid and biopsy specimens from 343 bronchoscopic procedures performed in 77 patients were analyzed. We also compared paired nasopharyngeal and BAL fluid specimens collected in a subgroup of 283 cases. The overall viral positivity rate was 29.3% in the upper respiratory tract specimens and 17.2% in the BAL samples (P < .001). We observed a significant association between the presence of respiratory symptoms and positive viral detection in the lower respiratory tract (P = .012). Conversely, acute rejection was not associated with the presence of viral infection (odds ratio, 0.41; 95% confidence interval, 0.20-0.88). The recovery of lung function was significantly slower when acute rejection and viral infection were both present. CONCLUSIONS: A temporal relationship exists between acute respiratory symptoms and positive viral nucleic acid detection in BAL fluid from lung transplant recipients. We provide evidence suggesting that respiratory viruses are not associated with acute graft rejection during the acute phase of infection.

Posaconazole salvage treatment in paediatric patients: a multicentre survey.

While a paediatric dosage has not been defined, posaconazole is occasionally being used in children. We conducted a multicentre retrospective survey and identified 15 patients (median age 10 years [range 3.6-17.5]) who received posaconazole salvage therapy for proven (9 patients) or probable (6 patients) invasive fungal infections. Posaconazole was administered for a median of 32 days (range 4-262) at a median dosage of 21 mg/kg (range 4.8-33.3). None of the patients discontinued therapy due to adverse events, which were mostly mild and observed in 11 patients. Complete or partial responses were observed in 4/7 patients with zygomycosis, 3/4 patients with invasive mould infection, 1/2 patients with invasive aspergillosis and 1/2 patients with chronic disseminated candidiasis. We conclude from the data that posaconazole displays favourable safety and tolerance and may be useful for management of individual paediatric patients with invasive infections.

Nocardiosis: updated clinical review and experience at a tertiary center.

Nocardiosis is a rare opportunistic disease that affects mainly patients with deficient cell-mediated immunity, such as those with acquired immunodeficiency syndrome (AIDS) or transplant recipients. Pulmonary disease is the most common presentation in immunosuppressed patients and approximately one-third have a disseminated disease. Primary cutaneous nocardiosis is more frequently observed in immunocompetent patients with direct inoculation of the organism through professional exposure. The diagnosis can be challenging, as signs and symptoms are not specific and a high index of clinical of suspicion is necessary. Although gram stain, modified acid-fast stain, and cultures remain as the standard diagnostic tools, novel molecular techniques have changed the taxonomy of these organisms and, in some instances, have facilitated their identification. The disease has a marked tendency to recur and a high morbidity and mortality rate in immunosuppressed patients. Treatment is usually prolonged and an associated antibiotic treatment is preferred for severe disease. Although sulfonamides in combination with other antibiotics are still the treatment of choice, other associations such as imipenem plus amikacin are preferred in some centers. Linezolid is a useful alternative therapeutic agent due to its oral availability and activity against most of the isolates studied. Twenty-eight cases of nocardiosis were diagnosed at our center between January 1989 and April 2009. We report the epidemiologic characteristics of Nocardia spp. observed in our institution and discuss the risk factors, clinical features, diagnosis, and management of the disease.

Disseminated Rhizopus microsporus infection cured by salvage allogeneic hematopoietic stem cell transplantation, antifungal combination therapy, and surgical resection.

Invasive Zygomycetes infection complicating prolonged neutropenia is associated with high mortality in the absence of immune recovery. We report a patient who developed disseminated zygomycosis due to Rhizopus microsporus during induction chemotherapy for acute myeloid leukemia. Rescue allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed as her only chance of cure of this infection and to treat refractory leukemia. Posaconazole combined with liposomal amphotericin B contained the zygomycosis during prolonged neutropenia due to allo-HSCT followed by intense immunosuppression for grade IV acute graft-versus-host disease. Surgical removal of all infected sites after immune recovery, with prolonged posaconazole treatment, ultimately cured the infection. New combination antifungal therapies might sufficiently control disseminated zygomycosis to allow allo-HSCT to be performed, assuring life-saving immune recovery. Surgery appears to be necessary for definite cure of these infections.

Neurophysiological patterns of ulnar nerve neuropathy in leprosy reactions.

BACKGROUND: Leprosy neuropathy, despite being primarily demyelinating, frequently leads to axonal loss. Neurophysiological examination of the nerves during Type 1 (T1R) and Type 2 reactions (T2R) may give some insight into the pathophysiological mechanisms. METHODS: Neurophysiological examinations were performed in 28 ulnar nerves during a clinical trial of steroid treatment effectiveness, 19 patients with T1R and nine with T2R. The nerves were monitored during a period of 6 months; there were eight assessments per nerve, for a total of 224 assessments. Nine neurophysiological parameters were assessed at three sites of the ulnar nerve. The compound motor action potential amplitudes elicited at wrist, elbow and above, as well as the conduction velocity and temporal dispersion across the elbow, were chosen to focus on the changes occurring in the parameters at the elbow tunnel. RESULTS AND CONCLUSION: Neurophysiological changes indicating axonal and demyelinating processes during both T1R and T2R were detected across the elbow. Changes in demyelination, i.e. a Conduction Block, as a primary event present during T2R, occurring as an acute phenomenon, were observed regularly; in T1R Temporal Dispersion, a subacute phenomenon, was seen. During treatment remyelination occurred after both types of reactions.

Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in adults.

BACKGROUND: The epidemiology of respiratory viruses and their potential clinical impact when recovered in lower respiratory specimens has not been established in the hospital setting. A study was performed to investigate the association between positive viral detection and respiratory infection in an at-risk population. METHODS: 299 adult patients who underwent bronchoalveolar lavage (BAL) procedures were enrolled in a hospital-based prospective cohort study. Descriptive epidemiology is presented of 17 different respiratory viruses detected by reverse transcription-polymerase chain reaction assays in BAL fluid specimens. Multivariate analysis was conducted to identify the clinical characteristics independently associated with the presence of virus. RESULTS: Of 522 BAL fluid specimens analysed, 81% were collected in adult transplant recipients or other immunocompromised patients. Overall, PCR assays identified viral nucleic acid in 91 BAL fluid samples (17.4%). Similar rates of virus-positive BAL fluid were found in the different subpopulations studied (p = 0.113). Coronaviruses were the most frequent (32.3%), followed by rhinovirus (22.6%), parainfluenza (19.5%), influenza (9.7%), respiratory synctial virus (8.6%), human metapneumovirus (4.2%) and bocavirus (3.1%). Multivariate analysis using mixed models showed that respiratory viral infections were associated with a lack of antibiotic treatment response (OR 2.2, 95% CI 1.2 to 4.1) and the absence of radiological infiltrate (OR 0.3, 95% CI 0.2 to 0.8). In lung transplant recipients in whom a respiratory infection was suspected, the respiratory viral detection rate was 24.4% compared with 13.8% overall in other patients (p = 0.02). CONCLUSIONS: In this cohort of hospitalised adults, respiratory viruses detected in BAL fluid specimens were associated with respiratory symptoms, absence of radiological infiltrates and a poor response to antibiotic therapy.

Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline.

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.

Clinical and bacteriological outcomes in hospitalised patients with community-acquired pneumonia treated with azithromycin plus ceftriaxone, or ceftriaxone plus clarithromycin or erythromycin: a prospective, randomised, multicentre study.

This study compared patients with moderate-to-severe community-acquired pneumonia (CAP) requiring hospitalisation, who received initial therapy with either intravenous ceftriaxone plus intravenous azithromycin, followed by step-down to oral azithromycin (n = 135), with patients who received intravenous ceftriaxone combined with either intravenous clarithromycin or erythromycin, followed by step-down to either oral clarithromycin or erythromycin (n = 143). Clinical and bacteriological outcomes were evaluated at the end of therapy (EOT; day 12-16) or at the end of study (EOS; day 28-35). At baseline, mean APACHE II scores were 13.3 and 12.6, respectively, with >50% of patients classified as Fine Pneumonia Severity Index (PSI) category IV or V. Clinical success rates (cure or improvement) in the modified intent-to-treat (MITT) population at EOT were 84.3% in the ceftriaxone/azithromycin group and 82.7% in the ceftriaxone/clarithromycin or erythromycin group. At EOS, MITT success rates (cure only) were 81.7% and 75.0%, respectively. Equivalent success rates in the clinically evaluable population were 83% and 87%, respectively, at EOT, and 79% and 78%, respectively, at EOS. MITT bacteriological eradication rates were 73.2% and 67.4%, respectively, at EOT, and 68.3% vs. 60.9%, respectively, at EOS. Mean length of hospital stay (LOS) was 10.7 and 12.6 days, and the mean duration of therapy was 9.5 and 10.5 days, respectively. The incidence of infusion-related adverse events was 16.3% and 25.2% (p 0.04), respectively. An intravenous-to-oral regimen of ceftriaxone/azithromycin was at least equivalent in efficacy and safety to the comparator regimen and appeared to be a suitable treatment option for hospitalised patients with CAP.

Secular trends of nocardia infection over 15 years in a tertiary care hospital.

AIMS: To assess the incidence of nocardia infection over 15 years in a tertiary care hospital. METHODS: Over a 15 year period, Nocardia spp were isolated from 20 patients hospitalised at the Geneva University Hospitals, Switzerland. RESULTS: Sixteen patients had one or more underlying conditions. The median time between symptom onset and diagnosis was 30 days. The most common initial unconfirmed diagnosis was pulmonary tuberculosis (four). The lung was involved in 16 cases, followed by the central nervous system (two) and skin (two); one patient had disseminated infection. The most common species identified was N asteroides. In vitro susceptibility testing was performed on 14 of 20 strains. All strains were susceptible to imipenem and amikacin. Initial treatment with trimethoprim/sulfamethoxazole (TMP/SMX) was started in 14 patients, although five patients had to be switched to another treatment because of side effects or lack of efficacy. A cure was observed in 15 patients, death in three, and relapse or complications in two. CONCLUSIONS: Nocardiosis can become a severe infection and mainly affects profoundly immunocompromised patients. Differential diagnosis often delays the time to diagnosis, which worsens the outcome. New diagnostic tools, such as the polymerase chain reaction, could provide more rapid and reliable results. TMT/SMX was the most commonly prescribed treatment, but needed to be changed for another treatment because of side effects or lack of efficacy in a considerable proportion of patients. Imipenem should be used as an alternative treatment for severely ill patients, and the sulfa combination for less severe infections.

Impact of positive legionella urinary antigen test on patient management and improvement of antibiotic use.

AIM: To assess the incidence of legionella infection over a 27 month period at a large university hospital. MATERIAL AND METHODS: The present retrospective cohort study enrolled patients with legionellosis, defined as those presenting a positive urinary antigen for legionella together with a medical history, clinical findings, and radiological findings consistent with pneumonia. These patients were evaluated to determine the relation between their test results and changes in treatment modalities. A control group of patients with pneumonia but a negative urinary antigen test for legionella were also analysed. RESULTS: Twenty seven of 792 assessed patients tested positive for legionella. In 22 of these patients, legionella active antibiotics were administered empirically. In seven patients, the test results prompted a legionella specific treatment, whereas in 12 cases, non-specific antibiotics were stopped within 24 hours. Overall, treatment was altered in more than half of the patients as a result of the test results. CONCLUSIONS: The urinary antigen may have a direct impact on clinical management of pulmonary legionellosis. However, patient comorbidities and individual clinical judgment are still important for determining the best treatment to be given in each individual case.

Influence of posture on gas exchange in artificially ventilated patients with focal lung disease.

Six patients were artificially ventilated for a focal lung disease localized to one lung in four cases and to both lower lobes in two. Despite an inspired oxygen concentration of 100% the mean PaO2 was 115 mmHg. The addition of PEEP slightly improved PaO2 in two patients but led to deterioration in four. We therefore studied the effects of posture. Patients with unilateral disease were placed in the lateral position with the healthy lung dependent. The two patients with both lower lobes involved were tilted into the Trendelenburg position. The mean PaO2 rose from 98.4 to 199.5 mmHg. Posture was maintained as long as a beneficial effect was demonstrable. The disappearance of this effect was associated either with recovery (three patients) or with the extension of the pneumonia (three patients). The improvement of gas exchange can be accounted for by the rearrangement of ventilation/perfusion relationships. This management could avoid the need for differential lung ventilation.

ARDS caused by herpes simplex virus pneumonia in a patient with Crohn's disease: a case report.

Pneumonia caused by herpes simplex virus type 1 (HSV1) is rare and occurs in severely immunosuppressed patients. HSV1 can be detected in bronchoalveolar lavage (BAL) from patients presenting with respiratory failure, but its direct effect on disease is difficult to prove. We demonstrate the causative role of HSV1 in the case of a 44-year-old male with Crohn's disease who presented to the intensive care unit with the acute respiratory distress syndrome after surgery. BAL cells were cultured and immunofluorescence confirmed the presence of HSV1 during the first weeks of illness. Increased IgG titers confirmed the diagnosis of a recurrent HSV1 infection. A lung biposy specimen showed fibroproliferation without pathogens. Immunosuppressive therapy had been stopped and acyclovir was introduced at this time. The diagnostic difficulties in this patient underline the importance of early recognition of viral infection as a potential cause of severe pneumonia in severely ill, immunocompromised patients.

Caspofungin--a new therapeutic option for oropharyngeal candidiasis.

Patients with AIDS are often severely immunocompromised. These patients commonly develop opportunistic infections such as oropharyngeal candidiasis whose treatment may prove to be difficult. Caspofungin belongs to a new class of antifungal agents that have a different mode of action to azoles and polyenes. This new agent is the first inhibitor of fungal glucan synthesis to receive approval for the treatment of mucosal and invasive candidiasis and invasive aspergillosis. Caspofungin is well-tolerated and represents a substantial improvement over existing therapeutic options for patients prone to azole-resistant candida infection or who cannot tolerate amphotericin B.

Prospective epidemiologic survey of patients with community-acquired pneumonia requiring hospitalization in Switzerland.

BACKGROUND: Community-acquired pneumonia (CAP) is a common problem and the principal infection requiring hospitalization, but its treatment is complicated by the difficulty in microbiological diagnosis and the increasing incidence of antibiotic resistance among respiratory pathogens. The purpose of this paper is to present the main epidemiologic features of patients with CAP requiring hospitalization in our country. METHODS: We enrolled three hundred and eighteen adult patients with CAP requiring hospitalization in seven large medical centers in Switzerland during two winter periods. The patients' mean age was 70.4 years. This study describes the epidemiology of these patients. Clinical, radiologic and microbiological evaluations were performed at study entry during treatment, and at 4 weeks post-therapy. For microbiological diagnostic purposes, sputum culture, throat swab culture, PCR, blood cultures, Legionella urinary antigen and serologic evaluations were also performed. RESULTS: Despite the higher mean age, the overall mortality rate was 8%, lower than in other comparable studies. The most common underlying diseases present at study entry were cardiac failure (23%), chronic obstructive pulmonary disease (20%), renal failure (15%), and diabetes (12%); 40% of the patients were smokers. Although dyspnea, cough and positive pulmonary auscultation findings were present in about 90% of patients, fever >38 degrees C was present in only 64%. The most frequently isolated respiratory pathogens were Streptococcus pneumoniae (12.6%), Haemophilus influenzae (6%), Staphylococcus aureus (1.6%), and Moraxella catarrhalis (1.6%). Atypical pathogens were frequently found, with the following distribution: Mycoplasma pneumoniae, 7.5%; Chlamydia pneumoniae, 5.3%; and Legionella pneumophila, 4.4%. The mean duration between onset of symptoms and hospital admission was 4.8 days, and the mean treatment duration was 12.1 days. Two weeks after the start of therapy, although clinical symptoms were absent, radiologic infiltrates were still present in 24% of patients. CONCLUSIONS: The microbiological diagnosis in CAP can be established in only about 50% of cases with the combination of several diagnostic tools. Epidemiologic surveys of CAP should be performed on a regular basis, regionally, as a way to improve the management of these infections.

Fungemia in HIV-infected patients: a 12-year study in a tertiary care hospital.

Opportunistic infections caused by fungi are common in human immunodeficiency virus (HIV)-infected patients. We focused on severe infections as indicated by detectable fungemia. Medical charts available for patients having positive blood cultures with fungi at the University of Geneva Hospital were retrospectively (1989 to 2000) reviewed. Of 328 patients with fungemia during the study period, 315 (96%) medical charts were accessible. Of these 315 patients, 37 (12.2%) were HIV-positive, and 13 (35.1%) died within 6 months from their episode of fungemia. This was a lower mortality rate than for the HIV seronegative patients (45.8%). The median and average age of the 34 HIV-positive patients was 37.2 years, and 24 (64.9%) were males. Cryptococcus neoformans (n = 14) and Candida albicans (n = 12) were the most frequently identified species, followed by Candida glabrata (n = 3), of which 3 were mixed C. albicans + C. glabrata, Histoplasma capsulatum (n = 2), and Penicillium marneffei (n = 2). The frequency decreased significantly (p < 0.007) from the time period 1993 to 1996 (n = 21) to the period 1997 to 2000 (n = 6). Fungemias in HIV-infected patients have declined significantly since 1996. This coincides with the introduction of highly active antiretroviral therapy (HAART).

Polyacrylonitrile membrane interposition between a xenograft and a patient in fulminant liver failure: the concept of xenohemodiafiltration in clinical practice.

Fulminant hepatic failure is an important cause of morbidity and mortality in intensive care units. Conventional therapies are not sufficiently effective. Liver transplantation may be life saving, but a "bridge therapy" is needed until transplantation is performed. Hepatic extracorporeal xenohemodiafiltration (XHDF) is aimed at the transitory support of a patient with fulminant hepatic failure. The first clinical case of XHDF is presented. The system consisted of cross-circulation between a porcine liver and a patient with fulminant liver failure through a polyacrylonitrile membrane. The procedure lasted for 5 hours and produced hemodynamic, biochemical, and metabolic improvements. Intracranial pressure decreased from 34 to 5 cm H2O, serum ammonia fell from 673 to 370 ng/dl, lactic acid from 11 to 5.3 mmol/L, and bilirubin from 7.4 to 2.5 mg/dl. Hemodynamic values were maintained stable throughout the procedure. The patient was able to undergo transplantation and remains alive 11 months later. XHDF is a clinical experimental method that can constitute an alternative clinical therapy to support patients with fulminant hepatic failure until an organ is available for transplantation.

Management of a high-output postoperative enterocutaneous fistula with a vacuum sealing method and continuous enteral nutrition.

A postoperative enterocutaneous fistula is one of the most complex medical problems. Its treatment may become long-lasting, wearisome, and its outcome often is disappointing. Here, we describe the use of a novel device to treat a 67-year-old patient with a postoperative, high-output enterocutaneous fistula. A semipermeable barrier was created over the fistula by vacuum packing a synthetic, hydrophobic polymer covered with a self-adherent surgical sheet. To set up the system, we constructed a vacuum chamber equipped with precision instruments that supplied subatmospheric pressures between 350 and 450 mm Hg. The intestinal content was, thus, kept inside the lumen, restoring bowel transit and physiology. The fistula output was immediately reduced from a median of 800 ml/day (range, 400-1,600 ml/day), to a median of 10 ml/day (range, 0-250 ml/day), which was readily collected by the apparatus. Oral feeding was reinitiated while both parenteral nutrition and octreotide were withdrawn. No septic complications occurred, and the perifistular skin stayed protected from irritating intestinal effluents. Both the fistula orifice and the wound defect fully healed after 50 days of treatment. We believe this method may serve as a useful tool to treat selected cases of high-output enterocutaneous fistulas without the need for octreotide or parenteral nutrition.

Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: a 6-year prospective candidaemia survey from the fungal infection network of Switzerland.

We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre® YeastOne™ test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.