Publications by authors named "Jacques Bille"

89 Publications

MAPT (Mono Antiplatelet Therapy) as Regular Regimen After COBRA PzF™ NanoCoated Coronary Stent (NCS) Implantation.

Cardiovasc Revasc Med 2020 06 18;21(6):785-789. Epub 2019 Oct 18.

Service de Cardiologie, GCS ES Axium Rambot, 21, Avenue Alfred Capus, 13 090 Aix en Provence, France.

Aims: To report procedural and 1-year outcomes following COBRA PzF NCS implantation in a routine daily setting with high bleeding risk (HBR) patients treated with clopidogrel as mono antiplatelet therapy (MAPT).

Methods: This is a prospective, consecutive, observational study in HBR patients who underwent PCI with COBRA PzF NCS and treated with clopidogrel alone at discharge. The primary endpoint was definite stent thrombosis at one month. The secondary endpoint was MACE (Cardiac Death, myocardial infarction (MI), target lesion revascularization (TLR)) at 12 months.

Results: From October 2015 to December 2018, 77 patients with 120 lesions were enrolled and treated. Mean age was 78.7 ± 8.89 years, 58.5% men and 18.2% had ACS. Patients included had a minimum of 2.0 inclusion LEADERS FREE criteria. Angiographic success was achieved in all cases. The primary endpoint occurred in 0%, no stent thrombosis was occurred. MACE at 12-months (available for 52 patients) was 3.8% including cardiac death 0%, MI 0% and TLR 3.8%. No severe bleeding events (BARC3-5) or stroke or late stent thrombosis were noted.

Conclusion: Clopidogrel as MAPT after COBRA PzF NCS implantation in HBR patients is feasible and an attractive option. One-year follow-up was associated with excellent clinical outcomes and should be confirmed with large randomised study.

Condensed Abstract: This is prospective registry of high bleeding risk patients treated with the COBRA PzF NCS and MAPT at discharge. The primary end point demonstrated no stent thrombosis. The rate of major cardiac adverse events (a composite of cardiovascular death, myocardial infarction and target lesion revascularisation) at 1 year was 3.8%. No severe bleeding events, stroke or late stent thrombosis were noted. One-year follow-up was associated with good clinical outcomes and compared favorably with current devices.
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http://dx.doi.org/10.1016/j.carrev.2019.10.007DOI Listing
June 2020

Femoral Versus Nonfemoral Peripheral Access for Transcatheter Aortic Valve Replacement.

J Am Coll Cardiol 2019 12;74(22):2728-2739

Paris Cardiovascular Research Center, INSERM Unit 970, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Cardiology Department, Paris, France.

Background: Femoral access is the gold standard for transcatheter aortic valve replacement (TAVR). Guidelines recommend reconsidering surgery when this access is not feasible. However, alternative peripheral accesses exist, although they have not been accurately compared with femoral access.

Objectives: This study compared nonfemoral peripheral (n-FP) TAVR with femoral TAVR.

Methods: Using the data from the national prospective French registry (FRANCE TAVI [French Transcatheter Aortic Valve Implantation]), this study compared the characteristics and outcomes of TAVR procedures according to whether they were performed through a femoral or a n-FP access, using a pre-specified propensity score-based matching between groups. Subanalysis during 2 study periods (2013 to 2015 and 2016 to 2017) and among low/intermediate-low and intermediate-high/high volume centers were performed.

Results: Among 21,611 patients, 19,995 (92.5%) underwent femoral TAVR and 1,616 (7.5%) underwent n-FP TAVR (transcarotid, n = 914 or trans-subclavian, n = 702). Patients in the n-FP access group had more severe disease (mean logistic EuroSCORE 19.95 vs. 16.95; p < 0.001), with a higher rate of peripheral vascular disease, known coronary artery disease, chronic pulmonary disease, and renal failure. After matching, there was no difference in the rate of post-procedural death and complications according to access site, except for a 2-fold lower rate of major vascular complications (odds ratio: 0.45; 95% confidence interval: 0.21 to 0.93; p = 0.032) and unplanned vascular repairs (odds ratio: 0.41; 95% confidence interval: 0.29 to 0.59; p < 0.001) in those who underwent n-FP access. The comparison of outcomes provided similar results during the second study period and in intermediate-high/high volume centers.

Conclusions: n-FP TAVR is associated with similar outcomes compared with femoral peripheral TAVR, except for a 2-fold lower rate of major vascular complications and unplanned vascular repairs. n-FP TAVR may be favored over surgery in patients who are deemed ineligible for femoral TAVR and may be a safe alternative when femoral access risk is considered too high.
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http://dx.doi.org/10.1016/j.jacc.2019.09.054DOI Listing
December 2019

Correction to: Catheter retention as a consequence rather than a cause of unfavorable outcome in candidemia.

Intensive Care Med 2018 03;44(3):405-407

Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.

In the original publication the members of the FUNGINOS network were provided in such a way that they could not be indexed as collaborators on PubMed.
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http://dx.doi.org/10.1007/s00134-018-5081-4DOI Listing
March 2018

Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study.

J Infect 2018 05 31;76(5):489-495. Epub 2018 Jan 31.

Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Department of Medicine, Ensemble Hospitalier de la Côte, Morges, Switzerland. Electronic address:

Objectives: Breakthrough candidemia (BTC) on fluconazole was associated with non-susceptible Candida spp. and increased mortality. This nationwide FUNGINOS study analyzed clinical and mycological BTC characteristics.

Methods: A 3-year prospective study was conducted in 567 consecutive candidemias. Species identification and antifungal susceptibility testing (CLSI) were performed in the FUNGINOS reference laboratory. Data were analyzed according to STROBE criteria.

Results: 43/576 (8%) BTC occurred: 37/43 (86%) on fluconazole (28 prophylaxis, median 200 mg/day). 21% BTC vs. 23% non-BTC presented severe sepsis/septic shock. Overall mortality was 34% vs. 32%. BTC was associated with gastrointestinal mucositis (multivariate OR 5.25, 95%CI 2.23-12.40, p < 0.001) and graft-versus-host-disease (6.25, 1.00-38.87, p = 0.05), immunosuppression (2.42, 1.03-5.68, p = 0.043), and parenteral nutrition (2.87, 1.44-5.71, p = 0.003). Non-albicans Candida were isolated in 58% BTC vs. 35% non-BTC (p = 0.005). 63% of 16 BTC occurring after 10-day fluconazole were non-susceptible (Candida glabrata, Candida krusei, Candida norvegensis) vs. 19% of 21 BTC (C. glabrata) following shorter exposure (7.10, 1.60-31.30, p = 0.007). Median fluconazole MIC was 4 mg/l vs. 0.25 mg/l (p < 0.001). Ten-day fluconazole exposure predicted non-susceptible BTC with 73% accuracy.

Conclusions: Outcomes of BTC and non-BTC were similar. Fluconazole non-susceptible BTC occurred in three out of four cases after prolonged low-dose prophylaxis. This implies reassessment of prophylaxis duration and rapid de-escalation of empirical therapy in BTC after short fluconazole exposure.
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http://dx.doi.org/10.1016/j.jinf.2017.12.018DOI Listing
May 2018

Immediate and 1-year follow-up with the novel nanosurface modified COBRA PzF stent.

Arch Cardiovasc Dis 2017 Dec 6;110(12):682-688. Epub 2017 Nov 6.

Department of cardiology, GCS ES-Axium-Rambot, 21, avenue Alfred-Capus, 13090 Aix-en-Provence, France.

Background: The COBRA PzF coronary stent, which has a unique nano-coating of Polyzene-F, was developed to reduce the risk of stent thrombosis.

Aims: To report procedural and 1-year clinical outcomes following COBRA PzF coronary stent implantation in a real-world percutaneous coronary intervention (PCI) registry.

Methods: All patients assigned to treatment with the COBRA PzF in the GCS Axium Rambot Center, Aix-en-Provence, France between February 2013 to June 2014 were prospectively enrolled.

Results: Among 100 patients (71% men, mean±standard error age 71.4±11.0 years), 38% had acute coronary syndromes. The population was consistent with real-world experience and included patients with multiple co-morbidities and 26% with diffuse multivessel disease. A total of 151 lesions were treated with 166 stents, including 26% of lesions with a type B2 or C classification. Pre- and post-procedural quantitative coronary angiography analyses showed a mean acute gain of 2.2±0.2mm. Angiographic success was achieved in all cases. One-year follow-up was available for all patients and the target vessel failure (composite of all-cause mortality, myocardial infarction or target vessel revascularization) rate was 12%, including 2% mortality (end-stage cardiomyopathy), 5% myocardial infarction (five periprocedural myocardial infarctions with isolated troponin elevation without chest pain or Q waves) and 5% target lesion revascularization. There were no cases of definite stent thrombosis.

Conclusion: The COBRA PzF stent was safe and effective in routine practice. One-year follow-up was associated with excellent clinical outcomes and compared favourably with current devices. These results are very promising in a real-world population of complex patients, and further study is warranted.
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http://dx.doi.org/10.1016/j.acvd.2017.04.010DOI Listing
December 2017

Catheter retention as a consequence rather than a cause of unfavorable outcome in candidemia.

Intensive Care Med 2017 06 7;43(6):935-939. Epub 2017 Mar 7.

Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.

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http://dx.doi.org/10.1007/s00134-017-4737-9DOI Listing
June 2017

Genome Sequences of Listeria monocytogenes Strains Responsible for Cheese- and Cooked Ham Product-Associated Swiss Listeriosis Outbreaks in 2005 and 2011.

Genome Announc 2016 Mar 10;4(2). Epub 2016 Mar 10.

Vetsuisse Faculty, Institute for Food Safety and Hygiene, University of Zurich, Zurich, Switzerland.

The complete genome sequences of three Listeria monocytogenes serotype 1/2a strains, Lm 3136, Lm 3163, and Lm N1546, which were responsible for listeriosis outbreaks in 2005 and 2011 in Switzerland, are presented here.
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http://dx.doi.org/10.1128/genomeA.00106-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786662PMC
March 2016

Polymorphisms in tumor necrosis factor-α increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients*.

Crit Care Med 2014 04;42(4):e304-8

1Infectious Diseases Service, Department of Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland. 2Division of Infectious Diseases and Hospital Epidemiology, Department of Medicine, Basel University Hospital, Basel, Switzerland. 3Adult Intensive Care Service, Lausanne University Hospital (CHUV), Lausanne, Switzerland. 4Intensive Care Unit, Basel University Hospital, Basel, Switzerland. 5Institute for Infectious Diseases, University of Bern, Bern, Switzerland. 6Division of Infectious Disease, Internal Medicine Centre, Hirslanden Klink, Aarau, Switzerland. 7Institute of Microbiology, Department of Laboratories, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

Objectives: To evaluate the influence of genetic polymorphisms on the susceptibility to Candida colonization and intra-abdominal candidiasis, a blood culture-negative life-threatening infection in high-risk surgical ICU patients.

Design: Prospective observational cohort study.

Setting: Surgical ICUs from two University hospitals of the Fungal Infection Network of Switzerland.

Patients: Eighty-nine patients at high risk for intra-abdominal candidiasis (68 with recurrent gastrointestinal perforation and 21 with acute necrotizing pancreatitis).

Measurements And Main Results: Eighteen single-nucleotide polymorphisms in 16 genes previously associated with development of fungal infections were analyzed from patient's DNA by using an Illumina Veracode genotyping platform. Candida colonization was defined by recovery of Candida species from at least one nonsterile site by twice weekly monitoring of cultures from oropharynx, stools, urine, skin, and/or respiratory tract. A corrected colonization index greater than or equal to 0.4 defined "heavy" colonization. Intra-abdominal candidiasis was defined by the presence of clinical symptoms and signs of peritonitis or intra-abdominal abscess and isolation of Candida species either in pure or mixed culture from intraoperatively collected abdominal samples. Single-nucleotide polymorphisms in three innate immune genes were associated with development of a Candida corrected colonization index greater than or equal to 0.4 (Toll-like receptor rs4986790, hazard ratio = 3.39; 95% CI, 1.45-7.93; p = 0.005) or occurrence of intra-abdominal candidiasis (tumor necrosis factor-α rs1800629, hazard ratio = 4.31; 95% CI, 1.85-10.1; p= 0.0007; β-defensin 1 rs1800972, hazard ratio = 3.21; 95% CI, 1.36-7.59; p = 0.008).

Conclusion: We report a strong association between the promoter rs1800629 single-nucleotide polymorphism in tumor necrosis factor-α and an increased susceptibility to intra-abdominal candidiasis in a homogenous prospective cohort of high-risk surgical ICU patients. This finding highlights the relevance of the tumor necrosis factor-α functional polymorphism in immune response to fungal pathogens. Immunogenetic profiling in patients at clinical high risk followed by targeted antifungal interventions may improve the prevention or preemptive management of this life-threatening infection.
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http://dx.doi.org/10.1097/CCM.0000000000000208DOI Listing
April 2014

β-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis.

Am J Respir Crit Care Med 2013 Nov;188(9):1100-9

1 Infectious Diseases Service, Department of Medicine.

Rationale: Life-threatening intraabdominal candidiasis (IAC) occurs in 30 to 40% of high-risk surgical intensive care unit (ICU) patients. Although early IAC diagnosis is crucial, blood cultures are negative, and the role of Candida score/colonization indexes is not established.

Objectives: The aim of this prospective Fungal Infection Network of Switzerland (FUNGINOS) cohort study was to assess accuracy of 1,3-β-d-glucan (BG) antigenemia for diagnosis of IAC.

Methods: Four hundred thirty-four consecutive adults with abdominal surgery or acute pancreatitis and ICU stay 72 hours or longer were screened: 89 (20.5%) at high risk for IAC were studied (68 recurrent gastrointestinal tract perforation, 21 acute necrotizing pancreatitis). Diagnostic accuracy of serum BG (Fungitell), Candida score, and colonization indexes was compared.

Measurements And Main Results: Fifty-eight of 89 (65%) patients were colonized by Candida; 29 of 89 (33%) presented IAC (27 of 29 with negative blood cultures). Nine hundred twenty-one sera were analyzed (9/patient): median BG was 253 pg/ml (46-9,557) in IAC versus 99 pg/ml (8-440) in colonization (P < 0.01). Sensitivity and specificity of two consecutive BG measurements greater than or equal to 80 pg/ml were 65 and 78%, respectively. In recurrent gastrointestinal tract perforation it was 75 and 77% versus 90 and 38% (Candida score ≥ 3), 79 and 34% (colonization index ≥ 0.5), and 54 and 63% (corrected colonization index ≥ 0.4), respectively. BG positivity anticipated IAC diagnosis (5 d) and antifungal therapy (6 d). Severe sepsis/septic shock and death occurred in 10 of 11 (91%) and 4 of 11 (36%) patients with BG 400 pg/ml or more versus 5 of 18 (28%, P = 0.002) and 1 of 18 (6%, P = 0.05) with BG measurement less than 400 pg/ml. β-Glucan decreased in IAC responding to therapy and increased in nonresponse.

Conclusions: BG antigenemia is superior to Candida score and colonization indexes and anticipates diagnosis of blood culture-negative IAC. This proof-of-concept observation in strictly selected high-risk surgical ICU patients deserves investigation of BG-driven preemptive therapy.
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http://dx.doi.org/10.1164/rccm.201211-2069OCDOI Listing
November 2013

Complete Genome Sequence of Listeria monocytogenes LL195, a Serotype 4b Strain from the 1983-1987 Listeriosis Epidemic in Switzerland.

Genome Announc 2013 Jan 31;1(1). Epub 2013 Jan 31.

Department of Computational Systems Biology, Faculty of Life Sciences, University of Vienna, Vienna, Austria.

The complete genome sequence of Listeria monocytogenes LL195, a serotype 4b clinical strain isolated during the 1983-1987 listeriosis epidemic in Switzerland, is presented.
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http://dx.doi.org/10.1128/genomeA.00152-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569335PMC
January 2013

Cerebral vasculitis complicating postoperative meningitis: the role of steroids revisited.

Swiss Med Wkly 2012 29;142:w13697. Epub 2012 Oct 29.

Service of Infectious Diseases, Clinique Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Meningitis due to Streptococcus pneumoniae is a rare complication of trans-sphenoidal surgery. We present the case of a patient who developed pneumococcal meningitis with associated bacteraemia after elective endoscopic trans-sphenoidal resection of a pituitary macro-adenoma. After initial treatment with ceftriaxone and dexamethasone, the patient made a good recovery and dexamethasone was discontinued. Two days later the patient's condition deteriorated rapidly, presenting focal and diffuse neurological deficits. Cerebral MRI revealed widespread punctate ischaemic-type lesions affecting both anterior and posterior vascular territories bilaterally and involving features consistent with cerebral vasculitis. Antibiotic treatment was broadened to include meropenem and dexamethasone was restarted, but the patient remained in a comatose state and died 14 days later. Steroid treatment may play a dual role in this poorly characterised infectious complication of trans-sphenoidal pituitary surgery. This possibility is discussed and the options for prophylaxis are reviewed.
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http://dx.doi.org/10.4414/smw.2012.13697DOI Listing
May 2013

Challenging recommended oral and intravenous voriconazole doses for improved efficacy and safety: population pharmacokinetics-based analysis of adult patients with invasive fungal infections.

Clin Infect Dis 2012 Aug 18;55(3):381-90. Epub 2012 May 18.

Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland.

Background: Recommended oral voriconazole (VRC) doses are lower than intravenous doses. Because plasma concentrations impact efficacy and safety of therapy, optimizing individual drug exposure may improve these outcomes.

Methods: A population pharmacokinetic analysis (NONMEM) was performed on 505 plasma concentration measurements involving 55 patients with invasive mycoses who received recommended VRC doses.

Results: A 1-compartment model with first-order absorption and elimination best fitted the data. VRC clearance was 5.2 L/h, the volume of distribution was 92 L, the absorption rate constant was 1.1 hour(-1), and oral bioavailability was 0.63. Severe cholestasis decreased VRC elimination by 52%. A large interpatient variability was observed on clearance (coefficient of variation [CV], 40%) and bioavailability (CV 84%), and an interoccasion variability was observed on bioavailability (CV, 93%). Lack of response to therapy occurred in 12 of 55 patients (22%), and grade 3 neurotoxicity occurred in 5 of 55 patients (9%). A logistic multivariate regression analysis revealed an independent association between VRC trough concentrations and probability of response or neurotoxicity by identifying a therapeutic range of 1.5 mg/L (>85% probability of response) to 4.5 mg/L (<15% probability of neurotoxicity). Population-based simulations with the recommended 200 mg oral or 300 mg intravenous twice-daily regimens predicted probabilities of 49% and 87%, respectively, for achievement of 1.5 mg/L and of 8% and 37%, respectively, for achievement of 4.5 mg/L. With 300-400 mg twice-daily oral doses and 200-300 mg twice-daily intravenous doses, the predicted probabilities of achieving the lower target concentration were 68%-78% for the oral regimen and 70%-87% for the intravenous regimen, and the predicted probabilities of achieving the upper target concentration were 19%-29% for the oral regimen and 18%-37% for the intravenous regimen.

Conclusions: Higher oral than intravenous VRC doses, followed by individualized adjustments based on measured plasma concentrations, improve achievement of the therapeutic target that maximizes the probability of therapeutic response and minimizes the probability of neurotoxicity. These findings challenge dose recommendations for VRC.
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http://dx.doi.org/10.1093/cid/cis437DOI Listing
August 2012

Diagnosis of invasive candidiasis in the ICU.

Ann Intensive Care 2011 Sep 1;1:37. Epub 2011 Sep 1.

Adult Critical Care Medicine and Burn Centre, Centre Hospitalier Universitaire Vaudois (CHUV) -- BH 08-619, Bugnon 46 CH-1011 Lausanne, Switzerland.

Invasive candidiasis ranges from 5 to 10 cases per 1,000 ICU admissions and represents 5% to 10% of all ICU-acquired infections, with an overall mortality comparable to that of severe sepsis/septic shock. A large majority of them are due to Candida albicans, but the proportion of strains with decreased sensitivity or resistance to fluconazole is increasingly reported. A high proportion of ICU patients become colonized, but only 5% to 30% of them develop an invasive infection. Progressive colonization and major abdominal surgery are common risk factors, but invasive candidiasis is difficult to predict and early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New nonculture-based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Both serologic (mannan, antimannan, and betaglucan) and molecular (Candida-specific PCR in blood and serum) have been applied as serial screening procedures in high-risk patients. However, although reasonably sensitive and specific, these techniques are largely investigational and their clinical usefulness remains to be established. Identification of patients susceptible to benefit from empirical antifungal treatment remains challenging, but it is mandatory to avoid antifungal overuse in critically ill patients. Growing evidence suggests that monitoring the dynamic of Candida colonization in surgical patients and prediction rules based on combined risk factors may be used to identify ICU patients at high risk of invasive candidiasis susceptible to benefit from prophylaxis or preemptive antifungal treatment.
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http://dx.doi.org/10.1186/2110-5820-1-37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224461PMC
September 2011

Multicenter, prospective clinical evaluation of respiratory samples from subjects at risk for Pneumocystis jirovecii infection by use of a commercial real-time PCR assay.

J Clin Microbiol 2011 May 2;49(5):1872-8. Epub 2011 Mar 2.

Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection. Microscopic diagnosis, including diagnosis using the Merifluor-Pneumocystis direct fluorescent antigen (MP-DFA) test, has limitations. Real-time PCR may assist in diagnosis, but no commercially validated real-time PCR assay has been available to date. MycAssay Pneumocystis is a commercial assay that targets the P. jirovecii mitochondrial large subunit (analytical detection limit, ≤ 3.5 copies/μl of sample). A multicenter trial recruited 110 subjects: 54 with transplants (40 with lung transplants), 32 with nonmalignant conditions, 13 with leukemia, and 11 with solid tumors; 9 were HIV positive. A total of 110 respiratory samples (92% of which were bronchoalveolar lavage [BAL] specimens) were analyzed by PCR. Performance was characterized relative to investigator-determined clinical diagnosis of PCP (including local diagnostic tests), and PCR results were compared with MP-DFA test results for 83 subjects. Thirteen of 14 subjects with PCP and 9/96 without PCP (including 5 undergoing BAL surveillance after lung transplantation) had positive PCR results; sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were 93%, 91%, 59%, and 99%, respectively. Fourteen of 83 subjects for whom PCR and MP-DFA test results were available had PCP; PCR sensitivity, specificity, PPV, and NPV were 93%, 90%, 65%, and 98%, respectively, and MP-DFA test sensitivity, specificity, PPV, and NPV were 93%, 100%, 100%, and 98%. Of the 9 PCR-positive subjects without PCP, 1 later developed PCP. The PCR diagnostic assay compares well with clinical diagnosis using nonmolecular methods. Additional positive results compared with the MP-DFA test may reflect low-level infection or colonization.
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http://dx.doi.org/10.1128/JCM.02390-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122670PMC
May 2011

Outbreak of Mycobacterium haemophilum infections after permanent makeup of the eyebrows.

Clin Infect Dis 2011 Feb 22;52(4):488-91. Epub 2011 Jan 22.

Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.

We report a Mycobacterium haemophilum outbreak after permanent make-up of the eyebrows performed by the same freelance artist. Twelve patients presented an eyebrow lesion and cervical lymphadenitis. All were treated with antibiotics. Surgery was required in 10 cases. M. haemophilum DNA was identified in the make-up ink.
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http://dx.doi.org/10.1093/cid/ciq191DOI Listing
February 2011

False-negative PCR result due to gene polymorphism: the example of Neisseria meningitidis.

J Clin Microbiol 2010 Dec 20;48(12):4590-1. Epub 2010 Oct 20.

Institute of Microbiology, University Hospital of Lausanne (CHUV), Bugnon 48, 1011 Lausanne, Switzerland.

Early treatment of meningococcal meningitis is mandatory but may negate the cerebrospinal fluid culture. Etiological diagnosis then mainly relies on PCR. Here, we report a case of false-negative results for real-time PCR for a Neisseria meningitidis serogroup B isolate with a polymorphism in the ctrA gene.
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http://dx.doi.org/10.1128/JCM.01766-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008480PMC
December 2010

Ultra-performance liquid chromatography mass spectrometry and sensitive bioassay methods for quantification of posaconazole plasma concentrations after oral dosing.

Antimicrob Agents Chemother 2010 Dec 4;54(12):5074-81. Epub 2010 Oct 4.

Quantitative Mass Spectrometry Facility, Faculty of Biology and Medicine, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.

Posaconazole (POS) is a new antifungal agent for prevention and therapy of mycoses in immunocompromised patients. Variable POS pharmacokinetics after oral dosing may influence efficacy: a trough threshold of 0.5 μg/ml has been recently proposed. Measurement of POS plasma concentrations by complex chromatographic techniques may thus contribute to optimize prevention and management of life-threatening infections. No microbiological analytical method is available. The objective of this study was to develop and validate a new simplified ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method and a sensitive bioassay for quantification of POS over the clinical plasma concentration range. The UPLC-MS/MS equipment consisted of a triple quadrupole mass spectrometer, an electrospray ionization (ESI) source, and a C(18) analytical column. The Candida albicans POS-hypersusceptible mutant (MIC of 0.002 μg/ml) Δcdr1 Δcdr2 Δflu Δmdr1 Δcan constructed by targeted deletion of multidrug efflux transporters and calcineurin genes was used for the bioassay. POS was extracted from plasma by protein precipitation with acetonitrile-methanol (75%/25%, vol/vol). Reproducible standard curves were obtained over the range 0.014 to 12 (UPLC-MS/MS) and 0.028 to 12 μg/ml (bioassay). Intra- and interrun accuracy levels were 106% ± 2% and 103% ± 4% for UPLC-MS/MS and 102% ± 8% and 104% ± 1% for bioassay, respectively. The intra- and interrun coefficients of variation were 7% ± 4% and 7% ± 3% for UPLC-MS/MS and 5% ± 3% and 4% ± 2% for bioassay, respectively. An excellent correlation between POS plasma concentrations measured by UPLC-MS/MS and bioassay was found (concordance, 0.96). In 26 hemato-oncological patients receiving oral POS, 27/69 (39%) trough plasma concentrations were lower than 0.5 μg/ml. The UPLC-MS/MS method and sensitive bioassay offer alternative tools for accurate and precise quantification of the plasma concentrations in patients receiving oral posaconazole.
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http://dx.doi.org/10.1128/AAC.00022-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981256PMC
December 2010

Multiplex ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, anidulafungin, and caspofungin.

Antimicrob Agents Chemother 2010 Dec 20;54(12):5303-15. Epub 2010 Sep 20.

Division of Clinical Pharmacology, Department of Medicine, BH18, Lab 218-226, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-1011 Lausanne, Switzerland.

Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 μg/ml; those of echinocandin quantification, 0.06 to 0.1 μg/ml), accurate (intra- and interassay biases of -9.9 to +5% and -4.0 to +8.8%, respectively), and precise (intra- and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 μg/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.
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http://dx.doi.org/10.1128/AAC.00404-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981284PMC
December 2010

New nonculture-based methods for the diagnosis of invasive candidiasis.

Authors:
Jacques Bille

Curr Opin Crit Care 2010 Oct;16(5):460-4

Institute of Microbiology, University Hospital CHUV, Lausanne, Switzerland.

Purpose Of Review: Invasive candidiasis is a severe infectious complication occurring mostly in onco-hematologic and surgical patients. Its conventional diagnosis is insensitive and often late, leading to a delayed treatment and a high mortality. The purpose of this article is to review recent contributions in the nonconventional diagnostic approaches of invasive candidiasis, both for the detection of the epidose and the characterization of the etiologic agent.

Recent Findings: Antigen-based tests to detect invasive candidiasis comprise a specific test, mannan, as well as a nonspecific test, beta-D-glucan. Both have a moderate sensitivity and a high specificity, and cannot be recommended alone as a negative screening tool or a positive syndrome driven diagnostic tool. Molecular-based tests still have not reached the stage of rapid, easy to use, standardized tests ideally complementing blood culture at the time of blood sampling. New tests (fluorescence in-situ hybridization or mass spectrometry) significantly reduce the delay of identification of Candida at the species level in positive blood cultures, and should have a positive impact on earlier appropriate antifungal therapy and possibly on outcome.

Summary: Both antigen-based and molecular tests appear as promising new tools to complement and accelerate the conventional diagnosis of invasive candidiasis with an expected significant impact on earlier and more focused treatment and on prognosis.
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http://dx.doi.org/10.1097/MCC.0b013e32833e04dfDOI Listing
October 2010

New Diagnostic Real-Time PCR for Specific Detection of Mycoplasma hominis DNA.

Int J Microbiol 2010 25;2010. Epub 2010 Jul 25.

Infectious Diseases Service, Department of Internal Medicine, University Hospital Center and University of Lausanne, 1011 Lausanne, Switzerland.

Mycoplasma hominis is a fastidious micro-organism causing genital and extragenital infections. We developed a specific real-time PCR that exhibits high sensitivity and low intrarun and interrun variabilities. When applied to clinical samples, this quantitative PCR allowed to confirm the role of M. hominis in three patients with severe extragenital infections.
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http://dx.doi.org/10.1155/2010/317512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913506PMC
July 2011

Interhuman transmission as a potential key parameter for geographical variation in the prevalence of Pneumocystis jirovecii dihydropteroate synthase mutations.

Clin Infect Dis 2010 Aug;51(4):e28-33

Institute of Microbiology, Swiss HIV Cohort Study, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

Background: Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations are associated with failure of prophylaxis with sulfa drugs. This retrospective study sought to better understand the geographical variation in the prevalence of these mutations.

Methods: DHPS polymorphisms in 394 clinical specimens from immunosuppressed patients who received a diagnosis of P. jirovecii pneumonia and who were hospitalized in 3 European cities were examined using polymerase chain reaction (PCR) single-strand conformation polymorphism. Demographic and clinical characteristics were obtained from patients' medical charts.

Results: Of the 394 patients, 79 (20%) were infected with a P. jirovecii strain harboring one or both of the previously reported DHPS mutations. The prevalence of DHPS mutations was significantly higher in Lyon than in Switzerland (33.0% vs 7.5%; P < .001). The proportion of patients with no evidence of sulfa exposure who harbored a mutant P. jirovecii DHPS genotype was significantly higher in Lyon than in Switzerland (29.7% vs 3.0%; P < .001). During the study period in Lyon, in contrast to the Swiss hospitals, measures to prevent dissemination of P. jirovecii from patients with P. jirovecii pneumonia were generally not implemented, and most patients received suboptimal prophylaxis, the failure of which was strictly associated with mutated P. jirovecii. Thus, nosocomial interhuman transmission of mutated strains directly or indirectly from other individuals in whom selection of mutants occurred may explain the high proportion of mutations without sulfa exposure in Lyon.

Conclusions: Interhuman transmission of P. jirovecii, rather than selection pressure by sulfa prophylaxis, may play a predominant role in the geographical variation in the prevalence in the P. jirovecii DHPS mutations.
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http://dx.doi.org/10.1086/655145DOI Listing
August 2010

Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae strains causing childhood infection in Burkina Faso.

Pak J Biol Sci 2009 Sep;12(18):1282-6

Unité de Formation et de Recherche en Sciences de la Vie et de la Terre (UFR/SVT), Université de Ouagadougou, 03 BP 7021, Ouagadougou 03, Burkina Faso.

In Burkina Faso, a Western African country, reports on pneumococci carriage, resistance patterns and serotypes are inconsistent. The present study was conducted in order to evaluate these parameters. Thus 860 nasopharyngeal swabs were collected from children attending vaccination centers for pneumococci isolation, identification and serotype determination. The susceptibility to 16 antibiotics was assayed as recommended by the National Committee for Clinical Laboratory Standard (NCCLS). The results revealed that the majority of children were of 2 to 24 months age and 73.4% of children were well vaccinated. A carriage rate of 50.6% was recoded among the children. The main serotypes were: 6 (22.22%); 23 (16.67%); 7 and 9 (3.70%); 4, 11, 14, 15, 20 and 24 (1.85%). Serotypesl9, 23, 6, 7 and 18 were linked to penicillin resistance. Globally, high resistance rates to: amikacin, tetracyclin, pefloxacin, cotrimoxazol and penicillins (resistance rates greater than 25%) were recorded; however the following antibiotics remained active on the strains: rifampicin, ceftriaxone, erythromycin, spectinomycin, chloramphenicol, vancomycin, lincomycin and ciprofloxacin.
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http://dx.doi.org/10.3923/pjbs.2009.1282.1286DOI Listing
September 2009

Molecular detection and identification of zygomycetes species from paraffin-embedded tissues in a murine model of disseminated zygomycosis: a collaborative European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) evaluation.

J Clin Microbiol 2010 Jun 7;48(6):2043-6. Epub 2010 Apr 7.

Institut Pasteur, Unité de Mycologie Moléculaire, 25, Rue du Dr. Roux, Paris 75724 Cedex 15, France.

The present study was performed to assess the interlaboratory reproducibility of the molecular detection and identification of species of Zygomycetes from formalin-fixed paraffin-embedded kidney and brain tissues obtained from experimentally infected mice. Animals were infected with one of five species (Rhizopus oryzae, Rhizopus microsporus, Lichtheimia corymbifera, Rhizomucor pusillus, and Mucor circinelloides). Samples with 1, 10, or 30 slide cuts of the tissues were prepared from each paraffin block, the sample identities were blinded for analysis, and the samples were mailed to each of seven laboratories for the assessment of sensitivity. A protocol describing the extraction method and the PCR amplification procedure was provided. The internal transcribed spacer 1 (ITS1) region was amplified by PCR with the fungal universal primers ITS1 and ITS2 and sequenced. As negative results were obtained for 93% of the tissue specimens infected by M. circinelloides, the data for this species were excluded from the analysis. Positive PCR results were obtained for 93% (52/56), 89% (50/56), and 27% (15/56) of the samples with 30, 10, and 1 slide cuts, respectively. There were minor differences, depending on the organ tissue, fungal species, and laboratory. Correct species identification was possible for 100% (30 cuts), 98% (10 cuts), and 93% (1 cut) of the cases. With the protocol used in the present study, the interlaboratory reproducibility of ITS sequencing for the identification of major Zygomycetes species from formalin-fixed paraffin-embedded tissues can reach 100%, when enough material is available.
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http://dx.doi.org/10.1128/JCM.02319-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884487PMC
June 2010

Geographic variation in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: an assessment from the ARTEMIS DISK Global Antifungal Surveillance Program.

Diagn Microbiol Infect Dis 2010 Jun 24;67(2):162-71. Epub 2010 Mar 24.

Medical Microbiology Division, Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Geographic differences in frequency and azole resistance among Candida glabrata may impact empiric antifungal therapy choice. We examined geographic variation in isolation and azole susceptibility of C. glabrata. We examined 23 305 clinical isolates of C. glabrata during ARTEMIS DISK global surveillance. Susceptibility testing to fluconazole and voriconazole was assessed by disk diffusion, and the results were grouped by geographic location: North America (NA) (2470 isolates), Latin America (LA) (2039), Europe (EU) (12 439), Africa and the Middle East (AME) (728), and Asia-Pacific (AP) (5629). Overall, C. glabrata accounted for 11.6% of 201 653 isolates of Candida and varied as a proportion of all Candida isolated from 7.4% in LA to 21.1% in NA. Decreased susceptibility (S) to fluconazole was observed in all geographic regions and ranged from 62.8% in AME to 76.7% in LA. Variation in fluconazole susceptibility was observed within each region: AP (range, 50-100% S), AME (48-86.9%), EU (44.8-88%), LA (43-92%), and NA (74.5-91.6%). Voriconazole was more active than fluconazole (range, 82.3-84.2% S) with similar regional variation. Among 22 sentinel sites participating in ARTEMIS from 2001 through 2007 (84 140 total isolates, 8163 C. glabrata), the frequency of C. glabrata isolation increased in 14 sites and the frequency of fluconazole resistance (R) increased in 11 sites over the 7-year period of study. The sites with the highest cumulative rates of fluconazole R were in Poland (22% R), the Czech Republic (27% R), Venezuela (27% R), and Greece (33% R). C. glabrata was most often isolated from blood, normally sterile body fluids and urine. There is substantial geographic and institutional variation in both frequency of isolation and azole resistance among C. glabrata. Prompt species identification and fluconazole susceptibility testing are necessary to optimize therapy for invasive candidiasis.
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http://dx.doi.org/10.1016/j.diagmicrobio.2010.01.002DOI Listing
June 2010

Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets.

J Clin Microbiol 2010 Apr 17;48(4):1481-3. Epub 2010 Feb 17.

Institute of Microbiology, University of Lausanne and University Hospital Center, Lausanne, Switzerland.

An ammonium chloride erythrocyte-lysing procedure was used to prepare a bacterial pellet from positive blood cultures for direct matrix-assisted laser desorption-ionization time of flight (MALDI-TOF) mass spectrometry analysis. Identification was obtained for 78.7% of the pellets tested. Moreover, 99% of the MALDI-TOF identifications were congruent at the species level when considering valid scores. This fast and accurate method is promising.
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http://dx.doi.org/10.1128/JCM.01780-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849571PMC
April 2010

Natural variability of in vitro adherence to fibrinogen and fibronectin does not correlate with in vivo infectivity of Staphylococcus aureus.

Infect Immun 2010 Apr 11;78(4):1711-6. Epub 2010 Jan 11.

Department of Fundamental Microbiology, University of Lausanne, 1015 Lausanne, Switzerland.

Adherence to fibrinogen and fibronectin plays a crucial role in Staphylococcus aureus experimental endocarditis. Previous genetic studies have shown that infection and carriage isolates do not systematically differ in their virulence-related genes, including genes conferring adherence, such as clfA and fnbA. We set out to determine the range of adherence phenotypes in carriage isolates of S. aureus, to compare the adherence of these isolates to the adherence of infection isolates, and to determine the relationship between adherence and infectivity in a rat model of experimental endocarditis. A total of 133 healthy carriage isolates were screened for in vitro adherence to fibrinogen and fibronectin, and 30 isolates were randomly chosen for further investigation. These 30 isolates were compared to 30 infective endocarditis isolates and 30 blood culture isolates. The infectivities of the carriage isolates, which displayed either extremely low or high adherence to fibrinogen and fibronectin, were tested using a rat model of experimental endocarditis. The levels of adherence to both fibrinogen and fibronectin were very similar for isolates from healthy carriers and members of the two groups of infection isolates. All three groups of isolates showed a wide range of adherence to fibrinogen and fibronectin. Moreover, the carriage isolates that showed minimal adherence and the carriage isolates that showed strong adherence had the same infectivity in experimental endocarditis. Adherence was proven to be important for pathogenesis in experimental endocarditis, but even the least adherent carriage strains had the ability to induce infection. We discuss the roles of differential gene expression, human host factors, and gene redundancy in resolving this apparent paradox.
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http://dx.doi.org/10.1128/IAI.01274-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849403PMC
April 2010

[Doctor, I have a lymph node].

Rev Med Suisse 2009 Apr;5(197):710-5

Institut de microbiologie, Département de pathologie et de médecine de laboratoire, CHUV, 1011 Lausanne.

To investigate a recently developed lymphadenopathy can be simple or complex. The medical history, presence or not of symptoms, the general physical examination, and the localization and characteristics of the adenopathy, most often lead to a diagnosis and therapy when indicated. Among young adults, the etiology is either infectious or reactive, rarely tumoral, as opposed to elderly persons. The most important step is to look at signs of severity (or non banality) such as an increased size, hard consistency, supra-clavicular location, an immunocompromised host, a history of Tb exposition. If present, these signs will trigger a biopsy with cyto- or histopathological examination mostly to rule out a malignant tumor. This article reviews the practical steps of an investigation of an isolated adenopathy in an adult patient.
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April 2009

Histoplasma capsulatum var. duboisii infection in a patient with AIDS: rapid diagnosis using polymerase chain reaction-sequencing.

Diagn Microbiol Infect Dis 2009 May 21;64(1):85-9. Epub 2009 Mar 21.

Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.

We describe an original case of disseminated infection with Histoplasma capsulatum (Hc) var. duboisii in an African patient with AIDS who migrated to Switzerland. The diagnosis of histoplasmosis was suggested using direct examination of tissues and confirmed in 24 h with a panfungal polymerase chain reaction assay. The variety duboisii of Hc was established using DNA sequencing of the polymorphic genomic region OLE. Molecular tools allow diagnosis of histoplasmosis in 24 h, which is drastically shorter than culture procedures.
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http://dx.doi.org/10.1016/j.diagmicrobio.2009.01.001DOI Listing
May 2009

Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines.

Eur J Pediatr 2009 Dec 24;168(12):1429-36. Epub 2009 Feb 24.

Child and Adolescent Department, Lausanne University Hospital, Lausanne, Switzerland.

Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization.
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http://dx.doi.org/10.1007/s00431-009-0943-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087130PMC
December 2009

Caspofungin for prevention of intra-abdominal candidiasis in high-risk surgical patients.

Intensive Care Med 2009 May 27;35(5):903-8. Epub 2009 Jan 27.

Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL), Rue du Bugnon 46, 1011 Lausanne, Switzerland.

Purpose: Thirty to forty percent of patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis develop intra-abdominal invasive candidiasis (IC). A corrected Candida colonization index (CCI) > or =0.4 is a powerful predictor of IC. Fluconazole prevents intra-abdominal IC in this setting, but azole-resistant Candida species are emerging. The aim of this study was to explore the efficacy and safety of caspofungin for prevention of intra-abdominal IC in high-risk surgical patients.

Methods: Prospective non-comparative single-center study in consecutive adult surgical patients with recurrent gastrointestinal perforation/anastomotic leakage or acute necrotizing pancreatitis. Preventive caspofungin therapy (70 mg, then 50 mg/day) was given until resolution of the surgical condition. Candida colonization index and CCI, occurrence of intra-abdominal IC and adverse events were monitored.

Results: Nineteen patients were studied: 16 (84%) had recurrent gastrointestinal perforation/anastomotic leakage and 3 (16%) acute necrotizing pancreatitis. The median duration of preventive caspofungin therapy was 16 days (range 4-46). The colonization index decreased significantly during study therapy, and the CCI remained <0.4 in all patients. Caspofungin was successful for prevention of intra-abdominal IC in 18/19 patients (95%, 1 breakthrough IC 5 days after inclusion). No drug-related adverse event requiring caspofungin discontinuation occurred.

Conclusion: Caspofungin may be efficacious and safe for prevention of intra-abdominal candidiasis in high-risk surgical patients. This needs to be further investigated in randomized trials.
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http://dx.doi.org/10.1007/s00134-009-1405-8DOI Listing
May 2009