Jean-Louis Golmard

Risk factors for neurosurgical site infections after craniotomy : a critical reappraisal of antibiotic prophylaxis on 4578 patients

The objective of this study was to evaluate incidence and risk factors of postoperative infections, with emphasis on antibiotic prophylaxis, in a series of 4578 craniotomies. A prospective database was implemented for surveillance of postcraniotomy infections. During period A, no antibiotic prophylaxis was prescribed for scheduled, clean craniotomies, lasting less than 4 h, whereas emergency, clean-contaminated or long-lasting craniotomies received cloxacillin or amoxicillin-clavulanate. During period B, prophylaxis was given to every craniotomy. The effect of prophylaxis on craniotomy infections, independently of other risk factors, was studied by multivariate analysis. The overall infection rate was 6.6%. CSF leak, male gender, surgical diagnosis, surgeon, early re-operation, surgical duration and absence of prophylaxis were independent risk factors. CSF leak had the highest odds ratio. Antibiotic prophylaxis decreased infection rate from 9.7% down to 5.8% in the entire population (p < 0.0001) mainly by decreasing rates in low risk patients from 10.0% down to 4.6% (p < 0.0001). Antibiotic prophylaxis in craniotomy is effective in preventing surgical site infections even in low-risk patients.

Risk factors for adult nosocomial meningitis after craniotomy: role of antibiotic prophylaxis.

OBJECTIVE To evaluate incidence and risk factors of postoperative meningitis, with special emphasis on antibiotic prophylaxis, in a series of 6243 consecutive craniotomies. METHODS Meningitis was individualized from a prospective surveillance database of surgical site infections after craniotomy. Ventriculitis related to external ventricular drainage or cerebrospinal fluid shunt were excluded. From May 1997 until March 1999, no antibiotic prophylaxis was prescribed for scheduled, clean, lasting less than 4 hours craniotomies, whereas emergency, clean-contaminated, or long-lasting craniotomies received cloxacillin or amoxicillin-clavulanate. From April 1999 until December 2003, prophylaxis was given to every craniotomy. Independent risk factors for meningitis were studied by a multivariate analysis. Efficacy of antibiotic prophylaxis in preventing meningitis was studied as well as consequences on bacterial flora. RESULTS The overall meningitis rate was 1.52%. Independent risk factors were cerebrospinal fluid leakage, concomitant incision infection, male sex, and surgical duration. Antibiotic prophylaxis reduced incision infections from 8.8% down to 4.6% (P < 0.0001) but did not prevent meningitis: 1.63% in patients without antibiotic prophylaxis and 1.50% in those who received prophylaxis. Bacteria responsible for meningitis were mainly noncutaneous in patients receiving antibiotics and cutaneous in patients without prophylaxis. In the former, microorganisms tended to be less susceptible to the prophylactic antibiotics administered. Mortality rate was higher in meningitis caused by noncutaneous bacteria as compared with those caused by cutaneous microorganisms. CONCLUSION Perioperative antibiotic prophylaxis, although clearly effective for the prevention of incision infections, does not prevent meningitis and tends to select prophylaxis resistant microorganisms.

Epidemiology of biliary atresia in France: a national study 1986-96

BACKGROUND/AIMS The reported incidence of biliary atresia varies from 5 to 32/100000 live births. The existence of seasonality and/or clustering is controversial. Based on a large population analysis, we examined the incidence of biliary atresia in France, and the space-time distribution of cases. METHODS All patients with biliary atresia living in France and born in the years 1986-96 were recorded. Geographic distribution, seasonality, time clustering and space-time clustering were analysed. Statistical analysis used the Chi square test, the Spearman nonparametric correlation test, the Walter and Elwood test for seasonality of events and Knox analysis for time and space-time clustering. RESULTS We identified 461 patients: 421 born in metropolitan France (incidence 5.12 [4.63-5.61]/100000 live births), and 40 born in overseas territories. No significant regional variation in incidence was found in metropolitan France, while the incidence was higher in French Polynesia (incidence 29.4 [15.4-43.3]/100000 live births) (p<0.001). Seasonality, time-clustering and time-space clustering could not be demonstrated. CONCLUSIONS 1) The incidence of BA was 5.7-fold higher in Polynesia than in metropolitan France. 2) Neither seasonal variation in incidence nor clustering was identified.

Clinical and Molecular Characterization of a Cohort of 161 Unrelated Women with Nonclassical Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency and 330 Family Members

CONTEXT Nonclassical congenital adrenal hyperplasia (NC-CAH) due to partial 21-hydroxylase deficiency is one of the most frequent autosomal recessive diseases. OBJECTIVE The aim of this study was to determine the genotype/phenotype relationship in probands and family members. PATIENTS AND METHODS A total of 161 NC-CAH unrelated women diagnosed on late-onset symptoms, mainly hirsutism, and post-ACTH 17-hydroxyprogesterone more than 10 ng/ml, and 330 of their relatives was explored. CYP21A2 was genotyped in 124 probands. RESULTS The most frequent mutation was V281L. One severe mutation was found in 63.7% of probands, and surprisingly two severe mutations in four probands. Contrasting with the absence of clinical differences, basal testosterone, and androstenedione, basal and post-ACTH 17-hydroxyprogesterone were significantly higher in probands carrying at least one severe mutation than in those with two mild mutations (P < 0.01). Among the 330 family members, 51 were homozygotes or compound heterozygotes, and 42 were clinically asymptomatic; 242 were heterozygotes and 37 unaffected. Post-ACTH 21-deoxycortisol (21dF) was significantly higher in heterozygotes than in unaffected, however, an overlap existed. In 12 heterozygotes, post-ACTH 21dF was below 0.55 ng/ml, the cutoff value usually accepted for suggesting heterozygosity. CONCLUSIONS The study of family members underlines the variable expression of NC-CAH even within a family, suggesting that modifier factors may modulate phenotype expression. Post-ACTH 21dF cannot reliably detect heterozygous subjects. Considering the high frequency of heterozygotes in the general population, it is essential to genotype the partner(s) of the patients with one severe mutation to offer genetic counseling.

Efficacy of High-dose Nebulized Colistin in Ventilator-associated Pneumonia Caused by Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii

Background:Colistin often remains the only active agent against multidrug-resistant Gram-negative pathogens. The aim of the study was to assess efficacy of nebulized colistin for treating ventilator-associated pneumonia (VAP) caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Methods:One hundred and sixty-five patients with VAP caused by P. aeruginosa and A. baumannii were enrolled in a prospective, observational, and comparative study. The sensitive strain group included 122 patients with VAP caused by P. aeruginosa and A. baumannii susceptible to &bgr;-lactams, aminoglycosides, or quinolones and treated with intravenous antibiotics for 14 days. The multidrug-resistant strain group included 43 patients with VAP caused by multidrug-resistant P. aeruginosa and A. baumannii and treated with nebulized colistin (5 million international units every 8 h) either in monotherapy (n = 28) or combined to a 3-day intravenous aminoglycosides for 7–19 days. The primary endpoint was clinical cure rate. Aerosol was delivered using vibrating plate nebulizer. Results:After treatment, clinical cure rate was 66% in sensitive strain group and 67% in multidrug-resistant strain group (difference −1%, lower limit of 95% CI for difference −12.6%). Mortality was not different between groups (23 vs. 16%). Among 16 patients with persisting or recurrent P. aeruginosa infection, colistin minimum inhibitory concentration increased in two patients. Conclusion:Nebulization of high-dose colistin was effective to treat VAP caused by multidrug-resistant P. aeruginosa or A. baumannii. Its therapeutic effect was noninferior to intravenous &bgr;-lactams associated with aminoglycosides or quinolones for treating VAP caused by susceptible P. aeruginosa and A. baumannii.

MALDI-TOF MS-based drug susceptibility testing of pathogens: The example of Candida albicans and fluconazole

MALDI‐TOF MS can be used for the identification of microorganism species. We have extended its application to a novel assay of Candida albicans susceptibility to fluconazole, based on monitoring modifications of the proteome of yeast cells grown in the presence of varying drug concentrations. The method was accurate, and reliable, and showed full agreement with the Clinical Laboratory Standards Institutes reference method. This proof‐of‐concept demonstration highlights the potential for this approach to test other pathogens.

Fertility in Women with Nonclassical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

OBJECTIVE In contrast to subfertility often reported in women suffering from the classical form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, fertility in nonclassical CAH (NC-CAH) has been rarely studied. Our objective was to evaluate fertility in NC-CAH women. MATERIAL AND METHODS We studied 190 NC-CAH women (161 probands + 29 first degree relatives). Only 20 probands had consulted for infertility (12%), either alone or associated with hirsutism or menstrual cycle disorders. The diagnosis was established on post-ACTH 17-hydroxyprogesterone 10 ng/ml or greater and further characterized by CYP21A2 gene analysis. RESULTS Ninety-five of the 190 women wanted pregnancy (aged 26.7 +/- 8.9 yr); 187 pregnancies occurred in 85 women, which resulted in 141 births in 82 of them. Ninety-nine pregnancies (52.9%) occurred before the diagnosis of NC-CAH (96 spontaneously and three with ovulation inducers) whereas 98 occurred after diagnosis (11 spontaneously and 77 with hydrocortisone treatment); 83% of pregnancies were obtained within 1 yr. The rate of miscarriages was 6.5% for pregnancies obtained with glucocorticoid treatment vs. 26.3% without. Two of the 141 infants (1.5%) were born with classical CAH. CONCLUSION Subfertility is mild in NC-CAH. However, the rate of miscarriages is lower in pregnancies occurring with glucocorticoid treatment and argues for treating NC-CAH women wanting pregnancy. In addition, considering the high rate of heterozygotes for CYP21A2 mutations in the general population, it is essential to genotype the partner of patients with a severe mutation to predict the risk of classical CAH and offer genetic counseling.

Rapid species diagnosis for invasive candidiasis using mass spectrometry.

Background Matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI TOF-MS) allows the identification of most bacteria and an increasing number of fungi. The potential for the highest clinical benefit of such methods would be in severe acute infections that require prompt treatment adapted to the infecting species. Our objective was to determine whether yeasts could be identified directly from a positive blood culture, avoiding the 1–3 days subculture step currently required before any therapeutic adjustments can be made. Methodology/Principal Findings Using human blood spiked with Candida albicans to simulate blood cultures, we optimized protocols to obtain MALDI TOF-MS fingerprints where signals from blood proteins are reduced. Simulated cultures elaborated using a set of 12 strains belonging to 6 different species were then tested. Quantifiable spectral differences in the 5000–7400 Da mass range allowed to discriminate between these species and to build a reference database. The validation of the method and the statistical approach to spectral analysis were conducted using individual simulated blood cultures of 36 additional strains (six for each species). Correct identification of the species of these strains was obtained. Conclusions/Significance Direct MALDI TOF-MS analysis of aliquots from positive blood cultures allowed rapid and accurate identification of the main Candida species, thus obviating the need for sub-culturing on specific media. Subsequent to this proof-of-principle demonstration, the method can be extended to other clinically relevant yeast species, and applied to an adequate number of clinical samples in order to establish its potential to improve antimicrobial management of patients with fungemia.

Improving outcomes of biliary atresia: French national series 1986-2009.

BACKGROUND & AIMS This study analyses the prognosis of biliary atresia (BA) in France since liver transplantation (LT) became widely available. METHODS The charts of all BA patients living in France and born between 1986 and 2009 were reviewed. Patients were divided into 3 cohorts according to their years of birth: 1986-1996, 1997-2002, and 2003-2009. RESULTS 1107 BA children were identified, 990 born in metropolitan France (incidence 1/18,400 live births). Kasai operation was performed in 1044 (94%), leading to complete clearance of jaundice (total serum bilirubin ≤ 20 μmol/L) in 38% of patients. Survival with native liver (SNL) after Kasai operation was 40%, 36%, and 30% at 5, 10, and 20 years, stable in the 3 cohorts. Median age at Kasai operation was 59 days, unchanged over time. Twenty-year SNL was 39%, 32%, 28%, and 19% after Kasai operation performed in the first, second, third months of life or thereafter (p=0.0002). 588 children underwent 692 LTs. Mortality without transplantation decreased over time: 16%, 7%, and 4% in the 3 cohorts (p<0.0001). Survival after transplantation was 83%, 82%, and 77% at 5, 10, and 20 years in the whole series. Five-year post-transplant survival was 75%, 90%, and 89% in the 3 cohorts (p<0.0001). In the whole series, overall BA patient survival was 81%, 80%, and 77% at 5, 10, and 20 years. Five-year BA patient overall survival increased over time: 72%, 88%, and 89% in the 3 cohorts (p<0.0001). CONCLUSIONS BA patients currently have an 89% live expectancy, and a 30% chance to reach adulthood without transplantation. Early Kasai operation, without age threshold, reduces the need for liver transplantation until adulthood.

Repetitive Behaviours in Patients with Gilles de la Tourette Syndrome: Tics, Compulsions, or Both?

Background Repetitive behaviours (RB) in patients with Gilles de la Tourette syndrome (GTS) are frequent. However, a controversy persists whether they are manifestations of obssessive-compulsive disorder (OCD) or correspond to complex tics. Methods 166 consecutive patients with GTS aged 15–68 years were recruited and submitted to extensive neurological, psychiatric and psychological evaluations. RB were evaluated by the YBOCS symptom checklist and Mini International Neuropsychiatric Interview (M.I.N.I), and classified on the basis of a semi-directive psychiatric interview as compulsions or tics. Results RB were present in 64.4% of patients with GTS (107/166) and categorised into 3 major groups: a ‘tic-like’ group (24.3%–40/166) characterised by RB such as touching, counting, ‘just right’ and symmetry searching; an ‘OCD-like’ group (20.5%–34/166) with washing and checking rituals; and a ‘mixed’ group (13.2%–22/166) with both ‘tics-like’ and ‘OCD-like’ types of RB present in the same patient. In 6.3% of patients, RB could not be classified into any of these groups and were thus considered ‘undetermined’. Conclusions The results confirm the phenomenological heterogeneity of RB in GTS patients and allows to distinguish two types: tic-like behaviours which are very likely an integral part of GTS; and OCD-like behaviours, which can be considered as a comorbid condition of GTS and were correlated with higher score of complex tics, neuroleptic and SSRIs treatment frequency and less successful socio-professional adaptation. We suggest that a meticulous semiological analysis of RB in GTS patients will help to tailor treatment and allow to better classify patients for future pathophysiologic studies. Trial Registration ClinicalTrials.gov NCT00169351