Laurent Raskine

Selective decontamination of the digestive tract in neurosurgical intensive care unit patients: a double-blind, randomized, placebo-controlled study.

The aim of this study was to assess, in a selected population, the effects of selective decontamination of the digestive tract on colonization of the oropharynx, trachea, stomach and rectum, and on the infection rate. An economical assessment was also performed. Design:A prospective, double-blind, randomized, placebo-controlled, dual-center trial. Setting:Two neurosurgical intensive care units. Patients:A total of 191 comatose patients admitted emergently and intubated within <24 hrs were enrolled. Of these patients, 68 were excluded because they either died, got an early infection, or were extubated within the first 5 days. A total of 123 patients were analyzed: 63 treated and 60 placebo patients. Interventions:Topical antibiotics (tobramycin, polymyxin E, amphotericin B) were applied in the oropharynx and in the stomach. Vanco-mycin was added in the oropharyngeal paste. Placebo patients received the same regimen (i.e., a suspension of fluid and a paste) but without antibiotics. No parenteral antibiotics were given during the study period. Measurements and Main Results:Broncho-pneumonia episodes were diagnosed with protected specimen brush or plugged telescoping catheter and other infections were diagnosed according to the Center for Disease Control of Atlanta criteria. Antibiotic costs and cost per survivor were calculated.Selective decontamination of the digestive tract significantly reduced Gram-negative bacilli colonization as well as the number of episodes of bronchopneumonia, urinary tract infections, and sinusitis. Despite the addition of vancomycin, Staphylococcus aureus remained the main potential pathogen causing tracheal colonization and subsequent bronchopneumonia. The reduction in bronchopneumonia rate was observed in head-trauma patients only. We were able to show that: a) the trachea was the main reservoir of microorganisms responsible for pneumonia; b) pneumonia developed after tracheal colonization. Total charges for antibiotics were 2.8 times higher in the treated group than in the placebo group; in calculating the cost per survivor, selective decontamination of the digestive tract might be beneficial due to the reduced length of stay. Conclusions:Selective decontamination of the digestive tract is an effective technique in reducing infectious morbidity in comatose neurosurgical patients. Because of its cost, this technique should be used only in selected populations. (Crit Care Med 1993; 21:1466–1473)

Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome.

Objective:Small intestinal bacterial overgrowth syndrome (SIBOS) is characterized by an abnormally high bacterial population level in the upper gut, exceeding 105 organisms/ml (5 log colony-forming unit (CFU)/ml). To understand its origin and select an appropriate antibiotic treatment, we have analyzed the bacterial populations contaminating the upper gut in SIBOS patients.Methods:Jejunal samples of 63 consecutive patients with diarrhea or malabsorption and conditions predisposing to SIBOS were cultured and antibiotic sensitivities determined.Results:Concentrations of total, microaerophilic, and anaerobic bacteria were confirmed in 55 patients with SIBOS (mean ± SE) 7.6 ± 0.8, 7.4 ± 0.9, and 6.1 ± 0.7 log CFU/ml, respectively. Mean number of bacterial genera was 4.6 ± 0.8. The main bacteria recovered were (mean ± SE log CFU/ml) Streptococcus (71%; 6.4 ± 0.8), Escherichia coli (69%; 7.2 ± 0.9), Staphylococcus (25%; 6.2 ± 0.6), Micrococcus (22%; 6.0 ± 0.7), Klebsiella (20%; 7.1 ± 0.8), Proteus (11%; 6.1 ± 0.8) for microaerophilic bacteria, and Lactobacillus (75%; 6.1 ± 1.1), Bacteroides (29%; 6.9 ± 1.3), Clostridium (25%; 5.5 ± 1.0), Veillonella (25%; 5.3 ± 0.7), Fusobacterium (13%; 4.8 ± 0.5), and Peptostreptococcus (13%; 6.1 ± 0.7) for anaerobic bacteria. Amoxicillin–clavulanic acid and cefoxitin were efficient on >90% of strains.Conclusions:Contaminating flora isolated in SIBOS include commonly identified oropharyngeal and colonic flora, but these occur in SIBOS at different levels from those usually found in their original location. These data may hopefully serve as a starting point to further therapeutic controlled studies.

The capacity of short-chain fructo-oligosaccharides to stimulate faecal bifidobacteria: a dose-response relationship study in healthy humans.

BackgroundShort-chain fructo-oligosaccharides (scFOS) are well-known for their bifidogenicity. In a large study comprising 200 healthy volunteers, we determined the bifidogenic properties of 7 non-digestible carbohydrates administered at a dose of 10 g/d in the diet; we analysed dose-response relationships of the bifidogenic substrates at doses ranging from 2.5 to 10 g/d in comparison with a placebo. The aim of this presentation is to give more details about the dose-response effects of short-chain fructo-oligosaccharides (scFOS).MethodsForty healthy volunteers (18 males, 22 females) eating their usual diets were randomly divided into 5 groups of 8 subjects and received scFOS at a dose of 2.5, 5.0, 7.5 and 10 g/d or a placebo for 7 d. Stools were collected before (day (d) 8) and at the end (day (d) 15) of sugar consumption, and tolerance was evaluated using a daily chart.Results (m ± SEM)Bifidobacteria counts increase was higher in scFOS than in placebo group for all doses tested [2.5 g/d (from 9.15 ± 0.59 to 9.39 ± 0.70; P = 0.02); 5 g/d (from 10.21 ± 0.21 to 10.67 ± 0.22; P = 0.03); 7.5 g/d (from 9.28 ± 0.49 to 9.85 ± 0.35;P = 0.01); 10 g/d (from 9.00 ± 0.81 to 10.18 ± 0.60; P = 0.003)]. A significant correlation between the ingested dose of scFOS and faecal bifidobacteria counts was observed at d15 (r2 = 0.307, P < 0.001). Total anaerobes increased at the dose of 10 g/d. No significant differences were found for Bacteroides, Lactobacillus, enterobacteria or pH in any group. The frequency of digestive symptoms was not different between scFOS at any of the doses tested and placebo. Bloating was significantly more intense during scFOS ingestion at doses of 2.5 and 5 g/d, but not at doses of 7.5 and 10 g/d. Excess flatus, borborygmi and abdominal pain did not differ from the placebo at any of the doses tested.ConclusionThis study showed that scFOS is bifidogenic and well tolerated at doses ranging from 2.5 to 10 g/d, and that there is a dose-response relationship in healthy volunteers.

Compassionate Use of Bedaquiline for the Treatment of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Interim Analysis of a French Cohort

BACKGROUND Bedaquiline is a new antibiotic that was approved for the treatment of multidrug-resistant (MDR) tuberculosis. We aimed to evaluate the short-term microbiological efficacy and the tolerability profile of bedaquiline. METHODS We performed a retrospective cohort study among patients with MDR tuberculosis receiving bedaquiline for compassionate use between January 2010 and July 2013 and evaluated at 6 months of bedaquiline treatment. RESULTS A total of 35 patients with MDR tuberculosis were included in the study. Nineteen (54%) had extensively drug-resistant (XDR) tuberculosis, and 14 (40%) had isolates resistant to fluoroquinolones (Fqs) or second-line injectables. Bedaquiline was associated with a median of 4 (range, 2-5) other drugs, including linezolid in 33 (94%) cases. At 6 months of bedaquiline treatment, culture conversion was achieved in 28 of 29 (97%) cases with culture-positive pulmonary tuberculosis at bedaquiline initiation. Median time to culture conversion was 85 days (range, 8-235 days). Variables independently associated with culture conversion were treatment with a Fq (P = .01), absence of lung cavities (P < .001), and absence of hepatitis C virus infection (P = .001). A total of 7 patients (20%) experienced a ≥60-ms increase in QT interval, leading to bedaquiline discontinuation in 2 (6%) cases. Severe liver enzyme elevation occurred in 2 patients (6%). During the study period, 1 death (3%) occurred and was reported as unrelated to tuberculosis or antituberculosis treatment. CONCLUSIONS The use of bedaquiline combined with other active drugs has the potential to achieve high culture conversion rates in complicated MDR and XDR tuberculosis cases, with a reassuring safety profile at 6 months of treatment.

Robustness of two MALDI-TOF mass spectrometry systems for bacterial identification

MALDI-TOF-MS systems (Microflex-Bruker Daltonics/BioTyper™ and Axima-Assurance-Shimadzu/SARAMIS-AnagnosTec) were assessed for bacterial identification. Focusing on bacteria difficult to identify routinely, 296 strains were identified by molecular biology techniques as gold standard. MALDI-TOF-MS identification provided correct results at genus and species level for 94.9%, 83.4% and 83.8%, 65.9% with Biotyper and Saramis respectively.

Factors associated with septic shock and mortality in generalized peritonitis: comparison between community-acquired and postoperative peritonitis.

IntroductionThe risk factors associated with poor outcome in generalized peritonitis are still debated. Our aim was to analyze clinical and bacteriological factors associated with the occurrence of shock and mortality in patients with secondary generalized peritonitis.MethodsThis was a prospective observational study involving 180 consecutive patients with secondary generalized peritonitis (community-acquired and postoperative) at a single center. We recorded peri-operative occurrence of septic shock and 30-day survival rate and analyzed their associations with patients characteristics (age, gender, SAPS II, liver cirrhosis, cancer, origin of peritonitis), and microbiological/mycological data (peritoneal fluid, blood cultures).ResultsFrequency of septic shock was 41% and overall mortality rate was 19% in our cohort. Patients with septic shock had a mortality rate of 35%, versus 8% for patients without shock. Septic shock occurrence and mortality rate were not different between community-acquired and postoperative peritonitis. Age over 65, two or more microorganisms, or anaerobes in peritoneal fluid culture were independent risk factors of shock. In the subgroup of peritonitis with septic shock, biliary origin was independently associated with increased mortality. In addition, intraperitoneal yeasts and Enterococci were associated with septic shock in community-acquired peritonitis. Yeasts in the peritoneal fluid of postoperative peritonitis were also an independent risk factor of death in patients with septic shock.ConclusionsUnlike previous studies, we observed no difference in incidence of shock and prognosis between community-acquired and postoperative peritonitis. Our findings support the deleterious role of Enterococcus species and yeasts in peritoneal fluid, reinforcing the need for prospective trials evaluating systematic treatment against these microorganisms in patients with secondary peritonitis.

Klebsiella oxytoca as an agent of antibiotic-associated hemorrhagic colitis.

BACKGROUND & AIMS Klebsiella oxytoca has been isolated from stools and colonic biopsy specimens of patients with Clostridium difficile-negative antibiotic-associated hemorrhagic colitis (AAHC), but the pathogenic role of the germ has not been established. The purpose of this study was to investigate the presence of K. oxytoca in patients with AAHC from a prospective cohort of patients with acute colitis, and to test the cytotoxicity on HEp-2 cells of K. oxytoca strains from patients with AAHC and healthy carriers. METHODS Colonic biopsy specimens and a sample of colonic fluid from 93 consecutive patients with acute colitis were cultured on selective media for 7 established pathogens and K. oxytoca. The 2 K. oxytoca strains isolated in the 4 patients with C. difficile-negative AAHC of this cohort and 105 additional K. oxytoca strains from patients with C. difficile-negative AAHC (n = 15) and healthy carriers (n = 90) were tested for cytotoxicity using a HEp-2 cell culture assay. RESULTS K. oxytoca was isolated in 50% (2 of 4) of the patients of the prospective cohort with C. difficile-negative AAHC compared with 2% (1 of 41) of the patients with acute colitis caused by established pathogens (P = 0.02). The rate of cytotoxic strains of K. oxytoca was higher in patients with AAHC (82%) than in healthy carriers (42%, P = 0.003). CONCLUSIONS We conclude that K. oxytoca is isolated with a significant high rate in patients with C. difficile-negative AAHC, and that K. oxytoca strains from patients with AAHC are cytotoxic more frequently on HEp-2 cells than strains from healthy carriers. These results strengthen the hypothesis of a causative role of K. oxytoca in some of the patients with AAHC.

Selection during Cefepime Treatment of a New Cephalosporinase Variant with Extended-Spectrum Resistance to Cefepime in an Enterobacter aerogenes Clinical Isolate

ABSTRACT Enterobacter aerogenes resistant to cefepime (MIC, 32 μg/ml) was isolated from a patient treated with cefepime for an infection caused by a strain of E. aerogenes overproducing its AmpC β-lactamase (MIC of cefepime, 0.5 μg/ml). The AmpC β-lactamase of the resistant strain had an L-293-P amino acid substitution and a high kcat/Km ratio for cefepime. Both of these modifications were necessary for resistance to cefepime.

Classification Algorithm for Subspecies Identification within the Mycobacterium abscessus Species, Based on Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

ABSTRACT Mycobacterium abscessus, as a species, has been increasingly implicated in respiratory infections, notably in cystic fibrosis patients. The species comprises 3 subspecies, which can be difficult to identify. Since they differ in antibiotic susceptibility and clinical relevance, developing a routine diagnostic tool discriminating Mycobacterium abscessus at the subspecies level is a real challenge. Forty-three Mycobacterium abscessus species isolates, previously identified by multilocus sequence typing, were analyzed by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). A subspecies identification algorithm, based on five discriminating peaks, was drawn up and validated by blind identification of a further 49 strains, 94% of which (n = 46) were correctly identified. Two M. abscessus subsp. massiliense strains were misidentified as M. abscessus subsp. abscessus, and for 1 other strain identification failed. Inter- and intralaboratory reproducibility tests were conclusive. This study presents, for the first time, a classification algorithm for MALDI-TOF MS identification of the 3 M. abscessus subspecies. MALDI-TOF MS proved effective in discriminating within the M. abscessus species and might be easily integrated into the workflow of microbiology labs.

Evaluation of the βLacta Test, a Rapid Test Detecting Resistance to Third-Generation Cephalosporins in Clinical Strains of Enterobacteriaceae

ABSTRACT For decades, third-generation cephalosporins (3GC) have been major drugs used to treat infections due to Enterobacteriaceae; growing resistance to these antibiotics makes the rapid detection of such resistance important. The βLacta test is a chromogenic test developed for detecting 3GC-resistant isolates from cultures on solid media within 15 min. A multicenter prospective study conducted in 5 French and Belgian hospitals evaluated the performance of this test on clinical isolates. Based on antibiotic susceptibility testing, strains resistant or intermediate to cefotaxime or ceftazidime were classified as 3GC resistant, and molecular characterization of this resistance was performed. The rates of 3GC resistance were 13.9% (332/2,387) globally, 9.4% in Escherichia coli (132/1,403), 25.6% in Klebsiella pneumoniae (84/328), 30.3% in species naturally producing inducible AmpC beta-lactamases (109/360), and 5.6% in Klebsiella oxytoca and Citrobacter koseri (7/124). The sensitivities and specificities of the βLacta test were, respectively, 87.7% and 99.6% overall, 96% and 100% for E. coli and K. pneumoniae, and 67.4% and 99.6% for species naturally producing inducible AmpC beta-lactamase. False-negative results were mainly related to 3GC-resistant strains producing AmpC beta-lactamase. Interestingly, the test was positive for all 3GC-resistant extended-spectrum beta-lactamase-producing isolates (n = 241). The positive predictive value was 97% and remained at ≥96% for prevalences of 3GC resistance ranging between 10 and 30%. The negative predictive values were 99% for E. coli and K. pneumoniae and 89% for the species producing inducible AmpC beta-lactamase. In conclusion, the βLacta test was found to be easy to use and efficient for the prediction of resistance to third-generation cephalosporins, particularly in extended-spectrum beta-lactamase-producing strains.