Effectiveness of antibacterial prophylaxis in children with acute leukemia: A report from a single institution over a 20-year period.

BACKGROUND: Infection is the major cause of treatment-related mortality in childhood acute leukemia, mainly due to bacterial translocation across the intestinal mucosa. Only a few studies have reported the impact of different antibacterial prophylaxis treatments on digestive tract flora and infection-related mortality. PROCEDURES: We performed a retrospective analysis of two different digestive tract decontamination modalities (selective or total digestive decontamination) in a large single-center series of 323 children during the induction treatment of acute leukemia between January 1995 and December 2014. We examined the impact of antibiotic prophylaxis and food regimen (sterile or selected) on the digestive tract flora during the period of antibacterial prophylaxis, on the frequency of bacteremia, and on antibiotic sensitivity. RESULTS: Only one Gram-negative (Klebsiella pneumonia) translocation occurred in the SDD group. No infection-related death occurred. Extended-spectrum beta-lactamase (ESBL) bacteria were observed in seven of 170 (4%) patients in the SDD group. The faecal-flora total suppression and faecal-flora Gram-negative bacilli suppression was 67 and 77%, respectively, in the TDD group with sterile food, 0 and 58%, respectively, in the SDD group with sterile food, and 6 and 63%, respectively, in the SDD group with selective food. CONCLUSIONS: This study gives a rationale not to use antibacterial prophylaxis systematically in children who receive induction treatment for acute leukemia; additionally, antibiotics should only be used in case of stool contamination by highly pathogenic bacteria with a high potential of translocation.

How to improve the collection and analysis of hospital antibiotic consumption: preliminary results of the ConsoRes software experimental implementation.

OBJECTIVE: The online software ConsoRes is used to collect and analyze data on antibiotic consumption and evolution of bacterial resistance in healthcare institutions in every hospital ward (HW). We report the first results of ConsoRes implementation in the northeast hospitals of France. METHODOLOGY: ConsoRes was implemented in January 2011, in nine volunteer hospitals after performing an onsite assessment. Five of these hospitals were already monitoring antibiotic consumption with a network such as Raisin ATB or Antibiolor, providing feedback on the various evaluation tools. RESULTS: The ConsoRes data collection import function meets expectations of pharmacists, bacteriologists, or clinicians since it is user friendly, prevents redundant data input, and allows data transfer to the national databases. Importing the hospital organizational structure prevents mistakes on consumption allocation, which was noted in the previous databases, and makes comparison and benchmark analysis reliable. ConsoRes also provides a rapid consumption data feedback to all registered users within the hospital, whether in charge of a ward (clinician) or having a transversal function (pharmacist, bacteriologist). The availability of an automatic standard report or of an online customized report is another major feature of ConsoRes. CONCLUSION: Besides providing surveillance, the concomitant analysis of local antibiotic consumption and bacterial resistance should have an educational impact by allowing each user to implement actions within the framework of antibiotic stewardship.

Desulfovibrio spp. survive within KB cells and modulate inflammatory responses.

Desulfovibrio are sulfate-reducing anaerobic gram-negative rods that have been proposed as potential periodontopathogens. We investigated the capacity of Desulfovibrio to invade epithelial cells and induce cytokine secretion from these cells. Desulfovibrio strains were co-cultured with KB cells and counts of intracellular bacteria evaluated up to 3 days after infection. Desulfovibrio desulfuricans and Desulfovibrio fairfieldensis were able to survive within epithelial cells. Intracytoplasmic location of both bacterial species was confirmed by confocal laser scanning microscopy and transmission electron microscopy. Invasion was sensitive to nocodazole, an inhibitor of microtubule polymerization, but not to cytochalasin D, a microfilament inhibitor, suggesting that microtubule rearrangements were involved in the internalization of Desulfovibrio strains by KB cells. Infection by Desulfovibrio resulted in increased production of IL-6 and IL-8 by KB cells. The ability of D. desulfuricans and D. fairfieldensis to survive within oral epithelial cells and to modulate the epithelial immune response may contribute to the initiation and progression of periodontal diseases.

Metronidazole resistance in Prevotella spp. and description of a new nim gene in Prevotella baroniae.

Nonduplicate clinical isolates of Prevotella spp. recovered from patients hospitalized between 2003 and 2006 in two French tertiary-care teaching hospitals were investigated for their susceptibility to metronidazole and the presence of nim genes. Of the 188 strains tested, 3 isolates displayed reduced susceptibility to metronidazole after 48 h of incubation, while 27 additional isolates exhibited heterogeneous resistance after prolonged incubation; all 30 of the isolates were nim negative. Among the remaining 158 isolates, 7 nim-positive isolates were detected. All of these strains were identified as Prevotella baroniae by 16S rRNA gene sequence analysis and contained a new nim gene, named nimI, as determined by DNA sequence analysis. Chromosomal localization of this single-copy gene was demonstrated in all clinical isolates as well as in type strain P. baroniae DSM 16972 by using Southern hybridization. No known associated insertion sequence elements were detected upstream of the nimI gene in any of the nim-positive strains by PCR mapping. After prolonged exposure to metronidazole, stable resistant subpopulations could be selected in nimI-positive Prevotella isolates (n = 6) as well as in nim-negative Prevotella isolates (n = 6), irrespective of their initial susceptibility to this antibiotic. This study is the first description of a new nitroimidazole resistance gene in P. baroniae which seems to be silent and which might be intrinsic in this species. Moreover, our findings highlight the fact that high-level resistance to metronidazole may be easily induced in both nim-positive and nim-negative Prevotella sp. strains.

[Glycopeptide-resistant Enterococcus outbreak in an ICU with simultaneous circulation of two different clones]. / Epidémie en réanimation médicochirurgicale d'Enterococcus faecium résistants aux glycopeptides (ERG) avec cocirculation de deux clones différents.

AIM OF THE STUDY: To describe specific difficulties to control a glycopeptide-resistant Enterococcus (GRE) outbreak occurring in an intensive care unit (ICU) during a regional epidemy. PATIENTS AND METHODS: Following identification of a GRE clinical isolate in ICU, systematic screening was performed on admission and then weekly, by anal swabs. GRE carriers were isolated according to two processes: first (week [W] 2-W8), cohorting of carriers in a dedicated sector of the ICU, with dedicated HCW; this required closing four of the 16 ICU beds. Second (W8-W29), a specific unit was created outside the ICU. VanA-genotypes and pulsed-field gel electrophoresis (PFGE) profiles were analyzed. RESULTS: During the first outbreak period (102 rectal swabs), two patients were found colonized at admission: the index case transferred from Nancy hospital, carrier of the Nancy epidemy PFGE profile strain, and one patient from the haemodialysis unit, carrier of a GRE strain presenting a different PFGE profile called the Thionville strain. Seven patients were newly identified as GRE colonized (2 by the Nancy strain and 5 by the Thionville strain). Defective running of the ICU was noted. During the second period (442 samples), six ICU patients were found colonized, including four at admission. No other case was identified in 16 weeks. Outbreak extension to other hospital units was checked at W19. The Thionville strain was not found in other regional hospitals. CONCLUSION: ICUs concentrate GRE colonization risk. This study demonstrates interest of PFGE. These low virulence bacteria have few direct pathological consequences, but they cause organizational problems in ICUs.

Prevotella nanceiensis sp. nov., isolated from human clinical samples.

Three strains of anaerobic, non-pigmented, Gram-negative bacilli isolated from various human clinical samples were characterized in terms of phenotypic and genotypic tests, including sequence analysis of 16S rRNA and rpoB genes. The strains were most closely related to the type strains of Prevotella marshii and Prevotella shahii on the basis of both 16S rRNA (89.8 and 89.0 % identity, respectively) and rpoB gene sequences (83.1 and 82.8 % identity, respectively). Phylogenetic analysis showed that the isolates constituted a robust homogeneous group distinct from known species in the genus Prevotella. The rrn skeleton (as determined by PFGE) and the DNA G+C content, determined to be 39.4 mol% for strain LBN 293(T), distinguished the novel isolates from the type strains of P. marshii and P. shahii. The three strains were saccharolytic and produced acetic, lactic and succinic acids as major metabolic end products. Polyphasic investigations supported the proposal of a novel species, Prevotella nanceiensis sp. nov., with LBN 293(T) (=AIP 261.03(T) =CIP 108993(T) =CCUG 54409(T)) as the type strain.

Respiratory infections associated with nontuberculous mycobacteria in non-HIV patients.

The incidence of nontuberculous mycobacteria (NTM) pulmonary diseases in HIV-negative patients was studied prospectively from January 1, 2001 to December 31, 2003 by 32 sentinel sites distributed throughout France. In total, 262 patients who yielded NTM isolates from respiratory clinical specimens, met the bacteriological, radiological and clinical criteria established by the American Thoracic Society for NTM respiratory disease. Among the 262 NTM isolates, 234 were slow-growing mycobacteria (125 Mycobacterium avium-intracellulare complex (MAC), 66 M. xenopi, 34 M. kansasii) and 28 were rapidly growing mycobacteria (25 M. abscessus complex). In the Paris area, M. xenopi was the most frequently isolated species, followed by MAC. Most patients (>50%), except those with M. kansasii, had underlying predisposing factors such as pre-existing pulmonary disease or immune deficiency. Asthenia, weight loss, chronic cough and dyspnoea were the most common clinical symptoms. The classical radiological appearance of NTM infections was indistinguishable from that observed in patients with pulmonary tuberculosis. In summary, the incidence of nontuberculous mycobacteria pulmonary infections in HIV-negative patients was estimated at 0.74, 0.73 and 0.72 cases per 100,000 inhabitants in 2001, 2002 and 2003, respectively.

Antimicrobial susceptibilities of Pasteurella strains isolated from humans.

The in vitro susceptibilities of 192 consecutive clinical strains of Pasteurella spp. isolated between 1996 and 2003 from soft tissue pus (n = 146), respiratory tract specimens (n = 38) and blood (n = 8) were studied by an agar dilution method. All isolates were susceptible to minocycline, cefotaxime, ofloxacin, ciprofloxacin and levofloxacin. Most strains were susceptible to moxifloxacin, amoxicillin, azithromycin and clarithromycin, whereas lower susceptibility rates to telithromycin (89.4%) were observed among respiratory tract isolates.

Mycobacterium xenopi and drinking water biofilms.

The ability of Mycobacterium xenopi to colonize an experimental drinking water distribution system (a Propella reactor) was investigated. M. xenopi was present in the biofilm within an hour following its introduction. After 9 weeks, it was always present in the outlet water (1 to 10 CFU 100 ml(-1)) and inside the biofilm (10(2) to 10(3) CFU cm(-2)). Biofilms may be considered reservoirs for the survival of M. xenopi.

Francisella tularensis bacteremia.

Bacteremia caused by Francisella tularensis is rare and has been reported mainly in the United States and infrequently in Europe. We report herein the first case of bacteremic F. tularensis pneumonia in an immunocompetent individual in southern Europe.

Antimicrobial susceptibilities of clinical Desulfovibrio isolates.

The antimicrobial susceptibilities of 16 clinical isolates of Desulfovibrio spp. were determined. All or most isolates were susceptible to imipenem (MIC(90) [MIC at which 90% of the isolates tested were inhibited], 0.5 microg/ml), metronidazole (MIC(90), 0.25 microg/ml), clindamycin (MIC(90), 4 microg/ml), and chloramphenicol (MIC(90), 16 microg/ml) but were resistant or intermediate to penicillin G (MIC(90), 64 microg/ml), piperacillin (MIC(90), 256 microg/ml), piperacillin-tazobactam (MIC(90), 256 microg/ml), cefoxitin (MIC(90), >256 microg/ml), and cefotetan (MIC(90), 64 microg/ml). Among isolates with decreased susceptibility to beta-lactams (n = 15), only six were beta-lactamase positive and susceptible to amoxicillin-clavulanate and ticarcillin-clavulanate.

Pharmacokinetic longitudinal studies of antibiotics administered via a permanent intraosseous device in micropigs.

BACKGROUND: In critically ill children, intraosseous (IO) administration of a medicine provides an alternate vascular access route when IV access is not readily available. We investigated the short and long-term efficacy and safety of a totally intraosseously implantable device. PROCEDURE: This study was undertaken in micropigs (i) to compare serum levels achieved by equal bolus dosages of two antibiotics (amikacin and vancomycin) administered through an intratibial needle, an intraosseous implantable device and central IV routes to determine whether standard parenteral dosing guidelines for antibiotics may be applied without modification for IO injection, and (ii) to show the efficiency of the implantable device over a prolonged period, as a permanent access to intraosseous space. RESULTS: The area under the plasma concentration time curves were similar for IV, intratibial and through the intraosseous implantable device, for intermittent administrations of amikacin and vancomycin, over a period of 6 months. However, vancomycin did not reach therapeutic levels via both IO routes. We did not find any alteration of amikacin and vancomycin pharmacokinetics over a period of 6 months using the implantable device. No complication occurred. CONCLUSIONS: Long-term administration of antibiotics through a totally implantable intraosseous device is feasible and safe in micropigs. Although the procedure seems promising, additional studies of the continuous infusion of chemotherapeutic agents, blood products and antimicrobial solutions are needed prior to use in humans.

Comparison of sludge and clinical isolates of Listeria monocytogenes.

AIMS: Listeria monocytogenes strains isolated in the same geographical area from sewage sludge and from patients presenting with listeriosis were compared. METHODS AND RESULTS: All isolates were typed by serotyping, phage typing and SmaI/ApaI pulsed-field gel electrophoresis (PFGE). Among the sludge isolates (n=32), 22 subtypes could be distinguished by the combination of all typing methods. The human isolates (n=11) were distributed into 10 subtypes which clearly differed from those observed among sludge isolates, except for one cluster formed by two related human isolates which showed high similarity in PFGE patterns (SmaI: 92%; ApaI: 89.5%) with one sludge isolate. CONCLUSION: These results suggest the existence of an epidemiological link between sludge and human isolates, but they may also be reflecting the distribution of L. monocytogenes types within the environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Sludge and human L. monocytogenes may be related but further epidemiological studies are necessary to elucidate this point.

Laboratory diagnosis of Clostridium difficile-associated diarrhea and colitis: usefulness of Premier Cytoclone A+B enzyme immunoassay for combined detection of stool toxins and toxigenic C. difficile strains.

Detection of Clostridium difficile toxins A and B in stools by Premier Cytoclone A+B enzyme immunoassay (EIA) was compared with detection by stool culture for C. difficile followed by detection of toxigenic isolates using the same EIA. Chart reviews were performed to evaluate the likelihood of C. difficile-associated diarrhea and colitis (CADC) for all patients with at least one positive toxin assay. While the toxins were detected in 58 of 85 consecutive CADC patients by both assays, CADC in 5 patients was detected only by stool toxin assay, and in 22 patients CADC was detected only by toxigenic culture. Our results suggest that for laboratories using a rapid toxin A+B EIA, direct toxin detection in stools should be combined with toxigenic culture in cases in which there is a negative stool toxin assay.

Anti-Helicobacter pylori activity of Aristolochia paucinervis Pomel extracts.

The anti-Helicobacter pylori effect of the extracts and the fractions obtained from Aristolochia paucinervis rhizome and leaves were studied against a reference strain of H. pylori by using the agar dilution method. Only the methanol extracts and the hexane fractions of either the rhizome or the leaves exhibited an inhibitory activity at a concentration of < or =128 microg/ml. The leaf hexane fraction APLH demonstrated a higher inhibitory activity (MIC: 4 microg/ml) than the rhizome hexane fraction APRH (MIC: 16 microg/ml), the leaf methanol extract APLM (MIC: 32 microg/ml) and the rhizome methanol extract APRM (MIC: 128 microg/ml). This inhibitory activity was confirmed for the active extracts and fractions against clinical isolates of H. pylori (n = 20) for which MIC50) and MIC90 were determined.

Bactericidal properties of the chloroform fraction from rhizomes of Aristolochia paucinervis Pomel.

The deffated chloroform fraction (APRC) obtained from the rhizomes of Aristolochia paucinervis Pomel (Aristolochiaceae) has a high bacteriostatic activity against bacterial strains like Clostridium perfringens ATCC 13124 and Enterococcus faecalis ATCC 29212. Here, we report the bactericidal activity of APRC against both strains which was evaluated by using time-to kill assays. The results showed that APRC produced an intense time-dependent bactericidal effect against C. perfringens, achieving over a 24 h-period a 5log10-unit decrease in CFU/ml at a concentration > or =1.25 x MIC. In contrast, when tested against E. faecalis, APRC exhibited a concentration-dependent killing activity at concentrations of 1.25 x MIC and 2.5 x MIC, yielding to a decrease of 1.5 and 2.5log10-unit in CFU/ml at 4 h, respectively. However, substantial regrowth of E. faecalis occurred within 24 h. Ultrastructural alterations were observed for both exposed microorganisms by scanning and transmission electron microscopy.

In vitro synergy between cefepime and vancomycin against methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis.

The in vitro activity of cefepime combined with vancomycin was assessed by the chequerboard method against 35 clinical isolates of methicillin-susceptible (MSSA, n = 8) or -resistant (MRSA, n = 10) Staphylococcus aureus and methicillin-susceptible (MSSE, n = 9) or -resistant (MRSE, n = 8) Staphylococcus epidermidis and S. aureus ATCC 25923 (MSSA). The combination was synergic against 16 isolates and additive/indifferent against 20. For 10 of the clinical isolates (two MSSA, three MRSA, two MSSE, three MRSE) and the reference strain, the interaction of cefepime and vancomycin was also determined by the time-kill method. Except for one MRSA isolate, synergic killing was demonstrated with clinically achievable concentrations of vancomycin (0.5-1 mg/L) and cefepime (methicillin-susceptible isolates: 0.5-1 mg/L; methicillin-resistant isolates: 2-64 mg/L).

Comparison of the in vitro activity of pristinamycin and quinupristin/dalfopristin against Streptococcus pneumoniae.

The in vitro activity of quinupristin/dalfopristin, a new injectable streptogramin, and pristinamycin was evaluated against 200 recently isolated clinical Streptococcus pneumoniae strains expressing various degrees of susceptibility to penicillin G and erythromycin. MICs were determined by the agar dilution method. All strains were susceptible to pristinamycin irrespective of their susceptibility to penicillin G or erythromycin (MIC90: 0.25 mg/L for each phenotype). The activity of quinupristin/dalfopristin was slightly lower than that of pristinamycin against 42 penicillin G-susceptible/erythromycin-susceptible strains (MIC90: 0.5 mg/L), 13 penicillin G-susceptible/erythromycin-resistant strains (MIC90: 1 mg/L), 25 penicillin G-intermediate or -resistant/erythromycin-susceptible strains (MIC90: 0.5 mg/L) and 120 penicillin G-intermediate or -resistant/erythromycin-resistant strains (MIC90: 0.5 mg/L). The activity of both streptogramins was not significantly altered in case of erythromycin resistance. Thus, both streptogramins might be useful for the treatment of penumococcal infections, especially in cases of multiresistant strains.

Acid secretion and response to pentagastrin or omeprazole in human fetal stomach xenografts.

BACKGROUND: The dual capacity of stomach tissue to secrete acid and to respond to secretagogues is indicative of the terminal stages of gastric functional maturation. In this study 6- to 10-week-old human fetal stomachs xenografted into nude mice were used to study parietal cells' functional maturation. METHODS: Thirty-four transplants were microsurgically grafted either inside a pouch created on the nude peritoneum (n = 15) or on the host stomach and esophagus (n = 19). The mucosa of transplanted tissues was analyzed by immunohistochemical techniques to detect gastric cells. Gastric cell secretions were collected before and after pentagastrin or omeprazole treatment. RESULTS: Parietal, G, and D cells were detected immunohistochemically only after 1 month of grafting. All xenografts actively secreted acid after 1 or 2 months' transplantation at each graft site. Acid secretion was significantly stimulated by intraperitoneally injected pentagastrin (mean pH +/- SD, 3.2 +/- 0.7 vs. 2.0 +/- 0.5; n = 10, P = 0.005) and was dramatically inhibited by intragastrically administered omeprazole (2.3 +/- 0.6 vs. 6.5 +/- 0.7; n = 15, P = 0.0007) after 5 hours. CONCLUSION: Stomach xenografts were able to develop normally. Parietal cells were physiologically mature with functional proton pumps and active gastrin receptors, as demonstrated after omeprazole and pentagastrin treatment, respectively. Because stomach xenografts matured very rapidly, it is possible that a stomach xenograft model can be used for further studies on the functional maturation of human gastric epithelial cells, as well as the factors that influence this maturation in humans.