PK/PD modeling of flunixin meglumine in a kaolin-induced inflammation model in piglets.

Flunixin is marketed in several countries for analgesia in adult swine but little is known about its efficacy in piglets. Thirty-two piglets (6-8 days old) were randomized to receive placebo saline (n = 11, group CONTROL) or flunixin meglumine intravenously at 2.2 (n = 11, group MEDIUM) or 4.4 (n = 10, group HIGH) mg/kg, 10 hr after subcutaneous injection of kaolin in the left metacarpal area. A hand-held algometer was used to determine each piglet's mechanical nociceptive threshold (MNT) from both front feet up to 50 hr after treatment (cut-off value of 24.5 newton). Serial venous blood samples were obtained to quantify flunixin in plasma using LC-MS/MS. A PKPD model describing the effect of flunixin on the mechanical nociceptive threshold was obtained based on an inhibitory indirect response model. A two-compartmental PK model was used. A significant effect of flunixin was observed for both doses compared to control group, with 4.4 mg/kg showing the most relevant (6-10 newton) and long-lasting effect (34 hr). The median IC50 was 6.78 and 2.63 mg/ml in groups MEDIUM and HIGH, respectively. The ED50 in this model was 6.6 mg/kg. Flunixin exhibited marked antinociceptive effect on kaolin-induced inflammatory hyperalgesia in piglets.

Antibiotic content of selective culture media for isolation of Capnocytophaga species from oral polymicrobial samples.

UNLABELLED: In oral microbiome, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of fastidious Capnocytophaga species. The performances of six culture media (blood agar, chocolate blood agar, VCAT medium, CAPE medium, bacitracin chocolate blood agar and VK medium) were compared with literature data concerning five other media (FAA, LB, TSBV, CapR and TBBP media). To understand variable growth on selective media, the MICs of each antimicrobial agent contained in this different media (colistin, kanamycin, trimethoprim, trimethoprim-sulfamethoxazole, vancomycin, aztreonam and bacitracin) were determined for all Capnocytophaga species. Overall, VCAT medium (Columbia, 10% cooked horse blood, polyvitaminic supplement, 3·75 mg l(-1) of colistin, 1·5 mg l(-1) of trimethoprim, 1 mg l(-1) of vancomycin and 0·5 mg l(-1) of amphotericin B, Oxoid, France) was the more efficient selective medium, with regard to the detection of Capnocytophaga species from oral samples (P < 0·001) and the elimination of commensal clinical species (P < 0·001). The demonstrated superiority of VCAT medium, related to its antibiotic content, made its use indispensable for the optimal isolation of Capnocytophaga species from polymicrobial samples. SIGNIFICANCE AND IMPACT OF THE STUDY: Isolation of Capnocytophaga species is important for the proper diagnosis and treatment of the systemic infections they cause and for epidemiological studies of periodontal flora. We showed that in pure culture, a simple blood agar allowed the growth of all Capnocytophaga species. Nonetheless, in oral samples, because of the abundance of commensal competitive flora, selective media with antibiotics are necessary for the recovery of Capnocytophaga species. The demonstrated superiority of VCAT medium made its use essential for the optimal detection of this bacterial genus. This work showed that extreme caution should be exercised when reporting the isolation of Capnocytophaga species from oral polymicrobial samples, because the culture medium is a determining factor.

Enantioselective pharmacokinetics of ketoprofen in piglets: the significance of neonatal age.

Following intravenous dose of 6mg/kg racemic ketoprofen, the chiral pharmacokinetics of ketoprofen was investigated in eight piglets aged 6 and 21days old. S-ketoprofen predominated over R-ketoprofen in plasma of the piglets in both age groups. The volumes of distribution of S-ketoprofen for the 6- and 21-day-old piglets were 241.7 (211.3-276.5) mL/kg and 155.0 (138.7-173.1) mL/kg, respectively, while the corresponding parameters for R-ketoprofen were 289.2 (250.3-334.2) mL/kg and 193.0 (168.7-220.8) mL/kg. The clearances of R-ketoprofen [948.4 (768.0-1171.2) mL/h/kg and 425 (319.1-566.0) mL/h/kg for the 6- and 21-day-old piglets, respectively] were significantly higher compared to the clearances of S-ketoprofen [57.3 (46.6-70.4) mL/h/kg and 33.8 (27.0-42.2) mL/h/kg for 6- and 21-day-old piglets, respectively]. The elimination half-life of S-ketoprofen was 3.4h for both age groups, while the elimination half-life of R-ketoprofen was 0.2h for the 6-day-old and 0.4h for the 21-day-old piglets. The clearances of both R- and S-ketoprofen were significantly higher in the 6-day-old piglets compared to when they were 21 days old. Furthermore, the volumes of distribution were larger in the youngest age group.

Pharmacokinetics and pharmacodynamic effects of meloxicam in piglets subjected to a kaolin inflammation model.

The pharmacokinetics and the analgesic, anti-inflammatory and antipyretic effects of meloxicam were investigated in a placebo controlled study in 2-week-old piglets. Inflammation was induced by a subcutaneous injection of kaolin in the left metacarpus, and 16 h later, meloxicam (0.6 mg/kg) or saline was administered intramuscularly. The absorption half-life was relatively short (0.19 h) and the elimination half-life was 2.6 h. Mechanical nociceptive threshold testing was used to evaluate the analgesic effect, but no significant effect of the meloxicam treatment was found. The skin temperature of the inflamed area increased after the kaolin injection, but no significant decrease in temperature was found after administration of meloxicam. Only limited pyresis was observed after the kaolin injection, and no significant antipyretic effect of meloxicam was found. The results indicated that this dose of meloxicam had very limited anti-inflammatory and analgesic effects in piglets.

Ketoprofen in piglets: enantioselective pharmacokinetics, pharmacodynamics and PK/PD modelling.

The chiral pharmacokinetics and pharmacodynamics of ketoprofen were investigated in a placebo-controlled study in piglets after intramuscular administration of 6 mg/kg racemic ketoprofen. The absorption half-lives of both enantiomers were short, and S-ketoprofen predominated over R-ketoprofen in plasma. A kaolin-induced inflammation model was used to evaluate the anti-inflammatory, antipyretic and analgesic effects of ketoprofen. Skin temperatures increased after the kaolin injection, but the effect of ketoprofen was small. No significant antipyretic effects could be detected, but body temperatures tended to be lower in the ketoprofen-treated piglets. Mechanical nociceptive threshold testing was used to evaluate the analgesic effects. The piglets in the ketoprofen-treated group had significantly higher mechanical nociceptive thresholds compared to the piglets in the placebo group for 12-24 h following the treatment. Pharmacokinetic/pharmacodynamic modelling of the results from the mechanical nociceptive threshold testing gave a median IC(50) for S-ketoprofen of 26.7 µg/mL and an IC(50) for R-ketoprofen of 1.6 µg/mL. This indicates that R-ketoprofen is a more potent analgesic than S-ketoprofen in piglets. Estimated ED(50) for racemic ketoprofen was 2.5 mg/kg.

Pharmacokinetics and pharmacodynamics of meloxicam in piglets.

The pharmacokinetics and pharmacodynamics of meloxicam in piglets (16-23 days old) were studied using a stratified parallel group design. One group (n = 13) received 0.4 mg/kg meloxicam intravenously, while the other group (n = 12) received physiological saline solution. A carrageenan-sponge model of acute inflammation was used to evaluate the effects of meloxicam. The plasma clearance was low (0.061 L/kg/h), the volume of distribution was low (0.19 L/kg) and the elimination half-life was short (2.7 h). At most time points, the mean concentration of meloxicam in plasma exceeded the concentrations in exudate indicating a limited accumulation of the drug at the site of the inflammation. There were significant differences between the groups in the exudate prostaglandin E2 (PGE2) concentration, but the inhibition of PGE2 in the meloxicam group was limited. The inhibition of thromboxane B(2) (TXB2) production in serum in the meloxicam group was extensive, but of shorter duration than the PGE2 inhibition in exudate.

[Monitoring of antibiotic resistance of gram negative anaerobes]. / Surveillance de la résistance aux antibiotiques des anaérobies stricts à Gram négatif.

MATERIAL AND METHOD: Using an agar reference method (Norma M11-A5, National Committee for Clinical and Laboratory Standards) the minimal inhibitory concentrations of nine antibiotics were determined for 376 anaerobic strains. The following strains were investigated: 254 Bacteroides fragilis group (including 143 B. fragilis), 122 other gram-negative anaerobes (Bacteroides spp., Prevotella, Fusobacterium, Porphyromonas, Suterella, Desulfomonas, Veillonella). RESULTS: In the B. fragilis group resistance rates were: coamoxyclav 2.8%, ticarcillin 27.5%, ticarcillin-clavulanic acid 1.9%, piperacillin-tazobactam 1.9%, cefoxitin 6.2%, imipenem 0.8%, clindamycin 28.3%, respectively. Based on previous studies, resistance to imipenem remained low in 2003 and was only observed for B. fragilis. Resistance to clindamycin was maintained around 25%. No metronidazole resistance was observed, but decreased susceptibility was found for B. fragilis, B. merdae and Prevotella, as in 4.3% of gram-negative anaerobes. DISCUSSION: This study confirms the high resistance rate of gram-negative anaerobes to clindamycin, the efficient activity of imipenem, beta-lactam/beta-lactamase inhibitor combinations and metronidazole. However, reduced metronidazole susceptibility seems to be increasing.

Prevalence and pathogenicity of Clostridium difficile in hospitalized patients. A French multicenter study.

BACKGROUND: Although Clostridium difficile is the main agent responsible for nosocomial diarrhea in adults, its prevalence in stool cultures sent to hospital microbiology laboratories is not clearly established. OBJECTIVES: To determine the prevalence of C difficile in inpatient stools sent to hospital microbiology laboratories and to assess the relationship between serotypes and toxigenicity of the strains isolated and the clinical data. METHODS: From January 18, 1993, to July 31, 1993, the presence of C difficile was systematically investigated in a case-control study on 3921 stool samples sent for stool culture to 11 French hospital microbiology laboratories. The prevalence of C difficile in this population (cases) was compared with that of a group of 229 random hospital controls matched for age, department, and length of stay (controls). Stool culture from controls was requested by the laboratory although not prescribed by the clinical staff. Serotype and toxigenesis of the strains isolated were compared. RESULTS: The overall prevalence of C difficile in the cases was twice the prevalence in the controls (9.7% vs 4.8%; P < .001) and was approximately 4 times as high in diarrheal stools (ie, soft or liquid) as in normally formed stools from controls (11.5% vs 3.3%; P < .001). The strains isolated from diarrheal stools were more frequently toxigenic than those isolated from normally formed stools. Serogroup D was never toxigenic, and its proportion was statistically greater in the controls than in the cases (45% vs 18%; chi 2 = 5.2; P < .05). Conversely, serogroup C was isolated only from the cases. Clostridium difficile was mainly found in older patients ( > 65 years), suffering from a severe disabling disease, who had been treated with antibiotics and hospitalized for more than 1 week in long-stay wards or in intensive care. CONCLUSIONS: This multicenter period prevalence study clearly supports the hypothesis of a common role of C difficile in infectious diarrhea in hospitalized patients. Disease associated with C difficile should therefore be systematically evaluated in diarrheal stools from inpatients.

Achromobacter bacteraemia outbreak in a paediatric onco-haematology department related to strain with high surviving ability in contaminated disinfectant atomizers.

BACKGROUND: Achromobacter spp. are Gram-negative bacilli from aqueous environments, occasionally involved in bacteraemia in immunocompromised hosts and in outbreaks. AIM: We describe the characteristics of an achromobacter bacteraemia outbreak in a paediatric onco-haematology department. METHODS: Throughout a one-year period, 16 blood cultures from seven patients were positive for Achromobacter sp. All patients were immunocompromised, febrile, and central venous catheter (CVC) holders. A microbiological study was performed in patients' rooms, completed with an analysis of the disinfectant atomizers (didecyl diammonium chloride 0.25%, Surfanios, DMA). In total, 41 clinical and environmental strains were analysed by enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction (PCR), repetitive PCR, and random amplified polymorphic DNA (RAPD)-PCR, and pulsed-field gel electrophoresis (PFGE). The bactericidal activity of DMA was studied on two Achromobacter sp. representative strains and one Pseudomonas aeruginosa reference strain, comparing biofilm and planktonic growth models. FINDINGS: The seven patients, including two severe cases, were successfully treated by systemic antimicrobial therapy and/or catheter removal. The 25 environmental isolates were recovered with the following chronology: hospital filtered tap water, disinfectant atomizers, and patients' rooms. All environmental, patient, and atomizer strains had identical PCR and PFGE patterns. The disinfectant susceptibility assay revealed that the strain isolated from the atomizers had high survival abilities in biofilm conditions and remained resistant to DMA after short contact periods. CONCLUSION: The use of disinfectant atomizers associated with the survival of Achromobacter in the atomizer pipes may explain the contamination and colonization of the CVC. Control measures (non-atomizer containers and use of sterile water) allowed the eradication of the source and the outbreak control.

Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

Metastatic cerebral abscesses due to Hemophilus paraphrophilus.

A patient who had a two-month history of nonspecific inflammatory disease experienced symptoms of raised intracranial pressure and meningitis. Computed tomographic scan showed multiple, small ring-enhancing hypodensities consistent with cerebral abscesses. The infective agent proved to be Hemophilus paraphrophilus, a fastidious, particularly slow-growing organism that was identified on blood cultures. An autopsy disclosed disseminated microabscesses and demonstrated typical pathologic changes of endocarditis complicating mitral valve prolapse.

Antibiotic susceptibility in aerobic gram-negative bacilli isolated in intensive care units in 39 French teaching hospitals (ICU study).

OBJECTIVE: Evaluation of the distribution and antibiotic susceptibility of the aerobic gram-negative bacilli (AGNB) isolated from patients in intensive care units (ICU study). DESIGN AND SETTING: Microbiological study carried out in 1991 in 39 teaching hospitals. A standardized method was used to determine the minimum inhibitory concentrations of 12 antibiotics against 3366 strains of AGNB (close to 100 strains per hospital) during a period of 3 months. RESULTS: The 2773 initial strains (i.e., the first AGNB isolate for a given species and a given patient) were mainly isolated from the respiratory tract (34.4%), urinary tract (23%), or blood (9.6%) and were mainly Pseudomonas aeruginosa (22.9%), Escherichia coli (22%), Acinetobacter (9.7%), and Klebsiella pneumoniae (8.3%). E. coli was prominent in urine and blood and P. aeruginosa in the respiratory tract. Overall, the rate of susceptibility of AGNB was 58 to 65% to piperacillin, cefotaxime, and gentamicin; 69 to 75% to aztreonam, tobramycin, and ciprofloxacin; 83% to ceftazidime; and 91% to imipenem. The overall rates of susceptibility were higher for the initial strains isolated from blood than for those from the urinary or respiratory tracts, mostly reflecting differences in species distribution. Susceptibility rates were lower for the 593 repeat strains (i.e., all the subsequent isolates for a given species and a given patient) than for the initial strains, mostly due to the higher proportion of resistant species (P. aeruginosa 45.9%) but also due to the difference in susceptibility rates for some species-antibiotic combinations. Concomitant resistance (i.e., resistance to several antibiotics due to independent mechanisms of resistance) was marked between beta-lactams and aminoglycosides or quinolones, particularly in P. aeruginosa and K. pneumoniae. CONCLUSIONS: Rates of resistance in AGNB as a whole and in particular species (P. aeruginosa, Klebsiella), as well as frequency of concomitant resistance found in the French ICU study, were higher than those found in ICU studies conducted with the same methodology in Belgium, The Netherlands, and Germany, which may reflect differences in case mix.

Clinical and microbiological epidemiology of Streptococcus pneumoniae bacteremia in eight French counties.

OBJECTIVE: To describe the incidence of pneumococcal bacteremia not associated with infection of the central nervous system, investigate the susceptibility of bacterial isolates to beta-lactams, evaluate risk factors for antibiotic resistance, and determine factors predicting patient outcome. METHODS: Over a period of 1 year, 919 Streptococcus pneumoniae isolates were collected from 919 patients with bacteremia in eight French counties. Their clinical and microbiological features were recorded. Univariate and multivariate analyses were used to determine risk factors for penicillin-non-susceptible pneumococcal bacteremia and predictors of fatal outcome. RESULTS: Of the 919 patients in the study, 27% were infected with penicillin-non-susceptible pneumococci (PNSP): 17.8% of the isolates were intermediate to penicillin, 7.2% were resistant to penicillin, 16% were intermediate to amoxicillin, and 11% were intermediate to cefotaxime; no PNSP were resistant to either of the last two antibiotics. The most common PNSP serotypes isolated were 14 (41%) and 23 (24%). A statistically significant relationship between PNSP infection and age below 5 years or above 60 years in the different counties was observed by univariate and multivariate analysis. Gender, origin of bacteremia, co-morbidity, immunodeficiency, previous hospitalization and nosocomial infection were not predisposing factors associated with PNSP. The mortality rate was 20.6%: there was no increase in mortality among patients with PNSP bacteremia. Age was the strongest risk factor for mortality, but immunodeficiency also seemed to have had an impact on mortality. Clinical outcome was more closely related to clinical conditions than to the susceptibility status of S. pneumoniae. CONCLUSION: Among cases of bacteremia, 27% were caused by PNSP, but this level varies according to the counties and the age of the patients. Infection-related mortality was high, but there was no increase related to penicillin G non-susceptibility of the infecting strain.

Susceptibility of Enterobacteriaceae to beta-lactam agents and fluoroquinolones: a 3-year survey in France.

OBJECTIVE: To assess trends in the susceptibility to beta-lactam agents and to fluoroquinolones of clinically relevant Enterobacteriaceae isolated over a 3-year period in 14 French hospital laboratories. METHODS: During the second quarter of 1996, 1997 and 1998, 180 consecutive non-duplicate isolates of Enterobacteriaceae were collected in each center. Sixteen beta-lactams and four quinolones were tested by the disk diffusion method. In addition, the double-disk synergy test was used to screen for the production of extended-spectrum beta-lactamase (ESBL). RESULTS: Totals of 2507, 2312 and 2506 clinical isolates were obtained in each period, respectively. The distribution of Enterobacteriaceae species according to clinical specimens and wards was similar in each study period. No significant variation in the susceptibility rates to beta-lactams and fluoroquinolones was observed, except in Klebsiella pneumoniae and Enterobacter aerogenes. The prevalence of ESBL-producing isolates decreased from 18% to 9% in the former, while it increased from 32% to 54% in the latter. At the same time, the susceptibility to ofloxacin and pefloxacin increased for K. pneumoniae (P < 0.003) and cephalosporinase-producing species (P < 0.05), except Enterobacter spp. CONCLUSION: Over the 3-year study period beta-lactams and fluoroquinolones remained highly active against Enterobacteriaceae clinical isolates, with the exception of E. aerogenes, probably as a result of the dissemination of multiresistant clones in French hospitals.

How to organise antibiotic prescription.

In recent years, efforts have been made in hospitals to improve antibiotic prescription. Most universities organise courses on the subject, which lead to a local university diploma. However, possessing such a diploma does not give entitlement to prescribe. In fact, most doctors prescribe antibiotics and such courses are only of interest to volunteer physicians. While some are very careful, the majority prescribe the drugs as they are rarely toxic. Others are refractory to any information and particularly to any training. Two methods are typically proposed to reduce unjustified prescription. As a result of imposed restrictions, only trained doctors having met the training standards are allowed to prescribe and have to keep to a limited budget. The persuasive method, on the other hand, opens the way for a wide scope of training courses, which are provided by industry; some are said to be biased as they encourage prescription and the risk of selecting resistant mutant bacteria is scarcely documented. This method does not always coincide with the training curricula. The industry is torn between declared objectives such as judicious drug use and prevailing commercial aims. As a result, prescription is not restrained by any objective limit. It should be noted that prescription varies greatly from one hospital to another and within a given hospital between one department and another. Certain departments prescribe much more than others and these (emergency, medical and surgical intensive care, respiratory disease) should be targeted first.

A 1-year study of antibiotic resistance among paediatric pneumococcal isolates in 1995 from four regions of France.

The main object of this study was to describe the features of antibiotic resistance in pneumococci from children in four regions of France in 1995. Despite the high prevalence (40%) of pneumococci with diminished susceptibilty to penicillin (PDSP), resistance to amoxycillin (0.8%) and cefotaxime (0.4%) was rare; 16% of pneumococci were resistant to penicillin G (PRP, MIC > 1 mg/l). PDSP showed the expected resistance to macrolides (67%) and cotrimoxazole (57%) and were predominantly serotypes 23F, 14, 9 and 6. This study by the Regional Pneumococcal Observatories confirms the high prevalence and the main characteristics of antibiotic resistance among pneumococci isolated from children. Nevertheless, the resistance to all antibiotics was lower than that found in French multicentre, nationwide surveys, possibly because of differences in the mode of strain collection and geographic origin.

Change of pneumococcal resistance to antibiotics in adults between 1995 and 1997: a study in eight French counties.

The main object of this study was to describe the evolution of antibiotic resistance in pneumococci from adults, in eight French counties of France between 1995 and 1997. Despite the high and increasing prevalence (23-35%) of pneumococci with diminished susceptibility to penicillin G (PSDP), resistance to amoxycillin (0.8-0.5%) and to cefotaxime (0-0.3%) was rare in both 1995 and 1997 respectively. The percentage of pneumococci resistant to penicillin G (PRP, minimum inhibitory concentration >1 mg/l) remained stable between the two periods. PSDP showed increased resistance to macrolides (30-41%), to cotrimoxazole (28-34%) and to tetracycline (19-25%). These figures are lower than those obtained over the same periods and the same regions in children. The distribution of PSDP serotypes isolated in adults was the same as that seen in children: by descending order serotypes 23, 14, 9 and 6. This study by the Regional Pneumococcal Observatories confirms the high prevalence and the main characteristics of antibiotic resistance among pneumococci with variations in levels of resistance with the age of patients, with the site of sampling and from one Observatory to another.

A seven-year survey of Klebsiella pneumoniae producing TEM-24 extended-spectrum beta-lactamase in Nice University Hospital (1994-2000).

The aim of this study was to investigate TEM-24-producing isolates of Klebsiella pneumoniae, and their clonal dissemination in Nice University Hospital. During the 1994-2000 period, a total of 263 non-repetitive isolates of ESBL-producing K. pneumoniae were collected. Most of these isolates were highly resistant in vitro to ceftazidime, cefotaxime and aztreonam, but susceptible to cefoxitin and imipenem. Resistance profile analysis revealed seven predominant antibiotypes (P1 to P7). Isoelectric focusing evidenced beta-lactamase activity, with a chromosomal penicillinase (pl 7.7), and one or two additional enzymes with pls ranging from 5.4 to 8.2 identified as presumed TEM-1 pl 5.4, TEM-3 pl 6.3, TEM-24 pl 6.5, SHV-3 pl 7.0, SHV-4 pl 7.8, SHV-5 pl 8.2, or other unidentified beta-lactamases. Among these K. pneumoniae, 130 isolates produced TEM-24, and 115 of them were highly resistant in vitro to quinolones (antibiotype P1). This phenotype was responsible for an outbreak in a medical intensive care unit from March to September 2000. Four isolates submitted were genetical sequenced, and shared 99.9% homology with tem-24 (GenBank no. X 65253). Pulsed-field gel electrophoresis and enterobacterial repetitive intergenic consensus polymerase chain reaction (PCR) (ERIC2-PCR) applied to 28 non-epidemic and six epidemic isolates yielded concordant results. Molecular typing revealed the persistence and dissemination of a single clone of TEM-24 producing K. pneumoniae in Nice Hospital during the seven-year study period.

Effects of combined topical metronidazole and mechanical treatment on the subgingival flora in deep periodontal pockets in cuspids and bicuspids.

The Effect on the subgingival microflora of a single topical administration of a 95% collagen and 5% metronidazole device in combination with debridement was investigated in 30 adult periodontitis patients in comparison with mechanical treatment alone. For each patient, plaque samples from test and control sites in cuspids and bicuspids were collected for culture and enumeration of total anaerobically cultivable bacteria (TA), black-pigmented anaerobes (BPA), and Actinobacillus actinomycetemcomitans (Aa). Spirochetes and fusiforms were quantified by direct microscopic examination after Giemsa staining. A decrease was observed for all parameters, and a significant difference in comparison with the control group was found for fusiforms. After treatment, a lower number of Aa positive sites were observed in the test group (13/25). These results show that a single application of topical metronidazole seems to be effective as adjunctive antimicrobial treatment in adult periodontitis.

Oral carriage of Helicobacter pylori: a review.

Helicobacter pylori is a microaerophilic, motile bacterium, especially adapted to life in the human stomach. The presence of H. pylori in the stomach is strongly associated with chronic gastritis and ulcer disease and is a risk factor for gastric cancers. The microorganism may be transmitted orally and has been detected in dental plaque, saliva, and feces, but the hypothesis that oral microflora may be a permanent reservoir of H. pylori is still controversial. A review of the literature suggests that the recovery of H. pylori in the mouth is probably intermittent, associated with gastroesophageal reflux but not with specific oral disease. Nonetheless, the PCR identification of oral H. pylori may become helpful, particularly in cases of gastritis or ulcer relapse after antimicrobial therapy. Eradication of oral H. pylori by local medication or periodontal procedures would rely on the precise identification of its ecological niche. Within family groups, prophylactic methods should be practiced to avoid oral carriage of H. pylori. The risk of iatrogenic transmission during dental care, however, is already circumscribed by standard professional hygiene procedures.