Dietary pectin-derived acidic oligosaccharides improve the pulmonary bacterial clearance of Pseudomonas aeruginosa lung infection in mice by modulating intestinal microbiota and immunity.

BACKGROUND: A predominantly T-helper type 2 (Th2) immune response is critical in the prognosis of pulmonary Pseudomonas aeruginosa infection. But the mucosal and systemic immune responses can be influenced by the intestinal microbiota. METHODS: We assessed the effect of microbiota compositional changes induced by a diet enriched in 5% acidic oligosaccharides derived from pectin (pAOS) on the immune response and outcome of chronic pulmonary P. aeruginosa infection in mice. RESULTS: pAOS promoted Th1 polarization by increasing interferon γ release, upregulating t-bet gene expression, decreasing interleukin 4 secretion, and downregulating gata3 gene expression. pAOS also sustained the release of keratinocyte chemoattractant, recruited polynuclear leukocytes and macrophages, stimulated M1 macrophage activation and interleukin 10 release, and decreased tumor necrosis factor α release in the lung. These effects led to increased bacterial clearance after the first and second P. aeruginosa infections. pAOS modified the intestinal microbiota by stimulating the growth of species involved in immunity development, such as Bifidobacterium species, Sutturella wadsworthia, and Clostridium cluster XIVa organisms, and at the same time increased the production of butyrate and propionate. CONCLUSION: These results suggest that pAOS may have beneficial effects by limiting the number and severity of pulmonary exacerbations in patients chronically infected with P. aeruginosa, such as individuals with cystic fibrosis.

Impact of fish oils on the outcomes of a mouse model of acute Pseudomonas aeruginosa pulmonary infection.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes pneumonia in immunocompromised humans and severe pulmonary damage in patients with cystic fibrosis. Imbalanced fatty acid incorporation in membranes, including increased arachidonic acid and decreased DHA concentrations, is known to play a critical role in chronic inflammation associated with bacterial infection. Other lipids, such as EPA and alkylglycerols, are also known to play a role in inflammation, particularly by stimulating the immune system, decreasing inflammation and inhibiting bacterial growth. In this context, the goal of the present study was to assess the effect of dietary DHA/EPA, in a 2:1 ratio, and alkylglycerols, as natural compounds extracted from oils of rays and chimeras, respectively, on the inflammatory reaction induced by P. aeruginosa pulmonary infection in mice. To this end, mice were fed with a control diet or isolipidic, isoenergetic diets prepared with oils enriched in DHA/EPA (2:1) or alkylglycerols for 5 weeks before the induction of acute P. aeruginosa lung infection by endotracheal instillation. In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries. By contrast, alkylglycerols did not affect the outcomes of P. aeruginosa infection. Our findings suggest that supplementation with ray oil enriched in DHA/EPA (2:1) can be considered as a preventive treatment for patients at risk for P. aeruginosa infection.

Abnormal expression of Muc5b in Cftr-null mice and in mammary tumors of MMTV-ras mice.

Gel-forming mucins are large, high molecular weight, and heavily O-glycosylated proteins that are responsible for the rheological properties of mucus gel. Among them, the mucin MUC5B has been implicated in breast cancer and cystic fibrosis. We obtained a new polyclonal serum, named CP1, which was isolated from a rabbit immunized with a mouse Muc5b peptide. The immunoprofile of Muc5b was determined on paraffin-embedded and frozen mouse tissue sections and showed a similar expression pattern in mouse to that in the human. The "nonmammary" mucin Muc5b was detected in all mammary tumors analyzed from MMTV-ras mice, suggesting that the CP1 antibody is a valuable tool for investigating the involvement of this mucin in mammary cancer. We also found that uninfected Cftr( -/- ) mice harbored more Clara cells, which were Muc5b-positive, than did their wild-type control littermates. The number of Muc5b-positive cells increased in Cftr( -/- ) mice infected experimentally with Pseudomonas aeruginosa, and the mice developed mucus plugs in their bronchi and bronchioles with a high frequency of Muc5b content (87%, Cohen's kappa = 0.82; p < 0.0001). These findings suggest that mice genetically deficient in the Cftr gene are predisposed to develop mucus plugs and that MUC5B may provide a valuable target for decreasing mucus viscosity in cystic fibrosis.

(n-3) long-chain PUFA differentially affect resistance to Pseudomonas aeruginosa infection of male and female cftr-/- mice.

The aim of this study was to determine whether oral supplementation with EPA/DHA (10.5 and 5.1% of fat, respectively) could improve the outcome of pulmonary P. aeruginosa infection in cftr(-/-) mice compared with wild-type (Wt) mice similarly treated. Because gender could influence the susceptibility of cftr-deficient mice, results were analyzed by gender. Wt and (-/-) mice were randomized for 6 wk to consume a control or EPA/DHA diet, infected with endotracheal injection of 5 × 10(7) CFU/mouse of P. aeruginosa, and killed 24 h later. Cftr(-/-) mice were more susceptible to infection than were Wt mice; (-/-) males had more neutrophils (P < 0.01) and a higher keratinocyte-derived chemokine (KC) level (P < 0.05), and (-/-) females had greater lung injury and mortality (P < 0.05). Female (-/-) mice were more susceptible than (-/-) males with a higher mortality and lung injury (P < 0.05). The EPA/DHA diet reduced neutrophil numbers and KC and IL-6 levels (P < 0.05) in (-/-) males and reduced mortality rate (P < 0.001), lung permeability, and IL-6 level (P < 0.05) in (-/-) females compared with (-/-) mice fed the control diet. These results were associated with a reduction in the pulmonary bacterial load (P < 0.05), an increase in the EPA/DHA concentration in cell membranes of (-/-) males and females (P < 0.01), and an increased weight gain only in males compared with (-/-) mice fed the control diet (P < 0.01). In conclusion, EPA/DHA improves the host resistance of (-/-) mice, although the beneficial effect differed in males and females.

Dietary (n-3) polyunsaturated fatty acids affect the kinetics of pro- and antiinflammatory responses in mice with Pseudomonas aeruginosa lung infection.

The underlying mechanisms by which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect host resistance to Pseudomonas aeruginosa are unclear. The aim of this study was to determine their role on the kinetic of pro- and antiinflammatory response in lung infection. Mice fed either a control diet or a diet enriched with EPA and DHA were infected intratracheally and we studied lung expression of proinflammatory markers [CXCL1, interleukin (IL)-6, tumor necrosis factor-alpha], antiinflammatory markers (IL-10, A20, and IkappaB alpha), and PPARalpha and PPARgamma. The inflammatory response was assessed using recruitment of neutrophils and macrophages into bronchoalveolar lavage fluid, bacterial clearance from the lung, pulmonary injury, and 7-d survival rate. Compared with the control group, EPA and DHA delayed the expression of proinflammatory markers during the first 2 h (P < 0.05), upregulated proinflammatory marker expression (P < 0.05), and induced overexpression of antiinflammatory markers at 8 h (P < 0.05), enhanced recruitment of neutrophils at 16 h (P < 0.05), and induced PPARalpha and PPARgamma overexpression at 4 and 8 h (P < 0.01), respectively. Pulmonary bacterial load decreased and pulmonary injury and mortality were reduced during the first 24 h (P < 0.05). In conclusion, EPA and DHA modulate the balance between pro- and antiinflammatory cytokines, alter the early response of the host to P. aeruginosa infection, and affect the early outcome of infection.

Direct antimicrobial susceptibility testing method for analysis of sputum collected from patients with cystic fibrosis.

BACKGROUND: Chronic Pseudomonas aeruginosa colonisation and subsequent exacerbations in patients with cystic fibrosis (CF) require antimicrobial treatment. But since multiple morphotypes and other Gram-negative bacteria with different antibiotic susceptibilities are often isolated inside the same sputum sample, bacteriological analysis is difficult. METHODS: To simplify this analysis, we explored a direct sputum antimicrobial susceptibility testing (DSST) method by applying E test directly on plates inoculated with the sputum. A total of 316 samples collected from CF patients were analysed and compared with standard procedures (SP) for the identification and antimicrobial susceptibility testing of all Gram-negative bacterial species. RESULTS: DSST was as efficient as SP to detect P. aeruginosa including the mucoid morphotype in monomicrobial specimen, but was less sensible to detect all Gram-negative bacteria present in the same sample. It allowed the direct reading of the MIC inhibiting all Gram-negative bacteria. Agreements between these global MICs with the cumulative antibiotics susceptibility of all Gram-negative bacteria measured by SP were excellent for tobramycin and imipenem (>96%) and satisfactory for ticarcillin, ceftazidime, aztreonam and ciprofloxacin (90.4% to 94.3%). In conclusion, the DSST method is an efficient and easy antibiotic susceptibility testing method.

Long-term dietary (n-3) polyunsaturated fatty acids show benefits to the lungs of Cftr F508del mice.

INTRODUCTION: The pro-inflammatory status of cystic fibrosis (CF) patients promotes pulmonary colonization with opportunist and pathogenic bacteria, which is favored by a sticky mucus. Oral supplementation with (n-3) long chain polyunsaturated fatty acids (LC-PUFA) has shown anti-inflammatory effects. The aim of this study was to demonstrate the positive effects of a long-term diet enriched in (n-3) LC-PUFA on the lungs of Cftr F508del mice. MATERIALS AND METHODS: Breeding CftrΔF508del/+ mice received a control diet or a diet enriched in (n-3) LC-PUFA for 5 weeks before mating, gestation and lactation. After weaning, the offspring were given the same diet as their mother until post-natal day 60. The effects of (n-3) LC-PUFA supplementation on the lungs were evaluated in homozygous Cftr F508del mice and their wild-type littermates after acute lung inflammation induced by Pseudomonas aeruginosa lipopolysaccharide (LPS) inhalation. RESULTS: (n-3) LC-PUFA enrichment of mothers contributes to enrichment of mammary milk and cell membrane of suckling pups. Cftr F508del mice exhibited growth retardation and lung damage with collapsed alveoli, hyperplasia of bronchial epithelial cells and inflammatory cell infiltration. The (n-3) LC-PUFA diet corrected the growth delay of Cftr F508del mice and decreased hyperplasia of bronchial epithelial cells. Besides decreasing metaplasia of Club cells after LPS inhalation, (n-3) LC-PUFA modulated lung inflammation and restricted lung damage. CONCLUSION: Long-term (n-3) LC-PUFA supplementation shows moderate benefits to the lungs of Cftr F508del mice.

Dietary n-3 fatty acids have suppressive effects on mucin upregulation in mice infected with Pseudomonas aeruginosa.

BACKGROUND: Mucin hypersecretion and mucus plugging in the airways are characteristic features of chronic respiratory diseases like cystic fibrosis (CF) and contribute to morbidity and mortality. In CF, Pseudomonas aeruginosa superinfections in the lung exacerbate inflammation and alter mucus properties. There is increasing evidence that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-inflammatory properties in many inflammatory diseases while n-6 PUFA arachidonic acid (AA) favors inflammatory mediators such as eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) that may enhance inflammatory reactions. This suggests that n-3 PUFAs may have a protective effect against mucus over-production in airway diseases. Therefore, we hypothesized that n-3 PUFAs may downregulate mucins expression. METHODS: We designed an absolute real-time PCR assay to assess the effect of a 5-week diet enriched either with n-3 or n-6 PUFAs on the expression of large mucins in the lungs of mice infected by P. aeruginosa. RESULTS: Dietary fatty acids did not influence mucin gene expression in healthy mice. Lung infection induced an increase of the secreted gel-forming mucin Muc5b and a decrease of the membrane bound mucin Muc4. These deregulations are modulated by dietary fatty acids with a suppressive effect of n-3 PUFAs on mucin (increase of Muc5b from 19-fold up to 3.6 x 10(5)-fold for the n-3 PUFAs treated group and the control groups, respectively, 4 days post-infection and decrease of Muc4 from 15-fold up to 3.2 x 10(4)-fold for the control and the n-3 PUFAs treated groups, respectively, 4 days post-infection). CONCLUSION: Our data suggest that n-3 PUFAs enriched diet represents an inexpensive strategy to prevent or treat mucin overproduction in pulmonary bacterial colonization.

Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids.

OBJECTIVES: Although n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) are used widely in the treatment of chronic inflammatory diseases, their effect in infectious disease requires a particular attention. METHODS: The present article discusses their anti-inflammatory and immune properties involved in the host defence and presents a systematic review of the effects of their oral administration on the prevention and outcome of experimental and clinical infections. RESULTS: At a dose corresponding to an human dose of 500 mg/day, n-3 LC-PUFAs intake is beneficial against experimental infections caused by extracellular pathogens including Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus by reducing inflammation, and reduces the incidence of pneumococcal infections in the elderly, but at 2-4-fold higher doses as occurs in some human intervention and/or during long-term it becomes detrimental in intestinal infections with Citrobacter rodentium or Helicobacter hepaticus by exacerbating anti-inflammatory response. They are also harmful against infections caused by intracellular pathogens as Mycobacterium tuberculosis, Salmonella, Influenza virus and Herpes simplex virus by affecting the immune cell response. CONCLUSION: The effects of n-3-LC-PUFAs on infections depend on the pathogen and the n-3 LC-PUFA dose and timing. Caution should be recommended for high-dose and long-term supplementation in humans.

Chronic pneumonia with Pseudomonas aeruginosa and impaired alveolar fluid clearance.

BACKGROUND: While the functional consequences of acute pulmonary infections are widely documented, few studies focused on chronic pneumonia. We evaluated the consequences of chronic Pseudomonas lung infection on alveolar function. METHODS: P. aeruginosa, included in agar beads, was instilled intratracheally in Sprague Dawley rats. Analysis was performed from day 2 to 21, a control group received only sterile agar beads. Alveolar-capillary barrier permeability, lung liquid clearance (LLC) and distal alveolar fluid clearance (DAFC) were measured using a vascular (131I-Albumin) and an alveolar tracer (125I-Albumin). RESULTS: The increase in permeability and LLC peaked on the second day, to return to baseline on the fifth. DAFC increased independently of TNF-alpha or endogenous catecholamine production. Despite the persistence of the pathogen within the alveoli, DAFC returned to baseline on the 5th day. Stimulation with terbutaline failed to increase DAFC. Eradication of the pathogen with ceftazidime did not restore DAFC response. CONCLUSIONS: From these results, we observe an adequate initial alveolar response to increased permeability with an increase of DAFC. However, DAFC increase does not persist after the 5th day and remains unresponsive to stimulation. This impairment of DAFC may partly explain the higher susceptibility of chronically infected patients to subsequent lung injury.

Relative expression of Pseudomonas aeruginosa virulence genes analyzed by a real time RT-PCR method during lung infection in rats.

The bacterial aspects of the events occurring during the first days of lung colonization by Pseudomonas aeruginosa are still unknown. The aim of this study was to develop a real time RT-PCR method for the direct quantification of the transcripts of three P. aeruginosa virulence genes: exoS, lasI and algD, during the first seven days of a rat lung infection. Our results document differences in bacterial gene expression throughout P. aeruginosa infection. ExoS transcripts levels were very high in the first days of infection, but a significant decrease was then progressively observed. Transcription of algD occurred on the 4th day and increased regularly over time suggesting a balance in the transcription of exoS and algD. The strong expression of exoS during the first 3 days was correlated to 29% of mortality among infected rats. On the contrary, the increase of algD expression after this period was associated to the development of a chronic infection with no further mortality. LasI transcription remained more constant throughout the infection.

Pectin-Derived Acidic Oligosaccharides Improve the Outcome of Pseudomonas aeruginosa Lung Infection in C57BL/6 Mice.

The administration of prebiotics as oligosaccharides (OS), by acting on intestinal microbiota, could modulate the immune and inflammatory response and represent a new strategy to improve the outcome of bacterial infection. The aim of this study was to determine whether pectin-derived acidic oligosaccharides (pAOS) could modulate the outcome of pulmonary P. aeruginosa (PA) infection in C57BL/6 mice, which develop a Th1 response to PA lung infection. Mice were randomized for 5 weeks to consume a control or a 5% pAOS diet and chronically infected by PA. Resistance to a second PA infection was also analyzed by reinfecting the surviving mice 2 weeks after the first infection. Compared with control mice, mice fed pAOS had reduced mortality (P<0.05). This improvement correlated with a better control of the inflammatory response with a lower neutrophil count on day 1 (P<0.05), a sustained neutrophil and macrophage recruitment on days 2 and 3 (P<0.01) a greater and sustained IL-10 release in lung (P<0.05) and a reduction of the Th1 response and M1 activation with a lower IFN-γ/IL-4 (P<0.01) and nos2/arg1 (P<0.05) ratios. These results coincided with a modulation of the intestinal microbiota as shown by an increased butyric acid concentration in feces (P<0.05). Moreover, pAOS decreased the bacterial load (P<0.01) in mice reinfected 2 weeks after the first infection, suggesting that pAOS could reduce pulmonary exacerbations. In conclusion, pAOS improved the outcome of PA infection in C57BL/6 mice by modulating the intestinal microbiota and the inflammatory and immune responses.

The role of bacterial vaginosis in preterm labor and preterm birth: a case-control study.

OBJECTIVE: To study the association between preterm labor and bacterial vaginosis; in women with preterm labor, to determine whether vaginosis modifies the risk of preterm delivery. STUDY DESIGN: Case-control study. We used Amsel's clinical criteria to test 102 patients hospitalized for preterm labor and 102 control patients for bacterial vaginosis. RESULTS: Patients with preterm labor were diagnosed with bacterial vaginosis significantly more often (13.8%, 95% confidence interval (CI) (7.7-22.0) than control patients (0.0%, 95% CI (0.0-3.6)) (P<0.001). Among the former, the time elapsed to delivery was identical regardless of the patient's bacterial vaginosis status (elapsed time: 35.9 versus 37.1 days, rate of spontaneous preterm birth 42.9 versus 43.2%, not significant). CONCLUSION: Bacterial vaginosis is associated with preterm labor. Nonetheless, it does not appear to predict preterm birth among these patients.

Application of quantitative PCR to the diagnosis and monitoring of Pseudomonas aeruginosa colonization in 5-18-year-old cystic fibrosis patients.

Early detection of Pseudomonas aeruginosa and early aggressive treatment are recommended to delay chronic infection in cystic fibrosis (CF) patients. The aim of this study was to assess a quantitative PCR (q-PCR) assay for the diagnosis of early P. aeruginosa colonization in 23 young CF patients (group A, age range 7-18 years) and to survey the eradication of P. aeruginosa in 10 young CF patients (group B, age range 5-18 years) after an initial antibiotic treatment. q-PCR results for consecutive sputum samples from each patient during a period of 18 months were compared with bacterial cultures during the same period plus an additional period of 12 months, and with concomitant clinical signs of pulmonary exacerbation. The q-PCR and bacterial cultures were negative for 17 of the 23 patients in group A and six of the 10 patients in group B during the study period. However, consecutive positive q-PCR results were observed for one patient in group A and three patients in group B, while the bacterial cultures for the same sputum sample remained negative. They preceded positive P. aeruginosa bacterial cultures at 7 and 8 months for two patients in group B. These positive results were associated with a worsening of the clinical status of patients, but pulmonary exacerbation appeared non-specific for the diagnosis of early P. aeruginosa colonization since pulmonary exacerbations were observed in patients in whom q-PCR or bacterial culture remained negative. In conclusion, q-PCR may be a useful additional tool to provide information on the P. aeruginosa status of CF patients.

Pseudomonas aeruginosa may accumulate drug resistance mechanisms without losing its ability to cause bloodstream infections.

In this study, we systematically investigated the resistance mechanisms to beta-lactams, aminoglycosides, and fluoroquinolones of 120 bacteremic strains of Pseudomonas aeruginosa. Pulsed-field gel electrophoresis genotyping showed that 97 of these strains were represented by a single isolate, 10 by 2 and 1 by 3 clonally related isolates, respectively. Seventy-five percent (90 out of 120) of the bacteremic P. aeruginosa strains displayed a significant resistance to one or more of the tested antimicrobials (up to 11 for 1 strain). These strains were found to harbor a great diversity of resistance mechanisms (up to 7 in 1 strain), leading to various levels of drug resistance. Interestingly, 11 and 36% of the isolates appeared to overproduce the MexAB-OprM and MexXY-OprM efflux systems, respectively. Altogether, our results show that P. aeruginosa may accumulate intrinsic (overproduction of cephalosporinase AmpC, increased drug efflux, fluoroquinolone target mutations, and deficient production of porin OprD) and exogenous (production of secondary beta-lactamases and aminoglycoside-modifying enzymes) resistance mechanisms without losing its ability to generate severe bloodstream infections. Consequently, clinicians should be aware that multidrug-resistant P. aeruginosa may remain fully pathogenic.

Omega-3 polyunsaturated fatty acids improve host response in chronic Pseudomonas aeruginosa lung infection in mice.

Pseudomonas aeruginosa is a gram-negative bacilli frequently encountered in human pathology. This pathogen is involved in a large number of nosocomial infections and chronic diseases. Herein we investigated the effects of polyunsaturated fatty acids (PUFA) in chronic Pseudomonas aeruginosa lung infection. C57BL/6 mice were fed for 5 wk with specifically designed diets with high contents in either omega-3 (omega-3) or omega-6 PUFA and compared to a control diet. P. aeruginosa included in agarose beads was then instilled intratracheally, and the animals were studied for 7 days. On the 4th day, the mice fed with the omega-3 diet had a higher lean body mass gain and a lower omega-6:omega-3 ratio of fatty acids extracted from the lung tissue compared with the other groups (P < 0.05). The omega-3 group had the lowest mortality. Distal alveolar fluid clearance (DAFC) as well as the inflammatory response and the cellular recruitment were higher in the omega-3 group on the 4th day. The effect on DAFC was independent of alpha-epithelial Na(+) channels (alpha-ENaC), beta-ENaC, and alpha(1)-Na-K-ATPase mRNA expressions, which were not altered by the different diets. In conclusion, a diet enriched in omega-3 PUFA can change lung membrane composition and improve survival in chronic pneumonia. This effect on survival is probably multifactorial involving the increased DAFC capacity as well as the optimization of the initial inflammatory response. This work suggests that a better control of the omega-6/omega-3 PUFA balance may represent an interesting target in the prevention and/or control of P. aeruginosa infection in patients.

Long-chain polyunsaturated fatty acids modulate lung inflammatory response induced by Pseudomonas aeruginosa in mice.

Polyunsaturated fatty acid (PUFA) immunomodulatory properties have been studied extensively in chronic infections. Few studies have focused on acute infection; thus, PUFA effects in a mouse model of Pseudomonas aeruginosa (PA)-induced lung injury were evaluated. C57BL/6 mice were randomized to be fed for 3 wk with an eicosapentaenoic acid (EPA) diet, an arachidonic acid (AA) diet, or a control diet [saturated fatty acids]. Lung injury was induced by intratracheal instillation of 10(7) CFU of PA per mouse. In each diet group, animals were studied either without or after PA-inducing lung injury. Evaluation criteria were early mortality; inflammatory response assessed with tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-10 levels in bronchoalveolar lavage; lung injury evaluation; and extravascular lung water, assessed 24 h after the injury. After PA-induced lung injury, no difference in early mortality was observed; TNF-alpha level was significantly higher in the EPA diet than in the other two diet groups. No difference for the other cytokines was found among the groups. Lung edema was also more important in the EPA group, consistent with the variations of TNF-alpha levels. Our study clearly shows that in PA-induced acute lung injury, n-3 PUFA induces differences in the inflammatory response with a higher level of lung edema. Modulation of the inflammatory response with n-3 PUFA can influence the response to a bacterial challenge.

Clinical and microbiological features of Inquilinus sp. isolates from five patients with cystic fibrosis.

Patients with cystic fibrosis (CF) may be colonized with unusual gram-negative bacilli whose identification is difficult and clinical impact unclear. We describe the clinical and microbiological features of five colonizations with organisms belonging to the recently described genus Inquilinus in CF patients. Isolates were identified from Burkholderia cepacia selective medium by means of 16S rRNA analysis. All of them were resistant to colistin, penicillins, cephalosporins, and monobactams but exhibited a remarkable susceptibility to imipenem. One of the five patients was transiently colonized with a nonmucoid isolate, whereas the four other patients were persistently colonized over the period of follow-up (8 to 21 months) with mucoid isolates. Pulsed-field gel electrophoresis of SpeI-digested genomic DNA was powerful for strain genotyping and demonstrated the clonality of Inquilinus sp. colonization for the two patients tested. Clinical evolution after the onset of Inquilinus was heterogeneous, but for at least one patient the lung function worsened and eradication of Inquilinus sp. was unsuccessful despite several imipenem courses. Finally, Inquilinus spp. may represent a new threat for CF patients due to their mucoid characteristic, their multiresistant pattern to antibiotics, and their ability to persist in the respiratory tract.

Continuous infusion of ceftazidime in the empiric treatment of febrile neutropenic children with cancer.

PURPOSE: Infection remains one of the most important complications in cancer therapy. The choice of antibiotics and the method of administration can affect results. Beta-lactam antibiotics can be administered by several short injections per day or by continuous infusion. The latter modality may provide superior pharmacokinetics. PATIENTS AND METHODS: The authors studied the pharmacokinetics of ceftazidime in children treated for malignancy and in febrile aplasia after chemotherapy. They received a continuous infusion of ceftazidime (200 mg/kg/day) after a loading dose (65 mg/kg/day) administered with amikacin (25 mg/kg/day) and vancomycin (50 mg/kg/day). RESULTS Twenty-three pharmacokinetic studies were performed. Mean ceftazidime serum levels were 31.1 +/- 11.9, 31.2 +/- 10, 32.4 +/- 11.6, 33 +/- 11.6, and 30.4 +/- 12.1 mg/L at 25, 27, 30, 36, and 43 hours, respectively. Treatment was tolerated well. There were no toxic or infectious deaths. CONCLUSIONS: Ceftazidime's time-dependent pharmacokinetics shows the advantage of continuous infusion. This study confirmed the feasibility and safety of this administration schedule in the empiric treatment of febrile neutropenic children with cancer.

Pasteurella multocida and intrauterine device: a woman and her pets.

Human infections with Pasteurella multocida are frequently attributed to transmission from animals. Although some cases of prosthetic implant infections have been described few gynecological cases have been reported. We describe a case of intrauterine device endometritis due to P. multocida.