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Impact of piperacillin resistance on the outcome of Pseudomonas ventilator-associated pneumonia.

BACKGROUND: The impact of antibiotic resistance on the outcome of infections due to Gram-negative bacilli, especially Pseudomonas, remains highly controversial. STUDY OBJECTIVE, DESIGN, AND PATIENTS: We evaluated the impact of piperacillin resistance on the outcomes of Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) for patients who had received appropriate empiric antibiotics before enrollment in the PNEUMA trial, a multicenter randomized study comparing 8 vs 15 days of antibiotics. RESULTS: Despite similar characteristics at intensive care unit (ICU) admission, patients infected with piperacillin-resistant Pseudomonas strains were more acutely ill at VAP onset and had a higher 28-day mortality rate (37 vs 19%; P = 0.04) than those with piperacillin-susceptible Pseudomonas VAP. Factors associated with 28-day mortality retained by multivariable analysis were: age (OR: 1.07; 95% CI: 1.03-1.12); female gender (OR: 4.00; 95% CI: 1.41-11.11); severe underlying comorbidities (OR: 2.73; 95% CI: 1.02-7.33); and SOFA score (OR: 1.17; 95% CI: 1.03-1.32), but piperacillin resistance did not reach statistical significance (OR: 2.00; 95% CI: 0.72-5.61). The VAP recurrence rates, either superinfection or relapse, and durations of mechanical ventilation and ICU stay did not differ as a function of Pseudomonas-resistance status. CONCLUSIONS: For patients with Pseudomonas VAP benefiting from appropriate empiric antibiotics, piperacillin resistance was associated with increased disease severity at VAP onset and higher 28-day crude mortality; however, after controlling for confounders, piperacillin-resistance was no longer significantly associated with 28-day mortality. The VAP recurrence rates and durations of ICU stay and mechanical ventilation did not differ for susceptible and resistant strains.

Aged↗

Lymphocyte responsiveness to Pseudomonas aeruginosa in cystic fibrosis: Relationship to status of pulmonary disease in sibling pairs.

Lymphocyte proliferative responses to Pseudomonas aeruginosa and Staphylococcus aureus were evaluated in six sibling pairs with cystic fibrosis. In each pair, one sibling had advanced clinical disease, whereas the other sibling was in good clinical condition. Three in this latter group had no clinically apparent Pseudomonas bronchitis. In all cases, the average responses to Pseudomonas isolated from each sibling pair were lower in the sibling with advanced clinical disease. This difference was not observed in the responses to Staphylococcus. Normal plasma or plasma from patients with CF in good clinical condition does not restore the responses in patients with advanced clinical disease. However, plasma from patients with low or no responses to Pseudomonas inhibits the responses of responding siblings. A progressive specific lymphocyte unresponsiveness to Pseudomonas may play an important role in the increasing destructiveness of chronic pulmonary Pseudomonas infection in cystic fibrosis.

Adolescent↗

Biocontrol of Pythium in the pea rhizosphere by antifungal metabolite producing and non-producing Pseudomonas strains.

AIMS: Four well-described strains of Pseudomonas fluorescens were assessed for their effect on pea growth and their antagonistic activity against large Pythium ultimum inocula. METHODS AND RESULTS: The effect of Pseudomonas strains on the indigenous soil microflora, soil enzyme activities and plant growth in the presence and absence of Pythium was assessed. Pythium inoculation reduced the shoot and root weights, root length, and the number of lateral roots. The effect of Pythium was reduced by the Pseudomonas strains. Strains F113, SBW25 and CHAO increased shoot weights (by 20%, 22% and 35%, respectively); strains Q2-87, SBW25 and CHAO increased root weights (14%, 14% and 52%). Strains SBW25 and CHAO increased root lengths (19% and 69%) and increased the number of lateral roots (14% and 29%). All the Pseudomonas strains reduced the number of lesions and the root and soil Pythium populations, while SBW25 and CHAO increased the number of lateral roots. Pythium inoculation increased root and soil microbial populations but the magnitude of this effect was Pseudomonas strain-specific. Pythium increased the activity of C, N and P cycle enzymes, while the Pseudomonas strains reduced this effect, indicating reduced plant damage. CONCLUSION: Strains SBW25 and CHAO had the greatest beneficial characteristics, as these strains produced the greatest reductions in the side effects of Pythium infection (microbial populations and enzyme activities) and resulted in significantly improved plant growth. Strain SBW25 does not produce antifungal metabolites, and its biocontrol activity was related to a greater colonization ability in the rhizosphere. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first critical comparison of such important strains of Ps. fluorescens showing disease biocontrol potential.

Pisum sativum↗

Pseudomonas aeruginosa folliculitis after shower/bath exposure.

BACKGROUND: Pseudomonas aeruginosa folliculitis (PF) can develop after exposure to contaminated water in heated swimming pools, whirlpools, and hot-tubes, or after diving suit dressing. METHODS: We observed and studied 14 cases of PF after shower/bath exposure, an underestimated pathogenic event. Cutaneous and environmental microbiological evaluations were performed. RESULTS: In our cases, the clinical expression of dermatitis was constant, PF being a clinically well recognizable skin infection, presenting with follicular, macular, and papulopustular lesions located on the lateral aspect of the trunk, axillary folds, hips, buttocks, and suprapubic area. In all cases, Pseudomonas aeruginosa was isolated from lesional skin; seven cases were serotyped revealing, in three cases, serotype 0 : 1, in two cases 0 : 8, in one case 0 : 10, and in one case 0 : 11. In three families, Pseudomonas aeruginosa was isolated in the well water. In a further three families, Pseudomonas aeruginosa was isolated from bathroom and kitchen components. CONCLUSIONS: Based on our experience, we suggest that shower/bath exposure should be definitively included amongst the possible pathogenic events causing PF. Pseudomonas aeruginosa is responsible for a number of clinical pictures, e.g. otitis externa, conjunctivitis, toe web intertrigo, green nail syndrome, infection of burns and wounds, and folliculitis. Pseudomonas aeruginosa folliculitis (PF) has been reported to develop as a consequence of exposure to contaminated water in heated swimming pools, whirlpools, and hot-tubes, or related to diving suits and leg waxing.1-4 We observed 14 cases of PF after shower/bath exposure. This is probably an underestimated pathogenic event; to our knowledge, only one case has been reported to date.5 In our patients, the clinical expression of dermatitis was constant, PF being a clinically well recognizable skin condition.

Adult↗

[Pseudomonas septicemia after endoscopic interventions on the bile duct system].

In the first half of 1982 there was an increase in septicaemia cases, especially among patients with biliary-tract drainage. The septicaemia incidence rose from 1.25% to 4.4%. The proportion of Pseudomonas septicaemias was especially high: of 20 patients (21 episodes of septicaemia) nine had infections with Pseudomonas aeruginosa alone, three a mixed septicaemia. In ten of these twelve patients there was impaired drainage by a malignant tumour. Three patients with a tumour stenosis died, mainly of the septicaemia. The cause of this increased incidence of Pseudomonas septicaemias lay in contamination of the instruments; it was in part sustained by the Endo-Washer. The connection between the septicaemia after endoscopic-retrograde cholangiography and recontamination of the endoscope was discovered after sero- and pyocin-typing of the Pseudomonas strains. By changing the methods of disinfection the Pseudomonas incidence among endoscopies fell. However, in individual samplings Pseudomonas can still be demonstrated on instruments as well as on the Endo-Washer.

Blood↗

Epidemiology of infections with Pseudomonas aeruginosa in burn patients: the role of hydrotherapy.

Pseudomonas aeruginosa remains a cause of serious wound infection and mortality in burn patients. By means of restriction fragment length polymorphism analysis and a DNA probe for the pilin gene of Pseudomonas, a lethal strain of nosocomial P. aeruginosa was identified as the cause of an outbreak of wound infections among burn patients. Environmental surveys suggested an association of the outbreak with hydrotherapy provided to many patients in a common facility. In a trial of burn wound care without hydrotherapy, overall mortality was reduced significantly, mortality associated with pseudomonas sepsis was eliminated, and the strain of P. aeruginosa associated with earlier mortality was eradicated. Moreover, fewer nosocomial pseudomonas infections, lower levels of pseudomonas resistance to aminoglycoside antibiotics, significantly fewer pseudomonas infections of skin graft donor sites, and later appearance of Pseodomonas species in burn patients were found during the period when hydrotherapy was not used.

Adolescent↗

The role of Pseudomonas aeruginosa in infections.

Pseudomonas aeruginosa, an organism ubiquitous in nature, has assumed an increasingly prominent role as the aetiological agent in serious infections in hospitalized patients. Pseudomonas has a number of pathogenic properties, which include its capsule, exotoxin A and various proteases. Although normal individuals infrequently carry this organism as part of their flora, patients with burns, malignancy, and after surgery often are colonized and subsequently infected with Pseudomonas. Infections produced by Pseudomonas include bacteraemia, respiratory infection, urinary tract infection, osteomyelitis, and infections of burns and soft tissues. Because of the resistance properties of Pseudomonas, therapy has been difficult. However, the development of highly effective antipseudomonas penicillins has brightened the picture. Nonetheless great progress can still be made in control and prevention of serious Pseudomonas infection.

Burns↗

Pseudomonas plecoglossicida sp. nov., the causative agent of bacterial haemorrhagic ascites of ayu, Plecoglossus altivelis.

A new Pseudomonas species, for which the name Pseudomonas plecoglossicida is proposed, was isolated from cultured ayu (Plecoglossus altivelis) with bacterial haemorrhagic ascites. The causative agent was similar to Pseudomonas putida biovar A in its phenotypic characteristics and on the basis of 16S rRNA gene sequence analysis, but it reduced nitrate to nitrite. Furthermore, it was distinguished phenotypically from Pseudomonas putida biovar A by utilization of D-malate, L-(+)-tartrate, m-tartrate and nicotinate. The levels of DNA-DNA hybridization between the isolate strain FPC 951T and other reference strains of Pseudomonas species, including Pseudomonas putida, were less than 50%. The G+C content of the DNA of FPC 951T was 62.8 mol%. Strain FPC 951T (= ATCC 700383T) is designated the type strain of the new species.

Animals↗

Pseudomonas psychrotolerans sp. nov.

Three yellow-pigmented, Gram-negative, rod-shaped, non-spore-forming bacterial strains, C36T, C37 and C39, were isolated in the Medical Clinic for Small Animals and Ungulates at the University for Veterinary Medicine in Vienna, Austria. On the basis of 16S rRNA gene sequence similarity, strain C36T was shown to belong to the genus Pseudomonas; Pseudomonas oleovorans DSM 1045T was the nearest relative (99.5 % sequence similarity). Other Pseudomonas species shared <97 % sequence similarity with strain C36T. The presence of Q-9 as the major ubiquinone, the predominance of putrescine and spermidine in its polyamine patterns and its fatty acid profile [i.e. the predominance of C(16 : 0), summed feature 3 (C(16 : 1)omega7c and/or 2-OH C(15 : 0) iso), C(18 : 1)omega7c and the presence of 3-OH C(10 : 0), 3-OH C(12 : 0) and 2-OH C(12 : 0)] were in agreement with identification of this strain as a member of the genus Pseudomonas. Physiological and biochemical characteristics and the results of genomic fingerprinting clearly differentiated strain C36T from its phylogenetic relative P. oleovorans DSM 1045T. Results from DNA-DNA hybridization showed that strain C36T represents a species that is distinct from P. oleovorans DSM 1045T. These data demonstrate that strain C36T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas psychrotolerans sp. nov. is proposed. The type strain is C36T (= LMG 21977T = DSM 15758T). Additionally, physiological, biochemical, chemotaxonomic and genomic fingerprints indicate that P. oleovorans ATCC 29347 may not be a member of the species P. oleovorans sensu stricto.

Animals↗

Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia.

Pneumonia is associated with elevated concentrations of the proinflammatory cytokine interleukin (IL)-1 in the pulmonary compartment. To study the role of IL-1 in the pathogenesis of Pseudomonas pneumonia, IL-1 receptor type 1 gene-deficient (IL-1R -/-) mice and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. The absence of the IL-1 signal attenuated the outgrowth of Pseudomonas in lungs, as reflected by an increasing number of colony-forming units (cfu) during Pseudomonas pneumonia in wild-type mice and a concurrently decreasing number of cfu during pulmonary infection in IL-1R -/- mice (P < 0.05, IL-1R -/- mice vs. wild-type mice). Influx of neutrophils was decreased in bronchoalveolar lavage fluids in IL-1R -/- mice compared with wild-type mice. Similarly, lung levels of cytokines (tumor necrosis factor-alpha, IL-6) and chemokines (macrophage inflammatory protein-2 and KC) were lower in IL-1R -/- mice 24 h postinoculation. Consistent with results obtained in IL-1R -/- mice, treatment of wild-type mice with IL-1R antagonist also diminished outgrowth of Pseudomonas when compared with wild-type mice treated with vehicle (P < 0.05). These results demonstrate that an absence or reduction in endogenous IL-1 activity improves host defense against Pseudomonas pneumonia while suppressing the inflammatory response.

Animals↗

Airway epithelial cell tolerance to Pseudomonas aeruginosa.

BACKGROUND: The respiratory tract epithelium is a critical environmental interface that regulates inflammation. In chronic infectious airway diseases, pathogens may permanently colonize normally sterile luminal environments. Host-pathogen interactions determine the intensity of inflammation and thus, rates of tissue injury. Although many cells become refractory to stimulation by pathogen products, it is unknown whether the airway epithelium becomes either tolerant or hypersensitive in the setting of chronic infection. Our goals were to characterize the response of well-differentiated primary human tracheobronchial epithelial cells to Pseudomonas aeruginosa, to understand whether repeated exposure induced tolerance and, if so, to explore the mechanism(s). METHODS: The apical surface of well-differentiated primary human tracheobronchial epithelial cell cultures was repetitively challenged with Pseudomonas aeruginosa culture filtrates or the bacterial media control. Toxicity, cytokine production, signal transduction events and specific effects of dominant negative forms of signaling molecules were examined. Additional experiments included using IL-1beta and TNFalpha as challenge agents, and performing comparative studies with a novel airway epithelial cell line. RESULTS: An initial challenge of the apical surface of polarized human airway epithelial cells with Pseudomonas aeruginosa culture filtrates induced phosphorylation of IRAK1, JNK, p38, and ERK, caused degradation of IkappaBalpha, generation of NF-kappaB and AP-1 transcription factor activity, and resulted in IL-8 secretion, consistent with activation of the Toll-like receptor signal transduction pathway. These responses were strongly attenuated following a second Pseudomonas aeruginosa, or IL-1beta, but not TNFalpha, challenge. Tolerance was associated with decreased IRAK1 protein content and kinase activity and dominant negative IRAK1 inhibited Pseudomonas aeruginosa--stimulated NF-kappaB transcriptional activity. CONCLUSION: The airway epithelial cell response to Pseudomonas aeruginosa entails adaptation and tolerance likely mediated, in part, by down-regulation of IRAK1.

Cell Line↗

Ventilator-associated pneumonia due to Pseudomonas aeruginosa.

OBJECTIVE: Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa has been associated with higher case fatality rates than VAP caused by other bacterial etiologies. The causes of this excess mortality are unclear. DESIGN: Retrospective review of 38 consecutive ventilated patients with Pseudomonas pneumonia, documented by highly reliable methods. Charts of five additional patients were unavailable for review. SETTING: Medical ICUs of a university-affiliated Veterans Affairs Medical Center and a university-affiliated municipal hospital. MEASUREMENTS: Prospectively collected hospital admission acute physiologic and chronic health examination (APACHE) II scores and cause of ICU admission. Retrospectively calculated organ failure and APACHE scores, VAP score. Clinical and microbiologic variables. Antibiotic treatment and outcome. Direct cause of death by standard definitions. RESULTS: Overall mortality was 69% (26/38), significantly higher than the APACHE II predicted mortality of 42.6% (p=0.037). At least 38% (10/26) of deaths were directly attributable to Pseudomonas VAP. Multivariate analysis of factors associated with death found infectious cause for ICU admission (odds ratio [OR]=8.67; 95% confidence interval [CI], 0.86 to 85.94) and number of organ dysfunctions on the day of diagnosis (OR=1.73, 95% CI, 1.02 to 2.92) were significant. Septic shock from Pseudomonas VAP, septic shock from subsequent infection, and multiple organ dysfunction syndrome were the most common immediate causes of death. Mortality increased linearly with increasing APACHE III score on the day of diagnosis. Of initial antibiotic regimens, 67% (26/36) were considered failures. Persistent pneumonia occurred in 35% of patients while recurrent pneumonia was unusual (1/38). CONCLUSIONS: Development of Pseudomonas pneumonia results in a mortality rate in excess of that due to the presenting illness. The attributable mortality determined by several means appears to approach 40%. The excess mortality appears to be related to the host defense response to the pneumonia rather than any characteristic of the pneumonia. Even standard antibiotic regimens fail frequently and do not prevent the excess mortality. Since at least 38% of deaths can be directly attributable to the Pseudomonas pneumonia, improvement in therapy is needed.

APACHE↗

Pseudomonas aeruginosa infection in cancer patients.

Pseudomonas aeruginosa is an important cause of infection in immunosuppressed patients, particularly those with cancer. However, it is being recognized with greater frequency in patients who appear to be immunocompetent. Changes in modern lifestyles have led to the appearance of some new manifestations of pseudomonas infection including corneal ulceration and keratitis associated with contact lenses, and hot-tub- or whirlpool-associated folliculitis. These represent additional hazards to patients with cancer. Many studies, both in animals and humans, have contributed to our knowledge of the pathogenesis, immunology, treatment, and prevention of pseudomonas infections. Although the aminoglycosides represented a significant step forward in the treatment of these infections, of greater importance was the discovery of the antipseudomonal penicillins. These antibiotics are more effective than the aminoglycosides in neutropenic patients, who are especially susceptible to pseudomonal infections. The older antipseudomonal penicillins (carbenicillin, tircarcillin) have largely been replaced by newer ones (mezlocillin, azlocillin, pipercillin) which are more potent in vitro against P. aeruginosa. Although the accepted therapeutic practice has been to utilize a penicillin in combination with an aminoglycoside, the introduction of newer beta lactam agents and fluoroquinolones with antipseudomonal properties offers the possibility of other approaches to combination therapy. These include the combination of a penicillin or a cephalosporin or the combination of a quinolone with an aminoglycoside or a betalactam antibiotic. However, the development of newer antimicrobial agents is not likely to be a lasting solution to the problem of pseudomonas infections. Since pseudomonas infection often progresses rapidly, optimal results will always depend upon the prompt initiation of appropriate therapy in febrile patients, particularly those who are at high risk. The use of granulocyte transfusions has proved to be of limited benefit. Early data with the use of monoclonal antibodies is promising, and the results of large-scale trials are eagerly awaited. It is hoped that continuing investigation of pseudomonas vaccines will lead to the discovery of effective prophylaxis for highly susceptible patients. It is also hoped that with the availability of GM-CSF it will become possible to reduce the period of risk for serious infections. Finally, a reduction in the frequency of microbiologically proven P. aeruginosa infections in cancer patients should not lead to the assumption that these organisms do not constitute a problem in such patients anymore. The use of prophylactic antibiotics and prompt empiric antibiotic coverage for therapy has resulted in this decline. Cultures are therefore unlikely to be positive with the same frequency as they were before antimicrobial prophylaxis and empiric antibiotic therapy became standard practice.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

Removal of copper ion by Pseudomonas spp.

Copper-resistant Pseudomonas sp. 41Y, Pseudomonas pseudomallei 13-1 and Pseudomonas aeruginosa 7 were used in the present study. When the latter two organisms were added to copper-containing 1/3 strength Tryptic Soy Broth, more than 99.5% of the copper ion was removed from the medium within 24 h. If copper solution was added to hog waste slurry, a reduction in the copper ion concentration could be detected only when the added bacteria started to grow in it, whereas in a mineral medium supplemented with glycerol-2-phosphate, both bacteria could remove about 50% of the copper ion from the medium within 24 h. When cell suspension of Pseudomonas sp. 41Y was autoclaved, no copper ion removal was observed. Different incubation temperatures, including 30 degrees C, 37 degrees C and 45 degrees C, had no effect on the percent of copper ion removed by both Pseudomonas sp. 41Y and P. pseudomallei 13-1. On the other hand, if the pH value of the solution was lowered from 8.2 to 6.0, there was a drastic decrease in copper removal. A similar reduction of copper ion removal ability was also observed with the addition of lead ion. When cells of Pseudomonas sp. 41Y were embedded in sodium alginate, there was a decrease in its ability to remove copper ion as compared to the free-living cells.

Chemical Precipitation↗

Treatment of Pseudomonas infections in peritoneal dialysis patients.

Pseudomonas species infections in the peritoneal dialysis population consist primarily of peritonitis or exit site infections. These organisms have traditionally proven difficult to eradicate, and the standard antibiotic regimen has carried the potential for nephrotoxicity. At our institution, all peritoneal dialysis patients with Pseudomonas exit site infections or peritonitis were treated with an antibiotic combination of intraperitoneal ceftazidime and oral ciprofloxacin. Treatment duration was dependent upon the site of infection. Recurrent exit site infections were treated with a repeated course of the antibiotics, and with surgical debridement and subsequent shaving of the external cuff of double-cuffed catheters. We saw a total of 11 Pseudomonas aeruginosa exit site infections in 7 patients (4 recurrent). Patients with recurrent infections were subsequently cured with the regimen as outlined above. Of 7 patients with Pseudomonas species peritonitis (aeruginosa, fluorescens, stutszeri, and maltophilia), 5 were cured with the initial antibiotic regimen. The 2 failures were both infected with Pseudomonas maltophilia, which is consistent with observed organism sensitivity data. The combination of ceftazidime and ciprofloxacin with the option for surgical debridement of the external cuff (in exit site infections) appears effective in the treatment of Pseudomonas species infections in the peritoneal dialysis population. Sensitivity data should be used to adjust the antibiotic regimen when appropriate.

Ceftazidime↗

[Therapy against intractable respiratory infections with Pseudomonas aeruginosa].

Patients with diffuse panbronchiolitis (DPB) are frequently affected by Pseudomonas aeruginosa superinfection. To elucidate the predisposing factors of Pseudomonas aeruginosa superinfection in patients with DPB, we analyzed the age of onset, duration of the disease, chest X-ray findings, blood gas levels, lung function, and bacteriological findings. These data were compared with those of patients who had not developed Pseudomonas aeruginosa superinfection. The administration of antibiotics and corticosteroids did not influence the incidence of Pseudomonas aeruginosa superinfection in DPB patients. The patients with long duration, more severe lung function and more deteriorated roentgenological findings developed Pseudomonas aeruginosa superinfection more easily. These infections in the lower respiratory tract significantly affect the prognosis of DPB patients. Using long-term administrations of a new quinolone antibacterial agent against DPB, acute exacerbations were controlled in some patients and the frequency of their admission to hospital was lessened. A multicomponent vaccine raised antibody titers against OEP, elastase, protease and exotoxin in DPB patients. Further clinical investigations are under way in our hospital to confirm the clinical usefulness of the Pseudomonas aeruginosa multicomponent vaccine in DPB from prophylactic and therapeutic points of view.

4-Quinolones↗

Successful treatment of adult respiratory distress syndrome by histamine and prostaglandin blockade in a porcine Pseudomonas model.

Porcine Pseudomonas adult respiratory distress syndrome (ARDS) has been shown to respond to combination therapy of 150 mg of cimetidine, 12.5 mg/kg of ibuprofen, 10 mg/kg of diphenhydramine, 0.2 mg/kg of ketanserin, and 30 mg/kg of methylprednisolone (CIDKM or Poly-5) given at 20 and 120 minutes after the onset of a continuous infusion of liver Pseudomonas aeruginosa, 5 X 10(8) colony-forming units (CFU) ml at 0.3 ml/20 kg/min. The present study was designed to determine the minimal, effective therapy by selective deletion of individual agents from CIDKM. Eight groups were studied: saline control (S, n = 9), Pseudomonas control (P, n = 8), and the following Pseudomonas plus treatment groups (each n = 5): CIDKM (cimetidine, ibuprofen, diphenhydramine, and ketanserin), CID (cimetidine, ibuprofen, and diphenhydramine), IC (ibuprofen and cimetidine), ID (ibuprofen and diphenhydramine), and CD (cimetidine and diphenhydramine). Pseudomonas alone produced severe ARDS with significant (p less than .05) decreases in PAO2 cardiac index, and systemic arterial pressure and significant increases in pulmonary artery pressure, extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux measured as slope index (SI). Full therapy, CIDKM or Poly-5, showed significant improvement in all parameters. Deletion of methylprednisolone did not significantly effect any parameter measured. The deletion of ketanserin, leaving CID, did not alter treatment efficacy, except for a significant decline in cardiac index at 3 hours. Deletion of ibuprofen from CID resulted in a failure to reverse pulmonary arterial hypertension, hypoxemia, elevated EVLW, and increased SI. Removal of either cimetidine or diphenhydramine from CID resulted in significant increases in EVLW compared with control levels and SI compared with both control levels and CID. These results indicate that a combination of both histamine H1 and H2 receptor blockers and the cyclooxygenase inhibitor, ibuprofen, is effective and essential in the treatment of hypoxemia, early pulmonary hypertension, and pulmonary microvascular injury in this fulminant model of porcine Pseudomonas ARDS.

Animals↗

Colonization of the Arabidopsis rhizosphere by fluorescent Pseudomonas spp. activates a root-specific, ethylene-responsive PR-5 gene in the vascular bundle.

Plants of which the roots are colonized by selected strains of non-pathogenic, fluorescent Pseudomonas spp. develop an enhanced defensive capacity against a broad spectrum of foliar pathogens. In Arabidopsis thaliana, this rhizobacteria-induced systemic resistance (ISR) functions independently of salicylic acid but requires responsiveness to jasmonic acid and ethylene. In contrast to pathogen-induced systemic acquired resistance (SAR), ISR is not associated with systemic changes in the expression of genes encoding pathogenesis-related (PR) proteins. To identify genes that are specifically expressed in response to colonization of the roots by ISR-inducing Pseudomonas fluorescens WCS417r bacteria, we screened a collection of Arabidopsis enhancer trap and gene trap lines containing a transposable element of the Ac/Ds system and the GUS reporter gene. We identified an enhancer trap line (WET121) that specifically showed GUS activity in the root vascular bundle upon colonization of the roots by WCS417r. Fluorescent Pseudomonas spp. strains P. fluorescens WCS374r and P. putida WCS358r triggered a similar expression pattern, whereas ISR-non-inducing Escherichia coli bacteria did not. Exogenous application of the ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC) mimicked the rhizobacteria-induced GUS expression pattern in the root vascular bundle, whereas methyl jasmonic acid and salicylic acid did not, indicating that the Ds element in WET121 is inserted in the vicinity of an ethylene-responsive gene. Analysis of the expression of the genes in the close vicinity of the Ds element revealed AtTLP1 as the gene responsible for the in cis activation of the GUS reporter gene in the root vascular bundle. AtTLP1 encodes a thaumatin-like protein that belongs to the PR-5 family of PR proteins, some of which possess antimicrobial properties. AtTLP1 knockout mutant plants showed normal levels of WCS417r-mediated ISR against the bacterial leaf pathogen Pseudomonas syringae pv. tomato DC3000, suggesting that expression of AtTLP1 in the roots is not required for systemic expression of ISR in the leaves. Together, these results indicate that induction of AtTLP1 is a local response of Arabidopsis roots to colonization by non-pathogenic fluorescent Pseudomonas spp. and is unlikely to play a role in systemic resistance.

Amino Acid Sequence↗