Acetic acid in the treatment of superficial wounds infected by Pseudomonas aeruginosa.
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Over a four year period 8 cases of Pseudomonas cepacia (PC) infection were diagnosed in our unit. Two patients developed PC septicemia following the insertion of porcine arterio venous grafts for hemodialysis access. Six developed PC peritonitis whilst on peritoneal dialysis and one a PC urinary tract infection following cystoscopy. Of the three patients who died two were known to have had PC septicemia. This infection was seen in patients whose host defence mechanisms were considerably impaired or when foreign or prosthetic material had been inserted. PC has developed a resistance to most broad spectrum antibiotics and antiseptics and is easily cultured in ordinary media. Prophylactic use of antibiotics such as the cephalosporins in peritoneal dialysis solutions appears to greatly increase the risk of developing serious infection with PC. Early detection and treatment of this unusual organism with appropriate antibiotics is mandatory.
The protective capacity of passively transferred immunoglobulin G (IgG) fractions from antitoxin (AT-IgG), antielastase (AE-IgG), and antilipopolysaccharide (ALPS-IgG) against Pseudomonas aeruginosa infection was evaluated in a murine burn wound sepsis model. Complete protection was afforded by homologous ALPS-IgG against intermediate challenge doses (10 50% lethal doses) of P. aeruginosa PA220, whereas AT-IgG and AE-IgG offered no significant protection (P less than 0.5). The simultaneous transfer of AT-IgG or AE-IgG with ALPS-IgG gave no additional protection above that seen with ALPS-IgG alone. The transfer of ALPS-IgG did not dramatically alter bacterial multiplication in the skin at the site of infection. However, bacteremia and infection of the liver were prevented. In parallel experiments, AT-IgG or AE-IgG did not significantly alter either the course of the infection or the number of bacteria seen in the blood, liver, or skin when compared with controls. ALPS-IgG administered 24 h before infection, at the time of infection, or 4 h postinfection provided complete protection. Even when ALPS-IgG was transferred at a time when the infection was well established locally in the skin (8 h postinfection), highly significant protection (P greater than 0.999) was obtained. Protection afforded by ALPS-IgG was serotype specific. These results indicate that antibody to lipopolysaccharide is of critical importance for protection against P. aeruginosa challenge in a relevant animal model.
The possibility of detecting P. aeruginosa antibodies in patients by means of indirect solid-phase EIA techniques is shown. This assay is carried out with the use of reagents produced in the USSR: polystyrene assay plates manufactured by the Lenigrad Medpolymer Works are used as carriers, P. aeruginosa vaccine (pyoimmunogen) obtained under semi-industrial conditions at the Mechnikov Central Research Institute for Vaccines and Sera is used as antigenic complex and the commercial preparation produced by the Gamaleia Research Institute of Epidemiology and Microbiology serves as conjugate. The studies have revealed that in 95% of cases the level of antibodies in the sera of patients with acute destructive pneumonia accompanied by pleural empyema, abscesses of internal organs and acute hematogenic osteomyelitis is essentially higher than the level of "normal" antibodies in healthy donors from whom biologically confirmed P. aeruginosa cultures can be isolated. In the groups of patients with similar nosological forms of diseases caused by other infective agents such difference in antibody titers is not detected. These results suggest that the detection of antibodies to P. aeruginosa in patients' sera by means of EIA can be used as an additional test for the diagnosis of P. aeruginosa infections.
Melioidosis, a severe, often fatal disease caused by infection with Pseudomonas pseudomallei, has been thought to be a rare endemic disease relatively limited to the areas 20 degrees on either side of the equator. However, an increasing number of people travelling to these areas are reportedly suffering from this disease. It is timely to review this disease for doctors who are unfamiliar with this disease. P. pseudomallei, first discovered by Whitmore and Krishnaswami in 1912, is a gram-negative aerobic rod, motile due to polar flagella, isolated from soil and natural waters in endemic areas, and presumably transmitted to human beings through skin abrasion, ingestion and inhalation. Associated underlying conditions must be searched for, such as diabetes mellitus and chronic renal failure. Clinical classification ranges from disseminated septicemic melioidosis, the most serious form, to subclinical melioidosis, the least serious form. Disseminated septicemic type is associated with high fever, multiple organ lesions with septic shock and high fatality rate within a few days after symptoms develop. This type of infection requires prompt institution of antimicrobial therapy as well as surgical intervention such as drainage. Antimicrobial agents should be carefully selected according to the susceptibility results of the isolates. During the suspected stage, ceftazidime is a drug of choice. Subclinical melioidosis associated with positive serologic test alone should be closely followed up against the potential reactivation of dormant infection with P. pseudomallei. We must certainly be aware of melioidosis and diagnose melioidosis as early as possible by completing the initial routine diagnostic procedures to febrile patients.
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OBJECTIVES: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in patients with cystic fibrosis. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudorandomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: We planned to assess the following outcomes: time to infection with Pseudomonas aeruginosa, pulmonary function, body mass index, Schwachman score, frequency of pulmonary infective exacerbations, days of antibiotic usage, days unable to carry out normal daily activities, adverse events, mortality, antibody levels to Pseudomonas aeruginosa and T cell proliferation and cytokine production in response to Pseudomonas aeruginosa. MAIN RESULTS: One trial which included 17 vaccinated patients, with follow up reported to 10 years met the inclusion criteria. Finding only a single trial, and the lack of information on our predefined outcomes limited analysis. REVIEWER'S CONCLUSIONS: There is a paucity of randomised controlled trials assessing the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. Increased understanding of modulation of the immune response by vaccination has led to the development of alternative vaccines. We suggest that there is an urgent need for newer vaccines to be evaluated in adequately-powered, multicentre randomised controlled trials examining clinically relevant end-points in addition to immunological variables. Such a trial should assess effectiveness over several years, and include follow-up of vaccinees who become colonised with Pseudomonas aeruginosa.
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It has been demonstrated that both hypercholesterolemia and infectious agents are contributing factors in atherosclerosis but their combined effect on the pulmonary vascular bed is not known. To answer this question, the authors tried to demonstrate the effects of recurrent infection on pulmonary parenchyma and vascular system in cholesterol-fed rats. Sixty-six rats were randomly divided into 4 groups: Groups I (control), II (cholesterol-rich diet), III (recurrent pulmonary Pseudomonas aeruginosa infection), IV (cholesterol-rich diet + recurrent infection). After 6 months serum cholesterol levels didn't increase in any of the groups. Central pulmonary artery wall thickness was increased in group IV (P < .0001). Although not significant, peripheral pulmonary artery wall thickness was increased in group IV. In rats fed on a cholesterol-rich diet, recurrent infection caused a significant increase in atherosclerosis, although serum cholesterol levels didn't increase. Infection and cholesterol-rich diet have a synergistic effect on atherosclerosis in the pulmonary vascular system in rats even in the absence of hypercholesterolemia.
The antibody levels in 18 batches of the preparations of human immunoglobulin, Immunovenin and Immunovenin-Intact, for intravenous injection were determined in the enzyme immunoassay with the use of the mixture of P. aeruginosa lipopolysaccharide antigens of seven immunotypes. The average antibody titers in these preparations were identical. The preparations were found to have protective action against P. aeruginosa experimental infection in mice.
The possibility of using tobramycin (Tb) in combination with P. aeruginosa polyvalent corpuscular vaccine (PaPCV) or pyocyanosis hyperimmune plasma (PHP) for the treatment of P. aeruginosa sepsis was experimentally studied. The combined use of Tb and PHP, administered in amounts corresponding to ED50 of each preparation used separately, ensured the survival of 90% of the infected mice, and the injected of PaPCV with ED50 of the antibiotic ensured the survival of 73% of the experimental animals. The combined use of Tb and the two immuno-preparations (PaPCV and PHP) for the treatment of P. aeruginosa infection proved to be more effective than their separate administrations.
PURPOSE: To demonstrate the constitutive expression and regulation of heparanase (heparan sulfate endoglycosidase) in the normal mouse eye and in mice intracorneally infected with Pseudomonas aeruginosa. METHODS: Naïve (unimmunized) and immunized C57BL/6J mice were infected with P. aeruginosa, and corneal heparanase gene and protein expression were detected by semiquantitative RT-PCR and immunoblot analysis. Immunohistochemistry was also applied to characterize corneal heparanase in naïve mice. RESULTS: Heparanase mRNA and protein expression were detected in uninfected corneas of C57BL/6J mice. Immunohistochemical studies indicated heparanase protein expression was primarily in the corneal epithelium before corneal infection and was also in the corneal stroma after infection. Immunohistochemical studies of uninfected and infected whole eyes of naïve mice indicated heparanase protein expression in most layers of the retina, but the expression did not appear to be upregulated during corneal infection. Staining was most intense in the inner photoreceptor layer of the retina. CONCLUSIONS: Heparanase was constitutively expressed in both the corneal epithelium and several retinal layers before intracorneal infection with P. aeruginosa. Temporal upregulation of corneal heparanase protein expression was detected in naïve mice during infection, most likely due to heparanase positive infiltrating cells, but the protein was not upregulated in corneas from immunized mice because they had a lower inflammatory response, associated with the restoration of corneal clarity. There did not appear to be temporal upregulation of heparanase expression in the retina of infected mice, as determined by immunohistochemistry.
Previous studies have demonstrated synergy between an aminoglycoside and a beta-lactam for treating Pseudomonas aeruginosa infections. Cystic fibrosis patients are prone to infection by this bacterium, which becomes very resistant with recurrent antibiotic treatments. The purpose of this study was to evaluate the susceptibility patterns of 122 isolates of P. aeruginosa isolated from cystic fibrosis patients to five individual antibiotics (tobramycin, ceftazidime, piperacillin, ticarcillin, and imipenem) and to four antibiotic combinations (tobramycin associated with one of the other antibiotics). Strains were selected because of their resistance to individual antimicrobial agents, which ranged from 21.3% for imipenem to 56.5% for tobramycin. By using an automated broth microdilution method, we were able to demonstrate synergy against 39 strains (32%) with tobramycin-ticarcillin, against 38 strains (31%) with tobramycin-piperacillin, against 47 strains (39%) with tobramycin-ceftazidime, and against 23 strains (19%) with tobramycin-imipenem. Of the 122 isolates, 77 (63%) were rendered significantly susceptible to at least one of the four antibiotic combinations by synergy. These results suggest that when appropriate technology is available, susceptibility to antibiotic combinations greatly improves the guide to antibiotic therapy for infections due to P. aeruginosa in cystic fibrosis patients.
Multilocus enzyme electrophoresis and ribotyping were used to characterize 83 strains of Pseudomonas cepacia, mostly isolated from cystic fibrosis (CF) patients, although a number of isolates from non-CF nosocomial infections and reference environmental strains were represented. Twenty enzyme electrophoretic types (ETs) were determined; of these, one clone (ET12) was associated with six of nine ribotypes (RTs) said to be geographically representative of the United Kingdom and all of the Ontario (Canada) isolates from CF patients. This clone was not associated with nosocomial infections or environmental strains and was never found in CF isolates from British Columbia or Nova Scotia, Canada, or a center in the eastern United States. Individual isolate EcoRI RT signatures did not cluster geographically as did the ET signatures by clonal analysis. Frequently RTs occurred in more than a single ET. Known point source focal nosocomial outbreaks were typified by single ETs and stable RTs. Dendrographic analysis of the strains grouped those strains from CF patients, nosocomial outbreaks, and environmental sources into separate ET families, and diversity analysis indicated that, with the exception of ET17, CF isolates clustered in unique and closely related ETs different from those from nosocomial and environmental sources. This study has also shown the potential of multilocus enzyme electrophoresis to monitor the intercontinental spread of P. cepacia strains in CF patients, and this may have a significant impact on plans for CF patient summer camps and design of infection control practices. Whether the intercontinental ET12 clone, which predominates in the United Kingdom and the province of Ontario, linked by summer camp acquisition, has increased virulence for CF patients remains to be established.
Sensitivity of 320 strains of P. aeruginosa to 12 antibiotics was studied. It was shown that tobramycin, gentamicin, polymyxin B, carbenicillin, and combinations of tobramycin and gentamicin with carbenicillin were the most effective. The synergism of the combinations was observed in 100 and 94.7 per cent of patients, respectively. One per cent dioxidine solution was shown to be highly active against 84.7 per cent of P. aeruginosa strains. Sensitivity of P. aeruginosa to surface active substances, such as N-cetylpyridinium chloride (N-CPC), rokkal and chlorhexidine was studied with the method of 2-fold serial dilutions. It was found that 66.6 per cent of the strains were sensitive to N-CPC in dilutions of 1:80--1:160. The respective figures for rokkal and chlorhexidine were 1:10--1:40 and 1:40. The drugs were used in treatment of patients with P. aeruginosa wound infections. Five patients were treated with intraosteal administration of gentamicin in a mixture for prolonged antiinflammation blockade. Investigation of the therapeutic concentrations revealed that high concentrations of gentamicin were attained in the wound even in an hour and maintained for 10 hours. No gentamicin was detected in the wound in 48 hours. The combined use of the antibacterial drugs provided efficacy of the chemotherapy.
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Twenty-six elderly patients with chronic leg ulcers infected by Pseudomonas aeruginosa or other aerobic Gram-negative rods were randomised to two treatment groups. The control group (eight patients) received conventional local therapy and the other group (18 patients) was treated with oral ciprofloxacin for three months in addition to conventional local therapy. In the beginning of the study both groups were comparable with the age of the patients and the associated diseases including impairment of arterial and venous circulation in the lower legs. Also the size, duration and the severity of the inflammation reaction in the leg ulcers were comparable before the start of the therapy. Ciprofloxacin was clinically more effective than the standard therapy in reducing the size of the ulcer (p less than 0.05). Also the need of extra systemic antibiotics decreased significantly in the ciprofloxacin group compared with the controls. In three out of eighteen ciprofloxacin treated patients the leg ulcers disappeared completely during the three months' study period compared with none in the control group. However, ciprofloxacin resistant strains, mainly staphylococci, appeared in the leg ulcers in 67% of the ciprofloxacin treated patients compared with 0% in the control group (p less than 0.01). No significant side-effects due to ciprofloxacin except the resistant strains were noticed. We conclude that oral long-term ciprofloxacin therapy is effective in the treatment of chronic leg ulcer infections due to Gram-negative rods but selection of ciprofloxacin resistant strains is a problem in this patient group.
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