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Pseudomonas pseudomallei infection from drowning: the first reported case in Taiwan.

We report a case of Pseudomonas pseudomallei infection, in which the patient acquired the bacteria by aspiration of river water after a drowning incident near Manila, the Philippines. The pulmonary form of melioidosis was noted at the onset, but septicemia developed at a later stage. Positive blood cultures were obtained 17 days after the accident. The patient was treated successfully with a combination of amikacin and cephalothin. This is the first report of P. pseudomallei infection documented in Taiwan.

Amikacin↗

The effect of antipolymorphonuclear leucocyte serum on Pseudomonas aeruginosa infection in rabbits.

Studies were made on the rate of phagocytosis and killing of Pseudomonas aeruginosa by phagocytic cells in the peritoneal cavity of rabbits. In sublethal and lethal infections the phagocytosed bacteria were killed very quickly. In antibody-protected animals, the polymorphs became loaded with liveing bacteria, but this had little effect on the decline in infection. In sublethal infections and in protected animals theproportion of intracellular bacteria labelled with 32O or [14C]uracil was high and antibody greatly enhanced phagocytosis. In lethal infections the rate of phagocytosis was insufficient to prevent the development of a fatal septicaemia. Antipolymorphonuclear leucocyte serum (APS) completely suppressed the normal polymorph response to infection and greatly reduced resistance. The macrophages in the peritoneum, which were not affected by APS, delayed bacterial growth for several hours but were eventually unable to control bacterial mutiplication. The outcome of infection appeared to depend almost entirely on the ratio of bacterial to phagocytes and the presence of antibody. Iron-binding proteins probably make a significant contribution to resistance by reducing the rate of multiplication of extracellular bacteria.

Animals↗

Kinetics of serum, tear, and corneal antibody responses in resistant and susceptible mice intracorneally infected with Pseudomonas aeruginosa.

The studies described here are aimed at determining the kinetics of antibody responses specific to Pseudomonas aeruginosa ATCC 19660 in sera, tears, and corneas of naturally resistant DBA/2 mice and susceptible C57BL/6 mice after intracorneal infection. Immunoglobulin (IgG) and IgM responses in sera were significantly greater in DBA/2 mice for the first 2 weeks postinfection. Little or no IgA was detected in the sera of mice from either strain. IgG was the predominant immunoglobulin class present in the corneas of the infected eyes from both mouse strains. However, differences in both the magnitude and the kinetics of the corneal IgG responses were noted between mouse strains. The kinetics of the corneal IgG responses were more similar to those of the serum IgG response than to those of the tear IgG response. Tear antibody responses in DBA/2 mice differed from those of C57BL/6 mice in two ways. First, there was a sharp increase in tear IgG levels 2 weeks after infection in DBA/2 mice that was not present in C57BL/6 mice. Second, IgA levels present in tears from the infected eyes of C57BL/6 mice dropped to nearly preinfection levels after the first week, whereas in DBA/2 mice, IgA levels remained elevated in the infected eyes after the first week. Determination of P. aeruginosa-specific antibody responses in the uninfected, contralateral control eyes revealed that IgA was detectable in the tears but not in the corneas of DBA/2 mice. Very little IgA was detected in the tears of the uninfected eyes of C57BL/6 mice. IgG was the only immunoglobulin class present in the uninfected corneas in both mouse strains tested. These results suggest that ocular IgA was made locally, whereas most ocular IgG may have originated from the serum, with some possible local synthesis. These immunological results indicate that DBA/2 and C57BL/6 mice respond differently to corneal challenge with P. aeruginosa.

Animals↗

The efficacy of honey in inhibiting strains of Pseudomonas aeruginosa from infected burns.

Because there is no ideal therapy for burns infected with Pseudomonas aeruginosa, there is sufficient need to investigate the efficacy of alternative antipseudomonal interventions. Honey is an ancient wound remedy for which there is modern evidence of efficacy in the treatment of burn wounds, but limited evidence for the effectiveness of its antibacterial activity against Pseudomonas. We tested the sensitivity of 17 strains of P. aeruginosa isolated from infected burns to two honeys with different types of antibacterial activity, a pasture honey and a manuka honey, both with median levels of activity. All strains showed similar sensitivity to honey with minimum inhibitory concentrations below 10% (vol/vol); both honeys maintained bactericidal activity when diluted more than 10-fold. Honey with proven antibacterial activity has the potential to be an effective treatment option for burns infected or at risk of infection with P. aeruginosa.

Anti-Bacterial Agents↗

Effect of Pseudomonas-induced chronic lung inflammation on specific cytotoxic T-cell responses to adenoviral vectors in mice.

A mouse model of chronic Pseudomonas-induced bronchopulmonary inflammation that mimics chronic cystic fibrosis (CF) lung disease was employed to determine whether this inflammatory milieu influences immune responses to adenoviral vectors. Pseudomonas-infected and control mice were inoculated intranasally with a second-generation type 2 adenovirus (Ad2) vector (Ad2/betagal-2). After 3 weeks, serum and airway Ad2-specific antibodies and Ad2 vector-directed, cytotoxic T-lymphocyte (CTL) activity in splenocytes were measured. No differences in humoral immunity were observed between Pseudomonas-infected mice and controls. However, there was a two- to three-fold increase in Ad-specific CTL activity in the Pseudomonas-infected mice compared to control mice. MHC class I-dependent antigen presentation by antigen-presenting cells (APC) from lungs of Pseudomonas-infected mice was also significantly increased compared to APC from control mice, suggesting a mechanism that may contribute to increased Ad-specific CD8+ CTL responses. It was concluded that Ad-specific CTL activity is enhanced in the setting of pre-existing chronic Pseudomonas-induced lung inflammation similar to CF lung disease, and that increased antigen presentation via MHC class I in this setting may be one underlying mechanism. These findings underscore the importance of considering the influence of the disease milieu when evaluating modes of gene therapy for such diseases in animal models.

Adenoviridae↗

Production of elastase, exotoxin A, and alkaline protease in sputa during pulmonary exacerbation of cystic fibrosis in patients chronically infected by Pseudomonas aeruginosa.

Secretion of Pseudomonas aeruginosa elastase, exotoxin A, and alkaline protease in sputum during bronchopulmonary exacerbations was examined in 18 cystic fibrosis patients chronically infected with this microorganism. The patients were studied during one or several exacerbation periods necessitating hospitalizations of 12 to 20 days. In all cases, P. aeruginosa was present in bronchial secretions at admission and was not eradicated after treatment. The P. aeruginosa density decreased significantly after antibiotic therapy but remained greater than 10(6) CFU/g of sputum in most cases. Significant amounts of P. aeruginosa exoproteins were measured in total homogenized bronchial secretions by immunoenzymatic assays. The detection of higher levels of exoproteins at admission, the significant decrease after treatment, and the absence of exoproteins during intercrisis phases constituted arguments for a renewal of virulence of P. aeruginosa during exacerbations. Nevertheless, the concomitant changes in bacteria load and the triggering of the inflammatory process and immune complex formation could also contribute to pulmonary exacerbations.

ADP Ribose Transferases↗

Scavenging of neutrophil-derived superoxide anion by 1-hydroxyphenazine, a phenazine derivative associated with chronic Pseudomonas aeruginosa infection: relevance to cystic fibrosis.

The airways of cystic fibrosis patients colonised by Pseudomonas aeruginosa contain the redox active phenazine derivative, 1-hydroxyphenazine (OHP). As the presence of reactive oxygen species is of importance to tissue damage in cystic fibrosis, OHP was investigated for its ability to reduce molecular oxygen to superoxide. In the presence of NADPH, OHP reduced cytochrome c in a dose-dependent manner. This effect was not inhibited by superoxide dismutase and demonstrates an electron transport role for OHP. The OHP/NADPH system was unable to reduce molecular oxygen to superoxide as judged by an inability to oxidase epinephrine to adrenochrome. However, using lucigenin-enhanced chemiluminescence to detect superoxide, it was found that pathophysiologically relevant concentrations of OHP (5-25 microM) effectively scavenged superoxide from a xanthine/xanthine oxidase system. Similarly, in the presence of OHP, superoxide availability from contact-activated neutrophils was substantially reduced. It is concluded that OHP is an efficient scavenger of superoxide and that electron transfer from superoxide to OHP represents a major mechanism for reduction of OHP in vivo. Reduced OHP has the potential to alter cellular function by participating in the reduction of iron-containing proteins and in this manner contribute to the pathogenesis of P. aeruginosa infection in cystic fibrosis.

Acridines↗

[Respiratory infection caused by Pseudomonas aeruginosa in patients with HIV infection].

OBJECTIVE: Descriptive study of severe respiratory infections caused by Pseudomonas aeruginosa in patients with HIV infection. METHODS: Review of clinical records of HIV-positive patients admitted in a tertiary hospital from 1-1-1990 to 9-30-1995. The patients included in this study were those with P. aeruginosa recovered from respiratory or blood samples and respiratory symptoms. RESULTS: Forty patients suffered 77 episodes. The incidence in the HIV-positive admitted population during the study period was 2.6% but 3.2% in the last year. Ninety-seven percent of patients met criteria for AIDS. Twenty-eight patients (70%) had other bacterial infections. In 78% of patients no classical predisposing factor was found for this infection. Twenty-seven patients (67.5%) came regularly to the day hospital or had been previously admitted to the hospital (recent hospitalization). Twenty-five episodes (32.5%) were tracheo-bronchitis and 50 pneumonias (65%), of which 14 (28%) were cavitated and 7 (14%) bacteremic. Forty-nine percent of episodes were recurrences. Ten out of 15 tracheo-bronchitis in the first episode recurred; the new episode was more severe in 7 patients. Five patients received secondary prophylaxis after the second episode (4 with tobramycin in aerosol and 1 with colistin in aerosol). Two patients had recurrences after 86 and 62 days (mean: 74; SD: 12). Eight out of the 11 patients who did not receive prophylaxis (73%) had recurrence after a mean of 23 days (SD: 10) (p = 0.002). The mortality rate associated with P. aeruginosa was 22.5%. CONCLUSIONS: The incidence of P. aeruginosa infections in our HIV-positive patients was 2.6% (3.2% in the last year). It is associated with severe immunosuppression and previous bacterial infection. The subacute involvement of the lower respiratory tract is most common. Over 50% of infections tend to recur more severely. The secondary prophylaxis increased the symptom-free period, although the number of patients who received it was small.

Adult↗

Mouse footpad infection by Pseudomonas aeruginosa: evidence for delayed hypersensitivity to specific bacterial antigen.

Mouse hind footpad inoculation with 1 x 10(7) viable Pseudomonas aeruginosa cells produces a long-lasting, self-limiting disease process characterized by a bacterial multiplication that parallels the swelling of the infected footpad. Regional popliteal and inguinal lymph nodes and spleen of infected animals show cellular modifications which are almost entirely due to lymphocyte proliferation, as indicated by sponteneous DNA synthesis experiments in vitro. Furthermore, mice which had been infected in their footpad either 20 or 27 days previously and challenged with P. aeruginosa antigens into the controlateral footpad show, 24 h later, a marked increase in regional popliteal lymph node weight, indicating the development of delayed hypersensitivity to Pseudomonas antigens.

Animals↗

Outbreak of severe Pseudomonas aeruginosa infections caused by a contaminated drain in a whirlpool bathtub.

During a 14-month period, 7 patients with hematological malignancies acquired serious infections caused by a single strain of multiply resistant Pseudomonas aeruginosa. A case-control study, culture surveys, and pulsed-field gel electrophoresis implicated a whirlpool bathtub on the unit as the reservoir. All case patients and 32% of control patients used this bathtub (P=.003). The epidemic strain was found only in cultures of samples taken from the bathtub. The drain of the whirlpool bathtub, which was contaminated with the epidemic strain, closed approximately 2.54 cm below the drain's strainer. Water from the faucet, which was not contaminated, became contaminated with P. aeruginosa from the drain when the tub was filled. The design of the drain allowed the epidemic strain to be transmitted to immunocompromised patients who used the whirlpool bathtub. Such tubs are used in many hospitals, and they may be an unrecognized source of nosocomial infections. This potential source of infection could be eliminated by using whirlpool bathtubs with drains that seal at the top.

Adult↗

Early TIMP gene expression after corneal infection with Pseudomonas aeruginosa.

PURPOSE: To evaluate the expression of tissue inhibitor of metalloproteinases (TIMP) mRNA in corneal tissues before and at early time points (6 and 12 hours and 1, 3, and 5 days) after corneal infection with Pseudomonas aeruginosa. METHODS: Ribonuclease protection assays were used to detect and quantitate TIMP mRNA expression in uninfected (wounded and unwounded) and in wounded corneas inoculated with P. aeruginosa. RESULTS: Expression of TIMP-1 mRNA was undetectable in either wounded or unwounded, uninfected corneal tissues, but it increased in a time-dependent manner with peak expression occurring at 3 days after corneal wounding and bacterial inoculation. Constitutive low-level mRNA expression of TIMP-2 was detected in both groups of uninfected corneal tissues; these groups remained essentially unchanged after corneal abrasion and bacterial inoculation. TIMP-3 mRNA was detected in uninfected (wounded and unwounded) corneal tissues and appeared to decrease in a time-dependent manner after corneal abrasion and bacterial inoculation. CONCLUSIONS: The evidence indicated that TIMPs were expressed in infected and in uninfected (wounded and unwounded) corneal tissues. In addition, these data suggested that TIMP expression appeared to be independently regulated.

Animals↗

Vaccines against Pseudomonas aeruginosa infection: 1. Experimental studies.

An experimental study of several types of vaccines against Pseudomonas aeruginosa has been carried out. Pyoimmunogen, a multi-component vaccine consisting mainly of heat-stable proteins (or polypeptides) with a molecular weight of 20 000 to 60 000, was prepared both by laboratory and production techniques using three or five selected strains of P. aeruginosa. The preparations obtained by both methods were found to be of low toxicity and to induce in mice and rats active immunity against challenge with homologous and some heterologous strains of P. aeruginosa, including the toxigenic PA-103 strain. The Pseudomonas vaccine (PV) was prepared from partly purified water-soluble protein antigens (molecular weight ranging from 10 000 to 100 000) obtained from one (mono-PV) or three (tri-PV) selected strains. Mono-PV was prepared by the method of ultrafiltration and tri-PV--by differential centrifugtion. Both types of vaccines proved effective in active mouse protection tests after challenge with homologous as well as with heterologous P. aeruginosa strains. Mono-PV is supposed to induce species-specific immunity against P. aeruginosa infection in mice.

Animals↗

Inhibition of Pseudomonas burn wound infection by mafenide dry foam.

The results of an in vivo evaluation of 8.5% mafenide dry foam are described. Using burned guinea pigs infected with Pseudomonas aeruginosa, mafenide was applied every 12 hr as the dry foam or as the commercially available ointment. After 156 hr of therapy with the medicated dosage forms, the previously infected areas did not demonstrate the presence of Pseudomonas. However, all nonmedicated, infected controls produced positive cultures. Both medicated dosage forms demonstrated equivalent efficacy in the inhibition of Pseudomonas on burn wounds.

Administration, Topical↗

Exogenous rh-urokinase modifies inflammation and Pseudomonas aeruginosa infection in a rat chronic pulmonary infection model.

The effect of recombinant human urokinase (rh-UK) in a rat model of chronic Pseudomonas aeruginosa pulmonary infection was studied. Efficacy was assessed by lung histology and quantitative bacteriology. Male Sprague-Dawley rats received 1 x 10(4) or 1 x 10(5) P. aeruginosa encapsulated in agar beads via the intratracheal route on day 1. Intratracheal administration of up to 12,500 units of rh-UK on day 21 led to a dose-dependent disappearance of viable organisms from the lungs by day 24 in rats receiving 10(4) organisms. In slightly longer term infections (30 days), rh-UK was still effective in facilitating the disappearance of the organisms from the lungs of most of the treated animals. rh-UK was effective in eliminating organisms when animals were infected with 10(4), but not 10(5) bacteria. In vitro analysis revealed that rh-UK was not directly toxic for the organisms. Histologically, lungs from short-term infected control animals exhibited acute inflammation, inflammatory cell infiltrates, and fibrin deposition. Histology of lungs from UK-treated, short-term infected rats revealed decreased airway inflammation and cellular infiltration compared with infected controls. Lungs from infected animals treated with 12,500 units of rh-UK were histologically indistinguishable from the lungs of uninfected control animals, except for the foreign body reaction. These results indicate that exogenous rh-UK may be efficacious in the treatment of pulmonary inflammation accompanying exposure to Gram-negative bacteria such as P. aeruginosa.

Animals↗

Amikacin therapy of exacerbations of Pseudomonas aeruginosa infections in patients with cystic fibrosis.

Amikacin, a new semisynthetic aminoglycoside antibiotic with activity against Pseudomonas aeruginosa, was used to treat 22 acute exacerbations of chronic pulmonary infections in 18 patients with cystic fibrosis. Patients ranged from 5 to 32 years of age and had mucoid P. aeruginosa isolated from sputum. The amikacin dose was usually 7.5 mg/kg every eight hours but was increased to 10 mg/kg and/or carbenicillin was added in selected cases depending on clinical course. Although P. aeruginosa was not eliminated from our patients' sputum except in two cases, there was a good clinical response in 19 of 22 courses. Significant improvement in chest x-ray films, spirometry, or arterial oxygen tension was documented in 11 of 17 courses. One instance of serum creatinine level elevation could not be attributed to this antibiotic. Two patients showed minimal (15 dB) unilateral high-frequency hearing loss on serial audiograms. Activity against many gentamicin-resistant strains and high blood levels are among the attractive properties of amikacin. Amikacin is clinically effective in treating Pseudomonas-associated pulmonary infections complicating cystic fibrosis.

Acute Disease↗

Azlocillin in respiratory tract infections with Pseudomonas aeruginosa in children with cystic fibrosis.

In 5 children with cystic fibrosis, 13 courses of lower respiratory infections due to Pseudomonas aeruginosa were treated with azlocillin, 100--200 mg/kg body weight intravenously every 8 h for 10--15 days. The clinical course during azlocillin treatment was more favourable than had been the case previously in the same patients when treated with combinations of carbenicillin and aminoglycosides. No side effects ascribable to azlocillin were observed, although one allergic reaction occurred, but this was probably elicited by another allergen. Upon repeated courses of treatment, the minimum inhibitory concentration of the infecting organisms increased steadily against both azlocillin and carbenicillin. It is concluded that azlocillin represents an important alternative in the treatment of lower respiratory tract infections due to P. aeruginosa in patients with cystic fibrosis.

Adolescent↗